Dermatologists and allergists professional societies, the American Academy of Dermatology, and the American Academy of Allergy, Asthma, and Immunology, have protested the inclusion of the black box warning. The AAAAI states "None of the information provided for the cases of lymphoma associated with the use of topical pimecrolimus or tacrolimus in AD indicate or suggest a causal relationship." Pharmacology
Pimecrolimus is an ascomycin macrolactam derivative. It has been shown in vitro that pimecrolimus binds to FKBP1A and also inhibits calcineurin. Thus pimecrolimus inhibits T-cell activation by inhibiting the synthesis and release of cytokines from T-cells. Pimecrolimus also prevents the release of inflammatory cytokines and mediators from mast cells.Pimecrolimus, like tacrolimus, belongs to the ascomycin class of macrolactam immunosuppressives, acting by the inhibition of T-cell activation by the calcineurin pathway and inhibition of the release of numerous inflammatory cytokines, thereby preventing the cascade of immune and inflammatory signals. Pimecrolimus has a similar mode of action to that of tacrolimus but is more selective, with no effect on dendritic (Langerhans) cells. It has lower permeation through the skin than topical steroids or topical tacrolimus although they have not been compared with each other for their permeation ability through mucosa. In addition, in contrast with topical steroids, pimecrolimus does not produce skin atrophy. References
External links
FDA News
NPS RADAR
Article about American Academy of Dermatology speaking out against black box warning Archived 2008-04-07 at the Wayback Machine
Report of the Calcineurin Task Force of the ACAAI and AAAAI
The affinity of estradiol valerate for the estrogen receptor has been reported to be 50 times less than that of estradiol, and estradiol valerate and estradiol cypionate have been found to possess similar affinity for the estrogen receptor. Both estradiol cypionate and estradiol valerate are rapidly cleaved into estradiol in the body, and estradiol valerate has been found to be unable to reach target tissues in any concentration of significance. As such, estradiol valerate is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol, and estradiol cypionate is described as a prodrug of estradiol similarly. Estradiol cypionate is of about 46% higher molecular weight than estradiol due to the presence of its C17β cypionate ester, and contains about 69% of the amount of estradiol by weight. Because estradiol cypionate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen. Effects on liver protein synthesis
A study compared the combination of 5 mg estradiol cypionate and 25 mg medroxyprogesterone acetate as a combined injectable contraceptive (which has been associated with peak estradiol levels of around 300 pg/mL) with an ethinylestradiol-containing combined birth control pill and found that whereas the birth control pill produced significant changes in coagulation parameters, there were no significant prothrombotic effects of the combined injectable contraceptive on levels of fibrinogen, factors VII and X, plasminogen, or the activated prothrombin time.