Malarone 62.5/25 Tablets
It is used to treat or prevent malaria.
Drug Class
Antimalarial
Pharmacologic Class
Hydroxynaphthoquinone; Biguanide, Dihydrofolate Reductase Inhibitor
Pregnancy Category
C
FDA Approved
Jun 1999
DEA Schedule
Not Controlled
Overview
What is this medicine?
Malarone is a medication used to prevent and treat malaria, a serious disease caused by parasites spread through mosquito bites. It contains two active ingredients, atovaquone and proguanil, which work together to kill the malaria parasites.
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
Take your medication at the same time every day.
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 to feel well.
If you vomit within 1 hour of taking your medication, take an additional dose.
If you need to, you can crush the tablet and mix it with condensed milk. Take the dose immediately after mixing, and do not store the mixture for future 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 place, 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. Check with your pharmacist for guidance on the best way to dispose of medications. You may also want to check if there are any 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 return to your regular schedule.
* Do not take two doses at the same time or take extra doses.
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
Take your medication at the same time every day.
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 to feel well.
If you vomit within 1 hour of taking your medication, take an additional dose.
If you need to, you can crush the tablet and mix it with condensed milk. Take the dose immediately after mixing, and do not store the mixture for future 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 place, 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. Check with your pharmacist for guidance on the best way to dispose of medications. You may also want to check if there are any 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 return to your regular schedule.
* Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take Malarone with food or a milky drink to help your body absorb the medicine better and reduce stomach upset.
- If you vomit within 1 hour of taking a dose, take another dose. If you vomit more than 1 hour after a dose, do not take another dose, but continue with your next scheduled dose.
- For malaria prevention, start taking the medicine 1 or 2 days before entering a malaria-risk area, continue taking it every day while in the area, and for 7 days after leaving the area.
- For malaria treatment, take the medicine once a day for 3 days.
- Even with medication, continue to protect yourself from mosquito bites by using insect repellent, wearing long sleeves and pants, and sleeping under mosquito nets.
- Complete the full course of medication, even if you feel better, to ensure all parasites are eliminated.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
For prophylaxis in adults weighing <40 kg: 1 tablet (62.5 mg atovaquone / 25 mg proguanil HCl) once daily. For treatment in adults weighing <40 kg: Dosing is weight-based, similar to pediatric treatment. For adults >=40 kg, the 250/100 mg tablet is typically used for both prophylaxis and treatment.
Condition-Specific Dosing:
Prophylaxis (<40 kg):
1 tablet (62.5/25 mg) once daily, starting 1-2 days before travel, daily during travel, and for 7 days after leaving endemic area.
Treatment (<40 kg):
Weight-based dosing, typically 2-8 tablets (62.5/25 mg) once daily for 3 days, depending on weight. (e.g., 31-40 kg: 8 tablets once daily for 3 days).
Pediatric Dosing
Neonatal:
Not established (contraindicated in infants <5 kg)
Infant:
Not established for infants <5 kg. For infants 5-8 kg (treatment): 2 tablets (62.5/25 mg) once daily for 3 days.
Child:
Prophylaxis (11-20 kg): 1 tablet (62.5/25 mg) once daily. Prophylaxis (21-30 kg): 1.5 tablets (62.5/25 mg) once daily. Prophylaxis (31-40 kg): 2 tablets (62.5/25 mg) once daily. Treatment (9-10 kg): 3 tablets (62.5/25 mg) once daily for 3 days. Treatment (11-20 kg): 4 tablets (62.5/25 mg) once daily for 3 days. Treatment (21-30 kg): 6 tablets (62.5/25 mg) once daily for 3 days. Treatment (31-40 kg): 8 tablets (62.5/25 mg) once daily for 3 days.
Adolescent:
For adolescents weighing <40 kg, follow child dosing. For adolescents >=40 kg, the adult 250/100 mg tablet is typically used.
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
Use with caution. For prophylaxis, consider alternative agents if CrCl 30-50 mL/min. For treatment, no specific adjustment but monitor closely.
Severe:
Contraindicated for prophylaxis in patients with CrCl <30 mL/min. Not recommended for treatment in patients with CrCl <30 mL/min.
Dialysis:
Not recommended for patients on dialysis due to limited data and potential for accumulation of proguanil and its metabolites.
Hepatic Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
Use with caution. Monitor for adverse effects. No specific dose adjustment recommendations available.
