tafenoquine (Rx)

Brand and Other Names:Krintafel, Arakoda
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

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

Malaria

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 chloroquine therapy for acute P vivax infection
  • 300 mg PO as a single dose
  • Coadminister tafenoquine on the first or second day of chloroquine therapy 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 PO 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

Dosage Modifications

Renal or hepatic impairment

  • Pharmacokinetics have not been studied in patients with renal or hepatic impairment
  • If administered to such patients, monitor for drug-related adverse reactions

Dosing Considerations

Limitation of use

  • Krintafel
    • Not indicated for treatment of acute P vivax malaria
    • Coadministration with antimalarials other than chloroquine is not recommended owing to risk of P vivax malaria recurrence

Prior to initiation

  • All patients: Test for glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Females of reproductive potential: Test for pregnancy

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 receiving chloroquine 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 chloroquine therapy for acute P vivax malaria

Dosage Modifications

Renal or hepatic impairment

  • Pharmacokinetics have not been studied in patients with renal or hepatic impairment
  • If administered to such patients, monitor for drug-related adverse reactions

Dosing Considerations

Limitation of use

Krintafel

  • Not indicated for treatment of acute P vivax malaria
  • Coadministration with antimalarials other than chloroquine is not recommended owing to risk of P vivax malaria recurrence

Prior to initiation

  • All patients: Test for glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Females of reproductive potential: Test for pregnancy
Next:

Interactions

Interaction Checker

and tafenoquine

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (16)

              • amantadine

                tafenoquine will increase the level or effect of amantadine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • amiloride

                tafenoquine will increase the level or effect of amiloride by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • cimetidine

                tafenoquine will increase the level or effect of cimetidine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • cisplatin

                tafenoquine will increase the level or effect of cisplatin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • dapsone topical

                tafenoquine, dapsone topical. unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration of dapsone topical with oral dapsone or antimalarial medications because of the potential for hemolytic reactions.

              • dofetilide

                tafenoquine will increase the level or effect of dofetilide by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • dopamine

                tafenoquine will increase the level or effect of dopamine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • famotidine

                tafenoquine will increase the level or effect of famotidine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • lamivudine

                tafenoquine will increase the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • memantine

                tafenoquine will increase the level or effect of memantine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • metformin

                tafenoquine will increase the level or effect of metformin by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • pindolol

                tafenoquine will increase the level or effect of pindolol by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • pramipexole

                tafenoquine will increase the level or effect of pramipexole by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • procainamide

                tafenoquine will increase the level or effect of procainamide by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • trimethoprim

                tafenoquine will increase the level or effect of trimethoprim by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              • varenicline

                tafenoquine will increase the level or effect of varenicline by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with 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.

              Monitor Closely (1)

              • bupivacaine implant

                tafenoquine, bupivacaine implant. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

              Minor (0)

                Previous
                Next:

                Adverse Effects

                >10%

                Arakoda

                • Vortex keratopathy (21-93%)
                • Headache (15-32%)
                • Diarrhea (5-18%)
                • Back pain (14%)
                • Asymptomatic methemoglobin elevations (13%)

                1-10%

                Arakoda

                • Nausea (5-7%)
                • Dizziness (1-5%)
                • Motion sickness (5%)
                • Vomiting (2-5%)
                • ALT increased/abnormal (4%)
                • Any sleep symptom (1-4%)
                • Hemoglobin decreased ≥ 3 g/dL (2.3%)
                • Insomnia (1-2%)
                • Abnormal dreams (2%)
                • Depression/depressed mood (1%)
                • Anxiety (1%)

                Krintafel

                • ≤3%
                • Psychiatric disorders: Anxiety, insomnia, abnormal dreams
                • Nervous system disorders: Somnolence
                • Laboratory investigations: Increased blood creatinine, increased blood methemoglobin, increased ALT
                • Immune system disorders: Hypersensitivity reactions (eg, angioedema, urticaria
                • Eye disorders: Vortex keratopathy, photophobia
                • Combined with chloroquine H5
                • Dizziness (8%)
                • Nausea (6%)
                • Vomiting (6%)
                • Decreased hemoglobin (5%)
                • Headache (5%)

                <1%

                Arakoda

                • 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
                Previous
                Next:

                Warnings

                Contraindications

                Krintafel or Arakoda

                • G6PD deficiency or unknown G6PD status
                • Breastfeeding by lactating female when infant is G6PD deficient or if G6PD status is unknown
                • Hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of tafenoquine

                Arakoda

                • History of psychotic disorders or current psychotic symptoms (ie, hallucinations, delusions, and/or 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

                Use during pregnancy or in breastfeeding women may cause hemolytic anemia in a G6PD-deficient fetus or infant, respectively (

                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 [Krintafel] or ~17 days [Arakoda]), 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 [Krintafel] or ~17 days [Arakoda), hypersensitivity signs or symptoms may delayed in onset and/or duration (see Contraindications)

                Drug interaction overview

                • Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro
                • Avoid coadministration with OCT2 or MATE substrates
                • If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on prescribing information
                • Lack of efficacy in reducing P. vivax malaria recurrence in treated patients when combined with an artemisinin-containing antimalarial was seen in a clinical trial; coadministration with antimalarials other than chloroquine is not recommended
                Previous
                Next:

                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.

                Previous
                Next:

                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

                Arakoda: Administered with a high-calorie, high-fat meal (~1000 calories [19% protein, 31% carbohydrate, and 50% fat])

                Peak plasma concentration

                • Arakoda: 147 ng/mL

                Peak plasma time

                • Arakoda: 14 hr
                • Krintafel: 12-15 hr

                AUC

                • Arakoda: 70 mcg⋅hr/mL

                Distribution

                • Protein bound: >99.5%

                Vd

                • Arakoda: 2470 L
                • Krintafel: ~1600 L

                Metabolism

                Arakoda

                • Slowly metabolized
                • Unchanged tafenoquine represented the only notable drug-related component in human plasma after a single oral dose

                Krintafel

                • Negligible metabolism observed in vitro in human liver microsomes and hepatocytes
                • Following oral administration, once daily for three days to healthy adults, unchanged tafenoquine represented the only notable drug-related component in plasma at ~3 days following the first dose

                Elimination

                • Excretion: Unknown

                Clearance

                • Arakoda: ~4.2 L/hr
                • Krintafel: ~3 L/hr

                Half-life

                • Arakoda: ~16.5 days
                • Krintafel: ~15 days
                Previous
                Next:

                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

                Previous
                Next:

                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Krintafel oral
                -
                150 mg tablet
                Arakoda oral
                -
                100 mg tablet

                Copyright © 2010 First DataBank, Inc.

                Previous
                Next:

                Patient Handout

                A Patient Handout is not currently available for this monograph.
                Previous
                Next:

                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                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.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                Additional Offers
                Email to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Email Forms to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Previous
                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.