clonidine/chlorthalidone (Rx)

Brand and Other Names:Clorpres
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Dosing & Uses

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Dosage Forms & Strengths

clonidine/chlorthalidone

tablet

  • 0.1mg/15mg
  • 0.2mg/15mg
  • 0.3mg/15mg

Hypertension

Not indicated for initial therapy

If the fixed dose combination represents the dose appropriate to the individual patient's needs, it may be more convenient than the separate components

Usual dose: 0.1-0.3 mg/15 mg PO qDay or q12hr

Maximum: 0.6 mg/30 mg PO qDay

Renal Impairment

Use caution in dosing/titrating patients with renal dysfunction

Cumulative effects of thiazides may develop with impaired renal function; dose adjustment may be necessary; azotemia may be precipitated

Hepatic Impairment

Use caution; not studied

Administration

Combination may be substituted for the titrated individual components

Withdraw gradually over a period of 2-4 days

Safety/efficacy not established

May benefit from lower initial dose

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Interactions

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              • alfentanil

                clonidine, alfentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • aminolevulinic acid oral

                aminolevulinic acid oral, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

              • aminolevulinic acid topical

                chlorthalidone increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

              • amitriptyline

                amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • amoxapine

                amoxapine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • atenolol

                clonidine, atenolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • azelastine

                clonidine, azelastine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

              • betaxolol

                clonidine, betaxolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • bisoprolol

                clonidine, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • bremelanotide

                bremelanotide will decrease the level or effect of clonidine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

              • brigatinib

                brigatinib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

              • buprenorphine

                clonidine, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • buprenorphine buccal

                clonidine, buprenorphine buccal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • buprenorphine subdermal implant

                clonidine, buprenorphine subdermal implant. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • buprenorphine transdermal

                clonidine, buprenorphine transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • buprenorphine, long-acting injection

                clonidine, buprenorphine, long-acting injection. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • butorphanol

                clonidine, butorphanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • calcium/magnesium/potassium/sodium oxybates

                clonidine, calcium/magnesium/potassium/sodium oxybates. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              • clomipramine

                clomipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • codeine

                clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • desipramine

                desipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • diltiazem

                clonidine, diltiazem. unknown mechanism. Avoid or Use Alternate Drug. Reports of sinus bradycardia resulting in hospitalization and pacemaker insertion reported with concomitant use. Possible life-threatening effect, monitor closely.

              • doxepin

                doxepin decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • esmolol

                clonidine, esmolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • ethanol

                clonidine, ethanol. Either increases toxicity of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • hydrocodone

                clonidine, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • hydromorphone

                clonidine, hydromorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • imipramine

                imipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • iobenguane I 131

                clonidine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

              • isocarboxazid

                isocarboxazid, chlorthalidone. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

              • levobunolol

                clonidine, levobunolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • lofepramine

                lofepramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • lofexidine

                lofexidine, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

                lofexidine, clonidine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

              • methyl aminolevulinate

                chlorthalidone, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

              • macimorelin

                clonidine, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may transiently elevate growth hormone (GH) concentrations may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.

              • maprotiline

                maprotiline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • meperidine

                clonidine, meperidine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • methadone

                clonidine, methadone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • metoclopramide intranasal

                clonidine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              • metoprolol

                clonidine, metoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • mirtazapine

                mirtazapine decreases effects of clonidine by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Risk of hypertensive urgency.

              • mobocertinib

                mobocertinib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

              • morphine

                clonidine, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • nadolol

                clonidine, nadolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • nalbuphine

                clonidine, nalbuphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • nebivolol

                clonidine, nebivolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • nortriptyline

                nortriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • opium tincture

                clonidine, opium tincture. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • orphenadrine

                clonidine, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

              • oxycodone

                clonidine, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • oxymorphone

                clonidine, oxymorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • pacritinib

                pacritinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              • pentazocine

                clonidine, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • perampanel

                clonidine, perampanel. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • ponesimod

                ponesimod, clonidine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Coadministration of ponesimod with drugs that decrease HR may have additive effects on decreasing HR and should generally not be initiated in these patients.

