Malaria, prophylaxis (Arakoda): Oral:
Prophylaxis (primary):
Note: May be used for up to 6 months of continuous dosing.
Loading regimen (prior to travel): 200 mg once daily for 3 days prior to travel to a malarious area.
Maintenance regimen (while in the malarious area): 200 mg once weekly, starting 7 days after the last dose of the loading regimen.
Terminal prophylaxis regimen (after leaving malarious area): 200 mg as a single dose, 7 days after the last dose of the maintenance regimen.
Missed dose:
Missed 1 loading (daily) dose: Administer a single 200 mg dose (so that a total of 3 daily loading doses have been taken); begin maintenance regimen 1 week after the last loading dose.
Missed 2 loading (daily) doses: Administer 200 mg once daily for 2 consecutive days (so that a total of 3 daily loading doses have been taken); begin maintenance regimen 1 week after the last loading dose.
Missed 1 maintenance (weekly) dose: Administer a single 200 mg dose on any day up to the time of the next scheduled weekly dose.
Missed 2 maintenance (weekly) doses: Administer a single 200 mg dose on any day up to the time of the next scheduled weekly dose.
Missed ≥3 maintenance (weekly) doses: Administer 200 mg once daily for 2 days up to the time of the next scheduled weekly dose.
Missed terminal prophylaxis dose: Administer 200 mg as a single dose as soon as remembered.
Presumptive antirelapse therapy : 300 mg as a single dose after leaving the malarious area, ideally overlapping with the last dose of the antimalarial used for prophylaxis. Note: Presumptive antirelapse therapy is not needed if primaquine or tafenoquine are taken for primary prophylaxis (CDC Yellow Book 2020).
Malaria, treatment (prevention of relapse) of P. vivax or P. ovale (Krintafel): Oral: 300 mg as a single dose on the first or second day of chloroquine therapy (CDC 2020a).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution and monitor for adverse reactions.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution and monitor for adverse reactions.
(For additional information see "Tafenoquine: Pediatric drug information")
Note: Prior to initiation of therapy, patients should be tested for G6PD deficiency, and females of childbearing potential should undergo pregnancy testing.
Malaria, prevention of relapse of Plasmodium vivax or Plasmodium ovale (radical cure):
Adolescents ≥16 years: Krintafel: Oral: 300 mg single dose on day 1 or 2 of chloroquine or hydroxychloroquine therapy (CDC 2020b).
Malaria, chemoprophylaxis:
Adolescents ≥18 years: Arakoda:
Loading regimen (prior to travel): Oral: 200 mg once daily for 3 days prior to travel to malarious area.
Maintenance regimen (while in the malarious area): Oral: 200 mg once weekly, starting 7 days after the last dose of the loading regimen; may be used for up to 6 months of continuous dosing.
Terminal prophylaxis regimen (after leaving malarious area): Oral: 200 mg as a single dose, 7 days after the last dose of the maintenance regimen.
Missed dose(s):
Loading doses:
Missed 1 loading (daily) dose: Administer a single 200 mg dose (so that a total of 3 daily loading doses have been taken); begin maintenance regimen 1 week after the last loading dose.
Missed 2 loading (daily) doses: Administer 200 mg once daily for 2 consecutive days (so that a total of 3 daily loading doses have been taken); begin maintenance regimen 1 week after the last loading dose.
Maintenance doses:
Missed 1 or 2 maintenance (weekly) dose(s): Administer a single 200 mg dose on any day up to the time of the next scheduled weekly dose.
Missed ≥3 maintenance (weekly) doses: Administer 200 mg once daily for 2 days up to the time of the next scheduled weekly dose.
Terminal prophylaxis:
Missed terminal prophylaxis dose: Administer 200 mg as a single dose as soon as remembered.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Adolescents ≥16 years: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution and monitor for adverse reactions.
Adolescents ≥16 years: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution and monitor for adverse reactions.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as succinate:
Krintafel: 150 mg
Tablet, Oral, as succinate [strength expressed as base]:
Arakoda: 100 mg
No
Oral: Administer with food. Swallow tablets whole; do not break, crush, or chew. If vomiting occurs ≤1 hour after dosing for prevention of relapse of P. vivax malaria, repeat dose once (do not attempt re-dosing more than once). When used for chemoprophylaxis, ensure the full course is completed, including loading regimen and the terminal dose.
