Berinert (C1 esterase inhibitor)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Complement 1 (C1)-esterase inhibitor is a naturally occurring inhibitor of certain serine proteases (e.g., C1 complement, kallikrein, coagulation factor XIIa, plasmin) involved in the complement, coagulation (e.g., contact), and fibrinolytic systems. C1-esterase inhibitor (human) is a preparation of C1-esterase inhibitor derived from pooled human plasma.
Complement 1 (C1)-esterase inhibitor is a naturally occurring serine protease inhibitor that principally regulates the activation of the complement and intrinsic coagulation (e.g., contact system) pathways. C1-esterase inhibitor also plays a role in the fibrinolytic system.
Hereditary angioedema (HAE) is an autosomal-dominant genetic disorder characterized by low plasma concentrations of endogenous or functional C1-esterase inhibitor. Such a deficiency leads to uncontrolled activation of the complement and contact system, resulting in increased vascular permeability and angioedema. Replacement therapy with C1-esterase inhibitor (human) increases plasma levels of C1-esterase inhibitor activity and provides an additional source of the enzyme in patients with HAE.
C1-esterase inhibitor regulates the contact system by inhibiting plasma kallikrein and coagulation factor XIIa, thus preventing formation of bradykinin, the presumed mediator of increased vascular permeability in HAE. C1-esterase inhibitor blocks both the spontaneous activation of C1 complement and formation of activated C1 complement, suppressing the classical complement pathway. During these processes, irreversible complexes are formed between the inhibitor and its target protease; the resulting complexes are then inactivated and removed from circulation.
C1-esterase inhibitor also exhibits inhibitory effects on plasmin.
Commercially available Cinryze(R) is a sterile, lyophilized concentrate of highly purified C1-esterase inhibitor (human) derived from pooled human plasma. To reduce the risk of viral transmission, the manufacturing process for Cinryze(R) includes a heat inactivation procedure and additional purification/viral inactivating steps (i.e., polyethylene glycol (PEG) precipitation, nanofiltration).
Berinert(R) is a sterile, lyophilized concentrate of highly purified C1-esterase inhibitor (human) derived from pooled human plasma. The manufacturing process for Berinert(R) includes 3 viral inactivation/reduction steps (i.e., pasteurization, hydrophobic interaction chromatography, nanofiltration) to reduce the risk of viral transmission.
Haegarda(R) is a sterile, lyophilized concentrate of highly purified C1-esterase inhibitor (human) derived from pooled human plasma. The manufacturing process for Haegarda(R) includes 3 viral inactivation/reduction steps (i.e., pasteurization, hydrophobic interaction chromatography, nanofiltration) to reduce the risk of viral transmission.
Following IV administration of Cinryze(R) in clinical studies, plasma concentrations of C1-esterase inhibitor increased immediately (i.e., within 1 hour). Plasma C4 levels appeared to increase 2-24 hours later, indicating consumption of C1-esterase inhibitor and stabilization of the complement activation system. Pharmacokinetic studies conducted with Cinryze(R) demonstrate that in patients with asymptomatic HAE, peak plasma concentrations of C1-esterase inhibitor generally occur approximately 4 hours after a single 1000-unit dose.
The mean half-life of C1-esterase inhibitor following administration of a single 1000-unit dose of Cinryze(R) in such asymptomatic HAE adultpatients was reported to be 56 hours. Using prophylactic doses of 500 or 1000 units given every 3-4 days, the mean steady-state half-life was reported to be approximately 34 hours in pediatric patients 7-11 years of age. Pharmacokinetic data indicate that in pediatric patients 7-11 years of age, total exposure to Cinryze(R) based on AUC and maximum serum concentrations is approximately 30% higher compared to adults at doses of 1000 units given every 3 to 4 days.
Little accumulation is observed when the drug is administered every 3 days. In patients with mild to severe HAE who received single doses (500-1500 units) of Berinert(R), the half-life of the drug was approximately 18 hours in adults and 17 hours in pediatric patients 6-13 years of age. In patients treated with Haegarda(R) 60 IU/kg subcutaneously twice weekly, the median time to peak plasma concentration was approximately 59 hours, and the median half-life was approximately 69 hours.
USES: This medication is used to help prevent swelling problems that occur with a certain immune disease passed down through families (hereditary angioedema-HAE). HAE is caused by low levels or improper function of a natural substance produced by the body (C1-inhibitor). Symptoms such as rapid swelling of the hands, feet, limbs, face, tongue, or throat can occur.
Swelling of the intestinal tract may cause symptoms such as abdominal cramps, diarrhea, or vomiting. Attacks of swelling may occur without reason. However, anxiety, stress, sickness, and surgery may trigger attacks in some people.
