Icatibant
Injection, Solution · Subcutaneous
Uses
Icatibant injection is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older. Icatibant injection is a bradykinin B2 receptor antagonist indicated for treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older. ( 1 )
Dosage and administration
30 mg injected subcutaneously in the abdominal area. ( 2.1 ) If response is inadequate or symptoms recur, additional injections of 30 mg may be administered at intervals of at least 6 hours. ( 2.1 ) Do not administer more than 3 injections in 24 hours. ( 2.1 ) Patients may self-administer upon recognition of an HAE attack. ( 2.2 ) 2.1 Recommended Dosing The recommended dose of Icatibant injection is 30 mg administered by subcutaneous (SC) injection in the abdominal area. Additional doses may be administered at intervals of at least 6 hours if response is inadequate or if symptoms recur. No more than 3 doses may be administered in any 24 hour period. 2.2 Administration Instructions Icatibant injection should be inspected visually for particulate matter and discoloration prior to administration. The drug solution should be clear and colorless. Do not administer if the product contains particulates or is discolored. Attach the provided 25 gauge needle to the syringe hub and screw on securely. Do not use a different needle. Disinfect the injection site and administer Icatibant injection by subcutaneous injection over at least 30 seconds. Discard unused portion. Patients may self-administer Icatibant injection upon recognition of symptoms of an HAE attack after training under the guidance of a healthcare professional [see Patient Counseling Information ( 17 )].
Dosage forms and strengths
Icatibant injection is supplied in a prefilled syringe delivering 30 mg icatibant. Each syringe delivers 3 mL solution with a concentration of 10 mg per mL. Injection: 10 mg per mL
Contraindications
None. None
Warnings and precautions
Laryngeal attacks: Following treatment of laryngeal attacks with Icatibant injection, advise patients to seek immediate medical attention. ( 5.1 ) 5.1 Laryngeal Attacks Given the potential for airway obstruction during acute laryngeal HAE attacks, patients should be advised to seek medical attention in an appropriate healthcare facility immediately in addition to treatment with Icatibant injection.
Side effects
The most commonly reported adverse reactions were injection site reactions, which occurred in almost all patients (97%) in clinical trials. Other common adverse reactions occurring in greater than 1% of patients included pyrexia, transaminase increase, dizziness, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The safety of icatibant was evaluated in three controlled trials that included 223 patients who received Icatibant injection 30 mg (n=113), placebo (n=75), or comparator (n=38). The mean age at study entry was 38 years (range 18 to 83 years), 64% were female, and 95% were white. The data described below represent adverse reactions observed from the two placebo-controlled trials, consisting of 77 patients who received Icatibant injection at a dose of 30 mg SC, and 75 who received placebo. The most frequently reported adverse reactions (occurring in greater than 1% of patients and at a higher rate with Icatibant injection versus placebo) are shown in Table 1. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 1 Adverse reactions observed in >1% of patients with acute attacks of HAE and at a higher rate with Icatibant injection versus placebo in the placebo-controlled trials a ICATIBANT INJECTION (N =77) Placebo (N = 75) System Organ Class Preferred Term Subjects (%) Subjects (%) General disorders and administration site conditions Injection site reaction b Pyrexia 75 (97) 3 (4) 25 (33) 0 Investigations Transaminase increased 3 (4) 0 Nervous system disorders Dizziness 2 (3) 1 (1) a Events occurring within 14 days of study drug administration b Injection site bruising, Injection site hematoma, Injection site burning, Injection site erythema, Injection site hypoesthesia, Injection site irritation, Injection site numbness, Injection site edema, Injection site pain, Injection site pressure sensation, Injection site pruritus, Injection site swelling, Injection site urticaria, and Injection site warmth The third trial was active-controlled and was comprised of 35 patients who received Icatibant injection 30 mg and 38 patients who received the comparator. Adverse reactions for Icatibant injection were similar in nature and frequency to those reported in Table 1. In all three controlled trials, patients were eligible for treatment of subsequent attacks in