Oral: Administer with food (to improve systemic absorption). Swallow tablets whole; do not break, crush, or chew tablets.
Arakoda: Chemoprophylaxis: Ensure the full course is completed, including loading regimen, maintenance regimen, and the terminal dose.
Krintafel: Prevention of relapse (radical cure): If vomiting occurs within 1 hour, give a repeat dose; do not redose more than 1 time.
Malaria, primary prophylaxis (Arakoda): Prophylaxis of malaria in patients ≥18 years of age.
Malaria, treatment (prevention of relapse) (Krintafel): Radical cure (prevention of relapse) of Plasmodium vivax malaria in patients ≥16 years of age who are receiving chloroquine therapy for acute P. vivax infection. Note: Centers for Disease Control and Prevention guidelines also recommend tafenoquine for radical cure (prevention of relapse) of malaria caused by Plasmodium ovale (CDC 2020a).
Limitation of use: Not indicated for the treatment of acute P. vivax malaria. Concomitant use with antimalarials other than chloroquine is not recommended due to increased risk of recurrence of P. vivax malaria.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Diarrhea (5% to 18%)
Hematologic & oncologic: Methemoglobinemia (13%)
Nervous system: Headache (15%)
Neuromuscular & skeletal: Back pain (14%)
Ophthalmic: Epithelial keratopathy (21% to 93%)
1% to 10%:
Gastrointestinal: Motion sickness (5%), nausea (5% to 7%), vomiting (5%)
Hematologic & oncologic: Decreased hemoglobin (2%)
Hepatic: Increased serum alanine aminotransferase (4%)
Hypersensitivity: Hypersensitivity reaction (≤3%, including angioedema)
Nervous system: Abnormal dreams (≤3%), anxiety (≤3%), depressed mood (≤1%), depression (≤1%), dizziness (1% to 5%), drowsiness (≤3%), insomnia (2% to 3%), sleep disorder (3% to 4%)
Ophthalmic: Photophobia (≤3%)
Renal: Increased serum creatinine (≤3%)
<1%:
Cardiovascular: Syncope
Dermatologic: Urticaria
Hematologic & oncologic: Anemia, hemolytic anemia, thrombocytopenia
Hepatic: Cholestatic jaundice, hyperbilirubinemia
Nervous system: Agitation, amnesia, ataxia, hyperacusis, hyperesthesia, hypoesthesia, neurosis, suicidal tendencies
Neuromuscular & skeletal: Tremor
Ophthalmic: Blurred vision, decreased visual acuity, night blindness, retinopathy, visual field defect, visual impairment, vitreous opacity
Otic: Meniere’s disease
Renal: Decreased estimated GFR (eGFR)
Hypersensitivity to tafenoquine, other 8-aminoquinolines, or any component of the formulation; G6PD deficiency or unknown G6PD status; breastfeeding when the infant is found to be G6PD deficient or if the G6PD status of the infant is unknown; when used for chemoprophylaxis, patients with a history of psychotic disorders or current psychotic symptoms (eg, hallucinations, delusions, grossly disorganized behavior)
Concerns related to adverse effects:
• Hemolytic anemia: Hemolytic anemia may occur in patients with G6PD deficiency; decreased hemoglobin levels were also reported in some G6PD-normal patients. Screen for G6PD deficiency prior to initiation of therapy. Use is contraindicated in patients with G6PD deficiency or unknown G6PD status. Because of the limitations of G6PD tests, be alert to the residual risk of hemolysis and monitor all patients for signs/symptoms of hemolysis (may be delayed in onset/duration due to long half-life of tafenoquine); ensure availability of adequate medical support and follow-up to manage hemolytic risk.
