Skip to Content

C1 Inhibitor (Recombinant)

Pronunciation

(cee won in HIB i ter ree KOM be nant)

Index Terms

  • C1 Esterase Inhibitor
  • C1-INH
  • C1-Inhibitor
  • Conestat Alfa
  • Recombinant C1 Inhibitor

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Ruconest: 2100 units (1 ea) [contains rabbit protein]

Brand Names: U.S.

  • Ruconest

Pharmacologic Category

  • C1 Esterase Inhibitor

Pharmacology

C1 inhibitor, a serine protease inhibitor (serpin), regulates the activation of the complement and contact system pathways by irreversibly binding target proteases. Suppression of contact system activation by C1 inhibitor through the inactivation of plasma kallikrein and factor XIIa is thought to modulate vascular permeability that leads to clinical manifestations of hereditary angioedema (HAE) attacks by preventing the generation of bradykinin.

Distribution

Vss: ~3 L

Onset of Action

Onset of symptom relief: Median: 90 minutes

Time to Peak

~0.3 hours

Half-Life Elimination

~2.5 hours

Use: Labeled Indications

Hereditary angioedema (treatment): Treatment of acute attacks of hereditary angioedema (HAE) in adult and adolescent patients

Limitations of use: Effectiveness not established in HAE patients with laryngeal attacks.

Off Label Uses

Hereditary angioedema (prophylaxis)

Data from a small pilot study displayed a significant reduction in hereditary angioedema (HAE) attacks after weekly administration of C1 inhibitor (recombinant) [Reshef 2013]. Subsequently, a small international phase II multicenter randomized double-blind placebo controlled crossover trial further supported the use of C1 inhibitor (recombinant) for prophylaxis of HAE in patients with frequent attacks (defined as a history of ≥4 HAE attacks per month for at least 3 consecutive months) and C1 inhibitor levels <50% of normal. Both weekly and twice-weekly administration of C1 inhibitor (recombinant) significantly reduced the number of HAE attacks after 4 weeks of therapy compared with placebo; however, the twice-weekly regimen resulted in more consistent achievement of at least 50% reduction in attacks [Riedl 2017].

Based on the International World Allergy Organization/European/Academy of Allergy and Clinical Immunology (WAO/EAACI) guideline for the management of hereditary angioedema, C1 inhibitor (recombinant) may be considered for short-term prophylaxis before procedures that induce an attack. Additional trials may be necessary to further define the role of a C1 inhibitor (recombinant) for this indication.

Contraindications

Life-threatening immediate hypersensitivity reactions, including anaphylaxis, to C1 esterase inhibitor preparations or any component of the formulation; allergy to rabbits or rabbit-derived products

Dosing: Adult

Hereditary angioedema (treatment): IV:

Weight <84 kg: 50 units/kg (maximum dose: 4,200 units) as a single dose

Weight ≥84 kg: 4,200 units as a single dose

Note: If attack symptoms persist, one additional dose may be administered; no more than 2 doses may be administered per 24 hours.

Hereditary angioedema (prophylaxis) (off-label use): IV:

Weight <84 kg: 50 units/kg (maximum dose: 4,200 units) twice weekly (Riedl 2017)

Weight ≥84 kg: 4,200 units twice weekly (Riedl 2017)

Note: May reduce frequency of administration to once weekly, ensuring maintenance of symptom control; once-weekly dosing was shown to be more effective than placebo but with the potential for more frequent attacks compared with twice-weekly dosing (Reshef 2013, Riedl 2017). Dosing more than twice weekly has not been studied.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hereditary angioedema (treatment): Adolescents: IV: Refer to adult dosing.

Hereditary angioedema (prophylaxis) (off-label): Adolescents: IV: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Reconstitution

Allow diluent and C1 inhibitor to warm to room temperature. Reconstitute with 14 mL SWFI. Slowly add SWFI and swirl slowly to mix; avoid foaming. Resulting concentration is 150 units/mL. If patient requires contents of ≥1 vial, contents of multiple vials may be pooled into a single syringe.

Administration

IV: Administer by a separate infusion line as a slow IV injection over ~5 minutes. Appropriately trained patients may self-administer upon recognition of an HAE attack.

Storage

Store intact vials at 2°C to 25°C (36°F to 77°F) for up to 48 months; do not freeze. Protect from light. Reconstituted solution may be stored at 2°C to 8°C (36°F to 46°F) for ≤8 hours; do not freeze. Discard unused portion.

Drug Interactions

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

Adverse Reactions

>10%:

Central nervous system: Headache (more common in adolescents than in adults)

Gastrointestinal: Abdominal pain (adolescents: ≥12%)

Respiratory: Oropharyngeal pain (adolescents: ≥12%)

1% to 10%:

Central nervous system: Vertigo (3%)

Dermatologic: Burning sensation of skin (2%), erythema (2%; marginatum)

Gastrointestinal: Diarrhea (≥2%), nausea (≥2%)

Hematologic & oncologic: C-reactive protein increased (2%), increased fibrin (2%), lipoma (2%)

Hypersensitivity: Angioedema (3%)

Immunologic: Antibody development (after repeat therapy exposure, non-neutralizing)

Neuromuscular & skeletal: Back pain (3%)

Respiratory: Sneezing (2%)

Postmarketing and/or case reports: Abdominal pain, anaphylaxis, arterial thromboembolism (in patients with risk factors), hypersensitivity reaction, skin rash, venous thromboembolism (in patients with risk factors)

Warnings/Precautions

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 hypersensitivity reactions to C1 inhibitor therapy, treatment should be discontinued and appropriate treatment should be instituted.

• Thrombotic events: Serious arterial and venous thromboembolic events have been reported at recommended doses in patients with risk factors (eg, presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, immobility). Closely monitor patients with preexisting risks for thrombotic events during and after administration.

Monitoring Parameters

Monitor for signs/symptoms of hypersensitivity reactions and thrombotic events. Prior to initiation for long-term prophylaxis, test for immunoglobulin E (IgE) antibodies against rabbit antigens; repeat testing annually or after 10 treatments, whichever occurs first (Craig 2012).

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Information related to use of C1 inhibitor (recombinant) in pregnancy is limited (Longhurst 2017).

C1 inhibitor (human) is preferred for the treatment and prophylaxis of hereditary angioedema (HAE) during pregnancy. Women with HAE should be monitored closely during pregnancy and for at least 72 hours after delivery (WAO/EEACI [Maurer 2018]).

Patient Education

• 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 diarrhea or nausea. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), severe dizziness, passing out, mouth discoloration, tachycardia, severe headache, or 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) (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 healthcare 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide