Icatibant Teva B.V.: Uses, Dosage & Side Effects
A selective bradykinin B2 receptor antagonist for the acute treatment of hereditary angioedema (HAE) attacks in adults, adolescents, and children aged 2 years and older
Icatibant Teva B.V. is a prescription medication containing icatibant, a selective bradykinin B2 receptor antagonist used for the symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults, adolescents, and children aged 2 years and older with C1-esterase-inhibitor deficiency. Administered as a subcutaneous injection, icatibant works by blocking the bradykinin B2 receptor, which is responsible for the excessive vascular permeability that causes the characteristic swelling episodes of HAE. This medication is a generic equivalent of the originator product Firazyr, approved through the European Medicines Agency (EMA).
Quick Facts
Key Takeaways
- Icatibant Teva B.V. is used to treat acute hereditary angioedema (HAE) attacks caused by C1-esterase-inhibitor deficiency, providing rapid symptom relief typically within 2 hours.
- It is administered as a single 30 mg subcutaneous injection and can be self-administered at home after proper training from a healthcare professional.
- The most common side effects are injection site reactions (redness, swelling, warmth, itching), which are generally mild and self-resolving.
- A maximum of 3 doses (90 mg) may be administered within 24 hours, with at least 6 hours between each dose.
- Icatibant is not suitable for long-term prevention of HAE attacks and should not be used as prophylactic therapy.
What Is Icatibant Teva B.V. and What Is It Used For?
Icatibant Teva B.V. contains the active substance icatibant, a synthetic decapeptide that acts as a selective and competitive antagonist at the bradykinin B2 receptor. Hereditary angioedema is a rare genetic disorder characterized by recurrent episodes of severe swelling (angioedema) that can affect the skin, gastrointestinal tract, upper airways, and other organs. These attacks are caused by a deficiency or dysfunction of C1-esterase inhibitor, a key regulatory protein in the complement and contact activation systems.
In patients with HAE, the deficiency of C1-esterase inhibitor leads to uncontrolled activation of the kallikrein-kinin system, resulting in excessive production of bradykinin. Bradykinin is a potent vasoactive peptide that binds primarily to B2 receptors on vascular endothelial cells, causing vasodilation and increased vascular permeability. This leads to the extravasation of plasma into surrounding tissues, producing the characteristic swelling and pain of HAE attacks.
By selectively blocking the bradykinin B2 receptor, icatibant interrupts this pathological cascade at a critical point, preventing bradykinin from exerting its vasodilatory and permeability-increasing effects. Clinical trials have demonstrated that icatibant provides statistically significant and clinically meaningful improvement in HAE symptoms compared to placebo, with a median time to onset of symptom relief of approximately 2 hours.
Icatibant Teva B.V. is a generic version of the originator product Firazyr, which was first authorized in the European Union in 2008. As a generic medicine, Icatibant Teva B.V. has been demonstrated to be bioequivalent to Firazyr, meaning it contains the same active substance, has the same pharmaceutical form and strength, and produces the same plasma levels of the drug in the body. It is approved for use in the European Union and other markets worldwide.
HAE affects an estimated 1 in 50,000 people globally. While attacks are unpredictable and can vary in frequency and severity, they can be life-threatening when they involve the larynx (throat), as airway obstruction can occur. Abdominal attacks can cause severe pain, nausea, vomiting, and diarrhea, and are sometimes misdiagnosed as surgical emergencies. Having an effective on-demand treatment like icatibant available is therefore crucial for patients with HAE to manage acute episodes promptly and reduce the risk of complications.
What Should You Know Before Taking Icatibant Teva B.V.?
Contraindications
Icatibant Teva B.V. is contraindicated in patients with known hypersensitivity to icatibant or to any of the excipients listed in the product formulation. If you have experienced an allergic reaction to icatibant in the past, you should not use this medication again. Although rare, allergic reactions including urticaria, rash, and pruritus have been reported in clinical studies and post-marketing surveillance.
Warnings and Precautions
Before using Icatibant Teva B.V., inform your healthcare provider about all your medical conditions, particularly:
- Ischemic heart disease or unstable angina: Bradykinin is thought to play a cardioprotective role. Blocking the B2 receptor may theoretically reduce this protection. Clinical data in patients with acute coronary syndromes are limited, so caution is advised.
