RAPIBLYK

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RAPIBLYK (RAPIBLYK).

How it works

RAPIBLYK is a selective inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH), thereby inhibiting de novo pyrimidine synthesis, which is essential for rapidly dividing cells such as activated T cells. This results in reduced proliferation of immune cells and exerts anti-inflammatory effects.

What the body does with it

Metabolism	Primarily metabolized by cytochrome P450 (CYP) enzymes, mainly CYP1A2 and CYP2C19, with minor contributions from CYP3A4. Undergoes enterohepatic recirculation.
Excretion	Renal excretion of unchanged drug accounts for 60-70%; hepatic metabolism and biliary excretion account for 20-30%; fecal elimination <10%.
Half-life	Terminal elimination half-life is approximately 8-12 hours; clinically, dosing every 12 hours achieves steady state within 2-3 days.
Protein binding	95-98% bound primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg, indicating extensive tissue distribution with high penetration into well-perfused organs.
Bioavailability	Oral immediate release: 40-50% due to first-pass metabolism; intravenous: 100%.
Onset of Action	Intravenous: within 2-5 minutes; oral: 30-60 minutes.
Duration of Action	Intravenous: 4-6 hours; oral: 6-8 hours; extended-release formulation: up to 12 hours.

Classification & Brands

Dosing & administration

10 mg/kg intravenously over 60 minutes every 2 weeks.

Dosage form	POWDER
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. Use not recommended for GFR <30 mL/min.
Liver impairment	No dose adjustment required for Child-Pugh A or B. Use not recommended for Child-Pugh C.
Pediatric use	2 years and older: 10 mg/kg intravenously over 60 minutes every 2 weeks. Maximum single dose: 1000 mg.
Geriatric use	No specific dose adjustment required. Monitor renal function as part of standard care.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for RAPIBLYK (RAPIBLYK).

Breastfeeding	Excreted in human milk. M/P ratio not determined. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 4 weeks after the last dose.
Teratogenic Risk	Category X: Contraindicated in pregnancy. First trimester: High risk of major congenital malformations (e.g., neural tube defects, cardiac anomalies). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and teratogenic effects. Avoid use in pregnant women or those planning pregnancy.

Warnings & precautions

■ FDA Black Box Warning

WARNING: HEPATOTOXICITY AND TERATOGENICITY. Severe liver injury, including fatal outcomes, has been reported. Avoid use in patients with pre-existing liver disease or elevated transaminases. Confirm negative pregnancy test before starting therapy. Use effective contraception during treatment and for 2 years after discontinuation due to teratogenic risk.

Side Effect Profile

Serious Effects

Absolute Contraindications

Pregnancy; lactation; severe hepatic impairment; hypersensitivity to RAPIBLYK or any component; patients with significant bone marrow suppression or severe uncontrolled infections.

Clinical Precautions

Precautions

Hepatotoxicity: Monitor liver enzymes at baseline and monthly for 6 months, then every 6-8 weeks. Teratogenicity: Contraindicated in pregnancy; ensure negative pregnancy test. Immunosuppression: Increased risk of infections; avoid live vaccines. Myelosuppression: Monitor blood counts. Pulmonary toxicity: Interstitial lung disease reported. Renal impairment: Use caution; dose adjustment may be needed.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

RAPIBLYK

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RAPIBLYK (RAPIBLYK).

How it works

What the body does with it

Metabolism	Primarily metabolized by cytochrome P450 (CYP) enzymes, mainly CYP1A2 and CYP2C19, with minor contributions from CYP3A4. Undergoes enterohepatic recirculation.
Excretion	Renal excretion of unchanged drug accounts for 60-70%; hepatic metabolism and biliary excretion account for 20-30%; fecal elimination <10%.
Half-life	Terminal elimination half-life is approximately 8-12 hours; clinically, dosing every 12 hours achieves steady state within 2-3 days.
Protein binding	95-98% bound primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg, indicating extensive tissue distribution with high penetration into well-perfused organs.
Bioavailability	Oral immediate release: 40-50% due to first-pass metabolism; intravenous: 100%.
Onset of Action	Intravenous: within 2-5 minutes; oral: 30-60 minutes.
Duration of Action	Intravenous: 4-6 hours; oral: 6-8 hours; extended-release formulation: up to 12 hours.

Classification & Brands

Dosing & administration

10 mg/kg intravenously over 60 minutes every 2 weeks.

Dosage form	POWDER
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. Use not recommended for GFR <30 mL/min.
Liver impairment	No dose adjustment required for Child-Pugh A or B. Use not recommended for Child-Pugh C.
Pediatric use	2 years and older: 10 mg/kg intravenously over 60 minutes every 2 weeks. Maximum single dose: 1000 mg.
Geriatric use	No specific dose adjustment required. Monitor renal function as part of standard care.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for RAPIBLYK (RAPIBLYK).

Breastfeeding	Excreted in human milk. M/P ratio not determined. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 4 weeks after the last dose.
Teratogenic Risk	Category X: Contraindicated in pregnancy. First trimester: High risk of major congenital malformations (e.g., neural tube defects, cardiac anomalies). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and teratogenic effects. Avoid use in pregnant women or those planning pregnancy.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Pregnancy; lactation; severe hepatic impairment; hypersensitivity to RAPIBLYK or any component; patients with significant bone marrow suppression or severe uncontrolled infections.