Atovaquone-Proguanil 250/100 Tabs
It is used to treat or prevent malaria.
Drug Class
Antimalarial
Pharmacologic Class
Atovaquone: Naphthoquinone; Proguanil: Dihydrofolate reductase inhibitor
Pregnancy Category
Category C
FDA Approved
Jun 2000
DEA Schedule
Not Controlled
Overview
What is this medicine?
Atovaquone-Proguanil is a medication used to prevent or treat malaria, a serious disease caused by parasites spread by mosquito bites. It works by killing the malaria parasites in your body. It's important to take this medication 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 follow the instructions closely.
General Instructions for All Uses:
Take your medication at the same time every day to establish a routine.
Take your medication with food or a milky drink to help your body absorb it.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
If you vomit within 1 hour of taking your medication, take an additional dose to ensure you receive the full amount. 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 directed 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 way to dispose of your medication. You may also want to check if there are drug take-back programs in your area.
What to Do If You Miss a Dose:
If you miss a dose, take it as soon as you remember.
If it is close to the time for your next dose, skip the missed dose and resume your regular schedule.
* Do not take two doses at the same time or take extra doses to make up for a missed dose.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely.
General Instructions for All Uses:
Take your medication at the same time every day to establish a routine.
Take your medication with food or a milky drink to help your body absorb it.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
If you vomit within 1 hour of taking your medication, take an additional dose to ensure you receive the full amount. 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 directed 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 way to dispose of your medication. You may also want to check if there are drug take-back programs in your area.
What to Do If You Miss a Dose:
If you miss a dose, take it as soon as you remember.
If it is close to the time for your next dose, skip the missed dose and resume your regular schedule.
* Do not take two doses at the same time or take extra doses to make up for a missed dose.
Lifestyle & Tips
- Always take this medication with food or a milky drink to help your body absorb it better.
- If you vomit within 1 hour of taking a dose, take another dose as soon as possible.
- Complete the full course of medication, even if you feel better, to ensure all parasites are killed.
- Continue to protect yourself from mosquito bites (e.g., use insect repellent, wear long sleeves/pants, sleep under mosquito nets) even while taking this medication.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Malaria Prophylaxis: 1 tablet (250 mg atovaquone/100 mg proguanil) orally once daily. Malaria Treatment: 4 tablets (1000 mg atovaquone/400 mg proguanil) orally once daily for 3 consecutive days.
Condition-Specific Dosing:
prophylaxis:
Start 1-2 days before entering endemic area, continue daily during stay, and for 7 days after leaving.
treatment:
Take with food or a milky drink.
Pediatric Dosing
Neonatal:
Not established (contraindicated for infants <5 kg).
Infant:
Not established (contraindicated for infants <5 kg).
Child:
Malaria Prophylaxis (weight-based): 5-8 kg: 1/2 pediatric tablet daily; 9-10 kg: 3/4 pediatric tablet daily; 11-20 kg: 1 pediatric tablet daily; 21-30 kg: 2 pediatric tablets daily; 31-40 kg: 3 pediatric tablets daily. Malaria Treatment (weight-based): 5-8 kg: 2 pediatric tablets daily for 3 days; 9-10 kg: 3 pediatric tablets daily for 3 days; 11-20 kg: 1 adult tablet daily for 3 days; 21-30 kg: 2 adult tablets daily for 3 days; 31-40 kg: 3 adult tablets daily for 3 days.
Adolescent:
If >40 kg, adult dosing applies.
Dose Adjustments
Renal Impairment:
Mild:
No adjustment needed.
Moderate:
No adjustment needed.
Severe:
Contraindicated for malaria prophylaxis in patients with CrCl <30 mL/min. Use with caution for treatment if benefits outweigh risks.
Dialysis:
Not recommended due to lack of data and high protein binding.
Hepatic Impairment:
Mild:
No adjustment needed.
Moderate:
No adjustment needed.
Severe:
Use with caution; monitor for adverse effects due to potential for increased proguanil exposure.
