Atovaquone and proguanil

Name: Atovaquone and proguanil

Atovaquone and Proguanil Drug Class

Atovaquone and Proguanil is part of the drug class:

  • Antimalarial biguanides

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Before Using atovaquone and proguanil

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For atovaquone and proguanil, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to atovaquone and proguanil or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on atovaquone and proguanil have been done only in patients who weigh more than 25 pounds (11 kilograms [kg]) for the prevention of malaria and more than 11 pounds (5 kg) for the treatment of malaria. There is no specific information comparing use of atovaquone and proguanil combination in patients of lesser weight.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of atovaquone and proguanil in the elderly with use in other age groups.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking atovaquone and proguanil, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using atovaquone and proguanil with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Aurothioglucose

Using atovaquone and proguanil with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Cholera Vaccine, Live
  • Dicumarol
  • Efavirenz
  • Rifabutin
  • Rifampin
  • Warfarin

Using atovaquone and proguanil with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Chloroquine
  • Indinavir
  • Tetracycline
  • Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of atovaquone and proguanil. Make sure you tell your doctor if you have any other medical problems, especially:

  • Diarrhea or vomiting—The amount of atovaquone and proguanil the body can absorb may be decreased.
  • Kidney disease or failure—Atovaquone and proguanil could cause your condition to become much worse.
  • Return of previously treated malaria—Atovaquone and proguanil may not work in treating the malaria again; your doctor may need to give you another type of medicine

What are some other side effects of Atovaquone and Proguanil?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Headache.
  • Belly pain.
  • Cough.
  • Upset stomach or throwing up.
  • Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Atovaquone and Proguanil Dosage and Administration

The daily dose should be taken at the same time each day with food or a milky drink. In the event of vomiting within 1 hour after dosing, a repeat dose should be taken.

Atovaquone and Proguanil hydrochloride pediatric tablets may be crushed and mixed with condensed milk just prior to administration to patients who may have difficulty swallowing tablets.

Prevention of Malaria

Start prophylactic treatment withAtovaquone and Proguanil hydrochloride tablets 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return.

Adults: One Atovaquone and Proguanil hydrochloride tablet(adult strength = 250 mg atovaquone/100 mg proguanil hydrochloride) per day.

Pediatric Patients: The dosage for prevention of malaria in pediatric patients is based upon body weight (Table 1).

Table 1. Dosage for Prevention of Malaria in Pediatric Patients

Weight (kg)

Atovaquone/ Proguanil HCl Total Daily Dose

Dosage Regimen

11-20

62.5 mg/25 mg

1 Atovaquone and Proguanil hydrochloride Pediatric Tablet daily

21-30

125 mg/50 mg

2 Atovaquone and Proguanil hydrochloride Pediatric Tablets as a single daily dose

31-40

187.5 mg/75 mg

3 Atovaquone and Proguanil hydrochloride Pediatric Tablets as a single daily dose

>40

250 mg/100 mg

1 Atovaquone and Proguanil hydrochloride Tablet (adult strength) as a single daily dose

Treatment of Acute Malaria

Adults: FourAtovaquone and Proguanil hydrochloride tablets(adult strength; total daily dose 1 g atovaquone/400 mg proguanil hydrochloride) as a single daily dose for 3 consecutive days.

Pediatric Patients: The dosage for treatment of acute malaria in pediatric patients is based upon body weight (Table 2).

Table 2. Dosage for Treatment of Acute Malaria in Pediatric Patients

Weight (kg)

Atovaquone/ Proguanil HCl Total Daily Dose

Dosage Regimen

5-8

125 mg/50 mg

2 Atovaquone and Proguanil hydrochloride Pediatric Tablets daily for 3 consecutive days

9-10

187.5 mg/75 mg

3 Atovaquone and Proguanil hydrochloride Pediatric Tablets daily for 3 consecutive days

11-20

250 mg/100 mg

1 Atovaquone and Proguanil hydrochloride Tablet (adult strength) daily for 3 consecutive days

21-30

500 mg/200 mg

2 Atovaquone and Proguanil hydrochloride Tablets (adult strength) as a single daily dose for 3 consecutive days

31-40

750 mg/300 mg

3 Atovaquone and Proguanil hydrochloride Tablets (adult strength) as a single daily dose for 3 consecutive days

>40

1 g/400 mg

4 Atovaquone and Proguanil hydrochloride Tablets (adult strength) as a single daily dose for 3 consecutive days

Renal Impairment

Do not useAtovaquone and Proguanil hydrochloride tablets for malaria prophylaxis in patients with severe renal impairment (creatinine clearance <30 mL/min) [See Contraindications (4.2)]. Use with caution for the treatment of malaria in patients with severe renal impairment, only if the benefits of the 3 day treatment regimen outweigh the potential risks associated with increased drug exposure. No dosage adjustments are needed in patients with mild (creatinine clearance 50 to 80 mL/min) or moderate (creatinine clearance 30 to 50 mL/min) renal impairment. [See Clinical Pharmacology (12.3).

