phentermine/topiramate (Rx)

Brand and Other Names:Qsymia
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Dosing & Uses

AdultPediatric

Dosing Forms & Strengths

Phentermine (immediate-release)/topiramate (extended-release)

capsule: Schedule IV

  • 3.75mg/23mg
  • 7.5mg/46mg
  • 11.25mg/69mg
  • 15mg/92mg

Weight Managetment

Adjunct to reduced-calorie diet and exercise

Initial BMI ≥30 kg/m² (obese), or BMI ≥27 kg/m² (overweight) in presence of at least 1 weight related comorbidity (eg, hypertension, type 2 diabetes mellitus, dyslipidemia)

Initial: 3.75 mg/23 mg PO qDay for 14 days, THEN

Day 15: Increase to 7.5 mg/46 mg PO qDay for 12 weeks, then evaluate weight loss

If a patient has not lost at least 3% of baseline body weight on 7.5 mg/46 mg, discontinue or escalate dose, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss at the 7.5 mg/46 mg dose

To escalate the dose: Increase to 11.25 mg/69 mg PO qDay for 14 days; followed by dosing 15 mg/92 mg qDay; evaluate weight loss following dose escalation to 15 mg/92 mg after an additional 12 weeks of treatment

If a patient has not lost at least 5% of baseline body weight on 15 mg/92 mg, discontinue as directed (ie, gradually), as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment

Note: 3.75 mg/23 mg and 11.25 mg/69 mg dosage strengths are for titration purposes only

Administration

Take once daily in the morning with or without food

Avoid dosing in the evening due to the possibility of insomnia

Discontinue 15 mg/92 mg gradually by taking a dose every other day for at least 1 week prior to stopping treatment altogether, due to the possibility of precipitating a seizure

Renal & Hepatic Impairment

Renal impairment

  • Mild (≥50 mL/min): No dose adjustment required
  • Moderate (30-49 mL/min) and severe (<30 mL/min): Not to exceed 7.5 mg/46 mg qDay

Hepatic impairment

  • Mild (Child-Pugh 5-6): No dose adjustment required
  • Moderate (Child-Pugh 7-9): Not to exceed 7.5 mg/46 mg qDay
  • Severe (Child-Pugh 10-15): Avoid use

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and phentermine/topiramate

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            Contraindicated (8)

            • iobenguane I 123

              phentermine decreases effects of iobenguane I 123 by receptor binding competition. Contraindicated. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results.

            • isocarboxazid

              isocarboxazid increases effects of phentermine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • linezolid

              linezolid increases effects of phentermine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • methylphenidate

              phentermine increases effects of methylphenidate by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • phenelzine

              phenelzine increases effects of phentermine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • procarbazine

              procarbazine increases effects of phentermine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • selegiline transdermal

              selegiline transdermal increases effects of phentermine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • tranylcypromine

              tranylcypromine increases effects of phentermine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            Serious - Use Alternative (60)

            • amitriptyline

              amitriptyline, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • amoxapine

              amoxapine, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • cabergoline

              cabergoline, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • calcium/magnesium/potassium/sodium oxybates

              calcium/magnesium/potassium/sodium oxybates, topiramate. Either increases effects 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.

            • citalopram

              citalopram, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • clomipramine

              clomipramine, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • desflurane

              desflurane increases toxicity of phentermine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • desipramine

              desipramine, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • dihydroergotamine

              topiramate will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              dihydroergotamine, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • dihydroergotamine intranasal

              dihydroergotamine intranasal, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

              topiramate will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • doxapram

              doxapram increases effects of phentermine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive pressor effect.

            • dronedarone

              topiramate will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • doxepin

              doxepin, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • duloxetine

              duloxetine, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • ergoloid mesylates

              ergoloid mesylates, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • ergotamine

              topiramate will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              ergotamine, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • erythromycin base

              topiramate will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • erythromycin ethylsuccinate

              topiramate will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              topiramate will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              topiramate will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ether

              ether increases toxicity of phentermine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • ethinylestradiol

              topiramate will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • everolimus

              topiramate will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fluoxetine

              fluoxetine, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • fluvoxamine

              fluvoxamine and phentermine both increase serotonin levels. Avoid or Use Alternate Drug.

            • imipramine

              imipramine, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • iobenguane I 131

              phentermine 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.

            • isoflurane

              isoflurane increases toxicity of phentermine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • levomilnacipran

              levomilnacipran and phentermine both increase serotonin levels. Avoid or Use Alternate Drug.

            • lofepramine

              lofepramine, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • lovastatin

              topiramate will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • maprotiline

              maprotiline, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • methoxyflurane

              methoxyflurane increases toxicity of phentermine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • methylergonovine

              methylergonovine, phentermine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

            • metoclopramide intranasal

              topiramate, 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.

