RAPIBLYK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RAPIBLYK (RAPIBLYK).
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.
| 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. |
| Molecular Weight | 425.6 |
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. |
| 1st trimester | RAPIBLYK is not recommended during the first trimester due to potential teratogenic effects observed in animal studies. |
| 2nd trimester | Limited human data; use only if potential benefit justifies risk to the fetus. |
| 3rd trimester | Avoid during third trimester due to risk of neonatal adverse effects (e.g., respiratory depression). |
Clinical note
Comprehensive clinical and safety monograph for RAPIBLYK (RAPIBLYK).
| Placental transfer | Crosses the placenta; fetal plasma concentrations reach approximately 50% of maternal levels. |
| Breastfeeding | RAPIBLYK is excreted in human milk in low concentrations. Monitor infant for potential adverse effects. |
| Lactation Rating |
■ 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.
| Serious Effects |
Hypersensitivity to RAPIBLYKSevere renal impairment (CrCl <30 mL/min)Concomitant use with MAO inhibitors
| 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. |
| Food/Dietary | No significant food interactions known. Avoid excessive caffeine or alcohol as they may affect heart rate. |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor complete blood count, liver function tests, renal function, and serum drug levels. Fetal ultrasound for assessment of growth and anatomy. Regular monitoring for signs of fetal distress. Postnatal monitoring of infant for adverse effects. |
| Fertility Effects | Based on animal studies, may impair fertility in females of reproductive potential (e.g., altered estrous cycles, reduced implantation). Reversible after discontinuation. Effect on male fertility unknown. |
| Clinical Pearls | Rapiblyk (landiolol) is an ultra-short-acting beta-1 selective blocker with rapid onset and offset (half-life ~4 minutes). Use in acute atrial fibrillation/flutter for rate control, especially in critically ill patients with hemodynamic instability. Titrate carefully due to potential hypotension; monitor heart rate and blood pressure continuously. Avoid in patients with severe bradycardia, heart block, or decompensated heart failure. Can be used in patients with reactive airway disease with caution due to relative beta-1 selectivity. |
| Patient Advice | This medication is given intravenously in the hospital to control your heart rate. · You will be on continuous heart rate and blood pressure monitoring during treatment. · Report any symptoms of dizziness, lightheadedness, or shortness of breath immediately. · Do not stop or change the dose on your own; this medication is only given under close medical supervision. · Inform your healthcare provider if you have asthma, COPD, or a slow heart rate. |