Malarone 250/100 Tablets
It is used to treat or prevent malaria.
Drug Class
Antimalarial
Pharmacologic Class
Hydroxynaphthoquinone (Atovaquone); Dihydrofolate Reductase Inhibitor, Prodrug (Proguanil)
Pregnancy Category
Category C
FDA Approved
Jul 2000
DEA Schedule
Not Controlled
Overview
What is this medicine?
Malarone is a combination medicine used to prevent and treat malaria, a serious disease caused by parasites spread through mosquito bites. It works by killing the malaria parasites in your body.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most out of your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
For all uses of this medication:
+ Take your dose 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 prescribed by your doctor or healthcare provider, even if you start to feel better.
+ 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. However, take the dose immediately after mixing and do not store it for later use.
Malaria Prevention: 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
To keep your medication safe and effective:
Store your medication at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure 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.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to explore drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take the missed dose as soon as you remember.
If it's 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 one.
To ensure you get the most out of your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
For all uses of this medication:
+ Take your dose 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 prescribed by your doctor or healthcare provider, even if you start to feel better.
+ 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. However, take the dose immediately after mixing and do not store it for later use.
Malaria Prevention: 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
To keep your medication safe and effective:
Store your medication at room temperature in a dry place, away from the bathroom.
Keep all medications in a secure 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.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to explore drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take the missed dose as soon as you remember.
If it's 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 one.
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 as soon as possible. If vomiting continues, consult a doctor.
- Continue taking the medicine for the full prescribed duration, even if you feel better, to ensure complete eradication of the parasites.
- For prophylaxis, start taking the medicine 1-2 days before entering a malaria-risk area, take it daily while in the area, and continue for 7 days after leaving the area.
- Use other protective measures against mosquito bites (e.g., insect repellent, bed nets, protective clothing).
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Prophylaxis: 1 tablet (250 mg atovaquone/100 mg proguanil) orally once daily. Treatment: 4 tablets (1000 mg atovaquone/400 mg proguanil) orally once daily for 3 days.
Condition-Specific Dosing:
prophylaxisDuration:
Start 1-2 days before travel, daily during travel, and for 7 days after leaving endemic area.
treatmentDuration:
3 days
Pediatric Dosing
Neonatal:
Not established (contraindicated in infants <5 kg for treatment, <11 kg for prophylaxis)
Infant:
Treatment (5-8 kg): 2 pediatric tablets (125 mg atovaquone/50 mg proguanil) once daily for 3 days. Prophylaxis (11-20 kg): 1 pediatric tablet (62.5 mg atovaquone/25 mg proguanil) once daily.
Child:
Prophylaxis (21-30 kg): 2 pediatric tablets once daily. Prophylaxis (31-40 kg): 3 pediatric tablets once daily. Treatment (9-10 kg): 3 pediatric tablets once daily for 3 days. Treatment (11-20 kg): 1 adult tablet once daily for 3 days. Treatment (21-30 kg): 2 adult tablets once daily for 3 days. Treatment (31-40 kg): 3 adult tablets once daily for 3 days.
Adolescent:
Prophylaxis (>40 kg): 1 adult tablet once daily. Treatment (>40 kg): 4 adult tablets once daily for 3 days.
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment for treatment. For prophylaxis, use with caution.
Moderate:
No dose adjustment for treatment. For prophylaxis, use with caution.
Severe:
Prophylaxis: Contraindicated (CrCl < 30 mL/min). Treatment: Use with caution (CrCl < 30 mL/min), monitor for adverse effects.
Dialysis:
Not recommended due to lack of data and high protein binding of atovaquone.
Hepatic Impairment:
Mild:
No dose adjustment.
Moderate:
No dose adjustment.
Severe:
No data available; use with caution.