- Recent stroke: Similar cardiovascular considerations apply to patients who have recently experienced a cerebrovascular event. The risk-benefit balance should be carefully evaluated.
- Laryngeal attacks: While icatibant has been used to treat laryngeal HAE attacks, patients should be advised to seek immediate medical attention in a facility equipped to manage potential airway compromise, even after administering icatibant. Laryngeal attacks are potentially life-threatening.
- Concurrent ACE inhibitor use: Angiotensin-converting enzyme (ACE) inhibitors work in part by reducing the degradation of bradykinin. Since icatibant blocks the bradykinin B2 receptor, the theoretical reduction in ACE inhibitor efficacy should be considered. However, clinically significant interactions have not been formally studied.
If you experience swelling in the throat or difficulty breathing during an HAE attack, administer icatibant immediately and then seek emergency medical care. Laryngeal attacks can rapidly progress to life-threatening airway obstruction. Do not delay seeking medical help even after self-administering icatibant.
Self-administration of icatibant should only be performed by patients who have been adequately trained by a healthcare professional. Patients should be taught to recognize the early signs of an HAE attack and understand when to administer the medication, how to perform the subcutaneous injection, and when to seek additional medical help. The first self-administered injection should ideally be performed under medical supervision.
Pregnancy and Breastfeeding
Icatibant is not recommended for use during pregnancy unless clearly necessary. Animal reproductive studies have shown adverse effects at doses exceeding the human therapeutic dose, including reduced implantation rates and embryo-fetal developmental effects. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should use effective contraception during treatment with icatibant.
It is not known whether icatibant or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to refrain from icatibant therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman. Given the short duration of treatment (single injection for acute attacks), the clinical significance may be limited.
Animal studies with icatibant at doses up to 2.5 times the maximum recommended human dose did not reveal any adverse effects on male or female fertility. However, reversible impairment of sperm motility was observed at higher doses. The relevance of these findings to human fertility is uncertain.
How Does Icatibant Teva B.V. Interact with Other Drugs?
Icatibant is a synthetic peptide that is metabolized by proteolytic enzymes rather than cytochrome P450 (CYP) enzymes. This means it is unlikely to participate in traditional pharmacokinetic drug-drug interactions involving CYP enzyme inhibition or induction. No formal clinical drug interaction studies have been conducted with icatibant. However, based on its mechanism of action and pharmacological properties, several theoretical interactions should be considered.
Because icatibant blocks the bradykinin B2 receptor, it may theoretically attenuate the pharmacological effects of medications that work through the bradykinin pathway. ACE inhibitors, which are widely used for hypertension and heart failure, exert part of their therapeutic effect by preventing the breakdown of bradykinin. By blocking the receptor that bradykinin acts on, icatibant could potentially reduce the efficacy of ACE inhibitors during the period of its activity.
It is important to note that the half-life of icatibant is short (approximately 1-2 hours), so any theoretical interaction with ACE inhibitors would be transient. Nevertheless, patients taking ACE inhibitors should inform their healthcare provider and be monitored appropriately when using icatibant for an acute HAE attack.
| Interacting Drug | Type | Effect | Recommendation |
|---|---|---|---|
| ACE Inhibitors (e.g., enalapril, ramipril, lisinopril) | Pharmacodynamic (theoretical) | Icatibant may attenuate the antihypertensive and cardioprotective effects of ACE inhibitors by blocking the bradykinin B2 receptor | Use with caution; monitor blood pressure. Interaction is transient due to short half-life of icatibant |
| Angiotensin II Receptor Blockers (ARBs) | None expected | ARBs do not act through the bradykinin pathway; no interaction anticipated | No dose adjustment required |
| Recombinant C1-esterase inhibitor (e.g., Berinert, Ruconest) | Pharmacodynamic (complementary) | Both target the same pathological cascade but via different mechanisms; may have additive benefit | Can be used sequentially if needed; no contraindication to combined use |
| Tranexamic acid | None clinically significant | Different mechanisms of action; tranexamic acid inhibits fibrinolysis while icatibant blocks B2 receptors | No known interaction; can be used concomitantly |
| Lanadelumab (prophylactic anti-kallikrein antibody) | None clinically significant | Different targets in the kallikrein-kinin pathway; icatibant can be used for breakthrough attacks | Icatibant can be used as rescue therapy for breakthrough attacks during lanadelumab prophylaxis |
Interactions with Food and Alcohol
No specific food interactions have been identified with icatibant. The medication is administered by subcutaneous injection, so gastrointestinal absorption is not relevant. No studies have examined the interaction between icatibant and alcohol. However, since HAE attacks themselves can cause significant symptoms, patients are generally advised to avoid alcohol during acute attacks to prevent masking of symptoms and dehydration.
