Clinical twisters: Pregnancy limits drug options

January 22, 2007

A 24-year-old woman, R.S., who is two months' pregnant, presents to your ER with a severe migraine that has lasted >48 hours. She reports having several migraines a week since she became pregnant, but until now has successfully "slept them off" in a quiet, dark room. Prior to her pregnancy, R.S. had used zolmitriptan nasal spray (Zomig, AstraZeneca) to abort migraines. She was also using amitriptyline 100 mg daily for prophylaxis. The neurologist on call is debating how to treat R.S. He requests a pharmacist consult. What do you recommend and why?

A 24-year-old woman, R.S., who is two months' pregnant, presents to your ER with a severe migraine that has lasted >48 hours. She reports having several migraines a week since she became pregnant, but until now has successfully "slept them off" in a quiet, dark room. Prior to her pregnancy, R.S. had used zolmitriptan nasal spray (Zomig, AstraZeneca) to abort migraines. She was also using amitriptyline 100 mg daily for prophylaxis. The neurologist on call is debating how to treat R.S. He requests a pharmacist consult. What do you recommend and why?

Upon addressing this case, it's important to remember that a migraine does not increase the risk of complications of pregnancy for the mother or fetus. Incidences of miscarriages, toxemia, abnormal labor, congenital anomalies, and stillbirths among migraineurs are comparable to those of the general population. In addition, it is important to understand that her previously efficacious regimen is no longer acceptable. There is insufficient clinical experience with zolmitriptan in pregnancy. Until more data are available, zolmitriptan should be avoided during pregnancy. Amitriptyline has been associated with teratogenic effects in both humans and animal.

Nonpharmacologic options such as rest and avoidance of light should be considered initially. If these options are insufficient, pharmacologic management may be instituted. Acetaminophen and codeine can be used; aspirin and NSAIDs such as ibuprofen and naproxen can be used as second-line agents. But they should not be used for long periods of time, and not during the last trimester due to the concerns about bleeding and early closure of the ductus arteriosus. If nausea and vomiting become an issue for R.S., metoclopramide can be used safely.

Tim Randolph, Pharm.D.Pharmacy Practice ResidentGaston Memorial HospitalGastonia, N.C.

Migraine is a chronic illness, yet treatment tends to focus on acute episodes, often resulting in ER situations. Despite paltry evidence of efficacy and numerous tolerability issues, narcotics are woefully overutilized for migraine sufferers, both at home and in the ER. More effective, better tolerated, but underprescribed injectable options include dihydroergotamine, sumatriptan (Imitrex, GlaxoSmithKline), valproic acid, magnesium, ketorolac, droperidol, metoclopramide, and corticosteroids.

First any fluid or electrolyte imbalances should be addressed. Next, we'd recommend a dihydroergotamine-antiemetic combination, as endorsed by the American Academy of Neurology, but dihydroergotamine could cause fetal harm. Pregnancy is the rare situation when a narcotic (morphine, hydromorphone-both FDA pregnancy risk factor B drugs) can be a treatment of choice. Intravenous magnesium (Factor B) could also be used.

Regardless of today's ER drug selections, R.S. requires better strategic care. We reject the ridiculous notion of "successfully slept them off," and, furthermore, unconsciousness is impractical for this mother-to-be. Rapid return to normal function is always the treatment goal. The best evidence supports use of migraine-specific drugs at the onset of an attack; unfortunately, many patients wait until their attack reaches a moderate or severe phase before treating. We do not know if R.S. is currently prescribed Zomig, but use at the onset might have avoided today's ER visit. Her use of any triptan should be reported to the manufacturer's pregnancy database.

Given her attack frequency, severity, ineffective prevention, ER visit, and pregnancy, consider referring R.S. to a headache specialist. The National Headache Foundation ( http://www.headaches.org/) lists "Physicians with Added Qualification in Headache Management."

Emphasis on nondrug choices (e.g., biofeedback) is warranted. Furthermore, after childbirth, R.S.' hormone levels, sleep, eating, exercise, and other habits will be strained, perhaps causing more attacks, further illustrating the need for evidence-based comprehensive care.