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Atovaquone and Proguanil Hydrochloride 250 mg; 100 mg Tablet, Film Coated, 100-count — NDC 68462-0404-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Atovaquone and Proguanil Hydrochloride 250 mg; 100 mg Tablet, Film Coated, 100-count — NDC 68462-404-01 (Billing 68462-0404-01)

by Glenmark Pharmaceuticals Inc.,USA · 100 TABLET, FILM COATED in 1 BOTTLE

This is a package of 100 tablets of Atovaquone and Proguanil Hydrochloride 250 mg; 100 mg Tablet, Film Coated from Glenmark Pharmaceuticals Inc.,USA, marketed since Sep 2011 and currently FDA-listed; retail pharmacies pay about $1.49 per tablet (NADAC). It is the main listing for this product, which comes in 2 package sizes.

NDC 68462-0404-01
🏷️ FDA NDC (as labeled) 68462-404-01 billing pads the product segment with a zero
This package
Contains100-count Cost per ea$1.49 NADAC Per package$148.58 / 100 tablets Pack sizes2 compare ↓
Also priced by: Medicaid pays $2.08/unit · Part D plans $2.82/unit — full pricing hub ↓
Main listing for product 68462-404 · Also comes in: 12 tablets 68462-404-67
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Oct 1, 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

NDC database record

One package, one record: these facts belong to NDC 68462-404-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
68462 labeler · 404 product · 01 package
Package marketed since
Sep 15, 2011
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
100 EA per package
Barcode (UPC)
0368462402016, 0368462404010
Medicaid fills, this package
10,539 prescriptions in the last four reported quarters
FDA record last changed
Oct 1, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68462-404-01
Product NDC 68462-404
11-digit billing NDC 68462040401
NCPDP billing unit EA — each (per item)
RxCUI 864675, 864681
UNII R71Y86M0WT, Y883P1Z2LT
UPC 0368462402016, 0368462404010
Application # ANDA091211
SPL Set ID 4b80d087-eaa7-448f-967e-344de7f16436
Established class (EPC) Antimalarial; Antiprotozoal
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2011-09-15
Route ORAL
Dosage form TABLET, FILM COATED
Substance ATOVAQUONE; PROGUANIL HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 13990002050320
GPI class Atovaquone-Proguanil HCl
GCN Seq No 045855
GCN 89891
HICL code 016487
Ingredient (HICL) Atovaquone/Proguanil Hcl
HIC1 code W
Therapeutic class — broad (HIC1) Anti-Infecting Agents
HIC2 code W4
Therapeutic class — intermediate (HIC2) Antiparasitics
HIC3 code W4A
Therapeutic class — specific (HIC3) Antimalarial Drugs
AHFS code 08:30.08.00
AHFS class Antimalarials
FDB label name ATOVAQUONE-PROGUANIL 250-100
FDB brand name Atovaquone-Proguanil Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 045855
  • GCN: 89891
  • GPI-14 (Medi-Span): 13990002050320
  • HICL (First Databank): 016487
  • AHFS class code: 08:30.08.00
  • RxCUI (RxNorm): 864675
Why two NDCs? The FDA registers this code as 68462-404-01 — a 5-3-2 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 product segment → 68462-0404-01. 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.

RxNorm drug class

This medicine belongs to the Antimalarial class.

Pharmacologic class Antimalarial
Drug family (ATC) Biguanides
How it works Dihydrofolate Reductase Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name ATOVAQUONE-PROGUANIL 250-100 Ingredient Atovaquone/Proguanil Hcl
📖 What it is MedlinePlus · NLM

Atovaquone and proguanil is used to prevent or treat certain kinds of malaria infections (a serious infection that is spread by mosquitoes in certain parts of the world). Atovaquone and proguanil is in a class of medications called antimalarials. It works by killing the organisms that cause malaria.

Read the full MedlinePlus article ↗
📗 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 eaPer package
Retail pharmacies payNADAC · weekly $1.486 $148.58 / 100 tablets
Medicaid paysCMS SDUD · 12 mo $2.08 $207.97 / 100 tablets
Medicare drug plans payPart D · Q2 2026 $2.82 $282.02 / 100 tablets
NADAC price history (per ea) — tap or hover for the price & month
Jan 2022 Aug 2022 Jan 2026 Sep 2026 $2.619 $1.478
▼ Down 32% over the last 24 months.
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 Per unit Per pack Marketing startMarketing endStatus
68462-0404-01 You're viewing this Main listing 100 TABLET, FILM COATED in 1 BOTTLE $1.49 / ea $148.58 2011-09-15 — Active
68462-0404-67 68462-404-67 2 BLISTER PACK in 1 CARTON / 12 TABLET, FILM COATED in 1 BLISTER PACK $1.49 / ea $35.66 2011-09-15 — Active

This pack has the lowest per-ea cost of the 2 priced pack sizes ($1.49 NADAC).