What Is the Correct Dosage of Icatibant Teva B.V.?
Icatibant Teva B.V. is supplied as a ready-to-use, pre-filled syringe containing 30 mg of icatibant in 3 mL of solution. The injection is administered subcutaneously (under the skin) into the abdominal area. Treatment should be initiated as early as possible after the onset of an HAE attack, as early treatment is associated with faster symptom relief and shorter attack duration.
Adults (18 years and older)
Standard Dose
One subcutaneous injection of 30 mg (one pre-filled syringe) into the abdominal area at the onset of symptoms. If symptoms persist or recur after 6 hours, a second 30 mg injection may be administered. If symptoms persist after a further 6 hours, a third injection may be given. Maximum dose: 3 injections (90 mg) per 24 hours.
| Patient Group | Single Dose | Maximum in 24h | Route | Notes |
|---|---|---|---|---|
| Adults (≥18 years) | 30 mg (3 mL) | 90 mg (3 injections) | Subcutaneous (abdomen) | Min. 6 hours between doses |
| Adolescents (12-17 years, ≥40 kg) | 30 mg (3 mL) | 90 mg (3 injections) | Subcutaneous (abdomen) | Same as adult dose; supervised use recommended |
| Children (2-11 years) | Weight-based dosing | Weight-based (max 3 doses) | Subcutaneous (abdomen) | Administered by healthcare professional; dose based on body weight |
| Elderly (≥65 years) | 30 mg (3 mL) | 90 mg (3 injections) | Subcutaneous (abdomen) | No dose adjustment required; limited data in elderly patients |
| Renal impairment | 30 mg (3 mL) | 90 mg (3 injections) | Subcutaneous (abdomen) | No dose adjustment required |
| Hepatic impairment | 30 mg (3 mL) | 90 mg (3 injections) | Subcutaneous (abdomen) | No dose adjustment required (metabolized by proteolysis, not hepatic enzymes) |
Children and Adolescents
Icatibant has been approved for use in children and adolescents aged 2 years and older based on pharmacokinetic modeling, clinical data from the FAST-3 pediatric sub-study, and post-marketing experience. For adolescents weighing 40 kg or more, the adult dose of 30 mg applies. For children aged 2 to 11 years, the dose is calculated based on body weight. Administration in younger children should be performed by or under the supervision of a healthcare professional.
The safety and efficacy of icatibant in children under 2 years of age have not been established. No data are available in this age group, and use is not recommended.
Elderly Patients
No dose adjustment is necessary in elderly patients (65 years and older). However, clinical experience with icatibant in elderly patients is limited. The pharmacokinetic properties of icatibant are not expected to be significantly altered in elderly patients, as the drug is metabolized by proteolytic enzymes rather than hepatic enzymes. Standard dosing recommendations apply, but patients should be monitored for any unusual adverse effects.
Missed Dose
Icatibant is not taken on a regular schedule. It is used as needed for acute HAE attacks. Therefore, the concept of a missed dose does not apply in the traditional sense. Patients should administer icatibant as soon as possible after recognizing the symptoms of an acute HAE attack. Delaying treatment may result in a longer time to symptom relief and potentially more severe attack episodes.
Overdose
No cases of overdose with icatibant have been reported in clinical trials or post-marketing experience. In clinical studies, single doses of up to 3.2 mg/kg body weight (approximately 7 times the recommended dose) were administered intravenously without significant adverse effects beyond those observed at therapeutic doses. In the event of a suspected overdose, the patient should be monitored and supportive care should be provided as needed. There is no specific antidote for icatibant.
What Are the Side Effects of Icatibant Teva B.V.?
Like all medicines, icatibant can cause side effects, although not everybody gets them. The safety profile of icatibant has been well characterized through clinical trials involving over 900 patients and extensive post-marketing surveillance. The most frequently observed adverse reactions are local injection site reactions, which occur in the vast majority of patients but are generally mild and transient.
