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Tafenoquine

Medically reviewed by Drugs.com. Last updated on Aug 13, 2020.

Pronunciation

(ta FEN oh kwin)

Index Terms

  • Arakoda
  • Tafenoquine Succinate

Dosage Forms

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

Brand Names: U.S.

  • Arakoda
  • Krintafel

Pharmacologic Category

  • Aminoquinoline (Antimalarial)
  • Antimalarial Agent

Pharmacology

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

Time to Peak

12 to 15 hours

Half-Life Elimination

15 to 16.5 days

Protein Binding

>99.5%

Use: Labeled Indications

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 appropriate antimalarial 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 2020).

Limitation of use: Not indicated for the treatment of acute P. vivax malaria; must be used in combination with appropriate antimalarial therapy.

Contraindications

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)

Dosing: Adult

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 or hydroxychloroquine therapy (CDC 2020).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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 P. vivax or Plasmodium ovale (radical cure):

Adolescents ≥16 years: Krintafel: Oral: 300 mg single dose on day 1 or 2 of appropriate antimalarial treatment (CDC 2019).

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.

Administration

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.

Dietary Considerations

Take with food.

Storage

Store in original package at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture. Use bottles of 30 tablets within 3 months of opening; do not remove the desiccant.

Drug Interactions

MATE1 Substrates: Tafenoquine may increase the serum concentration of MATE1 Substrates. 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. Consider therapy modification

OCT2 Substrates: Tafenoquine may increase the serum concentration of OCT2 Substrates. 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. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Headache (15%)

Gastrointestinal: Diarrhea (5% to 18%)

Hematologic & oncologic: Methemoglobinemia (13%)

Neuromuscular & skeletal: Back pain (14%)

Ophthalmic: Epithelial keratopathy (21% to 93%)

1% to 10%:

Central nervous system: Dizziness (1% to 5%), sleep disorder (3% to 4%), drowsiness (≤3%), abnormal dreams (2%), insomnia (2%), anxiety (≤1%), depressed mood (≤1%), depression (≤1%)

Gastrointestinal: Nausea (5% to 7%), motion sickness (5%), vomiting (5%)

Hematologic & oncologic: Decreased hemoglobin (2%)

Hepatic: Increased serum alanine aminotransferase (4%)

Hypersensitivity: Hypersensitivity reaction (≤3%)

Ophthalmic: Photophobia (≤3%)

Renal: Increased serum creatinine (≤3%)

<1%, postmarketing and/or case reports: Agitation, amnesia, anemia, ataxia, blurred vision, cholestatic jaundice, corneal disease, decreased estimated GFR (eGFR), decreased visual acuity, hemolytic anemia, hyperacusis, hyperbilirubinemia, hyperesthesia, hypoesthesia, Meniere disease, nocturnal amblyopia, psychoneurosis, retinopathy, suicidal ideation, syncope, thrombocytopenia, tremor, urticaria, visual field defect, visual impairment, vitreous opacity

Warnings/Precautions

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• 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.

Monitoring Parameters

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)

Reproductive Considerations

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.

Pregnancy Considerations

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 2020; 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 2020; CDC Yellow Book 2020). Consult current Centers for Disease Control and Prevention guidelines for the treatment of malaria during pregnancy.

Patient Education

What is this drug used for?

• It is used to prevent malaria.

• It is used to prevent malaria from coming back.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Headache

• Back pain

• Diarrhea

• Motion sickness

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Hemolytic anemia like severe loss of strength and energy, dark urine, or yellow skin

• Methemoglobinemia like blue or gray color of the lips, nails, or skin; abnormal heartbeat; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath

• Behavioral changes

• Mood changes

• Nightmares

• Trouble sleeping

• Sensing things that seem real but are not

• Confusion

• Severe dizziness

• Passing out

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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