Arakoda
(Tafenoquine)Arakoda Prescribing Information
ARAKODA is indicated for the prophylaxis of malaria in patients aged 18 years and older.
• All patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to prescribing ARAKODA. ()2.1 Tests to be Performed Prior to ARAKODA Dose InitiationAll patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to prescribing ARAKODA
[see Contraindications , Warnings and Precautions ].Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with ARAKODA
[see Use in Specific Populations ].• Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with ARAKODA. ()2.1 Tests to be Performed Prior to ARAKODA Dose InitiationAll patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to prescribing ARAKODA
[see Contraindications , Warnings and Precautions ].Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with ARAKODA
[see Use in Specific Populations ].
Regimen Name | Timing | Dosage |
Loading regimen | For each of the 3 days before travel to a malarious area | 200 mg (2 of the 100 mg tablets) once daily for 3 days |
Maintenance regimen | While in the malarious area | 200 mg (2 of the 100 mg tablets) once weekly – start 7 days after the last loading regimen dose |
Terminal prophylaxis regimen | In the week following exit from the malarious area | 200 mg (2 of the 100 mg tablets) one-time 7 days after the last maintenance dose |
• Administer ARAKODA with food. ()2.2 Recommended Dosage and Administration InstructionsThe recommended dosage of ARAKODA is described in Table 1below. ARAKODA can be administered for up to 6 months of continuous dosing.
Table 1: Recommended Dosage of ARAKODA in Patients (18 Years of Age and Older) Regimen NameTimingDosageLoading regimen
For each of the 3 days before travel to a malarious area
200 mg (2 of the 100 mg tablets) once
dailyfor 3 daysMaintenance regimen
While in the malarious area
200 mg (2 of the 100 mg tablets) once
weekly– start 7 days after the last loading regimen doseTerminal prophylaxis regimen
In the week following exit from the malarious area
200 mg (2 of the 100 mg tablets) taken one time, 7 days after the last maintenance dose
• Administer ARAKODA with food.[see Clinical Pharmacology ].• Swallow the tablet whole. Do not break, crush or chew the tablets.• Complete the full course of ARAKODA including the loading dose and the terminal dose.
Table 2: How to Replace Missed Doses of ARAKODA Dose(s) MissedHow to Replace Missed Dose(s):1 Loading dose
1 dose of 200 mg (2 of the 100 mg tablets) so that a total of 3 daily loading doses have been taken. Begin maintenance dose 1 week after the last loading dose.
2 Loading doses
2 doses of 200 mg (2 of the 100 mg tablets) on 2 consecutive days so that a total of 3 daily loading doses have been taken. Begin maintenance dose 1 week after the last loading dose.
1 Maintenance (weekly) dose
1 dose of 200 mg (2 of the 100 mg tablets) on any day up to the time of the next scheduled weekly dose.
2 Maintenance (weekly) doses
1 dose of 200 mg (2 of the 100 mg tablets) on any day up to the time of the next scheduled weekly dose.
3 or more Maintenance (weekly) doses
2 doses of 200 mg (2 of the 100 mg tablets), taken as 200 mg (2 of the 100 mg tablets) once daily for 2 days up to the time of the next weekly dose.
Terminal prophylaxis dose
1 dose of 200 mg (2 of the 100 mg tablets) as soon as remembered.
• See full prescribing information for instructions on how to replace missed doses. ()2.2 Recommended Dosage and Administration InstructionsThe recommended dosage of ARAKODA is described in Table 1below. ARAKODA can be administered for up to 6 months of continuous dosing.
Table 1: Recommended Dosage of ARAKODA in Patients (18 Years of Age and Older) Regimen NameTimingDosageLoading regimen
For each of the 3 days before travel to a malarious area
200 mg (2 of the 100 mg tablets) once
dailyfor 3 daysMaintenance regimen
While in the malarious area
200 mg (2 of the 100 mg tablets) once
weekly– start 7 days after the last loading regimen doseTerminal prophylaxis regimen
In the week following exit from the malarious area
200 mg (2 of the 100 mg tablets) taken one time, 7 days after the last maintenance dose
• Administer ARAKODA with food.[see Clinical Pharmacology ].• Swallow the tablet whole. Do not break, crush or chew the tablets.• Complete the full course of ARAKODA including the loading dose and the terminal dose.
