Dosing and uses of Ruconest (C1 esterase inhibitor recombinant)
Adult dosage forms and strengths
lyophilized powder for reconstitution
- 2100 IU/vial
Hereditary Angioedema
Indicated for treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE)
<84 kg: 50 IU/kg infused over 5 minutes; not to exceed 4200 IU/dose
≥84 kg: 4200 IU IV infused over 5 min
If the attack symptoms persist, may administer a second dose at the recommended dose level (not to exceed 4200 IU/dose)
Not to exceed 2 doses/24 hr
Dosing Considerations
Effectiveness is not established in HAE patients with laryngeal attacks
Pediatric dosage forms and strengths
lyophilized powder for reconstitution
- 2100 IU/vial
Hereditary Angioedema
Indicated for treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE)
Infants and children: Safety and efficacy not established
Adolescents
- <84 kg: 50 IU/kg IV infused over 5 minutes; not to exceed 4200 IU/dose
- ≥84 kg: 4200 IU IV infused over 5 min
- If the attack symptoms persist, may administer a 2nd dose at the recommended dose level (not to exceed 4200 IU/dose)
- Not to exceed 2 doses/24 hr
Dosing Considerations
Effectiveness is not established in HAE patients with laryngeal attacks
Ruconest (C1 esterase inhibitor recombinant) adverse (side) effects
1-10%
Headache (9%)
Nausea (2%)
Diarrhea (2%)
Postmarketing Reports
Abdominal pain
Rash
Warnings
Contraindications
History of allergy to rabbits or rabbit-derived products
History of life-threatening immediate hypersensitivity reactions to C1 esterase inhibitor preparations, including anaphylaxis
Cautions
Severe hypersensitivity reactions may occur during or after injection; signs and symptoms include hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and/or anaphylaxis
Serious arterial and venous thromboembolic (TE) events reported at recommended doses of plasma-derived C1-esterase inhibitor products in patients with risk factors; risk factors include indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility
Pregnancy and lactation
Pregnancy category: B; may use during pregnancy if clearly needed
Studies performed in rats and rabbits at doses up to 12.5 times the human could not exclude an effect on embryofetal development; no adequate and well-controlled studies in pregnant women
Lactation: Unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ruconest (C1 esterase inhibitor recombinant)
Mechanism of action
C1 esterase inhibitor (C1INH) is a normal constituent of human blood and is one of the serine protease inhibitors (serpins)
Human recombinant C1 esterase inhibitor purified from the milk of genetically modified (transgenic) rabbits; restores level of functional C1 esterase inhibitor in a patient’s plasma, thereby treating the acute attack of swelling
Patients with HAE have low levels of endogenous or functional C1 inhibitor; C1 inhibitor suppresses contact system activation through inactivation of plasma kallikrein and factor XIIa, modulating vascular permeability by preventing bradykinin generation
Absorption
Peak plasma concentration: 1.2-2.3 IU/mL
Peak plasma time: 0.31 hr
AUC: 3.3-10.6 IU•hr/mL
Distribution
Vd: 2.4-3 L
Elimination
Half-life: 2.4-2.7 hr
Clearance: 781-1207 mL/hr
Administration
IV Preparation
Ensure C1 esterase inhibitor recombinant and sterile water for injection (SWI) are at room temperature
Reconstitute each vial (2100 IU) by adding 14 mL SWI; add the diluent slowly to avoid forceful impact on the powder
Swirl the vial slowly to mix and avoid foaming
Visually inspect for particulate matter and discoloration after reconstitution and prior to administration; reconstituted solution should be colorless, clear, and free from visible particles
Do not use if the solution is cloudy, colored, or contains particulates
Resulting solution concentration is 150 IU/mL
Use the reconstituted product immediately, or within 8 hr if stored refrigerated
Discard partially used vials
IV Administration
Do not mix with other medicinal products; administer by a separate infusion line
Administer by slow IV injection over 5 minutes
For self-administration, provide the patient with instructions and training for IV injection outside of a clinic setting so patients may self-administer upon recognition of symptoms of an HAE attack
Discard any unused product
Storage
Unreconstituted vials
- Store in the original package in order to protect from light
- Shelf life: 48 months when stored at 2-25°C (36-77°F)
- Do not freeze
Reconstituted vials
- Contains no preservatives
- May store for 8 hr at 2-8°C (36-46°F)
- Do not freeze
