Berinert
(C1 esterase inhibitor (human))Dosage & Administration
For intravenous use only.
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Berinert Prescribing Information
BERINERT is a plasma-derived concentrate of C1 Esterase Inhibitor (Human) indicated for the treatment of acute abdominal, facial, or laryngeal hereditary angioedema (HAE) attacks in adult and pediatric patients.
The safety and efficacy of BERINERT for prophylactic therapy have not been established.
For intravenous use only.
Administer BERINERT at a dose of 20 International Units (IU) per kg body weight by intravenous injection. Doses lower than 20 IU/kg body weight should not be administered.
BERINERT is provided as a freeze-dried powder for reconstitution with the Sterile Water for Injection, USP provided. Store the vial in the original carton in order to protect from light. Do not freeze.
Preparation and Handling
- Check the expiration date on the product vial label and on the administration kit. Do not use any component that is beyond the expiration date. Do not use if any components are damaged or opened.
- Prepare and administer using aseptic techniques [see Dosage and Administration (2.2)].
- Use the silicone-free syringe, provided, for administration of BERINERT [see How Supplied/Storage and Handling (16)].
- After reconstitution and prior to administration, inspect BERINERT visually for particulate matter and discoloration. The reconstituted solution should be colorless, clear, and free from visible particles. Do not use if the solution is cloudy, discolored, or contains particulates.
- The BERINERT vial is for single use only. BERINERT contains no preservative. Any product that has been reconstituted should be used promptly. The reconstituted solution must be used within 8 hours. Discard partially used vials.
- Do not freeze the reconstituted solution.
Reconstitution and Administration
Each BERINERT vial containing 500 IU of C1 esterase inhibitor as a lyophilized concentrate for reconstitution with 10 mL of Sterile Water for Injection, USP provided.
Use either the Mix2Vial® transfer set provided with BERINERT [see How Supplied/Storage and Handling (16.1)] or a commercially available double-ended needle and vented filter spike.
Reconstitution
The procedures below are provided as general guidelines for the reconstitution and administration of BERINERT.
- Ensure that the BERINERT vial and diluent vial are at room temperature.
- Place the BERINERT vial, diluent vial and Mix2Vial transfer set on a flat surface.
- Remove the flip caps from the BERINERT and diluent vials. Wipe the vial stoppers with the alcohol swab provided. Allow to dry prior to opening the Mix2Vial transfer set package.
- Open the Mix2Vial transfer set package by peeling away the lid (Figure 1). Leave the Mix2Vial transfer set in the clear package.
Figure 1
- Place the diluent vial on a flat surface and hold the vial tightly. Grip the Mix2Vial transfer set together with the clear package and push the plastic spike at the blue end of the Mix2Vial transfer set firmly through the center of the stopper of the diluent vial (Figure 2).
Figure 2
- Carefully remove the clear package from the Mix2Vial transfer set. Make sure that you pull up only the clear package, and not the Mix2Vial transfer set (Figure 3).
Figure 3
- With the BERINERT vial placed firmly on a flat surface, invert the diluent vial with the Mix2Vial transfer set attached and push the plastic spike of the transparent adapter firmly through the center of the stopper of the BERINERT vial (Figure 4). The diluent will automatically transfer into the BERINERT vial.
Figure 4
- With the diluent and BERINERT vial still attached to the Mix2Vial transfer set, gently swirl the BERINERT vial to ensure that the BERINERT is fully dissolved (Figure 5). Do not shake the vial.
Figure 5
- With one hand, grasp the BERINERT-side of the Mix2Vial transfer set and with the other hand grasp the blue diluent-side of the Mix2Vial transfer set and unscrew (counter clockwise) the set into two pieces (Figure 6).
Figure 6
- Carefully look at reconstituted solution in each vial of BERINERT. It should be colorless, clear, and free from visible particles. Do not use the vial if the liquid looks cloudy, contains particles, or has changed color. Do not use if the expiration date on the label has expired.
- Draw air into the empty, sterile, silicone-free syringe provided. While the BERINERT vial is upright, screw the syringe to the Mix2Vial transfer set. Inject air into the BERINERT vial. While keeping the syringe plunger pressed, invert the system upside down and draw the concentrate into the syringe by pulling the plunger back slowly (Figure 7). If BERINERT is not immediately used, please store reconstituted solution in the vial.
Figure 7
- Now that the concentrate has been transferred into the syringe, firmly grasp the barrel of the syringe (keeping the plunger facing down) and unscrew (counter clockwise) the syringe from the Mix2Vial transfer set (Figure 8). Attach the syringe to a suitable intravenous administration set.
