ATOVAQUONE

ATOVAQUONE is an FDA-registered drug product whose active ingredient is ATOVAQUONE. It is labelled by AvKARE taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 73190-098, application ANDA202960, label effective 20260614. It is one of 7 FDA drug label records sharing the active ingredient ATOVAQUONE. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing ATOVAQUONE are most often described in connection with: atovaquone oral, pneumocystis jirovecii, pcp adults, adolescents aged, cannot tolerate, treatment mild-to-moderate, trimethoprim-sulfamethoxazole tmp-smx, oxygen diffusion. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE Atovaquone oral suspension is a quinone antimicrobial drug indicated for: Prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents aged 13 years and older who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). (1.1) Treatment of mild-to-moderate PCP in adults and adolescents aged 13 years and older who cannot tolerate TMP-SMX. (1.2) Limitations of Use (1.3) : Treatment of severe PCP (alveolar arterial oxygen diffusion gradient [(A-a)DO 2 ] >45 mm Hg) with atovaquone oral suspension has not been studied. The efficacy of atovaquone oral suspension in subjects who are failing therapy with TMP-SMX has also not been studied. 1.1 Prevention of Pneumocystis jirovecii Pneumonia Atovaquone oral suspension is indicated for the prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). 1.2 Treatment of Mild-to-Moderate Pneumocystis jirovecii Pneumonia Atovaquone oral suspension is indicated for the acute oral treatment of mild-to-moderate PCP in adults and adolescents (aged 13 years and older) who cannot tolerate TMP-SMX. 1.3 Limitations of Use Clinical experience with atovaquone oral suspension for the treatment of PCP has been limited to subjects with mild-to-moderate PCP (alveolar-arterial oxygen diffusion gradient [(A-a)DO 2 ] ≤45 mm Hg). Treatment of more severe episodes of PCP with atovaquone oral suspension has not been studied. The efficacy of atovaquone in subjects who are failing therapy with TMP-SMX has also not been studied.

2 DOSAGE AND ADMINISTRATION Prevention of PCP: 1,500 mg (10 mL) once daily with food. (2.1) Treatment of PCP: 750 mg (5 mL) twice daily with food for 21 days. (2.2) Supplied in Bottles: Shake bottle gently before use. (2.3) 2.1 Dosage for the Prevention of P. jirovecii Pneumonia The recommended oral dosage is 1,500 mg (10 mL) once daily administered with food. 2.2 Dosage for the Treatment of Mild-to-Moderate P. jirovecii Pneumonia The recommended oral dosage is 750 mg (5 mL) twice daily (total daily dose = 1,500 mg) administered with food for 21 days. 2.3 Important Administration Instructions Administer atovaquone oral suspension with food to avoid low plasma atovaquone concentrations that may limit response to therapy [see Warnings and Precautions (5.1) , Clinical Pharmacology (12.3) ]. Atovaquone Oral Suspension Bottle Shake bottle gently before administering the recommended dosage.

4 CONTRAINDICATIONS Atovaquone oral suspension is contraindicated in patients who develop or have a history of hypersensitivity reactions to atovaquone or any of the components of atovaquone oral suspension [see Warnings and Precautions (5.3) , Adverse Reactions (6.2) ] . Known serious allergic/hypersensitivity reaction to atovaquone or any of the components of atovaquone oral suspension. (4)

