Atovaquone-Proguanil 62.5/25 Tabs
It is used to treat or prevent malaria.
Drug Class
Antimalarial
Pharmacologic Class
Hydroxynaphthoquinone (Atovaquone) & Dihydrofolate Reductase Inhibitor (Proguanil)
Pregnancy Category
Category C
FDA Approved
Jul 2000
DEA Schedule
Not Controlled
Overview
What is this medicine?
Atovaquone-Proguanil is a combination medicine used to prevent malaria, a serious disease caused by parasites spread by mosquitoes. It works by killing the malaria parasites in your body. It's important to take this medicine exactly as prescribed, especially with food, to ensure it works effectively.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and adhere to the guidelines below.
General Administration Guidelines
Take your medication at the same time every day to establish a routine.
Always take your medication with food or a milky drink to help your body absorb it properly.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling better.
What to Do If You Vomit
If you vomit within 1 hour of taking your medication, take an additional dose to ensure you receive the full amount.
If you need to, you can crush the tablet and mix it with condensed milk. However, take the mixture immediately after preparing it, and do not store it for later use.
Preventing Malaria
If you are taking this medication to prevent malaria, start taking it before traveling to a high-risk area, as advised by your doctor.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom.
Keep all medications in a safe location, out of the reach of children and pets.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. Consult your pharmacist for guidance on the best disposal method, and consider participating in a drug take-back program in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember.
However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule.
Do not take two doses at the same time or take extra doses to make up for a missed one.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and adhere to the guidelines below.
General Administration Guidelines
Take your medication at the same time every day to establish a routine.
Always take your medication with food or a milky drink to help your body absorb it properly.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling better.
What to Do If You Vomit
If you vomit within 1 hour of taking your medication, take an additional dose to ensure you receive the full amount.
If you need to, you can crush the tablet and mix it with condensed milk. However, take the mixture immediately after preparing it, and do not store it for later use.
Preventing Malaria
If you are taking this medication to prevent malaria, start taking it before traveling to a high-risk area, as advised by your doctor.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom.
Keep all medications in a safe location, out of the reach of children and pets.
Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. Consult your pharmacist for guidance on the best disposal method, and consider participating in a drug take-back program in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember.
However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule.
Do not take two doses at the same time or take extra doses to make up for a missed one.
Lifestyle & Tips
- Take with food or a milky drink to help your body absorb the medicine better. If you vomit within 1 hour of taking a dose, take another dose.
- Continue taking the medicine daily for the entire prescribed duration, including for 7 days after leaving the malaria-risk area.
- Even with medication, take precautions to avoid mosquito bites (e.g., insect repellent, bed nets, protective clothing).
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
For malaria prophylaxis in adults weighing <40 kg: 1 tablet (62.5 mg Atovaquone / 25 mg Proguanil) orally once daily. For adults âĨ40 kg, the standard adult strength (250 mg/100 mg) is used.
Condition-Specific Dosing:
Malaria Prophylaxis (<40 kg):
1 tablet (62.5 mg Atovaquone / 25 mg Proguanil) orally once daily, starting 1-2 days before travel to endemic area, daily during travel, and for 7 days after leaving.
Pediatric Dosing
Neonatal:
Not established for infants <5 kg.
Infant:
For malaria prophylaxis in infants/children weighing 5-8 kg: 1/2 tablet (31.25 mg Atovaquone / 12.5 mg Proguanil) orally once daily.
Child:
For malaria prophylaxis in children weighing:
- 9-10 kg: 3/4 tablet (46.875 mg Atovaquone / 18.75 mg Proguanil) orally once daily.
- 11-20 kg: 1 tablet (62.5 mg Atovaquone / 25 mg Proguanil) orally once daily.
- 21-30 kg: 1.5 tablets (93.75 mg Atovaquone / 37.5 mg Proguanil) orally once daily.
- 31-40 kg: 2 tablets (125 mg Atovaquone / 50 mg Proguanil) orally once daily.
Adolescent:
For malaria prophylaxis in adolescents weighing >40 kg, the standard adult strength (250 mg/100 mg) is typically used. If 31-40 kg, 2 tablets (125 mg Atovaquone / 50 mg Proguanil) orally once daily.
Dose Adjustments
Renal Impairment:
Mild:
No dosage adjustment required (CrCl >50 mL/min).
Moderate:
No dosage adjustment required (CrCl 30-50 mL/min).
Severe:
Contraindicated for malaria treatment in patients with severe renal impairment (CrCl <30 mL/min). For prophylaxis, use with caution; consider alternative agents.
Dialysis:
Not recommended for patients on dialysis due to limited data and potential for accumulation of proguanil and its metabolites.
Hepatic Impairment:
Mild:
No dosage adjustment required.
Moderate:
No dosage adjustment required.
Severe:
No dosage adjustment required, but use with caution due to limited data.
