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Tafenoquine Tablets

TABLE OF CONTENTS

1. DESCRIPTION 8. USE IN SPECIFIC POPULATIONS
2. INDICATIONS AND USAGE 9. OVERDOSAGE
3. DOSAGE AND ADMINISTRATION 10. MECHANISM OF ACTION
4. CONTRAINDICATIONS 11. PHARMACODYNAMICS
5. WARNINGS AND PRECAUTIONS 12. PHARMACOKINETICS
6. ADVERSE REACTIONS 13. HOW SUPPLIED/STORAGE AND HANDLING
7. DRUG INTERACTIONS

 

1. DESCRIPTION

Tafenoquine succinate is an antimalarial agent for oral administration. The chemical name of tafenoquine succinate is (±) 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinoline succinate. The structural formula is shown below.

Empirical formula: C24H28F3N3O3 • C4H6O4 - Molecular weight: 581.6 g/mol as the H28 succinate salt (463.5 g/mol as free base)

Each tafenoquine tablet contains 150 mg of tafenoquine (equivalent to 188.2 mg tafenoquine succinate). Inactive ingredients include magnesium stearate, mannitol, and microcrystalline cellulose. The tablet film-coating inactive ingredients include hydroxypropylmethylcellulose, polyethylene glycol, red iron oxide, and titanium dioxide.

Each ARAKODA tablet contains 100 mg of tafenoquine (equivalent to 125.5 mg of tafenoquine succinate). Inactive ingredients include magnesium stearate, mannitol, and microcrystalline cellulose. The tablet film coating inactive ingredients include: hypromellose, iron oxide red, macrogol/polyethylene glycol and titanium dioxide.

2. INDICATIONS AND USAGE

ARAKODA is indicated for the prophylaxis of malaria in patients aged 18 years and older.

KRINTAFEL (tafenoquine) is indicated 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 [see Dosage and Administration (3.2)].

Limitation of Use

Tafenoquine is NOT indicated for the treatment of acute P. vivax malaria.

3. DOSAGE AND ADMINISTRATION

3.1 Tests to be Performed Prior to Treatment with Tafenoquine

All patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to prescribing tafenoquine [see Contraindications (4), Warnings and Precautions (5.1)].

Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with tafenoquine [see Use in Specific Populations (8.1, 8.3)].

3.2 Recommended Dosage and Administration Instructions of ARAKODA

The recommended dosage of ARAKODA is described in Table 1 below. 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)

• 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

3.3 Recommended Dosage and Administration of KRINTAFEL (Tafenoquine)

The recommended dose of tafenoquine in patients aged 16 years and older is a single dose of 300 mg administered as two 150-mg tablets taken together. Coadminister tafenoquine on the first or second day of the appropriate antimalarial therapy (e.g. chloroquine) for acute P. vivax malaria [see Clinical Studies].

Administer tafenoquine with food to increase systemic absorption [see Clinical Pharmacology].

Swallow tablets whole. Do not break, crush, or chew the tablets.

In the event of vomiting within 1 hour after dosing, a repeat dose should be given. Re-dosing should not be attempted more than once.

4. CONTRAINDICATIONS

Tafenoquine is contraindicated in:

• patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia [see Warnings and Precautions (5.1)].

• 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 Use in Specific Populations (8.2)].

• 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)]

• patients with known hypersensitivity to tafenoquine, other 8-aminoquinolines, or any component of tafenoquine [see Warnings and Precautions (5.5)].

5. WARNINGS AND PRECAUTIONS

5.1 Hemolytic Anemia

Due to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing must be performed before prescribing tafenoquine [see Dosage and Administration (3.1)]. Due to the limitations of 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 tafenoquine is contraindicated in patients with G6PD deficiency or unknown G6PD status [see Contraindications (4)]. Patients were excluded from clinical trials of tafenoquine if they had a G6PD enzyme activity level <70% of the site median value for G6PD normal activity [see Clinical Studies]. 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. Advise patients to seek medical attention if signs of hemolysis occur.