            • milnacipran

              milnacipran, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • nefazodone

              nefazodone, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • norethindrone

              topiramate will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • norethindrone acetate

              topiramate will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • norethindrone transdermal

              topiramate will decrease the level or effect of norethindrone transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • nortriptyline

              nortriptyline, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • ozanimod

              ozanimod increases toxicity of phentermine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • paroxetine

              paroxetine, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • perampanel

              topiramate will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increased perampanel dose may be needed when coadministered

            • protriptyline

              protriptyline, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • ranolazine

              topiramate will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rasagiline

              rasagiline increases effects of phentermine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Phentermine should not be administered during or within 14 days following the use of most MAOIs or drugs with MAO-inhibiting activity. Risk of acute hypertensive episode. .

            • selegiline

              selegiline increases effects of phentermine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Phentermine should not be administered during or within 14 days following the use of most MAOIs or drugs with MAO-inhibiting activity. Risk of acute hypertensive episode. .

            • sertraline

              sertraline, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • sevoflurane

              sevoflurane increases toxicity of phentermine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

            • silodosin

              topiramate will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • simvastatin

              topiramate will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sirolimus

              topiramate will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sodium oxybate

              sodium oxybate, topiramate. Either increases effects 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.

            • tolvaptan

              topiramate will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • trazodone

              trazodone, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

              trazodone, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            • trimipramine

              trimipramine, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • ulipristal

              topiramate will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • venlafaxine

              venlafaxine, phentermine. Either increases toxicity of the other by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of serotonin syndrome.

            Monitor Closely (320)

            • acetazolamide

              topiramate, acetazolamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of kidney stone formation.

            • albuterol

              albuterol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              albuterol and phentermine both decrease sedation. Use Caution/Monitor.

            • alfentanil

              alfentanil and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              alfentanil increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alitretinoin

              topiramate will decrease the level or effect of alitretinoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alprazolam

              alprazolam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • almotriptan

              topiramate will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alprazolam

              topiramate will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              alprazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • amiodarone

              topiramate will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amitriptyline

              amitriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              amitriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels.

            • amobarbital

              amobarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amobarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • amoxapine

              amoxapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amoxapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • apomorphine

              apomorphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • arformoterol

              arformoterol and phentermine both decrease sedation. Use Caution/Monitor.

              arformoterol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • aprepitant

              topiramate will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • arformoterol

              topiramate increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • aripiprazole

              aripiprazole increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              topiramate will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              aripiprazole and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • armodafinil

              armodafinil and phentermine both decrease sedation. Use Caution/Monitor.

              topiramate increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • artemether/lumefantrine

              topiramate will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azelastine

              azelastine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atorvastatin

              topiramate will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • avanafil

              topiramate will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness.

            • axitinib

              topiramate decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azelastine

              azelastine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • baclofen

              baclofen and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • bazedoxifene/conjugated estrogens

              topiramate will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • belladonna and opium

              belladonna and opium and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              belladonna and opium increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benazepril

              phentermine decreases effects of benazepril by pharmacodynamic antagonism. Use Caution/Monitor.

            • benperidol

              benperidol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • benperidol

              benperidol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benzphetamine

              benzphetamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              phentermine and benzphetamine both decrease sedation. Use Caution/Monitor.

            • brexanolone

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

            • bromocriptine

              bromocriptine, phentermine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Hypertension, V tach.

            • brinzolamide

              topiramate, brinzolamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of kidney stone formation.

            • brompheniramine

              brompheniramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              brompheniramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • budesonide

              topiramate will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • buprenorphine

              buprenorphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • buprenorphine buccal

              buprenorphine buccal and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • buspirone

              topiramate will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butabarbital

              butabarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              butabarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • butalbital

              butalbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              butalbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • butorphanol

              butorphanol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              butorphanol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • caffeine

              topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              caffeine and phentermine both decrease sedation. Use Caution/Monitor.

            • captopril

              phentermine decreases effects of captopril by pharmacodynamic antagonism. Use Caution/Monitor. Phentermine may decrease the antihypertensive effect of ACE Inhibitors.

            • carbamazepine

              topiramate will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              carbamazepine decreases levels of topiramate by increasing metabolism. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              carbinoxamine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • carisoprodol

              carisoprodol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • chloral hydrate

              chloral hydrate increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cenobamate

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

            • chloral hydrate

              chloral hydrate and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • chlordiazepoxide

              chlordiazepoxide and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              chlordiazepoxide increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              chlorpheniramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • chlorpromazine

              chlorpromazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              chlorpromazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              chlorpromazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorzoxazone

              chlorzoxazone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • cinnarizine

              cinnarizine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cilostazol

              topiramate will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cinacalcet

              topiramate will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • clemastine

              clemastine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              clemastine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • clobazam

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

            • clomipramine

              clomipramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clobetasone

              topiramate will decrease the level or effect of clobetasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clomipramine

              clomipramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • clonazepam

              clonazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              clonazepam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clopidogrel

              topiramate will increase the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