In Medicaid, this is the most-dispensed pack of this product — about 59% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 100-count package — 100 tablet, film coated in 1 bottle.
What NDC number is used to bill for this package of Atovaquone and Proguanil Hydrochloride 250 mg; 100 mg Tablet, Film Coated?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Atovaquone and Proguanil Hydrochloride 250 mg/1; 100 mg 00378-4162-01 Mylan 100 tablets $1.486 AB Availability likely —
Atovaquone and Proguanil HCl 250 mg/1; 100 mg 66993-0060-02 Prasco 100 tablets $1.486 AB Availability likely —
Atovaquone and Proguanil Hydrochloride 250 mg/1; 100 mg 68001-0245-00 BluePoint 100 tablets $1.486 AB Availability likely —
Atovaquone and Proguanil Hydrochloride 250 mg/1; 100 mgthis 68462-0404-01 Glenmark 100 tablets $1.486 AB Availability likely —
Malarone 250 mg/1; 100 mg 00173-0675-01 GlaxoSmithKline 100 tablets — AB FDA listed —
Atovaquone and Proguanil HCl 250 mg/1; 100 mg 50090-2980-00 A-S 7 tablets — AB FDA listed —
Atovaquone and Proguanil Hydrochloride 250 mg/1; 100 mg 51407-0869-01 Golden 100 tablets — AB FDA listed —
Atovaquone and Proguanil Hydrochloride 250 mg/1; 100 mg 63187-0879-24 Proficient 24 tablets — AB FDA listed —
Atovaquone and Proguanil Hydrochloride 250 mg/1; 100 mg 71335-3160-01 Bryant 10 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and 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

🏛️
2011
On the market since
Sep 2011
📍
2026
Currently FDA-listed
15 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

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.

What it looks like

Color Pink
ShapeRound
Imprint70;G
Size6 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII 36SFW2JZ0W
    Hypromellose 2910 is a plant-based thickening agent derived from cellulose. In medicines, it forms a protective coating on tablets or capsules and controls how quickly the drug dissolves and releases into your body.
  • UNII 2165RE0K14
    A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII LQA7B6G8JG
    A synthetic polymer made by combining water-soluble compounds. It acts as a surfactant and solubilizer to help mix oil and water-based ingredients, improving the medicine's texture and how active ingredients dissolve.
  • UNII B697894SGQ
    Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
  • UNII Q662QK8M3B
    Polyethylene glycol 8000 is a synthetic polymer made from ethylene oxide. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and add bulk to the medicine.
  • UNII U725QWY32X
    Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 5856J3G2A2
    A starch-based powder made from potatoes and processed with sodium. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the medicine can be absorbed.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

12 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

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

LabelerGlenmark Pharmaceuticals Inc.,USA
Application holderGLENMARK PHARMACEUTICALS LTD
FDA applicationANDA091211 (ANDA)
Labeler code68462
First marketedSep 2011
Product typeHuman Prescription Drug
Portfolio8 products on file

More NDCs from Glenmark Pharmaceuticals Inc.,USA labeler code 68462

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 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 121 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 tablets 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 ~3 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. • Pediatric Patients: Dosage based on body weight (see Table 1). Treatment ( 2.2 ): • Adults: Four adult strength tablets as a single daily dose for 3 days. • Pediatric Patients: Dosage based on body weight (see Table 2). 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. 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 to 20 62.5 mg/25 mg 1 Atovaquone and proguanil hydrochloride pediatric tablet daily 21 to 30 125 mg/50 mg 2 Atovaquone and proguanil hydrochloride pediatric tablets as a single daily dose 31 to 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

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. 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 to 8 125 mg/50 mg 2 Atovaquone and proguanil hydrochloride pediatric tablets daily for 3 consecutive days 9 to 10 187.5 mg/75 mg 3 Atovaquone and proguanil hydrochloride pediatric tablets daily for 3 consecutive days 11 to 20 250 mg/100 mg 1 Atovaquone and proguanil hydrochloride tablet (adult strength) daily for 3 consecutive days 21 to 30 500 mg/200 mg 2 Atovaquone and proguanil hydrochloride tablets (adult strength) as a single daily dose for 3 consecutive days 31 to 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

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 )] . 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 132 words ▾

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 contain 62.5 mg atovaquone USP and 25 mg proguanil hydrochloride USP.

