Tafenoquine is an oral antimalarial indicated for malaria prophylaxis in adults and for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged 16 years and older who are receiving appropriate antimalarial therapy for acute P. vivax infection. Tafenoquine is not indicated for the acute treatment of P. vivax infection. Screening of all patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency is necessary prior to tafenoquine use due to the risk for hemolytic anemia. Psychiatric adverse events have occurred with tafenoquine use and are more common in patients with a history of psychotic disorders. Due to the long half-life of tafenoquine, signs or symptoms of psychiatric events could be delayed in onset and/or duration.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer with food.
-Swallow tablets whole. Do not break, crush, or chew the tablets.
For radical cure (prevention of relapse) single-dose therapy:
-In the event of vomiting within 1 hour after dosing, repeat the dose. Do not attempt redosing more than once.
For multidose malaria prophylaxis therapy:
-For 1 loading dose missed, replace 1 dose of 200 mg so that total of 3 daily loading doses have been taken. Begin maintenance dose 1 week after last loading dose.
-For 2 loading doses missed, replace 2 doses of 200 mg on 2 consecutive days so that total of 3 daily loading doses have been taken. Begin maintenance dose 1 week after last loading dose.
-For 1 or 2 weekly maintenance doses missed, replace 1 dose of 200 mg on any day up to the time of the next scheduled weekly dose.
-For 3 or more weekly maintenance doses missed, replace 2 doses of 200 mg, taken as 200 mg once daily on 2 consecutive days up to the time of the next scheduled weekly dose.
-For terminal prophylaxis dose missed, replace 1 dose of 200 mg as soon as remembered.
Hemolytic anemia (less than 1%) has been observed with tafenoquine. In clinical trials, decreased hemoglobin was reported in 5% of G6PD-normal patients treated with tafenoquine and chloroquine and in 2.3% of patients receiving tafenoquine alone. Monitor patients for clinical signs or symptoms of hemolysis. Advise patients to seek medical attention if signs of hemolysis occur. Due to the long half-life of tafenoquine, signs or symptoms of hemolytic anemia could be delayed in onset and/or duration. Anemia and thrombocytopenia have also been reported in less than 1% of patients receiving tafenoquine during clinical trials.
Asymptomatic elevations in methemoglobin were observed in clinical trials with tafenoquine; increased blood methemoglobin was reported in 3% or less of patients treated with single-dose tafenoquine and in 13% of patients in multidose tafenoquine trials. Institute appropriate therapy if signs or symptoms of methemoglobinemia occur. Carefully monitor patients with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency. Advise patients to seek medical attention if signs of methemoglobinemia occur. Due to the long half-life of tafenoquine, signs or symptoms of methemoglobinemia could be delayed in onset and/or duration.
Psychiatric adverse reactions have been reported with tafenoquine use and include depression or depressed mood (1% or less) and anxiety (1% or less), which includes anxiety disorder, panic attack, and stress. Sleep disturbances (2.5%) have also been reported and include abnormal dreams (2% or less), insomnia (1% to 3%), nightmares, sleep disorder, and somnambulism. Agitation and neurosis have been reported in less than 1% of tafenoquine-treated patients. Prophylactic tafenoquine was discontinued in a patient that attempted suicide (0.1%). Psychosis was reported in 5 patients with a history of psychiatric disorders, such as psychosis or schizophrenia, who received doses different than the FDA-approved regimens. If psychotic symptoms (hallucinations, delusions, or grossly disorganized thinking or behavior) occur, consider discontinuation of tafenoquine 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 3 days or are severe. Due to the long half-life of tafenoquine, signs or symptoms of psychiatric events could be delayed in onset and/or duration.
Serious hypersensitivity reactions, such as angioedema (3% or less) and urticaria (3% or less), have been observed with tafenoquine use. Due to the long half-life of tafenoquine, signs or symptoms of hypersensitivity could be delayed in onset and/or duration. Institute appropriate therapy if hypersensitivity reactions occur. Discontinue tafenoquine prophylaxis, and do not readminister tafenoquine.