The frequency categories below are defined according to the Medical Dictionary for Regulatory Activities (MedDRA) convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and not known (frequency cannot be estimated from available data).
Very Common
Affects more than 1 in 10 patients
- Injection site reactions (erythema/redness, swelling, warmth, itching, pain, burning, induration, numbness) — reported in up to 97% of patients in clinical trials; typically mild to moderate and resolve within 1-6 hours
Common
Affects 1 to 10 in every 100 patients
- Nausea
- Headache
- Dizziness
- Pyrexia (fever)
- Rash
- Elevated liver transaminases
Uncommon
Affects 1 to 10 in every 1,000 patients
- Urticaria (hives)
- Pruritus (generalized itching)
- Abdominal pain (not related to HAE attack)
- Vomiting
- Erythema (generalized redness)
Rare
Affects 1 to 10 in every 10,000 patients
- Hypersensitivity reactions
- Anaphylactoid reactions
Injection site reactions are the most commonly reported side effect and occur in almost all patients. These typically appear within minutes of injection and may include redness, swelling, warmth, itching, burning, and pain at the injection site. These reactions are caused by the local pharmacological action of icatibant on bradykinin B2 receptors in the skin and are not allergic reactions. They are generally mild to moderate, do not require treatment, and resolve on their own within 1 to 6 hours.
If you experience any side effects that are severe, persistent, or concerning, contact your healthcare provider. Seek immediate medical attention if you develop signs of a serious allergic reaction such as difficulty breathing, severe swelling of the face or throat, rapid heartbeat, or a drop in blood pressure.
Long-Term Safety
Long-term safety data from open-label extension studies and post-marketing surveillance have not identified any new safety signals beyond those observed in controlled clinical trials. Patients who use icatibant repeatedly for multiple HAE attacks over time do not appear to develop tolerance (reduced efficacy) or experience cumulative toxicity. The short half-life of icatibant (1-2 hours) means that the drug is rapidly cleared from the body after each administration.
How Should You Store Icatibant Teva B.V.?
Proper storage of icatibant is essential to maintain the medication's efficacy and safety. The pre-filled syringes should be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze the product. If the solution has been frozen, it must be discarded and not used.
For convenience, particularly for patients who need to carry the medication with them for emergency use, icatibant may be stored at room temperature (up to 25°C / 77°F) for a single continuous period of up to 12 months. Once removed from the refrigerator, the product must not be returned to refrigerated storage. If not used within the 12-month room temperature period, the product must be discarded. It is recommended to note the date of removal from the refrigerator on the outer carton to track storage time.
Keep the pre-filled syringe in its original packaging to protect from light. Do not use icatibant after the expiry date stated on the syringe label and carton. Before injection, visually inspect the solution. The solution should be clear and colorless. Do not use the product if the solution is cloudy, discolored, or contains visible particles.
- Shelf life (refrigerated): As stated on the packaging (typically 3 years from manufacture)
- Room temperature storage: Up to 12 months at not more than 25°C (single period, do not return to refrigerator)
- Do not freeze
- Protect from light: Keep in original packaging
- Keep out of reach and sight of children
Dispose of used syringes in an appropriate sharps disposal container according to local requirements. Do not dispose of medications via household waste or wastewater. Ask your pharmacist how to properly dispose of medications you no longer use.
What Does Icatibant Teva B.V. Contain?
Each pre-filled syringe of Icatibant Teva B.V. contains the following:
Active Substance
- Icatibant (as acetate) — 30 mg per 3 mL (10 mg/mL)
Icatibant is a synthetic decapeptide with the chemical structure H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH. It has a molecular weight of approximately 1,304 daltons. The acetate salt form is used for improved stability and solubility.
Excipients (Inactive Ingredients)
- Sodium chloride — used as a tonicity agent to make the solution isotonic with body fluids
- Glacial acetic acid — pH adjuster to ensure solution stability
- Sodium hydroxide — pH adjuster
- Water for injections — solvent
This medicine contains less than 1 mmol sodium (23 mg) per dose, which means it is essentially sodium-free. This is relevant for patients on a sodium-restricted diet.
Description of the Product
Icatibant Teva B.V. is supplied as a clear, colorless solution for injection in a pre-filled glass syringe fitted with a stainless steel needle. Each syringe is designed for single use only. The syringe is presented in a blister pack within an outer carton. The product is intended for subcutaneous use only and should not be administered by any other route (intravenous, intramuscular, etc.).
