Tizanidine:

Enhanced sedative effect when co-administered with alcohol, sedatives, and hypnotics. Concomittant administration of anti-hypertensives, especially clonidine, increases the risk of hypotension. Muscle relaxant action is enhanced when co-administerd with lithium, propranalol, procainamide and quinidine.

Mefanamic acid:

Anticoagulant effect of oral anticoagulants may be increased. It reduces excretion of lithium and methotrexate, thereby increases their toxicity. The effect of sulphonylureas is enhanced. Mefanamic acid increases the risk of convulsions with quinolones and nephrotoxicity with cyclosporin It binds strongly to plasma proteins and therefore competition for non-specic sites on plasma occurs.

Painful muscle spasms

Drowsiness, fatigue, dry mouth Nausea, GI disturbances, diarrhea Hypotension, bradycardia, Hallucinations

Altered liver enzymes levels Rashes, Rarely thrombocytopenia, haemolytic anemia,and aplastic anemia

Severe hepatic impairment, renal impairment, active peptic ulceration disease, inflammatory bowel disease, GI bleeding, history of asthma, urticaria, or other allergic reactions after taking NDAIDs. In patients with known hypersensitivity to tizanadine or its ingredients

Special precautions:

Elderly Renal impairment, pregnancy and breast feeding

Concomittant administration of drugs that prolong QT interval.

GI side effects such as bleeding, ulceration of stomach, large intestine, and small intestine.

Anaphylactoid reactions, elevation of liver enzymes, acute prophria, pre-existing asthma, fluid retention, and edema.

Indication:

Painful muscle spasms

Dosage:

Tablet containg tizanidine 2mg + mefanamic acid 500mg three times daily.

Pharmacology:

Tizanidine is acentrally acting alpha 2 adrenergic agonist which include the release of excitatory aminoacids in spiral interneurons.It may also act by facilitating the action of glycine. Tizanidine has shown to reduce the H-reflux in humans and reduce abnormal co-ordination, which may in part contribute to its spasticity effects.The overal efect of these actions is thought to reduce facilitation of spinal motor neurons.

Mefanamic acid inhibits the cyclo-oxygenase enzyme, and thus exerts its anti-inflammatory activity by inhibition of postaglandin synthesis. It exerts the analgesic properties by acting through both central and peripheral pathways.Mefanamic acid is an efective analgesic in doses up to 1.5g daily.

Pharmacokinetics:

Following oral administration, tizanadine is almost completely absorbed . Half-life of tizanidine is approximately 2.5 hrs. Peak effect of the drug is seen 1 to 2 hrs after administration. The absolute bioavailability of tizanidine is approximately 40%, due to an extensive first pass metabolism in the liver and approximately 95% of the administered dose is metabolised.

Mefanamic acid is well absorbed after oral administration(>90%) with the peak plasma concentration occuring at 1-3 hrs. It has a half-life in the range of 3-4 hrs with a volume distribution of approximately 1.3L/Kg. It is 99% protein bound. Mefanamic acid is metabolised by cytochrome P450 enzyme to its metabolites. Approx 52% of mefanamic acid dose is excreted into the urine primarily as glucoronide of the drug itself and its metabolite. Twenty percent of the dose is excreted by the fecal route.

Rationale of the combination:

The goal of the theapy in patients with spasticity and muscular spasms include improvement in functional capacity by improving the muscle tone and relieve discomfort, which includes pain. A combination of an antispasmodic agent and analgesic agent will be ideal to suit both the purposes.

Tizanadine has been shown to be an effective agent in relieving spasms associated with various conditions and mefanamic acid has been shown to be an effective and potent analgesic agent acting by central and peripheral pathways.

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

Not available

Excerse caution while administering to pregnant and lactating mothers.