Version July 2025
Malaria, prophylaxis: Oral: 1 tablet (atovaquone 250 mg/proguanil 100 mg per tablet) once daily; start 1 to 2 days prior to entering a malaria-endemic area, continue throughout the stay and for 7 days after returning (Ref).
Malaria, treatment: Oral: 4 tablets (atovaquone 250 mg/proguanil 100 mg per tablet) once daily for 3 days. Note: If used for P. vivax or P. ovale, use in combination with primaquine. If used for severe malaria (after completion of IV therapy), use full 3-day schedule (Ref).
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute:
Prophylaxis: Use is contraindicated.
Treatment: No dosage adjustment necessary; however, use with extreme caution and only if the benefits outweigh the risks.
Mild-to-moderate impairment: No dosage adjustment necessary.
Severe impairment; No dosage adjustment provided in manufacturer’s labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Atovaquone and proguanil: Pediatric drug information")
Dosage guidance:
Dosage form information: Tablets are available in two strengths (pediatric and adult tablets) and both are used in pediatric patients depending upon patient weight; use extra caution.
Malaria, prophylaxis: Note: Begin 1 to 2 days prior to entering a malaria-endemic area; continue throughout the stay and for 7 days after leaving area.
Infants, Children, and Adolescents (limited data available in patients weighing 5 to <11 kg):
Pediatric tablet (Atovaquone 62.5 mg/proguanil 25 mg per tablet):
5 to <8 kg: Oral: 1/2 pediatric tablet once daily (atovaquone 31.25 mg/proguanil 12.5 mg per dose) (Ref).
8 to <10 kg: Oral: 3/4 pediatric tablet once daily (atovaquone 46.88 mg/proguanil 18.75 mg per dose) (Ref).
10 to <20 kg: Oral: 1 pediatric tablet once daily (atovaquone 62.5 mg/proguanil 25 mg per dose) (Ref).
20 to <30 kg: Oral: 2 pediatric tablets once daily (atovaquone 125 mg/proguanil 50 mg per dose) (Ref).
30 to <40 kg: Oral: 3 pediatric tablets once daily (atovaquone 187.5 mg/proguanil 75 mg per dose) (Ref).
Adult tablet (Atovaquone 250 mg/proguanil 100 mg per tablet):
≥40 kg: Oral: 1 adult tablet once daily (atovaquone 250 mg/proguanil 100 mg per dose) (Ref).
Malaria, treatment: Note: Patients with Plasmodium vivax or Plasmodium ovale should receive concomitant therapy with an antimalarial agent active against Plasmodium liver hypnozoites (antirelapse treatment) (eg, primaquine). If used for severe malaria (after completion of IV therapy), use full 3-day schedule (Ref).
Infants, Children, and Adolescents:
Pediatric tablet (Atovaquone 62.5 mg/proguanil 25 mg per tablet):
5 to <8 kg: Oral: 2 pediatric tablets once daily for 3 days (atovaquone 125 mg/proguanil 50 mg per dose) (Ref).
8 to <10 kg: Oral: 3 pediatric tablets once daily for 3 days (atovaquone 187.5 mg/proguanil 75 mg per dose) (Ref).
Adult tablet (Atovaquone 250 mg/proguanil 100 mg per tablet):
10 to <20 kg: Oral: 1 adult tablet once daily for 3 days (atovaquone 250 mg/proguanil 100 mg per dose) (Ref).
20 to <30 kg: Oral: 2 adult tablets once daily for 3 days (atovaquone 500 mg/proguanil 200 mg per dose) (Ref).
30 to <40 kg: Oral: 3 adult tablets once daily for 3 days (atovaquone 750 mg/proguanil 300 mg per dose) (Ref).
≥40 kg: Oral: 4 adult tablets once daily for 3 days (atovaquone 1,000 mg/proguanil 400 mg per dose) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Pediatric patients weighing ≥5 kg: Oral:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment:
Malaria prophylaxis: Use is contraindicated.
Malaria treatment: No dosage adjustment necessary; however, use with caution and only if the benefits outweigh the risks.
Pediatric patients weighing ≥5 kg: Oral:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: No dosage adjustment provided in manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. The following adverse reactions were reported in patients being treated for malaria. When used for prophylaxis, reactions are similar to those seen with placebo.
