Indications and Usage:
● Soft tissue injuries with spasm and inflammation,
● Neck / shoulder / back pain,
● Tendonitis / tenosynovitis / bursitis
● Musculoskeletal disorders
Rationale of Combination:
Product Description:
Given the multiple pathways involved in body's perception of pain, a combination therapy is well suited for pain management. Diclofenac acts by attenuation of peripheral prostaglandin synthesis(primarily) and has marked anti-inflammatory properties. Paracetamol acts centrally and inhibits brain prostaglandin synthesis which may partly account for its well documented activity to reduce fever and to induce analgesia. Chlorzoxazone being a centrally acting muscle relaxant, relieves muscular spasms. The combination exerts a better pain control due to action on different pathways of pain.
Pharmacology:
Diclofenac Potassium:
Diclofenac is a NSAIDs with anti-inflammatory, analgesic and antipyretic properties. It is rapidly and almost completely absorbed when administered as an oral dose. Food does not have a significant effect on the extent of oral absorption. At therapeutic concentrations it is more than 99% bound to plasma proteins. Diclofenac and/or its metabolites are rapidly and preferentially taken up and retained in inflamed tissues. It penetrates synovial fluid where concentrations may persist even when plasma concentrations fall. The terminal half-life is about 1 to 2 hours. Diclofenac acts by inhibiting cyclooxygenase, thus prevents the formation of prostaglandins, the mediators of inflammation. It also inhibits lipoxygenase thus preventing the synthesis of leukotrienes. Thus it acts on both the pathways and is a very potent anti-inflammatory drug/ medicine.
Paracetamol:
Paracetamol is an effective analgesic-antipyretic (relieves mild to moderate pain) and a weak anti-inflammatory agent. Paracetamol reduces fever by a direct action on the heat regulating centres to increase the dissipation of heat. It is readily absorbed from the g.i. tract with peak plasma concentrations occurring about 10 to 60 min. after oral administration. It is distributed into most body tissues.
Chlorzoxazone:
Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. It acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles. Blood levels of chlorzoxazone can be detected in people during the first 30 min. and peak levels may be reached, in about 1 to 2 hours after oral administration.
Adverse Effects:
● Drowsiness, dizziness, light- headedness, malaise, or overstimulation may be noted by an occasional patient.
● Rarely, a patient may note discoloration of the urine resulting from a phenolic metabolite of chlorzoxazone.
● Pregnancy & Lactation - Not recommended in pregnant and lactating women.
Contraindications:
Contraindicated in patients with known hypersensitivity to any of the ingredients.
Drug Interactions:
Diclofenac may increase the plasma concentrations of lithium, digoxin and methotrexate. It may increase the activity of anticoagulants, inhibit the activity of diuretics, enhance cyclosporine nephrotoxicity and precipitate convulsions when co-administered with quinolone derivatives. The risk of paracetamol toxicitymay be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce hepatic microsomal enzymes. Co-administration of paracetamol with rifampicin, isoniazid, chloramphenicol, antiepileptic drugs and antiviral drugs may be avoided. Metclopromide may incraese the absorption of paracetamol whereas excretion and plasma concentration may be altered when co-administered with probeneacid. The concomitant use of chlorzoxazone with alcohol or other CNS depressants may have an additive effect.
Over Dosage:
Overdosage may cause nausea, vomiting, pain abdomen, dizziness, somnolence, headache, sweating, pancreatitis, hepatic failure and acute renal failure. Treatment, if required, includes gastric lavage, activated charcoal and other symptomatic measures as per medical advic.