Dosing and uses of Berinert, Cinryze (C1 inhibitor human)
Adult dosage forms and strengths
lyophilized powder for injection
- 500 unit/vial
Hereditary Angioedema Acute Treatment
Berinert
- Indicated for the treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adults and children
- 20 units/kg IV infused slowly, not to exceed 4 mL/min
- Patients may self administer after completing education for IV administration
Hereditary Angioedema Prophylaxis
Cinryze
- Indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema
- 1,000 units IV q3-4Days; infuse over 10 minutes (ie, 1 mL/min)
Delayed Graft Function (Orphan)
Prevention and/or treatment of delayed graft function after solid organ transplantation
Orphan indication sponsor
- Pharming Technologies B.V.; Archimedesweg 4, Netherlands
Capillary Leakage Syndrome (Orphan)
Orphan indication sponsor
- Pharming Technologies B.V.; Archimedesweg 4, Netherlands
Pediatric dosage forms and strengths
lyophilized powder for injection
- 500 unit/vial
Hereditary Angioedema Acute Treatment
Berinert
- Indicated for the treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adults and children
- 20 units/kg IV infused slowly, not to exceed 4 mL/min
Hereditary Angioedema Prophylaxis
Cinryze
- Indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema
- Neonates and children: Safety and efficacy not established
- Adolescents: 1,000 units IV q3-4Days; infuse over 10 minutes (ie, 1 mL/min)
Berinert, Cinryze (C1 inhibitor human) adverse (side) effects
Berinert
>4%: nausea, vomiting, diarrhea, dysgeusia, headache, abdominal pain, muscle spasms, and pain
Rare: laryngeal edema, swelling (shoulder and chest), exacerbation of hereditary angioedema, and laryngospasm
Cinryze
>5%: URI, sinusitis, rash, & headache
Rare: death to non-catheter related foreign body embolus, pre-eclampsia, stroke, exacerbation of HAE attacks
Warnings
Contraindications
History of life-threatening immediate hypersensitivity reactions
Previous anaphylaxis to product
Cautions
Risk of: severe hypersensitivity; thrombotic events may occur; transmission of infectious disease from product potentially possible
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown; use with caution
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 Berinert, Cinryze (C1 inhibitor human)
Mechanism of action
Serine proteinase inhibitor
Increases plasma concentration of C1 inhibitor activity
HAE patients have low levels of endogenous or functional C1 inhibitor: presentation of HAE attacks are thought to be mediated primarily through contact system activation
C1 inhibitor suppresses contact system activation through inactivation of plasma kallikrein and Factor XIIa modulating vasc permeability by preventing bradykinin generation
Absorption
Cinryze
- Peak Plasma Concentration (1 dose): 0.68±0.08 U/mL
- Peak Plasma Time (Single dose): 3.9 +/- 7.3 hr
Distribution
Berinert
- Vd (mL/kg): 14.1-56.1 (adults); 31.9-54.0 (pediatrics)
Elimination
Berinert clearance (mL/kg/hr): 0.43-3.85 (adults); 0.98-1.1 (pediatrics)
Half-life
- Cinryze: (1 dose) 56 +/- 36 hr
- Berinert: 7.4-22.8 hr (adults); 7.4-22.5 hr (pediatrics)
Administration
IV Preparation
Do not use if turbid or discolored (should be colorless to slight blue)
Bring to room temp, cleanse stoppers with germicidal solution, allow to dry
Use double-ended transfer needle; invert diluent vial containing 5 mL SWI over upright & slightly angled vial of drug; then rapidly insert free end of needle through the drug's vial stopper at its center; vial vacuum will draw in diluent
Do NOT use product if there is no vacuum in viaL
Disconnect vials, discard diluent vial along w/ transfer needle, gently swirl to mix
Cinryze: Each reconstituted vial contains 5 mL of 100 U/mL solution
Cinryze: Reconstitute 2 vials for one dose
Berinert: Vials are reconstituted with 10 mL dilutent supplied
IV Administration
Administer at room temp within 3 hr (Cinryze) or 8 hr (Berinert) after reconstitution
To withdraw, introduce air in vial & withdraw drug solution
Attach needle or infusion set with winged adapter
Cinryze: Infuse at 1 mL/min over 10 min
Berinert: Infuse at no faster than 4 mL/min
Storage
Untampered vial may be stored at 2-25°C (36-77°F) for up to 1 year
Do not freeze
Protect from light
