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Icatibant: Drug information

Icatibant: Drug information
(For additional information see "Icatibant: Patient drug information" and see "Icatibant: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Firazyr;
  • Sajazir
Brand Names: Canada
  • Firazyr
Pharmacologic Category
  • Selective Bradykinin B2 Receptor Antagonist
Dosing: Adult
Hereditary angioedema attacks, treatment

Hereditary angioedema attacks, treatment:

Note: To minimize morbidity and mortality, should be self-administered (or administered by a caregiver) at the onset of an attack whenever possible (US HAEA [Busse 2021]).

SUBQ: 30 mg once; may repeat every 6 hours if response is inadequate or symptoms recur; maximum dose: 90 mg per 24 hours.

Dosing: Kidney Impairment: Adult

No dosage adjustment is recommended (has not been studied); icatibant is cleared by nonrenal mechanisms and is not expected to accumulate in patients with renal impairment.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

(For additional information see "Icatibant: Pediatric drug information")

Hereditary angioedema

Hereditary angioedema (HAE): Limited data available: Children ≥2 years and Adolescents: SubQ: 0.4 mg/kg once; maximum dose: 30 mg/dose. Dosing based on an open-label study of 32 patients (mean age: 12.3 ± 3.5 years) with HAE (Farkas 2017).

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; however, icatibant is cleared by nonrenal mechanisms and is not expected to accumulate in patients with renal impairment.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; however, based on adult experience, no change in systemic exposure was observed in patients with mild to moderate hepatic impairment.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

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

Solution, Subcutaneous:

Sajazir: 30 mg/3 mL (3 mL)

Solution, Subcutaneous [preservative free]:

Firazyr: 30 mg/3 mL (3 mL)

Generic: 30 mg/3 mL (3 mL)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Solution, Subcutaneous:

Firazyr: 30 mg/3 mL (3 mL)

Administration: Adult

SubQ: For SubQ injection only. Patients may self-administer upon recognition of an HAE attack. Inject into the abdomen over ≥30 seconds, using the 25 gauge needle provided. Inject 2 to 4 inches below belly button and away from any scars; do not inject into an area that is bruised, swollen, or painful.

Administration: Pediatric

SubQ: For SubQ administration only. For doses <30 mg, transfer the appropriate volume needed for dose from the prefilled syringe into a graduated syringe. Inject into the abdomen over ≥30 seconds. Inject 2 to 4 inches below belly button and at least 2 inches away from any scars; do not inject into an area that is bruised, swollen, or painful.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 3]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.

NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) for preparation. Double gloving, a gown, and (if dosage form allows) CSTDs are required during administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

Use: Labeled Indications

Hereditary angioedema attacks, treatment: Treatment of acute attacks of hereditary angioedema.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Local: Injection site reaction (97%)

1% to 10%:

Hepatic: Increased serum transaminase (4%)

Immunologic: Antibody development (4%; anti-icatibant, no association with efficacy observed)

Nervous system: Dizziness (3%)

Miscellaneous: Fever (4%)

Frequency not defined:

Dermatologic: Skin rash

Gastrointestinal: Nausea

Nervous system: Headache

Postmarketing: Dermatologic: Urticaria

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to icatibant acetate or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Airway obstruction: Airway obstruction may occur during acute laryngeal attacks of HAE. Patients with laryngeal attacks should be instructed to seek medical attention immediately in addition to treatment with icatibant.

• CNS effects: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Warnings: Additional Pediatric Considerations

Airway obstruction may occur during acute laryngeal attacks of HAE; due to smaller airway passages, this may occur more rapidly in pediatric patients. Patients with laryngeal attacks should seek medical attention immediately following icatibant administration.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Angiotensin-Converting Enzyme Inhibitors: Icatibant may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Pregnancy Considerations

Information related to the use of icatibant in pregnancy is limited (Boufleur 2014; Farkas 2016; Hakl 2018; Kaminsky 2017; Tran 2013; Zanichelli 2015).

When treatment for hereditary angioedema in pregnancy is needed, other agents are recommended (Betschel 2019; WAO/EEACI [Maurer 2018]).

Breastfeeding Considerations

It is not known if icatibant is present in breast milk.

Systemic absorption in infants is not expected following exposure via breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother

When treatment for hereditary angioedema in breastfeeding females is needed, other agents are recommended (Betschel 2019; WAO/EEACI [Maurer 2018]).