              • propranolol

                clonidine, propranolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • protriptyline

                protriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • remifentanil

                clonidine, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • sodium oxybate

                clonidine, sodium oxybate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • sotalol

                clonidine, sotalol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • sotorasib

                sotorasib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

              • squill

                chlorthalidone increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

              • sufentanil

                clonidine, sufentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • sufentanil SL

                clonidine, sufentanil SL. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • tapentadol

                clonidine, tapentadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • thalidomide

                clonidine, thalidomide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

              • timolol

                clonidine, timolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

              • tramadol

                clonidine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

              • trazodone

                trazodone decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              • tretinoin

                chlorthalidone, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

              • tretinoin topical

                chlorthalidone, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

              • trimipramine

                trimipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

              Monitor Closely (261)

              • abrocitinib

                abrocitinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor and titrate dose of P-gp substrate appropriately.

              • acebutolol

                acebutolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

                acebutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • aceclofenac

                aceclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • aldesleukin

                aldesleukin increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • acemetacin

                acemetacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • albiglutide

                chlorthalidone decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

              • albuterol

                albuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • aldesleukin

                aldesleukin increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • alprazolam

                clonidine, alprazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • amifostine

                amifostine, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

                amifostine, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

              • amiloride

                amiloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              • amiodarone

                clonidine, amiodarone. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration increases risk of bradycardia, sinus arrest, and AV block; monitor heart rate in patients on concomitant drugs that slow heart rate.

              • arformoterol

                arformoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • aripiprazole

                clonidine, aripiprazole. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • aspirin

                aspirin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • aspirin rectal

                aspirin rectal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • atenolol

                atenolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                atenolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

                clonidine, atenolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

              • avanafil

                avanafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

                avanafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • beclomethasone, inhaled

                beclomethasone, inhaled increases toxicity of chlorthalidone by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

              • benperidol

                clonidine, benperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • benazepril

                benazepril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

              • bendroflumethiazide

                bendroflumethiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • betaxolol

                betaxolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                clonidine, betaxolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

                betaxolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • bisoprolol

                bisoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                bisoprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • blinatumomab

                blinatumomab increases levels of clonidine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

              • bretylium

                chlorthalidone, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

              • bretylium

                clonidine, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

              • brexanolone

                brexanolone, clonidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

              • brodalumab

                brodalumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

              • bumetanide

                bumetanide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • buprenorphine, long-acting injection

                buprenorphine, long-acting injection decreases effects of chlorthalidone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

              • calcifediol

                chlorthalidone increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

              • candesartan

                candesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • captopril

                captopril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

              • carbenoxolone

                chlorthalidone and carbenoxolone both decrease serum potassium. Use Caution/Monitor.

              • carbidopa

                carbidopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

                carbidopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

              • carvedilol

                carvedilol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • celiprolol

                celiprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • celecoxib

                celecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • celiprolol

                celiprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                chlorthalidone decreases levels of celiprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • cenobamate

                cenobamate, clonidine. Either increases effects of the other by sedation. Use Caution/Monitor.

              • chlordiazepoxide

                clonidine, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • chlorothiazide

                chlorothiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • chlorpromazine

                clonidine, chlorpromazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • cholestyramine

                cholestyramine decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • choline magnesium trisalicylate

                choline magnesium trisalicylate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              • citalopram

                clonidine, citalopram. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • clobazam

                clonidine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

              • clonazepam

                clonidine, clonazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS depressant effects.

              • clorazepate

                clonidine, clorazepate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • clozapine

                clonidine, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • cornsilk

                cornsilk increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

              • cyclopenthiazide

                chlorthalidone and cyclopenthiazide both decrease serum potassium. Use Caution/Monitor.

              • daridorexant

                clonidine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

              • deflazacort

                chlorthalidone and deflazacort both decrease serum potassium. Use Caution/Monitor.

              • dexmethylphenidate

                dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.

              • diazepam

                clonidine, diazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • dichlorphenamide

                dichlorphenamide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • diclofenac

                diclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • difelikefalin

                difelikefalin and clonidine both increase sedation. Use Caution/Monitor.