Atovaquone and proguanil hydrochloride pediatric tablets 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. • Tablets (adult strength): 250 mg atovaquone and 100 mg proguanil hydrochloride. ( 3 ) • Pediatric tablets: 62.5 mg atovaquone and 25 mg proguanil hydrochloride. ( 3 )

⛔ Contraindications 124 words ▾

4 CONTRAINDICATIONS • 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 ) • Atovaquone and proguanil hydrochloride is contraindicated in individuals with known hypersensitivity reactions to atovaquone or proguanil hydrochloride or any component of the formulation [see Warnings and Precautions ( 5.4 ), Adverse Reactions ( 6.2 )]. • Atovaquone and proguanil hydrochloride is 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 )].

⚠️ 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 ) • Severe Cutaneous Adverse Reactions (SCARs): Cases of SCARs such as Stevens-Johnson syndrome (SJS) have been reported. SCARs can be life-threatening or fatal. If symptoms or signs of SCARs develop, discontinue atovaquone and proguanil hydrochloride immediately and institute appropriate therapy.

( 5.4 ) • 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. ( 5.5 )

5.1Vomiting and Diarrhea Absorption of atovaquone may be reduced in patients with diarrhea or vomiting. If atovaquone and proguanil hydrochloride is 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 or failure of chemoprophylaxis with atovaquone and proguanil hydrochloride, 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 Cutaneous Adverse Reactions Cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and erythema multiforme (EM) have been reported in patients treated with atovaquone and proguanil hydrochloride [see Adverse Reactions ( 6.2 )] . SCARs can be life-threatening or fatal. If symptoms or signs of SCARs develop, discontinue atovaquone and proguanil hydrochloride immediately and institute appropriate therapy.

Patients who have developed SCARs with the use of atovaquone and proguanil hydrochloride must not receive atovaquone and proguanil hydrochloride [see Contraindications ( 4 )].

5.5Severe 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 The following clinically significant adverse reactions are discussed in another section of the labeling: • Vomiting and Diarrhea [see Warnings and Precautions ( 5.1 )]. • Hepatotoxicity [see Warnings and Precautions ( 5.3 )]. • Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.4 )]. • 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 Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 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 atovaquone and proguanil hydrochloride 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 atovaqu… [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 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 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 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 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, 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 111 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, 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 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 are related to body weight. The values CL/F for both atovaquone and proguanil in subjects with body weight ≥11 kg are shown in Table 4.

Table 4. Apparent Clearance for Atovaquone and Proguanil in Patients as a Function of Body Weight Atovaquone Proguanil Body Weight n CL/F (L/h) Mean ± SD a (range) n CL/F (L/h) Mean ± SD a (range) 11 to 20 kg 159 1.34 ± 0.63 (0.52 to 4.26) 146 29.5 ± 6.5 (10.3 to 48.3) 21 to 30 kg 117 1.87 ± 0.81 (0.52 to 5.38) 113 40.0 ± 7.5 (15.9 to 62.7) 31 to 40 kg 95 2.76 ± 2.07 (0.97 to 12.5) 91 49.5 ± 8.30 (25.8 to 71.5) >40 kg 368 6.61 ± 3.92 (1.32 to 20.3) 282 67.9 ± 19.9 (14.0 to 145) a SD = Standard deviation. 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, t… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 26 words ▾

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

📦 How Supplied / Storage and Handling 156 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Atovaquone and proguanil hydrochloride tablets, containing 250 mg atovaquone, USP and 100 mg proguanil hydrochloride, USP 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 tablets 250 mg / 100 mg Bottle of 100 tablets (NDC 68462-404-01) Cartons of 24 tablets (NDC 68462-404-67) containing 2 x 12 Unit-Dose Blisters (NDC 68462-404-44). 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.

