Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

Serum protein binding is constant over the concentration range (0. Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of diclofenac.

This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. The use of aspirin in patients with aspirinsensitive asthma has been associated with severe bronchospasm which can be fatal. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.

Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. Because renal elimination is not a significant pathway of elimination for unchanged diclofenac, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary. The terminal halflife of unchanged diclofenac is approximately 2 hours. No differences in the pharmacokinetics of diclofenac have been detected in studies of patients with renal impairment.

For the relief of osteoarthritis, the recommended dosage is 100150 mg/day in divided doses (50 mg b. For the relief of rheumatoid arthritis, the recommended dosage is 150200 mg/day in divided doses (50 mg t. For the relief of ankylosing spondylitis, the recommended dosage is 100125 mg/day, administered as 25 mg q. Protect from moisture.

Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e. If these occur, patients should be instructed to stop therapy and seek immediate medical therapy. Patients should be informed of the signs of an anaphylactoid reaction (e.

In patients with renal dysfunction, peak concentrations of metabolites 4'hydroxyand 5hydroxydiclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects. However, diclofenac metabolites undergo further glucuronidation and sulfation followed by biliary excretion. One diclofenac metabolite 4'hydroxydiclofenac has very weak pharmacologic activity. Little or no free unchanged diclofenac is excreted in the urine.

Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.

However, animal reproduction studies are not always predictive of human response. There are no adequate and wellcontrolled studies in pregnant women. Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes and tinnitus. Gastrointestinal bleeding can occur.

Voltaren should not be given to patients with the aspirin triad. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Abrupt discontinuation of corticosteroids may lead to disease exacerbation.

Voltaren should be used with caution in patients with fluid retention or heart failure. However, even shortterm therapy is not without risk. 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 a nonsteroidal antiinflammatory drug may cause a dosedependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation.

If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e. This may indicate that they could enhance the toxicity of methotrexate. This response has been attributed to inhibition of renal prostaglandin synthesis. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%.

The molecular weight is 318. Food has no significant effect on the extent of diclofenac absorption. However, there is usually a delay in the onset of absorption of 1 to 4. Diclofenac is more than 99% bound to human serum proteins, primarily to albumin.