Table 2: How to Replace Missed Doses of ARAKODA Dose(s) MissedHow to Replace Missed Dose(s):1 Loading dose
1 dose of 200 mg (2 of the 100 mg tablets) so that a total of 3 daily loading doses have been taken. Begin maintenance dose 1 week after the last loading dose.
2 Loading doses
2 doses of 200 mg (2 of the 100 mg tablets) on 2 consecutive days so that a total of 3 daily loading doses have been taken. Begin maintenance dose 1 week after the last loading dose.
1 Maintenance (weekly) dose
1 dose of 200 mg (2 of the 100 mg tablets) on any day up to the time of the next scheduled weekly dose.
2 Maintenance (weekly) doses
1 dose of 200 mg (2 of the 100 mg tablets) on any day up to the time of the next scheduled weekly dose.
3 or more Maintenance (weekly) doses
2 doses of 200 mg (2 of the 100 mg tablets), taken as 200 mg (2 of the 100 mg tablets) once daily for 2 days up to the time of the next weekly dose.
Terminal prophylaxis dose
1 dose of 200 mg (2 of the 100 mg tablets) as soon as remembered.
ARAKODA tablets are dark pink, film-coated, capsule-shaped tablets debossed with ‘TQ100’ on one side containing 100 mg of tafenoquine.
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
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
A breastfed infant with G6PD deficiency is at risk for hemolytic anemia from exposure to ARAKODA. 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
There is no information regarding the presence of ARAKODA 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 ARAKODA and any potential effects on the breastfed infant from ARAKODA or from the underlying maternal condition.
Check the infant’s G6PD status before maternal breastfeeding commences. If an infant is G6PD-deficient, exposure to ARAKODA during breastfeeding may result in hemolytic anemia in the infant; therefore, advise the woman with an infant who has G6PD deficiency or whose G6PD status is unknown, not to breastfeed during treatment with ARAKODA and for 3 months after the final dose of ARAKODA.
ARAKODA is contraindicated in:
• patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia[see Warnings and Precautions (.)]5.2 G6PD Deficiency in Pregnancy and LactationPotential Harm to the FetusThe 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 ].Potential Harm to the Breastfeeding InfantA 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 ]. 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 ].• breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if the G6PD status of the infant is unknown[see Warnings and Precautions (.), Use in Specific Populations (5.3 MethemoglobinemiaAsymptomatic elevations in methemoglobin have been observed in the clinical trials of ARAKODA
[see Adverse Reactions ]. Institute appropriate therapy if signs or symptoms of methemoglobinemia occur[see Warnings and Precautions ]. 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.)]8.2 LactationRisk SummaryA breastfed infant with G6PD deficiency is at risk for hemolytic anemia from exposure to ARAKODA. 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 and Clinical Considerations].There is no information regarding the presence of ARAKODA 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 ARAKODA and any potential effects on the breastfed infant from ARAKODA or from the underlying maternal condition.
Clinical ConsiderationsCheck the infant’s G6PD status before maternal breastfeeding commences. If an infant is G6PD-deficient, exposure to ARAKODA during breastfeeding may result in hemolytic anemia in the infant; therefore, advise the woman with an infant who has G6PD deficiency or whose G6PD status is unknown, not to breastfeed during treatment with ARAKODA and for 3 months after the final dose of ARAKODA.
• patients with a history of psychotic disorders or current psychotic symptoms (i.e., hallucinations, delusions, and/or grossly disorganized behavior)[see Warnings and Precautions ()]5.4 Psychiatric EffectsIn 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 ]. 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 ]. 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 ].• patients with known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of ARAKODA[see Warnings and Precautions (5.5 Hypersensitivity ReactionsSerious 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 ]. Discontinue prophylaxis with ARAKODA and institute appropriate therapy if hypersensitivity reactions occur[see Warnings and Precautions ]. ARAKODA is contraindicated in patients who develop hypersensitivity to tafenoquine or any component of ARAKODA or other 8-aminoquinolines[see Contraindications ].)].