• Hypersensitivity reactions: Serious hypersensitivity reactions (eg, angioedema, urticaria) have been reported; reactions may be delayed in onset and/or duration (due to long half-life of tafenoquine). Discontinue use and institute appropriate treatment if a hypersensitivity reaction occurs; do not readminister in patients who have experienced hypersensitivity reactions to tafenoquine.
• Methemoglobinemia: Asymptomatic elevations in methemoglobin have been reported; carefully monitor patients with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency.
• Psychiatric effects: Psychiatric effects (eg, abnormal dreams, anxiety, depression, insomnia) have been reported and may be delayed in onset and/or duration (due to long half-life of tafenoquine). Psychosis was reported in patients with a history of psychiatric disorders following receipt of higher than approved doses. Use with caution in patients with a history of psychiatric illness; use for chemoprophylaxis is contraindicated in patients with a history of psychotic disorders or current psychotic symptoms. Consider discontinuation and prompt evaluation if psychotic symptoms occur; other psychiatric symptoms (eg, anxiety, changes in mood, insomnia, nightmares) should be promptly evaluated if moderate and last more than 3 days or if severe.
Disease-related concerns:
• G6PD deficiency: Screen for G6PD deficiency prior to therapy initiation. Use is contraindicated in patients with G6PD deficiency or unknown G6PD status.
Other warnings/precautions:
• Appropriate use: Concomitant use with antimalarials other than chloroquine is not recommended; lack of efficacy in reducing P. vivax recurrence has been reported when combined with an artemisinin-containing antimalarial.
• Delayed adverse reactions: Because of the long half-life of tafenoquine (~17 days), adverse reactions (eg, psychiatric effects, hemolytic anemia, methemoglobinemia, hypersensitivity reactions) that may occur could be delayed in onset and/or duration.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
MATE1/2-K Substrates (Clinically Relevant with Inhibitors): Tafenoquine may increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider therapy modification
OCT2 Substrates (Clinically Relevant with Inhibitors): Tafenoquine may increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Risk D: Consider therapy modification
Pregnancy status should be evaluated prior to therapy. When tafenoquine is used in females of reproductive potential, effective contraception should be used during therapy and for 3 months after the last dose.
Malaria infection in pregnant women may be more severe than in nonpregnant women and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, pregnant women and women who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, pregnant women should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2020a; CDC Yellow Book 2020).
Because tafenoquine may cause acute hemolytic anemia in a fetus with G6PD deficiency, tafenoquine should not be used in pregnant women. When treatment is needed, other agents are preferred (CDC 2020a; CDC Yellow Book 2020). Consult current Centers for Disease Control and Prevention guidelines for the treatment of malaria during pregnancy.
It is not known if tafenoquine is present in breast milk.
The G6PD status of the infant should be determined prior to breastfeeding. Use is contraindicated in patients breastfeeding an infant that is G6PD-deficient or whose status is unknown; breastfeeding should be withheld until 3 months after the last dose.
According to the manufacturer, the decision to breastfeed infants with normal G6PD status during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. However, until safety data are available, current guidelines do not recommend use in women who are breastfeeding (CDC 2020a; CDC Yellow Book 2020).
Take with food.
Pregnancy testing (females) and G6PD testing prior to administration; signs/symptoms of hemolysis, hypersensitivity reaction, methemoglobinemia, and psychiatric effects (onset and/or duration of symptoms may be delayed due to long half-life)
Tafenoquine is an 8-aminoquinoline antimalarial drug active against pre-erythrocytic (liver) forms (including hypnozoite [dormant stage]) and erythrocytic (asexual) forms, as well as gametocytes, of Plasmodium species, including P. falciparum and P. vivax. Activity against the pre-erythrocytic liver stage prevents development of the erythrocytic forms of the parasite, which are responsible for relapses in P. vivax malaria. Also causes red blood cell shrinkage in vitro.
Absorption: Absorption increased when administered with a high-calorie, high-fat meal
Distribution: Vd: 1,600 to 2,470 L
Protein binding: >99.5%
Half-life elimination: 15 to 16.5 days
Time to peak: 12 to 15 hours
Tablets (Arakoda Oral)
100 mg (per each): $21.38
Tablets (Krintafel Oral)
150 mg (per each): $19.20
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