Nervous system adverse effects have been reported with the use of tafenoquine. Dizziness and postural dizziness (1% to 8%) and headache (5% to 32%), such as sinus headache, migraine, and tension headache, were reported in tafenoquine-treated patients across all clinical trials. In a single-dose tafenoquine trial, somnolence (drowsiness) was reported in 3% or less of patients. Other nervous system disorders reported in less than 1% of tafenoquine-treated patients during multidose trials include amnesia, abnormal coordination, hyperesthesia, hypoesthesia, somnolence, syncope, and tremor.
Gastrointestinal adverse effects have been reported with tafenoquine. Diarrhea (5% to 18%), nausea (5% to 7%), and vomiting (2% to 6%) have been reported in tafenoquine-treated patients across all clinical trials.
Hyperbilirubinemia and jaundice due to cholestasis were reported in less than 1% of tafenoquine-treated patients during multidose trials. Increased bilirubin, increased blood creatinine, and decreased glomerular filtration rate were also reported in less than 1% of tafenoquine-treated patients in multidose trials. In a single-dose tafenoquine trial, altered laboratory investigations reported in 3% or less of patients include increased blood creatinine and elevated hepatic enzymes, specifically increased alanine aminotransferase. Increased or abnormal alanine aminotransferase was noted in 4% of tafenoquine-treated patients in multidose trials.
Vortex keratopathy was reported in 21% to 93% of patients receiving tafenoquine in multidose trials which included ophthalmic evaluations. Keratopathy did not result in any apparent functional visual changes and resolved within 1 year after stopping tafenoquine in all patients. Retinal abnormalities were noted in less than 1% of tafenoquine-treated patients in multidose trials. A total of 7 serious ocular adverse reactions were reported in tafenoquine-treated patients in multidose trials and included 5 reports of keratopathy and 2 reports of retinal disorders In a single-dose tafenoquine trial, eye disorders reported in 3% or less of patients include vortex keratopathy and photophobia. Eye disorders reported in less than 1% of patients receiving tafenoquine in multidose trials include night blindness, photophobia, blurred vision, reduced visual acuity, visual impairment, vitreous floaters, and visual field defect.
Back pain was reported in 14% of tafenoquine-treated patients during multidose trials.
Motion sickness, including vertigo and positional vertigo, was reported in 5% of tafenoquine-treated patients during multidose trials. Hyperacusis and Meniere's disease were reported in less than 1% of tafenoquine-treated patients.
Tafenoquine is contraindicated in patients with known tafenoquine or other 8-aminoquinoline hypersensitivity, such as primaquine hypersensitivity or iodoquinol hypersensitivity.
Perform testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to tafenoquine therapy in all patients. Tafenoquine is contraindicated in patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia. Due to the limitations of G6PD tests, there is a residual risk of hemolysis. Monitor patients for clinical signs or symptoms of hemolysis; ensure adequate medical support and follow-up to manage hemolytic risk are available. In clinical trials, declines in hemoglobin concentrations were reported in some G6PD-normal patients. Advise patients to seek medical attention if signs of hemolysis occur.
Monitor patients with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency for signs or symptoms of methemoglobinemia during tafenoquine therapy. Asymptomatic elevations in methemoglobin were observed in clinical trials with tafenoquine. Advise patients to seek medical attention if signs of methemoglobinemia occur. Institute appropriate therapy if signs or symptoms of methemoglobinemia occur.
Multidose tafenoquine therapy for malaria prophylaxis is contraindicated for use in patients with a history of psychotic disorders (psychosis) or current psychotic symptoms (i.e. hallucinations, delusions, and/or grossly disorganized behavior). If psychotic symptoms occur, consider discontinuation of tafenoquine 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 3 days or are severe. Weigh the benefit of single-dose tafenoquine therapy against the potential risk for psychiatric adverse reactions in patients with a history of a psychiatric event or illness. Depression and psychosis have occurred primarily in patients with a history of psychiatric disorders after receipt of single tafenoquine doses higher than the FDA-approved dosage. Due to the long half-life of tafenoquine, signs or symptoms of psychiatric events could be delayed in onset and/or duration.
Monitor for tafenoquine-associated adverse reactions if tafenoquine is administered to patients with hepatic impairment. The pharmacokinetics of tafenoquine have not been studied in patients with hepatic disease.
Monitor for tafenoquine-associated adverse reactions if tafenoquine is administered to patients with renal impairment or renal failure. The pharmacokinetics of tafenoquine have not been studied in patients with renal disease.
