FDA

Krintafel

Approved 20 Jul 2018OralTablet

Indications

KRINTAFEL is indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged 16 years and older who are receiving chloroquine therapy for acute P. vivax infection [see Dosage and Administration ( 2.2 )] . Limitations of Use

KRINTAFEL is NOT indicated for the treatment of acute P. vivax malaria.
Concomitant use of KRINTAFEL with antimalarials other than chloroquine is not recommended because of the risk of recurrence of P. vivax malaria [see Warnings and Precautions ( 5.6 )] . KRINTAFEL is an antimalarial indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged 16 years and older who are receiving chloroquine therapy for acute P. vivax infection. ( 1 ) Limitations of Use
KRINTAFEL is NOT indicated for the treatment of acute P. vivax malaria. ( 1 )
The concomitant use of KRINTAFEL with antimalarials other than chloroquine is not recommended because of the risk of recurrence of P. vivax malaria. ( 1 , 5.6 )

Contraindications

KRINTAFEL is contraindicated in:

Patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia [see Warnings and Precautions ( 5.1 )] .
Breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if the G6PD status of the infant is unknown [see Use in Specific Populations ( 8.2 )].
Patients with known hypersensitivity to tafenoquine, other 8-aminoquinolines, or any component of KRINTAFEL [see Warnings and Precautions ( 5.5 )] .
G6PD deficiency or unknown G6PD status. ( 4 )
Breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if G6PD status is unknown. ( 4 , 8.2 )
Known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of KRINTAFEL. ( 4 )

Warnings and precautions

Hemolytic Anemia : G6PD testing must be performed before prescribing KRINTAFEL due to the risk of hemolytic anemia. Monitor patients for clinical signs or symptoms of hemolysis. ( 5.1 )
G6PD Deficiency in Pregnancy or Lactation : KRINTAFEL may cause hemolytic anemia when administered to a pregnant woman with a G6PD-deficient fetus. KRINTAFEL is not recommended during pregnancy. A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to KRINTAFEL through breast milk. Check infant’s G6PD status before breastfeeding begins. ( 5.2 , 8.1 , 8.2 )

At a glance

Brand name: Krintafel
Active substance: tafenoquine succinate
Route: Oral
Dosage form: Tablet
Applicant: Glaxosmithkline
Status: Prescription
FDA approval: 20 Jul 2018
Application: NDA210795-001

Indications

KRINTAFEL is NOT indicated for the treatment of acute P. vivax malaria.
Concomitant use of KRINTAFEL with antimalarials other than chloroquine is not recommended because of the risk of recurrence of P. vivax malaria [see Warnings and Precautions ( 5.6 )] . KRINTAFEL is an antimalarial indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged 16 years and older who are receiving chloroquine therapy for acute P. vivax infection. ( 1 ) Limitations of Use
KRINTAFEL is NOT indicated for the treatment of acute P. vivax malaria. ( 1 )
The concomitant use of KRINTAFEL with antimalarials other than chloroquine is not recommended because of the risk of recurrence of P. vivax malaria. ( 1 , 5.6 )

Contraindications

KRINTAFEL is contraindicated in:

Patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia [see Warnings and Precautions ( 5.1 )] .
Breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if the G6PD status of the infant is unknown [see Use in Specific Populations ( 8.2 )].
Patients with known hypersensitivity to tafenoquine, other 8-aminoquinolines, or any component of KRINTAFEL [see Warnings and Precautions ( 5.5 )] .
G6PD deficiency or unknown G6PD status. ( 4 )
Breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if G6PD status is unknown. ( 4 , 8.2 )
Known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of KRINTAFEL. ( 4 )

Warnings and precautions

Hemolytic Anemia : G6PD testing must be performed before prescribing KRINTAFEL due to the risk of hemolytic anemia. Monitor patients for clinical signs or symptoms of hemolysis. ( 5.1 )
G6PD Deficiency in Pregnancy or Lactation : KRINTAFEL may cause hemolytic anemia when administered to a pregnant woman with a G6PD-deficient fetus. KRINTAFEL is not recommended during pregnancy. A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to KRINTAFEL through breast milk. Check infant’s G6PD status before breastfeeding begins. ( 5.2 , 8.1 , 8.2 )

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

The use of KRINTAFEL during pregnancy may cause hemolytic anemia in a fetus who is G6PD deficient. Treatment with KRINTAFEL during pregnancy is not recommended [see Warnings and Precautions ( 5.2 )] . Available data with use of KRINTAFEL in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, there were increased abortions, with and without maternal toxicity, when KRINTAFEL 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. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion, and stillbirth. Data Animal Data: Tafenoquine resulted in dose-related abortions when given orally to pregnant rabbits during organogenesis (Gestation Days 6 to 18) at doses of 7 mg/kg (about 0.4 times the clinical exposure based on body surface area comparisons) and above.