This medication increases the level of C1-inhibitor to help prevent attacks of sudden swelling due to hereditary angioedema.
Generic name: C1 esterase inhibitor
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Berinert
Indications
The following indications are listed for Berinert:
- Prevention Of Angioedema Attacks In Patient With Hereditary Angioedema
Also known as: Prevention Of Angioedema Attack In Hereditary Angioneurotic Edema, Prevention Of Angioedema Attacks In Patient With Hae, Prophylaxis Against Angioedema Attacks In Patient With Hae.
Dosing
Dosage of C1-esterase inhibitor (human) is expressed in international units (IU). One IU of C1-esterase inhibitor (human) (Cinryze(R)) is equivalent to the concentration of C1-esterase inhibitor present in 1 mL of normal plasma.
C1-esterase inhibitor (human) is administered by IV injection (Cinryze(R), Berinert(R)) or subcutaneous injection (Haegarda(R)) following reconstitution.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Formal drug interaction studies with C1-esterase inhibitor (human) have not been performed to date.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known life-threatening hypersensitivity reactions, including anaphylaxis, to C1-esterase inhibitor (human) or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse reactions (>=5%) observed with C1-esterase inhibitor (human) (Cinryze(R)) were headache, nausea, rash, vomiting, and fever.
The most common adverse reaction (>4% of subjects and greater than placebo) observed with C1-esterase inhibitor (human) (Berinert(R)) was dysgeusia.
The most common adverse reactions (>4%) observed with C1-esterase inhibitor (human) (Haegarda(R)) were injection site reactions, hypersensitivity, nasopharyngitis, and dizziness.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of C1-esterase inhibitor (human) (Cinryze(R)) have not been established in children younger than 6 years of age. Among the 24 patients studied in the approval trial of Cinryze(R), 4 patients were younger than 18 years of age (9, 14, 16, and 17 years of age). In a randomized, dose-ranging, cross-over study of Cinryze(R), 12 subjects ranged in age from 7-11 years of age.
Safety and efficacy of C1-esterase inhibitor (human) (Berinert(R)) were evaluated in 12 pediatric patients 10-16 years of age for the treatment of acute HAE attacks in an open-label extension and placebo-controlled studies. Berinert(R) was also evaluated in 18 pediatric patients ranging from 5-11 years in aregistry study. The safety profile observed in pediatric patients was similar to that in adult patients.
Limited data suggest that the half-life of Berinert(R) may be decreased and clearance increased in pediatric patients younger than 12 years of age compared with adults; however, the clinical importance of such findings is not known.
Safety and efficacy of C1-esterase inhibitor (human) (Haegarda(R)) were evaluated in 9 patients 8 to <17 years of agein 2 clinical studies. Results of the subgroup analysis by age were consistent with the overall study results.
Data are insufficient to inform the drug-associated risk of C1-esterase inhibitor (human) use in pregnancy.
In a retrospective study of 20 women, repeated doses of C1-esterase inhibitor (human) (Berinert(R)) up to 3500 IU per HAE attack resulted in no complications during delivery or harmful neonatal effects.
In the clinical study of C1-esterase inhibitor (human) (Haegarda(R)), 4 pregnant women ranging in age from 19-32 years received C1-esterase inhibitor (human). Patients received 40-60 IU/kg per dose via subcutaneous administration for 4-8 weeks (9-15 doses) during the first trimester of pregnancy. These women reported no complications during delivery and all women delivered healthy babies.
It is not known whether C1-esterase inhibitor (human) is distributed into human milk. Because many drugs are distributed into milk, the drug should be used with caution and only if clearly needed in nursing women.
The manufacturers of C1-esterase inhibitor (human) products make no specific dosage recommendations in geriatric patients. However, the manufacturers of Cinryze(R) and Haegarda(R) state that caution should be exerted with dosage selection in geriatric patients and that initial doses at the lower end of the dosage range should be considered, because of anincreased prevalence ofreduced hepatic, renal, and cardiac function, as well as other coexisting conditions in the geriatric patient population.
Clinical studies of C1-esterase inhibitor (human) (Cinryze(R) and Haegarda(R))did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. Other reported clinical experience has not identified differences in response to Cinryze(R) and Haegarda(R) between older and younger adults. C1-esterase inhibitor (human) (Berinert(R)) was evaluated in 27 geriatric subjects in a Registry Study, which found that thesafety profile in these patients was similar to that observed in the younger populations.
ICD codes
No ICD codes are available for this drug.
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Last reviewed · Source: First Databank (FDB) drug data
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