Figure 8
- If patient requires more than one vial, a new unused Mix2Vial transfer set and a new silicone-free syringe should be used for each BERINERT vial.
- Do not refrigerate after reconstitution. When reconstitution is carried out using aseptic technique, administration may begin within 8 hours, provided the solution has been stored at up to 30°C (86°F). Do not refrigerate or freeze the reconstituted solution. Only store the reconstituted solution in the vial.
- Do not mix BERINERT with other medicinal products. Administer BERINERT by a separate infusion line.
- Use aseptic technique when administering BERINERT.
- Use the silicone-free syringe provided in the administration kit [see How Supplied/Storage and Handling (16)].
- Follow recommended venipuncture guidelines for initiating intravenous therapy.
- Administer BERINERT by slow intravenous injection at a rate of approximately 4 mL per minute. Please refer to the illustration in step 6 of the self-administration section in the Patient Product Information (PPI) section.
- For self-administration, provide the patient with instructions and training for intravenous injection outside of a clinic setting so patients may self-administer BERINERT upon recognition of symptoms of an HAE attack [see Patient Counseling Information (17)].
- After administration, immediately discard any unused product and all used disposable supplies in accordance with local requirements.
- BERINERT is available in a single-dose vial that contains 500 IU of C1 esterase inhibitor as a lyophilized concentrate.
- Each vial must be reconstituted with 10 mL of Sterile Water for Injection, USP provided.
Pregnancy
Risk Summary
Background risk (general population)
A review of available data suggests that major birth defects occur in 2-4% of the U.S. general population and that miscarriage occurs in 15-20% of clinically recognized pregnancies, regardless of drug exposure.
Data
Risk in BERINERT patients
In a retrospective case collection study, 20 pregnant women ranging in age from 20 to 35 years received BERINERT with repeated doses up to 3,500 IU per HAE attack; these women reported no complications during delivery and no harmful effects on their 34 neonates.3 BERINERT should be given to a pregnant woman only if clearly needed.
Lactation
Risk Summary
It is not known whether BERINERT is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BERINERT is administered to a nursing woman.
Pediatric Use
Safety and efficacy of BERINERT have been evaluated in 12 pediatric patients with HAE (age range 10 to 16 years) in the placebo controlled and open-label extension studies. BERINERT was also evaluated in 18 pediatric patients with HAE (age range 5 to 11 years) in a Registry Study conducted in the US and Europe. The safety profile observed in the pediatric population was similar to that observed in adults. The pharmacokinetics of BERINERT were evaluated in 5 pediatric subjects (ages 6 through 13) [see Clinical Pharmacology (12.3)].
Geriatric Use
The safety and efficacy of BERINERT in the geriatric population have not been evaluated in controlled clinical studies. BERINERT was evaluated in 27 geriatric subjects (age range 65 to 83 years) with HAE in a Registry Study conducted in the US and Europe. The safety profile observed in the geriatric population was similar to that observed in the younger populations studied.
BERINERT is contraindicated in individuals who have experienced life-threatening hypersensitivity reactions, including anaphylaxis, to C1 esterase inhibitor preparations.
Hypersensitivity
Severe hypersensitivity reactions may occur. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reaction [see Patient Counseling Information (17)]. The signs and symptoms of hypersensitivity reactions may include hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and/or anaphylaxis during or after injection of BERINERT.
Because hypersensitivity reactions may have symptoms similar to HAE attacks, treatment methods should be carefully considered. In case of suspected hypersensitivity, immediately discontinue administration of BERINERT and institute appropriate treatment.
Thromboembolic Events
Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of C1 Esterase Inhibitor (Human) products, including BERINERT, following administration in patients with HAE. Risk factors may include the presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility. Benefits of treatment 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 BERINERT administration.
TE events have also been reported following administration of a C1 Esterase Inhibitor (Human) product when used for unapproved indications at higher than recommended doses1,2 [see Overdosage (10) and Nonclinical Toxicology (13.2)].
Transmissible Infectious Agents
Because BERINERT 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 minimized 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 a wide range of viruses [see Description (11)].
Despite these measures, such products may still potentially transmit disease and there is also the possibility that unknown infectious agents may be present in such products. However, since implementation of these measures, no case reports on suspected transmission of viruses have demonstrated a causal relationship to the administration of BERINERT.
All infections thought by a physician possibly to have been transmitted by BERINERT should be reported by lot number, by the physician, or other healthcare provider to the CSL Behring Pharmacovigilance Department at 1-866-915-6958.
Laryngeal HAE Attacks
Given the potential for airway obstruction during acute laryngeal HAE attacks, patients self-administering BERINERT should be advised to immediately seek medical attention in an appropriate healthcare facility after treatment with BERINERT.