Monitoring Parameters

Symptom relief; laryngeal symptoms or airway obstruction (immediate medical attention required in addition to icatibant therapy)

Mechanism of Action

Icatibant is a selective competitive antagonist for the bradykinin B2 receptor. Patients with HAE have an absence or dysfunction of C1-esterase-inhibitor which leads to the production of bradykinin. The presence of bradykinin may cause symptoms of localized swelling, inflammation, and pain. Icatibant inhibits bradykinin from binding at the B2 receptor, thereby treating the symptoms associated with acute attack.

Pharmacokinetics

Onset: Median time to 50% decrease of symptoms: ~2 hours

Duration: Inhibits symptoms caused by bradykinin for ~6 hours

Distribution: Vdss:

Children ≥2 years: 0.39 ± 0.11 L/kg (Farkas 2017)

Adolescents: 0.44 ± 0.18 L/kg (Farkas 2017)

Adults: 29 ± 8.7 L

Metabolism: Metabolized by proteolytic enzymes to metabolites (inactive)

Bioavailability: ~97%

Half-life elimination:

Children ≥2 years: 0.8 ± 0.04 hours (Farkas 2017)

Adolescents: 1.34 ± 0.96 hours (Farkas 2017)

Adults: 1.4 ± 0.4 hours

Time to peak:

Children ≥2 years: 0.42 ± 0.13 hours (Farkas 2017)

Adolescents: 0.55 ± 0.19 hours (Farkas 2017)

Adults: ~0.75 hours

Excretion: Urine (<10% unchanged)

Pricing: US

Solution (Firazyr Subcutaneous)

30 mg/3 mL (per mL): $4,459.00

Solution (Icatibant Acetate Subcutaneous)

30 mg/3 mL (per mL): $800.00 - $4,236.05

Solution (Sajazir Subcutaneous)

30 mg/3 mL (per mL): $4,000.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Firazyr (AT, AU, BB, BE, BR, CH, CZ, DE, DK, EE, ES, FR, GB, GR, HR, HU, IE, IL, KR, LT, LU, MT, NL, NO, NZ, PL, PT, RO, SE, SI, SK, TW);
  • Icanticure (TW)


For country code abbreviations (show table)
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  4. Betschel S, Badiou J, Binkley K, et al. The international/Canadian hereditary angioedema guideline. Allergy Asthma Clin Immunol. 2019;15:72. doi:10.1186/s13223-019-0376-8 [PubMed 31788005]
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  8. Craig T, Aygören-Pürsün E, Bork K, et al. WAO guideline for the management of hereditary angioedema. World Allergy Organ J. 2012;5(12):182-199. doi:10.1097/WOX.0b013e318279affa [PubMed 23282420]
  9. Farkas H, Kőhalmi KV, Veszeli N, et al. First report of icatibant treatment in a pregnant patient with hereditary angioedema. J Obstet Gynaecol Res. 2016;42(8):1026-1028. doi:10.1111/jog.13003 [PubMed 27093898]
  10. Farkas H, Reshef A, Aberer W, et al. Treatment Effect and Safety of Icatibant in Pediatric Patients with Hereditary Angioedema. J Allergy Clin Immunol Pract. 2017;5(6):1671-1678. doi:10.1016/j.jaip.2017.04.010 [PubMed 28601641]
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  12. Firazyr (icatibant) [product monograph]. Toronto, Ontario, Canada: Takeda Canada Inc; December 2020.
  13. Hakl R, Kuklínek P, Krčmová I, et al. Treatment of hereditary angioedema attacks with icatibant and recombinant C1 inhibitor during pregnancy. J Clin Immunol. 2018;38(7):810-815. doi:10.1007/s10875-018-0553-4 [PubMed 30280305]
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  16. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema: the 2017 revision and update. Allergy. Published online January 10, 2018. doi:10.1111/all.13384 [PubMed 29318628]
  17. Sinert R, Levy P, Bernstein JA, et al; CAMEO Study Group. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017;5(5):1402-1409. doi:10.1016/j.jaip.2017.03.003 [PubMed 28552382]
  18. Straka BT, Ramirez CE, Byrd JB, et al. Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema. J Allergy Clin Immunol. 2017;140(1):242-248. doi:10.1016/j.jaci.2016.09.051 [PubMed 27913306]
  19. Tran YD, de Malmanche T. Management dilemmas in a case of angioedema with normal C1 inhibitor function during pregnancy. Intern Med J. 2013;43(11):1259. doi:10.1111/imj.12281 [PubMed 24237653]
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