Valdecoxib-

Concomittant administered of valdecoxib and aspirin may result in an increased risk of gastrointestinal ulcerations. Concomittant administration of valdecoxib with lithium resulted in reduction inlithium serum clerance, decrease in lithium renal serum clerance and increae in serum lithium exposure. Valdecoxib exposure increased with concomittant administration of fluconazole and ketoconazole.

Tizanidine-

Enhanced sedative when co-administered with alcohol sedatives and hypnotics. Concomitant administeration of antihypertensives,especially clonidine, increases the risk of hypotension. Muscle relaxant action is enhanced when co-administered with lithium,propranolol, procainamide and quinidine.

Musculo-skeletal disorders

Dry mouth, somnolence, asthenia, dizziness, phasryngitis, pain, headache, flu syndrome,myalgia.

Severe hepatic impairment Renal impairment Active peptic ulceration disease, Gastrointesatinal bleeding, history of asthma, Urticaria, or other alergic reactions after takingaspirin or other NSAIDs In patients with known hypersentivity to tizanidine orvaldecoxib or its ingredients

Special precations- Elderly, renal impairment, pregnancy,breast feeding, Concomitant of drugs that prolong QT interval Gastrointestinal side effects as bleeding, ulceration of stomach, large intestine and small intestine Anaphylactoid reactions Elevated liver enzymes, pre-existing asthma,fluid tretension and edema.

Musculo-skeletal disorders

Pharmacology- Valecoxib- Valdecoxib actsby inhibition of prostaglandin synthesis primarily through inhibition of cyclooxygenase -2 (COX-2). At therapeutic plasma concentrations in humans valdecoxib does not inhibit cyclooxygenase -1 (Cox-1)

Tizanidine- Is a centrally acting alpha-2 adrenergic agonist, which inhibits the release of excitatory aminoacids in spinal interneurons. It may also act by facilitating the action of glycine.

Pharmacokinetics- Valdecoxib following oral administration peak plasma concentrations are reached in approximately 3 hrs. The absolute biovailability is 83%. Admnistered with a high fat meal, delays the time to peak by 1-2 hrs. 98% of the drug is bound to plasma proteins, The eliminatioin half-life is 8-11 hours. Following oral administration tizanidine is completely absorbed . Half-life is approximately 2.5hrs.Peak effect of the drug is seen 1-2 hrs. The absolute bioavilability of tizanidine is approx 40%,due to extensive first pas metabolism in the liver. Rationale for combination- Tizanidine has been shown to be an effective agent in relieving spasms associated with various conditions, and valdecoxib have beenshown to be en effective and potent NSAID. As with other COX-2 selective inhibitors, valdecoxib apperas to produce less gastrointestinal toxicity than conventional nonselective NSAIDs.

A combination of these agents will be a useful option in improving muscle tone and relieving pain in painful muscle spasms associated with various spinal disorders.

Administered with a high fat meal, delays the time to peak by 1-2 hrs

Excercise caution while using during pregnancy and lactation.