Tafenoquine use during pregnancy is not recommended. Advise females of reproductive potential to avoid pregnancy during treatment with tafenoquine. If pregnancy occurs during prophylactic tafenoquine use, discontinue tafenoquine as soon as possible and switch to an alternative prophylactic drug for malaria during pregnancy. Use of tafenoquine during pregnancy may cause hemolytic anemia in a glucose-6-phosphate dehydrogenase (G6PD)-deficient fetus. Even if a pregnant woman is G6PD-normal, the fetus could be G6PD-deficient. Available data with tafenoquine use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, increased abortions were observed 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. No fetotoxicity was observed at doses about 1.5 times the clinical exposure based on body surface area comparisons in a similar study in rats. Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth.
There is no information regarding the presence of tafenoquine in human breast milk, the effects on the breast-fed infant, or the effects on milk production. Test the infant for G6PD deficiency before tafenoquine is given to a woman who is breast-feeding. Tafenoquine is contraindicated in breast-feeding women when the infant is glucose-6-phosphate dehydrogenase (G6PD)-deficient or infant G6PD status is unknown, due to the risk of hemolytic anemia from exposure to tafenoquine through breast milk. If an infant is G6PD-deficient or status is unknown, withhold breast-feeding for 3 months after the last tafenoquine dose. In a breast-feeding GDPD-normal infant, consider the benefits of breast-feeding along with the mother's clinical need for tafenoquine and any potential effects on the breast-fed infant from tafenoquine or the underlying maternal condition.
Tafenoquine is associated with reproductive risk. Verify pregnancy status in females of reproductive potential with pregnancy testing prior to tafenoquine use. Discuss contraception requirements with the patient. Advise females of reproductive potential to avoid pregnancy or use effective contraception for 3 months after the last tafenoquine dose.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Plasmodium falciparum, Plasmodium vivax
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the radical cure (prevention of relapse) of malaria due to P. vivax or P. ovale* in patients who are receiving appropriate antimalarial therapy for acute infection:
Oral dosage (Krintafel):
Adults: 300 mg PO as a single dose on the first or second day of the appropriate antimalarial therapy. Guidelines recommend for chloroquine-susceptible P. vivax or P. ovale in combination with chloroquine or hydroxychloroquine. The FDA-approved labeling indicates tafenoquine only for use with chloroquine due to recurrence demonstrated in patients receiving artemisinin-based therapy.
Adolescents 16 to 17 years: 300 mg PO as a single dose on the first or second day of the appropriate antimalarial therapy. Guidelines recommend for chloroquine-susceptible P. vivax or P. ovale in combination with chloroquine or hydroxychloroquine. The FDA-approved labeling indicates tafenoquine only for use with chloroquine due to recurrence demonstrated in patients receiving artemisinin-based therapy.
For malaria prophylaxis:
Oral dosage (Arakoda):
Adults: 200 mg PO once daily for 3 days prior to entry into endemic area, then 200 mg PO once weekly starting 7 days after the last loading dose and continuing during travel to malarious area as maintenance regimen, then 200 mg PO once at 7 days after the last maintenance dose in the week after leaving the area as terminal prophylaxis regimen. Tafenoquine may be administered for up to 6 months of continuous dosing. Recommended for travel to all areas.
Adolescents* 16 to 17 years: 200 mg PO once daily for 3 days prior to entry into endemic area, then 200 mg PO once weekly starting 7 days after the last loading dose and continuing during travel to malarious area as maintenance regimen, then 200 mg PO once at 7 days after the last maintenance dose in the week after leaving the area as terminal prophylaxis regimen. Tafenoquine may be administered for up to 6 months of continuous dosing. Recommended for travel to all areas.
Maximum Dosage Limits:
-Adults
300 mg PO as single dose for radical cure (prevention of relapse) of P.vivax malaria; 200 mg/day PO for 3 days, then 200 mg/week PO for malaria prophylaxis.
-Geriatric
300 mg PO as single dose for radical cure (prevention of relapse) of P.vivax malaria; 200 mg/day PO for 3 days, then 200 mg/week PO for malaria prophylaxis.
-Adolescents
16 to 17 years: 300 mg PO as single dose for radical cure (prevention of relapse) of P.vivax malaria; safety and efficacy have not been established for malaria prophylaxis.