              • diflunisal

                diflunisal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • digoxin

                digoxin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                chlorthalidone increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Hypokalemia increases digoxin effects.

              • dobutamine

                dobutamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • dopexamine

                dopexamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • doxazosin

                clonidine, doxazosin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

              • doxylamine

                clonidine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • dronabinol

                clonidine, dronabinol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • droperidol

                clonidine, droperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • drospirenone

                drospirenone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              • dulaglutide

                dulaglutide, clonidine. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

              • dupilumab

                dupilumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

              • eluxadoline

                eluxadoline increases levels of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

              • empagliflozin

                empagliflozin, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of empagliflozin with diuretics results in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

              • ephedrine

                ephedrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • epinephrine

                epinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • epinephrine inhaled

                clonidine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              • epinephrine racemic

                epinephrine racemic and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • eprosartan

                eprosartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • escitalopram

                clonidine, escitalopram. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • esketamine intranasal

                esketamine intranasal, clonidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

                esketamine intranasal, clonidine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

              • esmolol

                esmolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

                clonidine, esmolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

                esmolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • estazolam

                clonidine, estazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • ethacrynic acid

                ethacrynic acid and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • etodolac

                etodolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • exenatide injectable solution

                chlorthalidone decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

              • exenatide injectable suspension

                chlorthalidone decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

              • fenoprofen

                fenoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • fentanyl

                fentanyl decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

              • fentanyl intranasal

                fentanyl intranasal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

              • fentanyl transdermal

                fentanyl transdermal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

              • fentanyl transmucosal

                fentanyl transmucosal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

              • ferric maltol

                ferric maltol, clonidine. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

              • flibanserin

                flibanserin increases levels of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Increase monitoring of concentrations of drugs transported by P-gp that have a narrow therapeutic index if coadministered with flibanserin.

              • fluoxetine

                clonidine, fluoxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • fluphenazine

                clonidine, fluphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • flurazepam

                clonidine, flurazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • flurbiprofen

                flurbiprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • fluvoxamine

                fluvoxamine, clonidine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. CNS derpressant effects enhanced.

              • formoterol

                formoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • furosemide

                furosemide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • ganaxolone

                clonidine and ganaxolone both increase sedation. Use Caution/Monitor.

              • gentamicin

                chlorthalidone and gentamicin both decrease serum potassium. Use Caution/Monitor.

              • glycerol phenylbutyrate

                glycerol phenylbutyrate will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index.

              • guanfacine

                clonidine, guanfacine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

              • haloperidol

                clonidine, haloperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

                clonidine increases toxicity of haloperidol by Other (see comment). Use Caution/Monitor. Comment: High doses of clonidine IV may increase arrhythmogenic potential (QT-prolongation, ventricular fibrillation) of high dose haloperidol IV in patients experiencing alcoholic delirium.

              • hydrochlorothiazide

                chlorthalidone and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

              • hydroxyzine

                clonidine, hydroxyzine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • ibuprofen

                ibuprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • ibuprofen IV

                ibuprofen IV increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

                chlorthalidone will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

              • iloperidone

                clonidine, iloperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • indacaterol, inhaled

                chlorthalidone, indacaterol, inhaled. serum potassium. Use Caution/Monitor. Combination may increase risk of hypokalemia.

                indacaterol, inhaled, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Caution is advised in the coadministration of indacaterol neohaler with non-potassium-sparing diuretics.

              • indapamide

                chlorthalidone and indapamide both decrease serum potassium. Use Caution/Monitor.

              • indomethacin

                indomethacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • insulin degludec

                chlorthalidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

                clonidine, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.

              • insulin degludec/insulin aspart

                chlorthalidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

                clonidine, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.

              • insulin inhaled

                chlorthalidone decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

                clonidine, insulin inhaled. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.

              • irbesartan

                irbesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • isavuconazonium sulfate

                isavuconazonium sulfate will increase the level or effect of clonidine by Other (see comment). Use Caution/Monitor. Isavuconazonium sulfate, an inhibitor of P-gp and CYP3A4, may increase the effects or levels of sensitive P-gp or CYP3A4 substrates, which may require dose adjustment.

