Corticosteroid (Topical/Ophthalmic Implant)
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Systemic corticosteroids are known to cause dose-related developmental toxicity (i.e., growth restriction and structural anomalies) in animals and humans. The limited pregnancy experience with fluocinolone does not appear to represent a risk, probably because the systemic amounts were insufficient to cause embryo or fetal toxicity. Although the amount of topical fluocinolone reaching the systemic circulation is uncertain, suppression of the hypothalamic–pituitary–adrenal (HPA) axis has been observed when other topically fluorinated corticosteroids were used for long periods in nonpregnant patients (see Fluocinonide). Use of occlusive dressings will increase the amount absorbed. Because the amounts absorbed systemically from topical fluocinolone are unknown and probably highly variable, a less-potent agent should be considered for pregnant women requiring long-term topical corticosteroid therapy. Fluocinolone is not absorbed systemically in detectable amounts from the ocular implant, so the embryo–fetal risks from this therapy appear to be negligible.
FETAL RISK SUMMARY
Fluocinolone is a potent, synthetic, fluorinated corticosteroid that has anti-inflammatory, antipyretic, and vasoconstrictive properties. It is available in various topical formulations as a cream, ointment, solution, shampoo, and oil in concentrations ranging from 0.01% to 0.2%. It also is available as an ocular implant (0.59 mg) that is indicated for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye (3). Topical fluocinolone is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses (1,2). Systemic absorption of detectable amounts has not been observed after administration of the ocular implant (3). However, systemic absorption probably occurs with topical use. The degree of absorption is affected by inflammation, integrity of the epidermal barrier, and the use of occlusive dressings. Suppression of the HPA axis is a potential complication after topical use (1,2) and has occurred with other fluorinated corticosteroids (see Fluocinonide).
A number of animal reproduction studies have demonstrated that corticosteroids cause developmental toxicity (growth restriction, structural anomalies, and death) (see Hydrocortisone). Potent topical corticosteroids also can cause structural anomalies after dermal application (2,3).
It is not known if fluocinolone crosses the human placenta. The molecular weight (about 453 as the acetonide) is low enough that exposure of the embryo and fetus should be expected from the amounts absorbed systemically. The placenta does contain an enzyme that degrades corticosteroids (e.g., see Betamethasone, Dexamethason, Hydrocortisone, and Prednisolone), although active drug still crosses.
The use of fluocinolone for the treatment of pruritus vulvae in 17 pregnant women was described in a 1967 reference (4). Typically, the treatment was given five to seven times over a 24-hour period before voluntarily discontinuance after two or three days. No information was given about the pregnancy outcomes.
A large 1997 case–control study of the teratogenic potential of oral and topical corticosteroids involving 1,923,413 total births from 1980 to 1994 was conducted with the Hungarian Case–Control Surveillance of Congenital Abnormalities (5). Among the 20,830 malformed case infants, 73 (0.35%) used a topical corticosteroid during the 1st trimester compared with 118 (0.33%) of the 35,727 normal control infants (p = 0.69). The number of cases and controls that used topical fluocinolone cream was 16 and 47, respectively (5).
A 2003 review stated that a topical product containing fluocinolone, hydroquinone, and tretinoin (Tri-Luma®) was effective for the treatment of melasma, a localized facial hyperpigmentation also known as the “mask of pregnancy” (6). Tretinoin, when given systemically, is a known human teratogen (see Tretinoin [Systemic]) and, although the systemic bioavailability is poor, concerns have been raised with topical tretinoin (see Tretinoin [Topical]). Thus, the safest course is to avoid use of the combination in pregnancy, at least during the 1st trimester.
BREASTFEEDING SUMMARY
No reports describing the use of fluocinolone during human lactation have been located.
If fluocinolone reaches the systemic circulation, the molecular weight (about 453 as the acetonide) is low enough that excretion into breast milk should be expected. The amount of topically applied fluocinolone reaching the systemic circulation is uncertain, but suppression of the HPA axis has been observed with other topically applied fluorinated corticosteroids (see Fluocinonide) in nonpregnant patients. Because of this uncertainty, if a nursing woman requires long-term topical therapy, consideration should be given to a less-potent corticosteroid.
References
1.Product information. Synalar Cream 0.025%. MEDICIS, The Dermatology Company, 2007.
2.Product information. Synalar Solution 0.01%. MEDICIS, The Dermatology Company, 2007.
3.Product information. Retisert. Bausch & Lomb, 2005.
4.Godat J. Effective treatment of pruritus vulvae due to Candida. J La State Med Soc 1967;119:203–4.
5.Czeizel AE, Rockenbauer M. Population-based case-control study of teratogenic potential of corticosteroids. Teratology 1997;56:335–40.
6.Stulberg DI, Clark N, Tovey D. Common hyperpigmentation disorders in adults: part II. Melanoma, seborrheic keratoses, acanthosis nigricans, melasma, diabetic dermopathy, tinea versicolor, and postinflammatory hyperpigmentation. Am Fam Physician 2003;68:1963–8.