Dosing & Uses
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 antimicrobials#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 antimicrobials#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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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)
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
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 antimicrobials#antimalarials other than chloroquine is not recommended
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.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
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
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Krintafel oral - | 150 mg tablet |  | |
| Arakoda oral - | 100 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
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