              • isoproterenol

                isoproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • ivabradine

                ivabradine, clonidine. Either decreases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.

              • ixekizumab

                ixekizumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

              • juniper

                juniper, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Juniper may potentiate or interfere with diuretic therapy. Juniper has diuretic effects, but may cause kidney damage at large doses.

              • ketoprofen

                ketoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • ketorolac

                ketorolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • ketorolac intranasal

                ketorolac intranasal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              • labetalol

                labetalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • lasmiditan

                lasmiditan, clonidine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

              • lemborexant

                lemborexant, clonidine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

              • levalbuterol

                levalbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • levodopa

                levodopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

                levodopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

              • levomilnacipran

                levomilnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor. Because levomilnacipran decreases reuptake of NE, it may antagonize clonidine antihypertensive effect.

              • lily of the valley

                chlorthalidone increases toxicity of lily of the valley by Other (see comment). Use Caution/Monitor. Comment: Increased risk of cardiac toxicity due to K+ depletion.

              • liraglutide

                chlorthalidone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

              • lithium

                chlorthalidone increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

              • lorazepam

                clonidine, lorazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • lornoxicam

                lornoxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • losartan

                losartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • loxapine

                clonidine, loxapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • loxapine inhaled

                clonidine, loxapine inhaled. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • lurasidone

                lurasidone increases effects of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

                lurasidone increases effects of clonidine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

              • maitake

                maitake increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

              • methyldopa

                clonidine, methyldopa. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

              • maraviroc

                maraviroc, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

              • meclofenamate

                meclofenamate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • mefenamic acid

                mefenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • meloxicam

                meloxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • metaproterenol

                metaproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • methoxsalen

                methoxsalen, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

              • methyclothiazide

                chlorthalidone and methyclothiazide both decrease serum potassium. Use Caution/Monitor.

              • methylphenidate transdermal

                methylphenidate transdermal decreases effects of chlorthalidone by anti-hypertensive channel blocking. Use Caution/Monitor.

              • metolazone

                chlorthalidone and metolazone both decrease serum potassium. Use Caution/Monitor.

              • metoprolol

                metoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                clonidine, metoprolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

                metoprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • metyrosine

                clonidine, metyrosine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • mometasone inhaled

                mometasone inhaled increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

              • midazolam intranasal

                midazolam intranasal, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

              • milnacipran

                milnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor.

              • mycophenolate

                chlorthalidone will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

              • nabilone

                clonidine, nabilone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • nabumetone

                nabumetone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • nadolol

                nadolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                nadolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • naproxen

                naproxen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • nebivolol

                nebivolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

                clonidine, nebivolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

              • nebivolol

                nebivolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • neratinib

                neratinib increases levels of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Neratinib inhibits P-gp transport. Caution if coadministered with a P-gp substrate with a narrow therapeutic index.

              • nitazoxanide

                nitazoxanide, chlorthalidone. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

              • nitroglycerin rectal

                nitroglycerin rectal, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

                nitroglycerin rectal, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

              • nitroprusside sodium

                nitroprusside sodium, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

              • norepinephrine

                norepinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • olanzapine

                clonidine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • oliceridine

                oliceridine decreases effects of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor for signs of diminished diuresis and/or effects on blood pressure and increase dosage of the diuretic as needed. .

              • olmesartan

                olmesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • olodaterol inhaled

                chlorthalidone and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

              • oritavancin

                oritavancin will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP3A4 inducer; caution if coadministered with CYP3A4 substrates that have a narrow therapeutic index

              • ospemifene

                chlorthalidone, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

              • oxaprozin

                oxaprozin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • oxazepam

                clonidine, oxazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • palbociclib

                palbociclib will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclib

              • paliperidone

                clonidine, paliperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • parecoxib

                parecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • paroxetine

                clonidine, paroxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • penbutolol

                penbutolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

                penbutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • perphenazine

                clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • pindolol

                pindolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • pimozide

                clonidine, pimozide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • pindolol

                pindolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • pirbuterol

                pirbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • piroxicam

                piroxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • pitolisant

                pitolisant will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

              • pivmecillinam

                pivmecillinam, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

              • porfimer

                chlorthalidone, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

              • potassium acid phosphate

                potassium acid phosphate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              • potassium chloride