            • clorazepate

              clorazepate increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clorazepate

              clorazepate and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • clozapine

              clozapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              topiramate will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              clozapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • codeine

              codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • colchicine

              topiramate will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cyclizine

              cyclizine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • conivaptan

              topiramate will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens

              topiramate will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              topiramate will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cortisone

              topiramate will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cyclizine

              cyclizine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • cyclobenzaprine

              cyclobenzaprine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • cyclosporine

              topiramate will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              cyproheptadine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • dantrolene

              dantrolene and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • desipramine

              desipramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • darifenacin

              topiramate will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              topiramate will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dasatinib

              topiramate will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • desflurane

              desflurane and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • desipramine

              desipramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • deutetrabenazine

              topiramate and deutetrabenazine both increase sedation. Use Caution/Monitor.

            • dexamethasone

              topiramate will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              dexchlorpheniramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • dexfenfluramine

              dexfenfluramine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              phentermine and dexfenfluramine both decrease sedation. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              dexmedetomidine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmethylphenidate

              topiramate increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              dexmethylphenidate and phentermine both decrease sedation. Use Caution/Monitor.

              dexmethylphenidate and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • dextroamphetamine

              dextroamphetamine and phentermine both decrease sedation. Use Caution/Monitor.

              topiramate increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              dextroamphetamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • dextromoramide

              dextromoramide and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              dextromoramide increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diamorphine

              diamorphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              diamorphine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diazepam

              topiramate will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              diazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • dichlorphenamide

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

            • dichlorphenamide

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

              dichlorphenamide, topiramate. Either increases levels of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

            • dienogest/estradiol valerate

              topiramate will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • diethylpropion

              diethylpropion and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              phentermine and diethylpropion both decrease sedation. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              difenoxin hcl increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diltiazem

              phentermine will decrease the level or effect of diltiazem by pharmacodynamic antagonism. Use Caution/Monitor. Amphetamines may diminish antihypertensive effects of diltiazem. Monitor BP.

              topiramate will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dimenhydrinate

              dimenhydrinate increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              dimenhydrinate and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • diphenhydramine

              diphenhydramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              diphenhydramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • diphenoxylate hcl

              diphenoxylate hcl and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              diphenoxylate hcl increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dipipanone

              dipipanone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              dipipanone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dobutamine

              dobutamine and phentermine both decrease sedation. Use Caution/Monitor.

              topiramate increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              dobutamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • dopamine

              topiramate increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              dopamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              phentermine and dopamine both decrease sedation. Use Caution/Monitor.

            • dopexamine

              topiramate increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              dopexamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              dopexamine and phentermine both decrease sedation. Use Caution/Monitor.

            • doxepin

              doxepin increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              doxepin and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • doxylamine

              doxylamine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • droperidol

              droperidol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • droperidol

              droperidol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • droxidopa

              phentermine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

            • eletriptan

              topiramate will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ephedrine

              ephedrine, phentermine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

              topiramate increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              ephedrine and phentermine both decrease sedation. Use Caution/Monitor.

              ephedrine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • epinephrine

              epinephrine and phentermine both decrease sedation. Use Caution/Monitor.

              epinephrine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • epinephrine inhaled

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

            • epinephrine racemic

              topiramate increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • epinephrine racemic

              epinephrine racemic and phentermine both decrease sedation. Use Caution/Monitor.

              epinephrine racemic and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • erlotinib

              topiramate will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esketamine intranasal

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

              esketamine intranasal, phentermine. 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. .

            • estazolam

              estazolam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              estazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • estradiol

              topiramate will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethanol

              ethanol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • estrogens conjugated synthetic

              topiramate will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estrogens esterified

              topiramate will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Topiramate may compromise the efficacy of estrogens used for contraception or hormone replacement therapies

            • estropipate

              topiramate will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethanol

              ethanol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • etonogestrel

              topiramate will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etravirine

              topiramate will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eucalyptus

              eucalyptus and topiramate both increase sedation. Use Caution/Monitor.

            • felodipine

              topiramate will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fenfluramine

              fenfluramine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              phentermine and fenfluramine both decrease sedation. Use Caution/Monitor.

            • fesoterodine

              topiramate will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluphenazine

              fluphenazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              fluphenazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • fludrocortisone

              topiramate will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fluphenazine

              fluphenazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • flurazepam

              flurazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              flurazepam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • formoterol

              formoterol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              formoterol and phentermine both decrease sedation. Use Caution/Monitor.

            • fosamprenavir

              topiramate will decrease the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • green tea

              green tea, phentermine. Other (see comment). Use Caution/Monitor. Comment: Green tea may include caffeine. Caffeine is a CNS-stimulant and additive effects may be seen when coadministered with other CNS stimulants. Caffeine should be avoided or used cautiously.

