The only serious adverse reaction observed in clinical studies of CINRYZE was cerebrovascular accident.
The most common adverse reactions observed were headache, nausea, rash, and vomiting.
Because CINRYZE is a therapeutic protein, there is potential for immunogenicity. Using a validated assay there was no evidence of antibody development following administration of CINRYZE. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of anti-C1 Esterase Inhibitor antibody positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibody development across products cannot be made.
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Twenty-four subjects were evaluated in the randomized, placebo-controlled, crossover, routine prophylaxis trial.
There were no serious adverse reactions in the randomized, placebo-controlled, crossover, routine prophylaxis trial.
Adverse reactions in the randomized, placebo-controlled, crossover, routine prophylaxis trial (n=24) that occurred in at least two subjects ( ≥ 8%) receiving CINRYZE are given in the following table:
Table 2: Adverse Reactions in the Randomized, Placebo-Controlled, Crossover, Routine Prophylaxis Trial
|Adverse Reaction||Number of Adverse Reactions||Number of Subjects
(N = 24)
In an open-label follow-on trial, 146 patients received a median of 243.5 days of CINRYZE (maximum = 959 days).
The most common adverse reaction observed was headache. No patients were discontinued due to an adverse reaction.
Adverse reactions in the open-label follow-on trial (n=146) that occurred in at least three subjects ( ≥ 2%) receiving CINRYZE, are given in the following table:
Table 3 : Adverse Reactions in the Open-Label Follow-On Trial
|Adverse Reaction||Number (%) of Subjects
(N=146) with Adverse Reaction
|Number (%) of Infusion Days
(N=11,435) with Adverse Reaction
|Headache||28 (19)||62 (0.5)|
|Nausea||26 (18)||29 (0.3)|
|Rash||15 (10)||30 (0.3)|
|Vomiting||15 (10)||17 (0.1)|
|Pyrexia||7 (5)||7 ( < 0.1)|
|Catheter Site Pain||4 (3)||5 ( < 0.1)|
|Dizziness||3 (2)||4 ( < 0.1)|
|Erythema||3 (2)||3 ( < 0.1)|
|Pruritus||3 (2)||4 ( < 0.1)|
More than 14,000 doses of CINRYZE have been administered to over 260 different patients in all completed, controlled and open-label clinical studies. All patients who were evaluated were found negative for seroconversion to parvovirus B19, Hepatitis B, Hepatitis C and HIV. (See WARNINGS AND PRECAUTIONS, Transmissible Infectious Agents)
Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.
Postmarketing adverse reactions include local infusion site reactions (including inflammation or hematoma at the infusion site) and hypersensitivity.
Postmarketing thromboembolic events have been reported, including catheter-related and deep venous thromboses, transient ischemic attack, and stroke.