                potassium chloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              • potassium citrate

                potassium citrate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              • pramipexole

                clonidine, pramipexole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • prazosin

                clonidine, prazosin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

              • probenecid

                chlorthalidone will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

              • prochlorperazine

                clonidine, prochlorperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • promethazine

                clonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • propranolol

                propranolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

                propranolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • quazepam

                clonidine, quazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • sacubitril/valsartan

                sacubitril/valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • quetiapine

                clonidine, quetiapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • ribociclib

                ribociclib will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

              • risperidone

                clonidine, risperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • rolapitant

                rolapitant will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Oral rolapitant (P-gp inhibitor) may increase plasma concentrations of P-gp substrates and may result in potential adverse reactions. Monitor possible adverse reactions if concomitant use of P-gp substrates and rolapitant can not be avoided.

              • ropeginterferon alfa 2b

                ropeginterferon alfa 2b will increase the level or effect of clonidine by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

              • ropinirole

                clonidine, ropinirole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • rotigotine

                clonidine, rotigotine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • rufinamide

                clonidine, rufinamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • salicylates (non-asa)

                salicylates (non-asa) increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • salmeterol

                salmeterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • salsalate

                salsalate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • sarilumab

                sarilumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

              • schisandra

                schisandra will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • secukinumab

                secukinumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

              • serdexmethylphenidate/dexmethylphenidate

                serdexmethylphenidate/dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.

              • sertraline

                clonidine, sertraline. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • shark cartilage

                chlorthalidone, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

              • sodium sulfate/?magnesium sulfate/potassium chloride

                sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              • sodium sulfate/potassium sulfate/magnesium sulfate

                sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

                chlorthalidone and sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

              • sofosbuvir/velpatasvir

                sofosbuvir/velpatasvir increases levels of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.

              • sotalol

                sotalol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

                sotalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • spironolactone

                spironolactone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              • stiripentol

                stiripentol, clonidine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

              • succinylcholine

                succinylcholine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • sulfasalazine

                sulfasalazine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • sulindac

                sulindac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • tadalafil

                tadalafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

                tadalafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • teduglutide

                teduglutide increases levels of clonidine by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

              • telmisartan

                telmisartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • telotristat ethyl

                telotristat ethyl will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.

              • temazepam

                clonidine, temazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • temocillin

                temocillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

              • terbutaline

                terbutaline and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • thioridazine

                clonidine, thioridazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • thiothixene

                clonidine, thiothixene. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • ticarcillin

                ticarcillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

              • timolol

                timolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

                timolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              • tolfenamic acid

                tolfenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • triazolam

                clonidine, triazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • tolmetin

                tolmetin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • tolvaptan

                tolvaptan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • toremifene

                chlorthalidone, toremifene. Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics decrease renal calcium excretion and may increase risk of hypercalcemia in patients taking toremifene.

              • torsemide

                torsemide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

              • triamterene

                triamterene increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              • trientine

                chlorthalidone decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

              • trifluoperazine

                clonidine, trifluoperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • umeclidinium bromide/vilanterol inhaled

                umeclidinium bromide/vilanterol inhaled and chlorthalidone both decrease serum potassium. Modify Therapy/Monitor Closely. Electrocardiographic changes and/or hypokalemia associated with non?potassium-sparing diuretics may worsen with concomitant beta-agonists, particularly if recommended dose is exceeded

              • ustekinumab

                ustekinumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

              • valsartan

                valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • verapamil

                clonidine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.

                verapamil, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.

              • vilanterol/fluticasone furoate inhaled

                vilanterol/fluticasone furoate inhaled and chlorthalidone both decrease serum potassium. Modify Therapy/Monitor Closely. Beta-agonists may acutely worsen ECG changes and/or hypokalemia resulting from non-potassium-sparing diuretics

              • vilazodone

                clonidine, vilazodone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • vitamin D

                chlorthalidone increases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Combination may increase hypercalcemic effect of vitamin D analogs. Use with caution.