Pharmacology
Mechanism of Action
Atovaquone selectively inhibits parasite mitochondrial electron transport at the cytochrome bc1 complex, leading to collapse of mitochondrial membrane potential and inhibition of nucleic acid synthesis. Proguanil, a prodrug, is metabolized to cycloguanil, which inhibits plasmodial dihydrofolate reductase, thereby disrupting deoxythymidylate synthesis and DNA replication. The combination acts synergistically to inhibit two different pathways in the parasite.
Pharmacokinetics
Absorption:
Bioavailability:
Atovaquone: ~23% (increased significantly with fatty meal); Proguanil: ~40-60%
Tmax:
Atovaquone: 2-8 hours; Proguanil: 3-6 hours
FoodEffect:
Atovaquone absorption is significantly increased (2-3 fold) when taken with food, especially fatty meals. Proguanil absorption is not significantly affected by food.
Distribution:
Vd:
Atovaquone: ~6.5 L/kg; Proguanil: ~25 L/kg
ProteinBinding:
Atovaquone: >99% (primarily to albumin); Proguanil: ~75%
CnssPenetration:
Limited
Elimination:
HalfLife:
Atovaquone: 2-3 days (48-72 hours); Proguanil: 12-21 hours (cycloguanil: 12-21 hours)
Clearance:
Not available
ExcretionRoute:
Atovaquone: Primarily fecal (>94%, largely unchanged); Proguanil: Renal (40-60%, with ~10% as cycloguanil)
Unchanged:
Atovaquone: >94% (feces); Proguanil: ~40% (urine)
Pharmacodynamics
OnsetOfAction:
Rapid, within hours of first dose for antimalarial activity.
PeakEffect:
Achieved with steady-state concentrations after several days of dosing.
DurationOfAction:
Provides protection for 24 hours with daily dosing; requires 7 days post-travel dosing due to atovaquone's long half-life and to eliminate residual parasites.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of a severe skin reaction (Stevens-Johnson syndrome), such as:
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Red or irritated eyes
+ Sores in the mouth, throat, nose, or eyes
Strange or odd dreams
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only have mild ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Headache
Cough
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Feeling dizzy, tired, or weak
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of a severe skin reaction (Stevens-Johnson syndrome), such as:
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Red or irritated eyes
+ Sores in the mouth, throat, nose, or eyes
Strange or odd dreams
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only have mild ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Headache
Cough
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Feeling dizzy, tired, or weak
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing)
- Severe stomach upset (persistent vomiting or diarrhea)
- Signs of liver problems (yellowing eyes/skin, dark urine, severe stomach pain)
- Unusual bleeding or bruising
- Signs of malaria despite prophylaxis (fever, chills, headache, muscle aches, fatigue)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have kidney problems or any history of kidney disease.
* If you are currently taking rifabutin or rifampin, as these medications may interact with this drug.
This list is not exhaustive, and it is crucial to disclose all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you have. Your doctor and pharmacist need this information to ensure safe treatment. Do not start, stop, or modify the dosage of any medication without first consulting your doctor to confirm that it is safe to do so in conjunction with this medication.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have kidney problems or any history of kidney disease.
* If you are currently taking rifabutin or rifampin, as these medications may interact with this drug.
This list is not exhaustive, and it is crucial to disclose all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health problems you have. Your doctor and pharmacist need this information to ensure safe treatment. Do not start, stop, or modify the dosage of any medication without first consulting your doctor to confirm that it is safe to do so in conjunction with this medication.
Precautions & Cautions
Important Warnings and Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Liver Problems
Liver damage has been associated with this drug, and in severe cases, it may lead to the need for a liver transplant. Discuss this risk with your doctor to understand the potential consequences.
Effectiveness and Gastrointestinal Issues
If you experience vomiting or diarrhea, the effectiveness of this medication may be reduced. Consult your doctor to determine the best course of action.
Pregnancy and Breastfeeding
If you are pregnant, planning to become pregnant, or breastfeeding, you must discuss the benefits and risks of this medication with your doctor to ensure the well-being of both you and your baby.
Malaria Prevention
In addition to taking this medication, it is crucial to implement other preventive measures to minimize the risk of malaria transmission. These measures include:
Using window screens and bed netting
Applying insect repellent (containing 10% to 35% DEET) to skin and clothing
Treating clothing and nets with permethrin spray
Avoiding the use of most insect repellents on children
* Reducing outdoor activities during evening and nighttime hours
If you develop a fever while in or after leaving a malaria-infested area, contact your doctor immediately.
Pregnancy and Travel to Malaria-Infested Areas
If you are pregnant and plan to travel to an area where malaria is prevalent, consult your doctor beforehand to discuss the potential risks and determine the best approach to protect your health.
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Liver Problems
Liver damage has been associated with this drug, and in severe cases, it may lead to the need for a liver transplant. Discuss this risk with your doctor to understand the potential consequences.
Effectiveness and Gastrointestinal Issues
If you experience vomiting or diarrhea, the effectiveness of this medication may be reduced. Consult your doctor to determine the best course of action.
Pregnancy and Breastfeeding
If you are pregnant, planning to become pregnant, or breastfeeding, you must discuss the benefits and risks of this medication with your doctor to ensure the well-being of both you and your baby.
