C1 Inhibitor (Human)
(cee won in HIB i ter HYU man)
- C1 Esterase Inhibitor
- Human C1 Inhibitor
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Berinert: 500 units
Solution Reconstituted, Intravenous [preservative free]:
Cinryze: 500 units (1 ea)
Brand Names: U.S.
- Blood Product Derivative
- C1 Esterase Inhibitor
C1 inhibitor, one of the serine proteinase inhibitors found in human blood, plays a role in regulating the complement and intrinsic coagulation (contact system) pathway, and is also involved in the fibrinolytic and kinin pathways. C1 inhibitor therapy in patients with C1 inhibitor deficiency, such as HAE, is believed to suppress contact system activation via inactivation of plasma kallikrein and factor XIIa, thus preventing bradykinin production. Unregulated bradykinin production is thought to contribute to the increased vascular permeability and angioedema observed in HAE.
Vss: Berinert: Children and Adolescents: (6 to 13 years, n=5): 0.02 L/kg (range: 0.017 to 0.026 L/kg); Adults: 0.018 L/kg (range: 0.011 to 0.028 L/kg)
Onset of Action
Berinert: Onset of symptom relief: Median: 15 minutes per attack; Cinryze: Pediatric patients 6 to 17 years: Median: 30 minutes per attack; for the majority of patient unequivocal symptom relief reported within 1 hour (range: 15 to 135 minutes) (Lumry 2013)
Cinryze: Increased plasma C1 inhibitor levels observed ~1 hour or less
Time to Peak
Cinryze: ~4 hours
Duration of Action
Time to complete resolution of HAE symptoms: Berinert: Median: 8.4 hours
Children Children 3 to <12 years: Berinert: 16.7 hours
Adults (following a single dose): Berinert: 22 hours (range: 17 to 24 hours); Cinryze: 56 hours (range: 11 to 108 hours)
Special Populations: Children
Compared with adults, the half-life was shorter and clearance was faster (Berinert).
Use: Labeled Indications
Berinert: Treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adult and adolescent patients
Cinryze: Routine prophylaxis against angioedema attacks in adult and adolescent patients with HAE
History of anaphylactic or life-threatening hypersensitivity reactions to human C1 inhibitor or any component of the formulation
IV: Adolescents and Adults:
Routine prophylaxis against hereditary angioedema (HAE) attacks (Cinryze): 1,000 units every 3 to 4 days
Treatment of abdominal, facial, or laryngeal HAE attacks (Berinert): 20 units/kg
Dosage adjustment in renal impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Allow vial and diluent (sterile water for injection) to come to room temperature prior to reconstitution. Reconstitute each vial with 5 mL (Cinryze), 10 mL (Berinert 500 units), or 3 mL (Berinert 1,500 units [Canadian product]) of sterile water for injection using a double-ended transfer needle or the provided transfer set. A silicone-free syringe may be required for reconstitution and administration (refer to manufacturer's labeling). Do not use product if there is no vacuum in the vial. After combining with diluent, gently swirl vial (do not shake) to completely dissolve powder. Reconstituted product should be clear and colorless or slightly blue (Cinryze only); do not use if turbid, discolored, or contains particles. The provided filter needle or transfer set should be used to withdraw the reconstituted product. Remove filter needle and attach reconstituted solution to infusion set or appropriate needle for infusion. Do not mix with other medicinal products.
Berinert (500 units): Administer intravenously at ~4 mL/minute by a separate infusion line; use within 8 hours of reconstitution (Canadian labeling recommends use immediately after reconstitution).
Berinert (1,500 units) [Canadian product]: Administer intravenously by slow injection by a separate infusion line; use immediately after reconstitution.
Cinryze: Administer intravenously at 1 mL/minute (over 10 minutes); use within 3 hours of reconstitution.
Self-administration: Following patient training and instructions on self-administration, patient may self-administer treatment (Berinert) or prophylaxis (Cinryze) therapy. Epinephrine should be available during self-administration in the event of an acute, severe hypersensitivity reaction. Patient suffering from an acute laryngeal HAE attack and self-administering should be informed to seek immediate medical attention following treatment (potential for airway obstruction to occur).
Store intact vials at 2°C to 25°C (36°F to 77°F); do not freeze. Store in original carton; protect from light. Use within 3 hours (Cinryze) or 8 hours (Berinert) of reconstitution (Canadian labeling recommends immediate use after reconstitution); do not refrigerate or freeze reconstituted solution. Discard any unused product.
Androgens: May enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
Estrogen Derivatives: May enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
Progestins: May enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
Central nervous system: Headache
1% to 10%:
Central nervous system: Dizziness, fever
Dermatologic: Erythema, pruritus, rash
Gastrointestinal: Abdominal pain/discomfort, abnormal taste, vomiting, xerostomia
Genitourinary: Vulvovaginal fungal infection
Local: Infusion-related reactions
Respiratory: Nasopharyngitis,upper respiratory tract infection
Miscellaneous: Flu-like syndrome, hereditary angioedema attack symptoms exacerbated, viral infection
<1% (Limited to important or life-threatening): Anaphylactic reaction, chills, hypersensitivity reaction, injection site erythema, injection site pain, shock, stroke, thrombotic events, transient ischemic attack
Concerns related to adverse effects:
• Hypersensitivity: Severe hypersensitivity reactions (eg, urticaria, hives, tightness of the chest, wheezing, hypotension, anaphylaxis) may occur during or after administration. Signs/symptoms of hypersensitivity reactions may be similar to the attacks associated with hereditary angioedema, therefore, consideration should be given to treatment methods. In the event of acute hypersensitivity reactions to C1 inhibitor therapy, treatment should be discontinued and epinephrine should be available.
• Thrombotic events: Serious arterial and venous thromboembolic events have been reported at recommended doses and when used off-label at doses higher than recommended. Risk factors may include the presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility. Consider potential risk of thrombosis with use, and closely monitor patients with preexisting risks for thrombotic events.
Dosage form specific issues:
• Human plasma: Product of human plasma; may potentially contain infectious agents (eg, viruses and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
• Self-administration: Due to the potential for airway obstruction, patients suffering from an acute laryngeal HAE attack and self-administering should be informed to immediately seek medical attention following treatment.
Monitor for signs/symptoms of hypersensitivity reactions and thrombotic events.
Pregnancy Risk Factor
Animal reproduction studies have not been conducted. Although information related to use during pregnancy is limited, plasma-derived human C1 inhibitor concentrate is the preferred treatment for HAE during pregnancy (Baker, 2013; Caballero, 2012). Women with HAE should be monitored closely during pregnancy and for at least 72 hours after delivery (Caballero, 2012).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea or parageusia. Have patient report immediately to prescriber severe dizziness, syncope, mouth discoloration, tachycardia, angina, hemoptysis, dyspnea, edema of extremities, significant headache, strength differences from one side to another, difficulty speaking or thinking, change in balance, or blurred vision (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.