Doses higher than 7 mg/kg were also associated with maternal toxicity (mortality and reduced body weight gain). In a similar study in rats, doses of 3, 10, or 30 mg/kg/day resulted in maternal toxicity (enlarged spleen, reduced body weight, and reduced food intake) but no fetotoxicity at the high dose (equivalent to the clinical exposure based on body surface area comparisons). There was no evidence of malformations in either species.

In a pre- and postnatal development study in rats, tafenoquine administered throughout pregnancy and lactation produced maternal toxicity and a reversible decrease in offspring body weight gain and decrease in motor activity at 18 mg/kg/day, which is equivalent to about 0.6 times the clinical dose based on body surface area comparisons.

Adverse reactions

The following clinically significant adverse reactions have been observed with KRINTAFEL and are discussed in detail in the Warnings and Precautions section:

Hemolytic anemia [see Warnings and Precautions ( 5.1 )]
Methemoglobinemia [see Warnings and Precautions ( 5.3 )]
Psychiatric effects [see Warnings and Precautions ( 5.4 )]
Hypersensitivity reactions [see Warnings and Precautions ( 5.5 )] Common adverse reactions (≥5%) were dizziness, nausea, vomiting, headache, and decreased hemoglobin. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect exposure to 4,129 subjects, of whom 810 received a 300-mg single dose of KRINTAFEL. KRINTAFEL was evaluated in patients with P. vivax malaria (n = 483) in 3 randomized, double-blind trials including a placebo-controlled trial comparing KRINTAFEL plus chloroquine (n = 260) with chloroquine alone (Trial 1), a placebo-controlled dose-ranging trial (Trial 2) (n = 57) [see Clinical Studies ( 14 )] , and a hematologic safety trial (Trial 3, NCT02216123) (n = 166).

In Trial 1, in patients with P. vivax malaria, the most common adverse reactions reported in ≥5% of patients treated with KRINTAFEL are listed in Table 1 . Patients included in the trial had a mean age of 35 (range: 16 to 79 years), were 75% male and from the following regions: 70% Latin America (Brazil and Peru), 19% Southeast (SE) Asia (Thailand, Cambodia, and the Philippines), and 11% Africa (Ethiopia). Table 1. Selected Adverse Reactions a Reported in ≥5% of Patients with P. vivax Malaria Receiving KRINTAFEL in a Randomized, Active-Controlled Trial (Trial 1) a Adverse reactions reported prior to Day 29 as subsequent adverse reactions can be confounded by recurrence of malaria or retreatment with another agent from the quinoline class.

Adverse Reaction Chloroquine KRINTAFEL + Chloroquine (n = 133) (n = 260) % % Dizziness 3 8 Nausea 7 6 Vomiting 5 6 Decreased Hemoglobin 2 5 Headache 7 5 Other Adverse Reactions Reported with KRINTAFEL Clinically significant adverse reactions with KRINTAFEL 300-mg single dose in clinical trials (n = 810) in ≤3% of subjects are listed below: Psychiatric Disorders: Anxiety, insomnia, abnormal dreams. Nervous System Disorders: Somnolence.

Laboratory Investigations: Increased blood creatinine, increased blood methemoglobin, increased alanine aminotransferase. Immune System Disorders: Hypersensitivity reactions (e.g., angioedema, urticaria) [see Contraindications ( 4 ), Warnings and Precautions ( 5.5 )] . Eye Disorders: Vortex keratopathy, photophobia.

Krintafel

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Krintafel

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.2G6PD Deficiency in Pregnancy or Lactation Potential Harm to the Fetus

5.3Methemoglobinemia

5.4Psychiatric Effects

5.5Hypersensitivity Reactions

Interactions

7.1Effect of

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Official product information