Dosage Forms and Strengths

Each Atovaquone and Proguanil hydrochloride tablet (adult strength) contains 250 mg atovaquone USP and 100 mg proguanil hydrochloride USP. Atovaquone and Proguanil hydrochloride tablets are pinkish brown to brown colored, circular, biconvex beveled edge, film-coated tablets with ‘404’ debossed on one side and ‘G’ debossed on the other side.

Atovaquone and Proguanil hydrochloride pediatric tablets, containing 62.5 mg atovaquone USP and 25 mg proguanil hydrochloride USP, are pinkish brown to brown colored, circular, biconvex beveled edged, film coated tablets with ‘70’ debossed on one side and ‘G’ debossed on the other side.

Pronunciation

(a TOE va kwone & pro GWA nil)

Dosing Geriatric

Refer to adult dosing.

Dosing Hepatic Impairment

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment; No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Drug Interactions

Antihepaciviral Combination Products: May decrease the serum concentration of Proguanil. Monitor therapy

Antipsychotic Agents (Phenothiazines): Antimalarial Agents may increase the serum concentration of Antipsychotic Agents (Phenothiazines). Monitor therapy

Artemether: May enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Dapsone (Systemic): May enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of 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. Consider therapy modification

Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Consider therapy modification

Efavirenz: May decrease the 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. Consider therapy modification

Etoposide: Atovaquone may increase the serum concentration of Etoposide. Management: Consider separating the administration of atovaquone and etoposide by at least 1 to 2 days. Monitor therapy

Etoposide Phosphate: Atovaquone may increase the serum concentration of Etoposide Phosphate. Management: Consider separating the administration of atovaquone and etoposide by at least 1 to 2 days. Monitor therapy

Indinavir: Atovaquone may decrease the serum concentration of Indinavir. Monitor therapy

Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination

Metoclopramide: May decrease the serum concentration of Atovaquone. Management: Consider alternatives to metoclopramide when possible; atovaquone should only be used with metoclopramide if no other antiemetics are available. Consider therapy modification

Rifamycin Derivatives: May decrease the serum concentration of Atovaquone. Avoid combination

Ritonavir: May decrease the serum concentration of Atovaquone. Avoid combination

Tetracycline: May decrease the serum concentration of Atovaquone. Monitor therapy

Typhoid Vaccine: Proguanil may diminish the therapeutic effect 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. Consider therapy modification

Warfarin: Proguanil may enhance the anticoagulant effect of Warfarin. Monitor therapy

Pregnancy Risk Factor C Pregnancy Considerations

Adverse events were not observed with the combination of atovaquone/proguanil in animal reproduction studies. The pharmacokinetics of atovaquone and proguanil may be altered during pregnancy (Wilby 2011). Malaria infection in pregnant women may be more severe than in nonpregnant women. Because P. falciparum malaria can cause maternal death and fetal loss, pregnant women traveling to malaria-endemic areas must use personal protection against mosquito bites. Atovaquone/proguanil may be used as an alternative treatment of malaria in pregnant women; consult current CDC guidelines (CDC 2013).

Dose Adjustments

No dosage adjustment necessary in patients with CrCl greater than or equal to 30 mL/min

For patients with CrCl less than 30 mL/min, atovaquone-proguanil is contraindicated for prophylaxis of plasmodium falciparum malaria.

It may be used with caution for the treatment of malaria in patients with severe renal impairment (CrCl less than 30 mL/min), only if the benefits of the 3-day regimen outweigh the potential risks associated with increased drug exposure.

Dialysis

Data not available

Atovaquone / proguanil Breastfeeding Warnings

There are no data on the excretion of atovaquone into human milk. Proguanil is excreted into human milk in small quantities. There are no data on adverse effects from proguanil in the nursing infant. The manufacturer recommends that caution be used when administering atovaquone-proguanil to nursing women.

In a rat study, atovaquone milk concentration was 30% of maternal plasma concentration. However, assumptions on excretion of drugs into human breast milk cannot be drawn based on animal data due to the difference in composition of breast milk between species.

How should this medicine be used?

The combination of atovaquone and proguanil comes as a tablet to take by mouth. If you are taking atovaquone and proguanil to prevent malaria, you will probably start taking it once daily 1 or 2 days before you travel to an area where malaria is common, and then continue during your time in the area and for 7 days after you return. If you are taking atovaquone and proguanil to treat malaria, you will probably take it once daily for 3 days in a row. Always take atovaquone and proguanil with food or a milky drink. Take atovaquone and proguanil at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take atovaquone and proguanil exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you have trouble swallowing the tablets, they may be crushed and mixed with condensed milk just before taking them.

If you vomit within 60 minutes after you take atovaquone and proguanil, take another full dose.

In case of emergency/overdose

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include the following:

  • rash
  • grey-bluish color of lips and/or skin
  • headache
  • tiredness
  • shortness of breath
  • vomiting
  • stomach pain or discomfort
  • hair loss
  • dry, cracked skin on palms of hands or bottom of feet
  • canker sores
(web3)