Pharmacology
Mechanism of Action
Atovaquone is a hydroxynaphthoquinone that selectively inhibits the Plasmodium falciparum electron transport chain at the cytochrome bc1 complex, disrupting mitochondrial function and pyrimidine biosynthesis. Proguanil is a prodrug that is metabolized to cycloguanil, a dihydrofolate reductase inhibitor. Cycloguanil inhibits parasitic DNA synthesis and replication by interfering with the folate metabolism pathway, which is essential for the synthesis of purines and pyrimidines.
Pharmacokinetics
Absorption:
Bioavailability:
Atovaquone: ~23% (increased by fatty meal); Proguanil: ~50%
Tmax:
Atovaquone: 1-8 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: 0.6 L/kg; Proguanil: 42 L/kg
ProteinBinding:
Atovaquone: >99%; Proguanil: 75%
CnssPenetration:
Limited
Elimination:
HalfLife:
Atovaquone: 2-3 days (adults); Proguanil: 12-21 hours; Cycloguanil: 12-21 hours
Clearance:
Not available
ExcretionRoute:
Atovaquone: Primarily fecal (>94% unchanged); Proguanil: Renal (40-60% unchanged proguanil, 10% cycloguanil)
Unchanged:
Atovaquone: >94% (feces); Proguanil: 40-60% (urine)
Pharmacodynamics
OnsetOfAction:
Rapid (within hours for antimalarial activity)
PeakEffect:
Not specifically defined for antimalarial effect, but related to peak plasma concentrations of active compounds.
DurationOfAction:
Sustained antimalarial activity due to long half-life of atovaquone and cycloguanil.
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
Most people taking this medication will not experience severe side effects. However, some may encounter mild or moderate side effects. If you experience any of the following symptoms, contact your doctor if they bother you or do not go away:
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 not mentioned here. 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
Most people taking this medication will not experience severe side effects. However, some may encounter mild or moderate side effects. If you experience any of the following symptoms, contact your doctor if they bother you or do not go away:
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 not mentioned here. 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 allergic reaction (rash, itching/swelling, severe dizziness, trouble breathing)
- Severe stomach pain, persistent nausea/vomiting, or diarrhea
- Yellowing of skin or eyes (jaundice)
- Unusual bleeding or bruising
- Signs of treatment failure (e.g., persistent fever, chills, body aches after starting treatment for malaria)
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 symptoms you experienced.
If you have kidney problems or any 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, before starting, stopping, or changing the dose of any medication, you must consult with your doctor to avoid potential interactions or complications.
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 symptoms you experienced.
If you have kidney problems or any 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, before starting, stopping, or changing the dose of any medication, you must consult with your doctor to avoid potential interactions or complications.
Precautions & Cautions
Important Warnings and Cautions
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
This medication can cause liver problems, which in rare cases can be severe and may require 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 if you have any concerns about the impact of these symptoms on the medication's efficacy.
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 best possible outcome for you and your baby.
Malaria Prevention
To effectively prevent malaria, it is crucial to 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
- Minimizing outdoor activities during evening and nighttime hours when mosquitoes are most active
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 where malaria is present, consult your doctor beforehand to discuss the potential risks and necessary 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
This medication can cause liver problems, which in rare cases can be severe and may require 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 if you have any concerns about the impact of these symptoms on the medication's efficacy.
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 best possible outcome for you and your baby.
Malaria Prevention
To effectively prevent malaria, it is crucial to 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
- Minimizing outdoor activities during evening and nighttime hours when mosquitoes are most active
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 where malaria is present, consult your doctor beforehand to discuss the potential risks and necessary precautions.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Abdominal pain
- Diarrhea
- Headache
- Dizziness
- Rash
What to Do:
There is no specific antidote. Treatment is symptomatic and supportive. Call 1-800-222-1222 (Poison Control) or seek immediate medical attention.