              • voclosporin

                voclosporin will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Coadministration of voclosporin (a P-gp inhibitor) increases exposure and risk of adverse reactions of P-gp substrates. For certain P-gp substrates with a narrow therapeutic window, refer to prescribing information of these substrates for dosage modifications, if needed.

              • vortioxetine

                clonidine, vortioxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • xipamide

                xipamide increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor.

                xipamide increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor.

              • ziprasidone

                clonidine, ziprasidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              • zotepine

                clonidine, zotepine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

              Minor (152)

              • acarbose

                chlorthalidone decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, acarbose. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • aceclofenac

                chlorthalidone will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • agrimony

                agrimony increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • acemetacin

                chlorthalidone will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • acyclovir

                chlorthalidone will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • agrimony

                agrimony increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

              • albuterol

                albuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • aminohippurate sodium

                chlorthalidone will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • arformoterol

                arformoterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • aspirin

                chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • aspirin rectal

                chlorthalidone will increase the level or effect of aspirin rectal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • aspirin/citric acid/sodium bicarbonate

                chlorthalidone will increase the level or effect of aspirin/citric acid/sodium bicarbonate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • balsalazide

                chlorthalidone will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • bendroflumethiazide

                bendroflumethiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • birch

                birch increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

              • bitter melon

                bitter melon, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • brimonidine

                brimonidine increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

                brimonidine increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • budesonide

                budesonide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • chlorpropamide

                clonidine decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, chlorpropamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • calcitriol topical

                calcitriol topical, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

              • calcium acetate

                chlorthalidone increases levels of calcium acetate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

              • calcium carbonate

                chlorthalidone increases levels of calcium carbonate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

              • calcium chloride

                chlorthalidone increases levels of calcium chloride by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

              • calcium citrate

                chlorthalidone increases levels of calcium citrate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

              • calcium gluconate

                chlorthalidone increases levels of calcium gluconate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

              • carbenoxolone

                chlorthalidone, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

              • cefadroxil

                cefadroxil will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • cefamandole

                cefamandole will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • cefpirome

                cefpirome will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • celecoxib

                chlorthalidone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • cephalexin

                cephalexin will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • chlorothiazide

                chlorothiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • chlorpropamide

                chlorthalidone will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

                chlorthalidone decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • choline magnesium trisalicylate

                chlorthalidone will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • colestipol

                colestipol decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

              • cornsilk

                cornsilk increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • corticotropin

                corticotropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

              • cortisone

                cortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • cosyntropin

                cosyntropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

              • cyclopenthiazide

                chlorthalidone will increase the level or effect of cyclopenthiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • cyclosporine

                clonidine increases levels of cyclosporine by unknown mechanism. Minor/Significance Unknown.

              • deflazacort

                deflazacort, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • dexamethasone

                dexamethasone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • diazoxide

                diazoxide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

              • diclofenac

                chlorthalidone will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • diflunisal

                chlorthalidone will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • dobutamine

                dobutamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • dopexamine

                dopexamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • ephedrine

                ephedrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • epinephrine

                epinephrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • epinephrine racemic

                epinephrine racemic, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • epoprostenol

                epoprostenol increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

              • etodolac

                chlorthalidone will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • fenbufen

                chlorthalidone will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • fenoprofen

                chlorthalidone will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • fludrocortisone

                fludrocortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • flurbiprofen

                chlorthalidone will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • fo-ti

                fo-ti increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia (theoretical).

              • folic acid

                chlorthalidone decreases levels of folic acid by increasing renal clearance. Minor/Significance Unknown.

