Tizanidine is a short-acting drug for the management of spasticity. Tizanidine is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons.
Indications:
•Trauma Surgery: In sports injuries, sprains, laceration, fractures, dislocation and osteoarthritis etc. It reduces inflammation and pain thus helps faster healing and repair.
• Surgery: Reduces Post Operative Edema at injection sites. Reduces internal tissue edema and inflammation caused at post-operative handling. Reduction in edema reduces chances of rupture at tissue site as well as risk of graft rejection along with reduction in pain .
• Plastic Surgery: Reduces Post Operative Edema and restores micro-circulation at the site of graft rejection.
• Respiratory Medicine: Breaks down complex sputum molecules in smaller peptides with lower viscosity, helping in expectorating them more easily. Reduced viscosity of secretion helps in better antibiotic penetration to enable control over stubborn infections like bronchitis, lung abscess and bronchectasis. Nimesulide helps in controlling pain and inflammation.
• Infections: Mucolytic activity in sinuses, ear cavities and anti-inflammatory activity in upper respiratory tract organs help in faster resolution, better antibiotic bioavailability and faster cure rates.
• Dermatology: Used in acute painful inflamed dermatoses.
• Dentistry: Helps better control over dental infections and inflammation.
• Obstetrics & Gyneacology: The anti-inflammatory activity helps in resolution of post- partum haematomas, breast engorgements and pregnancy-related thrombophlebitis.
Rationale of Combination:
Product Description
Various inflammatory painful conditions in which NSAIDs are used are often accompanied with muscle spasm. Since, Tizanidine is a myotonolytic agent and is helpful in management of muscular spasm, the combination of the two drugs will be helpful in managing such conditions. It is seen that the overall consumption of NSAIDs for the management of pain is reduced when Tizanidine is given in combination to NSAIDs. Tizanidine helps in improving the gastric safety profile of NSAIDs when given with them.
Pharmacology:
Nimesulide
Nimesulide - After oral administration of Nimesulide 50 to 200 mg to healthy adult volunteers, peak serum concentrations of 1.98 to 9.85 mg/L are achieved within 1.22 to 3.17 hours. The drug is extensively bound (99%) to plasma proteins and has an estimated apparent volume of distribution of 0.19 to 0.35 L/kg following oral administration. Nimesulide is extensively metabolised (1 to 3% of a dose is excreted unchanged in the urine) to several metabolites which are excreted mainly in the urine (≈ 70%) or the faeces (≈ 20%). The elimination half-life of 4- Hydroxy-Nimesulide ranges from 2.89 to 4.78 hours and is generally similar to or slightly higher than that of the parent compound (1.56 to 4.95 h).
Tizanidine
Tizanidine - Moderate interpatient variation has been demonstrated in the pharmacokinetics of Tizanidine, but maximum plasma concentrations appear to be reached in 0.75 to 2 hours after administration. Between 53 and 66% of the dose is absorbed and food has no effect on the pharmacokinetics of this drug.The bioavailability of Tizanidine is estimated to be 21% and there is a low propensity for plasma protein binding (about 30%). Extensive first-pass metabolism of Tizanidine occurs, with less than 3% of unchanged drug excreted. Total recovery analysis indicated that 19 to 23% of the administered dose is excreted in the faeces, and 53 to 66% in the urine.
Adverse Effects:
Nimesulide
• Gastrointestinal disturbances
• Epigastralgia,
• Nausea
• Diarrhoea
• Rash and pruritus
Tizanidine
• Dry mouth
• Drowsiness
• Hallucinations
• Muscle weakness and dizziness
Contraindications:
• Hypersensitivity to any of the ingredients of the preparation.
• Contraindicated in patients of active peptic ulcer disease, moderate to severe hepatic impairment and severe renal failure.
• Should be used with great caution in patients with compromised renal function, cirrhosis of liver, congestive heart failure, renovascular disease or those who are volume or salt depleted.
Drug Interactions:
Nimesulide
Nimesulide - Due to the extensive plasma protein binding Nimesulide may be displaced from the binding site by concurrent administration of Fenofibrate, Salicylic acid, Valproic acid and Tolbutamide. Moreover, Nimesulide may displace Salicylic acid, Methotrexate and Furosemide from binding sites. Nimesulide reduced the diuretic effect for concomitantly administered Furosemide. Although Nimesulide does not appear to interact with Warfarin, in clinical practice, interaction with oral anticoagulants or other highly protein bound drugs cannot be ruled out. Nimesulide may cause enzymatic induction of Theophylline when administered concomitantly with it. Nimesulide had no significant effect on fasting blood and glucose tolerance in patients treated with anitdiabetic agents.
Tizanidine
Tizanidine - Coadministration of other antihypertensive drugs including diuretics may cause hypotension and bradycardia. Other sedatives such as alcohol, barbiturates and benzodiazepines may enhance the sedation or drowsiness caused by Tizanidine.
Precautions and Warning:
Usage in pregnancy and nursing mothers:
No well-controlled studies are available regarding the use of nimesulide or Tizanidine in pregnancy and lactation. Avoid the use of this medicament in such cases.
Potentially fatal
Nimesulide possesses a risk of hepatotoxicity