WARNINGS
As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to diclofenac.
Diclofenac sodium should be given with caution to patients with the aspirin triad. The triad typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.
PRECAUTIONS
General
Solaraze® (diclofenac sodium) Gel should be used with caution in patients with active gastrointestinal ulceration or bleeding and severe renal or hepatic impairments. Solaraze® should not be applied to open skin wounds, infections, or exfoliative dermatitis. It should not be allowed to come in contact with the eyes.
The safety of the concomitant use of sunscreens, cosmetics or other topical medications and Solaraze® is unknown.
Information for Patients
In clinical studies, localized dermal side effects such as contact dermatitis, exfoliation, dry skin and rash were found in patients treated with Solaraze® at a higher incidence than in those with placebo.
Patients should understand the importance of monitoring and follow-up evaluation, the signs and symptoms of dermal adverse reactions, and the possibility of irritant or allergic contact dermatitis. If severe dermal reactions occur, treatment with Solaraze® may be interrupted until the condition subsides. Exposure to sunlight and the use of sunlamps should be avoided.
Safety and efficacy of the use of Solaraze® together with other dermal products, including cosmetics, sunscreens, and other topical medications on the area being treated, have not been studied.
Drug Interactions
Although the systemic absorption of Solaraze® is low, concomitant oral administration of other NSAIDs such as aspirin at anti-inflammatory/analgesic doses should be minimized.
Carcinogenesis, Mutagenesis, Impairment of Fertility
There did not appear to be any increase in drug-related neoplasms following daily topical applications of diclofenac sodium gel for 2 years at concentrations up to 0.035% diclofenac sodium and 2.5% hyaluronate sodium in albino mice. (Note: Solaraze® contains 3% diclofenac sodium.) When administered orally for 2 years, diclofenac showed no evidence of carcinogenic potential in rats given diclofenac sodium at up to 2 mg/kg/day (3 times the estimated systemic human exposureBased on body surface area and assuming 10% bioavailability following topical application of 2 g Solaraze® Gel per day (1 mg/kg diclofenac sodium).), or in mice given diclofenac sodium at up to 0.3 mg/kg/day in males and 1 mg/kg/day in females (25% and 83%, respectively, of the estimated systemic human exposure).
A photococarcinogenicity study with up to 0.035% diclofenac in the Solaraze® vehicle gel was conducted in hairless mice at topical doses up to 2.8 mg/kg/day. Median tumor onset was earlier in the 0.035% group (Solaraze® contains 3% diclofenac sodium).
Diclofenac was not genotoxic in in vitro point mutation assays in mammalian mouse lymphoma cells and Ames microbial test systems, or when tested in mammalian in vivo assays including dominant lethal and male germinal epithelial chromosomal studies in mice, and nucleus anomaly and chromosomal aberration studies in Chinese hamsters. It was also negative in the transformation assay utilizing BALB/3T3 mouse embryo cells.
Fertility studies have not been conducted with Solaraze® Gel. Diclofenac sodium showed no evidence of impairment of fertility after oral treatment with 4 mg/kg/day (7 times the estimated systemic human exposure) in male or female rats.
Pregnancy
Teratogenic Effects
Pregnancy Category B
The safety of Solaraze® (diclofenac sodium) Gel has not been established during pregnancy. However, reproductive studies performed with diclofenac sodium alone at oral doses up to 20 mg/kg/day (15 times the estimated systemic human exposureBased on body surface area and assuming 10% bioavailability following topical application of 2 g Solaraze® Gel per day (1 mg/kg diclofenac sodium).) in mice, 10 mg/kg/day (15 times the estimated systemic human exposure) in rats, and 10 mg/kg/day (30 times the estimated systemic human exposure) in rabbits have revealed no evidence of teratogenicity despite the induction of maternal toxicity. In rats, maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival.
Diclofenac has been shown to cross the placental barrier in mice and rats. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should not be used during pregnancy unless the benefits to the mother justify the potential risk to the fetus. Because of the risk to the fetus resulting in premature closure of the ductus arteriosus, diclofenac should be avoided in late pregnancy.
Labor and Delivery
The effects of diclofenac on labor and delivery in pregnant women are unknown. Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), use of diclofenac during late pregnancy should be avoided and, as with other nonsteroidal anti-inflammatory drugs, it is possible that diclofenac may inhibit uterine contractions and delay parturition.
Nursing Mothers
Because of the potential for serious adverse reactions in nursing infants from diclofenac sodium, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Actinic keratoses is not a condition seen within the pediatric population. Solaraze® should not be used by children.
Geriatric Use
Of the 211 subjects treated with Solaraze® in controlled clinical studies, 143 subjects were 65 and over. Of those 143 subjects, 55 subjects were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
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