Zolterol SR

Diclofenac Na.

Zolterol SR Tablet 75mg: active ingredient: Diclofenac sodium 75 mg.
Zolterol SR Tablet 100mg: active ingredient: Diclofenac sodium 100 mg.

Pharmacology: Prostaglandins are known to contribute significantly in the pathogenesis of inflammation, pain and fever. The formation of precursors of prostaglandins and thromboxanes from arachidonic acid is reduced in the presence of diclofenac as it inhibits the activity of the enzyme cyclo-oxygenase.
As an antirheumatic and anti-inflammatory drug, diclofenac may act peripherally in inflamed tissues and block pain impulse generation possibly by reducing prostaglandin activities and inhibition of synthesis and actions of the local mediators involved in such responses.
Diclofenac also works as an antipyretic by acting centrally on the hypothalamic heat-regulating centre to increase peripheral vasodilation which then increases blood flow through the skin, sweating and heat loss. This central action in the hypothalamus may be due to the reduction of prostaglandin activity.
Pharmacokinetics: Diclofenac is almost completely absorbed from the SR tablet. The peak plasma concentration of Zolterol SR tablet is lower than the conventional tablet as it is released more slowly. Absorption of Zolterol SR tablet is slower when taken with or after meal than when taken in an empty stomach. However, the amount of diclofenac absorbed is not affected by food.
No accumulation in plasma happens after repeated oral administration if the recommended dosage intervals are adhered to. More than 99% of diclofenac is bound to plasma proteins at therapeutic level. Diclofenac also penetrates synovial fluid where its concentration might persist even when plasma concentrations fall.
Only about 50% of diclofenac reaches the systemic circulation in the unchanged form due to first-pass metabolism through the liver. Diclofenac is metabolised mainly by glucuronidation after hydroxylation. For patients suffering from impaired hepatic function (chronic hepatitis, non-decompensated liver cirrhosis), the pharmacokinetics and metabolism of diclofenac are similar in patients without liver disease.
The terminal half-life of diclofenac is 1-2 hours. Most of the dose (65%) is eliminated in the forms of glucuronide and sulphate conjugates in the urine and the rest in the form of metabolites through the bile (about 35%) in the faeces. Less than 1% is excreted as unchanged. In patients with impaired renal function, no accumulation of diclofenac has been reported.

Zolterol SR tablet is indicated for the chronic therapy of the following conditions: musculoskeletal and joint disorders such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and spondyloarthritis; peri-articular disorders such as bursitis and tendinitis; non-articular rheumatism; painful syndromes of the vertebral column; soft tissue disorders such as sprains and strains; and painful postoperative and post-traumatic inflammation and swelling.

Adult: One 100 mg SR tablet or one 75 mg SR tablet daily (i.e. maximum daily dose 100 mg). It should be swallowed whole with liquid, do not crush or chew. In the case of elderly patients and patients with low body weight, the initial dosage is 75-100 mg daily. For chronic treatment and in mild cases, a dose of one 75 mg SR tablet daily is sufficient. If symptoms are most severe during the night or in the morning, Zolterol SR tablet should be taken preferably in the evening.
To minimize the potential risk for an adverse cardiovascular event, the lowest effective dose for the shortest possible duration should be used.
Route of administration: Oral.

Overdosage of diclofenac produces no typical clinical picture. However the recommended treatment is to prevent absorption by emptying the stomach via gastric lavage and administering activated charcoal.
Instituting supportive and symptomatic treatment is necessary for complications such as renal failure, respiratory depression, hypotension, convulsions and gastrointestinal effects.

Diclofenac is contraindicated in patients suffering from peptic ulcer disease/haemorrhage, or those having a history of gastrointestinal bleeding or perforation related to previous NSAID therapy, active, or history of recurrent peptic ulcer/haemorrhage, or history of hypersensitivity to diclofenac, aspirin or other NSAIDs.
Diclofenac is also contraindicated (i) in patients with severe heart failure and (ii) for the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery.
Similar to other NSAIDs, diclofenac should not be prescribed to patients having attacks of asthma and allergic reaction, such as allergic rhinitis, urticaria, angioedema or skin rash that are precipitated by aspirin or other NSAIDs and during pregnancy.

Risk of GI Ulceration, Bleeding and Perforation with NSAID: Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time, with or without warning symptoms, in patients treated with NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common, usually developing early in therapy, prescribers should remain alert for ulceration and bleeding in patients treated with NSAIDs even in the absence of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Patients with prior history of serious adverse events and other risk factors associated with peptic ulcer disease (e.g. alcoholism, smoking and corticosteroid therapy) are at increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less than other individuals and account for most spontaneous reports for fatal GI events.

