Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old.
Dicyclomine is an anticholinergic that blocks muscarinic receptors. Dicyclomine is used to treat intestinal hypermotility, the symptoms of Irritable Bowel Syndrome (IBS) (also known as spastic colon). It is a smooth muscle relaxant.

Indications:

Dicyclomine:
• Colicky pain
• Irritable bowel syndrome(IBS)

Nimesulide:
• Painful inflammatory conditions associated with -
• Musculoskeletal system, Dysmenorrhea, Thrombophlebitis, Gout
• Dental pain
• ENT infection
• Osteoarthritis
• Rheumatoid arthritis
• Gynecological disorder
• Low back pain
• Post operative pain
• Fever

Rationale of Combination:

Product Description:
This Non Steroidal Anti Inflammatory Drug, Nimesulide reduces prostaglandin synthesis by the inhibition of cyclo oxygenase enzyme2 selectively. This is a weaker inhibition .So it produces weaker analgesic property. Its potent anti-inflammatory activity is due to its action on various stages of inflammation. Dicyclomine is an anticholinergic drug. It exerts its action by inhibiting muscarinic (((cholinergic))) receptors on smooth muscles and prevents the effect of Acetylcholine. Inhibition of Acetylcholine produces relaxation of smooth muscles of gastrointestinal tract and genitourinary tract and reduces the painful spasm and cramp. Thus combination is indicated in G.I spasm, Dysmenorrhea, Rheumatoid arthritis, Pain, Inflammation and Fever.

Pharmacology:

Nimesulide:
Absorption: Completely absorbed after oral administration.
Distribution: Widely distributed in the body and extensively bind to the plasma proteins i.e.99%.
Metabolism: It is metabolized in liver to its metabolites.4-hydroxyl derivative is its one active metabolite.
Excretion: Excreted via urine and bile.

Dicyclomine:
Absorption: About 70 % of the drug is absorbed after oral administration.
Distribution: It is extensively distributed in tissue mainly in protein bound (((99%))) form. It readily crosses blood brain barrier.
Metabolism: Dicyclomine undergoes hepatic metabolism.
Excretion: It is excreted mainly in the urine and small amount in the faeces.

Adverse Effects:

Nimesulide:
● Nausea
● Diarrhea
● Heart burn
● Skin rash/ Pruritis
● Headache
● Somnolence

Dicyclomine:
• Constipation
• Dry mouth
• Nausea
• Abdominal discomfort
• Palpitations
• Tachycardia
• Urine retention

Contraindications:

Dicyclomine:
●Hypersensitivity to Dicyclomine and other anticholinergic drugs
●Narrow angle glaucoma
●Obstructive gastro intestinal tract
●Reflux oesophagitis
●Severe ulcerative colitis
●Myasthenia gravis
●Unstable cardiovascular status in acute haemorrhage

Nimesulide:

● Hypersensitivity to this drug
● Active peptic ulcer
● Hepatic impairment

Drug Interactions:

Nimesulide:
Fenofibrate, Salicyclic acid, Valproic acid and Tolbutamide: These drugs displace nimesulide from the plasma binding sites.
Methotrexate and Frusemide: These drugs may be displaced from plasma proteins by nimesulide.
Warfarin: Exercise caution since efficacy may be increased.
Theophylline: Efficacy of slow release theophylline preparations reduced.

Dicyclomine:
Possible antagonism is indicated with Donepezil, rivastigmineand galantamine. May cause additional anticholenergic effects and enhanced adverse toxic effects if coadministered with trospium and tripolidine.
● Avoid alcohol.
● Take this medication 30 minutes before meals.

Precautions and Warning:
The medication should be taken with care by pateints suffering the following ailments:
● Renal impairment
● Heart failure
● Alcohol abuse
● Colitis
● Crohns disease
● Hemarrhoids
● Hepatic failure
● Rectal irritation or bleeding
● Renal impairment
● Hyperthyroidism
● Autonomic neuropathy
● Hypertension
● Coronary artery disease