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Atovaquone and Proguanil HCl atovaquone and proguanil hydrochloride 250; 100 mg; mg Tablet, Film Coated, 10-count — NDC 63629-5531-1 (Billing 63629-5531-01) · Product 63629-5531

by Bryant Ranch Prepack · 10 TABLET, FILM COATED in 1 BOTTLE (63629-5531-1)

NDC 63629-5531-1 (billing 63629-5531-01) is a package of 10 tablets of Atovaquone and Proguanil HCl atovaquone and proguanil hydrochloride 250; 100 mg; mg Tablet, Film Coated from Bryant Ranch Prepack, no longer marketed, no longer in the FDA NDC Directory. It is the main listing for product NDC 63629-5531, which comes in 4 package sizes.

NDC 63629-5531-01
🏷️ FDA NDC (as labeled) 63629-5531-1 billing pads the package segment with a zero
This package
Contains10-count Pack sizes4 compare ↓
Main listing for product 63629-5531 · Also comes in: 5 tablets 63629-5531-3 12 tablets 63629-5531-4 24 tablets 63629-5531-2
Rx only Brand Discontinued Non-controlled ⚠ Inactivated by FDA ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 21, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️
Excluded from the active FDA NDC Directory. FDA inactivated this product’s listing record, so it is excluded from the active NDC Directory. The listing was last certified through Dec 2023. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 63629-5531-1
Product NDC 63629-5531
11-digit billing NDC 63629553101
Application # NDA021078
SPL Set ID 7d124c6f-dbdb-48ee-8fd2-9880fdf9d765
Mechanism of action Antimalarial [EPC], Antimalarial [EPC], Antiprotozoal [EPC], Dihydrofolate Reductase Inhibitors
DEA schedule Non-controlled
Marketing category NDA AUTHORIZED GENERIC
Marketing status Discontinued
FDA listing status Inactivated by FDA (certified through Dec 2023)
Route ORAL
Dosage form TABLET, FILM COATED
Substance ATOVAQUONE; PROGUANIL HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS
Quick answers for NDC 63629-5531-1
  • 11-digit billing NDC: 63629553101
Why two NDCs? The FDA registers this code as 63629-5531-1 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 63629-5531-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

Clinical

📗 Our plain-language guide HelloPharmacist
  • It can actually do both. If you're traveling to an area where malaria is a risk, you can take it to prevent infection — starting a day or two before you leave, every day while you'...
  • What exactly is this medicine for — is it for treating malaria I already have, or for preventing it?
  • Yes — it really does matter, especially for atovaquone. Taking it with a fatty food or a milky drink can increase the amount your body absorbs by two to three times compared to tak...
  • Does it really matter that I take this with food? What if I'm not hungry?
📖 Read our full Atovaquone and Proguanil guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 5 tablets 12 tablets 24 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
63629-5531-01 63629-5531-1 You're viewing this Main listing 10 TABLET, FILM COATED in 1 BOTTLE (63629-5531-1) 2015-01-21 — Inactivated by FDA
63629-5531-02 63629-5531-2 24 TABLET, FILM COATED in 1 BOTTLE (63629-5531-2) 2015-01-20 — Inactivated by FDA
63629-5531-03 63629-5531-3 5 TABLET, FILM COATED in 1 BOTTLE (63629-5531-3) 2015-01-23 — Inactivated by FDA
63629-5531-04 63629-5531-4 12 TABLET, FILM COATED in 1 BOTTLE (63629-5531-4) 2021-12-22 — Inactivated by FDA

You're viewing one of 4 pack sizes for this product.

Pack size FAQ

What quantity is in NDC 63629-5531-01?
NDC 63629-5531-01 is a 10-count package — 10 tablet, film coated in 1 bottle.
What is the difference between NDC 63629-5531-01 and NDC 63629-5531-03?
Both are Atovaquone and Proguanil HCl atovaquone and proguanil hydrochloride 250; 100 mg; mg Tablet, Film Coated — the drug itself is identical. NDC 63629-5531-01 is the 10-count package, while NDC 63629-5531-03 is the 5 tablets package.
What NDC number is used to bill for this package of Atovaquone and Proguanil HCl atovaquone and proguanil hydrochloride 250; 100 mg; mg Tablet, Film Coated?
Bill NDC 63629-5531-01 — the 11-digit billing format is 63629553101. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Atovaquone and Proguanil HCl 250; 100 mg/1; mgthis 63629-5531-01 Bryant 10 tablets — AB Discontinued —
About this product: this is an authorized generic — the brand-name product marketed without its brand name. Other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

📍
2026
Currently FDA-listed
listed with the FDA
🔓
·
Generic versions listed
see equivalents
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerBryant Ranch Prepack
Application holderGLAXOSMITHKLINE
FDA applicationNDA021078 (NDA AUTHORIZED GENERIC)
Labeler code63629
Product typeHuman Prescription Drug
Portfolio4,436 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 120 words ▾

1 INDICATIONS AND USAGE Atovaquone and Proguanil Hydrochloride tablets are an antimalarial indicated for: • prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. ( 1.1 ) • treatment of acute, uncomplicated P. falciparum malaria. ( 1.2 )

1.1Prevention of Malaria Atovaquone and Proguanil Hydrochloride tablets are indicated for the prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported.

1.2Treatment of Malaria Atovaquone and Proguanil Hydrochloride tablets are indicated for the treatment of acute, uncomplicated P. falciparum malaria. Atovaquone and proguanil hydrochloride have been shown to be effective in regions where the drugs chloroquine, halofantrine, mefloquine, and amodiaquine may have unacceptable failure rates, presumably due to drug resistance.

⏱️ Dosage and Administration ~2 min read ▾

2 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 tablets may be crushed and mixed with condensed milk just prior to administration to patients who may have difficulty swallowing tablets. • Atovaquone and Proguanil Hydrochloride tablets should be taken with food or a milky drink.