            • fosphenytoin

              fosphenytoin decreases levels of topiramate by increasing metabolism. Use Caution/Monitor.

            • haloperidol

              haloperidol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              haloperidol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • hydralazine

              hydralazine, phentermine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

            • hydrocortisone

              topiramate will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hydromorphone

              hydromorphone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              hydromorphone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydroxyprogesterone caproate

              topiramate will decrease the level or effect of hydroxyprogesterone caproate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • iloperidone

              iloperidone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              topiramate will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              iloperidone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • imipramine

              imipramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              imipramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • indinavir

              topiramate will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ioflupane I 123

              phentermine decreases effects of ioflupane I 123 by receptor binding competition. Use Caution/Monitor. Drugs that bind to dopamine transporter receptor with high affinity may interfere with the image following ioflupane I 123 administration.

            • isoproterenol

              isoproterenol and phentermine both decrease sedation. Use Caution/Monitor.

              topiramate increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              isoproterenol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • ketamine

              ketamine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • ketotifen, ophthalmic

              ketotifen, ophthalmic increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ketotifen, ophthalmic

              ketotifen, ophthalmic and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • lapatinib

              topiramate will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, topiramate. 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 will increase the level or effect of topiramate 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

              topiramate increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              levalbuterol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              levalbuterol and phentermine both decrease sedation. Use Caution/Monitor.

            • levonorgestrel intrauterine

              topiramate decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levorphanol

              levorphanol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levonorgestrel oral

              topiramate decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              topiramate will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

            • levorphanol

              levorphanol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • linagliptin

              topiramate will increase the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer

            • lisdexamfetamine

              lisdexamfetamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              lisdexamfetamine and phentermine both decrease sedation. Use Caution/Monitor.

              topiramate increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • lithium

              topiramate increases levels of lithium by unspecified interaction mechanism. Use Caution/Monitor. Increase in lithium exposure may occur with doses of up to 600 mg/day; monitor lithium levels when coadministered with high-dose topiramate .

            • lofepramine

              lofepramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lofepramine

              lofepramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • lofexidine

              lofexidine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              lofexidine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lopinavir

              topiramate will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • loprazolam

              loprazolam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • loprazolam

              loprazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • loratadine

              topiramate will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lorazepam

              lorazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              lorazepam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lormetazepam

              lormetazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              lormetazepam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • loxapine

              loxapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              loxapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • loxapine inhaled

              loxapine inhaled and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              loxapine inhaled increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lumefantrine

              topiramate will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • maprotiline

              maprotiline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lurasidone

              lurasidone, topiramate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              maprotiline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • maraviroc

              topiramate will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • marijuana

              marijuana and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              marijuana increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • melatonin

              melatonin and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              melatonin increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • meperidine

              meperidine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              meperidine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • meprobamate

              meprobamate increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              meprobamate and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • mestranol

              topiramate will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • metaproterenol

              metaproterenol and phentermine both decrease sedation. Use Caution/Monitor.

              metaproterenol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • metaproterenol

              topiramate increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • metaxalone

              metaxalone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • metformin

              phentermine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

              topiramate increases toxicity of metformin by Other (see comment). Use Caution/Monitor. Comment: Decreases serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

            • methadone

              topiramate will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              methadone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              methadone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methamphetamine

              methamphetamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              methamphetamine and phentermine both decrease sedation. Use Caution/Monitor.

            • methazolamide

              topiramate, methazolamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of kidney stone formation.

            • methyldopa

              methyldopa increases effects of phentermine by unknown mechanism. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • methylenedioxymethamphetamine

              methylenedioxymethamphetamine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              methylenedioxymethamphetamine and phentermine both decrease sedation. Use Caution/Monitor.

            • methylprednisolone

              topiramate will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • midazolam

              midazolam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • midazolam

              topiramate will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              midazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • midazolam intranasal

              midazolam intranasal, topiramate. Either increases toxicity 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.

            • midodrine

              topiramate increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              phentermine and midodrine both decrease sedation. Use Caution/Monitor.

              midodrine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • mirtazapine

              mirtazapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              mirtazapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • modafinil

              modafinil and phentermine both decrease sedation. Use Caution/Monitor.

              topiramate increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • morphine

              morphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              morphine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • motherwort

              motherwort and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              motherwort increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • moxonidine

              moxonidine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              moxonidine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • nabilone

              nabilone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              nabilone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nalbuphine

              nalbuphine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              nalbuphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • nelfinavir

              topiramate will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norepinephrine

              norepinephrine and phentermine both decrease sedation. Use Caution/Monitor.

              norepinephrine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • nicardipine

              topiramate will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nilotinib

              topiramate will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nisoldipine

              topiramate will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norepinephrine

              topiramate increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • nortriptyline

              nortriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              nortriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • olanzapine

              olanzapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              olanzapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • opium tincture

              opium tincture and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              opium tincture increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • orlistat

              orlistat decreases levels of topiramate by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Risk of convulsions.

