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Migraines --CGRP--Constipation

Migraine is the most prevalent neurological disorder worldwide and it has immense impact on quality of life. Release of CGRP ( calcitonin gene-related peptide) is released during migraine  induction of migraine attacks. It causes inflammation of coverings of brain leading to pain. Two different classes of drugs blocking CGRP receptors have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor.

Erenumab (brand name Aimovig), targets the calcitonin gene-related peptide receptor (CGPCR) for the prevention of migraine.

Dosing:

Migraine; Prophylaxis




Injection administered in the abdomen, thigh, or upper arm subcutaneously, 70 mg subQ once a month; may go up to 140 mg subQ once a month.




WARNINGS AND PRECAUTIONS--

1. Hypersensitivity Reactions: If a serious hypersensitivity reaction occurs, discontinue administration of AIMOVIG and initiate appropriate therapy. Hypersensitivity reactions can occur within hours to more than one week after administration.

2. Constipation with Serious Complications: Serious complications of constipation may occur.

3. Hypertension: New-onset or worsening of pre-existing hypertension may occur. 

ADVERSE REACTIONS------------------------------ The most common adverse reactions in AIMOVIG clinical studies (occurring in at least 3% of treated patients and more often than placebo) are injection site reactions and constipation.

The gastrointestinal (digestive) tract contains CGRP proteins. Some studies suggest that CGRP may play an important role in maintaining the movement of the bowels.

Dealing with constipation:

There were cases that required hospitalization, including cases where surgery was necessary. In a majority of these cases, the onset of constipation was reported after the first dose of AIMOVIG; however, patients have also presented with constipation later on in treatment. AIMOVIG was discontinued in most reported cases of constipation with serious complications.

Monitor for severe constipation and manage with medications as needed (Docusate, polyethylene glycol, senna, bisacodyl). The concurrent use of medications associated with decreased gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation-related complications. 

Agents causing constipation: Gastrointestinal Agents

  1. Aluminum hydroxide containing Antacids
  2. H2 Receptor Antagonists (e.g. Ranitidine)
  3. Proton Pump Inhibitors (e.g. Omeprazole)
  4. Sucralfate
  5. Ondansetron (Zofran)
  6. Phenothiazines (e.g. Chlorpromazine, Promethazine)

Agents causing constipation: Anticholinergic Medications

  1. See Anticholinergic Medications
  2. Diphenhydramine (Benadryl)
  3. Tricyclic Antidepressants
  4. Oxybutynin

Agents causing constipation: Cardiovascular Medications

  1. Beta-Adrenergic Receptor Agonists
  2. Calcium Channel Blockers

Agents causing constipation: Diabetes Medications

  1. Incretin Mimetics (e.g. Exenatide, Liraglutide )
  2. Pramlintide (Symlin)

Agents causing constipation: others

  1. Alcohol
  2. Opioid Analgesics
  3. Interferon alfa
  4. Levodopa
  5. Cyclosporine (Sandimmune)
  6. Lithium

VII. References

  1. (2013) Prescr Lett 20(6):34
  2. Careyva (2016) Am Fam Physician 94(12): 980-6 [PubMed]





Reference: https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/aimovig/aimovig_pi_hcp_english.ashx

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