Prophylaxis ( 2.1 ) : • Start prophylaxis 1 or 2 days before entering a malaria‑endemic area and continue daily during the stay and for 7 days after return. • Adults: One adult strength tablet per day. Treatment ( 2.2 ) : • Adults: Four adult strength tablets as a single daily dose for 3 days. Renal Impairment ( 2.3 ) : • Do not use for prophylaxis of malaria in patients with severe renal impairment. • Use with caution for treatment of malaria in patients with severe renal impairment.

2.1Prevention of Malaria Start prophylactic treatment with Atovaquone 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.

2.2Treatment of Acute Malaria Adults Four Atovaquone 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.

2.3Renal Impairment Do not use Atovaquone 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 49 words ▾

3 DOSAGE FORMS AND STRENGTHS Each Atovaquone and Proguanil Hydrochloride tablet (adult strength), containing 250 mg atovaquone and 100 mg proguanil hydrochloride, is pink, film‑coated, round, biconvex and engraved with “GX CM3” on one side. Tablets (adult strength): 250 mg atovaquone and 100 mg proguanil hydrochloride. ( 3 )

⛔ Contraindications 124 words ▾

4 CONTRAINDICATIONS • Atovaquone and Proguanil Hydrochloride tablets are contraindicated in individuals with known hypersensitivity reactions (e.g., anaphylaxis, erythema multiforme or Stevens-Johnson syndrome, angioedema, vasculitis) to atovaquone or proguanil hydrochloride or any component of the formulation. • Atovaquone and Proguanil Hydrochloride tablets are contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min) because of pancytopenia in patients with severe renal impairment treated with proguanil [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] . • Known serious hypersensitivity reactions to atovaquone or proguanil hydrochloride or any component of the formulation.

( 4 ) • Prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min). ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS • Atovaquone absorption may be reduced in patients with diarrhea or vomiting. If used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered. In patients with severe or persistent diarrhea or vomiting, alternative antimalarial therapy may be required.

( 5.1 ) • In mixed P. falciparum and Plasmodium vivax infection, P. vivax relapse occurred commonly when patients were treated with atovaquone and proguanil hydrochloride alone. ( 5.2 ) • In the event of recrudescent P. falciparum infections after treatment or prophylaxis failure, patients should be treated with a different blood schizonticide. ( 5.2 ) • Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use.

( 5.3 ) • Atovaquone and proguanil hydrochloride has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria. Patients with severe malaria are not candidates for oral therapy. ( 5.4 )

5.1Vomiting and Diarrhea Absorption of atovaquone may be reduced in patients with diarrhea or vomiting. If Atovaquone and Proguanil Hydrochloride tablets are used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered. [See Dosage and Administration ( 2 ).] Vomiting occurred in up to 19% of pediatric patients given treatment doses of atovaquone and proguanil hydrochloride. In the controlled clinical trials, 15.3% of adults received an antiemetic when they received atovaquone/proguanil and 98.3% of these patients were successfully treated.

In patients with severe or persistent diarrhea or vomiting, alternative antimalarial therapy may be required.

5.2Relapse of Infection In mixed P. falciparum and Plasmodium vivax infections, P. vivax parasite relapse occurred commonly when patients were treated with atovaquone and proguanil hydrochloride alone. In the event of recrudescent P. falciparum infections after treatment with Atovaquone and Proguanil Hydrochloride tablets or failure of chemoprophylaxis with Atovaquone and Proguanil Hydrochloride tablets, patients should be treated with a different blood schizonticide.

5.3Hepatotoxicity Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use of atovaquone and proguanil hydrochloride.

5.4Severe or Complicated Malaria Atovaquone and proguanil hydrochloride has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria, including hyperparasitemia, pulmonary edema, or renal failure. Patients with severe malaria are not candidates for oral therapy.

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS • Prophylaxis: Common adverse reactions (≥4%) in adults were diarrhea, dreams, oral ulcers, and headache; these events occurred in a similar or lower proportion of subjects receiving atovaquone and proguanil hydrochloride than an active comparator. Common adverse reactions (≥5%) in pediatric patients included abdominal pain, headache, cough, and vomiting. ( 6.1 ) • Treatment: Common adverse reactions (≥5%) in adolescents and adults were abdominal pain, nausea, vomiting, headache, diarrhea, asthenia, anorexia, and dizziness.

Common adverse reactions (≥6%) in pediatric patients included vomiting, pruritus, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Because the tablets contain atovaquone and proguanil hydrochloride, the type and severity of adverse reactions associated with each of the compounds may be expected. The lower prophylactic doses of atovaquone and proguanil hydrochloride were better tolerated than the higher treatment doses.

Prophylaxis of P. falciparum Malaria In 3 clinical trials (2 of which were placebo-controlled) 381 adults (mean age: 31 years) received atovaquone and proguanil hydrochloride for the prophylaxis of malaria; the majority of adults were black (90%) and 79% were male. In a clinical trial for the prophylaxis of malaria, 125 pediatric patients (mean age: 9 years) received atovaquone and proguanil hydrochloride; all subjects were black and 52% were male. Adverse experiences reported in adults and pediatric patients considered attributable to therapy occurred in similar proportions of subjects receiving atovaquone and proguanil hydrochloride or placebo in all studies.

Prophylaxis with atovaquone and proguanil hydrochloride was discontinued prematurely due to a treatment‑related adverse experience in 3 of 381 (0.8%) adults and 0 of 125 pediatric patients. In a placebo‑controlled study of malaria prophylaxis with atovaquone and proguanil hydrochloride involving 330 pediatric patients (aged 4 to 14 years) in Gabon, a malaria-endemic area, the safety profile of atovaquone and proguanil hydrochloride was consistent with that observed in the earlier prophylactic studies in adults and pediatric patients.