Pharmacology
Mechanism of Action
Atovaquone selectively inhibits parasite mitochondrial electron transport, disrupting pyrimidine synthesis. Proguanil is metabolized to cycloguanil, which inhibits parasite dihydrofolate reductase, disrupting DNA synthesis. The combination acts synergistically to inhibit two different pathways in the parasite, leading to antimalarial activity.
Pharmacokinetics
Absorption:
Bioavailability:
Atovaquone: Variable, significantly increased (2-3 fold) with food. Proguanil: Well absorbed (approx. 60%).
Tmax:
Atovaquone: 2-6 hours. Proguanil: 3-5 hours.
FoodEffect:
Atovaquone absorption is significantly enhanced when taken with food, especially a fatty meal.
Distribution:
Vd:
Atovaquone: Approximately 1.7 L/kg. Proguanil: Approximately 25 L/kg.
ProteinBinding:
Atovaquone: >99% (primarily to albumin). Proguanil: Approximately 75%.
CnssPenetration:
Limited for Atovaquone. Proguanil and its metabolite cycloguanil show some CNS penetration.
Elimination:
HalfLife:
Atovaquone: 2-3 days (48-72 hours). Proguanil: 12-21 hours. Cycloguanil: 12-21 hours.
Clearance:
Atovaquone: Primarily fecal. Proguanil: Renal and fecal.
ExcretionRoute:
Atovaquone: Primarily fecal. Proguanil: Renal (approx. 40-60%) and fecal (approx. 30%).
Unchanged:
Atovaquone: >94% in feces. Proguanil: Approximately 40% renally.
Pharmacodynamics
OnsetOfAction:
Rapid, typically within days for clinical effect.
PeakEffect:
Clinical efficacy is observed with sustained therapeutic concentrations.
DurationOfAction:
Daily dosing maintains therapeutic levels; half-lives support once-daily administration.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
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. Although many people may not experience any side effects or only minor 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:
Headache
Cough
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Feeling dizzy, tired, or weak
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
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. Although many people may not experience any side effects or only minor 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:
Headache
Cough
Diarrhea
Stomach pain
Upset stomach
Vomiting
Decreased appetite
Feeling dizzy, tired, or weak
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult 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 or persistent nausea, vomiting, or diarrhea (may indicate poor absorption or need for re-dosing)
- Severe skin rash or allergic reaction (hives, swelling of face/throat, difficulty breathing)
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Unusual bleeding or bruising
- Severe headache or dizziness
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, 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, to your doctor and pharmacist. This will help ensure that it is safe to take this medication in conjunction with your other medications and health conditions.
Remember, do not start, stop, or adjust the dosage of any medication without first consulting your doctor to confirm that it is safe to do so.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, 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, to your doctor and pharmacist. This will help ensure that it is safe to take this medication in conjunction with your other medications and health conditions.
Remember, do not start, stop, or adjust the dosage of any medication without first consulting your doctor to confirm that it is safe to do so.
Precautions & Cautions
Important Warnings and Precautions
When taking this medication, it is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are using this drug.
Liver Problems
Liver damage has been associated with this medication, 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, inform your doctor. You will need to discuss the benefits and risks of using this medication 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 when mosquitoes are most active
Fever and Malaria Symptoms
If you develop a fever while traveling in or after leaving a malaria-endemic area, contact your doctor immediately.
Pregnancy and Travel to Malaria-Endemic Areas
If you are pregnant and plan to travel to an area with a high risk of malaria transmission, consult your doctor to discuss the potential risks and determine the best approach to protect your health.
When taking this medication, it is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are using this drug.
Liver Problems
Liver damage has been associated with this medication, 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, inform your doctor. You will need to discuss the benefits and risks of using this medication 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 when mosquitoes are most active
Fever and Malaria Symptoms
If you develop a fever while traveling in or after leaving a malaria-endemic area, contact your doctor immediately.
Pregnancy and Travel to Malaria-Endemic Areas
If you are pregnant and plan to travel to an area with a high risk of malaria transmission, consult your doctor to discuss the potential risks and determine the best approach to protect your health.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Abdominal pain
- Headache
- Rash
- No specific symptoms of overdose have been reported in humans, but high doses could exacerbate side effects.
