Dosing & Uses
Dosage Forms & Strengths
IV, lyophilized powder for reconstitution injection
- 500 unit/vial (Berinert, Cinryze)
SC, lyophilized powder for reconstitution (Haegarda)
- 2000 IU/vial
- 3000 IU/vial
Hereditary Angioedema Acute Treatment
Berinert
- Indicated for the treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adults and children
- 20 units/kg IV infused slowly, not to exceed 4 mL/min
- Patients may self administer after completing education for IV administration
Hereditary Angioedema Prophylaxis
Cinryze
- Indicated for routine prophylaxis against angioedema attacks in adolescents and adults patients with hereditary angioedema
- 1,000 units IV q3-4Days; infuse over 10 minutes (ie, 1 mL/min)
Haegarda
- Indicated for routine prophylaxis against angioedema attacks in adolescents and adults with hereditary angioedema
- 60 IU/kg SC twice weekly (every 3-4 days)
Kidney Transplant Rejection (Orphan)
Cinryze: Orphan designation for treatment of acute antibody-mediated rejection following kidney transplantation
Sponsor
- Shire ViroPharma, Inc; 300 Shire Way; Lexington, Massachusetts
Delayed Graft Function (Orphan)
Prevention and/or treatment of delayed graft function after solid organ transplantation
Orphan indication sponsor
- Pharming Technologies B.V.; Archimedesweg 4, Netherlands
Capillary Leakage Syndrome (Orphan)
Orphan indication sponsor
- Pharming Technologies B.V.; Archimedesweg 4, Netherlands
Dosage Forms & Strengths
IV, lyophilized powder for reconstitution injection
- 500 unit/vial (Berinert, Cinryze)
SC, lyophilized powder for reconstitution (Haegarda)
- 2000 IU/vial
- 3000 IU/vial
Hereditary Angioedema Acute Treatment
Berinert
- Indicated for the treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adults and children
- 20 units/kg IV infused slowly, not to exceed 4 mL/min
Hereditary Angioedema Prophylaxis
Cinryze
- Indicated for routine prophylaxis against angioedema attacks in adults, adolescents and pediatric patients (≥6 years) with HAE
- <6 years: Safety and efficacy not established
-
6-11 years
- 500 units IV q3-4Days; infuse over 5 minutes (ie, 5 mL/min)
- Adjust dose according to individual response, up to 1,000 units q3-4Days
-
≥12 years
Haegarda
Adverse Effects
Berinert
>4%: nausea, vomiting, diarrhea, dysgeusia, headache, abdominal pain, muscle spasms, and pain
Rare: laryngeal edema, swelling (shoulder and chest), exacerbation of hereditary angioedema, and laryngospasm
Cinryze
>5%: URI, sinusitis, rash, & headache
Rare: death to non-catheter related foreign body embolus, pre-eclampsia, stroke, exacerbation of HAE attacks
Warnings
Contraindications
History of life-threatening immediate hypersensitivity reactions (ie, anaphylaxis)
Cautions
Severe hypersensitivity reactions may occur; if hypersensitivity occurs, discontinue infusion and institute appropriate treatment; immediately have epinephrine available for treatment of acute severe hypersensitivity reaction (see Contraindications)
Serious arterial and venous thromboembolic (TE) events reported; 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; monitor patients with known risk factors for TE events during and after drug administration
Pregnancy & Lactation
Pregnancy
There are no data with C1 inhibitor human use in pregnant women to inform a drug associated risk
Animal reproduction studies have not been conducted
It is unknown whether drug can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity; administer to a pregnant woman only if clearly needed
Lactation
There are no data regarding the presence of C1 inhibitor human in human milk, the effects on the breastfed infant, or the effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Serine proteinase inhibitor
Increases plasma concentration of C1 inhibitor activity
HAE patients have low levels of endogenous or functional C1 inhibitor: presentation of HAE attacks are thought to be mediated primarily through contact system activation
C1 inhibitor suppresses contact system activation through inactivation of plasma kallikrein and Factor XIIa modulating vasc permeability by preventing bradykinin generation
Absorption
Cinryze
- Peak plasma concentration: 0.68 units/mL (single dose); 0.85 units/mL (double dose)
- Peak plasma time: 3.9 hr (single dose); 2.7 hr (double dose)
- AUC: 74.5 units·hr/mL (single dose); 95.9 units·hr/mL (double dose)
Distribution
Berinert
- Vd (mL/kg): 14.1-56.1 (adults); 31.9-54.0 (pediatrics)
Elimination
Clearance
- Berinert (mL/kg/hr): 0.43-3.85 (adults); 0.98-1.1 (pediatrics)
- Cinryze: 0.85 mL/min (single dose); 1.17 mL/min (double dose)
Half-life
- Cinryze: 36 hr (single dose); 62 hr (double dose)
- Berinert: 7.4-22.8 hr (adults); 7.4-22.5 hr (pediatrics)
Administration
IV Preparation
Do not use if turbid or discolored (should be colorless to slight blue)
Bring to room temp, cleanse stoppers with germicidal solution, allow to dry
Use double-ended transfer needle; invert diluent vial containing 5 mL SWI over upright & slightly angled vial of drug; then rapidly insert free end of needle through the drug's vial stopper at its center; vial vacuum will draw in diluent
Do NOT use product if there is no vacuum in vial
Disconnect vials, discard diluent vial along w/ transfer needle, gently swirl to mix
Cinryze: Each reconstituted vial contains 5 mL of 100 U/mL solution
Cinryze: Reconstitute 2 vials for one dose
Berinert: Vials are reconstituted with 10 mL dilutent supplied
IV Administration
