Drugs, Pregnancy & Lactation

Antimigraine agents in pregnancy and lactation


 

Migraine is a common neurovascular disorder with episodic attacks of throbbing headache, nausea/vomiting, photophobia, and phonophobia. Migraine symptoms will lessen in up to 70% of pregnant women, usually during the second and third trimesters, but will worsen in 4%-8%, and new-onset migraine may account for as many as 16% of all cases of the disorder in pregnancy.

Prevention of migraines

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A 2002 review by Goadsby PJ et al. (N Engl J Med. 2002 Jan 24;346[4]:257-70) identified 11 drugs or drug classes for the prevention of migraine attacks. Four agents that are available in the United States were thought to have proven efficacy or were well accepted: metoprolol, propranolol, amitriptyline, and valproate. Valproate should not be used during pregnancy because it is a known teratogen and can cause other fetal problems throughout gestation. Metoprolol, a cardioselective beta-blocker, is a risk for intrauterine growth restriction (IUGR) in the second/third trimesters.

Three other agents are not available in the United States: flunarizine (an agent with calcium channel blocking activity) and two serotonin antagonists, pizotifen and methysergide (a semisynthetic ergot alkaloid). Based on the drug class, flunarizine probably is compatible with pregnancy. Ergot alkaloids, including methysergide, are contraindicated in pregnancy.

Verapamil (Calan, Isoptin) and the selective serotonin reuptake inhibitors (SSRIs) were widely used, but the reviewers concluded that there was poor evidence of benefit.

Use of the SSRI antidepressants in the third trimester may cause newborn toxicity.

Only amitriptyline, verapamil, and low-dose propranolol (30-40 mg/day) have sufficient data to classify as compatible throughout pregnancy, but higher doses of propranolol may cause IUGR and other fetal/neonatal toxicity.

Gerald G. Briggs, clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane

Gerald G. Briggs

Two agents, gabapentin (Neurontin) and topiramate (Topamax), were considered promising agents for migraine prophylaxis. However, topiramate is best avoided in pregnancy. There are inadequate human data to assess the risk of gabapentin and topiramate, therefore both agents should be avoided in the first trimester.

Breastfeeding: Prevention therapy

Based on their potential for harm, topiramate and valproate should not be used during breastfeeding. All of the other drugs probably are compatible with breastfeeding, but the nursing infant should be monitored for adverse effects common in nonpregnant adults.

Acute treatment of migraines

There are 11 single-agent drugs that are indicated for the acute treatment of migraine.

Almotriptan (Axert) is available as an oral tablet. There are no human pregnancy data and the animal data suggest low risk. However, there is a possible risk of preterm birth.

Dihydroergotamine (Migranal, D.H.E. 45) is available for injection and nasal spray. It is contraindicated, especially near term (it has oxytocic properties), and the animal data suggest risk of IUGR.

Eletriptan (Relpax) is an oral tablet. There are no human data and the animal data suggest low risk. There is a possible risk of preterm birth.

Ergotamine (Ergomar), an oral tablet, is contraindicated in pregnancy and breastfeeding (see above and below).

Methysergide (Sansert) is contraindicated but is not available in United States.

Frovatriptan (Frova) has no human pregnancy data. The animal data suggests low risk but there is the possibility of preterm birth.

There are 93 cases in pregnancy for naratriptan (Amerge) but none during breastfeeding. The drug did not cause major defects in animals but did produce dose-related embryo and fetal development toxicity. In addition, the data did suggest a possible increase in preterm births.

For the rizatriptan (Maxalt, Maxalt-MLT) tablet, animal data suggest low risk. There was exposure to the drug in more than 81 human pregnancy cases. Although there was no evidence of birth defects, the data raised the concern of preterm birth.

There is no evidence that sumatriptan (Alsuma, Imitrex, Imitrex Statdose, Sumavel DosePro, Zecuity) is a human teratogen but there is a possible increase in preterm birth. The drug was teratogenic in one animal species. This agent is available as a tablet and for injection.

There is no human pregnancy data for zolmitriptan (Zomig; Zomig-ZMT) but, as with all triptans, there is a possible risk of preterm birth. The animal data suggest low risk. It is available as an oral tablet.

There are three multiagent products that can be used to treat migraines. There are no published human pregnancy data for these combination products. The combination oral drug sumatriptan and naproxen (Treximet) is best avoided in pregnancy because first trimester exposure to the NSAID naproxen may cause embryo-fetal harm (structural anomalies and abortion) or close to term (premature closure of the ductus arteriosus) and other newborn toxicities.

Caffeine and ergotamine (Cafergot, Migergot) tablets should be considered contraindicated in pregnancy and breastfeeding. Although small, infrequent doses of this product do not appear to be fetotoxic or teratogenic, idiosyncratic responses may occur with ergotamine that endanger the fetus.

The third product, acetaminophen, dichloralphenazone, and isometheptene (Epidrin, LarkaDrin, Migragesic IDA) is an over-the-counter tablet. It does not appear to be related to embryo-fetal harm, but its effectiveness is unknown.

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