Novartis has informed healthcare professionals regarding changes in the Warnings and Precautions section of the Voltaren Gel ( Diclofenac sodium topical gel ) 1% prescribing information.

Voltaren Gel is a non-steroidal anti-inflammatory drug ( NSAID ) indicated for the relief of the pain of osteoarthritis of joints amenable to topical treatment, such as the knees and those of the hands.
Voltaren Gel has not been evaluated for use on joints of the spine, hip, or shoulder.

Hepatic effects

Elevations of one or more liver tests may occur during therapy with Diclofenac sodium. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continued therapy. Borderline elevations ( i.e. less than 3 times the ULN [ULN = the upper limit of normal range] ) or greater elevations of transaminases occurred in about 15% of Diclofenac-treated patients. Of the markers of hepatic function, ALT ( SGPT ) is recommended for the monitoring of liver injury.

In clinical trials, meaningful elevations ( i.e., more than 3 times the ULN ) of AST ( SGOT ) ( ALT was not measured in all studies ) occurred in about 2% of approximately 5,700 patients at some time during Diclofenac treatment. In a large, open-label, controlled trial of 3,700 patients treated for 2-6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of patients and included marked elevations ( i.e., more than 8 times the ULN ) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline ( less than 3 times the ULN ), moderate ( 3-8 times the ULN ), and marked ( > 8 times the ULN ) elevations of ALT or AST was observed in patients receiving Diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.
Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with Diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations.

In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with Diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.

Physicians should measure transaminases periodically in patients receiving long-term therapy with Diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with Diclofenac. However, severe hepatic reactions can occur at any time during treatment with Diclofenac.
If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur ( e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc. ), Diclofenac sodium should be discontinued immediately. To minimize the possibility that hepatic injury will become severe between transaminase measurements, physicians should inform patients of the warning signs and symptoms of hepatotoxicity ( e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms ), and the appropriate action patients should take if these signs and symptoms appear. To minimize the potential risk for an adverse liver related event in patients treated with Diclofenac sodium, the lowest effective dose should be used for the shortest duration possible. Caution should be exercised in prescribing Diclofenac sodium with concomitant drugs that are know to be potentially hepatotoxic ( e.g., antibiotics, anti-epileptics ).

Source: FDA, 2009

XagenaMedicine2009


Link: Xapedia - Medical Encyclopedia