Drug Interactions
Contraindicated Interactions
- Rifampin (significant decrease in atovaquone concentrations, leading to loss of efficacy)
- Rifabutin (significant decrease in atovaquone concentrations, leading to loss of efficacy)
Major Interactions
- Tetracycline (decreases atovaquone plasma concentrations)
- Metoclopramide (decreases atovaquone plasma concentrations)
- Warfarin (may increase INR, requiring close monitoring)
- Indinavir (decreases indinavir plasma concentrations)
- Etoposide (atovaquone may increase etoposide exposure)
Moderate Interactions
- Antacids (may reduce atovaquone absorption if taken concurrently, separate administration)
- Other highly protein-bound drugs (theoretical potential for displacement, but not clinically significant for most)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Renal function (CrCl)
Rationale: Proguanil is renally eliminated; contraindicated for prophylaxis in severe renal impairment.
Timing: Before initiation, especially if renal impairment is suspected.
Liver function tests (LFTs)
Rationale: Both drugs are metabolized/eliminated via the liver; caution in severe hepatic impairment.
Timing: Before initiation, especially if hepatic impairment is suspected.
Routine Monitoring
Clinical response to treatment
Frequency: Daily during treatment, then as needed
Target: Resolution of fever and parasitemia
Action Threshold: Persistent or worsening symptoms, or continued parasitemia, may indicate treatment failure or resistance.
INR (if on warfarin)
Frequency: Closely monitor after initiation and dose changes
Target: Individualized therapeutic range
Action Threshold: INR outside target range; adjust warfarin dose as needed.
Symptom Monitoring
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Headache
- Dizziness
- Insomnia
- Rash
- Oral ulcers
- Signs of treatment failure (persistent fever, worsening symptoms of malaria)
Special Patient Groups
Pregnancy
Category C. Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Not recommended for malaria prophylaxis in pregnant women with severe renal impairment (CrCl < 30 mL/min).
Trimester-Specific Risks:
First Trimester:
Limited data, but generally avoided unless essential.
Second Trimester:
Considered safer than first trimester, but still use with caution.
Third Trimester:
Considered safer than first trimester, but still use with caution.
Lactation
Not recommended. Atovaquone and cycloguanil (active metabolite of proguanil) are excreted into breast milk. The amount of atovaquone in breast milk is low, but the effects on a nursing infant are unknown. Proguanil and cycloguanil are excreted in higher amounts.
Infant Risk:
Risk L3 (Moderately Safe - potential for adverse effects, monitor infant for rash, diarrhea, or other signs of toxicity).
Pediatric Use
Specific weight-based dosing is available for both prophylaxis and treatment. Contraindicated for treatment in infants weighing less than 5 kg and for prophylaxis in infants weighing less than 11 kg.
Geriatric Use
No specific dose adjustment is required based on age alone. However, monitor renal function in elderly patients, as proguanil is renally eliminated and renal impairment is more common in this population.
Clinical Information
Clinical Pearls
- Always take Malarone with food or a milky drink to maximize absorption and minimize gastrointestinal side effects.
- For malaria prophylaxis, strict adherence to the dosing schedule (starting before, during, and for 7 days after travel) is crucial for efficacy.
- Malarone is generally well-tolerated but can cause GI upset; taking it at bedtime may help if nausea is an issue.
- It is not effective against hypnozoite forms of P. vivax or P. ovale, so a terminal prophylaxis with primaquine may be needed for these species if exposure is suspected.
- Inform patients about potential drug interactions, especially with rifampin/rifabutin, tetracycline, and warfarin.
Alternative Therapies
- Mefloquine (Lariam)
- Doxycycline
- Chloroquine (for sensitive areas)
- Primaquine (for P. vivax/ovale radical cure or terminal prophylaxis)
- Tafenoquine (Arakoda, Krintafel)
Cost & Coverage
Average Cost:
Varies widely, typically $150-$300+ per 30 tablets (brand)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (generic often Tier 1 or 2)
General Drug Facts
If your symptoms or health condition do not improve or worsen over time, 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'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 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 overdose, including the medication taken, the amount, and the time it occurred.