The most common treatment‑emergent adverse events with atovaquone and proguanil hydrochloride were abdominal pain (13%), headache (13%), and cough (10%). Abdominal pain (13% vs. 8%) and vomiting (5% vs.

3%) were reported more often with atovaquone and proguanil hydrochloride than with placebo. No patient withdrew from the study due to an adverse experience with atovaquone and proguanil hydrochloride. No routine laboratory data were obtained during this study.

Non‑immune travelers visiting a malaria‑endemic area received atovaquone and proguanil hydrochloride (n = 1,004) for prophylaxis of malaria in 2 active-controlled clinical trials. In one study (n = 493), the mean age of subjects was 33 years and 53% were male; 90% of subjects were white, 6% of subjects were black, and the remaining were of other racial/ethnic groups. In the other study (n = 511), the mean age of subjects was 36 years and 51% were female; the majority of subjects (97%) were white.

Adverse experiences occurred in a similar or lower proportion of subjects receiving atovaquone and proguanil hydrochloride than an active comparator ( Table 1 ). Fewer neuropsychiatric adverse experiences occurred in subjects who received atovaquone and proguanil hydrochloride than mefloquine. Fewer gastrointestinal adverse experiences occurred in subjects receiving atovaquone and proguanil hydrochloride than chloroquine/proguanil.

Compared w… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS • Administration with rifampin or rifabutin is known to reduce atovaquone concentrations; concomitant use with Atovaquone and Proguanil Hydrochloride tablets is not recommended. ( 7.1 ) • Proguanil may potentiate anticoagulant effect of warfarin and other coumarin-based anticoagulants. Caution advised when initiating or withdrawing Atovaquone and Proguanil Hydrochloride tablets in patients on anticoagulants; coagulation tests should be closely monitored.

( 7.2 ) • Tetracycline may reduce atovaquone concentrations; parasitemia should be closely monitored. ( 7.3 )

7.1Rifampin/Rifabutin Concomitant administration of rifampin or rifabutin is known to reduce atovaquone concentrations [see Clinical Pharmacology ( 12.3 )] . The concomitant administration of Atovaquone and Proguanil Hydrochloride tablets and rifampin or rifabutin is not recommended.

7.2Anticoagulants Proguanil may potentiate the anticoagulant effect of warfarin and other coumarin-based anticoagulants. The mechanism of this potential drug interaction has not been established. Caution is advised when initiating or withdrawing malaria prophylaxis or treatment with Atovaquone and Proguanil Hydrochloride tablets in patients on continuous treatment with coumarin-based anticoagulants.

When these products are administered concomitantly, coagulation tests should be closely monitored.

7.3Tetracycline Concomitant treatment with tetracycline has been associated with a reduction in plasma concentrations of atovaquone [see Clinical Pharmacology ( 12.3 )] . Parasitemia should be closely monitored in patients receiving tetracycline.

7.4Metoclopramide While antiemetics may be indicated for patients receiving Atovaquone and Proguanil Hydrochloride tablets, metoclopramide may reduce the bioavailability of atovaquone and should be used only if other antiemetics are not available [see Clinical Pharmacology ( 12.3 )] .

7.5Indinavir Concomitant administration of atovaquone and indinavir did not result in any change in the steady‑state AUC and C max of indinavir but resulted in a decrease in the C trough of indinavir [see Clinical Pharmacology ( 12.3 )] . Caution should be exercised when prescribing atovaquone with indinavir due to the decrease in trough concentrations of indinavir.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Renal impairment: contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment. ( 8.6 )

8.1Pregnancy Risk Summary Available data from published literature and postmarketing experience with use of atovaquone and proguanil hydrochloride in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes . The proguanil component of Atovaquone and Proguanil Hydrochloride tablets acts to inhibit parasitic dihydrofolate reductase; however, pregnant women and females of reproductive potential should continue folate supplementation to prevent neural tube defects [see Clinical Pharmacology ( 12.4 )] .

Pregnant women with malaria are at increased risk for adverse pregnancy outcomes (see Clinical Considerations). Atovaquone administered by oral gavage to pregnant rats and rabbits during the period of organogenesis was not associated with fetal malformations at plasma exposures approximately 7 times and equal to, respectively, the estimated human exposure for the treatment of malaria based on AUC. Proguanil administered to pregnant rats and rabbits during the period of organogenesis was not associated with embryo-fetal toxicity at maternally toxic plasma exposures approximately 0.07 and 0.8 times, respectively, the estimated human exposure for treatment of malaria based on AUC (see Data) .

The combination of atovaquone and proguanil hydrochloride given orally by gavage during the period of organogenesis was not associated with embryo-fetal developmental effects in pregnant rats or rabbits at atovaquone:proguanil hydrochloride doses of 50:20 mg/kg/day and 100:40 mg/kg/day, respectively (1.7 and 0.1 times and 0.3 and 0.5 times, respectively, the estimated human exposure for treatment of malaria). In a pre- and post-natal study with atovaquone and another pre-and post-natal study with proguanil, neither compound impaired the growth, development, or reproductive ability of first generation offspring at maternal AUC exposures of approximately 7.3 and 0.04 times, respectively, the estimated human AUC exposure for treatment of malaria (see Data) .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth. Data Animal Data: Atovaquone: Atovaquone administered in oral doses of 250, 500, and 1,000 mg/kg/day during organogenesis (Gestation Day [GD] 6 to GD15) in pregnant rats did not cause maternal or embryo-fetal toxicity at doses up to 1,000 mg/kg/day corresponding to maternal plasma exposures up to 7.3 times the estimated human exposure for the treatment of malaria based on AUC.