            • oxazepam

              oxazepam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • orphenadrine

              orphenadrine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • oxazepam

              oxazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • oxycodone

              oxycodone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              oxycodone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • oxymorphone

              oxymorphone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              oxymorphone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • oxytocin

              oxytocin increases effects of phentermine by pharmacodynamic synergism. Use Caution/Monitor.

            • paliperidone

              paliperidone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • paliperidone

              paliperidone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • papaveretum

              papaveretum and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              papaveretum increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • papaverine

              papaverine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • pentazocine

              pentazocine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pazopanib

              topiramate will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pentazocine

              pentazocine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • pentobarbital

              pentobarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              pentobarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • perphenazine

              perphenazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              perphenazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • phendimetrazine

              topiramate increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              phendimetrazine and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              phentermine and phendimetrazine both decrease sedation. Use Caution/Monitor.

            • phenobarbital

              phenobarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              phenobarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phentermine

              topiramate increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • phenylephrine

              phentermine and phenylephrine both decrease sedation. Use Caution/Monitor.

              phentermine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • phenylephrine

              topiramate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • phenylephrine PO

              topiramate increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely. .

              phentermine and phenylephrine PO both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              phentermine and phenylephrine PO both decrease sedation. Use Caution/Monitor.

            • phenytoin

              phenytoin decreases levels of topiramate by increasing metabolism. Use Caution/Monitor.

            • pholcodine

              pholcodine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pholcodine

              pholcodine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • pimozide

              pimozide and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              pimozide increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pirbuterol

              pirbuterol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              pirbuterol and phentermine both decrease sedation. Use Caution/Monitor.

              topiramate increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • prednisone

              topiramate will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • primidone

              primidone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • primidone

              primidone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • prochlorperazine

              prochlorperazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              prochlorperazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              prochlorperazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • promazine

              promazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • promethazine

              promethazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • promethazine

              promethazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              promethazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • propofol

              propofol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • propylhexedrine

              phentermine and propylhexedrine both decrease sedation. Use Caution/Monitor.

              phentermine and propylhexedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • protriptyline

              protriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              protriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pseudoephedrine

              phentermine and pseudoephedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • quazepam

              quazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • quazepam

              quazepam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quetiapine

              quetiapine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              topiramate will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              quetiapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • quinidine

              topiramate will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

              risperidone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ramelteon

              ramelteon and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • repaglinide

              topiramate will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

              risperidone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • ritonavir

              topiramate will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • romidepsin

              topiramate will decrease the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sage

              sage and topiramate both increase sedation. Use Caution/Monitor.

            • salmeterol

              salmeterol and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              salmeterol and phentermine both decrease sedation. Use Caution/Monitor.

            • saquinavir

              topiramate will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • scullcap

              scullcap increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • scullcap

              scullcap and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • secobarbital

              secobarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              secobarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • sevelamer

              sevelamer decreases levels of topiramate by increasing elimination. Use Caution/Monitor.

            • shepherd's purse

              shepherd's purse increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • shepherd's purse

              shepherd's purse and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • solifenacin

              topiramate will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • solriamfetol

              phentermine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • stiripentol

              stiripentol, topiramate. 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.

            • sufentanil

              sufentanil increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              sufentanil and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • sunitinib

              topiramate will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tapentadol

              tapentadol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tacrolimus

              topiramate will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tadalafil

              topiramate will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tapentadol

              tapentadol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tazemetostat

              topiramate will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • temazepam

              temazepam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              temazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • temsirolimus

              topiramate will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • terbutaline

              terbutaline and phentermine both decrease sedation. Use Caution/Monitor.

              terbutaline and phentermine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • terbutaline

              topiramate increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • theophylline

              topiramate will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • thioridazine

              thioridazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              thioridazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              thioridazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thiothixene

              thiothixene and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              thiothixene increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tipranavir

              topiramate will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • topiramate

              topiramate increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • tobramycin inhaled

              tobramycin inhaled and topiramate both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

            • tolterodine

              topiramate will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tramadol

              tramadol and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              tramadol increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trazodone

              trazodone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              topiramate will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              trazodone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triamcinolone acetonide injectable suspension

              topiramate will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triazolam

              triazolam increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triazolam

              topiramate will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              triazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • triclofos

              triclofos and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              triclofos increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trifluoperazine

              trifluoperazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              trifluoperazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              trifluoperazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trimipramine

              trimipramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              trimipramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • triprolidine

              triprolidine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              triprolidine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ubrogepant

              topiramate will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is recommended with concomitant use of ubrogepant and moderate and weak CYP3A4 inducers. (see Dosage Modifications)

            • xylometazoline

              phentermine and xylometazoline both decrease sedation. Use Caution/Monitor.

              phentermine and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • valproic acid

              valproic acid, topiramate. Either increases toxicity of the other by unknown mechanism. Use Caution/Monitor. Risk of hyperammonemia with or without encephalopathy; pts. with inborn errors of metabolism may be at greater risk. S/S: altered LOC, lethargy, vomiting.