an open-label extension. Patients were treated with Icatibant injection 30 mg and could receive up to 3 doses of Icatibant injection 30 mg administered at least 6 hours apart for each attack. A total of 225 patients were treated with 1,076 doses of 30 mg Icatibant injection for 987 attacks of acute HAE. Adverse reactions similar in nature and frequency were observed to those seen in the controlled phase of the trials. Other adverse reactions reported included rash, nausea, and headache in patients exposed to Icatibant injection. The safety of self-administration was evaluated in a separate, open-label trial in 56 patients with HAE. In this trial, the safety profile of Icatibant injection in patients who self-administered Icatibant injection was similar in nature and frequency to that of patients whose therapy was administered by healthcare professionals. 6.2 Immunogenicity Across repeated treatment in the controlled trials, 4 patients tested positive for anti-icatibant antibodies. Three of these patients had subsequent tests which were negative. No hypersensitivity or anaphylactic reactions were reported with Icatibant injection. No association between anti-icatibant antibodies and efficacy was observed. 6.3 Postmarketing Experience The following adverse reactions have been identified during post approval use of Icatibant injection: urticaria. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Drug interactions
7.1 ACE Inhibitors Icatibant injection is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where Icatibant injection may attenuate the antihypertensive effect of ACE inhibitors. Clinical trials to date have excluded subjects taking ACE inhibitors.
Use in specific populations
Elderly patients demonstrate increased systemic exposure to icatibant. Differences in efficacy and safety between elderly and younger patients have not been identified. ( 8.5 ) 8.1 Pregnancy Risk Summary Available data from published literature and the pharmacovigilance database with Icatibant injection (icatibant) use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, icatibant, administered by the subcutaneous route during the period of organogenesis, did not cause structural abnormalities in rats or rabbits; however, premature birth and abortion were observed in rabbits at doses approximately 0.025 times the maximum recommended human dose (MRHD) and higher. Decreased embryofetal survival was observed in rabbits at a subcutaneous dose that was 13 times the MRHD. In a pre -and post-natal development study in rats, delayed parturition was observed at subcutaneous doses 0.5 times the MRHD and higher, which resulted in deaths of dams at doses 2 times the MRHD and higher. Fetal death and early pup deaths were observed with doses 2 times the MRHD ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study with rats that received icatibant from gestation days 7 to 18, there was no evidence of any treatment-related structural abnormalities or effects on embryo-fetal survival with maternal doses up to 2.7 times the MRHD (on a mg/m 2 basis with maternal subcutaneous doses up to 25 mg/kg/day). In a fertility and early embryonic development study with rats, icatibant increased pre-implantation loss at a dose that was 7 times the MRHD (on an AUC basis at a maternal dose of 10 mg/kg/day). In an embryo-fetal development study with rabbits that received icatibant from gestation days 7 to 18, premature birth and abortion rates increased at doses approximately 0.025 times the MRHD and higher (on a mg/m 2 basis at maternal subcutaneous doses of 0.1 mg/kg and higher). Icatibant treatment resulted in dose-related decreases of total implantations and total number of live fetuses as well as dose-related increases of percent pre-implantation loss at a dose that was 13 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 10 mg/kg/day). There was no evidence of any treatment-related structural abnormalities with maternal doses up to 13 times the MRHD (on an AUC basis with maternal subcutaneous doses up to 10 mg/kg/day). In a pre- and post-natal development study in the rat, dams received icatibant by the subcutaneous route at doses of 1, 3, and 10 mg/kg/day from gestation day 6 to post-partum (PPD) day 20. Delayed parturition was observed at doses 0.5 times the MRHD and higher (on an AUC basis with maternal subcutaneous doses of 1 mg/kg/day and higher), which resulted in deaths of dams at doses 2 times the MRHD and higher (on an AUC basis with maternal subcutaneous doses of 3 mg/kg/day and higher). Fetal death and increased pup deaths through PPD 4 were observed with doses 2 times the MRHD (on an AUC with a maternal subcutaneous dose of 3 mg/kg/day and higher). Impairment of pup righting reflex and decreased pup hair growth were also observed at 7 times the MRHD (on an AUC basis with a maternal dose of 10 mg/kg). Icatibant and the M2 metabolite were found in maternal milk following subcutaneous administration of icatibant. The no effect dose for F1 pups was identified at a dose 0.5 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 1 mg/kg/day). A no effect dose was not identified for F 0 maternal toxicity. 