openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions may occur. Epinephrine should be immediately available to treat any acute severe hypersensitivity reactions ( 5.1 ). Thrombotic events have been reported in patients receiving Cinryze for routine prophylaxis. Thrombotic events also have been reported in patients receiving off-label high dose C1 esterase inhibitor therapy ( 5.2 ). Monitor patients with known risk factors for thrombotic events. CINRYZE is made from human plasma and may contain infectious agents e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent. ( 5.3 ) 5.1 Sensitivity Severe hypersensitivity reactions may occur. The signs and symptoms of hypersensitivity reactions may include the appearance of hives, urticaria, tightness of the chest, wheezing, hypotension and/or anaphylaxis experienced during or after injection of CINRYZE. Because hypersensitivity reactions may have symptoms similar to HAE attacks, treatment methods should be carefully considered. In case of hypersensitivity, CINRYZE infusion should be discontinued and appropriate treatment instituted. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reaction. (See Patient Counseling Information [ 17 ]) 5.2 Thrombotic Events Thrombotic events have been reported in association with C1 esterase inhibitor products when used off-label at high doses. 2 Animal studies have supported a concern about the risk of thrombosis from intravenous administration of C1 esterase inhibitor products. 3 (see Sections 10 OVERDOSAGE and 13.2 Animal Toxicology and/or Pharmacology ) In an open label trial further investigating the use of CINRYZE for prevention (n=146) of HAE attacks, 5 serious thrombotic events (including myocardial infarction, deep vein thrombosis, pulmonary embolism and 2 events of cerebrovascular accident) occurred. Subjects had underlying risk factors for thrombotic events. Patients with known risk factors for thrombotic events should be monitored closely while taking CINRYZE. 5.3 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 (CJD) agent [ 11 ]. ALL infections thought by a physician possibly to have been transmitted by CINRYZE should be reported by the physician or other healthcare provider to ViroPharma Biologics, Inc. [(877) 945-1000]. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient. (See Patient Counseling Information [ 17 ])
6 ADVERSE REACTIONS The most serious adverse events observed in clinical studies of CINRYZE have been death due to non-catheter related foreign body embolus, pre-eclampsia resulting in emergency C-section, stroke, and exacerbation of HAE attacks, none of which have been considered drug related. The most common drug related adverse reactions observed at a rate ≥ 5% were upper respiratory tract infection, sinusitis, rash, and headache. In the clinical trial, the most common adverse reactions observed by ≥ 5% of subjects after receiving CINRYZE were upper respiratory tract infection, sinusitis, rash, and headache. ( 5.1 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ViroPharma Biologics, Inc. at (877) 945-1000 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. Routine Prophylaxis Twenty-four subjects were evaluated in study LEVP2005-1/B for routine prophylaxis. There were no treatment-emergent serious adverse reactions in study LEVP2005-1/B. Adverse reactions in trial LEVP2005-1/B that occurred in at least two subjects during CINRYZE prophylaxis, irrespective of the causality assessment, are given in the following table: Table 2 Adverse Reactions in Routine Prophylaxis Study LEVP2005-1/B Irrespective of Causality Adverse Reaction Number of Adverse Events Number of Subjects (N = 24) Sinusitis 8 5 Rash 7 5 Headache 4 4 Upper respiratory tract infection 3 3 Viral upper respiratory tract infection 5 3 Bronchitis 2 2 Limb injury 2 2 Back pain 2 2 Pain in extremity 2 2 Pruritus 2 2 More than 9000 doses of CINRYZE have been administered to over 180 patients in all controlled and open label clinical studies. All patients were evaluated and found negative for seroconversion to parvovirus B19, Hepatitis B, Hepatitis C and HIV. No clinically relevant antibody formation was seen in clinical trials of prophylaxis. 6.2 Postmarketing Experience 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 pain, rash, erythema, inflammation or hematoma at the infusion site). Postmarketing thrombotic events have been reported, including catheter-related and deep venous thromboses, transient ischemic attack, and stroke. Patients with known risk factors for thrombotic events should be monitored closely. (See Section 5.2 Thrombotic events in WARNINGS AND PRECAUTIONS)