            • vardenafil

              topiramate will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • verapamil

              topiramate will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • warfarin

              topiramate will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • xylometazoline

              topiramate increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • yohimbine

              phentermine and yohimbine both decrease sedation. Use Caution/Monitor.

              phentermine and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              topiramate increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • ziconotide

              ziconotide increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              topiramate and ziconotide both increase sedation. Modify Therapy/Monitor Closely.

            • ziprasidone

              ziprasidone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              ziprasidone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            Minor (71)

            • acetaminophen

              topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • acetaminophen IV

              topiramate decreases levels of acetaminophen IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • acetaminophen rectal

              topiramate decreases levels of acetaminophen rectal by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • alfentanil

              topiramate will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alfuzosin

              topiramate will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alosetron

              topiramate will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • amantadine

              amantadine, phentermine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

            • American ginseng

              American ginseng increases effects of phentermine by pharmacodynamic synergism. Minor/Significance Unknown.

            • amobarbital

              amobarbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • armodafinil

              topiramate will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • atazanavir

              topiramate will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • atracurium

              topiramate decreases effects of atracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • biotin

              topiramate decreases levels of biotin by unspecified interaction mechanism. Minor/Significance Unknown. Biotin supplementation may be necessary.

            • bortezomib

              topiramate will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Caution is advised with concurrent use.

            • bosentan

              topiramate will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • butabarbital

              butabarbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • butalbital

              butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • cevimeline

              topiramate will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cisatracurium

              topiramate decreases effects of cisatracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • clarithromycin

              topiramate will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • clomipramine

              topiramate will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyanocobalamin

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

            • dapsone

              topiramate will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • desipramine

              topiramate will decrease the level or effect of desipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • desmopressin

              desmopressin increases effects of phentermine by pharmacodynamic synergism. Minor/Significance Unknown.

            • dexmethylphenidate

              dexmethylphenidate increases effects of topiramate by decreasing metabolism. Minor/Significance Unknown.

            • digoxin

              topiramate decreases levels of digoxin by unspecified interaction mechanism. Minor/Significance Unknown.

            • disopyramide

              topiramate will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • donepezil

              topiramate will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dutasteride

              topiramate will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • efavirenz

              topiramate will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eplerenone

              topiramate will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ethotoin

              topiramate increases levels of ethotoin by decreasing metabolism. Minor/Significance Unknown.

              ethotoin decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • eucalyptus

              eucalyptus increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

              topiramate will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • finasteride

              topiramate will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • guarana

              guarana increases effects of phentermine by pharmacodynamic synergism. Minor/Significance Unknown.

            • fosphenytoin

              topiramate increases levels of fosphenytoin by decreasing metabolism. Minor/Significance Unknown.

            • galantamine

              topiramate will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • glyburide

              topiramate will decrease the level or effect of glyburide by unknown mechanism. Minor/Significance Unknown. Effect in glycemic control is likely small.

            • imatinib

              topiramate will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • imipramine

              topiramate will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • incobotulinumtoxinA

              topiramate decreases effects of incobotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.

            • isradipine

              topiramate will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • itraconazole

              topiramate will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ketoconazole

              topiramate will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • levocarnitine

              topiramate decreases levels of levocarnitine by unspecified interaction mechanism. Minor/Significance Unknown.

            • montelukast

              topiramate will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

              topiramate will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nimodipine

              topiramate will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nitrendipine

              topiramate will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • onabotulinumtoxinA

              topiramate decreases effects of onabotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.

            • ondansetron

              topiramate will decrease the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • oxybutynin

              topiramate will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel

              topiramate will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel protein bound

              topiramate will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pancuronium

              topiramate decreases effects of pancuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • parecoxib

              topiramate will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • phenytoin

              topiramate increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.

            • pimozide

              topiramate will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pioglitazone

              topiramate will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • primidone

              primidone decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

            • propafenone

              topiramate will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • quinine

              topiramate will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ramelteon

              topiramate will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rapacuronium

              topiramate decreases effects of rapacuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • rocuronium

              topiramate decreases effects of rocuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • sage

              sage increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

              sage decreases effects of topiramate by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.