5.2 G6PD Deficiency in Pregnancy or Lactation

Potential Harm to the Fetus

The use of tafenoquine 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 tafenoquine during pregnancy is not recommended and to avoid pregnancy or use effective contraception for 3 months after the dose of tafenoquine [see Use in Specific Populations (8.1, 8.3)].

Potential Harm to the Breastfeeding Infant

A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to tafenoquine through breast milk. Infant G6PD status should be checked before breastfeeding begins. Tafenoquine 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 for 3 months after the dose of tafenoquine [see Use in Specific Populations (8.2)].

5.3 Methemoglobinemia

Asymptomatic elevations in methemoglobin have been observed in the clinical trials of tafenoquine [see Adverse Reactions (6.1)]. Institute appropriate therapy if signs or symptoms of methemoglobinemia occur. Carefully monitor individuals with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency. Advise patients to seek medical attention if signs of methemoglobinemia occur.

5.4 Psychiatric Effects

Psychiatric adverse reactions including anxiety (<1%), abnormal dreams (<1%), and insomnia (3%) have been reported in clinical trials of tafenoquine [see Adverse Reactions (6.1)]. Two cases of depression and 2 cases of psychosis have occurred primarily in patients with a history of psychiatric disorders following receipt of single doses of tafenoquine that were higher than the approved 300-mg dose (350 mg to 600 mg). Safety and effectiveness of tafenoquine have not been established at doses or regimens other than the approved regimen; use of tafenoquine at doses or regimens other than a 300-mg single dose is not approved by FDA.

The benefit of treatment with tafenoquine must be weighed against the potential risk for psychiatric adverse reactions in patients with a history of psychiatric illness. Due to the long half-life of tafenoquine (approximately 15 days), signs or symptoms of psychiatric adverse reactions that may occur could be delayed in onset and/or duration [see Clinical Pharmacology].

5.5 Hypersensitivity Reactions

Serious hypersensitivity reactions (e.g., angioedema, urticaria) have been observed with administration of tafenoquine [see Adverse Reactions (6.1)]. Institute appropriate therapy if hypersensitivity reactions occur. Do not re-administer tafenoquine. Tafenoquine is contraindicated in patients who develop hypersensitivity to tafenoquine or any component of tafenoquine or other 8-aminoquinolines [see Contraindications (4)].

Due to the long half-life of tafenoquine (approximately 15 days), signs or symptoms of hypersensitivity adverse reactions that may occur could be delayed in onset and/or duration [see Clinical Pharmacology]. Advise patients to seek medical attention if signs of hypersensitivity occur.

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].

6. ADVERSE REACTIONS

The following clinically significant adverse reactions have been observed with tafenoquine and are discussed in detail in the Warnings and Precautions section:

• Hemolytic anemia [see Warnings and Precautions (5.1)]

• Methemoglobinemia [see Warnings and Precautions (5.3)]

• Psychiatric effects [see Warnings and Precautions (5.4)]

• Hypersensitivity reactions [see Warnings and Precautions (5.5)]

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.

The safety data described below reflect exposure to 4,129 subjects, of whom 810 received a 300-mg single dose of tafenoquine. Tafenoquine was evaluated in patients with P. vivax malaria (n = 483) in 3 randomized, double-blind trials including a placebo-controlled trial comparing tafenoquine plus chloroquine (n = 260) with chloroquine alone (Trial 1), a placebo-controlled dose-ranging trial (Trial 2) (n = 57) [see Clinical Studies], and a hematologic safety trial (Trial 3, NCT02216123) (n = 166).

In Trial 1, in patients with P. vivax malaria, the most common adverse reactions reported in ≥5% of patients treated with tafenoquine are listed in Table 3. Patients included in the trial had a mean age of 35 (range: 16 to 79 years), were 75% male and from the following regions: 70% Latin America (Brazil and Peru), 19% Southeast (SE) Asia (Thailand, Cambodia, and the Philippines), and 11% Africa (Ethiopia).

