Cinryze
(C1 esterase inhibitor (human))Dosage & Administration
For Intravenous Use Only
Routine Prophylaxis Dosing
Adults and adolescents (12 years old and above)
| Indication | Dose | Infusion rate |
| Routine prophylaxis against HAE attacks | 1,000 IU Intravenous every 3 or 4 days * | 1 mL/min (10 min) |
Children (6 to 11 years old)
| Indication | Dose | Infusion rate |
| Routine prophylaxis against HAE attacks | 500 IU Intravenous every 3 or 4 days * | 1 mL/min (5 min) |
By using PrescriberAI, you agree to the AI Terms of Use.
Cinryze Prescribing Information
CINRYZE is a C1 esterase inhibitor indicated for routine prophylaxis against angioedema attacks in adults, adolescents, and pediatric patients (6 years old and above) with Hereditary Angioedema (HAE).
For intravenous use only.
Dose
| Patient Population | Indication | Dose | Infusion Rate |
|---|---|---|---|
| |||
| Adults and adolescents (12 years old and above) | Routine prophylaxis against HAE attacks | 1,000 International Units (IU) * Intravenous (IV) every 3 or 4 days. For patients who have not responded adequately, doses up to 2,000 IU (not exceeding 80 IU/kg) every 3 or 4 days may be considered based on individual patient response. | 1 mL/min (10 min) |
| Pediatric patients (6 to 11 years old) | Routine prophylaxis against HAE attacks | 500 IU, Intravenous (IV) every 3 or 4 days. The dose may be adjusted according to individual response, up to 1,000 IU every 3 or 4 days. | 1 mL/min (5 min) |
Preparation
- Protect CINRYZE from light prior to reconstitution.
- A silicone-free syringe is recommended for reconstitution and administration of CINRYZE.
- Inspect the reconstituted product for particulate matter prior to administration; do not use if particles are observed or if solution is turbid. The reconstituted solution is colorless to slightly blue.
- Each vial of CINRYZE is for single use only. Promptly use any vial that has been entered and discard partially used vials in accordance with biohazard procedures. CINRYZE contains no preservative.
- Do not mix CINRYZE with other materials.
- Do not use if frozen.
- Do not use after expiration date.
- Use aseptic technique during the reconstitution procedure.
- Bring the CINRYZE (powder) and Sterile Water for Injection, USP (diluent) to room temperature if refrigerated.
- Remove caps from the CINRYZE and diluent vials.
- Cleanse stoppers with an alcohol wipe or swab and allow them to dry prior to use.
- Remove protective covering from the top of the Mix2Vial transfer device package. Do not remove the device from the package.
- Note: Diluent vial must be accessed prior to the vial of CINRYZE to prevent loss of vacuum.
Reconstitution
Sterile Water for Injection USP is required for reconstitution. CINRYZE is supplied with Sterile Water for Injection USP [see How Supplied/Storage and Handling (16)].
One vial of reconstituted CINRYZE is used for a single 500 IU dose. Two vials of reconstituted CINRYZE are combined for a single 1,000 IU dose.
- Place diluent on a flat surface and insert the blue end of the device into the diluent vial, pushing down until the spike penetrates through the center of the diluent vial stopper and the device snaps in place (Figure 1). The Mix2Vial transfer device must be positioned completely vertical prior to penetrating the stopper closure.
Figure 1 
- Remove the plastic package and discard it (Figure 2). Take care not to touch the exposed end of the device.
Figure 2 
- Place vial of CINRYZE on a flat surface. Invert diluent vial containing 5 mL of Sterile Water for Injection, USP, and insert the clear end into the CINRYZE vial, pushing down until the spike penetrates the rubber stopper and the device snaps into place. The Mix2Vial transfer device must be positioned completely vertical prior to penetrating the stopper closure. The Sterile Water for Injection, USP will automatically flow into the vial of CINRYZE (Figure 3), because the vacuum in the vial will draw in the diluent. If there is no vacuum in the vial, do not use the product.
Figure 3 
- Gently swirl (do not shake) the CINRYZE vial until all powder is dissolved. Be sure that CINRYZE is completely dissolved (Figure 4).
Figure 4 
- Disconnect the Sterile Water for Injection, USP vial by turning it counterclockwise (Figure 5). Do not remove the clear end of the Mix2Vial transfer device from the vial of CINRYZE.
Figure 5 
One vial of reconstituted CINRYZE contains 5 mL of C1 esterase inhibitor at a concentration of 100 IU/mL. Reconstitute one vial of CINRYZE for one 500 IU dose. Reconstitute two vials of CINRYZE for one 1,000 IU dose. Repeat steps 1 to 5 above using an additional package containing a Mix2Vial transfer device to reconstitute the second of two vials of CINRYZE. Do not reuse the Mix2Vial transfer device. CINRYZE must be administered at room temperature within 3 hours after reconstitution. For higher doses up to 2,000 IU (not exceeding 80 IU/kg) additional vial(s) will need to be reconstituted.
Administration
The procedures below are provided as general guidelines for the reconstitution and administration of CINRYZE. Use either the Mix2Vial® transfer device or a commercially available double-ended needle.
Always work on a clean surface and wash your hands before performing the following procedures.
