Tafenoquine

5 WARNINGS AND PRECAUTIONS • Hemolytic Anemia : G6PD testing must be performed before prescribing ARAKODA due to the risk of hemolytic anemia. Monitor patients for signs or symptoms of hemolysis. ( 5.1 ) • G6PD Deficiency in Pregnancy or Lactation : ARAKODA may cause fetal harm when administered to a pregnant woman with a G6PD-deficient fetus. ARAKODA is not recommended during pregnancy. A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to ARAKODA through breast milk. Check infant’s G6PD status before breastfeeding begins. ( 5.2 , 8.1 , 8.2 ) • Methemoglobinemia : Asymptomatic elevations in blood methemoglobin have been observed. Initiate appropriate therapy if signs or symptoms of methemoglobinemia occur. ( 5.3 ) • Psychiatric Effects : Serious psychotic adverse reactions have been observed in patients with a history of psychosis or schizophrenia, at doses different from the approved dose. If psychotic symptoms (hallucinations, delusions, or grossly disorganized thinking or behavior) occur, consider discontinuation of ARAKODA therapy and, evaluation by a mental health professional as soon as possible. ( 5.4 ) • Hypersensitivity Reactions : Serious hypersensitivity reactions have been observed with administration of ARAKODA. If hypersensitivity reactions occur, institute appropriate therapy. ( 5.5 ) • Delayed Adverse Reactions : Due to the long half-life of ARAKODA (approximately 17 days), psychiatric effects, hemolytic anemia, methemoglobinemia, and hypersensitivity reactions may be delayed in onset and/or duration. ( 5.6 , 12.3 ) 5.1 Hemolytic Anemia Due to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing must be performed before prescribing ARAKODA [see Contraindications ( 4 )] . Due to the limitations with G6PD tests, physicians need to be aware of residual risk of hemolysis and adequate medical support and follow-up to manage hemolytic risk should be available. Treatment with ARAKODA is contraindicated in patients with G6PD deficiency or unknown G6PD status [see Contraindications ( 4 )] . In clinical trials, declines in hemoglobin levels were reported in some G6PD-normal patients [see Adverse Reactions ( 6.1 )] . Monitor patients for clinical signs or symptoms of hemolysis [see Warnings and Precautions ( 5.6 )] . Advise patients to discontinue ARAKODA and seek medical attention if signs of hemolysis occur. 5.2 G6PD Deficiency in Pregnancy and Lactation Potential Harm to the Fetus The use of ARAKODA during pregnancy may cause hemolytic anemia in a G6PD-deficient fetus. Even if a pregnant woman has normal levels of G6PD, the fetus could be G6PD deficient. Advise females of reproductive potential that treatment with ARAKODA during pregnancy is not recommended and to avoid pregnancy or use effective contraception during treatment and for 3 months after the last dose of ARAKODA. If a pregnancy is detected during ARAKODA use, discontinue ARAKODA as soon as possible and switch to an alternative prophylactic drug for malaria during pregnancy [see Use in Specific Populations ( 8.1 and 8.3 )] . Potential Harm to the Breastfeeding Infant A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to ARAKODA through breast milk. Infant G6PD status should be checked before breastfeeding begins. ARAKODA is contraindicated in breastfeeding women when the infant is found to be G6PD deficient or the G6PD status of the infant is unknown [see Contraindications ( 4 )] . Advise the woman with a G6PD-deficient infant or if the G6PD status of the infant is unknown not to breastfeed during treatment with ARAKODA and for 3 months after the final dose [see Use in Specific Populations ( 8.2 )] . 5.3 Methemoglobinemia Asymptomatic elevations in methemoglobin have been observed in the clinical trials of ARAKODA [see Adverse Reactions ( 6.1 )] . Institute appropriate therapy if signs or symptoms of methemoglobinemia occur [see Warnings and Precautions ( 5.6 )] . Carefully monitor individuals with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency. Advise patients to discontinue ARAKODA and seek medical attention if signs of methemoglobinemia occur. 5.4 Psychiatric Effects In patients receiving ARAKODA in clinical trials, psychiatric adverse reactions included sleep disturbances (2.5%), depression/depressed mood (0.3%), and anxiety (0.2%) [see Adverse Reactions ( 6.1 )] . ARAKODA was discontinued in a subject with an adverse reaction of suicide attempt (0.1%). Subjects with a history of psychiatric disorders were excluded from three of five ARAKODA trials in which mefloquine was included as a comparator. Psychosis was reported in three patients with a history of psychosis or schizophrenia who received tafenoquine doses (350 mg to 500 mg single dose, or 400 mg daily for 3 days) different from the approved ARAKODA regimen. Safety and effectiveness of ARAKODA have not been established at doses or regimens other than the approved regimen; use of ARAKODA at doses or regimens other than a 200-mg weekly dose is not approved by FDA. ARAKODA is contraindicated in patients with a history of psychotic disorders or current psychotic symptoms [see Contraindication ( 4 )] . If psychotic symptoms (hallucinations, delusions, or grossly disorganized thinking or behavior) occur, consider discontinuation of ARAKODA and prompt evaluation by a mental health professional as soon as possible. Other psychiatric symptoms, such as changes in mood, anxiety, insomnia, and nightmares, should be promptly evaluated by a medical professional if they are moderate and last more than three days or are severe [see Warnings and Precautions ( 5.6 )] . 5.5 Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., angioedema and urticaria) have been observed with administration of tafenoquine. Hypersensitivity reactions have been reported in clinical trials of ARAKODA [see Adverse Reactions ( 6.1 )] . Discontinue prophylaxis with ARAKODA and institute appropriate therapy if hypersensitivity reactions occur [see Warnings and Precautions ( 5.6 )] . ARAKODA is contraindicated in patients who develop hypersensitivity to tafenoquine or any component of ARAKODA or other 8-aminoquinolines [see Contraindications ( 4 )] . 5.6 Delayed Adverse Reactions, Including Hemolytic Anemia, Methemoglobinemia, Psychiatric Effects, and Hypersensitivity Reactions Adverse reactions including hemolytic anemia, methemoglobinemia, psychiatric effects, and hypersensitivity reactions were reported with the use of ARAKODA or tafenoquine in clinical trials [see Warnings and Precautions ( 5.1 , 5.3 , 5.4 , 5.5 )] . Due to the long half-life of ARAKODA (approximately 17 days), psychiatric effects, hemolytic anemia, methemoglobinemia, and signs or symptoms of hypersensitivity reactions that may occur could be delayed in onset and/or duration. Advise patients to seek medical attention if signs of hypersensitivity occur [see Clinical Pharmacology ( 12.3 )] .