Sorry, you need to enable JavaScript to visit this website.

ARTHROTEC® (misoprostol, diclofenac sodium) Nonclinical Toxicology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term animal studies to evaluate the potential for carcinogenesis and animal studies to evaluate the effects on fertility have been performed with each component of ARTHROTEC given alone.

The carcinogenicity potential of ARTHROTEC (diclofenac sodium and misoprostol) has not been studied in animals. In a 24 month rat carcinogenicity study, misoprostol administered orally at doses up to 2.4 mg/kg/day (14.4 mg/m2/day, 24 times the recommended maximum human dose of 0.6 mg/m2/day) was not tumorigenic. In a 21 month mouse carcinogenicity study, misoprostol administered orally at doses up to 16 mg/kg/day (48 mg/m2/day), 80 times the recommended maximum human dose based on body surface area, was not tumorigenic.

In a 24 month rat carcinogenicity study, diclofenac sodium administered orally at up to 2 mg/kg/day (12 mg/m2/day) was not tumorigenic. In a 24 month mouse carcinogenicity study, oral diclofenac sodium at doses up to 0.3 mg/kg/day (0.9 mg/m2/day, 0.006 times the recommended maximum human dose based on body surface area) in males and 1 mg/kg/day (3 mg/m2/day, 0.02 times the recommended maximum human dose based on body surface area) in females was not tumorigenic.

Mutagenesis

ARTHROTEC (diclofenac sodium and misoprostol combinations in 250:1 ratio) was not genotoxic in the Ames test, the Chinese hamster ovary cell (CHO/HGPRT) forward mutation test, the rat lymphocyte chromosome aberration test, or the mouse bone marrow micronucleus test.

Impairment of Fertility

The effects of ARTHROTEC (diclofenac sodium and misoprostol) on male or female fertility have not been studied in animals; however, there are data with diclofenac sodium and misoprostol given alone. Misoprostol, when administered to male and female breeding rats in an oral dose range of 0.1 to 10 mg/kg/day (0.6 to 60 mg/m2/day, 1 to 100 times the recommended maximum human dose based on body surface area) produced dose-related pre- and postimplantation losses and a significant decrease in the number of live pups born at the highest dose (60 mg/m2/day, 100 times the recommended maximum human dose based on body surface area). Diclofenac sodium at oral doses up to 4 mg/kg/day (24 mg/m2/day, 0.16 times the recommended maximum human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

13.2 Animal Toxicology

A reversible increase in the number of normal surface gastric epithelial cells occurred in the dog, rat, and mouse during long-term toxicology studies with misoprostol. No such increase has been observed in humans administered misoprostol for up to 1 year. An apparent response of the female mouse to misoprostol in long-term studies at 100 to 1000 times the human dose was hyperostosis, mainly of the medulla of sternebrae. Hyperostosis did not occur in long-term studies in the dog and rat and has not been seen in humans treated with misoprostol.

What's New

No Current Announcements.

Therapeutic Area

Contact Pfizer Medical

Report an Adverse Event
1-800-438-1985

Search

Please enter your search term(s) for ARTHROTEC®

Contact Pfizer

Need to report an Adverse Event, Side Effect or Product Quality Concern?

Contact Pfizer Safety to report an adverse event, side effect or concern about the quality of a Pfizer product: (800) 438-1985

You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns at 1-800-FDA-1088 or www.fda.gov/MedWatch

Have a Medical Question on a Pfizer Prescription Medicine?
Contact Pfizer Medical Information to speak with a professional regarding your medical question on a Pfizer prescription product: (800) 438-1985
Have a Question on a Pfizer Over-the-Counter Product?
For Pfizer Consumer Healthcare non-prescription or over-the-counter products such as Advil, Centrum, Nexium or Thermacare, call (800) 322-3129
Have a Question about Pfizer Clinical Trials?
If you are looking for information about Pfizer studies currently recruiting new patients in your area, you can begin your search on our website. For questions about a Pfizer Clinical Trial, call (800) 718-1021 or email [email protected]
Need Information on Pfizer’s Patient Assistance Programs?

Pfizer RxPathways® connects eligible patients, regardless of their insurance status, to a range of assistance programs that offer insurance support, co-pay help, and medicines for free or at a savings. For more information, please call (844) 989-7284 or visit www.PfizerRxPathways.com.

Eligible patients can register for valuable savings offers for nearly 40 brand name medications. Visit www.MyPfizerBrands.com for more information.