• 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 Hemolytic AnemiaDue to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing must be performed before prescribing ARAKODA
[see Contraindications ]. 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 ]. In clinical trials, declines in hemoglobin levels were reported in some G6PD-normal patients[see Adverse Reactions ]. Monitor patients for clinical signs or symptoms of hemolysis[see Warnings and Precautions ]. Advise patients to discontinue ARAKODA and seek medical attention if signs of hemolysis occur.• 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 G6PD Deficiency in Pregnancy and LactationPotential Harm to the FetusThe 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 ].Potential Harm to the Breastfeeding InfantA 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 ]. 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 ].,8.1 PregnancyRisk SummaryThe use of ARAKODA during pregnancy may cause hemolytic anemia in a fetus who is G6PD-deficient. Treatment with ARAKODA during pregnancy is not recommended. 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 Warnings and Precautions ]. Available data with use of ARAKODA 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, 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 about 1.5 times the clinical exposure (based on body surface area comparisons) in a similar study in rats.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical ConsiderationsDisease-Associated Maternal and/or Embryo/Fetal Risk:Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion and stillbirth.
DataAnimal Data:Tafenoquine resulted in dose-related abortions when given orally to pregnant rabbits during organogenesis (Gestation Days 6 to 18), at doses of 7 mg/kg (about 0.4 times the clinical exposure based on body surface area comparisons) and above. Doses higher than 7 mg/kg were also associated with maternal toxicity (mortality and reduced body weight gain). In a similar study in rats, doses of 3, 10, or 30 mg/kg/day resulted in maternal toxicity (enlarged spleen, reduced body weight and reduced food intake) but no fetotoxicity at the high dose (about 1.5 times the clinical exposure based on body surface area comparisons). There was no evidence of malformations in either species. In a pre- and postnatal development study in rats, tafenoquine administered throughout pregnancy and lactation produced maternal toxicity and a reversible decrease in offspring body weight gain and decrease in motor activity at 18 mg/kg/day, which is equivalent to about 0.6 times the clinical dose based on body surface area comparisons.
)8.2 LactationRisk SummaryA breastfed infant with G6PD deficiency is at risk for hemolytic anemia from exposure to ARAKODA. 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 and Clinical Considerations].There is no information regarding the presence of ARAKODA 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 ARAKODA and any potential effects on the breastfed infant from ARAKODA or from the underlying maternal condition.
Clinical ConsiderationsCheck the infant’s G6PD status before maternal breastfeeding commences. If an infant is G6PD-deficient, exposure to ARAKODA during breastfeeding may result in hemolytic anemia in the infant; therefore, advise the woman with an infant who has G6PD deficiency or whose G6PD status is unknown, not to breastfeed during treatment with ARAKODA and for 3 months after the final dose of ARAKODA.
• Methemoglobinemia: Asymptomatic elevations in blood methemoglobin have been observed. Initiate appropriate therapy if signs or symptoms of methemoglobinemia occur. ()5.3 MethemoglobinemiaAsymptomatic elevations in methemoglobin have been observed in the clinical trials of ARAKODA
[see Adverse Reactions ]. Institute appropriate therapy if signs or symptoms of methemoglobinemia occur[see Warnings and Precautions ]. 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.• 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 Psychiatric EffectsIn 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 ]. 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 ]. 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 ].• Hypersensitivity Reactions: Serious hypersensitivity reactions have been observed with administration of ARAKODA. If hypersensitivity reactions occur, institute appropriate therapy. ()5.5 Hypersensitivity ReactionsSerious 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 ]. Discontinue prophylaxis with ARAKODA and institute appropriate therapy if hypersensitivity reactions occur[see Warnings and Precautions ]. ARAKODA is contraindicated in patients who develop hypersensitivity to tafenoquine or any component of ARAKODA or other 8-aminoquinolines[see Contraindications ].• 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 Delayed Adverse Reactions, Including Hemolytic Anemia, Methemoglobinemia, Psychiatric Effects, and Hypersensitivity ReactionsAdverse 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 ]. 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 PharmacokineticsAbsorptionA food effect study was not conducted with the 100 mg ARAKODA tablet. In majority of the clinical trials, tafenoquine was administered under fed conditions. Table 5provides the pharmacokinetics of tafenoquine following single dose administration of 200 mg ARAKODA (two 100-mg ARAKODA tablets) in 65 healthy adult subjects under fed conditions. In this study, ARAKODA was administered with a high-calorie, high-fat meal (approximately 1000 calories with 19% protein, 31% carbohydrate, and 50% fat).