Reconstitution, product administration, and handling of the administration set, and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted CINRYZE, in an appropriate container.
One vial of reconstituted CINRYZE is used for a single 500 IU dose.
Two vials of reconstituted CINRYZE are combined for a single 1,000 IU dose.
For higher doses of up to 2,000 IU, combine the contents of the relevant number of vials.
Instructions for Use
- Use aseptic technique.
- After reconstitution, the solution should be clear with no evidence of turbidity. Reconstituted solution should be colorless to slightly blue. Do not use if solution is turbid or otherwise discolored.
- Please refer to the illustrations in steps 7 to 9 included within the Patient Information Leaflet. Utilizing a sterile, disposable 10 mL syringe, draw back the plunger to admit 5 mL air into the syringe.
- Attach the syringe onto the top of the clear end of the Mix2Vial transfer device by turning it clockwise.
- Invert the vial and inject air into the solution and then slowly withdraw the reconstituted CINRYZE into the syringe.
- Detach the syringe from the vial by turning it counterclockwise and releasing it from the clear end of the Mix2Vial transfer device.
- For a 1,000 IU dose, using the same syringe, repeat steps 3 to 6 with a second vial of CINRYZE to make the complete dose.
- Promptly administer CINRYZE after preparation in the syringe and do not use if particles are observed or if the solution is turbid.
- Attach a suitable needle or infusion set with winged adapter and inject intravenously. As a guideline, administer CINRYZE by intravenous injection at a rate of 1 mL per minute. A single dose of 500 IU (reconstituted in 5 mL) of CINRYZE should be administered over 5 minutes. A single dose of 1,000 IU (reconstituted in 10 mL) of CINRYZE should be administered over 10 minutes. [see Dosage and Administration (2)]. Please refer to the illustration in step 3 of the self-administration section within the Patient Information Leaflet.
- Dispose of all unused solution, the empty vial(s), and the used needles and syringes in an appropriate container for throwing away waste that might hurt others if not handled properly.
- CINRYZE (Freeze-Dried powder for Reconstitution) is a lyophilized preparation available in a single-dose vial that contains 500 IU human C1 esterase inhibitor.
- Each vial must be reconstituted with 5 mL of Sterile Water for Injection, USP (diluent).
- One reconstituted vial must be used to make a single, 500 IU, dose. Two reconstituted vials must be used to make a single, 1,000 IU dose.
Pregnancy
Risk Summary
There are no data with CINRYZE use in pregnant women to inform a drug associated risk. Animal reproduction studies have not been conducted with CINRYZE. It is unknown whether CINRYZE can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. CINRYZE should be given to a pregnant woman only if clearly needed.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal data
In an embryo fetal development study (C1 inhibitor administered during the period of organogenesis) in rats, there was no maternal or fetal toxicity at doses up to 400 U/kg/day that provided an exposure similar to that in humans after a 1,000 U dose.
Lactation
Risk Summary
There are no data regarding the presence of CINRYZE in human milk, the effects 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 CINRYZE and any potential adverse effects on the breastfed child from CINRYZE or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of CINRYZE have been evaluated in 12 pediatric subjects with HAE (age range 7 to 11 years old) in a pediatric randomized, dose-ranging, crossover routine prophylaxis trial. [see Clinical Studies (14)]. Additionally, four of the 24 subjects in the pediatric/adult randomized, placebo-controlled, crossover, routine prophylaxis trial, were under the age of 18 years (9, 14, 16, and 17 years of age). Overall, the safety and tolerability of CINRYZE are similar in pediatric, adolescent, and adult subjects. The pharmacokinetics of CINRYZE was evaluated in pediatric subjects (7 to 11 years old). [see Clinical Pharmacology (12)].
Geriatric Use
Clinical studies of CINRYZE 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.
CINRYZE is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis, to the product.
Hypersensitivity Reactions
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.
Consider treatment methods carefully because hypersensitivity reactions may have symptoms similar to HAE attacks.
In case of hypersensitivity, discontinue CINRYZE infusion and institute appropriate treatment. Have epinephrine immediately available for treatment of acute severe hypersensitivity reaction. [see Patient Counseling Information (17)].
Thromboembolic Events
Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of C1 esterase inhibitor (human) products, including CINRYZE, following administration in patients with HAE. Risk factors may include presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives, certain androgens, morbid obesity, and immobility. Benefits of CINRYZE for routine prophylaxis 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 CINRYZE administration.
TE events have been reported following administration of a C1 esterase inhibitor (human) product when used off-label at higher than labeled doses1.
In an open-label trial further investigating the use of CINRYZE for prevention (n=146) of HAE attacks, 5 serious TE events (including myocardial infarction, deep vein thrombosis, pulmonary embolism and 2 events of cerebrovascular accident) occurred. Subjects had underlying risk factors for TE events.
In the post-approval open-label study (n=20) there were no systemic TE events in subjects who received CINRYZE up to 2,500 U (not exceeding 100 U/kg) every 3 or 4 days for up to 12 months. One subject developed a blood clot in an intravenous central catheter, which was treated without systemic complication. [see Adverse Reactions (6.1)].
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 disease (CJD) agent [see Description (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 Takeda Pharmaceuticals U.S.A., Inc. [1-877-TAKEDA-7 (1-877-825-3327)]. 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)]