Tafenoquine

Indications

Tafenoquine is used for: Malaria

Adult Dose

Malaria Prevention of relapse following treatment of acute P vivax infection 150mg preparation Indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged ?16 yr who are receiving appropriate antimalarial therapy for acute P vivax infection 300 mg PO as a single dose Coadminister tafenoquine on the first or second day of the appropriate antimalarial therapy (eg, chloroquine) for acute P vivax malaria Prophylaxis when traveling to malarious area 100mg preparation Indicated for malaria prophylaxis in patients aged >18 years Complete the full treatment course of Arakoda including the loading dose and the terminal dose Loading regimen For each of the 3 days before travel to a malarious area: 200 mg PO qDay for 3 days Maintenance regimen While in malarious area: 200 mg once weekly starting 7 days after the last loading regimen dose Terminal prophylaxis regimen In the week following exit from the malarious area: 200 mg PO as a single, one-time dose, taken 7 days after the last maintenance dose

Child Dose

Malaria Prevention of relapse following treatment of acute P vivax infection Indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients who are receiving appropriate antimalarial therapy for acute P vivax infection <16 years: Safety and efficacy not established >16 years 150mg preparation 300 mg PO as a single dose Coadminister tafenoquine on the first or second day of the appropriate antimalarial therapy (eg, chloroquine) for acute P vivax malaria

Renal Dose

Administration

Administer with food to increase systemic absorption Swallow tablets whole; do not break, crush, or chew

Contra Indications

Patients with G6PD deficiency or unknown G6PD status owing to the risk of hemolytic anemia Breastfeeding by lactating women of infants found to be G6PD deficient or if infant G6PD status is unknown Known hypersensitivity to tafenoquine, other 8-aminoquinolines, or any component of tafenoquine History of psychotic disorders or current psychotic symptoms (ie, hallucinations, delusions, grossly disorganized behavior)

Precautions

Owing to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing must be performed before prescribing; advise patients to seek medical attention if signs of hemolysis occur (see Contraindications and Dosing Considerations) Use during pregnancy or in breastfeeding women may cause hemolytic anemia in a G6PD-deficient fetus or infant, respectively (see Contraindications and Pregnancy and Lactation) Asymptomatic methemoglobin elevations observed; initiate appropriate therapy if signs or symptoms of methemoglobinemia occur; carefully monitor individuals with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency Psychiatric adverse reactions (eg, anxiety, abnormal dreams, insomnia) reported in clinical trials; benefit of treatment must be weighed against the potential risk for psychiatric adverse reactions in patients with a history of psychiatric illness; owing to long half-life (~15 days), signs or symptoms of psychiatric adverse reactions that may occur could be delayed in onset and/or duration

Pregnancy-Lactation

Pregnancy Available data in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, it is recommended to avoid use during pregnancy Use during pregnancy may cause hemolytic anemia in a G6PD-deficient fetus Clinical considerations Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth Pregnancy testing Verify the pregnancy status in females of reproductive potential prior to initiating treatment Contraception May cause hemolytic anemia in a G6PD-deficient fetus Advise females of reproductive potential that treatment during pregnancy is not recommended and to avoid pregnancy or use effective contraception for 3 months after the tafenoquine dose Animal studies In animal studies, there were increased abortions, with and without maternal toxicity, when tafenoquine was given orally to pregnant rabbits at and above doses equivalent to about 0.4 times the clinical exposure based on body surface area comparisons No fetotoxicity was observed at doses equivalent to the clinical exposure (based on body surface area comparisons) in a similar study in rats Lactation Use in breastfeeding women may cause hemolytic anemia in a G6PD-deficient infant Infant G6PD status should be checked before breastfeeding begins; if an infant is G6PD deficient, advise not to breastfeed for 3 months after the dose No data are available regarding the presence of tafenoquine in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production In a breastfed infant with normal G6PD, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential effects on the breastfed infant

Interactions

Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro Avoid coadministration with drugs that are OCT2 or MATE substrates If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug

Adverse Effects

Side effects of Tafenoquine : >10% Headache (15-32%) Vortex keratopathy (21%) Diarrhea (5-18%) Back pain (14%) Asymptomatic methemoglobin elevations (13%) 1-10% Dizziness (8%) Nausea (6%) Vomiting (6%) Decreased hemoglobin (5%) Headache (5%) Insomnia (3%)

Mechanism of Action

Antiplasmodial 8-aminoquinoline derivative with activity against the P vivax lifecycle, including hypnozoites It is active against preerythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of P vivax; activity against the preerythrocytic liver stages of the parasite prevents the development of the erythrocytic forms of the parasite, which are responsible for relapses in P vivax malaria