Gepants are small molecules (unlike the large injectable preventative antibodies), that block the CGRP receptor. They are a new class of medication, and, depending on the agent, can be useful for treating migraines acutely and or preventatively.

Unlike the monthly, injectable, monoclonal antibody preventative medications that target CGRP, gepants are available in pill or orally disintegrating tablet forms. The oral administration, and the short half-life of the gepant medications, may be a more convenient and acceptable treatment option to some people.

As a class of medication, gepants provide a lesser likelihood of acute pain relief at 2 hours than some triptans. It does seem however that they are better tolerated. Many patients with migraine will not take triptans because of side effects such as neck pain, nausea, chest tightening, fatigue, muscle cramps and dizziness. These issues were not seen with the gepants, and used acutely, nausea was the most common side effect, although was noted only slightly above that of a placebo pill. (1.2% vs 0.8%) ¹. Another interesting situation with the medication class, is that their frequent use does not seem to be associated with worsening migraine (Medication Overuse Headache). In fact, fewer migraines occurred over time. This of course led to the agents being studied for preventative treatment.

Considering preventative treatment, the medications can be effective in up to 60% of treated patients with episodic migraine, who may experience a 50% reduction in monthly migraine days. Constipation was the most commonly reported adverse event, observed in ~7% of patients studied ².

There are potential drug interactions for the gepants that are important to consider when prescribing the medications. This relates to processing through a liver pathway (CYP3A4), and therefore use of the medication could alter the effectiveness of other drugs using this same pathway. Your prescribing doctor will require a list of all your medications and will advise accordingly. It is also important to note that none of the gepants are recommended in pregnancy or breastfeeding. The development of the first generation of gepants many years ago were stopped due to liver toxicity, reassuringly however the new generation of gepants has not shown liver abnormalities above the placebo rate.

Recently this medication has been TGA approved and will be available via private prescription in the near future. It is hoped that there will be many patients who may benefit from this additional treatment option.