Haegarda
(C1 esterase inhibitor (human))Dosage & Administration
For subcutaneous use after reconstitution only.
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Haegarda Prescribing Information
HAEGARDA is a plasma-derived concentrate of C1 Esterase Inhibitor (Human) (C1-INH) indicated for routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in patients 6 years of age and older.
After reconstitution, for subcutaneous use only.
HAEGARDA is intended for self (or caregiver)-administration after reconstitution at a dose of 60 International Units (IU) per kg body weight by subcutaneous (S.C.) injection twice weekly (every 3 or 4 days). The patient or caregiver should be trained on how to administer HAEGARDA.
HAEGARDA is provided as a freeze-dried powder for reconstitution with Sterile Water for Injection, USP.
Preparation and Handling
- Check the expiration date on the product vial label. Do not use beyond the expiration date.
- Work on a clean surface and wash hands before performing the following procedures.
- Prepare and administer using aseptic techniques [see Dosage and Administration (2.2)].
- Use a silicone-free syringe for reconstitution and administration.
- Each vial of HAEGARDA is for single-dose only. Promptly use the reconstituted solution. The solution must be used within 8 hours. Discard partially used vials. HAEGARDA contains no preservative.
- Do not freeze the reconstituted solution.
Reconstitution and Administration
Use either the Mix2Vial® transfer set provided with HAEGARDA or a commercially available double-ended needle and vented filter spike [see How Supplied/Storage and Handling (16)].
Reconstitution
The procedures below are provided as general guidelines for the reconstitution and administration of HAEGARDA.
HAEGARDA Reconstitution Instructions
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Administration
For subcutaneous injection only.
- Train the patient or caregiver on how to self-administer HAEGARDA.
- Do not mix HAEGARDA with other medicinal products.
- Visually inspect the final solution for particles and discoloration prior to administration, and whenever solution and container permit. Do not use if particles or discoloration is observed.
- Attach the syringe containing the reconstituted HAEGARDA solution to a hypodermic needle or subcutaneous infusion set and administer by subcutaneous injection. Adapt the rate of administration to the comfort level of the patient.
- Inject in the abdominal area or other subcutaneous injection sites. Rotate injection sites so that the same site is not used repeatedly.
- Administer HAEGARDA at room temperature and within 8 hours after reconstitution. Following administration, discard any unused solution and all administration equipment in an appropriate manner as per local requirements.
HAEGARDA is available as a white lyophilized powder supplied in single-dose vials containing 2000 or 3000 IU of C1-INH.
- The 2000 IU vial must be reconstituted with 4 mL of Sterile Water for Injection, USP.
- The 3000 IU vial must be reconstituted with 5.6 mL of Sterile Water for Injection, USP.
Pregnancy
Risk Summary
There are no prospective clinical data from HAEGARDA use in pregnant women. C1-INH is a normal component of human plasma. Animal developmental or reproduction toxicity studies have not been conducted with HAEGARDA. In the U.S. general population, the estimated background risk of major birth defects occurs in 2-4% of the general population and miscarriage occurs in 15-20% of clinically recognized pregnancies.
Data
In a retrospective case collection study, 22 pregnant women with type I HAE and ranging in age from 20 to 38 years received C1-INH doses of 500 or 1000 IU per I.V. administration for the treatment of acute attacks before, during, and/or after pregnancy (total of 35 pregnancies). No adverse events were associated with C1-INH treatment before, during, or after pregnancy.1
In an observational registry (overall 318 subjects) data were collected on 11 pregnancies in 10 subjects (16 to 40 years old) receiving up to 3000 IU C1-INH (I.V. administration) to treat or prevent HAE attacks. No adverse events were associated with C1-INH treatment.2
In the randomized, open-label, active treatment-controlled, study (Study 2), four pregnant women with type I HAE and ranging in age from 19 to 32 years received C1-INH (S.C. administration). Patients received 40-60 IU/kg per S.C. administration for 4 – 8 weeks (9 - 15 doses) during the first trimester. These women reported no complications during delivery and all women delivered healthy babies.
Lactation
Risk Summary
There is no information regarding the excretion of HAEGARDA in human milk, the effect on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for HAEGARDA and any potential adverse effects on the breastfed infant from HAEGARDA or from the underlying maternal condition.
Data
In a retrospective case collection study, breastfeeding was documented for neonates from 21 of 35 births with a median duration of 4.8 months (ranging from 1 to 34 months). Mothers were treated postpartum with C1-INH doses up to 1000 IU per I.V. administration for the treatment of acute HAE attacks. No adverse events to the mothers were associated with C1-INH treatment after pregnancy. No information regarding the effect on the breastfed infant was reported.1
Pediatric Use
The safety and effectiveness of HAEGARDA were evaluated in a subgroup of nine patients 8 to <17 years of age, in the randomized, double-blind, placebo-controlled, crossover, routine prophylaxis trial (Study 1) and the randomized, open-label, active treatment-controlled study (Study 2). Results of subgroup analysis by age were consistent with overall study results.
Geriatric Use
The safety and effectiveness of HAEGARDA were evaluated in a subgroup of nine subjects 65 to 72 years of age, eight subjects who received the high 60 IU/kg dose and one subject who received the 40 IU/kg dose, in the randomized, double-blind, placebo-controlled, crossover, routine prophylaxis trial (Study 1) and in the randomized, open-label, active treatment-controlled study (Study 2). Clinical studies of HAEGARDA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
HAEGARDA is contraindicated in individuals who have experienced life-threatening hypersensitivity reactions, including anaphylaxis, to C1-INH preparations or its excipients [see Description (11)].
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)].
Initiate individualized treatment in case of an acute HAE attack.
Hypersensitivity
Severe hypersensitivity reactions may occur. The signs and symptoms of hypersensitivity reactions may include hives (local and generalized), tightness of the chest, difficulty breathing, wheezing, hypotension, and/or anaphylaxis during or after injection of HAEGARDA. In case of severe hypersensitivity, discontinue HAEGARDA administration and institute appropriate treatment. Epinephrine should be immediately available for treatment of severe hypersensitivity reaction [see Patient Counseling Information (17)].
Thromboembolic Events
At the recommended subcutaneous dose, a causal relationship between thromboembolic events (TEEs) and the use of HAEGARDA has not been established [see Patient Counseling Information (17)]. Thrombosis has occurred in treatment attempts with high doses of C1-INH intravenous (I.V.) for prevention or therapy of capillary leak syndrome before, during or after cardiac surgery (unapproved indication and dose).
Transmissible Infectious Agents
Because HAEGARDA is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by processes demonstrated to inactivate and/or remove certain viruses during manufacturing [see Description (11) and Patient Counseling Information (17)]. Despite these measures, such products may still contain human pathogenic agents, including those not yet known or identified. Thus, the risk of transmission of infectious agents cannot be totally eliminated.
All infections thought by a physician possibly to have been transmitted by HAEGARDA should be reported by lot number, by the physician or other healthcare provider, to the CSL Behring Pharmacovigilance Department at 1-866-915-6958.