In pregnant rabbits, atovaquone administered in oral doses of 300, 600, and 1,200 mg/kg/day by gavage during organogenesis (GD6 to GD18) was associated with decreased fetal body length at a maternally toxic dose of 1,200 mg/kg/day corresponding to plasma exposures that were approximately 1.3 times the estimated human exposure during treatment of malaria based on AUC. In a pre- and post-natal study in rats, atovaquone administered in oral doses of 250, 500, and 1,000 mg/kg/day from GD15 until Lactation Day (LD) 20 did not impair the growth or developmental effects in first generation offspring at doses up to 1,000 mg/kg/day corresponding to AUC exposures of approximately 7.3 times the estimated human exposure during treatment of malaria.

Atovaquone crossed the placenta and was present in fetal rat… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Available data from published literature and postmarketing experience with use of atovaquone and proguanil hydrochloride in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes . The proguanil component of Atovaquone and Proguanil Hydrochloride tablets acts to inhibit parasitic dihydrofolate reductase; however, pregnant women and females of reproductive potential should continue folate supplementation to prevent neural tube defects [see Clinical Pharmacology ( 12.4 )] .

Pregnant women with malaria are at increased risk for adverse pregnancy outcomes (see Clinical Considerations). Atovaquone administered by oral gavage to pregnant rats and rabbits during the period of organogenesis was not associated with fetal malformations at plasma exposures approximately 7 times and equal to, respectively, the estimated human exposure for the treatment of malaria based on AUC. Proguanil administered to pregnant rats and rabbits during the period of organogenesis was not associated with embryo-fetal toxicity at maternally toxic plasma exposures approximately 0.07 and 0.8 times, respectively, the estimated human exposure for treatment of malaria based on AUC (see Data) .

The combination of atovaquone and proguanil hydrochloride given orally by gavage during the period of organogenesis was not associated with embryo-fetal developmental effects in pregnant rats or rabbits at atovaquone:proguanil hydrochloride doses of 50:20 mg/kg/day and 100:40 mg/kg/day, respectively (1.7 and 0.1 times and 0.3 and 0.5 times, respectively, the estimated human exposure for treatment of malaria). In a pre- and post-natal study with atovaquone and another pre-and post-natal study with proguanil, neither compound impaired the growth, development, or reproductive ability of first generation offspring at maternal AUC exposures of approximately 7.3 and 0.04 times, respectively, the estimated human AUC exposure for treatment of malaria (see Data) .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth. Data Animal Data: Atovaquone: Atovaquone administered in oral doses of 250, 500, and 1,000 mg/kg/day during organogenesis (Gestation Day [GD] 6 to GD15) in pregnant rats did not cause maternal or embryo-fetal toxicity at doses up to 1,000 mg/kg/day corresponding to maternal plasma exposures up to 7.3 times the estimated human exposure for the treatment of malaria based on AUC.

In pregnant rabbits, atovaquone administered in oral doses of 300, 600, and 1,200 mg/kg/day by gavage during organogenesis (GD6 to GD18) was associated with decreased fetal body length at a maternally toxic dose of 1,200 mg/kg/day corresponding to plasma exposures that were approximately 1.3 times the estimated human exposure during treatment of malaria based on AUC. In a pre- and post-natal study in rats, atovaquone administered in oral doses of 250, 500, and 1,000 mg/kg/day from GD15 until Lactation Day (LD) 20 did not impair the growth or developmental effects in first generation offspring at doses up to 1,000 mg/kg/day corresponding to AUC exposures of approximately 7.3 times the estimated human exposure during treatment of malaria.

Atovaquone crossed the placenta and was present in fetal rat and rabbit tissue. Proguanil: Proguanil administered orally to pregnant rats during organogenesis (GD6 to GD17) was not associated with fetal malformation… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 109 words ▾

8.4Pediatric Use Prophylaxis of Malaria Safety and effectiveness have not been established in pediatric patients who weigh less than 11 kg. The efficacy and safety of atovaquone and proguanil hydrochloride have been established for the prophylaxis of malaria in controlled trials involving pediatric patients weighing 11 kg or more [see Clinical Studies ( 14.1 )]. Treatment of Malaria Safety and effectiveness have not been established in pediatric patients who weigh less than 5 kg.

The efficacy and safety of atovaquone and proguanil hydrochloride for the treatment of malaria have been established in controlled trials involving pediatric patients weighing 5 kg or more [see Clinical Studies ( 14.2 )].

🧓 Geriatric Use 76 words ▾

8.5Geriatric Use Clinical trials of atovaquone and proguanil hydrochloride did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, the higher systemic exposure to cycloguanil, and the greater frequency of concomitant disease or other drug therapy. [See Clinical Pharmacology ( 12.3 ).]

🆘 Overdosage 153 words ▾

10 OVERDOSAGE There is no information on overdoses of atovaquone and proguanil hydrochloride substantially higher than the doses recommended for treatment. There is no known antidote for atovaquone, and it is currently unknown if atovaquone is dialyzable. Overdoses up to 31,500 mg of atovaquone have been reported.

In one such patient who also took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose. Overdoses of proguanil hydrochloride as large as 1,500 mg have been followed by complete recovery, and doses as high as 700 mg twice daily have been taken for over 2 weeks without serious toxicity.

Adverse experiences occasionally associated with proguanil hydrochloride doses of 100 to 200 mg/day, such as epigastric discomfort and vomiting, would be likely to occur with overdose. There are also reports of reversible hair loss and scaling of the skin on the palms and/or soles, reversible aphthous ulceration, and hematologic side effects.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Atovaquone and Proguanil Hydrochloride tablets, a fixed-dose combination of atovaquone and proguanil hydrochloride, is an antimalarial agent [see Microbiology ( 12.4 )] .

12.2Pharmacodynamics Cardiac Effects The effect of atovaquone and proguanil hydrochloride on the QT interval is unknown in humans.

12.3Pharmacokinetics Absorption Atovaquone is a highly lipophilic compound with low aqueous solubility. The bioavailability of atovaquone shows considerable inter‑individual variability. Effect of Food: Atovaquone and Proguanil Hydrochloride tablets should be taken with food or a milky drink.

