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Firazyr

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Firazyr

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Laryngeal Attacks

Given the potential for airway obstruction during acute laryngeal HAE attacks, patients should be advised to seek medical attention in an appropriate healthcare facility immediately in addition to treatment with FIRAZYR.

Patient Counseling Information

Information for Patients

Patients may self-administer FIRAZYR upon recognition of an HAE attack after training under the guidance of a healthcare professional.

Patients with laryngeal symptoms should seek medical attention immediately in an appropriate healthcare facility after administration of FIRAZYR [see WARNINGS AND PRECAUTIONS].

Injection site reactions are reported in most patients after administration of FIRAZYR. Other adverse reactions reported after administration of FIRAZYR include pyrexia, increase in transaminases, dizziness, and rash [see ADVERSE REACTIONS].

Tiredness, drowsiness, and dizziness have been reported following the use of FIRAZYR. Patients should be advised not to drive or use machinery if they feel tired or dizzy.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies to determine the carcinogenic potential of icatibant have not been conducted.

Icatibant tested negative for genotoxicity in the in vitro Ames bacterial reverse mutation test, in vitro Chinese hamster bone marrow chromosome aberration assay, and in vivo mouse micronucleus test.

Daily subcutaneous administration of icatibant to rats and dogs caused ovarian, uterine, and testicular atrophy/degeneration and adverse effects on the mammary and prostate glands. In rats, testicular atrophy, reduced prostate gland secretion, decreased testosterone levels and degenenerate corpora lutea occurred at doses greater than or equal to 3 mg/kg (approximately 5-fold greater than the MRHD in males and 2-fold greater than the MRHD in females on an AUC basis) and a decrease in developing ovarian follicles, mammary gland masculinization, and uterine atrophy occurred at doses greater than or equal to 10 mg/kg (approximately 6-fold greater than MRHD in females on an AUC basis). In dogs, reduced sperm counts and uterine atrophy occurred at doses greater than or equal to 1 mg/kg (approximately 2-fold greater than the MRHD on an AUC basis). Atrophy of the testes and prostate with decreased testosterone levels, decreased ovary size and decreased number of developing follicles occurred at a dose of 10 mg/kg (approximately 30-fold greater than the MRHD in males and 15-fold greater than at the MRHD in females on an AUC basis).

In contrast to the effects of daily icatibant administration, toxicity to the ovary, uterus, testis, mammary gland, and prostate did not occur in dogs treated twice a week for 9 months. AUC exposures from a dose of 3 mg/kg in these dogs were 5- and 3-fold the MRHD exposures in men and women, respectively. Sperm counts and testosterone remained unaffected over the course of the study in male dogs dosed twice a week.

Reproduction studies in male mice and rats with daily administration of icatibant found no effects on fertility or reproductive performance with intravenous doses up 81 mg/kg (approximately 5-fold greater than the MRHD on a mg/m² basis) or subcutaneous doses up to 10 mg/kg (approximately 11-fold greater than the MRHD on an AUC basis), respectively.

Use In Specific Populations

Pregnancy

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Icatibant was not teratogenic in rats or rabbits; however, it caused delayed parturition, fetal death, and preimplantation loss in rats and premature birth, abortion, fetal death, and pre-implantation loss in rabbits. FIRAZYR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Delayed parturition and fetal death in rats occurred at 0.5 and 2-fold, respectively, the maximum recommended human dose (MRHD) (on an AUC basis at maternal doses of 1 and 3 mg/kg, respectively). Increased pre-implantation loss in rats occurred at 7-fold the MRHD (on an AUC basis at a maternal dose of 10 mg/kg). In rabbits, premature birth and abortion rates increased at a dose that was less than 1/40th the MRHD (on a mg/m² basis at a maternal dose of 0.1 mg/kg). Studies in rabbits also indicated that preimplantation loss and increased fetal deaths occurred at 13-fold greater than the MRHD (on an AUC basis at a maternal dose of 10 mg/kg).

Nonteratogenic effects: Impairment of pup air-righting reflex and decreased pup hair growth in rats occurred at 7-fold the MRHD (on an AUC basis at a maternal dose of 10 mg/kg).

Labor and Delivery

There are no human studies that have investigated the effects of FIRAZYR on preterm labor or labor at term; however, animal studies showed that icatibant causes delayed parturition and associated fetal death in rats and premature birth and abortion in rabbits. Delayed parturition occurred in rats at 0.5-fold times the MRHD (on an AUC basis at a maternal dose of 1 mg/kg).

Nursing Mothers

Because many drugs are excreted in human milk, caution should be exercised when FIRAZYR is administered to a nursing woman. Icatibant is excreted into the milk of lactating rats.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Geriatric Use

Clinical studies of FIRAZYR did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients are likely to have increased systemic exposure to FIRAZYR compared to younger (18-45 years) patients [see CLINICAL PHARMACOLOGY]. Since other reported clinical experience has not identified differences in efficacy and safety between elderly and younger patients, no dose adjustment is recommended.

Hepatic Impairment

FIRAZYR was studied in patients with mild to moderate (Child Pugh scores of 5 to 8) hepatic impairment. No change in systemic exposure is noted in these patient populations. No dose adjustment is required in patients with hepatic impairment [see CLINICAL PHARMACOLOGY].

Renal Impairment

Although a formal renal impairment study has not been conducted, 10 of 37 patients treated with FIRAZYR had hepatorenal syndrome with glomerular filtration rate (GFR) below 60 mL/min. FIRAZYR is cleared non-renally and hence it is not expected to show any change in systemic exposure in patients with impaired renal function. No dose adjustment is required in patients with renal impairment [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 9/1/2011
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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