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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 (P. vivax) infection, P. vivax relapse occurred commonly when patients were treated with MALARONE 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 MALARONE immediately and institute appropriate therapy. ( 5.4 ) • MALARONE 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 ) 5.1 Vomiting and Diarrhea Absorption of atovaquone may be reduced in patients with diarrhea or vomiting. If MALARONE 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 MALARONE. 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 (P. vivax) infections, P. vivax parasite relapse occurred commonly when patients were treated with MALARONE alone. In the event of recrudescent P. falciparum infections after treatment with MALARONE or failure of chemoprophylaxis with MALARONE, patients should be treated with a different blood schizonticide. 5.3 Hepatotoxicity Elevated liver laboratory tests and cases of hepatit...
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adverse reactions
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 MALARONE 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 GlaxoSmithKline at 1-888-825-5249 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 MALARONE contains 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 MALARONE 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 MALARONE 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 MALARONE; 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 MALARONE or placebo in all studies. Prophylaxis with MALARONE 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 ...
adverse reactions table
Table 3. Adverse Reactions in Active-Controlled Clinical Trials of MALARONE for Prophylaxis of P. falciparum Malariaa Adverse experiences that started while receiving active study drug. b Mean duration of dosing based on recommended dosing regimens.Adverse ExperiencePercent of Subjects with Adverse Experiencesa(Percent of Subjects with Adverse Experiences Attributable to Therapy)Study 1Study 2MALARONEn = 493(28 days)bMefloquinen = 483(53 days)bMALARONEn = 511(26 days)bChloroquine plus Proguaniln = 511(49 days)bDiarrhea38(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