Label Changes for:
Arthrotec (diclofenac sodium/misoprostol) Oral Tablets
Changes have been made to the WARNINGS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
- In another clinical trial where over 17,000 patients received diclofenac for a mean of 18 months, hepatitis was rarely observed.
- In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and usually occur within 1-6 months, but can occur at any time during treatment with diclofenac.
Metabolic and Nutritional
- oalanine aminotransferase and aspartate aminotransferase increased
- add contraindication for patients with active gastrointestinal bleeding
- add that the use of diclofenac/misoprostol with concomitant NSAIDs including COX-2 inhibitors should be avoided.
expand Skin Reactions subsection
- remove statement that nursing mothers should not take Arthrotec
- revise statement about renal function in Ace Inhibitors subsection
- add Tacrolimus subsection
- add data to Nursing Mothers subsection
add the following subsections:
- Pregnancy, puerperium and perinatal conditions
- Congenital, familial and genetic disorders
- expand upon the following subsections:
- Body as Whole
- Female Reproductive Disorders
- Hemic and lymphatic system subsection
- Metabolic and nutritional subsection
- Skin and appendages subsection
- Urinary subsection
- Clarify that caution should be exercised in nursing mothers
- Add that broken tablets should not be taken
- Use caution when dosing diclofenac with CYP2C9 inhibitors (e.g. voriconazole). Concomitant use of CYP2C9 inhibitors may enhance toxicity of diclofenac due to an increase in systemic exposure to diclofenac. When concomitant use of CYP2C9 inhibitors is necessary, the total daily dose of diclofenac should not exceed the lowest recommended dose of ARTHROTEC 50 twice daily (see DOSAGE AND ADMINISTRATION).
- In a published study, single dose diclofenac (50 mg) was coadministered with the last dose of voriconazole (400 mg every 12 hours on Day 1, followed by 200 mg every 12 hours on Day 2). The mean Cmax and AUC of diclofenac were increased by 2.1-fold and 1.8-fold respectively when coadministered with voriconazole compared to diclofenac alone.
- Use caution when dosing diclofenac with CYP2C9 inducers (e.g. rifampin). Concomitant use of CYP2C9 inducers may lead to compromised efficacy due to a decrease in systemic exposure to diclofenac. The separate products of misoprostol and diclofenac should be used if a higher dose of diclofenac is deemed necessary.
- In a published study, single dose diclofenac (50 mg) was coadministered with the last dose of voriconazole (400 mg every12 hours on Day 1, followed by 200 mg every 12 hours on Day 2). The mean Cmax and AUC of diclofenac were increased by 2.1-fold and 1.8- fold respectively when coadministered with voriconazole compared to diclofenac alone.