Administer at room temp within 3 hr (Cinryze) or 8 hr (Berinert) after reconstitution
To withdraw, introduce air in vial & withdraw drug solution
Attach needle or infusion set with winged adapter
Cinryze: Infuse at 1 mL/min over 10 min
Berinert: Infuse at no faster than 4 mL/min
SC Preparation
Use silicone-free syringe for reconstitution and administration
Ensure lyophilized powder and sterile water for injection (SWI) are at room temperature
2000 IU vial: Must reconstitute with 4 mL SWI
3000 IU vial: Must reconstitute with 6 mL SWI
Use Mix2Vial according to package instructions to reconstitute lyophilized powder
Do not shake vial (gently swirl until powder dissolved)
Once reconstituted, use SC solution within 8 hr
SC Administration
Attach the syringe containing reconstituted solution to a hypodermic needle or SC infusion set and administer by SC injection in abdominal area or other SC injection sites
Adapt SC injection/infusion rate to patient comfort level
Rotate injection sites
Storage
Berinert, Cinryze
- Untampered Unopened vial may be stored at 2-25°C (36-77°F) for period stated on the vial/container up to 1 year
- Do not freeze
- Protect from light
Haegarda
Unopened vial
- Store at up temperature up to 30°C (86°F) until expiration date
- Protect from light, by keeping vial in original container until ready to reconstitute
- Do not freeze
Reconstituted solution
- Store reconstituted solution at room temperature for up to 8 hr
- Do not freeze
- Single-use vials; discard any unused solution
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Berinert intravenous - | 500 unit (10 mL) kit |  | |
| Cinryze intravenous - | 500 unit (5 mL) vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
C1 esterase inhibitor intravenous
C1-ESTERASE INHIBITOR - INJECTION
COMMON BRAND NAME(S): Cinryze
USES: This medication is used to help prevent swelling problems that occur with a certain immune disease passed down through families (hereditary angioedema-HAE). HAE is caused by low levels or improper function of a natural substance produced by the body (C1-inhibitor). Symptoms such as rapid swelling of the hands, feet, limbs, face, tongue, or throat can occur. Swelling of the intestinal tract may cause symptoms such as abdominal cramps, diarrhea, or vomiting. Attacks of swelling may occur without reason. However, anxiety, stress, sickness, and surgery may trigger attacks in some people. This medication increases the level of C1-inhibitor to help prevent attacks of sudden swelling due to hereditary angioedema.
HOW TO USE: Read the Patient Information Leaflet and Instructions for Use if available from your pharmacist before you start using this medication and each time you get a refill. If you have any questions, ask your doctor or pharmacist.This medication is given by injection into a vein as directed by your doctor, usually every 3 or 4 days. The dosage is based on your medical condition and response to treatment.If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. The solution is normally clear and colorless to slightly blue, depending on the brand. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.Use this medication regularly to get the most benefit from it.Tell your doctor if your condition does not improve or if it worsens.
SIDE EFFECTS: Headache may occur. Other side effects are uncommon. If you notice any unusual side effects, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may rarely cause blood clots (such as pulmonary embolism, stroke, heart attack, deep vein thrombosis), especially when used at high doses. You may be at increased risk for blood clots if you have a history of blood clots, heart/blood vessel disease, heart failure, stroke, or if you are immobile (such as on very long plane flights or being bedridden). If you use estrogen-containing products, these may also increase your risk. Before using this medication, if you have any of these conditions report them to your doctor or pharmacist. Get medical help right away if any of these side effects occur: shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, confusion, sudden dizziness/fainting, new pain/swelling/warmth in the groin/calf, sudden/severe headaches, trouble speaking, numbness/weakness on one side of the body, sudden vision changes.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before using C1-inhibitor, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood clots (such as in the lungs, legs).This medication is made from human blood. Even though the blood is carefully tested and this medication goes through a special manufacturing process, there is an extremely small chance that you may get infections from the medication (for example, virus infections such as hepatitis). Consult your doctor or pharmacist for more information.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Before traveling, talk to your doctor to make sure you have enough of this medication.
MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule. Do not double the dose to catch up.
STORAGE: Store the unmixed vial in the original carton in the refrigerator or at room temperature away from light. Do not freeze. After mixing, use this medication right away or within 3 hours. Do not refrigerate the mixed solution. Discard any unused portion. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised July 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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