Table 3. Selected Adverse Reactionsa Reported in ≥5% of Patients with P. Vivax Malaria Receiving Tafenoquine in a Randomized, Active-Controlled Trial (Trial 1)

a Adverse reactions reported prior to Day 29 as subsequent adverse reactions can be confounded by recurrence of malaria or retreatment with another agent from the quinoline class.

Table 4: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Pooled Trials 1, 2, 4, and 5 (Non-Deployed Subjects)

1 Trials 2 and 4 included mefloquine arm in addition to placebo

2 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly

3 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly

4 Includes headache, sinus headache, migraine and tension headache

5 Includes dizziness and dizziness postural

6 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism.

Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the active-control Trial 3 conducted in military personnel deployed to malaria endemic areas are presented in Table 5.

Table 5: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Trial 3 (Deployed Subjects)

1 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly

2 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly

3 Includes headache, sinus headache, migraine and tension headache

4 Includes dizziness and dizziness postural

5 Includes motion sickness, vertigo and vertigo positional

6 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism

7 Includes abnormal dreams, nightmares

8 Includes anxiety disorder, panic attack and stress.

Clinically Significant Adverse Reactions in Trials 1 to 5 (Overall Safety Population)

Clinically significant adverse reactions with ARAKODA (200 mg daily for 3 days, followed by 200 mg weekly) in Trials 1 to 5 (n= 825) are described below:

Ocular Adverse Reactions

Vortex keratopathy was reported in 21% to 93% of subjects receiving ARAKODA in the trials which included ophthalmic evaluations (Trials 3, 5, and Trial 6 (NCT # 01290601, an active-control trial in patients from Thailand with P. vivax malaria. The keratopathy did not result in any apparent functional visual changes and resolved within one year after drug cessation in all patients. Retinal abnormalities were noted in less than 1% of subjects receiving ARAKODA.

A total of 7 serious ocular adverse reactions (SARs) were reported in ARAKODA-treated subjects in the trials which included ophthalmic evaluations: 5 reports of keratopathy and two reports of retinal disorders.

Laboratory Abnormalities

Methemoglobinemia: Asymptomatic methemoglobin elevations were observed in 13% of subjects receiving ARAKODA.

Hemoglobin decrease: Hemoglobin decreases of ≥ 3 g/dL were observed in 2.3% of subjects receiving ARAKODA.

Adverse Reactions Reported in < 1% of Subjects Receiving ARAKODA in Trials 1 to 5

The following selected adverse reactions were reported in subjects receiving ARAKODA in Trials 1 to 5 at a rate of less than 1%.

Blood and lymphatic system disorders: hemolytic anemia, anemia, thrombocytopenia

Ear and labyrinth disorders: hyperacusis, Meniere’s disease

Eye disorders: night blindness, photophobia, blurred vision, visual acuity reduced, visual impairment, vitreous floaters

Hepatobiliary disorders: hyperbilirubinemia, jaundice cholestatic

Immune system disorders: hypersensitivity

Investigations: blood bilirubin increased, blood creatinine increased, glomerular filtration rate decreased

Nervous system disorders: amnesia, coordination abnormal, hyperesthesia, hypoesthesia, somnolence, syncope, tremor, visual field defect

Psychiatric disorders: agitation, neurosis

Skin and subcutaneous tissue disorders: urticaria.

Other Adverse Reactions Reported with Tafenoquine

Clinically significant adverse reactions with tafenoquine 300-mg single dose in clinical trials (n = 810) in ≤3% of subjects are listed below:

Psychiatric Disorders: Anxiety, insomnia, abnormal dreams.

Nervous System Disorders: Somnolence.

Laboratory Investigations: Increased blood creatinine, increased blood methemoglobin, increased alanine aminotransferase.

Immune System Disorders: Hypersensitivity reactions (e.g., angioedema, urticaria) [see Contraindications (4), Warnings and Precautions (5.5)].

Eye Disorders: Vortex keratopathy, photophobia.

