The Food and Drug Administration has approved three members of a new class of drugs designed to prevent migraine headaches and known as calcitonin gene-related peptide (CGRP) receptor antagonists. The three drugs are erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality).
Migraine headaches cause severe and debilitating pain that can be accompanied by nausea, vomiting, and heightened sensitivity to light and sound. Migraines are associated with excessive cerebral vasodilation, which is now believed to result from a trigger (such as stress, certain foods, or hormonal changes) that sets off a chain of events originating in the brainstem. The brainstem then produces significant atypical dilation of the cranial blood vessels, which mechanically activates sensory fibers from the trigeminal nerve in the vessel wall. These activated fibers then send pain impulses to the upper brain, which prompts the fibers to release vasoactive substances such as CGRP, which intensifies vasodilation, leading to leaky blood vessels. This induces mast cells to release compounds that cause more sensory nerve fiber stimulation, more release of CGRP, and more vasodilation.
The primary mechanism of action of CGRP receptor antagonists is to block the effects of CGRP. All three drugs are monoclonal antibodies. They are designed to prevent future migraine headaches, not to treat current headaches. All three drugs are given monthly by subcutaneous injection (the site of administration did not alter the rate of absorption). Fremanezumab-vfrm can alternatively be given every three months (quarterly). Patients who need a higher dose of erenumab-aooe may require two injections (one given directly after the other). Prior to starting a monthly schedule, galcanezumab-gnlm requires a loading dose of two injections.
Injection site reactions (such as pain, redness, and itching) are the most common adverse effects of all three drugs. The drugs' labeling states that hypersensitivity reactions are possible, but not common. Erenumab-aooe lists constipation as an additional common adverse effect and warns that the needle cap of the prefilled injector is made of rubber and could cause allergic responses in patients with latex allergies. Otherwise, these drugs are well tolerated.
All three drugs may provoke an immune response (immunogenicity) causing patients to build up antibodies against the drugs. These drugs are broken down by the same pathways as endogenous immunoglobulin G.
Nurses should tell patients to store these medications in the refrigerator. They should also teach patients how to administer these products as monthly subcutaneous injections and provide patients and their families with information about common site reactions and how to recognize signs and symptoms of hypersensitivity reactions. For specific information on administration techniques or clinical trial data, see the label for erenumab-aooe at http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761077s000lbl.pdf, fremanezumab-vfrm at http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761089s000lbl.pdf, and galcanezumab-gnlm at http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761063s000lbl.pdf.