8.2 Lactation Risk Summary There are no data on the presence of icatibant in human milk, the effects on the breastfed infant, or the effects on milk production. Icatibant and the M2 metabolite were found in rat milk following subcutaneous administration of icatibant (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. However, systemic absorption of icatibant in infants is not expected after oral exposure through breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Icatibant injection and any potential adverse effects on the breastfed child from Icatibant injection or from the underlying maternal condition. Data Animal Data Icatibant is excreted into the milk of lactating rats at concentrations that sometimes slightly exceeded those measured in the maternal plasma. 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Juvenile Toxicity Data Subcutaneous daily administration of icatibant to young rats during the juvenile period of development (postnatal days 22-70) delayed the sexual maturation of male reproductive tissues (atrophy of testes and epididymides) at exposures approximating one-third or greater the MRHD on a mg/m 2 basis. Impaired fertility and reproductive performance were also observed in male rats at the end of the postnatal treatment period at exposures approximating the MRHD or greater on a mg/m 2 basis. No effects were observed in females at exposures approximating 3-fold the MRHD on a mg/m 2 basis. The observed tissue findings in males were consistent with those seen in sexually mature rats and dogs and are attributed to antagonism of the bradykinin B2 receptor and subsequent effects on gonadotropins. The observed effects may be a consequence of daily icatibant administration.
Pregnancy
8.1 Pregnancy Risk Summary Available data from published literature and the pharmacovigilance database with Icatibant injection (icatibant) use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, icatibant, administered by the subcutaneous route during the period of organogenesis, did not cause structural abnormalities in rats or rabbits; however, premature birth and abortion were observed in rabbits at doses approximately 0.025 times the maximum recommended human dose (MRHD) and higher. Decreased embryofetal survival was observed in rabbits at a subcutaneous dose that was 13 times the MRHD. In a pre -and post-natal development study in rats, delayed parturition was observed at subcutaneous doses 0.5 times the MRHD and higher, which resulted in deaths of dams at doses 2 times the MRHD and higher. Fetal death and early pup deaths were observed with doses 2 times the MRHD ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study with rats that received icatibant from gestation days 7 to 18, there was no evidence of any treatment-related structural abnormalities or effects on embryo-fetal survival with maternal doses up to 2.7 times the MRHD (on a mg/m 2 basis with maternal subcutaneous doses up to 25 mg/kg/day). In a fertility and early embryonic development study with rats, icatibant increased pre-implantation loss at a dose that was 7 times the MRHD (on an AUC basis at a maternal dose of 10 mg/kg/day). In an embryo-fetal development study with rabbits that received icatibant from gestation days 7 to 18, premature birth and abortion rates increased at doses approximately 0.025 times the MRHD and higher (on a mg/m 2 basis at maternal subcutaneous doses of 0.1 mg/kg and higher). Icatibant treatment resulted in dose-related decreases of total implantations and total number of live fetuses as well as dose-related increases of percent pre-implantation loss at a dose that was 13 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 10 mg/kg/day). There was no evidence of any treatment-related structural abnormalities with maternal doses up to 13 times the MRHD (on an AUC basis with maternal subcutaneous doses up to 10 mg/kg/day). In a pre- and post-natal development study in the rat, dams received icatibant by the subcutaneous route at doses of 1, 3, and 10 mg/kg/day from gestation day 6 to post-partum (PPD) day 20. Delayed parturition was observed at doses 0.5 