Indication CINRYZE® (C1 esterase inhibitor [human]) is indicated for routine prophylaxis against angioedema attacks in adults, adolescents and pediatric patients (6 years of age and older) with Hereditary Angioedema (HAE).
CINRYZE has been proven to reduce the frequency, severity, duration of attacks, and the number of days of swelling of hereditary angioedema (HAE) attacks in adults and adolescents.1
Adults and adolescents: Primary endpoint analysis
The efficacy of CINRYZE in preventing HAE attacks in adult and adolescent patients was evaluated based on the number of HAE attacks during the 12-week treatment period with CINRYZE compared with the number of attacks during the 12-week placebo treatment period.1
CINRYZE significantly reduced the mean number of HAE attacks vs. placebo (p<0.0001). The number (standard deviation) of HAE attacks was 6.1 (5.4) while taking CINRYZE vs. 12.7 (4.8) on placebo.1
CINRYZE has been proven to reduce the frequency of HAE attacks.1
Primary efficacy outcome REDUCTION IN FREQUENCY OF ATTACKS
Mean number of HAE attacks over 12 weeks
In 20 out of 22 patients taking CINRYZE, attack frequency was reduced.1
Prevention of HAE attacks : clinical trial results by subject1
Percent Reduction in Attack Frequency
Percent Reduction in Attack Frequency
The effectiveness of CINRYZE prophylaxis in reducing the number of HAE attacks was variable among the 22 subjects in a controlled clinical trial.1
20 patients experienced a reduction in attack frequency
Ranging from a 100% to 1% reduction in number of attacks
4 patients experienced no attacks during a 12-week period
2 patients experienced an increase in attack frequency
One patient showed an 8% increase in attacks
One patient showed an 85% increase in attacks
The pivotal trial was a randomized, double-blind, placebo-controlled, multicenter, crossover study of adults and adolescents designed to establish the safety (n=24) and efficacy (n=22) of CINRYZE prophylaxis in patients with a history of at least 2 HAE attacks per month. In addition to the primary efficacy analysis of attack frequency, secondary endpoints included the duration and severity of attacks and the number of days of swelling.1
Prevention with CINRYZE reduced the severity and duration of HAE attacks and days of swelling.1
Reduced attack severity REDUCTION IN MEAN SEVERITY OF ATTACKS
Mean severity of HAE attacks (Score from 1 to 3)
Severity: 1=Mild, 2=Moderate, 3=Severe
CINRYZE significantly reduced the mean severity of HAE attacks vs. placebo (p<0.01).
Mean severity of HAE attacks (SD): CINRYZE 1.3 (0.85) vs. placebo 1.9 (0.36)
Mean treatment effect (placebo minus CINRYZE) was 0.58 (95% CI, 0.19, 0.97)
Reduced attack duration REDUCTION IN MEAN DURATION OF ATTACKS
Mean duration of HAE attacks (Days)
CINRYZE significantly reduced the mean duration of HAE attacks vs. placebo (p<0.01).
Mean duration of HAE attacks in days (SD): CINRYZE 2.1 (1.13) vs. placebo 3.4 (1.4)
Mean treatment effect (placebo minus CINRYZE) was 1.23 (95% CI, 0.49, 1.96)
Reduced number of days of swelling REDUCTION IN DAYS OF SWELLING OVER 12 WEEKS
Mean number of days of swelling
CINRYZE significantly reduced the mean number of days of swelling vs. placebo (p<0.01).
Days of swelling (SD): CINRYZE 10.1 (10.73) vs. placebo 29.6 (16.9)
Mean treatment effect (placebo minus CINRYZE) was 19.5 (95% CI, 11.94, 27.06)
Contraindications: CINRYZE is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis, to the product.
Hypersensitivity Reactions: Severe hypersensitivity reactions may occur during or after administration of CINRYZE. Consider treatment methods carefully, because hypersensitivity reactions may have symptoms similar to HAE attacks. In case of hypersensitivity, discontinue CINRYZE infusion and institute appropriate treatment. Have epinephrine immediately available for treatment of an acute severe hypersensitivity reaction.
Thromboembolic Events: Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of C1 Esterase Inhibitor (Human) products, including CINRYZE, following administration in patients with HAE. Risk factors may include presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives, certain androgens, morbid obesity, and immobility. Benefits of CINRYZE for routine prophylaxis of HAE attacks should be weighed against the risks of TE events in patients with underlying risk factors. Monitor patients with known risk factors for TE events during and after CINRYZE administration.
Transmissible Infectious Agents: Because CINRYZE is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. ALL infections thought by a physician possibly to have been transmitted by CINRYZE should be reported to Shire Medical Information at 1-800-828-2088.
Adverse Reactions: The only serious adverse reaction observed in clinical studies of CINRYZE was cerebrovascular accident. The most common adverse reactions (≥5%) observed were headache, nausea, rash, vomiting, and fever. Post marketing adverse reactions include local infusion site reactions and hypersensitivity. Post marketing thromboembolic events have been reported, including catheter-related and deep venous thromboses, transient ischemic attack, and stroke.
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To report SUSPECTED ADVERSE REACTIONS, contact Shire Medical Information at 1-800-828-2088 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.