6 ADVERSE REACTIONS The following adverse reactions are discussed in another section of the labeling: Hepatotoxicity [see Warnings and Precautions (5.2) ]. Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] . PCP Prevention: The most frequent adverse reactions (≥25% that required discontinuation) were diarrhea, rash, headache, nausea, and fever. (6.1) PCP Treatment: The most frequent adverse reactions (≥14% that required discontinuation) were rash (including maculopapular), nausea, diarrhea, headache, vomiting, and fever. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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. Additionally, because many subjects who participated in clinical trials with atovaquone had complications of advanced human immunodeficiency virus (HIV) disease, it was often difficult to distinguish adverse reactions caused by atovaquone from those caused by underlying medical conditions. PCP Prevention Trials In 2 clinical trials, atovaquone oral suspension was compared with dapsone or aerosolized pentamidine in HIV-1-infected adolescent (13 to 18 years) and adult subjects at risk of PCP (CD4 count <200 cells/mm 3 or a prior episode of PCP) and unable to tolerate TMP-SMX. Dapsone Comparative Trial: In the dapsone comparative trial (n = 1,057), the majority of subjects were white (64%), male (88%), and receiving prophylaxis for PCP at randomization (73%); the mean age was 38 years. Subjects received atovaquone oral suspension 1,500 mg once daily (n = 536) or dapsone 100 mg once daily (n = 521); median durations of exposure were 6.7 and 6.5 months, respectively. Adverse reaction data were collected only for adverse reactions requiring discontinuation of treatment, which occurred at similar frequencies in subjects treated with atovaquone oral suspension or dapsone (Table 1). Among subjects taking neither dapsone nor atovaquone at enrollment (n = 487), adverse reactions requiring discontinuation of treatment occurred in 43% of subjects treated with dapsone and 20% of subjects treated with atovaquone oral suspension. Gastrointestinal adverse reactions (nausea, diarrhea, and vomiting) were more frequently reported in subjects treated with atovaquone oral suspension (Table 1). Table 1. Percentage (>2%) of Subjects with Selected Adverse Reactions Requiring Discontinuation of Treatment in the Dapsone Comparative PCP Prevention Trial Adverse Reaction All Subjects Atovaquone Oral Suspension 1,500 mg/day (n = 536) % Dapsone 100 mg/day (n = 521) % Rash 6.3 8.8 Nausea 4.1 0.6 Diarrhea 3.2 0.2 Vomiting 2.2 0.6 Aerosolized Pentamidine Comparative Trial: In the aerosolized pentamidine comparative trial (n = 549), the majority of subjects were white (79%), male (92%), and were primary prophylaxis patients at enrollment (58%); the mean age was 38 years. Subjects received atovaquone oral suspension once daily at a dose of 750 mg (n = 188) or 1,500 mg (n = 175) or received aerosolized pentamidine 300 mg every 4 weeks (n = 186); the median durations of exposure were 6.2, 6.0, and 7.8 months, respectively. Table 2 summarizes the clinical adverse reactions reported by ≥20% of the subjects receiving either the 1,500-mg dose of atovaquone oral suspension or aerosolized pentamidine. Rash occurred more often in subjects treated with atovaquone oral suspension (46%) than in subjects treated with aerosolized pentamidine (28%). Treatment-limiting adverse reactions occurred in 25% of subjects treated with atovaquone oral suspension 1,500 mg once daily and in 7% of subjects treated with aerosolized pentamidine. The most frequent adverse reactions requiring discontinuation of dosing in the group receiving atovaquone oral suspension 1,500 mg once daily were rash (6%), diarrhea (4%), and nausea (3%). The most frequent adverse reaction requiring discontinuation of dosing in the group receiving aerosolized pentamidine was bronchospasm (2%). Table 2. Percentage (≥20%) of Subjects with Selected Adverse Reactions in the Aerosolized Pentamidine Comparative PCP Prevention Trial Adverse Reaction Atovaquone Oral Suspension 1,500 mg/day (n = 175) % Aerosolized Pentamidine (n = 186) % Diarrhea 42 35 Rash 39 28 Headache 28 22 Nausea 26 23 Fever 25 18 Rhinitis 24 17 Other reactions occurring in ≥10% of subjects receiving the recommended dose of atovaquone oral suspension (1,500 mg once daily) included vomiting, sweating, flu syndrome, sinusitis, pruritus, insomnia, depression, and myalgia. PCP Treatment Trials Safety information is presented from 2 clinical efficacy trials of the atovaquone tablet formulation: 1) a randomized, double-blind trial comparing atovaquone tablets with TMP-SMX in subjects with acquired immunodeficiency syndrome (AIDS) and mild-to-moderate PCP [(A-a)DO 2 ] ≤45 mm Hg and PaO 2 ≥60 mm Hg on room air; 2) a randomized, open-label trial comparing atovaquone tablets with intravenous (IV) pentamidine isethionate in subjects with mild-to-moderate PCP who could not tolerate trimethoprim or sulfa antimicrobials. TMP-SMX Comparative Trial: In the TMP-SMX comparative trial (n = 408), the majority of subjects were white (66%) and male (95%); the mean age was 36 years. Subjects received atovaquone 750 mg (three 250-mg tablets) 3 times daily for 21 days or TMP 320 