Source: Registered Drug Product Database (NG) Publisher: Manufactured by: JIANGSU RUINIAN QUANJIN PHARM. CO. LTD., Chuanbu Village, Dingshu Town, Yixing City, Jiangsu Provide China Marketed by: FRESHBORN INDUSTRIES LTD., Plot 18, Jesus Estate, Ijegun Egba, Satellite Town, Lagos State, Nigeria
Pharmacotherapeutic category: non-steroidal anti-inflammatory drugs (NSAIDs)
It is therapeutic sub group classification: musculo-skeletal system/anti-inflammatory and anti-rheumatic products/non-steroids/acetic acid derivatives and related substances
Diclofenac as Injection is a nonsteroidal agent with marked analgesic/antiinflammatory properties. It is an inhibitor of prostaglandin synthetase, (cyclooxygenase). Diclofenac Potassium in vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to the concentrations reached in human beings. When used concomitantly with opioids for the management of post-operative pain, diclofenac Potassium often reduces the need for opioids.
The analgesic efficacy of Diclofenac 25, 50 and 75 mg injection was evaluated in two pivotal dental pain studies. Patients with moderate to severe pain following dental impaction surgery were included in these studies. In one study the analgesic efficacy of Diclofenac 25, 50 and 75 mg/ml subcutaneously administered was compared to placebo. Diclofenac at all strengths produced a statistically significant higher pain relief (as measured on the VAS) compared to placebo.
Pharmacotherapeutic group: Other Analgesics and Antipyretics
Paracetamol is a clinically proven analgesic and antipyretic. Paracetamol may act predominantly by inhibiting prostaglandin synthesis in the central nervous system and to a lesser extent through a peripheral action by blocking pain impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation. Paracetamol produces antipyresis by acting centrally on the hypothalamic heat-regulating center to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in thehypothalamus.
Intramuscular injection:
After administration of Diclofenac 75 mg/ml as injection by the i.m. route, absorption is rapid and the mean peak ug/ml equals approximately 8 μmol/L) reached is after 34 minutes.
The area under the concentration curve AUC0-t is 250.07 ± 46.89 μg/ml.min. I mean peak plasma concentration for intramuscular Diclofenac (75mg/3ml) is 2.242 ± 0.566 μg/ml which is reached - after is 246.70 ± 27 39 minutes. 74μg/ml and AUC after i.m. administration is about twice as large as it is following oral or rectal administration as this route avoids "first pass" metabolism.
Subcutaneous injection:
After administration of Diclofenac 75 mg/ml as injection by the s.c. route, absorption is rapid and the mean peak plasma concentrations of 2.138 ± 0.646 μg/ml (2.5 μg/ml equals Approximately 8 μmol/l) is reached is 261.94 in ± 4053 min.2
In comparative clinical studies the mean peak plasma concentration for intramuscular Voltarol is 2.242 ± 0.566 μg/ml at 27 minutes and the AUC0-t is 246.70 ± 39.74 μg/mlA.min. subcutaneous dose of 75 mg of Diclofenac was bioequivalent to an intramuscularly administered dose of Voltarol 75 mg/3 ml in terms of AUC and Cmax. The AUC after subcutaneous administration is about twice as large as it is following oral or rectal administration as this route avoids "first-pass" metabolism. Dose linearity in terms of AUC has been demonstrated for diclofenac absorbed after subcutaneous administration. Cmax was found to be not proportional to dose, withmean Cmax values of 1090 ng/ml, 1648.9 ng/ml and 1851.1 ng/ml with the 25 mg, 50 mg and 75 mg dose of Diclofenac respectively.
The active substance is 99.7% protein bound, mainly to albumin (99.4%). Diclofenac enters the synovial fluid, where maximum concentrations are measured 2-4 hours after the peak plasma values have been attained. The apparent half-life for elimination from the synovial fluid is 3-6 hours. Two hours after reaching the peak plasma values, concentrations of the active substance are already higher in the synovial fluid than they are in the plasma and remain higher for up to 12 hours.
Biotransformation of diclofenac takes place partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and methoxylation, resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.
Total systemic clearance of diclofenac in plasma is 263 ± 56 mL/min (mean value ± SD). The terminal half-life in plasma is 1-2 hours. Four of the metabolites, including the two active ones, also have short plasma half-lives of 1-3 hours. About 60% of the administered dose is excreted in the urine in the form of the glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% is excreted as unchanged substance. The rest of the dose is eliminated as metabolites throughthe bile in the faeces.
No relevant age-dependent differences in the drug's absorption, metabolism or excretion have been observed.
In patients suffering from renal impairment, no accumulation of the unchanged active substance can be inferred from the singledose kinetics when applying the usual dosage schedule. At a creatinine clearance of Paracetamol.
Paracetamol is distributed throughout most body tissues. About 25% of Paracetamol in blood is bound to plasma proteins. The plasma half-life is 1.25 to 3 hours but may be increased by liver damage and following overdose. Paracetamol is metabolized in the liver. About 85% of a dose of Paracetamol is excreted in urine as free and conjugated Paracetamol within 24 hours.
No new preclinical safety studies have been performed on Potassium diclofenac. The safety profile of the medicinal product is well-established. The local tolerance study demonstrated that the formulation does not present any significant unexpected local 16th May 2016 Diclofenac & Paracetamol 19 toxicity by either the intramuscular or subcutaneous routes of administration.
Not available.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.