Dietary fat taken with atovaquone increases the rate and extent of absorption, increasing AUC 2 to 3 times and C max 5 times over fasting. The absolute bioavailability of the tablet formulation of atovaquone when taken with food is 23%. Distribution Atovaquone is highly protein bound (>99%) over the concentration range of 1 to 90 mcg/mL.

A population pharmacokinetic analysis demonstrated that the apparent volume of distribution of atovaquone (V/F) in adult and pediatric patients after oral administration is approximately

8.8L/kg. Proguanil is 75% protein bound. A population pharmacokinetic analysis demonstrated that the apparent V/F of proguanil in adult and pediatric patients older than 15 years with body weights from 31 to 110 kg ranged from 1,617 to 2,502 L.

In pediatric patients 15 years and younger with body weights from 11 to 56 kg, the V/F of proguanil ranged from 462 to 966 L. In human plasma, the binding of atovaquone and proguanil was unaffected by the presence of the other. Elimination The elimination half‑life of atovaquone is about 2 to 3 days in adult patients.

The elimination half‑life of proguanil is 12 to 21 hours in both adult patients and pediatric patients, but may be longer in individuals who are slow metabolizers. The main routes of elimination are hepatic biotransformation and renal excretion. Metabolism: In a study where 14 C‑labeled atovaquone was administered to healthy volunteers, greater than 94% of the dose was recovered as unchanged atovaquone in the feces over 21 days.

There was little or no excretion of atovaquone in the urine (less than 0.6%). There is indirect evidence that atovaquone may undergo limited metabolism; however, a specific metabolite has not been identified. Between 40% to 60% of proguanil is excreted by the kidneys.

Proguanil is metabolized to cycloguanil (primarily via cytochrome P450 2C19 [CYP2C19]) and 4-chlorophenylbiguanide. Excretion: A population pharmacokinetic analysis in adult and pediatric patients showed that the apparent clearance (CL/F) of both atovaquone and proguanil is related to body weight. The values CL/F for both atovaquone and proguanil in subjects with body weight ≥11 kg are shown in Table 2 .

Table 2. Apparent Clearance for Atovaquone and Proguanil in Patients as a Function of Body Weight a SD = Standard deviation. Body Weight Atovaquone Proguanil n CL/F (L/h) Mean ± SD a (range) n CL/F (L/h) Mean ± SD a (range) 11-20 kg 159 1.34 ± 0.63 (0.52 - 4.26) 146 29.5 ± 6.5 (10.3 - 48.3) 21-30 kg 117 1.87 ± 0.81 (0.52 - 5.38) 113 40.0 ± 7.5 (15.9 - 62.7) 31-40 kg 95 2.76 ± 2.07 (0.97 - 12.5) 91 49.5 ± 8.30 (25.8 - 71.5) >40 kg 368 6.61 ± 3.92 (1.32 - 20.3) 282 67.9 ± 19.9 (14.0 - 145) The pharmacokinetics of atovaquone and proguanil in patients with body weight less than 11 kg have not been adequately characterized.

Specific Populations Pediatric Patients: The pharmacokinetics of proguanil and cycloguanil are similar in adult patients and pediatric patients. However, the elimination half‑life of atovaquone is shorter in pediatric patients (1 to 2 days) than in adult patients (2 to 3 days). In clinical trials, plasma trough concentrations of atovaquone and proguanil in pediatric patients weighing 5 to 40 kg were within the range observed in adults after dosing by body weight.

Geriatric Patients: In a single‑dose study, the pharma… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 27 words ▾

12.1Mechanism of Action Atovaquone and Proguanil Hydrochloride tablets, a fixed-dose combination of atovaquone and proguanil hydrochloride, is an antimalarial agent [see Microbiology ( 12.4 )] .

📦 How Supplied / Storage and Handling 33 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING NDC: 63629-5531-1: 10 Tablets in a BOTTLE NDC: 63629-5531-2: 24 Tablets in a BOTTLE NDC: 63629-5531-3: 5 Tablets in a BOTTLE NDC: 63629-5531-4: 12 Tablets in a BOTTLE

📋 Description 171 words ▾

11 DESCRIPTION Atovaquone and Proguanil Hydrochloride tablets (adult strength), for oral administration, contain a fixed‑dose combination of the antimalarial agents atovaquone and proguanil hydrochloride. The chemical name of atovaquone is trans -2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione. Atovaquone is a yellow crystalline solid that is practically insoluble in water.

It has a molecular weight of 366.84 and the molecular formula C 22 H 19 ClO 3 . The compound has the following structural formula: The chemical name of proguanil hydrochloride is 1-(4-chlorophenyl)-5-isopropyl-biguanide hydrochloride. Proguanil hydrochloride is a white crystalline solid that is sparingly soluble in water.

It has a molecular weight of 290.22 and the molecular formula C 11 H 16 ClN 5 •HCl. The compound has the following structural formula: Each Atovaquone and Proguanil Hydrochloride tablet (adult strength) contains 250 mg of atovaquone and 100 mg of proguanil hydrochloride. The inactive ingredients are low-substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, poloxamer 188, povidone K30, and sodium starch glycolate.

The tablet coating contains hypromellose, polyethylene glycol 400, polyethylene glycol 8000, red iron oxide, and titanium dioxide.