Pharmacology
Mechanism of Action
Malarone is a fixed-dose combination of atovaquone and proguanil HCl, which act synergistically against Plasmodium falciparum. Atovaquone, a hydroxynaphthoquinone, selectively inhibits parasite mitochondrial electron transport at the cytochrome bc1 complex, leading to the collapse of mitochondrial membrane potential and inhibition of nucleic acid synthesis. Proguanil HCl, a biguanide, is metabolized to cycloguanil, which inhibits plasmodial dihydrofolate reductase (DHFR). Inhibition of DHFR disrupts folate metabolism, thereby inhibiting DNA synthesis and cell replication in the parasite. This dual mechanism targets different pathways, reducing the likelihood of resistance development.
Pharmacokinetics
Absorption:
Bioavailability:
Atovaquone: ~23% (increased significantly with food); Proguanil: Well absorbed (absolute bioavailability not precisely quantified).
Tmax:
Atovaquone: 2-5 hours; Proguanil: 3-6 hours.
FoodEffect:
Atovaquone absorption is significantly increased (2-3 fold) when taken with food, especially fatty food. Proguanil absorption is not significantly affected by food.
Distribution:
Vd:
Atovaquone: ~0.6 L/kg; Proguanil: ~25 L/kg.
ProteinBinding:
Atovaquone: >99% (primarily to albumin); Proguanil: ~75%.
CnssPenetration:
Limited for both atovaquone and proguanil/cycloguanil.
Elimination:
HalfLife:
Atovaquone: 62-107 hours (2-3 days); Proguanil: 12-21 hours; Cycloguanil: 12-16 hours.
Clearance:
Not readily available as a single rate, but primarily via excretion.
ExcretionRoute:
Atovaquone: Primarily fecal (>94% unchanged); Proguanil: Renal (40-60% unchanged, 10% as cycloguanil), also fecal.
Unchanged:
Atovaquone: >94% (feces); Proguanil: 40-60% (urine).
Pharmacodynamics
OnsetOfAction:
Rapid, typically within hours of first dose.
PeakEffect:
Peak plasma concentrations reached within 2-6 hours.
DurationOfAction:
Daily dosing maintains therapeutic levels due to half-lives.
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 minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, 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, 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.
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 minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, 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, 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 nausea or vomiting (especially if unable to keep down doses)
- Severe diarrhea
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Unusual bleeding or bruising
- Severe allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing)
- Persistent or worsening headache
- Unusual fatigue or weakness
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 discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your existing treatments and health conditions.
Remember, do not start, stop, or adjust the dosage of any medication without first consulting your doctor to ensure your safety and the effectiveness of your treatment plan.
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 discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your existing treatments and health conditions.
Remember, do not start, stop, or adjust the dosage of any medication without first consulting your doctor to ensure your safety and the effectiveness of your treatment plan.
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 Damage Risk
Liver problems, which can be severe, have been associated with this medication. In rare cases, liver transplantation may be required. 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, plan to become pregnant, or are breastfeeding, inform your doctor. A discussion about the benefits and risks of this medication to both you and your baby is necessary to ensure safe use.
Malaria Prevention
To effectively prevent malaria, use this medication in conjunction with other preventive measures, including:
- 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
Seek Medical Attention for Fever
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 with malaria, consult your doctor beforehand to discuss the associated risks and determine the best approach for your protection.
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 Damage Risk
Liver problems, which can be severe, have been associated with this medication. In rare cases, liver transplantation may be required. 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, plan to become pregnant, or are breastfeeding, inform your doctor. A discussion about the benefits and risks of this medication to both you and your baby is necessary to ensure safe use.
Malaria Prevention
To effectively prevent malaria, use this medication in conjunction with other preventive measures, including:
- 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
Seek Medical Attention for Fever
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 with malaria, consult your doctor beforehand to discuss the associated risks and determine the best approach for your protection.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Abdominal pain
- Diarrhea
- Rash
What to Do:
Seek immediate medical attention or call a Poison Control Center (1-800-222-1222). Treatment is generally supportive and symptomatic. There is no specific antidote.
Drug Interactions
Contraindicated Interactions
- Rifampin
- Rifabutin
Major Interactions
- Metoclopramide
- Tetracycline
- Warfarin
Moderate Interactions
- Indinavir
- Etoposide
Monitoring
Baseline Monitoring
Renal function (CrCl)
Rationale: To assess appropriate dosing and contraindications, especially in patients with pre-existing renal impairment.