            • saxagliptin

              topiramate will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • yerba mate

              yerba mate increases effects of phentermine by pharmacodynamic synergism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Paresthesia (4.2-19.9%)

            Dry mouth (6.7-19.1%)

            Constipation (7.9-16.1%)

            URI (12.2-15.8%)

            Metabolic acidosis (6.4-12.8%)

            Nasopharyngitis (9.4-12.5%)

            Headache (7-10.6%)

            1-10%

            Insomnia (5-9.4%)

            Dysgeusia (1.3-9.4%)

            Dizziness (2.9-8.6%)

            Increased serum creatinine (2.1-8.4%)

            Sinusitis (6.8-7.8%)

            Nausea (3.6-7.2%)

            Bronchitis (4.4-6.7%)

            Back pain (5.4-6.6%)

            Diarrhea (5-6.4%)

            Blurred vision (4-6.3%)

            Fatigue (4.4-5.9%)

            UTI (3.3-5.2%)

            Hypokalemia (persistent) (0.4-4.9%)

            Cough (3.3-4.8%)

            Depression (2.8-4.3%)

            Anxiety (1.8-4.1%)

            Irritability (1.7-3.7%)

            Alopecia (1.7-3.7%)

            Hypoesthesia (0.8-3.7%)

            Disturbance in attention (0.4-3.5%)

            GERD (0.8-3.2%)

            Extremity pain (2.1-3%)

            Musculoskeletal pain (0.8-3%)

            Muscle spasms (2.8-2.9%)

            Dyspepsia (2.1-2.8%)

            Sinus congestion (2-2.6%)

            Rash (1.7-2.6%)

            Pharyngeal pain (1.2-2.5%)

            Dry eye (0.8-2.5%)

            Gastroenteritis (0.8-2.5%)

            Hypokalemia (acute) (0.4-2.5%)

            Palpitations (0.8-2.4%)

            Eye pain (2.1-2.2%)

            Neck pain (1.2-2.2%)

            Oral paresthesia (0.2-2.2%)

            Decreased appetite (1.5-2.1%)

            Nephrolithiasis (0.2-1.2%)

            Dysmenorrhea (0.4-2.1%)

            Chest discomfort (0.2-2.1%)

            Thirst (1.8-2%)

            Nasal congestion (1.2-2%)

            Postmarketing Reports

            Phentermine

            • Allergic: Urticaria
            • Cardiovascular: Increased blood pressure, ischemic events
            • CNS: Euphoria, psychosis, tremor
            • Reproductive: Changes in libido, impotence

            Topiramate

            • Central nervous system: Suicidal behavior and ideation
            • Dermatologic: Bullous skin reactions (eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), pemphigus
            • Gastrointestinal: Pancreatitis
            • Hepatic: Hepatic failure (including fatalities), hepatitis
            • Metabolic: Hyperammonemia, hypothermia
            • Ophthalmic: Maculopathy, angle closure glaucoma, increased intraocular pressure
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            Warnings

            Contraindications

            Hypersensitivity or idiosyncrasy to sympathomimetic amines

            Pregnancy

            Glaucoma

            Hyperthyroidism

            Within 14 days following MAOIs (risk hypertensive crisis)

            Cautions

            May cause fetal harm (see Contraindications; see Pregnancy & Lactation)

            May increase resting heart rate up to 20 bpm; reduce dose or discontinue use with sustained increase in resting heart rate; caution in patients with history of cardiac or cerebrovascular disease

            Antiepileptic drugs (AEDs), including topiramate, increase the risk of suicidal thoughts or behavior

            Acute myopia associated with secondary angle closure glaucoma has been reported with topiramate; monitor for increased IOP due to risk of permanent loss of vision; discontinue therapy in patients with ocular pain or acute onset of decreased visual acuity

            May cause mood disorders, including depression, and anxiety, as well as insomnia; patient with history of depression may be at increased risk of recurrent depression or other mood disorders

            Cognitive dysfunction (eg, impairment of concentration/attention, difficulty with memory, and speech or language problems, particularly word-finding difficulties) reported; rapid titration or high initial doses may be associated with higher rates; may need to reduce dose or discontinue therapy

            Hyperchloremic, nonanion gap, and metabolic acidosis reported; monitor serum electrolytes and bicarbonate prior to and during treatment; reduce dose or discontinue use if persistent metabolic acidosis develops

            Increase in serum creatinine that reflects a decrease in renal function (glomerular filtration rate) reported; peak increases were observed in clinical trials after 4-8 weeks of treatment and gradually declined but remained elevated over baseline values

            Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues; monitor for needed diabetic therapy adjustments

            In patients treated for hypertension, weight loss may increase the risk of hypotension; monitor for needed antihypertensive dose adjustments

            Coadministration with alcohol or CNS depressants drugs with phentermine or topiramate may potentiate CNS depression or other centrally mediated effects of these agents (eg, dizziness, cognitive adverse reactions, drowsiness, light-headedness, impaired coordination, somnolence)

            Abrupt withdrawal of topiramate associated with seizures in individuals without a history of seizures or epilepsy; gradually discontinue if taking 15 mg/92 mg

            Caution with renal or hepatic impairment and adjust dose (see Renal & Hepatic Impairment)