7. DRUG INTERACTIONS

7.1 Effect of Tafenoquine on Organic Cation Transporter-2 (OCT2) and Multidrug and Toxin Extrusion (MATE) Substrates

The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates in humans is unknown. However, in vitro observations suggest the potential for increased concentrations of these substrates [see Clinical Pharmacology] which may increase the risk of toxicity of these drugs.

Avoid coadministration of tafenoquine with OCT2 and MATE substrates (e.g., dofetilide, metformin). If coadministration cannot be avoided, monitor for drug-related toxicities and consider dosage reduction if needed based on approved product labeling of the coadministered drug.

8. USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

The use of tafenoquine during pregnancy may cause hemolytic anemia in a fetus who is G6PD deficient. Treatment with tafenoquine during pregnancy is not recommended [see Warnings and Precautions (5.2)]. Available data with use of tafenoquine 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 equivalent to 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 Considerations

Disease-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.

Data

Animal 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 (equivalent to 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 Lactation

Risk Summary

A breastfed infant with G6PD deficiency is at risk for hemolytic anemia from exposure to tafenoquine. Infant G6PD status should be checked before breastfeeding begins. Tafenoquine 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), Clinical Considerations].

There is no information 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 tafenoquine and any potential effects on the breastfed infant from tafenoquine or from the underlying maternal condition.

Clinical Considerations

Check the infant’s G6PD status before maternal breastfeeding commences. If an infant is G6PD deficient, exposure to tafenoquine 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 for 3 months after the dose of tafenoquine.

8.3 Females and Males of Reproductive Potential

Pregnancy Testing

Verify the pregnancy status in females of reproductive potential prior to initiating treatment with tafenoquine [see Warnings and Precautions, (5.2), Use in Specific Populations (8.1)].

Contraception

Tafenoquine may cause hemolytic anemia in a G6PD-deficient fetus [see Warnings and Precautions (5.2), Use in Specific Populations (8.1)]. Advise females of reproductive potential that treatment with tafenoquine during pregnancy is not recommended and to avoid pregnancy or use effective contraception for 3 months after the dose of tafenoquine.

8.4 Pediatric Use

The safety and effectiveness of tafenoquine have been established in pediatric patients aged 16 years and older. Use of tafenoquine in these pediatric patients is supported by evidence from adequate and well-controlled studies of tafenoquine [see Clinical Studies].

Safety and effectiveness of tafenoquine in pediatric patients younger than 16 years have not been established.

8.5 Geriatric Use

Clinical trials of tafenoquine did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients [see Clinical Pharmacology].

8.6 Renal Impairment

The pharmacokinetics of tafenoquine have not been studied in patients with renal impairment. If tafenoquine is administered to such patients, monitoring for adverse reactions associated with tafenoquine is needed [see Warnings and Precautions (5), Adverse Reactions (6)].

8.7 Hepatic Impairment

The pharmacokinetics of tafenoquine have not been studied in patients with hepatic impairment. If tafenoquine is administered to such patients, monitoring for adverse reactions associated with tafenoquine is needed [see Warnings and Precautions (5), Adverse Reactions (6)].

9. OVERDOSAGE

Hemoglobin decline and methemoglobinemia may be encountered in an overdose with tafenoquine. Treatment of overdosage consists of institution of appropriate symptomatic and/or supportive therapy.

10. MECHANISM OF ACTION

Tafenoquine is an 8-aminoquinoline antimalarial drug.

Mechanism of Action

Tafenoquine, an 8-aminoquinoline antimalarial, is active against the liver stages including the hypnozoite (dormant stage) of P. vivax. In addition to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro. The molecular target of tafenoquine is not known.

Antimicrobial Activity

Tafenoquine is active against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of P. vivax. The activity of tafenoquine against the pre-erythrocytic liver stages of the parasite prevents the development of the erythrocytic forms of the parasite, which are responsible for relapses in P. vivax malaria [see Clinical Studies].

Resistance

A potential for development of resistance of Plasmodium species to tafenoquine was not evaluated.

