1. Medicines
  2. Neuroscience
  3. AIMOVIG® (erenumab)
  4. Mechanism of Action

Mechanism of Action

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Prescribing Information

Migraine Pathophysiology

 

Migraine is a common and highly debilitating neurological condition.6 It typically presents as a unilateral throbbing/pulsating head pain, which is moderate to severe in intensity and may worsen with physical activity.3-5 Migraine is more than just a bad headache, often involving a range of additional symptoms.3,4

Migraine is a primary headache disorder, and can be classified into two major subtypes according to the International Classification of Headache Disorders 3rd edition (ICHD-3)5:

  • Migraine without aura:
    “Recurrent headache disorder manifesting in attacks lasting 4-72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity and association with nausea and/or photophobia (sensitivity to light) and phonophobia (sensitivity to sound).”5

  • Migraine with aura:
    “Recurrent attacks, lasting minutes, of unilateral fully reversible visual, sensory or other central nervous system symptoms that usually develop gradually and are usually followed by headache and associated migraine symptoms.”5

Migraine can be further categorized as chronic or episodic:

  • Episodic migraine: Headaches occur on less than 15 days per month.5

  • Chronic migraine: Headache occurs on 15 or more days per month for more than 3 months, and has the features of migraine headache on at least 8 days per month5

For more information about the classifications of migraine visit The International Classification of Headache Disorders - ICHD-3.

 

Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in migraine pathophysiology1,3

  • Migraine involves the activation of the trigeminovascular system3
  • CGRP is a 37-amino acid neuropeptide encoded by the calcitonin gene widely distributed in both the CNS and PNS. When CGRP is released in migraine, it is a potent dilator of peripheral and cerebral blood vessels7
  • CGRP (calcitonin gene-related peptide) signaling plays a key role in migraine pathophysiology by modulating nociceptive signaling within the trigeminovascular system1,3
  • Levels of CGRP, within the trigeminal nerve’s sensory fibres, have been shown to increase during a migraine attack1,3
  • The interaction of CGRP with CGRP receptors is believed to contribute to migraine pathophysiology3

 

Aimovig® is the first and only a-CGRP receptor therapy designed to prevent migraine1,2

Aimovig® (erenumab) is a 100% human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor . The CGRP receptor This is located at sites that are relevant to migraine pathophysiology, such as the trigeminal ganglion.1

Aimovig® potently and specifically competes with the binding of CGRP and inhibits its function at the CGRP receptor, and has no significant activity against other calcitonin family of receptors.1,2 Aimovig® has been found to be > 5,000-fold more selective for the CGRP receptor than for other human calcitonin family receptors.2

 

Watch this short video to learn more about the unique mode of action of Aimovig®

 

References

  1. Aimovig SmPC available at www.medicines.ie [accessed July 2021]
  2. Shi L, et al. J Pharmacol Exp Ther 2016; 356: 223-231.
  3. Russo AF. Annu Rev Pharmacol Toxicol. 2015;55:533-552.
  4. What is migraine? Migraine Trust https://migrainetrust.org/understand-migraine/what-is-migraine/#page-sec... [Accessed July 2021]
  5. International Classification of Headache Disorders 3rd edition (ICHD-3) https://ichd-3.org/1-migraine/ [Accessed July 2021]
  6. Neurological Conditions – Migraine. Brain Research UK Migraine – Neurological condition (brainresearchuk.org.uk) [Accessed August 2021]
  7. Amara SG et al. Nature 1982; 298:240–44
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IE 154241 September 2021
Neuroscience
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*AIMOVIG® IS PCRS REIMBURSABLE FOR CHRONIC MIGRAINE PATIENTS WITH THREE OR MORE PREVIOUS PROPHYLACTIC TREATMENT FAILURES.
ABBREVIATED PRESCRIBING INFORMATION

▼ Aimovig® (erenumab) 70 mg and 140 mg solution for injection in pre-filled pen

Important note: Before prescribing, consult full prescribing information.

Presentation: Aimovig 70 mg solution for injection in pre-filled pen. Each pre-filled pen contains 70 mg erenumab. Aimovig 140 mg solution for injection in pre-filled pen. Each pre-filled pen contains 140 mg erenumab.

Indications: Aimovig is indicated for prophylaxis of migraine in adults who have at least 4 migraine days per month.