mg plus SMX 1,600 mg 3 times daily for 21 days; median durations of exposure were 21 and 15 days, respectively. Table 3 summarizes all clinical adverse reactions reported by ≥10% of the trial population regardless of attribution. Nine percent of subjects who received atovaquone and 24% of subjects who received TMP-SMX discontinued therapy due to an adverse reaction. Among the subjects who discontinued, 4% of subjects receiving atovaquone and 8% of subjects in the TMP-SMX group discontinued therapy due to rash. The incidence of adverse reactions with atovaquone oral suspension at the recommended dose (750 mg twice daily) was similar to that seen with the tablet formulation. Table 3. Percentage (≥10%) of Subjects with Selected Adverse Reactions in the TMP-SMX Comparative PCP Treatment Trial Adverse Reaction Atovaquone Tablets (n = 203) % TMP-SMX (n = 205) % Rash (including maculopapular) 23 34 Nausea 21 44 Diarrhea 19 7 Headache 16 22 Vomiting 14 35 Fever 14 25 Insomnia 10 9 Two percent of subjects treated with atovaquone and 7% of subjects treated with TMP-SMX had therapy prematurely discontinued due to elevations in ALT/AST. Pentamidine Comparative Trial: In the pentamidine comparative trial (n = 174), the majority of subjects in the primary therapy trial population (n = 145) were white (72%) and male (97%); the mean age was 37 years. Subjects received atovaquone 750 mg (three 250-mg tablets) 3 times daily for 21 days or a 3- to 4-mg/kg single pentamidine isethionate IV infusion daily for 21 days; the median durations of exposure were 21 and 14 days, respectively. Table 4 summarizes the clinical adverse reactions reported by ≥10% of the primary therapy trial population regardless of attribution. Fewer subjects who received atovaquone reported adverse reactions than subjects who received pentamidine (63% vs. 72%). However, only 7% of subjects discontinued treatment with atovaquone due to adverse reactions, while 41% of subjects who received pentamidine discontinued treatment for this reason. Of the 5 subjects who discontinued therapy with atovaquone, 3 reported rash (4%). Rash was not severe in any subject. The most frequently cited reasons for discontinuation of pentamidine therapy were hypoglycemia (11%) and vomiting (9%). Table 4. Percentage (≥10%) of Subjects with Selected Adverse Reactions in the Pentamidine Comparative PCP Treatment Trial (Primary Therapy Group) Adverse Reaction Atovaquone Tablets (n = 73) % Pentamidine (n = 71) % Fever 40 25 Nausea 22 37 Rash 22 13 Diarrhea 21 31 Insomnia 19 14 Headache 18 28 Vomiting 14 17 Cough 14 1 Sweat 10 3 Monilia, oral 10 3 Laboratory abnormality was reported as the reason for discontinuation of treatment in 2 of 73 subjects (3%) who received atovaquone, and in 14 of 71 subjects (20%) who received pentamidine. One subject (1%) receiving atovaquone had elevated creatinine and BUN levels and 1 subject (1%) had elevated amylase levels. In this trial, elevated levels of amylase occurred in subjects (8% versus 4%) receiving atovaquone tablets or pentamidine, respectively. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of atovaquone oral suspension. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders Methemoglobinemia, thrombocytopenia. Immune System Disorders Hypersensitivity reactions including angioedema, bronchospasm, throat tightness, and urticaria. Eye Disorders Vortex keratopathy. Gastrointestinal Disorders Pancreatitis. Hepatobiliary Disorders Hepatitis, fatal liver failure. Skin and Subcutaneous Tissue Disorders Erythema multiforme (EM), Stevens-Johnson syndrome (SJS), skin desquamation, and drug reaction with eosinophilia and systemic symptoms (DRESS). Renal and Urinary Disorders Acute renal impairment. To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www. fda.gov/medwatch

FDA lists 7 drug label records with ATOVAQUONE as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

5 FDA recall record(s) match this product name or manufacturer. A match means the firm or product name appears in the enforcement report; confirm lot numbers and dates against the official FDA notice before acting.

What is ATOVAQUONE used for?
1 INDICATIONS AND USAGE Atovaquone oral suspension is a quinone antimicrobial drug indicated for: Prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents aged 13 years and older who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). (1.1) Treatment of mild-to-moderate PCP in adults and adolescents aged 13 years and older who cannot tolerate TMP-SMX. (1.2) Limitations …

Who makes ATOVAQUONE?
AvKARE is the labeler of record for ATOVAQUONE. 7 FDA label records share the active ingredient ATOVAQUONE, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does ATOVAQUONE come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is ATOVAQUONE prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing ATOVAQUONE?
Yes. 7 FDA drug label records list ATOVAQUONE as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has ATOVAQUONE been recalled?
5 FDA recall record(s) match this product name or manufacturer. Review the recall and safety notices section on this page and confirm lot numbers against the official FDA enforcement report.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.