Cinryze

Drug overview for CINRYZE (c1 esterase inhibitor):

Generic name: C1 esterase inhibitor
Drug class: C1 Esterase Inhibitors (Prophylaxis)
Therapeutic class: Hematological Agents

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.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for CINRYZE (c1 esterase inhibitor) have been approved by the FDA:

Indications:
Prevention of angioedema attacks in patient with hereditary angioedema

Professional Synonyms:
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 information for CINRYZE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
CINRYZE 500 UNIT VIAL	Maintenance	Adults infuse 1,000 unit by intravenous route every 4 days
CINRYZE 500 UNIT VIAL-DILUENT	Maintenance	Adults infuse 1,000 unit by intravenous route every 4 days

Moderate List
Thrombotic disorder

The following adverse reaction information is available for CINRYZE (c1 esterase inhibitor):

Overview
Severe
Less Severe

Adverse reaction overview.

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 3 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Hypersensitivity drug reaction Severe pain Thrombotic disorder

There are 9 less severe adverse reactions.

More Frequent	Less Frequent
Abdominal pain with cramps Diarrhea Headache disorder Muscle spasm Nausea Pain Vomiting	Dysgeusia

Rare/Very Rare
Injection site sequelae

The following precautions are available for CINRYZE (c1 esterase inhibitor):

Pediatric
Pregnant
Lactation
Geriatric

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.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

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.

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.

Prevention of angioedema attack in hereditary angioedema
D84.1	Defects in the complement system