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Atovaquone / Proguanil Hydrochloride

Pronunciation: uh-TOE-vuh-KWONE/pro-GWAHN-ill HIGH-droe-KLOR-ide
Class: Antimalarial preparation

Trade Names

Malarone
- Tablets 250 mg atovaquone and 100 mg proguanil hydrochloride

Malarone Pediatric
- Tablets 62.5 mg atovaquone and 25 mg proguanil hydrochloride

Pharmacology

Atovaquone inhibits mitochondrial electron transport in parasites, causing inhibition of nucleic acid synthesis.

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Proguanil exerts its effect by means of the metabolite cycloguanil, which inhibits dihydrofolate reductase in the malarial parasite, disrupting deoxythymidylate synthesis.

Indications and Usage

Prophylaxis of Plasmodium falciparum malaria; treatment of acute, uncomplicated P. falciparum malaria.

Contraindications

Prophylaxis of P. falciparum in patients with severe renal function impairment (Ccr less than 30 mL/min); hypersensitivity to any component of the product.

Dosage and Administration

Malaria Prevention

Start prophylaxis 1 or 2 days before entering a malaria-endemic area and continue during the stay and for 7 days after return.

Adults

PO 250 mg atovaquone/100 mg proguanil daily.

Children

PO Based on body weight. 11 to 20 kg: 62.5 mg atovaquone/25 mg proguanil daily; 21 to 30 kg: 125 mg atovaquone/50 mg proguanil daily; 31 to 40 kg: 187.5 mg atovaquone/75 mg proguanil; more than 40 kg: 250 mg atovaquone/100 mg proguanil.

Treatment of Acute Malaria
Adults

PO 1 g atovaquone/400 mg proguanil as a single daily dose for 3 consecutive days.

Children

PO Based on body weight. 5 to 8 kg: 125 mg atovaquone/50 mg proguanil daily for 3 consecutive days; 9 to 10 kg: 187.5 mg atovaquone/75 mg proguanil daily for 3 consecutive days; 11 to 20 kg: 250 mg atovaquone/100 mg proguanil daily for 3 consecutive days; 21 to 30 kg: 500 mg atovaquone/200 mg proguanil daily for 3 consecutive days; 31 to 40 kg: 750 mg atovaquone/300 mg proguanil daily for 3 consecutive days; more than 40 kg: 1 g atovaquone/400 mg proguanil daily for 3 consecutive days.

General Advice

  • Administer with food or a milky drink.
  • Tablets may be crushed and mixed with condensed milk for children who have difficulty swallowing tablets.
  • Repeat dose if vomiting occurs within 1 h after dosing.
  • If dose is missed, take as soon as possible, then return to normal dosing. If dose is skipped, do not double next dose.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F).

Drug Interactions

Metoclopramide

May reduce the bioavailability of atovaquone, decreasing the therapeutic effect.

Rifamycins (eg, rifampin, rifabutin)

Because atovaquone concentrations may be reduced, coadministration is not recommended.

Tetracycline

May reduce plasma concentrations of atovaquone, decreasing the therapeutic effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache, anorexia, dizziness, abnormal dreams, insomnia (5% or more); psychotic events (eg, hallucinations), seizures (postmarketing).

Dermatologic

Pruritus (1% or more); angioedema, photosensitivity, urticaria, erythema multiforme, Stevens-Johnson syndrome (postmarketing).

EENT

Visual difficulties (2%).

GI

Abdominal pain, nausea, vomiting, diarrhea, oral ulcers (5% or more); gastritis (3%); dyspepsia (2%).

Respiratory

Cough (5% or more).

Miscellaneous

Asthenia (5% or more); anaphylaxis (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established for the treatment of malaria in children weighing less than 5 kg or for the prophylaxis of malaria in children weighing less than 11 kg.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Atovaquone/proguanil is contraindicated for malaria prophylaxis in patients with severe renal function impairment (Ccr less than 30 mL/min). May be used with caution for treatment of malaria in patients with severe renal function impairment if benefits of 3-day treatment regimen outweigh potential risks associated with increased drug exposure.

Diarrhea/Vomiting

Absorption of atovaquone/proguanil may be reduced. Consider use of antiemetic in patient who has frequent or persistent vomiting. Consider alternative antimalarial therapy in patients with severe or persistent diarrhea or vomiting.

Recrudescent

In the event of recrudescent P. falciparum infections after treatment or failure of chemoprophylaxis with atovaquone/proguanil, treat patients with a different blood schizonticide.

Severe malaria

Because atovaquone/proguanil has not been evaluated for treatment of cerebral malaria or other severe manifestations of complicated malaria, patients with these conditions are not candidates for oral therapy.

Overdosage

Symptoms

Epigastric discomfort, rash, vomiting.

Patient Information

  • Advise patient to take tablets with food or milky drink at about the same time each day.
  • Advise parents or caregivers that pediatric tablets may be crushed and mixed with condensed milk for children who have difficulty swallowing the tablets.
  • Instruct patient to repeat dose if vomiting occurs within 1 h of taking a dose.
  • Advise patient that if a dose is missed to take the dose as soon as remembered, then return to their normal dosing schedule. Advise patient that if it is nearing time for the next dose or if a dose is skipped to not double the next dose.
  • Instruct patient taking medication for prophylaxis that medication should be taken daily, beginning 1 to 2 days prior to arrival in malaria-infected area, while in the malaria-infected area, and for 7 days after leaving the malaria-infected area.
  • Advise patient that protective clothing, insect repellants, and bednets are important components of malaria prophylaxis.
  • Advise patient to notify health care provider of the following: severe or persistent vomiting or diarrhea, other bothersome side effects, or if therapy is prematurely discontinued for any reason.
  • Advise women taking folate supplements that the folate supplements can be continued while taking this medication.
  • Advise patient to seek health care and inform a doctor about possible contact with malaria if a febrile illness develops during or after return from a malaria-risk area.
  • Advise pregnant women that falciparum malaria carries a higher risk of death and serious complications in pregnant women than in the general population.
  • Advise pregnant women taking folate supplements to continue taking the supplement with atovaquone/proguanil.

Copyright © 2009 Wolters Kluwer Health.

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