Atovaquone and proguanil hydrochloride pediatric tablets 62.5 mg / 25 mg Bottle of 100 tablets (NDC 68462-402-01). Storage Conditions Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

📋 Description ~1 min read ▾

11 DESCRIPTION Atovaquone and proguanil hydrochloride tablets (adult strength) and Atovaquone and proguanil hydrochloride pediatric tablets, for oral administration, contain a fixed-dose combination of the antimalarial agents atovaquone, USP and proguanil hydrochloride, USP. The chemical name of atovaquone, USP is trans -2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione. Atovaquone, USP is a yellow crystalline solid that is freely soluble in N-methyl-2-pyrrolidone and in tetrahydrofuran; soluble in chloroform; sparingly soluble in acetone and dimethyl sulfoxide; slightly soluble in octanol, ethyl acetate, polyethylene glycol 200; very slightly soluble in 0.1N sodium hydroxide; insoluble in water.

It has a molecular weight of 366.84 g/mol and the molecular formula C 22 H 19 ClO 3 . The compound has the following structural formula: The chemical name of proguanil hydrochloride, USP is 1-(4-chlorophenyl)-5-isopropyl-biguanide hydrochloride. Proguanil hydrochloride, USP is a white crystalline powder slightly soluble in water, sparingly soluble in alcohol, practically insoluble in methylene chloride.

It has a molecular weight of 290.22 g/mol 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, USP and 100 mg of proguanil hydrochloride, USP and each atovaquone and proguanil hydrochloride pediatric tablet contains 62.5 mg of atovaquone, USP and 25 mg of proguanil hydrochloride, USP. The inactive ingredients in both tablets are colloidal silicon dioxide, ferric oxide red, hypromellose 2910, low substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, poloxamer 188, polyethylene glycol 400, polyethylene glycol 8000, povidone K30, sodium starch glycolate and titanium dioxide. atovaquonestructure proguanilstructure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Important Administration Instructions • Advise patients to take atovaquone and proguanil hydrochloride tablets at the same time each day with food or a milky drink [see Dosage and Administration ( 2 )] . • Advise patients to take a repeat dose of atovaquone and proguanil hydrochloride if vomiting occurs within 1 hour after dosing [see Dosage and Administration ( 2 )] . • Advise patients 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. Severe Cutaneous Adverse Reactions (SCARs) Advise patients about the signs and symptoms of serious skin manifestations. Instruct patients to stop taking atovaquone and proguanil hydrochloride immediately and promptly report the first signs or symptoms of skin rash, mucosal lesions, or any other sign of hypersensitivity [see Warnings and Precautions ( 5.4 )] .

Hepatotoxicity 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 [see Warnings and Precautions ( 5.3 )] . Advise patients to immediately report symptoms such as yellowing of the skin or eyes, dark urine, pale stools, abdominal pain, nausea, vomiting, fatigue, or itching. Distributed by: Glenmark Pharmaceuticals Inc., USA Elmwood Park, NJ 07407 Questions?

1 (888) 721-7115 www.glenmarkpharma-us.com April 2026 logo

🧬 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 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 are related to body weight. The values CL/F for both atovaquone and proguanil in subjects with body weight ≥11 kg are shown in Table 4.

Table 4. Apparent Clearance for Atovaquone and Proguanil in Patients as a Function of Body Weight Atovaquone Proguanil Body Weight n CL/F (L/h) Mean ± SD a (range) n CL/F (L/h) Mean ± SD a (range) 11 to 20 kg 159 1.34 ± 0.63 (0.52 to 4.26) 146 29.5 ± 6.5 (10.3 to 48.3) 21 to 30 kg 117 1.87 ± 0.81 (0.52 to 5.38) 113 40.0 ± 7.5 (15.9 to 62.7) 31 to 40 kg 95 2.76 ± 2.07 (0.97 to 12.5) 91 49.5 ± 8.30 (25.8 to 71.5) >40 kg 368 6.61 ± 3.92 (1.32 to 20.3) 282 67.9 ± 19.9 (14.0 to 145) a SD = Standard deviation. 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% Cl: 1.70, 3.28). T max was longer in elderly subjects… [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 6. Table 6.

Prevention of Parasitemia a in Placebo-Controlled Clinical Trials of Atovaquone and Proguanil hydrochloride for Prophylaxis of P. falciparum Malaria in Residents of Malaria-Endemic Areas Atovaquone and Proguanil hydrochloride Placebo Total number of patients randomized 326 343 Failed to complete study 57 46 Developed parasitemia ( P. falciparum ) 2 92 a Free of parasitemia during the 10- to 12-week period of prophylactic therapy. 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 tablet 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 7.