What to Do:
There is no specific antidote. Treatment should be symptomatic and supportive. Contact a poison control center immediately (e.g., 1-800-222-1222 in the US) or seek emergency medical attention.
Drug Interactions
Contraindicated Interactions
- Rifampin
- Rifabutin
Major Interactions
- Metoclopramide
- Tetracycline
- Warfarin
Moderate Interactions
- Etoposide
- Indinavir
Monitoring
Baseline Monitoring
Renal function (CrCl)
Rationale: To assess suitability for use, especially for prophylaxis in severe renal impairment.
Timing: Before initiation
Hepatic function (LFTs)
Rationale: To assess baseline liver status, especially in patients with severe hepatic impairment.
Timing: Before initiation
Routine Monitoring
Clinical response (resolution of malaria symptoms)
Frequency: Daily during treatment course
Target: Symptom resolution, negative parasite smears
Action Threshold: Persistent or worsening symptoms, parasitemia
Adverse effects (e.g., GI upset, rash)
Frequency: Daily during treatment, periodically during prophylaxis
Target: Absence or mild, tolerable side effects
Action Threshold: Severe or intolerable adverse effects requiring discontinuation
INR (if on warfarin)
Frequency: Regularly, especially upon initiation or discontinuation
Target: Therapeutic INR range
Action Threshold: INR outside target range
Symptom Monitoring
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Headache
- Rash
- Fever
- Jaundice
- Unusual bleeding or bruising
Special Patient Groups
Pregnancy
Generally not recommended for use during pregnancy unless the potential benefits outweigh the risks. Limited human data suggest no increased risk of major birth defects, but animal studies have shown some adverse effects. Proguanil is a folate antagonist, and folate supplementation is important if used.
Trimester-Specific Risks:
First Trimester:
Limited data; potential theoretical risk due to proguanil's folate antagonism. Folate supplementation is crucial.
Second Trimester:
Limited data; generally considered safer than first trimester if use is necessary.
Third Trimester:
Limited data; generally considered safer than first trimester if use is necessary.
Lactation
Use with caution. Proguanil is excreted into breast milk in clinically significant amounts. Atovaquone excretion into breast milk is limited. The infant's exposure to proguanil may lead to folate deficiency, especially in infants with G6PD deficiency or those receiving other folate antagonists.
Infant Risk:
Potential for adverse effects in the breastfed infant from proguanil (e.g., folate deficiency, methemoglobinemia in G6PD deficient infants). Monitor infant for adverse effects.
Pediatric Use
Dosing is weight-based. Contraindicated for malaria prophylaxis in infants weighing less than 5 kg. Safety and efficacy for treatment in infants weighing less than 5 kg have not been established.
Geriatric Use
No specific dose adjustment is required based on age alone. However, elderly patients may have reduced renal or hepatic function, which should be considered when prescribing and monitoring.
Clinical Information
Clinical Pearls
- Always instruct patients to take Atovaquone-Proguanil with food or a milky drink to maximize absorption and efficacy.
- If a patient vomits within 1 hour of taking a dose, they should take another full dose.
- This combination is not effective against hypnozoites of P. vivax or P. ovale and therefore does not prevent relapses from these species. A terminal prophylaxis with primaquine may be needed if exposure to these species is likely.
- Contraindicated for malaria prophylaxis in patients with severe renal impairment (creatinine clearance <30 mL/min).
- Advise patients to continue mosquito bite prevention measures even while taking the medication.
Alternative Therapies
- Mefloquine (for prophylaxis and treatment)
- Doxycycline (for prophylaxis and treatment)
- Chloroquine (where sensitive, for prophylaxis and treatment)
- Primaquine (for terminal prophylaxis of P. vivax/ovale, or as treatment for P. falciparum in specific cases)
- Artemether-Lumefantrine (for treatment)
Cost & Coverage
Average Cost:
$50 - $200+ per 30 tablets (generic)
Generic Available:
Yes
Insurance Coverage:
Often Tier 2 or Tier 3, depending on insurance plan and formulary.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't 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 reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.