Timing: Prior to initiation, particularly if renal impairment is suspected.
Hepatic function (LFTs)
Rationale: To assess baseline liver status, especially in patients with pre-existing hepatic impairment, though no specific dose adjustment is recommended for mild-moderate impairment.
Timing: Prior to initiation, if hepatic impairment is suspected.
Routine Monitoring
INR (International Normalized Ratio)
Frequency: Regularly, especially upon initiation or discontinuation of Malarone, and with dose changes.
Target: Therapeutic range for underlying condition.
Action Threshold: Significant deviation from target range; adjust warfarin dose as needed.
Clinical response to treatment/prophylaxis
Frequency: Daily during treatment; ongoing during prophylaxis.
Target: Resolution of malaria symptoms; absence of malaria infection.
Action Threshold: Lack of clinical improvement or development of new symptoms; consider alternative therapy or re-evaluation.
Adverse effects monitoring
Frequency: Regularly throughout therapy.
Target: Absence of severe or intolerable side effects.
Action Threshold: Development of severe nausea, vomiting, diarrhea, abdominal pain, headache, rash, or other significant adverse events; consider symptomatic treatment or discontinuation.
Symptom Monitoring
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Headache
- Dizziness
- Insomnia
- Rash
- Oral ulcers
- Hair loss (rare)
Special Patient Groups
Pregnancy
Category C. Malarone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited human data are available. Animal studies have shown some evidence of developmental toxicity at high doses.
Trimester-Specific Risks:
First Trimester:
Limited data. Use only if clearly needed.
Second Trimester:
Limited data. Use only if clearly needed.
Third Trimester:
Limited data. Use only if clearly needed.
Lactation
L3 (Moderate risk). Atovaquone and proguanil (and its active metabolite cycloguanil) are excreted into human breast milk. The amount of drug transferred to the infant is small, but potential risks to the infant are unknown. Weigh the benefits of breastfeeding against the potential risks to the infant. Consider alternative antimalarials if possible, or monitor the infant for adverse effects.
Infant Risk:
Potential for infant exposure and unknown effects. Risk of methemoglobinemia in G6PD deficient infants (theoretical for proguanil). Monitor for rash, diarrhea, or other adverse effects.
Pediatric Use
Approved for children weighing 5 kg or more. Dosing is weight-based. Contraindicated for prophylaxis in infants weighing less than 11 kg due to the fixed-dose combination. For treatment, it can be used in children weighing 5 kg or more.
Geriatric Use
No specific dose adjustment is required based on age alone. However, geriatric patients are more likely to have decreased renal function, which may necessitate dose adjustment or avoidance in severe renal impairment. Monitor renal function.
Clinical Information
Clinical Pearls
- Always take Malarone with food or a milky drink to maximize absorption and minimize gastrointestinal side effects.
- Malarone is effective against drug-resistant Plasmodium falciparum but is not effective against the hypnozoite liver stages of P. vivax or P. ovale, so it does not prevent relapses from these species.
- It is a good option for short-term travel to malaria-endemic areas due to its short post-travel dosing requirement (7 days).
- Patients should be advised to seek medical attention if they develop fever or flu-like symptoms during or after travel, even if they have taken Malarone for prophylaxis.
- Ensure patients understand the specific dosing regimen (daily for prophylaxis, 3 days for treatment) and the importance of adherence.
Alternative Therapies
- Mefloquine (Lariam)
- Doxycycline
- Chloroquine (where resistance is not an issue)
- Hydroxychloroquine
- Primaquine (for P. vivax/ovale radical cure or terminal prophylaxis)
- Tafenoquine (Arakoda, Krintafel - for prophylaxis or radical cure)
- Artemisinin-based combination therapies (ACTs) for treatment (e.g., Artemether/Lumefantrine, Dihydroartemisinin/Piperaquine)
Cost & Coverage
Average Cost:
Varies widely, typically $100-$300+ per 30 tablets (62.5/25 mg)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (preferred or non-preferred brand/generic), may require prior authorization for travel prophylaxis.
General Drug Facts
If your symptoms or health issues persist or worsen, it's 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 be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to 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 details about the medication, including the amount taken and the time it happened, to help healthcare professionals provide the best possible care.