Chemical Name:Diclofenac Potassium
Therapeutic Category:Anti-inflammatory drugs
Pharmacologic Category:Nonsteroidal anti-inflammatory drug
Composition:Diclofenac Potassium 50mg
DICLOFENAC-K ELSAAD: Each film-coated tablet contains 50 mg Diclofenac Potassium.
2- PHARMACOLOGICAL CLASSIFICATION:
Nonsteroidal anti-inflammatory drugs (NSAIDs).
3- PHARMACOLOGICAL PROPERTIES:
Mechanism of action/pharmacodynamics:
DICLOFENAC-K ELSAAD (diclofenac potassium) is a non steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities.
The mechanism of action of DICLOFENAC-K ELSAAD (diclofenac potassium), like that of other NSAIDs, is related to prostaglandin synthetase inhibition.
Absorption & Bioavailability:
Diclofenac is 100% absorbed after oral administration. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available. Peak plasma levels are achieved approximately after 1 hour.
The apparent volume of distribution (V/F) of diclofenac potassium is 1.3 L/kg.
Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Diclofenac diffuses into and out of the synovial fluid.
Five diclofenac metabolites have been identified in human plasma and urine.
The major diclofenac metabolite, 4'-hydroxy-diclofenac, has very weak pharmacologic activity. The
formation of 4'-hydroxy-diclofenac is primarily mediated by CPY2C9. Both diclofenac and its
oxidative metabolites followed by biliary excretion.
Approximately 65% of the dose is excreted in the urine and approximately
35% in the bile as conjugates of unchanged diclofenac plus metabolites. The terminal half-life of unchanged diclofenac is approximately 2 hours.
DICLOFENAC-K ELSAAD (diclofenac potassium) is indicated:
For treatment of primary dysmenorrhea
For relief of mild to moderate pain
For relief of the signs and symptoms of osteoarthritis
For relief of the signs and symptoms of rheumatoid arthritis
-DICLOFENAC-K ELSAAD (diclofenac potassium) is contraindicated in patients with known hypersensitivity to diclofenac.
-DICLOFENAC-K ELSAAD (diclofenac potassium) should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
The most frequently reported adverse effects occurring are:
Gastrointestinal disturbances including:( abdominal pain, constipation, diarrhea, dyspepsia,
flatulence, gross bleeding, perforation, heartburn, nausea, GI ulcers and vomiting) - Abnormal renal function- anemia –dizziness- edema - elevated liver enzymes – headaches –increased bleeding time – pruritus -rashes and tinnitus.
8- WARNINGS AND PRECAUTIONS:
- Gastrointestinal Risk:
NSAIDs cause an increased risk of serious gastrointestinal adverse events including inflammation ,bleeding ,ulceration ,and perforation of the stomach or intestines , These event can occur at any time during use and without warning symptoms ,elderly patients are at greater risk for gastrointestinal events.
- Cardiovascular And Cerebrovascular Effects:
Appropriate monitoring is required for patients with a history of hypertension and /or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy ,including diclofenac.
Clinical trial and epidemiological data suggest that use of diclofenac particularly at high dose (150mg daily) and in long term treatment may be associated with a small increased risk of arterial thrombotic events.
Patients with uncontrolled hypertension ,congestive heart failure ,established ischemic heart disease ,peripheral arterial disease and/or cerebrovascular disease should only be treated with diclofenac after careful consideration .
Similar consideration should be made before initiating longer term treatment of patient with risk factor of cardiovascular events (e.g. hypertension , hyperlipidemia , diabetes mellitus and smoking).
- Hepatic Effects:
close medical surveillance is required when prescribing DICLOFENAC-K ELSAAD to patients with impairment of hepatic function as their condition may be exacerbated .
As with other NSAIDs , including diclofenac , values of one or more liver enzymes may increase .
During prolonged treatment with diclofenac regular monitoring of hepatic function indicated as a precautionary measure.
If abnormal liver function tests persist or worsen , clinical signs or symptoms consistent with liver disease develop or if other manifestations occur ( eosinophilia, rash) DICLOFENAC –K ELSAAD should be discontinued .
Hepatitis may occur with diclofenac without prodromal symptoms
Caution is called for when using diclofenac in patients with hepatic porphyria , since it may trigger attack.
- In cases with advanced kidney disease, treatment with DICLOFENAC-K ELSAAD is not recommended. If NSAID therapy, however must be initiated, close monitoring of the patient's kidney function is advisable.
- DICLOFENAC-K ELSAAD should be used with caution in all patients with preexisting asthma.
- The use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
- Patients on long-term treatment with NSAIDs, including DICLOFENAC-K ELSAAD, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
In late pregnancy, as with other NSAIDs, DICLOFENAC-K ELSAAD should be avoided.
A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
9- DRUG INTERACTIONS:
- Concomitant administration of diclofenac and aspirin is not generally recommended because of the potential of increased adverse effects.
- Caution should be used when NSAIDs are administered concomitantly with methotrexate, because
they could enhance the toxicity of methotrexate.
a.Diclofenac, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. (e.g. , cyclosporine)
b.NSAIDs may diminish the antihypertensive effect of ACE inhibitors.
c.Diclofenac can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure, as well as to assure diuretic
d.NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
e.The effects of warfarin and NSAIDs on GI bleeding are synergistic.
f.Diclofenac is metabolized by cytochrome P450 enzymes, predominantly by CYP2C9. Co-administration of diclofenac with CYP2C9 inhibitors (e.g.voriconazole) may enhance the exposure and toxicity of diclofenac whereas co-administration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac.
g. Diclofenac may raise plasma concentrations of lithium and digoxin.
10- POSOLOGY AND METHOD OF ADMINISTRATION:
-For treatment of pain or primary dysmenorrhea the recommended dosage is 50 mg t.i.d.
In some patients an initial dose of 100 mg of DICLOFENAC-K ELSAAD (diclofenac potassium) , followed by 50-mg doses, will provide better relief.
-For the relief of osteoarthritis the recommended dosage is 100-150 mg/day in divided doses, 50
mg b.i.d. or t.i.d.
-For the relief of rheumatoid arthritis the recommended dosage is 150-200 mg/day in divided doses,
50 mg t.i.d. or q.i.d.
Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea,
vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal
bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur,
but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and
may occur following an overdose.
Patients should be managed by symptomatic and supportive care following a NSAID overdose.
There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2
g/kg in children) may be indicated in patients seen within 4 hours of ingestion following a large overdose.
12- PACKAGE AND COMPOSITION:
DICLOFENAC-K ELSAAD: 20 Film-coated tablets package.
Store at temperature between (15-30)°C and protect from moisture .