Table 7. Prevention of Parasitemia a in Active-Controlled Clinical Trials of Atovaquone and Proguanil hydrochloride for Prophylaxis of P. falciparum Malaria in Non-Immune Travelers Atovaquone and proguanil hydrochloride 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 Free of parasitemia during the period of prophylactic therapy. 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… [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.

📄 Recent Major Changes 11 words ▾

Warnings and Precautions, Severe Cutaneous Adverse Reactions ( 5.4 ) 3/2026

📄 Package Label / Principal Display Panel 30 words ▾

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 68462-404-01 Atovaquone and Proguanil Hydrochloride Tablets 250 mg/100 mg label250mg100mg

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 68462-402-01 Atovaquone and Proguanil Hydrochloride Tablets 62.5 mg/25 mg label62pt5mg25mg100s

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

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
10.5K
Units reimbursed last 4 qtrs
379.7K
Gross reimbursed last 4 qtrs
$789.7K
Avg / prescription
$74.93
Avg / unit
$2.0797
Latest quarter Q1 2026
1.9KRx
Medicaid pays / ea
$2.0797
gross reimbursed
vs
NADAC / ea
$1.4858
acquisition cost
=
Spread
+$0.5939
+40% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
50% FFS 50% MCO
Fee-for-service · 5,313 Rx Managed care · 5,226 Rx
State Medicaid map
Alaska: no data reported AK Maine: 3,326 units · 238 per 100k residents ME Washington: 16,013 units · 205 per 100k residents WA Idaho: 702 units · 35.7 per 100k residents ID Montana: 774 units · 68.4 per 100k residents MT North Dakota: no data reported ND Minnesota: 48,085 units · 838 per 100k residents MN Wisconsin: 2,307 units · 39.0 per 100k residents WI Michigan: no data reported MI New York: 96,198 units · 492 per 100k residents NY Vermont: 1,201 units · 186 per 100k residents VT New Hampshire: 871 units · 62.1 per 100k residents NH Oregon: 6,162 units · 146 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: 1,654 units · 51.6 per 100k residents IA Illinois: 3,979 units · 31.7 per 100k residents IL Indiana: 511 units · 7.4 per 100k residents IN Ohio: 5,963 units · 50.6 per 100k residents OH Pennsylvania: 9,181 units · 70.8 per 100k residents PA New Jersey: 7,430 units · 80.0 per 100k residents NJ Massachusetts: 31,059 units · 444 per 100k residents MA California: 74,619 units · 192 per 100k residents CA Utah: 323 units · 9.5 per 100k residents UT Colorado: 3,680 units · 62.6 per 100k residents CO Nebraska: 574 units · 29.0 per 100k residents NE Missouri: no data reported MO Kentucky: 237 units · 5.2 per 100k residents KY West Virginia: no data reported WV Virginia: 10,253 units · 118 per 100k residents VA Maryland: 24,855 units · 402 per 100k residents MD Connecticut: 14,836 units · 410 per 100k residents CT Rhode Island: 1,088 units · 99.4 per 100k residents RI Arizona: 1,427 units · 19.2 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 6,555 units · 60.5 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: 1,953 units · 17.7 per 100k residents GA D.C.: 3,527 units · 519 per 100k residents DC Hawaii: no data reported HI Texas: 364 units · 1.2 per 100k residents TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.2838
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Minnesota 838 /100k
2 D.C. 519 /100k
3 New York 492 /100k
4 Massachusetts 444 /100k
5 Connecticut 410 /100k
6 Maryland 402 /100k
7 Maine 238 /100k
8 Washington 205 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
100 tablets this page68462-0404-01 10,539 Rx · $789,676
12 tablets68462-0404-67 7,468 Rx · $501,213
Drug total (last 4 qtrs): 18,007 Rx · 623,077 units · $1,290,888 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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 Hydrochloride — the ingredient across all brands.

Top reported reactions

Nausea189
Diarrhoea170
Vomiting150
Pyrexia149
Headache131
Malaria123
Dizziness112

Age at onset

Neonate6
Child7
Adolescent1
Adult39
Elderly7

Reporter sex

2,119 reports

Serious outcomes

Hospitalization513
Disabling112
Death33
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 75 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.
← 68462-0402-01 · Glenmark 68462-0405-30 · Glenmark →
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.