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Patients should be instructed: • to take Atovaquone and Proguanil Hydrochloride tablets at the same time each day with food or a milky drink. • to take a repeat dose of Atovaquone and Proguanil Hydrochloride tablets if vomiting occurs within 1 hour after dosing. • to take a dose as soon as possible if a dose is missed, then return to their normal dosing schedule. However, if a dose is skipped, the patient should not double the next dose. • that rare serious adverse events such as hepatitis, severe skin reactions, neurological events, and hematological events have been reported when atovaquone and proguanil hydrochloride was used for the prophylaxis or treatment of malaria. • to consult a healthcare professional regarding alternative forms of prophylaxis if prophylaxis with Atovaquone and Proguanil Hydrochloride tablets is prematurely discontinued for any reason. • that protective clothing, insect repellents, and bed nets are important components of malaria prophylaxis. • that no chemoprophylactic regimen is 100% effective; therefore, patients should seek medical attention for any febrile illness that occurs during or after return from a malaria-endemic area and inform their healthcare professional that they may have been exposed to malaria. • that falciparum malaria carries a higher risk of death and serious complications in pregnant women than in the general population.

Pregnant women anticipating travel to malarious areas should discuss the risks and benefits of such travel with their physicians. Manufactured for: Prasco Laboratories Mason, OH 45040 USA APH-PS:4PI

🍼 Nursing Mothers 172 words ▾

8.2Lactation Risk Summary There are no data on the presence of atovaquone in human milk; however, proguanil is present in human milk. Atovaquone is present in rat milk (see Data) . When a drug is present in animal milk, it is likely the drug will be present in human milk.

There are no data on the effects of atovaquone and proguanil on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Atovaquone and Proguanil Hydrochloride tablets and any potential adverse effect on the breastfed child from Atovaquone and Proguanil Hydrochloride tablets or from the underlying maternal condition. Data In a rat study with doses of 10 and 250 mg/kg, given orally by gavage on postpartum Day 11, atovaquone concentrations in the milk were 30% of the concurrent atovaquone concentrations in the maternal plasma at both doses.

The concentration of drug in animal milk does not necessarily predict the concentration of drug in human milk.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Atovaquone is a highly lipophilic compound with low aqueous solubility. The bioavailability of atovaquone shows considerable inter‑individual variability. Effect of Food: Atovaquone and Proguanil Hydrochloride tablets should be taken with food or a milky drink.

Dietary fat taken with atovaquone increases the rate and extent of absorption, increasing AUC 2 to 3 times and C max 5 times over fasting. The absolute bioavailability of the tablet formulation of atovaquone when taken with food is 23%. Distribution Atovaquone is highly protein bound (>99%) over the concentration range of 1 to 90 mcg/mL.

A population pharmacokinetic analysis demonstrated that the apparent volume of distribution of atovaquone (V/F) in adult and pediatric patients after oral administration is approximately

8.8L/kg. Proguanil is 75% protein bound. A population pharmacokinetic analysis demonstrated that the apparent V/F of proguanil in adult and pediatric patients older than 15 years with body weights from 31 to 110 kg ranged from 1,617 to 2,502 L.

In pediatric patients 15 years and younger with body weights from 11 to 56 kg, the V/F of proguanil ranged from 462 to 966 L. In human plasma, the binding of atovaquone and proguanil was unaffected by the presence of the other. Elimination The elimination half‑life of atovaquone is about 2 to 3 days in adult patients.

The elimination half‑life of proguanil is 12 to 21 hours in both adult patients and pediatric patients, but may be longer in individuals who are slow metabolizers. The main routes of elimination are hepatic biotransformation and renal excretion. Metabolism: In a study where 14 C‑labeled atovaquone was administered to healthy volunteers, greater than 94% of the dose was recovered as unchanged atovaquone in the feces over 21 days.

There was little or no excretion of atovaquone in the urine (less than 0.6%). There is indirect evidence that atovaquone may undergo limited metabolism; however, a specific metabolite has not been identified. Between 40% to 60% of proguanil is excreted by the kidneys.

Proguanil is metabolized to cycloguanil (primarily via cytochrome P450 2C19 [CYP2C19]) and 4-chlorophenylbiguanide. Excretion: A population pharmacokinetic analysis in adult and pediatric patients showed that the apparent clearance (CL/F) of both atovaquone and proguanil is related to body weight. The values CL/F for both atovaquone and proguanil in subjects with body weight ≥11 kg are shown in Table 2 .

Table 2. Apparent Clearance for Atovaquone and Proguanil in Patients as a Function of Body Weight a SD = Standard deviation. Body Weight Atovaquone Proguanil n CL/F (L/h) Mean ± SD a (range) n CL/F (L/h) Mean ± SD a (range) 11-20 kg 159 1.34 ± 0.63 (0.52 - 4.26) 146 29.5 ± 6.5 (10.3 - 48.3) 21-30 kg 117 1.87 ± 0.81 (0.52 - 5.38) 113 40.0 ± 7.5 (15.9 - 62.7) 31-40 kg 95 2.76 ± 2.07 (0.97 - 12.5) 91 49.5 ± 8.30 (25.8 - 71.5) >40 kg 368 6.61 ± 3.92 (1.32 - 20.3) 282 67.9 ± 19.9 (14.0 - 145) The pharmacokinetics of atovaquone and proguanil in patients with body weight less than 11 kg have not been adequately characterized.

Specific Populations Pediatric Patients: The pharmacokinetics of proguanil and cycloguanil are similar in adult patients and pediatric patients. However, the elimination half‑life of atovaquone is shorter in pediatric patients (1 to 2 days) than in adult patients (2 to 3 days). In clinical trials, plasma trough concentrations of atovaquone and proguanil in pediatric patients weighing 5 to 40 kg were within the range observed in adults after dosing by body weight.

