Valeant Pharmaceuticals Introduces Redesigned Migranal Delivery System at the American Headache Society’s 47th Annual Meeting

Additional Data on the Safety and Efficacy of Dihydroergotamine as

a Viable Treatment for Migraine Presented at the Society’s Annual

Meeting

Valeant Pharmaceuticals International (NYSE:VRX) unveiled its redesigned Migranal(R) (dihydroergotamine mesylate, USP) nasal sprayer, and presented supportive data regarding the safety and efficacy of dihydroergotamine in the treatment of migraine at the American Headache Society’s 47th Annual Meeting, which took place from June 23 – 26, in Philadelphia, Pa.

Valeant’s exhibition at the Society’s meeting focused on Migranal, which is indicated in the acute treatment of migraine headache with or without aura. The nasal formulation provides broad receptor coverage(a), acting on central(a) and peripheral pain components in the brain, and has been proven to work at any time during a migraine(1-4). Migranal provides patients with rapid, complete and long-lasting relief(3&5). In fact, 27 percent of patients had resolution of their migraine in 30 minutes, with 86 percent of patients reporting no recurrence of migraine for 24 hours following administration of Migranal(5). As well, Migranal has been shown to be safe, and a well-tolerated formulation. In clinical trials, only 1.4 percent of patients discontinued use due to adverse events, of which the most common were rhinitis, dizziness and facial edema(2&6).

The redesign of the Migranal nasal sprayer improves drug delivery for the patient. The patient is no longer required to break a glass ampule and assemble a complicated delivery system before administering the drug. Now, patients simply open the vial at the time of use, insert a ready-to-use spray pump, secure and prime the pump, and then spray the recommended dose in each nostril.

(a) The clinical significance of this activity is unknown and may be linked to the important safety information listed below.

“The enhancement made to Migranal Nasal Spray is significant in that it allows patients to administer the drug with greater ease, even during a painful migraine,” said Timothy C. Tyson, Valeant’s president and chief executive officer. “The Migranal-product enhancement and the new data presented at the Society’s meeting continue to reflect Valeant’s dedication to providing safe and effective treatment options, while also improving ease-of-use at all levels.”

“A high percentage of migraine patients who are treated with other acute treatments fail to respond completely or have limited response,” said Stephen Silberstein, M.D. at Thomas Jefferson University. “Dihydroergotamines work at multiple receptor sites(a) within both the central(a) and peripheral pain components of migraine. Dihydroergotamine is effective for use any time during a migraine and is an effective first-line therapy.”

Patricia Pozo-Rosich, M.D. from Thomas Jefferson University, on Friday, June 24, presented data from a study titled, “Dihydroergotamine (DHE) Reverses Central Sensitization in the Trigeminal Nucleus Caudalis.” The study investigated the effects of dihydroergotamine in a rat model of migraine.

In addition, five posters surrounding dihydroergotamine were presented and displayed during the Society’s meeting, including:

— “DHE-45 for Migraine with Cutaneous Allodynia (CA)” –

Presented by Stephen Silberstein, M.D. from Thomas Jefferson

University in Philadelphia, Pa.

— “Chronic Headache and Repetitive Dihydroergotamine Nasal Spray

Treatment” – Presented by James Weintraub, DO from the

Michigan Head Pain & Neurological Institute in Ann Arbor,

Mich.

— “Dihydroergotamine Nasal Spray (Migranal NS) For Pre-Emption

of Menstrual/Early Morning Migraines” – Presented by John

Claude Krusz, Ph.D., M.D. from Anodyne Headache and PainCare

in Dallas, Texas.

— “Dihydroergotamine Nasal Spray for Detoxifying Refractory

Headache Patients” – Presented by Lawrence Robbins, M.D. from

Rush Medical College in Northbrook, Ill.

— “Dihydroergotamine Nasal Spray for Relief of Chronic Headache”

– Presented by Michele Fisher, MS, PA-C from Gosy & Associates

Pain Treatment Center in Williamsville, N.Y.

(a) The clinical significance of this activity is unknown and may be linked to the important safety information listed below.

About Migranal(R)

Migranal Nasal Spray is an alternative for migraine relief. The active ingredient used in Migranal Nasal Spray has been used for more than 50 years to safely and effectively treat migraine.

About Valeant

Valeant Pharmaceuticals International (NYSE:VRX) is a global, publicly traded, research-based specialty pharmaceutical company that discovers, develops, manufactures and markets products primarily in the areas of neurology, infectious disease and dermatology. More information about Valeant can be found at www.valeant.com.

IMPORTANT SAFETY INFORMATION

Migranal Nasal Spray is indicated for the acute treatment of migraine with or without aura.

     Serious and/or life-threatening peripheral ischemia has been     associated with the coadministration of dihydroergotamine with     potent CYP3A4 inhibitors including protease inhibitors and     macrolide antibiotics. Because CYP3A4 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.  

Migranal Nasal Spray and D.H.E.45 should not be given to patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal’s variant angina. Migranal and D.H.E.45 also should not be given to patients with uncontrolled hypertension, patients who have used 5-HT1 agonists, ergotamine-containing or ergot-type medications or methysergide within the last 24 hours, or patients with hemiplegic or basilar migraine. Migranal Nasal Spray and D.H.E.45 are also contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery, and severely impaired hepatic or renal function. Migranal Nasal Spray and D.H.E.45 should not be administered to pregnant women or nursing mothers.

Serious cardiac events, including some that have been fatal, have occurred following use of D.H.E.45, but are extremely rare. During clinical studies and the foreign postmarketing experience with Migranal Nasal Spray, there have been no fatalities due to cardiac events.

The most commonly reported adverse events in clinical trials for Migranal Nasal Spray were rhinitis, altered sense of taste, application site reactions, dizziness, nausea and vomiting. Adverse events associated with discontinuation were rhinitis, dizziness, facial edema, cold sweats, accidental trauma, depression, elective surgery, somnolence, allergy, vomiting, hypotension and paresthesia.

Postmarketing experience for D.H.E.45 has occasionally reported vasospasm, parathesia, hypertension, dizziness, anxiety, dyspnea, headache, flushing, diarrhea, rash, increased sweating, and pleural and retroperitoneal fibrosis after long-term use of dihydroergotamine.

 Sources:  (1) Mathew NT. Dosing and administration of ergotamine tartrate and     dihydroergotamine. Headache. 1997;37(suppl 1):S26-S32. (2) Silberstein SD, McCrory DC. Ergotamine and dihydroergotamine:     history, pharmacology, and efficacy. Headache. 2003;43:144-166. (3) Logemann CD, Rankin LM. Newer intranasal migraine medications. Am     Fam Physician. 2000;61:180-186. (4) Goadsby PJ. Is the mechanism of action of dihydroergotamine     unique? Clinical Update on Dihydroergotamine. 1997:3-4. (5) Gallagher RM. Acute treatment of migraine with dihydroergotamine     nasal spray. Arch Neurol. 1996;53:1285-1291. (6) Migranal (package insert). Costa Mesa, Calif.: Valeant     Pharmaceuticals International; 2005.