Table 5. Mean (%CV) Pharmacokinetic Parameters of Tafenoquine Following Single Oral Administration of Two 100-mg ARAKODA Tablets Under Fed Conditions in Healthy Adult Subjects (N=65) ParameterValueaCoefficient of Variance (CV)
bMedian and (Range)
cPlasma tafenoquine AUCinfincreased by 41% when tafenoquine was administered as an investigational capsule formulation with a high-calorie, high-fat meal compared with the fasted state.Cmax
147 ng/mL (20.7%)a
Tmax
14 hr (6 – 72 hr)b
AUCinf
70 hr*mcg/mL (24.6%)a, c
Following administration of a single dose of tafenoquine orally under fasted conditions in healthy adult subjects, AUC and Cmaxincreased dose proportionally over the dose range from 100 mg to 400 mg. When healthy adult subjects received once-weekly administrations of 200 mg tafenoquine orally for ten weeks without a loading dose under fasting conditions, the mean plasma accumulation ratio of tafenoquine was approximately 4.4.
DistributionTafenoquine is greater than 99.5% bound to protein in humans. The apparent volume of distribution of tafenoquine in healthy adult subjects is 2470 L [Inter-Individual Variability (IIV): 24.1 %].
EliminationThe apparent oral clearance of tafenoquine is approximately 4.2 L/hr (IIV: 23.6 %) in healthy adult subjects. The mean terminal half-life following administration of ARAKODA is approximately 16.5 days (range: 10.8 days to 27.3 days) in healthy adult subjects.
MetabolismNegligible metabolism of tafenoquine was observed in vitro in human liver microsomes and hepatocytes. Following administration of tafenoquine orally, once daily for three days to healthy adult subjects, unchanged tafenoquine represented the only notable drug-related component in plasma at approximately 3 days following the first dose of tafenoquine.
ExcretionThe full excretion profile of tafenoquine in humans is unknown.
Specific PopulationsThe pharmacokinetics of tafenoquine were not significantly impacted by age, sex, ethnicity, and body weight. The effect of renal or hepatic impairment on tafenoquine pharmacokinetics is unknown.
Drug Interaction StudiesClinical StudiesNo clinically significant effects on the pharmacokinetics of substrates of cytochrome P450 isoenzymes (CYP)1A2 (caffeine), CYP2D6 (desipramine), CYP2C9 (flurbiprofen), or CYP3A4 (midazolam) were observed following coadministration with tafenoquine in healthy adult subjects.
In Vitro Studies Where Drug Interaction Potential Was Not Further Evaluated ClinicallyTafenoquine inhibited metformin transport via human OCT2, MATE1 and MATE2-K transporters
[see Drug Interactions ].Tafenoquine is not an inhibitor of human breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), Organic anion transporter 1/3 (OAT1 or OAT3), Organic anion transporting polypeptide 1B1/1B3 (OATP1B1 or OATP1B3) mediated transport at clinically relevant concentrations. Tafenoquine is also not a substrate of human OATP1B1 or OATP1B3 at clinically relevant concentrations. It is inconclusive as to whether tafenoquine is a substrate of P-gp and/or BCRP mediated transport.