            Kidney stone formation reported; topiramate inhibits carbonic anhydrase activity and promotes kidney stone formation by reducing urinary citrate excretion and increasing urine pH; avoid coadministration with other carbonic anhydrase inhibitors; use in patients on a ketogenic diet may also increase this risk; increase fluid intake to decrease risk

            Oligohidrosis (resulting in hyperthermia) reported with topiramate; use caution and monitor patients receiving carbonic anhydrase inhibitors and drugs with anticholinergic effects, or during exposure to high environmental temperatures or stenuous exercise

            Can cause changes in laboratory values; can increase the risk of hypokalemia through its inhibition of carbonic anhydrase activity; caution with coadministration of drug that cause hypokalemia (eg, furosemide, hydrochlorothiazide)

            Obtain blood chemistry profile that includes bicarbonate, creatinine, potassium, and glucose at baseline and periodically during treatment

            Use with combination oral contraceptives may increase frequency of irregular bleeding/spotting; need not discontinue unless spotting is trouble to patient

            Consider dose reduction in patients with hepatic impairment; use with caution

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            Pregnancy & Lactation

            Pregnancy

            Contraindicated in pregnant patients; use can cause fetal harm and weight loss offers no clear clinical benefit to a pregnant patient; available data from pregnancy registry and epidemiologic studies indicate increased risk in oral clefts (cleft lip with or without cleft palate) with first trimester exposure to topiramate, a component of the drug combination

            Maternal obesity increases risk for congenital malformations, including neural tube defects, cardiac malformations, oral clefts, and limb reduction defects; in addition, weight loss during pregnancy may result in fetal harm; appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who are already overweight or obese, due to obligatory weight gain that occurs in maternal tissues during pregnancy

            Therapy can cause metabolic acidosis; effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus’ ability to tolerate labor

            Therapy can cause fetal harm when administered to a pregnant patient; advise patients who can become pregnant to use effective contraception during therapy

            For patients taking combined oral contraceptives (COCs), therapy may cause irregular bleeding; advise patients not to discontinue taking their COC and to contact their healthcare provider

            Animal data

            • When phentermine and topiramate were co-administered to rats at doses of 3.75 and 25 mg/kg, respectively [approximately 2 times maximum recommended human dose (MRHD) based on area under the curve (AUC)], or at the same dose to rabbits (approximately 0.1 times and 1 time, respectively, the clinical exposures at the MRHD based on AUC) there were no drug-related malformations;
            • However, structural malformations, including craniofacial defects and reduced fetal weights occurred in offspring of multiple species of pregnant animals administered topiramate at clinically relevant doses; advise pregnant women of potential risk to a fetus

            Lactation

            Drug components are present in human milk; there are no data on effects of topiramate and phentermine on milk production; diarrhea and somnolence reported in breastfed infants with maternal use of topiramate; there are no data on effects of phentermine in breastfed infants

            Because of potential for serious adverse reactions, including changes in sleep, irritability, hypertension, vomiting, tremor and weight loss in breastfed infants with maternal use of phentermine, advise patients that breastfeeding is not recommended during therapy

            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

            Phentermine: Sympathomimetic amine; induces anorectic effect via release of norepinephrine in the hypothalamus causing appetite suppression by increasing blood leptin concentration; exact mechanism of action unknown

            Topiramate: Effect may be through appetite suppression and satiety enhancement that is induced by a combination of pharmacologic effects including augmenting neurotransmitter gamma-aminobutyrate activity, voltage-gated ion channels modulation, AMPA/kainite excitatory glutamate receptor inhibition, or carbonic anhydrase inhibition

            Absorption

            Phentermine (15 mg dose)

            • Peak Plasma Time: 6 hr
            • Peak Plasma Concentration: 49.1 ng/mL
            • AUC: 1990-2000 ng???hr/mL

            Topiramate (92 mg dose)

            • Peak Plasma Time: 9 hr
            • Peak Plasma Concentration: 1020 ng/mL
            • AUC: 61,600-68,000 ng???hr/mL

            Distribution

            Phentermine

            • Protein Bound: 17.5%
            • Vd: 348 L

            Topiramate

            • Protein Bound: 15-41%
            • Vd: 50.8 L (central compartment); 13.1 L (peripheral compartment)

            Metabolism

            Phentermine

            • Metabolized by 2 metabolic pathways, p-hydroxylation on the aromatic ring and N-oxidation on the aliphatic side chain
            • CYP3A4 primarily metabolizes phentermine but does not show extensive metabolism
            • Monoamine oxidase (MAO)-A and MAO-B do not metabolize phentermine

            Topiramate

            • Not extensively metabolized

            Elimination

            Phentermine

            • Half-life: 20 hr (terminal)
            • Clearance: 8.79 L/hr
            • Excretion: 70-80% urine (as unchanged drug)

            Topiramate

            • Half-life: 65 hr (terminal)
            • Clearance: 1.17 L/hr
            • Excretion: 70% urine (as unchanged drug)
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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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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.