The mean peak plasma concentration of 1. Significant drug plasma concentrations persist when levels would have dropped almost to baseline values following entericcoated tablet administration. In pharmacokinetic studies no accumulation of diclofenac sodium was found following repeated once daily administration of diclofenac sodium slow release 100 mg tablets or repeated twice daily administration of diclofenac sodium slow release 75 mg tablets.

If such symptoms develop, this drug should be discontinued and an ophthalmologic examination performed. Ophthalmic examination should be carried out at periodic intervals in any patient receiving this drug for an extended period of time. Although these pharmacokinetic interactions do not appear to be clinically relevant, there is no proven advantage in using these two medications together.

If this drug is to be used in the presence of impaired liver function, it must be done under strict observation. Caution is called for when using diclofenac sodium in patients with hepatic porphyria, since diclofenac sodium may trigger an attack. Physicians should be alert to the development of infection in patients receiving the drug.

No accumulation occurs provided the recommended dosage intervals are observed. Enteric coating may delay the onset of absorption from 25 and 50 mg tablets. The bioavailability remains the same under both conditions.

The mean changes were observed to be less than 1 second in both instances, and are unlikely to be clinically important. Persistently abnormal or worsening renal, hepatic or hematological test values should be followed up carefully since they may be related to therapy. Fatalities have occurred on occasion, particularly in the elderly.

Suppositories have a more rapid onset, but slower rate of absorption than oral entericcoated tablets. Cmax is approximately 2/3 of that produced by an equivalent 50 mg entericcoated tablet oral dose. Tmax occurs within 1 hour.

As with other prostaglandin inhibitors, this applies particularly to the last 3 months of pregnancy, because of the possibility of uterine inertia and/or premature closing of the ductus arteriosus. The highest diclofenac level observed in the breast milk of 6 patients receiving oral diclofenac sodium doses of 350 mg day 1, followed by 250 mg day 2, was smaller than 5 ng/g. By extrapolation, an infant of 3 kg, consuming 500 g/day (with a maximum concentration of 5 ng/g) of breast milk, would receive less than 0.

Dosage adjustment may be required. Dosage adjustment of lithium may be required. Special caution is therefore recommended and frequent laboratory tests should be performed to check that the desired response to the anticoagulant is being maintained.

From a clinical efficacy standpoint, diclofenac sodium 75 mg has activity similar to 3. Although diclofenac sodium does not alter the course of the underlying disease, it has been found to relieve pain, reduce fever, swelling and tenderness, and increase mobility in patients with rheumatic disorders of the types listed. The plasma concentrations show a linear relationship to the amount of drug administered.

These patients appear to have a higher risk for development of adverse reactions. The dosage should be reduced to the lowest level that will provide control of symptoms adjusted when necessary and closely supervised. Safety and dosages for the pediatric age group have not been established.

Adverse reactions reported in clinical trials and spontaneous reports are summarized below.

In these cases lower doses of diclofenac should be considered. Urine output, serum urea, and serum creatinine should be carefully monitored. During longterm therapy, kidney function should be monitored periodically.

This elevation above plasma concentrations can be maintained for up to 12 hours. The synovial fluid elimination halflife is at least 3 times greater than that for plasma. These phenolic metabolites are largely inactive, and (along with the parent compound) are mostly converted to glucuronide conjugates.

If peptic ulceration is suspected or confirmed, or if gastrointestinal bleeding occurs, diclofenac sodium should be discontinued, appropriate treatment instituted and the patient closely monitored. The safety in pregnancy and lactation has not been established and its use is therefore not recommended. It should only be used during pregnancy for the most compelling reasons, and then only at the lowest effective dose.

Concomitant treatment with potassiumsparing diuretics may be associated with increased serum potassium, thus making it necessary to monitor levels. Elevated blood concentrations of methotrexate may occur, increasing toxicity. Statistically significant changes in prothrombin and partial thromboplastin times have been reported in normal volunteers.

About 1% of an oral dose is excreted unchanged in urine. Known or suspected hypersensitivity to the drug. Fatal anaphylactoid reactions have occurred in such individuals.

These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. Patients manifesting abnormal liver function test voltaren tablets sr 75 mg, or signs or symptoms that suggest liver dysfunction, should be evaluated for evidence of progression to a more severe hepatic reaction, while on therapy with diclofenac sodium. If abnormal liver function test results persist or worsen, or if systemic manifestations or clinical signs consistent with liver disease develop, discontinue diclofenac sodium treatment.

In humans there have been reports of acute interstitial nephritis with hematuria, proteinuria, and occasionally nephrotic syndrome. In patients with prerenal conditions leading to reduction in renal blood flow or blood volume, renal prostaglandins have a supportive role in the maintenance of renal perfusion. Patients at greatest risk are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, and the elderly.

The apparent volume of distribution is 0. Singledose (oral or i. Synovial fluid concentrations exceed plasma levels within 4 to 6 hours of administration.

Liver function should be monitored during longterm treatment with this drug. Minimize hepatic injury risk by informing patients of hepatotoxicity symptoms. Patients will then be alerted that nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness and "flulike" symptoms, are signs of possible liver injury.

Bone marrow functional abnormalities, although rare, could have severe consequences. Diclofenac sodium should be used with caution in patients with cardiac decompensation, hypertension, renal diseases and in those recovering from surgical operations under general anesthesia and other voltaren tablets sr 75 mg predisposing to fluid retention. Serum electrolytes should be monitored periodically during longterm therapy, especially in those patients at risk.



The mean terminal drug halflife in plasma is 1. In humans about 60% of the drug and its metabolites are eliminated in the urine and the balance through bile in the feces. More than 90% of an oral dose is accounted for in elimination products within 72 hours.

The mode of action is not fully known but it does not act through the pituitaryadrenal axis. Diclofenac inhibits prostaglandin synthesis by interfering with the action of prostaglandin synthetase. This inhibitory effect may partially explain its actions.

Patients experiencing these symptoms should be made aware that these side effects may occur, and be cautioned against operating machinery or motor vehicles should they experience any of these. Appropriate treatment should be instituted and the patient should be closely monitored. Patients on longterm diclofenac sodium treatment should have their hemopoietic system evaluated periodically.

Suppositories are contraindicated in patients with any inflammatory lesions of rectum or anus and in patients with recent history of rectal or anal bleeding. Patients should be instructed to contact their physician immediately if they experience symptoms or signs suggestive of peptic ulceration or gastrointestinal bleeding. These reactions can occur at any time during treatment, without warning symptoms or signs.