times the MRHD and higher (on an AUC basis with maternal subcutaneous doses of 1 mg/kg/day and higher), which resulted in deaths of dams at doses 2 times the MRHD and higher (on an AUC basis with maternal subcutaneous doses of 3 mg/kg/day and higher). Fetal death and increased pup deaths through PPD 4 were observed with doses 2 times the MRHD (on an AUC with a maternal subcutaneous dose of 3 mg/kg/day and higher). Impairment of pup righting reflex and decreased pup hair growth were also observed at 7 times the MRHD (on an AUC basis with a maternal dose of 10 mg/kg). Icatibant and the M2 metabolite were found in maternal milk following subcutaneous administration of icatibant. The no effect dose for F1 pups was identified at a dose 0.5 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 1 mg/kg/day). A no effect dose was not identified for F 0 maternal toxicity.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Juvenile Toxicity Data Subcutaneous daily administration of icatibant to young rats during the juvenile period of development (postnatal days 22-70) delayed the sexual maturation of male reproductive tissues (atrophy of testes and epididymides) at exposures approximating one-third or greater the MRHD on a mg/m 2 basis. Impaired fertility and reproductive performance were also observed in male rats at the end of the postnatal treatment period at exposures approximating the MRHD or greater on a mg/m 2 basis. No effects were observed in females at exposures approximating 3-fold the MRHD on a mg/m 2 basis. The observed tissue findings in males were consistent with those seen in sexually mature rats and dogs and are attributed to antagonism of the bradykinin B2 receptor and subsequent effects on gonadotropins. The observed effects may be a consequence of daily icatibant administration. Toxicity to the testis did not occur in dogs treated twice a week for 9 months [see Carcinogenesis, Mutagenesis, Impairment of Fertility ( 13.1 )].
Geriatric use
8.5 Geriatric Use Clinical studies of Icatibant injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients are likely to have increased systemic exposure to Icatibant injection compared to younger (18-45 years) patients [see Clinical Pharmacology ( 12.3 )] . Since other reported clinical experience has not identified differences in efficacy and safety between elderly and younger patients, no dose adjustment is recommended.
Overdosage
In a clinical study evaluating a 90 mg dose (30 mg in each of 3 subcutaneous sites), the adverse event profile was similar to that seen with 30 mg administered in a single subcutaneous site. In another clinical study, a dose of 3.2 mg/kg administered intravenously (approximately 8 times the therapeutic dose for HAE) caused erythema, itching and hypotension in healthy subjects. No therapeutic intervention was necessary.
Description
Icatibant injection (icatibant) is a synthetic decapeptide with five non-proteinogenic amino acids. The chemical structure of icatibant acetate is presented in Figure 1. Figure 1 Chemical Structure Chemical name: D-Arginyl-L-arginyl-L-prolyl-L[(4R)-4-hydroxyprolyl]-glycyl-L[3-(2-thienyl)alanyl]-Lseryl-D-(1,2,3,4-tetrahydroisoquinolin-3-ylcarbonyl)-L[(3aS,7aS) octahydroindol-2-ylcarbonyl]-L arginine, acetate salt Icatibant injection is provided as a sterile, isotonic, and buffered solution of icatibant acetate in a single-dose, prefilled syringe for subcutaneous administration. Each mL of the solution contains 10 mg of icatibant (free base) which is equivalent to 11.38 mg of icatibant acetate. Each prefilled syringe delivers 3 mL of solution equivalent to a 30 mg icatibant dose. The solution is clear and colorless. The solution also contains sodium chloride (isotonicity reagent), glacial acetic acid (buffering agent), sodium hydroxide (pH adjuster) and water for injection with a pH of approximately 5.5. The solution does not contain preservatives. Pharmacological class: Icatibant is a bradykinin B2 receptor antagonist. icatibant-structure
Mechanism of action
12.1 Mechanism of Action Icatibant is a competitive antagonist selective for the bradykinin B2 receptor, with an affinity similar to bradykinin. Hereditary angioedema is caused by an absence or dysfunction of C1-esterase-inhibitor, a key regulator of the Factor XII/kallikrein proteolytic cascade that leads to bradykinin production. Bradykinin is a vasodilator which is thought to be responsible for the characteristic HAE symptoms of localized swelling, inflammation, and pain. Icatibant inhibits bradykinin from binding the B2 receptor and thereby treats the clinical symptoms of an acute, episodic attack of HAE.