>10%:
Gastrointestinal: Abdominal pain (17%), nausea (12%), vomiting (children: 10% to 13%; adults: 12%)
Hepatic: Increased serum ALT (27%; increased liver function test values typically normalized after ~ 4 weeks), increased serum AST (17%; increased liver function test values typically normalized after ~4 weeks)
1% to 10%:
Central nervous system: Headache (10%), dizziness (5%)
Dermatologic: Pruritus (children: 6%)
Gastrointestinal: Diarrhea (children: 6%; adults: 8%), anorexia (5%)
Neuromuscular & skeletal: Weakness (8%)
<1%, postmarketing, and/or case reports: Anaphylaxis (rare), anemia (rare), angioedema, cholestasis, erythema multiforme (rare), hallucination, hepatic failure (case report), hepatitis (rare), neutropenia, pancytopenia (with severe renal impairment), psychotic reaction (rare), seizure (rare), skin photosensitivity, skin rash, Stevens-Johnson syndrome (rare), stomatitis, urticaria, vasculitis (rare)
Hypersensitivity to atovaquone, proguanil, or any component of the formulation; prophylactic use in severe renal impairment (CrCl <30 mL/minute)
Concerns related to adverse events:
• Hepatic effects: Increased transaminase levels and hepatitis have been reported with prophylactic use; single case report of hepatic failure requiring transplantation documented. Monitor closely and use caution in patients with existing hepatic impairment. Elevations in AST/ALT may persist for up to 4 weeks following treatment (Looareesuwan, 1999).
Disease-related concerns:
• Diarrhea/vomiting: Absorption of atovaquone may be decreased in patients who have diarrhea or vomiting; monitor closely and consider use of an antiemetic. If severe, consider use of an alternative antimalarial.
• Malaria: Appropriate use: Not indicated for cerebral malaria or other severe manifestations of complicated malaria. Delayed cases of P. falciparum malaria may occur after stopping prophylaxis; travelers returning from endemic areas who develop febrile illnesses should be evaluated for malaria. Recrudescent infections or infections following prophylaxis with this agent should be treated with alternative agent(s).
• Renal impairment: Use with caution in patients with preexisting renal disease. May use with caution for treatment of malaria in patients with severe renal impairment (CrCl <30 mL/minute) if benefit outweighs risk. Contraindicated for prophylactic use in severe renal impairment due to the risk of pancytopenia in patients with severe renal impairment treated with proguanil.
Special populations:
• Obesity: Treatment failures have been reported in patients >100 kg (case reports); follow-up monitoring is recommended (Durand, 2008).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Malarone: Atovaquone 250 mg and proguanil hydrochloride 100 mg
Generic: Atovaquone 250 mg and proguanil hydrochloride 100 mg
Tablet, Oral, (pediatric):
Malarone: Atovaquone 62.5 mg and proguanil hydrochloride 25 mg
Generic: Atovaquone 62.5 mg and proguanil hydrochloride 25 mg
Yes
Tablets (Atovaquone-Proguanil HCl Oral)
62.5-25 mg (per each): $2.54 - $2.69
250-100 mg (per each): $6.86 - $7.26
Tablets (Malarone Oral)
62.5-25 mg (per each): $2.99
250-100 mg (per each): $8.24
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Malarone: Atovaquone 250 mg and proguanil hydrochloride 100 mg
Generic: Atovaquone 250 mg and proguanil hydrochloride 100 mg
Tablet, Oral, (pediatric):
Malarone Pediatric: Atovaquone 62.5 mg and proguanil hydrochloride 25 mg
Administer with food or milk-based drink at the same time each day. If vomiting occurs within 1 hour of administration, repeat the dose. For patients who have difficulty swallowing tablets, tablets may be crushed and mixed with condensed milk just prior to administration.
Oral: Administer with food or milk-based drink at the same time each day. For patients who have difficulty swallowing tablets, tablets may be crushed and mixed with a small amount of something sweet (eg, condensed milk, chocolate syrup, chocolate spread) just prior to administration (Ref).
Vomiting: If vomiting occurs within 1 hour of administration, repeat the dose.