Geriatric Patients: In a single‑dose study, the pharmacokinetics of atovaquone, proguanil, and cycloguanil were compared in 13 elderly subjects (aged 65 to 79 years) with those of 13 younger subjects (aged 30 to 45 years). In the elderly subjects, the extent of systemic exposure (AUC) of cycloguanil was increased (point estimate: 2.36, 90% CI: 1.70, 3.28). T max was longer in elderly subjects (median: 8… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 19 words ▾

12.2Pharmacodynamics Cardiac Effects The effect of atovaquone and proguanil hydrochloride on the QT interval is unknown in humans.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Prevention of P. falciparum Malaria Atovaquone and proguanil hydrochloride was evaluated for prophylaxis of P. falciparum malaria in 5 clinical trials in malaria-endemic areas and in 3 active-controlled trials in non‑immune travelers to malaria-endemic areas. Three placebo-controlled trials of 10 to 12 weeks’ duration were conducted among residents of malaria-endemic areas in Kenya, Zambia, and Gabon. The mean age of subjects was 30 (range: 17 to 55), 32 (range: 16 to 64), and 10 (range: 5 to 16) years, respectively.

Of a total of 669 randomized patients (including 264 pediatric patients aged 5 to 16 years), 103 were withdrawn for reasons other than falciparum malaria‑ or drug‑related adverse events (55% of these were lost to follow-up and 45% were withdrawn for protocol violations). The results are listed in Table 4 . Table 4.

Prevention of Parasitemiaa in Placebo-Controlled Clinical Trials of Atovaquone and Proguanil Hydrochloride for Prophylaxis of P. falciparum Malaria in Residents of Malaria-Endemic Areas a Free of parasitemia during the 10- to 12-week period of prophylactic therapy. Atovaquone and Proguanil HCl Placebo Total number of patients randomized 326 343 Failed to complete study 57 46 Developed parasitemia ( P. falciparum ) 2 92 In another study, 330 Gabonese pediatric patients (weighing 13 to 40 kg and aged 4 to 14 years) who had received successful open‑label radical cure treatment with artesunate, were randomized to receive either atovaquone and proguanil hydrochloride (dosage based on body weight) or placebo in a double‑blind fashion for 12 weeks.

Blood smears were obtained weekly and any time malaria was suspected. Nineteen of the 165 children given atovaquone and proguanil hydrochloride and 18 of 165 patients given placebo withdrew from the study for reasons other than parasitemia (primary reason was lost to follow-up). One out of 150 evaluable patients (<1%) who received atovaquone and proguanil hydrochloride developed P. falciparum parasitemia while receiving prophylaxis with atovaquone and proguanil hydrochloride compared with 31 (22%) of the 144 evaluable placebo recipients.

In a 10‑week study in 175 South African subjects who moved into malaria‑endemic areas and were given prophylaxis with 1 atovaquone and proguanil hydrochloride daily, parasitemia developed in 1 subject who missed several doses of medication. Since no placebo control was included, the incidence of malaria in this study was not known. Two active-controlled trials were conducted in non‑immune travelers who visited a malaria‑endemic area.

The mean duration of travel was 18 days (range: 2 to 38 days). Of a total of 1,998 randomized patients who received atovaquone and proguanil hydrochloride or controlled drug, 24 discontinued from the study before follow-up evaluation 60 days after leaving the endemic area. Nine of these were lost to follow-up, 2 withdrew because of an adverse experience, and 13 were discontinued for other reasons.

These trials were not large enough to allow for statements of comparative efficacy. In addition, the true exposure rate to P. falciparum malaria in both trials is unknown. The results are listed in Table 5 .

Table 5. Prevention of Parasitemia a in Active-Controlled Clinical Trials of Atovaquone and Proguanil Hydrochloride for Prophylaxis of P. falciparum Malaria in Non-Immune Travelers a Free of parasitemia during the period of prophylactic therapy. Atovaquone and Proguanil HCl Mefloquine Chloroquine plus Proguanil Total number of randomized patients who received study drug 1,004 483 511 Failed to complete study 14 6 4 Developed parasitemia ( P. falciparum ) 0 0 3 A third randomized, open‑label study was conducted which included 221 otherwise healthy pediatric patients (weighing ≥11 kg and aged 2 to 17 years) who were at risk of contracting malaria by traveling to an endemic area.

The mean duration of travel was 15 days (range: 1 to 30 days). Prophylaxis with atovaquone and proguanil h… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Genotoxicity studies have not been performed with atovaquone in combination with proguanil. Effects of atovaquone and proguanil hydrochloride on male and female reproductive performance are unknown. Atovaquone A 24-month carcinogenicity study in CD rats was negative for neoplasms at doses up to 500 mg/kg/day corresponding to approximately 54 times the average steady-state plasma concentrations in humans during prophylaxis of malaria.

In CD-1 mice, a 24‑month study showed treatment‑related increases in incidence of hepatocellular adenoma and hepatocellular carcinoma at all doses tested (50, 100, and 200 mg/kg/day) which correlated with at least 15 times the average steady‑state plasma concentrations in humans during prophylaxis of malaria. Atovaquone was negative with or without metabolic activation in the Ames Salmonella mutagenicity assay, the mouse lymphoma mutagenesis assay, and the cultured human lymphocyte cytogenetic assay. No evidence of genotoxicity was observed in the in vivo mouse micronucleus assay.

Atovaquone administered by oral gavage in doses of 100, 300, or 1,000 mg/kg/day to adult male rats from 73 days prior to mating until 20 days after mating and to adult female rats from 14 days prior to mating until LD20 did not impair male or female fertility or early embryonic development at doses up to 1,000 mg/kg/day corresponding to plasma exposures of approximately 7.3 times the estimated human exposure for the treatment of malaria based on AUC. Proguanil No evidence of a carcinogenic effect was observed in 24-month studies conducted in CD-1 mice at doses up to 16 mg/kg/day corresponding to 1.5 times the average human plasma exposure during prophylaxis of malaria based on AUC, and in Wistar Hannover rats at doses up to 20 mg/kg/day corresponding to 1.1 times the average human plasma exposure during prophylaxis of malaria based on AUC.

