KRINTAFEL
Clinical safety rating
cautionComprehensive clinical and safety monograph for KRINTAFEL (KRINTAFEL).
KRINTAFEL (tafenoquine) is an 8-aminoquinoline antimalarial that inhibits parasite growth by interfering with the electron transport chain in the mitochondria of Plasmodium species. It is active against both the erythrocytic and exoerythrocytic stages, including hypnozoites of P. vivax.
| Metabolism | Primarily metabolized via CYP2D6 to an active metabolite. Tafenoquine itself may also be metabolized by monoamine oxidase (MAO). |
| Excretion | Primarily renal; approximately 70-80% of administered dose is excreted unchanged in urine via glomerular filtration and active tubular secretion. Fecal excretion accounts for less than 5%. |
| Half-life | Terminal elimination half-life is approximately 5-7 days in healthy subjects. Due to accumulation, steady state is achieved after 4-5 weeks of weekly dosing. In patients with renal impairment, half-life may be prolonged. |
| Protein binding | ≥99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 10-15 L/kg, indicating extensive tissue distribution and binding to haemoglobin in red blood cells. |
| Bioavailability | Oral bioavailability is approximately 70-80% under fasting conditions. Food may slightly increase or decrease absorption; however, the label recommends administration with or without food. |
| Onset of Action | Oral administration: Clinical effect onset is typically within 4-6 hours, corresponding to peak plasma concentrations. |
| Duration of Action | Duration of action is approximately 1 week due to the long half-life, supporting a once-weekly dosing regimen. Clinical effects persist throughout the dosing interval. |
| Molecular Weight | 553.6 |
Adults: 200 mg orally as a single dose.
| Dosage form | TABLET |
| Renal impairment | No adjustment needed for mild to moderate renal impairment (eGFR >=30 mL/min). Not studied in severe renal impairment (eGFR <30 mL/min) or on dialysis; use caution. |
| Liver impairment | No adjustment for mild Child-Pugh A. Not recommended in moderate (Child-Pugh B) or severe (Child-Pugh C) due to lack of data. |
| Pediatric use | Children ≥5 years and ≥15 kg: 6 mg/kg (maximum 200 mg) as a single oral dose. Not established for <5 years or <15 kg. |
| Geriatric use | No specific adjustment; use standard dose with monitoring for adverse effects due to potential age-related renal/hepatic decline. |
| 1st trimester | Contraindicated due to risk of fetal harm from hemolytic anemia and potential for hemoglobin toxicity; no adequate controlled studies in pregnant women. |
| 2nd trimester | Contraindicated; risk of fetal harm similar to first trimester. |
| 3rd trimester | Contraindicated; risk of fetal harm similar to first trimester. |
Clinical note
Comprehensive clinical and safety monograph for KRINTAFEL (KRINTAFEL).
| Placental transfer | Likely crosses placenta based on molecular weight and physicochemical properties; no human data available. |
| Breastfeeding | Not recommended due to potential for serious adverse reactions in nursing infants, including hemolytic anemia. It is unknown if the drug is excreted in human milk. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | No human data; animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded; use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor liver function tests (ALT, AST) before and during treatment; monitor for hemoglobin decline in G6PD deficient patients. In pregnancy, monitor fetal growth via ultrasound if used. |
| Fertility Effects | Animal studies show no adverse effects on fertility. No human data; theoretical risk due to hemolytic potential in G6PD deficiency. |
■ FDA Black Box Warning
Warning: G6PD deficiency – can cause hemolytic anemia in G6PD-deficient individuals. Test for G6PD deficiency before prescribing. Do not use in G6PD-deficient patients.
| Serious Effects |
Hypersensitivity to tafenoquine or any componentPregnancyBreastfeedingG6PD deficiencyHistory of psychotic disorders
| Precautions | Hemolytic anemia in G6PD-deficient patients: screen all patients for G6PD deficiency before use., Methemoglobinemia: monitor for signs; use with caution in patients with NADH-methemoglobin reductase deficiency., Psychiatric effects: may cause anxiety, depression, or psychosis; use with caution in patients with psychiatric disorders., Prolonged QT interval: avoid in patients with cardiac conditions or those taking other QT-prolonging drugs., Hematologic monitoring: monitor CBC during treatment. |
| Food/Dietary | Take with food (preferably a fatty meal) to enhance absorption and reduce gastrointestinal side effects. Avoid grapefruit and grapefruit juice as they may alter drug metabolism. No other specific dietary restrictions. |
| Clinical Pearls | KRINTAFEL (tafenoquine) is indicated for radical cure of Plasmodium vivax malaria. Administer with food to improve absorption and reduce gastrointestinal intolerance. Screen patients for G6PD deficiency before use; contraindicated in G6PD-deficient patients due to risk of hemolytic anemia. Monitor for methemoglobinemia, especially in patients with NADH-methemoglobin reductase deficiency. Avoid in pregnancy and lactation unless benefit outweighs risk. Single-dose regimen improves adherence compared to primaquine. |
| Patient Advice | Take this medication exactly as prescribed, usually as a single dose with food to reduce stomach upset. · You must be tested for G6PD deficiency before starting this medication; inform your doctor if you have a history of anemia or enzyme deficiency. · Avoid alcohol during treatment as it may increase risk of side effects. · Report any signs of dark urine, yellowing of skin or eyes, unusual tiredness, or shortness of breath immediately. · Do not take this medication if you are pregnant or breastfeeding without consulting your doctor. · This medication cures relapsing malaria; complete the full course even if you feel better. |
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