Dosage and administration: Adults: The recommended dose of Aimovig is 70 mg administered subcutaneously every 4 weeks. Some patients may benefit from a dosage of 140 mg once every 4 weeks. Each 140 mg dose is given either as one subcutaneous injection of 140 mg or as two subcutaneous injections of
70 mg. Aimovig is intended for patient self-administration in the abdomen, thigh, or, if someone else is giving the injection, also into the outer area of the upper arm. Administration should be performed by an individual who has been trained to administer the product. The needle cover of Aimovig prefilled pen contains dry natural rubber, which may cause allergic reactions in individuals sensitive to latex.

Special populations: Paediatric patients: The safety and effectiveness of Aimovig has not been studied in paediatric patients.

Elderly (aged 65 years and over): The safety and effectiveness of Aimovig has not been studied in elderly patients. No dose adjustment is necessary as the pharmacokinetics of erenumab are not affected by age.

Renal impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment.

Hepatic impairment: No studies have been performed in patients with hepatic impairment. Hepatic clearance is not a major clearance pathway for erenumab.

Contraindications: Hypersensitivity to the active substance or to any of the excipients.

Warnings and precautions: Hypersensitivity reactions: Serious hypersensitivity reactions, including rash, angioedema, and anaphylactic reactions, have been reported with erenumab in post-marketing experience. These reactions may occur within minutes, although some may occur more than one week after treatment. In that context, patients should be warned about the symptoms associated with hypersensitivity reactions. If a serious or severe hypersensitivity reaction occurs, initiate appropriate therapy and do not continue treatment with erenumab. Constipation: Constipation is a common undesirable effect of Aimovig and is usually mild or moderate in intensity. In a majority of the cases, the onset was reported after the first dose of Aimovig; however patients have also experienced constipation later on in the treatment. In most cases constipation resolved within three months. In the post marketing setting, constipation with serious complications has been reported with erenumab. In some of these cases hospitalisation was required, including cases where surgery was necessary. History of constipation or the concurrent use of medicinal products associated with decreased gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation related complications. Patients should be warned about the risk of constipation and advised to seek medical attention in case constipation does not resolve or worsens. Patients should seek medical attention immediately if they develop severe constipation. Constipation should be managed promptly as clinically appropriate. For severe constipation, discontinuation of treatment should be considered. Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Latex sensitive individuals: The removable cap of the Aimovig pre-filled pen contains dry natural rubber latex, which may cause Allergic reactions in individuals sensitive to latex Pregnancy, lactation, fertility: Pregnancy: There are a limited amount of data from the use of erenumab in pregnant women. As a precautionary measure it is preferable to avoid the use of Aimovig during pregnancy. Lactation: It is not known whether erenumab is present in human milk. The use of Aimovig could be considered during breastfeeding only if clinically needed. Fertility: There is no data available on the impact of Aimovig on male and female fertility. Animal studies showed no impact on female and male fertility.

Adverse drug reactions: Common (≥1/100 to <1/10): Hypersensitivity reactions including anaphylaxis, angioedema, rash, swelling/oedema and urticaria. Injection site reactions, constipation, muscle spasm, pruritus.

Interactions: No effect on exposure of co-administered medicinal products is expected based on the metabolic pathway of monoclonal antibodies. No interactions with oral contraceptives (ethinyl estradiol and norgestimate) or sumatriptan were observed in studies with healthy volunteers.

Legal Category: POM.

Marketing Authorisation Holder: Novartis Europharm Ltd, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland.

Marketing Authorisation Numbers: EU/1/18/1293/001 006.

Date of last revision of Abbreviated Prescribing Information: September 2020.

Full prescribing information is available upon request from: Novartis Ireland Limited, Vista Building, Elm Park Business Campus, Merrion
Road, Dublin 4, Ireland, Tel: + 353 1 220 4100 or at
www.medicines.ie. Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu.

 

▼ This medicinal product is subject to additional monitoring. Reporting suspected adverse reactions of the medicinal product is important to Novartis and the HPRA. It allows continued monitoring of the benefit/risk profile of the medicinal product. All suspected adverse reactions should be reported via HPRA Pharmacovigilance, website: www.hpra.ie. Adverse events could also be reported to Novartis preferably via www.report.novartis.com or by email: [email protected] or by calling
01 2080 612.