Brand Name: DYSMEF FORTE
Generic Name: Mefenamic acid 500 mg + Dicyclomine 20 mg
Preparation: Tablet
Pharmacological Category: Antispasmodic

Mechanism of Action (MOA)
Mefenamic acid inhibits synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase isoenzymes, (COX-I and COX-II). It may also inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity and inhibit neutrophil aggregation.

Dicyclomine shows direct smooth muscle relaxant effects. It also blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands and CNS to some extent.

Pharmacokinetics
Mefenamic acid
Absorption: Absorbed from the gastrointestinal tract
Peak Plasma Concentrations: About 2 to 4hours after ingestion
Protein Binding: More than 90%
Distribution: Distributed in to breast milk
Metabolism: Metabolised by the cytochrome P450 isoenzyme (CYP2C9) to 3- hydroxymethyl mefenamic acid, which may then be oxidised to 3- carboxymefenamic acid
Elimination Half-life: About 2 to 4 hours
Excretion: Urine (over 50%)

Dicyclomine
Absorption: Rapid and well absorbed orally
Peak Plasma Concentrations: 60 to 90 minutes
Protein Binding: Greater than 99%
Distribution: Extensive distribution in tissues
Metabolism: Not available
Elimination Half-life: 1.8 hours
Excretion: Urine (80%); feces (8%)

Indications and Dosage
• Dysmenorrhoea
• Menorrhagia
• Gastro-intestinal spasm
Dose: 1 tab TID

Side Effects
Mefenamic acid
• Common: gastrointestinal discomfort, nausea, diarrhoea
• Others: peptic ulceration, severe gastrointestinal bleeding, drowsiness and effects on the blood such as thrombocytopenia, occasionally haemolytic anemia
• Rare: aplastic anaemia
• Overdosage: Convulsion

Dicyclomine:
• Common: mouth dryness, thirst, reduced bronchial secretions, dilatation of the pupils (mydriasis) with loss of accommodation (cycloplegia) and photophobia, flushing and dryness of the skin, transient bradycardia followed by tachycardia, palpitations, arrhythmias, and difficulty in micturition, as well as reduction in the tone and motility of the gastrointestinal tract leading to constipation and hypersensitivity reactions
• Overdosage: hyperthermia, hypertension, increased respiratory rate, nausea and vomiting; A rash may appear on the face or upper trunk.
• Toxic doses: restlessness, confusion, excitement, ataxia, incoordination, paranoid and psychotic reactions, hallucinations and delirium, and occasionally seizures; in severe intoxication: CNS depression, coma, circulatory and respiratory failure and death

Contraindications
Mefenamic acid: Inflammatory bowel disease, active peptic ulceration, severe heart failure, hypersensitivity to mefenamic acid, aspirin or other NSAIDs

Dicylcomine: Prostatic enlargement, paralytic ileus or pyloric stenosis, myasthenia gravis, angle closure glaucoma or with a narrow angle between the iris and the cornea, children with high ambient temperature

Warnings/ Precautions
Mefenamic acid
• Treatment should be stopped if diarrhoea and rashes occur.
• Blood counts and liver and renal function should be monitored during long-term therapy.
• Drowsiness may affect the performance of skilled tasks.
• May be taken with or after food or milk. Also, H2-antagonist and PPI may be used to reduce the risk of gastrointestinal effects.
• May give a false positive in some tests for the presence of the bile in the urine.
• Caution in patients with hypertension, infections, asthma or allergic disorders, haemorrhagic disorders, impaired renal or hepatic function and history of peptic ulceration.
• Caution in the elderly and may need to be given in reduced doses.

Dicyclomine
• Caution in children and elderly, who may be more susceptible to its adverse effects.
• In patients with ulcerative colitis its use may lead to ileus or megacolon, and its effects on the lower oesophageal sphincter may exacerbate reflux.
• Caution is generally advisable in any patient with diarrhoea.
• May cause blurred vision, dizziness, and other effects that may impair a patient’s ability to perform skilled tasks such as driving.
• Use cautiously in patients with fever because of the risk of provoking hyperthermia.
• Caution in conditions characterized by tachycardia such as thyrotoxicosis, heart failure, and in cardiac surgery, where they may further accelerate the heart rate.
• Care is required in patients with acute myocardial infarction, as ischaemia and infarction may be made worse, and in patients with hypertension.
• May cause confusion, especially in the elderly.
• Reduced bronchial secretion caused may be associated with the formation of mucous plugs.

Drug Interactions
Mefenamic acid
• NSAIDs enhance the effects of oral anticoagulants.
• NSAIDs increase the plasma concentrations of lithium, methotrexate and cardiac glycosides.
• Increased risk of nephrotoxicity if given with ACE inhibitors, cyclosporin, tacrolimus, or diuretics. Increased risk of hyperkalaemia if given with ACE inhibitors and potassium
sparing diuretics.
• The antihypertensive effects of some antihypertensives including ACE inhibitors, beta blockers, and diuretics may be reduced.
• Convulsions may occur if given with quinolones.
• NSAIDs may increase the effects of phenytoin and sulfonylurea antidiabetics.
• Use of more than one NSAID together should be avoided because of the increased risk of adverse effects.
• The risk of gastrointestinal bleeding and ulceration associated with NSAIDs is increased when used with corticosteroids, the SSRIs, the SNRI venlafaxine, the antiplatelets or possibly, alcohol, bisphosphonates or pentoxifylline.
• There may be an increased risk of haematotoxicity if used with zidovudine.
• Ritonavir may increase the plasma concentrations of NSAIDs.

Dicyclomine
• The effects of dicylcomine may be enhanced by use with other drugs having antimuscarinic properties, such as amantadine, some antihistamines, phenothiazines, antipsychotics, and tricyclic antidepressants.
• MAOIs may possibly enhance the effects of dicyclomine.
• The reduction in gastric motility caused by dicyclomine may affect the absorption of other drugs. Dicyclomine may also antagonise the gastrointestinal effects of cisapride, domperidone, and metoclopramide.
• Dicyclomine and parasympathomimetics may counteract each other’s effects.

Pregnancy Category: C; D if used for prolonged periods, or near term (premature closure of ductusarteriosus)

Presentation
DYSMEF FORTE: 10 X 10’s