Patients are advised as a precautionary measure to monitor their renal function, hepatic function, blood counts and signs of hypersensitivity reactions during prolonged treatment with diclofenac.
In patients with kidney, liver or cardiac impairment and coagulation defects, diclofenac has to be used cautiously and doses kept as low as possible. Renal functions of these patients should be monitored.
In rare cases, diclofenac has been associated with serious liver injury.
Like other NSAIDs, diclofenac may trigger allergic reactions including anaphylactic reactions even if the patient is receiving the medication for the first time.
Patients should inform physician immediately if symptoms such as chills, fever or muscle aches and pains occur shortly before or together with a skin rash as these symptoms may indicate a serious reaction to the medication.
Patients experiencing central nervous effects such as dizziness or blurred vision should not drive or operate machinery.
Cardiovascular and Cerebrovascular Risk: Treatment with diclofenac is not recommended in patients with pre-existing cardiovascular disease or cerebrovascular disease, or presenting risk factors for cardiovascular disease. For these patients, treatment options other than NSAIDs, particularly COX-2 inhibitors and diclofenac, should be considered first.
Diclofenac, particularly at higher doses (150 mg per day), is associated with an increased risk of serious cardiovascular adverse events (such as myocardial infarction, stroke or thrombotic events which can be fatal) that is comparable to COX-2 inhibitors. Evidence suggests that the risk may increase with the dose and duration of use.
There is no consistent evidence that the concurrent use of aspirin mitigates the possible increased risk of serious cardiovascular thrombotic events associated with NSAID use.
Hypertension: NSAIDs may lead to the onset of new hypertension or worsening the pre-existing hypertension and patients taking antihypertensive with NSAIDs may have an impaired antihypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure could be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.
Heart Failure: Fluid retention and oedema have been observed in some patients taking NSAIDs, therefore caution is advised in patients with fluid retention or heart failure.
Gastrointestinal Risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. Caution is advised in patients with risk factors for gastrointestinal events e.g. the elderly, those with the history of serious gastrointestinal events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the drug should be withdrawn immediately.
Doctors should warn patient about signs and symptoms of serious gastrointestinal toxicity.
The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse events.
Renal Effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of diclofenac in patients with advanced renal disease. Therefore, treatment with diclofenac is not recommended in these patients with advanced renal disease. If therapy must be initiated, close monitoring of the patient's renal function is advisable.
Severe Skin Reactions: Severe cutaneous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), have been reported with diclofenac sodium. Patients treated with diclofenac sodium should be closely monitored for signs of hypersensitivity reactions. Discontinue diclofenac sodium immediately if rash occurs.
Use in Pregnancy & Lactation: Diclofenac should not be given during pregnancy because of possible risks such as the premature closure of the ductus arteriosus leading to persistent pulmonary hypertension in the newborn and suppression of uterine contractility.
The amount of diclofenac that passes into the breast milk is in such small quantity that no unwanted effects on the infant are likely to occur.
Use in Children: Due to the high active substance content, Zolterol SR tablet is not recommended for children.
Use in the Elderly: Should be used with caution in geriatrics, as they are susceptible to side effects of diclofenac especially gastrointestinal bleeding and ulceration/perforation. In cases where gastrointestinal ulceration and bleeding occurs during treatment, Zolterol SR tablet should be discontinued with advice from physician.

Diclofenac should not be given during pregnancy because of possible risks such as the premature closure of the ductus arteriosus leading to persistent pulmonary hypertension in the newborn and suppression of uterine contractility.
The amount of diclofenac that passes into the breast milk is in such small quantity that no unwanted effects on the infant are likely to occur.

Side effects are variable in severity and frequency. Gastrointestinal epigastric pain, nausea, vomiting and diarrhoea are occasionally reported. Dyspepsia may be minimised by taking with food or milk.
Other side effects include hypersensitivity reactions (such as rashes, angioedema, bronchospasm), headache, dizziness, vertigo, photosensitivity, loss of hair, haematuria and hearing disturbances (e.g. tinnitus).
Blood disorders and fluid retention may occur. Renal failure may be provoked especially in patients with pre-existing renal impairment. Elevation of serum aminotransferase activity in the liver has been occasionally reported.

Diclofenac has been reported to increase the plasma concentrations of digoxin and lithium when used concurrently, therefore their levels should be monitored.
Although clinical studies have shown that diclofenac prescribed together with oral antidiabetic agents does not influence their efficacy, isolated cases have been reported of hypoglycaemic and hyperglycaemic reactions leading to an adjustment in the dosage of antidiabetic drugs.
Concurrent use of potassium-sparing diuretics may increase the serum potassium levels leading to hyperkalaemia.
Concomitant administration of corticosteroids, glucocorticoids or potassium supplements may increase the risk of gastrointestinal side effects.
Patients receiving diclofenac and anticoagulant or thrombolytic therapy concomitantly may induce gastrointestinal ulceration or bleeding.
With usual doses, diclofenac may be less likely to significantly alter platelet aggregation than other NSAIDs.
Concurrent use of two or more NSAIDs, including aspirin is not recommended since it may increase the risk of gastrointestinal side effects, including ulceration or haemorrhage. Inhibition of renal prostaglandin activity by NSAIDs may increase the risk of cyclosporine-induced nephrotoxicity.
Concurrent use with methotrexate may increase the risk of agranulocytosis or bone marrow depression. Therefore, NSAID therapy should not be resumed until the methotrexate plasma concentration has decreased to a non-toxic level, usually at least 12 hours.

Store below 25°C in a cool dry place.
Protect from moisture and heat.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AB05 - diclofenac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.

P₁S₁S₃