C1 Inhibitor (Human)

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

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C1 inhibitor, one of the serine proteinase inhibitors found in human blood, plays a role in regulating the complement and intrinsic coagulation (contact system) pathway, and is also involved in the fibrinolytic and kinin pathways. C1 inhibitor therapy in patients with C1 inhibitor deficiency, such as HAE, is believed to suppress contact system activation via inactivation of plasma kallikrein and factor XIIa, thus preventing bradykinin production. Unregulated bradykinin production is thought to contribute to the increased vascular permeability and angioedema observed in HAE.

Distribution

Berinert: Vss: Children and Adolescents: (6 to 13 years, n=5): 0.02 L/kg (range: 0.017 to 0.026 L/kg); Adults: 0.018 L/kg (range: 0.011 to 0.028 L/kg)

Haegarda: Vd: Adolescents and Adults: 0.05 L/kg

Berinert: Onset of symptom relief: Median: 15 minutes per attack; Cinryze: Pediatric patients 6 to 17 years: Median: 30 minutes per attack; for the majority of patient unequivocal symptom relief reported within 1 hour (range: 15 to 135 minutes) (Lumry 2013)

Cinryze: Increased plasma C1 inhibitor levels observed ~1 hour or less

Time to Peak

Cinryze: ~4 hours; Haegarda: 59 hours

Androgens: May enhance the thrombogenic effect of C1 inhibitors. Monitor therapy

Estrogen Derivatives: May enhance the thrombogenic effect of C1 inhibitors. Monitor therapy

Progestins: May enhance the thrombogenic effect of C1 inhibitors. Monitor therapy

Frequency not defined.

>10%:

Central nervous system: Headache

Gastrointestinal: Nausea

1% to 10%:

Central nervous system: Dizziness

Dermatologic: Erythema, pruritus, skin rash

Gastrointestinal: Abdominal distress, abdominal pain, dysgeusia, vomiting, xerostomia

Hypersensitivity: Angioedema (including exacerbation of hereditary angioedema)

Infection: Fungal infection (vulvovaginal), viral infection

Respiratory: Flu-like symptoms, nasopharyngitis, upper respiratory tract infection

Miscellaneous: Fever, infusion-related reaction

<1% (Limited to important or life-threatening): Anaphylaxis, cerebrovascular accident, chest pain, deep vein thrombosis, erythema at injection site, hypersensitivity reaction, migraine, pain at injection site, pain (not otherwise specified), shock, swelling, thrombosis, transient ischemic attacks

Concerns related to adverse effects:

• Hypersensitivity: Severe hypersensitivity reactions (eg, urticaria, hives, tightness of the chest, wheezing, hypotension, anaphylaxis) may occur during or after administration. Signs/symptoms of hypersensitivity reactions may be similar to the attacks associated with hereditary angioedema, therefore, consideration should be given to treatment methods. In the event of acute or severe hypersensitivity reactions, discontinue treatment immediately.

• Thrombotic events: Serious arterial and venous thromboembolic events have been reported at recommended intravenous doses and when used off-label at doses higher than recommended. 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. Consider potential risk of thrombosis with use, and closely monitor patients with preexisting risks for thrombotic events.

Dosage form specific issues:

• Human plasma: Product of human plasma; may potentially contain infectious agents (eg, viruses, the variant Creutzfeldt-Jakob disease [vCJD] agent and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.

Other warnings/precautions:

• Self-administration: Due to the potential for airway obstruction, patients suffering from an acute laryngeal hereditary angioedema (HAE) attack and self-administering should be informed to immediately seek medical attention following treatment.

Animal reproduction studies have not been conducted. Although information related to use during pregnancy is limited, plasma-derived human C1 inhibitor concentrate is the preferred treatment for HAE during pregnancy (Baker 2013; Caballero 2012). Women with HAE should be monitored closely during pregnancy and for at least 72 hours after delivery (Caballero 2012).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, or bad taste. Have patient report immediately to prescriber signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; tachycardia; or coughing up blood), severe dizziness, passing out, severe headache, mouth discoloration, or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.