tafenoquine (Rx)

Brand and Other Names:Krintafel, Arakoda
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 100mg (Arakoda)
  • 150mg (Krintafel)

Malaria

Also see Administration

Prevention of relapse following treatment of acute P vivax infection

  • Krintafel only
  • 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

  • Arakoda only
  • 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

Dosing Considerations

Limitation of use: Not indicated for treatment of acute P vivax malaria

Tests prior to initiation

  • All patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Pregnancy testing is recommended for females of reproductive potential

Dosage Forms & Strengths

tablet

  • 150mg (Krintafel)

Malaria

Prevention of relapse following treatment of acute P vivax infection

  • Krintafel: 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
    • Krintafel only
    • 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
    • Also see Administration

Dosing Considerations

Limitation of use: Not indicated for treatment of acute P vivax malaria

Tests prior to initiation

  • All patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Pregnancy testing is recommended for females of reproductive potential
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Interactions

Interaction Checker

and tafenoquine

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10% (Arakoda)

            Headache (15-32%)

            Vortex keratopathy (21%)

            Diarrhea (5-18%)

            Back pain (14%)

            Asymptomatic methemoglobin elevations (13%)

            1-10% (Arakoda)

            Nausea (5-7%)

            Motion sickness (5%)

            Vomiting (2-5%)

            Dizziness (1-5%)

            Increased ALT (4%)

            Any sleep symptom (1-4%)

            Hemoglobin decreased (2.3%)

            Abnormal dreams (2%)

            Insomnia (1-2%)

            Depression/depressed mood (1%)

            Anxiety (1%)

            1-10% (Krintafel)

            Dizziness (8%)

            Nausea (6%)

            Vomiting (6%)

            Decreased hemoglobin (5%)

            Headache (5%)

            Insomnia (3%)

            ≤3%

            • Nervous system disorders: Somnolence
            • Laboratory investigations: Increased blood creatinine, increased blood methemoglobin, increased alanine aminotransferase
            • Immune system disorders: Hypersensitivity reactions (eg, angioedema, urticaria)
            • Eye disorders: Vortex keratopathy, photophobia

            <1% Arakoda

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

            Ear and labyrinth disorders: Hyperacusis, Meniere 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

            <1% (Krintafel)

            Anxiety

            Abnormal dreams

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            Warnings

            Contraindications

            Krintafel or Arakoda

            • 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

            Arakoda

            • History of psychotic disorders or current psychotic symptoms (ie, hallucinations, delusions, grossly disorganized behavior)

            Cautions

            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

            Serious hypersensitivity reactions (eg, angioedema, urticaria) reported; initiate appropriate therapy and do not readminister tafenoquine; owing to long half-life (~15 days), hypersensitivity signs or symptoms may delayed in onset and/or duration (see Contraindications)

            Arakoda: Delayed adverse reactions including hemolytic anemia, methemoglobinemia, psychiatric effects, and hypersensitivity may occur owing to the long half-life (~days) and repeated dosing

            Drug interaction overview

            • 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
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            Pregnancy

            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

            Also see Contraindications and Cautions

            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

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            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

            Absorption

            Peak plasma time: 12-15 hr (Krintafel); 14 hr (Arakoda)

            Peak plasma concentration: 147 ng/mL (Arakoda)

            AUC: 70 hr·mcg/mL (Arakoda)

            Food effect: AUC increased by 41% and peak plasma concentration by 31% when administered with a high-calorie, high-fat meal (~1000 calories with 15% protein, 25% carbohydrate, and 60% fat) compared with fasted state

            Distribution

            Protein bound: >99.5%

            Vd: 1600 L (Krintafel); 2470 L (Arakoda)

            Metabolism

            Undergoes slow metabolism; unchanged tafenoquine represented the only notable drug-related component in human plasma after a single oral dose

            Elimination

            Half-life: 15 days (Krintafel); 16.5 days (Arakoda)

            Clearance: 3 L/hr (Krintafel); 4.2 L/hr (Arakoda)

            Full excretion profile unknown; over a 6-day collection period, renal elimination of unchanged tafenoquine was low

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            Administration

            Oral Administration

            Administer with food to increase systemic absorption

            Swallow tablets whole; do not break, crush, or chew

            Arakoda: Complete full course including loading and terminal dose

            Missed dose(s)

            • Krintafel
              • In the event of vomiting within 1 hr after dosing, a repeat dose should be given; do not redose more than once
            • Arakoda
              • 1 loading dose missed: Replace with 1 dose of 200 mg 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 missed: Replace with 2 doses of 200 mg 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 missed: 1 dose of 200 mg on any day up to the time of the next scheduled weekly dose
              • 2 maintenance (weekly) doses missed: 1 dose of 200 mg on any day up to the time of the next scheduled weekly dose
              • ≥3 maintenance (weekly) doses missed: 2 doses of 200 mg, taken as 200 mg once daily for 2 days up to the time of the next weekly dose
              • Terminal prophylaxis dose missed: 1 dose of 200 mg as soon as remembered

            Storage

            Store at 20-25°C (68-77°F); excursions permitted at temperatures between 15-30°C (59-86°F)

            Krintafel and Arakoa: Store in the original package to protect from moisture

            Krintafel: Keep the bottle tightly closed and do not remove the desiccant

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
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            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.