ORLADEYO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORLADEYO (ORLADEYO).
Oral C1 esterase inhibitor (C1-INH) replacement. ORLADEYO increases plasma levels of functional C1-INH, thereby inhibiting the contact system and reducing vascular permeability. It acts as a regulator of complement and contact system activation.
| Metabolism | Primary metabolic pathway is proteolytic degradation; not metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily unchanged drug excreted in feces (77.1%) and urine (14.5%) after oral administration; biliary excretion contributes to fecal elimination. |
| Half-life | Terminal elimination half-life approximately 44–50 hours in healthy subjects; at steady state, effective half-life supports once-daily dosing. |
| Protein binding | Approximately 99.1% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is about 0.47 L/kg (mean ~35 L), consistent with distribution mostly in extracellular fluid. |
| Bioavailability | Absolute oral bioavailability is approximately 68% after a single 110 mg dose under fasted conditions. |
| Onset of Action | Reduction in hereditary angioedema attack rate observed by week 2 of oral therapy; maximum effect achieved by week 4. |
| Duration of Action | Sustained efficacy over 24 hours with once-daily dosing; continuous therapy required to maintain suppression of angioedema attacks. |
110 mg orally twice daily with food.
| Dosage form | PELLETS |
| Renal impairment | For eGFR 30-89 mL/min: no adjustment. For eGFR 15-29 mL/min: 110 mg once daily. For eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: 110 mg twice daily. Child-Pugh B: 110 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Approved for ages ≥12 years: 110 mg orally twice daily with food. For patients <12 years: not established. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider age-related decline in GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORLADEYO (ORLADEYO).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. The molecular weight (~600 Da) suggests likely excretion into milk. Use caution; consider developmental benefit of breastfeeding versus mother's need for drug. |
| Teratogenic Risk | No human data available. In animal studies, oral berotralstat (Orladeyo) did not produce fetal malformations at exposures up to 6 times the human clinical exposure. However, fetal growth retardation was observed at maternally toxic doses. Therefore, use only if benefit justifies risk; avoid in first trimester unless essential. |
■ FDA Black Box Warning
No Black Box Warning.
| Serious Effects |
["History of life-threatening immediate hypersensitivity reactions (including anaphylaxis) to C1 inhibitor preparations."]
| Precautions | ["Hypersensitivity reactions, including anaphylaxis, may occur. Thrombotic events have been reported in patients receiving C1-INH products, especially those with indwelling catheters. Monitor for signs/symptoms of thrombosis. Use with caution in patients with known risk factors for thrombosis."] |
Loading safety data…
| Fetal Monitoring | Monitor for maternal adverse effects (GI upset, headache, elevated liver enzymes) and fetal growth via ultrasound if used during pregnancy. No specific fetal monitoring required beyond routine obstetric care. |
| Fertility Effects | In animal studies, no impairment of male or female fertility at exposures up to 6 times the maximum recommended human dose. Human data lacking. |