              • formoterol

                formoterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • forskolin

                forskolin increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

                forskolin increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • ganciclovir

                chlorthalidone will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • glimepiride

                clonidine decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, glimepiride. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • glimepiride

                chlorthalidone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • glipizide

                chlorthalidone decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine, glipizide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                clonidine decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              • glyburide

                clonidine, glyburide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              • goldenrod

                goldenrod increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

              • insulin aspart

                clonidine decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, insulin aspart. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • hydrochlorothiazide

                chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • hydrocortisone

                hydrocortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • ibuprofen

                chlorthalidone will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • indapamide

                chlorthalidone will increase the level or effect of indapamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • indomethacin

                chlorthalidone will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • insulin aspart

                chlorthalidone decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • insulin detemir

                clonidine decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                chlorthalidone decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine, insulin detemir. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • insulin glargine

                chlorthalidone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine, insulin glargine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                clonidine decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              • insulin glulisine

                clonidine, insulin glulisine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              • insulin lispro

                chlorthalidone decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, insulin lispro. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • insulin NPH

                clonidine, insulin NPH. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                clonidine decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                chlorthalidone decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • insulin regular human

                clonidine decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, insulin regular human. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • isoproterenol

                isoproterenol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • maitake

                maitake increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • ketoprofen

                chlorthalidone will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • ketorolac

                chlorthalidone will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • ketorolac intranasal

                chlorthalidone will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • L-methylfolate

                chlorthalidone decreases levels of L-methylfolate by increasing renal clearance. Minor/Significance Unknown.

              • levalbuterol

                levalbuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • lornoxicam

                chlorthalidone will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • magnesium chloride

                chlorthalidone decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.

              • magnesium citrate

                chlorthalidone decreases levels of magnesium citrate by increasing renal clearance. Minor/Significance Unknown.

              • magnesium hydroxide

                chlorthalidone decreases levels of magnesium hydroxide by increasing renal clearance. Minor/Significance Unknown.

              • magnesium oxide

                chlorthalidone decreases levels of magnesium oxide by increasing renal clearance. Minor/Significance Unknown.

              • magnesium sulfate

                chlorthalidone decreases levels of magnesium sulfate by increasing renal clearance. Minor/Significance Unknown.

              • meclofenamate

                chlorthalidone will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • mefenamic acid

                chlorthalidone will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • meloxicam

                chlorthalidone will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • mesalamine

                chlorthalidone will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • metaproterenol

                metaproterenol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • metformin

                chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • methyclothiazide

                chlorthalidone will increase the level or effect of methyclothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • miglitol

                clonidine decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, miglitol. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • methylprednisolone

                methylprednisolone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • metolazone

                chlorthalidone will increase the level or effect of metolazone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • miglitol

                chlorthalidone decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • minoxidil

                chlorthalidone increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

              • nabumetone

                chlorthalidone will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • naproxen

                chlorthalidone will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • nateglinide

                clonidine decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, nateglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • noni juice

                noni juice increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

              • octacosanol

                octacosanol increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • norepinephrine

                norepinephrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • octacosanol

                octacosanol increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

              • oxaprozin

                chlorthalidone will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • parecoxib

                chlorthalidone will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • pioglitazone

                clonidine, pioglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              • pirbuterol

                pirbuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • reishi

                reishi increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • piroxicam

                chlorthalidone will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • prednisolone

                prednisolone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • prednisone

                prednisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • reishi

                reishi increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

              • repaglinide

                chlorthalidone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • rose hips

                rose hips will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • rosiglitazone

                clonidine decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, rosiglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • rosiglitazone

                chlorthalidone decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • salicylates (non-asa)

                chlorthalidone will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • salmeterol

                salmeterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              • salsalate

                chlorthalidone will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • saxagliptin

                clonidine decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, saxagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • shepherd's purse

                shepherd's purse, chlorthalidone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

                shepherd's purse, clonidine. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

              • sitagliptin

                clonidine, sitagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              • sulfadiazine

                chlorthalidone increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

              • tacrolimus

                clonidine increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.

              • sulfamethoxazole

                chlorthalidone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

                chlorthalidone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

              • sulfasalazine

                chlorthalidone will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • sulfisoxazole

                chlorthalidone increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

              • sulindac

                chlorthalidone will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • terbutaline

                terbutaline, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

                chlorthalidone, terbutaline. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

              • tizanidine

                tizanidine increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

                tizanidine increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

              • tolazamide

                chlorthalidone decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, tolazamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

              • tolbutamide

                clonidine decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

                clonidine, tolbutamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

              • tolfenamic acid

                chlorthalidone will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • treprostinil

                treprostinil increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • tolmetin

                chlorthalidone will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • treprostinil

                treprostinil increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

              • triamcinolone acetonide injectable suspension

                triamcinolone acetonide injectable suspension, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

              • trilostane

                trilostane, chlorthalidone. Other (see comment). Minor/Significance Unknown. Comment: Trilostane reduces K+ loss while maintaining the natriuretic effect. Mechanism: inhibition of mineralocorticoid steroid synthesis.

