Treximet

Product
Treximet

Approval Date
April 18, 2008

Release Date
Mid-May (expected)

Companies
GlaxoSmithKline, Pozen

Class
Triptan + non-steroidal anti-inflammatory

Indication
Acute treatment of migraine attacks with or without aura inadults

Active Ingredients
Sumatriptan and Naproxen Sodium

Agency Roster
Euro RSCG Tonic

Marketing Strategy/Execution
Treximet combines the active ingredient in GlaxoSmithKline’s Imitrex with theNSAID naproxen in a pill designed to target multiple mechanisms of migraine.Co-developed by Pozen and marketed by GSK, the drug is set to hit pharmacyshelves by mid-May. Imitrex has rung up blockbuster sales but is losing patentprotection later this year. And insurers may be hesitant to put Treximet ontheir formularies when cheap, generic copies of sumatriptan become available—nomatter how attractive the proposition of having a fixed-dose combinationmigraine drug is to physicians and patients.

The Market

Physician Outlook
Our recent physician research on migraines shows that threein five Neurologists would prescribe Trexima /Treximet once launched, which islarger than the proportion of PCPs who would do so. This mirrors the resultsreported in the previous year thus suggesting that the questions rose inphysician’s minds regarding the safety and efficacy of Treximet due to it longFDA approval timing may not be an impediment to prescription uptake. However,PCP’s are more focused on the move of Imitrex to generic status as well as theOTC availability of generic naproxen sodium rather than Treximet as theirsecond most important improvement needed in the migraine category is cost.

— Kim E. Lazarus, VP, GfK Market Measures

Also in the Pipeline(courtesy of Adis R&D Insight)
No competitor compounds in phase III or pre-registration, US

Pharmacology
Treximet is a combination product that treats migraine headaches viamultiple mechanisms: sumatriptan selectively vasoconstrictsintracranial/extracerebral blood vessels and inhibits trigeminalsensory nerve activation and the release of vasoactive neuropeptides,while naproxen inhibits the production of prostaglandin mediators ofinflammation.

Clinical Trials
The efficacy of Treximet was established in two randomized,double-blind, multicenter, parallel-group studies which used placebo,sumatriptan, and naproxen sodium as comparison treatments.

Adverse Reactions
Dizziness, somnolence, paresthesia, nausea, dyspepsia, dry mouth, GIulcers/bleed, abdominal pain, chest or neck/throat/jaw discomfort/pain,fatigue.

Adults
Swallow whole. 1 tab once; may repeat once after 2 hours; max 2tabs/day. The safety of treating an average of more than 5 migraines ina 30-day period has not been established.

Children
Not recommended.

Contraindications
Aspirin allergy or triad syndrome (asthma, rhinitis, nasal polyps),hypotension with prior NSAID or aspirin use. History, symptoms, orsigns of ischemic cardiac (eg, MI, angina pectoris, silent myocardialischemia), cerebrovascular (eg, stroke, TIA), or peripheral vascular(eg, ischemic bowel disease, Raynaud) syndromes. Vasospastic coronaryartery disease (CAD). Uncontrolled hypertension (HTN). Significantunderlying cardiovascular disease. Basilar or hemiplegic migraine.Coronary artery bypass surgery. Hepatic impairment (esp. elderly).Within 24hrs of ergot-type drugs (eg, methysergide, dihydroergotamine)or other 5-HT₁ agonists. During or within 2 weeks after discontinuing MAO-type A inhibitors.3rd trimester pregnancy.

Precautions
Confirm diagnosis. Avoid excessive use. Likelihood of unrecognizedcoronary artery disease (HTN, hypercholesterolemia, men over age 40,postmenopausal women, obese, smokers, diabetes, strong family history);not recommended; exclude underlying cardiovascular disease, supervise1st dose, consider monitoring ECG. Active peptic ulcer. History of GIdisease or bleeding disorders. Monitor for GI bleed. Severe renaldysfunction (CrCl<30mL/min): not recommended. Impaired renal orhepatic function. Anemia. Asthma. Heart failure. Edema. Dehydration.HTN. Seizure disorders. Elderly. Debilitated. Pregnancy (Cat.C; seeContraindications). Labor & delivery, nursing mothers: notrecommended.

Interactions
Ergotamines, other 5-HT1 agonists, MAOIs: see Contraindications. Avoidaspirin, other NSAIDs. Serotonin syndrome with SSRIs (eg, citalopram,fluoxetine), SNRIs (eg, duloxetine, venlafaxine). May potentiatemethotrexate, lithium. May antagonize diuretics, antihypertensives (eg,?-blockers). Increased risk of renal toxicity with ACEIs, diuretics.Increased risk of GI bleed with oral corticosteroids, anticoagulants(monitor), alcohol. Probenecid increases naproxen levels and delayselimination. May interfere with tests for 17-ketogenic steroids, 5-HIAA.