KRINTAFEL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KRINTAFEL (KRINTAFEL).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KRINTAFEL (KRINTAFEL).

Breastfeeding	No data on human milk excretion; M/P ratio unknown. Risk to infant cannot be ruled out; consider stopping breastfeeding due to potential adverse effects.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["G6PD deficiency (absolute)","History of psychotic disorder (absolute)","Breastfeeding (relative; avoid unless infant G6PD normal)","Pregnancy (relative; avoid unless benefit outweighs risk)"]

Clinical Precautions

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."]

Clinical Tips & Counseling

Drug interactions

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KRINTAFEL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KRINTAFEL (KRINTAFEL).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KRINTAFEL (KRINTAFEL).

Breastfeeding	No data on human milk excretion; M/P ratio unknown. Risk to infant cannot be ruled out; consider stopping breastfeeding due to potential adverse effects.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["G6PD deficiency (absolute)","History of psychotic disorder (absolute)","Breastfeeding (relative; avoid unless infant G6PD normal)","Pregnancy (relative; avoid unless benefit outweighs risk)"]