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warnings and cautions
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 tablets 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 tablets have 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 ) 5.1 Vomiting 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 tablets. 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. 5.2 Relapse 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 tablets 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. 5.3 Hepatotoxicity Elevated liver laboratory tests and cases of hepatitis and hepatic failure requirin...
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adverse reactions
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 tablets 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 Mylan at 1-877-446-3679 (1-877-4-INFO-RX) 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. 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 tablets 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 tablets 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 tablets; 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 tablets or placebo in all studies. Prophylaxis with atovaquone and proguanil hydrochloride tablets 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 ...
adverse reactions table
Percent of Subjects with Adverse ExperiencesAdverse experiences that started while receiving active study drug. (Percent of Subjects with Adverse Experiences Attributable to Therapy)Study 1Study 2Atovaquone and Proguanil Hydrochloride Tablets n = 493 (28 days)Mean duration of dosing based on recommended dosing regimens.Mefloquine n = 483 (53 days)Atovaquone and Proguanil Hydrochloride Tablets n = 511 (26 days)Chloroquine plus Proguanil n = 511 (49 days)Diarrhea38(8)36(7)34(5)39(7)Nausea14(3)20(8)11(2)18(7)Abdominal pain17(5)16(5)14(3)22(6)Headache12(4)17(7)12(4)14(4)Dreams7(7)16(14)6(4)7(3)Insomnia5(3)16(13)4(2)5(2)Fever9(< 1)11(1)8(< 1)8(< 1)Dizziness5(2)14(9)7(3)8(4)Vomiting8(1)10(2)8(0)14(2)Oral ulcers9(6)6(4)5(4)7(5)Pruritus4(2)5(2)3(1)2(< 1)Visual difficulties2(2)5(3)3(2)3(2)Depression< 1(< 1)5(4)< 1(< 1)1(< 1)Anxiety1(< 1)5(4)< 1(< 1)1(< 1)