              • trimethoprim

                chlorthalidone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

              • valganciclovir

                chlorthalidone will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • verteporfin

                chlorthalidone, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

              • vildagliptin

                clonidine, vildagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

                chlorthalidone decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

                clonidine decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

              • willow bark

                chlorthalidone will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

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              Adverse Effects

              Frequency Not Defined

              No adverse effects specific to the combination have been observed; adverse effects limited to those previously reported with clonidine and chlorthalidone

              Clonidine

              • Orthostatic hypotension
              • Bradycardia
              • Syncope
              • Arrhythmia
              • Chest pain
              • Atrioventricular block
              • Flushing
              • Drowsiness
              • Fatigue
              • Malaise
              • Rash
              • Anorexia, weight gain
              • Dry mouth
              • Nausea/vomiting
              • Abnormal LFTs

              Chlorthalidone

              • Blurred vision, xanthopsia
              • Constipation
              • Diarrhea
              • Dizziness
              • Electrolyte abnormalities
              • Headache, vasculitis
              • Hyperglycemia
              • Hyperuricemia
              • Hypotension
              • Impotence
              • Loss of appetite
              • Muscular spasticity, restlessness
              • Nausea/vomiting
              • Paresthesia
              • Photosensitivity, phototoxicity
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              Warnings

              Contraindications

              Hypersensitivity to either component or sulfonamide derivatives

              Cautions

              Bronchospastic disease

              DM, hyperuricemia or gout, hypotension, SLE

              Chlorthalidone may cause fluid or electrolyte imbalance including hyponatremia, hypochloremic alkalosis, or hypokalemia

              History of depression

              Liver disease

              May aggravate digitalis toxicity

              Patients allergic to sulfa may show cross-sensitivity

              May impair ability to perform hazarous tasks

              Risk of male sexual dysfunction

              Renal impairment

              Severe coronary insufficiency, recent MI, conduction disturbances, cerebrovascular disease, chronic renal failure, Raynaud's disease, thromboangiitis obliteran

              Sudden cessation of clonidine treatment has resulted in subjective symptoms such as nervousness, agitation and headache, accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma

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              Pregnancy & Lactation

              Pregnancy Category: C

              Lactation: excreted in breast milk, use caution

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Clonidine/chlorthalidone is a fixed-combination tablet that combines a central alpha-2 stimulator, clonidine and a diuretic, chlorthalidone

              Clonidine produces central alpha 2-adrenergic stimulation, which results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature; this results in decreased peripheral vascular resistance, decreased systolic and diastolic blood pressure, and decreased heart rate

              Chlorthalidone, a monosulfonamyl diuretic, inhibits Na & Cl reabsorption in cortical-diluting segment of ascending loop of Henle

              Pharmacokinetics

              Clonidine

              • Half-Life: 12-16 hr (normal renal function); 41 hr (impaired renal function)
              • Onset: 0.51 hr
              • Metabolism: Liver
              • Excretion: Urine (40-60%)
              • Duration: 6-10 hr
              • Peak plasma time: 3-5 hr (immediate release); 7-8 hr (extended release)
              • Vd: 2.1 L/kg
              • Protein binding: 20-40%
              • Bioavailability: 75-85% (immediate release); 89% (extended release)

              Chlorthalidone

              • Duration: 24-72 hr
              • Onset: 2-6 hr (peak effect)
              • Metabolism: Liver
              • Protein binding: 75%
              • Bioavailability: 60-65%
              • Excretion: Urine (50-65%)
              • Half-life: 40-60 hr (normal renal function); prolonged in renal impairment; 81 hr (anuria)
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              Patient Handout

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              Formulary

              FormularyPatient Discounts

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              Tier Description
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.