C1-esterase inhibitor, recombinant

General

Pronunciation:
C1 es-ter-ase in-hib-it-or re-kom-bin-ant


Trade Name(s)

  • Ruconest

Ther. Class.

antiangioedema agents

Pharm. Class.

enzyme inhibitors

Indications

Treatment of acute attacks of hereditary angioedema.

Action

Replaces C1-esterase inhibitor which is deficient in patients with hereditary angioedema. C1 inhibitor is necessary in preventing the chain of events which alter vascular permeability resulting in life-threatening swelling in hereditary angioedema.

Therapeutic Effect(s):

Decreased intensity of hereditary angioedema attacks.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: 2.4–2.7 hr.

TIME/ACTION PROFILE (symptom relief)

ROUTEONSETPEAKDURATION
IVwithin 1 hrunknown16–24 hr

Contraindication/Precautions

Contraindicated in:

  • Known/suspected hypersensitivity to rabbits/rabbit-derived products
  • Previous immediate hypersensitivity reactions to C1-esterase inhibitor preparations.

Use Cautiously in:

  • Presence of indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility (↑ risk of thromboembolism)
  • OB:  C1-esterase inhibitor (human) is preferred for the treatment of hereditary angioedema during pregnancy;
  • Pedi:  Children <13 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

CV: THROMBOEMBOLIC EVENTS

EENT: oropharyngeal pain

GI: abdominal pain, diarrhea, nausea

Neuro: headache

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

IV (Adults and Children  ≥13 yr and ≥84 kg): 4,200 units as a single dose; a 2nd dose may be given if symptoms persist (not to exceed 2 doses/24 hr).

IV (Adults and Children  ≥13 yr and <84 kg): 50 units/kg as a single dose; a 2nd dose may be given if symptoms persist (not to exceed 2 doses/24 hr).

Availability

Lyophilized powder for injection: 2,100 units/vial

Assessment

  • Monitor for signs/symptoms of hypersensitivity reactions (rash, urticaria, pruritus, flushing, dizziness, vomiting, abdominal pain) and angioedema (swelling of throat, lips, tongue, face, dyspnea, wheezing, hoarseness).  If reaction occurs,  discontinue C1-esterase inhibitor immediately and provide supportive care.
  • Monitor for signs/symptoms of venous thromboembolism such as pulmonary embolism (chest pain, dyspnea, tachycardia) or deep vein thrombosis (calf pain or tenderness, lower extremity edema, localized warmth or erythema) or stroke (headache, facial numbness, unilateral weakness, aphasia, eye pain or swelling, vision changes).  If thromboembolic event suspected,  discontinue C1-esterase inhibitor.

Implementation

IV Administration

  • Intermittent Infusion:  Medication and diluent vials should be at room temperature before mixing.  Reconstitution: Reconstitute by withdrawing 14 mL of sterile water for injection. Add diluent slowly; avoid forceful impact on powder. Swirl slowly to mix; avoid foaming. Repeat with 2nd vial. Solution should be clear and colorless; do not administer solutions that are discolored or contain particulate matter. Use solution immediately or may be refrigerated for ≤ 8 hr; do not freeze.
  • Rate: Inject slowly over 5 min.
  • Y-Site Incompatibility:
    • Do not administer other drugs through same IV line.

Patient/Family Teaching

  • Explain purpose and side effects of C1-esterase inhibitor. Do not stop receiving drug without consulting health care provider. If an appointment is missed, reschedule as soon as possible. Advise patient to read  Patient Information  before starting and periodically during therapy in case of changes.
  • May be self-administered with proper training. Patient must be able to recognize the signs/symptoms of hereditary angioedema and must have the dexterity and comprehension to self-administer injection. Instruct patient or caregiver in correct technique for injection, storage, and place to discard syringes and needles. Advise patient to seek medical attention immediately in addition to injection due to potential for laryngeal edema. Instruct patient to record lot number from vial. At first sign of hereditary angioedema attack, prepare injection. Bring C1-esterase inhibitor with you to health care facility. Notify health care provider immediately if swelling does not decrease after injection.
  • Advise patient to notify health care provider immediately if signs/symptoms of hypersensitivity reactions or thrombosis occur.
  • Caution patient to consult health care provider of planning to travel.
  • Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Decrease in intensity of symptoms of hereditary angioedema.