Malaria, prophylaxis: Prophylaxis of Plasmodium falciparum malaria, including areas where chloroquine resistance has been reported. Note: CDC also recommends atovaquone/proguanil as prophylaxis for other Plasmodium species (CDC Yellow Book 2024).
Malaria, treatment: Treatment of acute, uncomplicated P. falciparum malaria. Note: Guidelines also recommend atovaquone/proguanil for nonfalciparum malaria and as oral treatment for severe malaria after completion of IV therapy or as interim therapy pending IV therapy (CDC 2023).
Malarone may be confused with mefloquine
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Amodiaquine: May increase adverse/toxic effects of Atovaquone. Specifically, the risk for extrapyramidal side effects may be increased. Risk C: Monitor
Amodiaquine: May increase adverse/toxic effects of Proguanil. Specifically, the risk for extrapyramidal side effects may be increased. Risk C: Monitor
Antihepaciviral Combination Products: May decrease serum concentration of Proguanil. Risk C: Monitor
Artemether and Lumefantrine: Antimalarial Agents may increase adverse/toxic effects of Artemether and Lumefantrine. Management: Artemether/lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. If combined, monitor patients for increased toxicities of both agents, including QTc interval prolongation. Risk D: Consider Therapy Modification
CYP2C19 Inhibitors (Moderate): May increase serum concentration of Proguanil. CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Proguanil. Risk C: Monitor
CYP2C19 Inhibitors (Strong): May increase serum concentration of Proguanil. CYP2C19 Inhibitors (Strong) may decrease active metabolite exposure of Proguanil. Risk C: Monitor
Dapsone (Systemic): Antimalarial Agents may increase adverse/toxic effects of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may increase adverse/toxic effects of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider Therapy Modification
Dapsone (Topical): Antimalarial Agents may increase adverse/toxic effects of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Consider avoidance of this combination when possible. If combined, closely monitor for signs/symptoms of hemolytic reactions. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider Therapy Modification
Efavirenz: May decrease serum concentration of Atovaquone. Management: Consider alternatives to the use of atovaquone with efavirenz when possible. If this combination must be used, monitor for evidence of reduced atovaquone clinical effectiveness. Risk D: Consider Therapy Modification
Ethinyl Estradiol-Containing Products: May decrease active metabolite exposure of Proguanil. Risk C: Monitor
Etoposide Phosphate: Atovaquone may increase serum concentration of Etoposide Phosphate. Management: Consider separating the administration of atovaquone and etoposide by at least 1 to 2 days. Risk C: Monitor
Etoposide: Atovaquone may increase serum concentration of Etoposide. Management: Consider separating the administration of atovaquone and etoposide by at least 1 to 2 days. Risk C: Monitor
Indinavir: Atovaquone may decrease serum concentration of Indinavir. Risk C: Monitor
Ketoconazole (Systemic): May increase serum concentration of Atovaquone. Risk C: Monitor
Metoclopramide: May decrease serum concentration of Atovaquone. Management: Consider alternatives to metoclopramide when possible; atovaquone should only be used with metoclopramide if no other antiemetics are available. Risk D: Consider Therapy Modification
Nirmatrelvir and Ritonavir: May decrease serum concentration of Atovaquone. Risk C: Monitor
Nirmatrelvir and Ritonavir: May decrease serum concentration of Proguanil. Risk C: Monitor
Pyrimethamine: May increase adverse/toxic effects of Proguanil. Risk C: Monitor
Rifabutin: Atovaquone may decrease serum concentration of Rifabutin. Rifabutin may decrease serum concentration of Atovaquone. Risk X: Avoid
RifAMPin: Atovaquone may increase serum concentration of RifAMPin. RifAMPin may decrease serum concentration of Atovaquone. Risk X: Avoid
Ritonavir: May decrease serum concentration of Atovaquone. Risk C: Monitor
Ritonavir: May decrease serum concentration of Proguanil. Risk C: Monitor
Tetracycline (Systemic): May decrease serum concentration of Atovaquone. Risk C: Monitor
Typhoid Vaccine: Proguanil may decrease therapeutic effects of Typhoid Vaccine. This applies only to the oral (live) typhoid vaccine. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with proguanil. When possible, proguanil should not be started within 10 days of the last vaccine dose. Risk D: Consider Therapy Modification
Vitamin K Antagonists: Proguanil may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Atovaquone taken with dietary fat significantly increases the rate and extent of absorption; AUC is increased 2-3 times and Cmax is increased 5 times as compared to administration during a fasted state. Management: Administer with food or milk-based drink at the same time each day.
Patients who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, precautions should be taken to avoid mosquito bites and effective prophylactic medications should be used. Medications considered acceptable for the prophylaxis of malaria during pregnancy may be used in patients trying to conceive. Atovaquone/proguanil is not recommended for use in pregnant patients (CDC 2023; CDC Yellow Book 2024).
Outcome data following maternal use of atovaquone and proguanil during pregnancy are limited (Andrejko 2019; Gutman 2019; Mayer 2018).
The pharmacokinetics of atovaquone and proguanil may be altered during pregnancy (Burger 2016).
Malaria infection during pregnancy may be more severe than in nonpregnant people and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant patients are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant patients should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2023; CDC Yellow Book 2024).
Due to limited data, atovaquone/proguanil is not preferred for use during pregnancy. However, atovaquone/proguanil may be used as an alternative treatment of malaria caused by chloroquine-resistant P. falciparum in pregnant patients when other treatment options are not available or not being tolerated; consult current CDC guidelines (CDC 2023).
Proguanil is present in breast milk; excretion of atovaquone is not known.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Other sources note that this combination is not recommended if breastfeeding infants <5 kg (safety data are limited concerning therapeutic use in infants <5 kg) (Boggild 2007; CDC Yellow Book 2024).
Must be taken with food or milk-based drink.
Liver and renal function; closely monitor response to treatment in patients with vomiting or diarrhea and in patients >100 kg (Durand, 2008)
Atovaquone: Selectively inhibits parasite mitochondrial electron transport.
Proguanil: The metabolite cycloguanil inhibits dihydrofolate reductase, disrupting deoxythymidylate synthesis. Together, atovaquone/cycloguanil affect the erythrocytic and exoerythrocytic stages of development.
Absorption:
Atovaquone: The rate and extent of absorption is increased when administered with dietary fat.
Proguanil: Extensive.
Distribution: Vd/F (following oral administration):
Atovaquone: Children and Adults: ~8.8 L/kg.
Proguanil: Children >15 years and Adults and 31 to 110 kg: 1,617 to 2,502 L; Pediatric patients ≤15 years and 11 to 56 kg: 462 to 966 L; concentrated in erythrocytes.
Protein binding:
Atovaquone: >99%.
Proguanil: 75%.
Metabolism: Proguanil: Hepatic to active metabolites, cycloguanil (via CYP2C19) and 4-chlorophenylbiguanide.
Bioavailability: Atovaquone/proguanil: 23% when administered with food.
Half-life elimination:
Atovaquone: 2-3 days (adults), 1-2 days (children).
Proguanil: 12-21 hours.
Excretion:
Atovaquone: Feces (>94% as unchanged drug); urine (<0.6%).
Proguanil: Urine (40% to 60%).
Altered kidney function: In patients with moderate renal impairment (CrCl 30-50 mL/minute), mean oral clearance for proguanil was reduced by ~35% compared with patients with normal renal function CrCl >80 mL/minute). In patients with severe renal impairment (CrCl <30 mL/minute), atovaquone Cmax and AUC are reduced, but the elimination half-lives for proguanil and cycloguanil are prolonged, with corresponding increases in AUC, resulting in the potential of drug accumulation and toxicity with repeated dosing.
Hepatic function impairment: Atovaquone elimination half-life was increased in patients with moderate hepatic impairment. Proguanil AUC, Cmax, and elimination half-life were increased and cycloguanil (metabolite) AUC and Cmax were decreased and elimination half-life was increased in patients with mild hepatic impairment. Proguanil AUC and Cmax were increased in patients with moderate hepatic impairment. The pharmacokinetics of atovaquone, proguanil, and cycloguanil have not been studied in patients with severe hepatic impairment.
Older adult: AUC was increased, Tmax was longer, and elimination half-life was longer in elderly subjects (~15 hours) compared to younger subjects (~8 hours).