13 to 15 years: Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Alogliptin; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Canagliflozin; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Dapagliflozin; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Dofetilide: (Contraindicated) Coadministration of dofetilide and tafenoquine is contraindicated due to the potential for increased dofetilide concentrations and arrhythmias (QT prolongation and torsade de pointes). The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like dofetilide, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Dofetilide is eliminated by cationic renal secretion, and tafenoquine may interfere with the renal elimination of dofetilide.
Empagliflozin; Linagliptin; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Empagliflozin; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Ertugliflozin; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Glipizide; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Glyburide; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Linagliptin; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Metformin; Repaglinide: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Metformin; Saxagliptin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Metformin; Sitagliptin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Penicillamine: (Major) Do not use penicillamine concurrently with antimalarials due to an increased risk of severe hematologic and renal adverse reactions.
Pioglitazone; Metformin: (Moderate) Consider the benefits and risks of coadministration of tafenoquine and metformin due to the potential for increased metformin concentrations and lactic acidosis. If coadministration cannot be avoided, monitor for metformin-related toxicities, and consider metformin dosage reduction, if needed. The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates, like metformin, in humans is unknown; however, in vitro observations suggest the potential for increased concentrations of OCT2 and MATE substrates. Tafenoquine may interfere with these common renal tubular transport systems involved in the renal elimination of metformin.
Rabies Vaccine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
Tafenoquine is an 8-aminoquinoline antimalarial drug that is active against all stages of Plasmodium species that include the hypnozoite (dormant stage) in the liver. Tafenoquine is active against the pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of P. falciparum and P. vivax. The activity against the pre-erythrocytic liver stages of the parasite prevents the development of the erythrocytic forms, which are responsible for malaria relapse. In vitro studies with the erythrocytic forms of P. falciparum suggest that tafenoquine may exert its effect by inhibiting hematin polymerization and inducing apoptotic-like death of the parasite. The molecular target of tafenoquine is not known. In addition to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro.
Studies with the erythrocytic forms of P. falciparum suggest a potential for cross-resistance with primaquine, an 8-aminoquinoline; however, the clinical relevance of this finding is unknown.
Tafenoquine is administered orally. Protein binding of tafenoquine is more than 99.5%, and the apparent volume of distribution is approximately 1,600 to 2,470 L.
Tafenoquine undergoes slow, negligible metabolism. Unchanged tafenoquine represented the only notable drug-related component in human plasma after a single oral dose or once daily dosing for 3 days. The full excretion profile of tafenoquine is unknown. Over a 6-day collection period, renal elimination of unchanged tafenoquine was low. The apparent oral clearance of tafenoquine is approximately 3 to 4.2 L/hour, and the average terminal half-life is approximately 15 to 16.5 days.
Affected cytochrome P450 isoenzymes and drug transporters: OCT2, MATE-1, MATE2-K
Tafenoquine has been shown to be a human organic cation transporter-2 (OCT2) and multidrug and toxin extrusion transporter (MATE-1, MATE2-K) inhibitor in vitro; however, clinical drug interaction studies with tafenoquine and OCT2 and MATE substrates have not been conducted.
-Route-Specific Pharmacokinetics
Oral Route
Maximum tafenoquine plasma concentrations were generally observed 12 to 15 hours after oral administration. After single- and multiple-oral doses, tafenoquine whole blood concentrations were on average 67% higher than corresponding plasma values. After a single 200 mg dose, the mean Cmax was 147 ng/mL and the mean AUC was 70 hour x mcg/mL. Plasma tafenoquine AUC increased by 41% and Cmax increased by 31% when a single tafenoquine dose was administered with a high-calorie, high-fat meal compared to the fasted state.
-Special Populations
Hepatic Impairment
The pharmacokinetics of tafenoquine have not been studied in patients with hepatic impairment.
Renal Impairment
The pharmacokinetics of tafenoquine have not been studied in patients with renal impairment.
Geriatric
Pharmacokinetics of tafenoquine were not significantly impacted by age.
Gender Differences
Pharmacokinetics of tafenoquine were not significantly impacted by gender.
Ethnic Differences
Pharmacokinetics of tafenoquine were not significantly impacted by ethnicity.
Obesity
Pharmacokinetics of tafenoquine were not significantly impacted by body weight.