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New Safety Warnings! Dihydroergotamine (DHE 45 INJECTION, MIGRANAL NASAL SPRAY) for Migraine Headache

Worst Pills, Best Pills Newsletter article November, 2002

On July 31, 2002, the strongest type of drug safety warning that the Food and Drug Administration (FDA) can require, a black box warning, was added to the professional product labeling, or “package insert,” for the migraine headache drug dihydroergotamine (DHE 45 INJECTION, MIGRANAL NASAL SPRAY). The new warning involved numerous drug interactions between dihydroergotamine and other drugs that can raise the blood levels of dihydroergotamine leading to a life-threatening contraction of blood...

On July 31, 2002, the strongest type of drug safety warning that the Food and Drug Administration (FDA) can require, a black box warning, was added to the professional product labeling, or “package insert,” for the migraine headache drug dihydroergotamine (DHE 45 INJECTION, MIGRANAL NASAL SPRAY). The new warning involved numerous drug interactions between dihydroergotamine and other drugs that can raise the blood levels of dihydroergotamine leading to a life-threatening contraction of blood vessels (vasospasm) that can block the flow of blood to the brain and other areas of the body.

Dihydroergotamine should only be used where a clear diagnosis of migraine headache has been established and should not be used for chronic daily administration.

The complete text of the black box warning appears below.

The new warning states that dihydroergotamine should not be used together with drugs that inhibit a particular liver enzyme that breaks down, or metabolizes, dihydroergotamine, known as CYP 3A4. These drugs are: the anti-fungals ketoconazole (NIZORAL) and itraconazole (SPORANOX); the protease inhibitors used for HIV-AIDS ritonavir (NORVIR, KALETRA), nelfinavir (VIRACEPT), and indinavir (CRIXIVAN); and the antibiotics erythromycin (ERYTHROCIN, EES), clarithromycin (BIAXIN), and troleandomycin (TAO). The use of these drugs results in the inability to clear dihydroergotamine from the body and causes the drug to accumulate.

Other less potent CYP 3A4 inhibitors also pose a risk and should be used with caution in combination with dihydroergotamine. These include saquinavir (INVIRASE), nefazodone (SERZONE), fluconazole (DIFLUCAN), grapefruit juice, fluoxetine (PROZAC), fluvoxamine (LUVOX), zileuton (ZYFLOR), and clotrimazole (MYCELEX).

Dihydroergotamine is one of a number of drugs that have FDA-approved written information specifically for patients. Unfortu-nately, it appears that many pharmacists do not distribute the FDA-approved information. Rather, patients are given written information produced by unregulated commercial information vendors that often is inaccurate or omits important safety information or both.

Because there are a number of very serious adverse reactions associated with the use of dihydroergotamine we have reprinted sections of the FDA-approved patient information for dihydroergotamine nasal spray below. This information could be much better with the addition of more detail. The information for the nasal spray is essentially the same as that for the injectable form of the drug.

What You Can Do

If you are now using dihydroergotamine for the treatment of migraine headache and have answered yes to any of the questions posed, talk to your doctor immediately about another treatment.

Excerpts From the FDA Approved Patient Information for Dihydroergotamine Nasal Spray:

Do not use Migranal (dihydroergotamine) Nasal Spray if you:

• are pregnant or nursing.
• have any disease affecting your heart, arteries, or circulation.
• are taking certain anti-HIV medications (protease inhibitors).
• are taking a macrolide antibiotic such as troleandomycin, clarithromycin or erythromycin.

Important questions to consider before using Migranal (dihydroergotamine) Nasal Spray

Please answer the following questions before you use your Migranal (dihydroergotamine) Nasal Spray. If you answer YES to any of these questions or are unsure of the answer, you should talk to your doctor before using Migranal (dihydroergotamine) Nasal Spray.

• Do you have high blood pressure?
• Do you have chest pain, shortness of breath, heart disease, or have you had any surgery on your heart arteries?
• Do you have risk factors for heart disease (such as high blood pressure, high cholesterol, obesity, diabetes, smoking, strong family history of heart disease, or you are postmenopausal or a male over 40)?
• Do you have any problems with blood circulation in your arms or legs, fingers, or toes?
• Are you pregnant? Do you think you might be pregnant? Are you trying to become pregnant? Are you sexually active and not using birth control? Are you breast feeding?
• Have you ever had to stop taking this or any other medication because of an allergy or bad reaction?
• Are you taking any other migraine medications, erythromycin or other antibiotics, or medications for blood pressure prescribed by your doctor, or other medicines obtained from your drugstore without a doctor’s prescription?
• Do you smoke?
• Have you had, or do you have, any disease of the liver or kidney?
• Is this headache different from your usual migraine attacks?
• Are you using Migranal (dihydroergotamine) Nasal Spray or other dihydroergotamine mesylate containing drugs on a daily basis?
• Are you taking a protease inhibitor for HIV therapy?
• Are you taking a macrolide class of antibiotic?

Serious or potentially life-threatening reductions in blood flow to the brain or extremities have been reported rarely due to interactions between Migranal (dihydroergotamine) Nasal Spray and protease inhibitors or macrolide antibiotics.

REMEMBER TO TELL YOUR DOCTOR IF YOU HAVE ANSWERED YES TO ANY OF THESE QUESTIONS BEFORE YOU USE MIGRANAL (dihydroergotamine) NASAL SPRAY.

Side Effects [adverse reactions] To Watch Out For

In clinical trials, most migraine patients have used Migranal (dihydroergotamine) Nasal Spray without serious side effects. You may experience some nasal congestion or irritation, altered sense of taste, sore throat, nausea, vomiting, dizziness, and fatigue after using Migranal (dihydroergotamine) Nasal Spray. These side effects are temporary and usually do not require you to stop using Migranal (dihydroergotamine) Nasal Spray. Although the following reactions rarely occur, they can be serious and should be reported to your physician immediately:

• Numbness or tingling in your fingers and toes
• Pain, tightness, or discomfort in your chest
• Muscle pain or cramps in your arms and legs
• Weakness in your legs
• Temporary speeding or slowing of your heart rate
• Swelling or itching

 

 New Black Box Warning for Dihydroergotomine

WARNING
Serious and/or life-threatening perpheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics.  Because CYP 3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased.  Hence, concomitant use of these medications is contraindicated.

Disclaimer

The information on this website is not intended to substitute for professional medical advice, diagnosis, or treatment. Consult your doctor before changing or discontinuing any medication.