Malaria Prevention
In addition to taking this medication, it is crucial to implement other preventive measures to minimize the risk of malaria transmission. These measures include:
Using window screens and bed netting
Applying insect repellent (containing 10% to 35% DEET) to skin and clothing
Treating clothing and nets with permethrin spray
Avoiding the use of most insect repellents on children
* Reducing outdoor activities during evening and nighttime hours
If you develop a fever while in or after leaving a malaria-infested area, contact your doctor immediately.
Pregnancy and Travel to Malaria-Infested Areas
If you are pregnant and plan to travel to an area where malaria is prevalent, consult your doctor beforehand to discuss the potential risks and determine the best approach to protect your health.
Overdose Information
Overdose Symptoms:
- No specific symptoms of overdose have been reported, but may include exaggerated side effects like nausea, vomiting, diarrhea, rash.
What to Do:
Seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment is supportive and symptomatic.
Drug Interactions
Major Interactions
- Rifampin/Rifabutin (decreased atovaquone levels)
- Metoclopramide (decreased atovaquone levels)
Moderate Interactions
- Tetracycline (decreased atovaquone levels)
- Warfarin (increased INR/bleeding risk)
- Indinavir (decreased indinavir levels)
- Efavirenz (decreased atovaquone levels)
- Ritonavir (decreased atovaquone levels)
Minor Interactions
- Antacids (potential for decreased absorption if taken concurrently)
Monitoring
Baseline Monitoring
Weight
Rationale: To determine appropriate pediatric dosing.
Timing: Before initiation of therapy.
Renal function (CrCl)
Rationale: To assess suitability for use, especially in severe impairment.
Timing: Before initiation, if renal impairment is suspected.
Routine Monitoring
Adherence to dosing regimen
Frequency: Daily during prophylaxis period
Target: Consistent daily intake with food
Action Threshold: Missed doses may reduce efficacy; advise patient to take as soon as remembered, but not double dose.
INR (if on warfarin)
Frequency: More frequently during co-administration and for a period after discontinuation
Target: Individualized therapeutic range
Action Threshold: Significant increase in INR; adjust warfarin dose as needed.
Symptom Monitoring
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Headache
- Dizziness
- Insomnia
- Rash
- Oral ulcers
- Hair loss (rare)
- Signs of severe malaria (e.g., fever, chills, severe headache, confusion, seizures, jaundice, dark urine) if prophylaxis fails
Special Patient Groups
Pregnancy
Category C. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited human data suggest no increased risk of major birth defects, but animal studies show some adverse effects. Consult with a healthcare provider and consider CDC guidelines for malaria prophylaxis in pregnancy.
Trimester-Specific Risks:
First Trimester:
Limited data, but generally considered acceptable if other options are not suitable or effective for the specific region.
Second Trimester:
Generally considered acceptable if indicated.
Third Trimester:
Generally considered acceptable if indicated.
Lactation
Atovaquone and proguanil are excreted into breast milk. The amount of atovaquone is low, but proguanil and its active metabolite cycloguanil are present in higher concentrations. While generally considered compatible with breastfeeding by some experts, the infant receives subtherapeutic doses for malaria prophylaxis. Monitor breastfed infants for potential adverse effects (e.g., diarrhea, rash). Use with caution, especially in infants with G6PD deficiency.
Infant Risk:
Low risk of adverse effects, but not sufficient for infant prophylaxis. Potential for G6PD deficiency in infant to be a concern with proguanil.
Pediatric Use
Dosing is weight-based and specific for prophylaxis. Not recommended for infants weighing less than 5 kg. Contraindicated for treatment of malaria in children with severe renal impairment (CrCl <30 mL/min).
Geriatric Use
No specific dosage adjustment required based on age alone. However, elderly patients are more likely to have decreased renal function, which may necessitate dose adjustment or avoidance in severe renal impairment. Monitor for adverse effects and drug interactions.
Clinical Information
Clinical Pearls
- Always take with food or a milky drink to maximize absorption and efficacy, especially for atovaquone.
- Complete the full 7-day post-travel course to ensure eradication of any remaining parasites.
- This strength (62.5/25 mg) is primarily for pediatric prophylaxis or for adults weighing less than 40 kg. Ensure correct strength is prescribed for the patient's weight.
- Patients should be advised that no antimalarial drug is 100% effective, and they should still take measures to prevent mosquito bites.
- Contraindicated for malaria treatment in patients with severe renal impairment (CrCl <30 mL/min) due to proguanil accumulation.
Alternative Therapies
- Doxycycline (for prophylaxis)
- Mefloquine (for prophylaxis)
- Chloroquine (for prophylaxis in sensitive areas)
- Primaquine (for prophylaxis, especially for P. vivax/ovale)
- Tafenoquine (for prophylaxis)
Cost & Coverage
Average Cost:
$150 - $300 per 30 tablets (62.5/25 mg)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (preferred brand or non-preferred brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it is a good idea to consult with your pharmacist. If you have any questions or concerns about this medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.