Proguanil was negative with or without metabolic activation in the Ames Salmonella mutagenicity assay and the mouse lymphoma mutagenesis assay. No evidence of genotoxicity was observed in the in vivo mouse micronucleus assay. Cycloguanil, the active metabolite of proguanil, was also negative in the Ames test, but was positive in the mouse lymphoma assay and the mouse micronucleus assay.

These positive effects with cycloguanil, a dihydrofolate reductase inhibitor, were significantly reduced or abolished with folinic acid supplementation. Proguanil administered orally in doses of 4, 8, and 16 mg/kg/day to male rats from 29 days prior to mating until 27 days after mating and to females from 15 days prior to mating through GD7 revealed no adverse effects on adult male or female fertility or early embryonic development at doses up to 16 mg/kg/day (up to 0.04 times the average human exposure for the treatment of malaria based on AUC).

Fertility studies of proguanil in animals at exposures similar to or greater than those observed in humans have not been conducted.

13.2Animal Toxicology and/or Pharmacology Fibrovascular proliferation in the right atrium, pyelonephritis, bone marrow hypocellularity, lymphoid atrophy, and gastritis/enteritis were observed in dogs treated with proguanil hydrochloride for 6 months at a dose of 12 mg/kg/day (approximately 3.9 times the recommended daily human dose for malaria prophylaxis on a mg/m 2 basis). Bile duct hyperplasia, gall bladder mucosal atrophy, and interstitial pneumonia were observed in dogs treated with proguanil hydrochloride for 6 months at a dose of 4 mg/kg/day (approximately 1.3 times the recommended daily human dose for malaria prophylaxis on a mg/m 2 basis).

Mucosal hyperplasia of the cecum and renal tubular basophilia were observed in rats treated with proguanil hydrochloride for 6 months at a dose of 20 mg/kg/day (approximately 1.6 times the recommended daily human dose for malaria prophylaxis on a mg/m 2 basis). Adverse heart, lung, liver, and gall bladde… [Excerpted — this section continues on DailyMed.]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Genotoxicity studies have not been performed with atovaquone in combination with proguanil. Effects of atovaquone and proguanil hydrochloride on male and female reproductive performance are unknown. Atovaquone A 24-month carcinogenicity study in CD rats was negative for neoplasms at doses up to 500 mg/kg/day corresponding to approximately 54 times the average steady-state plasma concentrations in humans during prophylaxis of malaria.

In CD-1 mice, a 24‑month study showed treatment‑related increases in incidence of hepatocellular adenoma and hepatocellular carcinoma at all doses tested (50, 100, and 200 mg/kg/day) which correlated with at least 15 times the average steady‑state plasma concentrations in humans during prophylaxis of malaria. Atovaquone was negative with or without metabolic activation in the Ames Salmonella mutagenicity assay, the mouse lymphoma mutagenesis assay, and the cultured human lymphocyte cytogenetic assay. No evidence of genotoxicity was observed in the in vivo mouse micronucleus assay.

Atovaquone administered by oral gavage in doses of 100, 300, or 1,000 mg/kg/day to adult male rats from 73 days prior to mating until 20 days after mating and to adult female rats from 14 days prior to mating until LD20 did not impair male or female fertility or early embryonic development at doses up to 1,000 mg/kg/day corresponding to plasma exposures of approximately 7.3 times the estimated human exposure for the treatment of malaria based on AUC. Proguanil No evidence of a carcinogenic effect was observed in 24-month studies conducted in CD-1 mice at doses up to 16 mg/kg/day corresponding to 1.5 times the average human plasma exposure during prophylaxis of malaria based on AUC, and in Wistar Hannover rats at doses up to 20 mg/kg/day corresponding to 1.1 times the average human plasma exposure during prophylaxis of malaria based on AUC.

Proguanil was negative with or without metabolic activation in the Ames Salmonella mutagenicity assay and the mouse lymphoma mutagenesis assay. No evidence of genotoxicity was observed in the in vivo mouse micronucleus assay. Cycloguanil, the active metabolite of proguanil, was also negative in the Ames test, but was positive in the mouse lymphoma assay and the mouse micronucleus assay.

These positive effects with cycloguanil, a dihydrofolate reductase inhibitor, were significantly reduced or abolished with folinic acid supplementation. Proguanil administered orally in doses of 4, 8, and 16 mg/kg/day to male rats from 29 days prior to mating until 27 days after mating and to females from 15 days prior to mating through GD7 revealed no adverse effects on adult male or female fertility or early embryonic development at doses up to 16 mg/kg/day (up to 0.04 times the average human exposure for the treatment of malaria based on AUC).

Fertility studies of proguanil in animals at exposures similar to or greater than those observed in humans have not been conducted.

📄 Package Label / Principal Display Panel 7 words ▾

Atovaq/ Proguanil Hcl 250/ 100mg Tab. Label

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Atovaquone and Proguanil HCl (this brand).

Top reported reactions

Nausea23
Pneumonia18
Vomiting18
Cholelithiasis17
Schizophrenia17
Oedema Peripheral13
Asthma-chronic Obstructive Pulmonary Disease Overlap Syndrome12

Age at onset

Adolescent1
Adult10
Elderly4

Reporter sex

66 reports
Male · 28%
Female · 72%

Serious outcomes

Hospitalization28
Death6
Disabling1
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 14 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
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Orange Book / therapeutic-equivalence data ✓ Available
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“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 63629-5531-1, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 63629-5531-01, written without dashes as 63629553101. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 63629-5531-01, the first segment (63629) is the labeler code FDA assigned to Bryant Ranch Prepack; the middle segment (5531) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) identifies this exact package size and type. Together they name one specific package of one specific product.
Does this product come in other package sizes?
Yes — the FDA directory lists 3 other package presentations of this same product, including 5 tablets (63629-5531-03), 12 tablets (63629-5531-04), 24 tablets (63629-5531-02). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Bryant Ranch Prepack is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 63629-5512-01 · Bryant 63629-5628-01 · Bryant →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.