11. PHARMACODYNAMICS

Cardiac Electrophysiology

The effect of tafenoquine on the QTc interval was evaluated in a Phase 1 randomized, single-blind, placebo-and positive-controlled, parallel-group thorough QTc study in 260 healthy adult subjects. At a cumulative dose of 1,200 mg (400 mg/day for 3 days; 4 times the maximum recommended dose), tafenoquine did not prolong the QTc interval to any clinically relevant extent.

Exposure-Response Relationships

A saturable relationship between tafenoquine exposure (AUC) and clinical response (recurrence-free rate at 6 months) was identified. Tafenoquine exposures achieved with doses of 300 mg and higher are on the plateau of the exposure-response curve. Use of tafenoquine at doses or regimens other than a 300-mg single dose is not approved by the FDA.

12. PHARMACOKINETICS

Absorption

Maximum plasma concentrations were generally observed 12 to 15 hours following oral administration.

Food Effect: Plasma tafenoquine AUC increased by 41% and Cmax increased by 31% when administered as an investigational capsule formulation with a high-calorie, high-fat meal (approximately 1,000 calories with 15% protein, 25% carbohydrate, and 60% fat) compared with the fasted state.

Distribution

Protein binding of tafenoquine is >99.5%. The apparent oral volume of distribution is ~1,600 L. Following single-and multiple-oral-dose administration, tafenoquine whole blood concentrations were on average 67% higher than corresponding plasma values.

Elimination

The apparent oral clearance of tafenoquine is approximately 3 L/h. The average terminal half-life is approximately 15 days.

Metabolism: Tafenoquine undergoes slow metabolism. Unchanged tafenoquine represented the only notable drug-related component in human plasma after a single oral dose of tafenoquine.

Excretion: The full excretion profile of tafenoquine in humans is unknown. Over a 6-day collection period, renal elimination of unchanged tafenoquine was low.

Specific Populations

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 Studies

Clinical Studies: No clinically significant effects on tafenoquine pharmacokinetics were observed following coadministration with chloroquine, dihydroartemisinin-piperaquine, or artemether-lumefantrine in healthy subjects.

No clinically significant effects on the pharmacokinetics of dihydroartemisinin, piperaquine, artemether, lumefantrine, or substrates of cytochrome P450 isoenzymes (CYP)1A2 (caffeine), CYP2D6 (desipramine), CYP2C8 (chloroquine), CYP2C9 (flurbiprofen), or CYP3A4 (midazolam, chloroquine) were observed following coadministration of tafenoquine in healthy subjects.

In Vitro Studies Where Drug Interaction Potential Was Not Further Evaluated Clinically: Tafenoquine inhibited metformin transport via human OCT2, MATE-1, and MATE2-K transporters. Clinical drug interaction studies with tafenoquine and OCT2 and MATE substrates have not been conducted [see Drug Interactions (7)].

The effect of tafenoquine on substrates of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptides 1B1/1B3 (OATP1B1/OATP1B3) is unknown.

13. HOW SUPPLIED/STORAGE AND HANDLING

How Supplied:

KRINTAFEL tablets contain 150 mg of tafenoquine (equivalent to 188.2 mg tafenoquine succinate) and are pink, film-coated, capsule-shaped, and debossed with ‘GS J11’ on one side. KRINTAFEL is supplied as follows:

• Bottle of 30 tablets with child-resistant closure (NDC 0173-0889-13). Bottles contain a desiccant. Once opened, use within 3 months.

• Unit Dose Pack of 2 tablets in a bottle with child-resistant closure (NDC 0173-0889-39). Bottles contain a desiccant.

ARAKODA tablets contain 100 mg of tafenoquine (equivalent to 125.5 mg of tafenoquine succinate) and are dark pink, film-coated, capsule-shaped, and debossed with ‘TQ100’ on one side.

ARAKODA tablets are packed in polyamide aluminum and PVC formable laminate backed blisters with a peelable polyethylene terephthalate aluminum foil cover. Each blister card contains 8 tablets. Each carton contains 16 tablets (2 blister cards) (NDC 71475-257-01).

Storage and Handling:

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store in the original package to protect from moisture. Keep the bottle tightly closed and do not remove the desiccant.

Rx only

Rev 08/18