How supplied
16.1 How Supplied Icatibant injection is supplied as a sterile, clear colorless solution in single-dose, prefilled syringe for subcutaneous administration. Each syringe delivers 3 mL of a sterile solution of icatibant 30 mg (as icatibant acetate). Each glass syringe has a bromobutyl plunger stopper, which is not made of latex natural rubber. Icatibant injection is available in cartons containing one single-dose, prefilled syringe and one 25 G Luer lock needle. NDC 62332-654-03. Icatibant injection is also available in a pack containing 3 cartons; each carton contains one single-dose, prefilled syringe and one 25 G Luer lock needle. NDC 62332-654-09. 16.2 Storage and Handling Keep out of the reach of children. Store between 2 to 25° C (36 to 77° F). Do not freeze. Store in carton until time of administration.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). 17.1 Information for Patients Patients may self-administer Icatibant injection upon recognition of an HAE attack after training under the guidance of a healthcare professional. Patients with laryngeal symptoms should seek medical attention immediately in an appropriate healthcare facility after administration of Icatibant injection [see Warnings and Precautions ( 5.1 )]. Injection site reactions are reported in most patients after administration of Icatibant injection. Other adverse reactions reported after administration of Icatibant injection include pyrexia, increase in transaminases, dizziness, and rash [see Adverse Reactions ( 6.1 )]. Tiredness, drowsiness, and dizziness have been reported following the use of Icatibant injection. Patients should be advised not to drive or use machinery if they feel tired or dizzy. Manufactured by: Alembic Pharmaceuticals Limited Karakhadi 391450, Gujarat, India. Manufactured for: Alembic Pharmaceuticals, Inc. Bedminster, NJ 07921, USA. Revised: January 2025
Label text from the FDA structured product label by Alembic Pharmaceuticals Inc. (revised Jul 1, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Icatibant Acetate in 7 products
Icatibant NDC products (7)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 62332-654 | Icatibant Acetate 30 mg/3mL Injection | Alembic Pharmaceuticals Inc. | ANDA |
| 46708-654 | Icatibant Acetate 30 mg/3mL Injection | Alembic Pharmaceuticals Limited | ANDA |
| 69097-664 | Icatibant Acetate 30 mg/3mL Injection | Cipla USA Inc. | ANDA |
| 55150-351 | Icatibant Acetate 30 mg/3mL Injection, Solution | Eugia US LLC | ANDA |
| 63323-574 | Icatibant Acetate 10 mg/mL Injection, Solution | Fresenius Kabi USA, LLC | ANDA |
| 24201-207 | Icatibant Acetate 30 mg/3mL Injection, Solution | Hikma Pharmaceuticals USA Inc. | ANDA |
| 0093-3066 | Icatibant Acetate 10 mg/mL Injection, Solution | Teva Pharmaceuticals USA, Inc. | ANDA |
Frequently asked questions
What is Icatibant used for?
Icatibant injection is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older. Icatibant injection is a bradykinin B2 receptor antagonist indicated for treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older. ( 1 )
What are the side effects of Icatibant?
The most commonly reported adverse reactions were injection site reactions, which occurred in almost all patients (97%) in clinical trials. Other common adverse reactions occurring in greater than 1% of patients included pyrexia, transaminase increase, dizziness, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or FDA at… See the full label for the complete list.
Who makes Icatibant?
Icatibant is listed by 7 labelers in the FDA NDC directory, including Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, Cipla USA Inc., Eugia US LLC.