Frequently Asked Questions About Icatibant Teva B.V.
Icatibant Teva B.V. is a generic version of Firazyr, the original branded icatibant product. Both medications contain the same active substance (icatibant 30 mg), have the same pharmaceutical form (solution for injection in pre-filled syringe), and work in the same way. Icatibant Teva B.V. has been demonstrated to be bioequivalent to Firazyr through rigorous regulatory evaluation. The main differences may be in packaging, price, and availability. Generic medications typically cost less than their branded counterparts, potentially improving patient access to this important treatment.
No, icatibant is an on-demand treatment for acute HAE attacks only. It is not approved or recommended for the prevention (prophylaxis) of HAE attacks. For long-term prevention, other medications are available, including C1-esterase inhibitor concentrates (Cinryze, Berinert), lanadelumab (Takhzyro), and berotralstat (Orladeyo). Your healthcare provider can help you determine the most appropriate prophylactic treatment for your specific situation.
You should inject icatibant as soon as possible after recognizing the symptoms of an acute HAE attack. Clinical experience suggests that early treatment leads to faster symptom resolution and shorter overall attack duration. Patients are encouraged to carry their icatibant syringes with them at all times so they can treat an attack immediately, wherever they are. Delaying treatment may result in more severe symptoms and a longer recovery period.
While icatibant is specifically approved for hereditary angioedema (HAE), there has been growing clinical interest and evidence supporting its use in ACE inhibitor-induced angioedema, which is also mediated by bradykinin. Several case reports, case series, and small clinical trials have shown promising results. However, this remains an off-label use and is not included in the approved product labeling. The decision to use icatibant for ACE inhibitor-induced angioedema should be made by a specialist physician based on individual clinical circumstances.
Icatibant may have minor influence on the ability to drive and use machines. Some patients experience dizziness after injection. If you feel dizzy after administering icatibant, you should not drive or operate machinery until the symptom has resolved. It is also important to consider that the HAE attack itself may significantly impair your ability to perform these activities due to pain, swelling, and other symptoms.
If your symptoms persist or return after the first injection, you may administer a second dose of icatibant at least 6 hours after the first injection. If symptoms still persist, a third dose may be given at least 6 hours after the second injection. The maximum dose is 3 injections (90 mg) within a 24-hour period. If your symptoms do not improve after 3 injections or if you are concerned about the severity of your attack, seek immediate medical attention. Laryngeal attacks always warrant emergency medical care, even after self-treatment.
References
- European Medicines Agency (EMA). Icatibant Teva B.V. - Summary of Product Characteristics. EMA/CHMP/2020. Available at: www.ema.europa.eu
- Cicardi M, Banerji A, Bracho F, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010;363(6):532-541. doi:10.1056/NEJMoa0906393
- Lumry WR, Li HH, Levy RJ, et al. Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011;107(6):529-537.
- Maurer M, Magerl M, Betschel S, et al. The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update. World Allergy Organ J. 2022;15(3):100627. doi:10.1016/j.waojou.2022.100627
- Zuraw BL, Busse PJ, White M, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363(6):513-522.
- Bas M, Greve J, Stelter K, et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015;372(5):418-425. doi:10.1056/NEJMoa1312524
- World Health Organization (WHO). Model List of Essential Medicines - 23rd list, 2023. Geneva: World Health Organization.
- Bork K, Siedlecki K, Bosch S, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc. 2000;75(4):349-354.
- Caballero T, Farkas H, Bouillet L, et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol. 2012;129(2):308-320.
- British National Formulary (BNF). Icatibant. National Institute for Health and Care Excellence (NICE). Available at: bnf.nice.org.uk
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in immunology, allergy medicine, and clinical pharmacology.
iMedic Medical Editorial Team — Specialists in clinical pharmacology and immunology with documented academic background and clinical experience in rare disease management.
iMedic Medical Review Board — Independent panel of medical experts who review all content according to international guidelines (WHO, EMA, FDA, WAO/EAACI).
Evidence Standard: All medical claims in this article are based on Level 1A evidence from systematic reviews, randomized controlled trials, and international consensus guidelines. Content follows the GRADE evidence framework.
Conflict of Interest: The iMedic Medical Editorial Team has no commercial relationships with pharmaceutical companies. All content is independently produced without industry funding or sponsorship.
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