atovaquone/proguanil (Rx)

Brand and Other Names:Malarone
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

atovaquone/proguanil

tablet

  • 250mg/100mg

Malaria

Prophylaxis

  • 250 mg/100 mg (1 tablet) PO daily, beginning 1-2 days before travel to malaria-endemic area and continued until 7 days after return

Treatment

  • 1 g/400 mg (4 tablets) PO daily for 3 days

Dosing considerations

  • In event of vomiting within 1 hour of dose, repeat dose
  • In geriatric patients, cautious dose selection is necessary because of decreased hepatic/renal/cardiac function and increased systemic exposure to cycloguanil

Dosing Modifications

CrCl <30 mL/min: Prophylactic use not recommended; only use for treatment if benefits of therapy greatly outweigh risks

CrCl 30-80 mL/min: No dosage adjustments necessary

Administration

Take at same time daily with food or milky drink

For children with difficulty swallowing, may be crushed and mixed with condensed milk just before administration

Dosage Forms & Strengths

atovaquone/proguanil

tablet

  • 62.5mg/25mg

Malaria

Prophylaxis

  • <11 kg: Safety and efficacy not established
  • 11-20 kg: 62.5 mg/25 mg (1 pediatric tablet) PO daily
  • 21-30 kg: 125 mg/50 mg (2 pediatric tablets) PO daily
  • 31-40 kg: 187.5 mg/75 mg (3 pediatric tablets) PO daily
  • >40 kg: 250 mg/100 mg (1 adult tablet) PO daily, beginning 1-2 days before travel to malaria-endemic area and continued until 7 days after return

Treatment

  • <5 kg: Safety and efficacy not established
  • 5-8 kg: 125 mg/50 mg (2 pediatric tablets) PO daily for 3 days
  • 9-10 kg: 187.5 mg/75 mg (3 pediatric tablets) PO daily for 3 days
  • 11-20 kg: 250 mg/100 mg (1 adult tablet) PO daily for 3 days
  • 21-30 kg: 500 mg/200 mg (2 adult tablets) PO daily for 3 days
  • 31-40 kg: 750 mg/300 mg (3 adult tablets) PO daily for 3 days
  • >40 kg: 1 g/400 mg (4 adult tablets) PO daily for 3 days

Dosing considerations

  • In event of vomiting within 1 hour of dose, repeat dose
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Interactions

Interaction Checker

and atovaquone/proguanil

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (2)

              • dapsone topical

                proguanil, dapsone topical. unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration of dapsone topical with oral dapsone or antimalarial medications because of the potential for hemolytic reactions.

                atovaquone, dapsone topical. unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration of dapsone topical with oral dapsone or antimalarial medications because of the potential for hemolytic reactions.

              • efavirenz

                efavirenz decreases levels of atovaquone by unspecified interaction mechanism. Avoid or Use Alternate Drug.

              Monitor Closely (4)

              • bupivacaine implant

                atovaquone, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

                proguanil, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

              • efavirenz

                efavirenz decreases levels of proguanil by unspecified interaction mechanism. Use Caution/Monitor. May decrease serum concentrations of the active metabolite of proguanil.

              • indinavir

                indinavir will decrease the level or effect of atovaquone by unknown mechanism. Modify Therapy/Monitor Closely.

              • metoclopramide intranasal

                metoclopramide intranasal will increase the level or effect of atovaquone by Other (see comment). Use Caution/Monitor. Metoclopramide may decrease the absorption of atovaquone. Monitor for reduced therapeutic effect of atovaquone.

              Minor (2)

              • metoclopramide

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

              • tetracycline

                tetracycline decreases levels of atovaquone by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Effect may be minor, due to pharmacodynamic synergism.

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              Adverse Effects

              >10%

              Abdominal pain (3-31%)

              Transaminase increases (17-27%)

              Headache (3-14%)

              Vomiting (1-13%)

              Nausea (12%)

              1-10%

              Asthenia (8%)

              Diarrhea (1-8%)

              Pruritus (6%)

              Anorexia (5%)

              Dizziness (5%)

              Dyspepsia (1-4%)

              Gastritis (0-3%)

              <1%

              Fever

              Cough

              Postmarketing Reports

              Hematologic/lymphatic: Neutropenia, anemia (rarely), pancytopenia (patients with severe renal impairment treated with proguanil)

              Immunologic: Allergic reactions, including angioedema, urticaria, and rare cases of anaphylaxis and vasculitis

              Neurologic: Rare cases of seizures and psychotic events (eg, hallucinations)

              GI: Stomatitis

              Hepatic: Elevated liver function tests (LFTs), rare cases of hepatitis, cholestasis

              Skin: Photosensitivity, rash, and rare cases of erythema multiforme and Stevens-Johnson syndrome

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              Warnings

              Contraindications

              Hypersensitivity

              Prophylaxis in severe renal impairment (CrCl <30 mL/min)

              Cautions

              Administration does not provide radical cure, nor does it prevent delayed primary attacks of P vivax and P ovale

              Patients with severe malaria are not candidates for oral therapy; not evaluated in treatment of cerebral malaria or severe manifestations of malaria (eg, hyperparasitemia, pulmonary edema, renal failure)

              Hepatitis and increased transaminase levels reported with prophylactic use; monitor closely; use caution with existing hepatic impairment; hepatic enzyme elevations may persist for four weeks after treatment has ended

              Not for treatment of cerebral malaria or other severe manifestations of complicated malaria

              Absorption may be reduced in patients with diarrhea or vomiting; monitor closely, and consider antiemetic use; if severe, use alternative antimalarial

              Monotherapy may result in parasite relapse of P vivax malaria

              Recrudescent P falciparum infection or chemoprophylactic failure after monotherapy should be treated with different schizonticide

              Prophylaxis should not be prematurely discontinued; delayed cases of P. falciparum malaria may occur

              Complete prophylaxis includes therapy, protective clothing, insect repellents, and bednets

              No chemoprophylactic regimen is 100% effective; patient should seek medical care for any febrile illness that occurs

              Treatment failure reported in patients >100 kg; monitoring and follow up recommended in this patient group

              P falciparum malaria carries higher risk of death and serious complications in pregnant women; patient should discuss risks and benefits of travel, and if travel cannot be avoided, additional prophylaxis, including protective clothing, must be employed

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              Pregnancy & Lactation

              Pregnancy category: C

              Lactation: Proguanil is excreted into milk in small quantities, but excretion of atovaquone is unknown; use with caution

              Pregnancy Categories

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

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

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

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

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

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Antiparasitic activity

              Atovaquone: Selective inhibitor of parasite mitochondrial electron transport

              Proguanil: Primary effect through metabolite cycloguanil, a dihydrofolate reductase inhibitor in malaria parasite, which leads to disruption of deoxythymidylate synthesis

              Absorption

              Bioavailability: Oral absorption of atovaquone is poor but increases to 23% with high-fat meal (AUC increased 2-3 times and Cmax 5 times over fasting); administer with food or milk; proguanil is extensively absorbed

              Distribution

              Protein bound: Atovaquone, >99%; proguanil, 75%

              Vd: Atovaquone, 8.8 L/kg

              Metabolism

              Proguanil is metabolized to cycloguanil (primarily by CYP2C19)

              Elimination

              Half-life: Atovaquone, 2-3 days; proguanil, 12-21 hr

              Clearance: Atovaquone, 1.32-6.61 L/hr; proguanil, 29.5-67.9 L/hr

              Excretion: Atovaquone, feces as unchanged drug (94%); proguanil, urine (40-60%)

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              Patient Handout

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              Formulary

              FormularyPatient Discounts

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              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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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.