◉ Summary of Use during Lactation:Topical triamcinolone has not been studied during breastfeeding. Since only extensive application of the most potent corticosteroids may cause systemic effects in the mother, it is unlikely that short-term application of topical corticosteroids would pose a risk to the breastfed infant by passage into breastmilk. However, it would be prudent to use the least potent drug on the smallest area of skin possible. It is particularly important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Triamcinolone can be applied to the breast or nipple area, but should be wiped off thoroughly prior to nursing. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. Any topical corticosteroid should be wiped off thoroughly prior to nursing if it is being applied to the breast or nipple area.
◉ Effects in Breastfed Infants:Topical application of a corticosteroid with relatively high mineralocorticoid activity (isofluprednone acetate) to the mother's nipples resulted in prolonged QT interval, cushingoid appearance, severe hypertension, decreased growth and electrolyte abnormalities in her 2-month-old breastfed infant. The mother had used the cream since birth for painful nipples.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date. Adequate endogenous adrenocorticoid levels are necessary for normal lactation.
◉ Summary of Use during Lactation:Because no information is available on the use of oral or injectable triamcinolone during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. However, use of triamcinolone as a nasal spray or local injections, such as for tendinitis, would not be expected to cause any adverse effects in breastfed infants. Expert opinion considers inhaled and oral corticosteroids acceptable to use during breastfeeding. Local injections, such as for tendinitis, would not be expected to cause any adverse effects in breastfed infants, but might occasionally cause temporary loss of milk supply. See also Triamcinolone, Topical.
◉ Effects in Breastfed Infants:None reported with any corticosteroid.
◉ Effects on Lactation and Breastmilk:A mother was nursing her 14-month-old 3 to 7 times daily. She had 5.7 mg of betamethasone sodium phosphate and acetate mixture injected into her shoulder for bursitis with no effect on lactation. Four weeks later, she continued to have pain in her thoracic cervical regions and was diagnosed with neural sensitization. She had 80 to 120 mg of triamcinolone diacetate injected into her cervical and thoracic spine epidurally and into the facets. Three days later, she noticed a decrease in milk supply and a reduced ejection reflex which continued to worsen over the next 5 days. She began using a breast pump with frequent pumping and domperidone as a galactogogue. Her milk slowly increased over several days and was normal by 21 days after the injection when she stopped domperidone. At that time, her serum prolactin levels were elevated. The decrease in the mother's milk supply was possibly caused by the corticosteroid injections. A dose of depot methylprednisolone injected into the wrist has also been reported to cause temporary cessation of lactation.
A study of 46 women who delivered an infant before 34 weeks of gestation found that a course of another corticosteroid (betamethasone, 2 intramuscular injections of 11.4 mg of betamethasone 24 hours apart) given between 3 and 9 days before delivery resulted in delayed lactogenesis II and lower average milk volumes during the 10 days after delivery. Milk volume was not affected if the infant was delivered less than 3 days or more than 10 days after the mother received the corticosteroid. An equivalent dosage regimen of triamcinolone might have the same effect.
A study of 87 pregnant women found that betamethasone given as above during pregnancy caused a premature stimulation of lactose secretion during pregnancy. Although the increase was statistically significant, the clinical importance appears to be minimal. An equivalent dosage regimen of triamcinolone might have the same effect.
A nursing mother who was 7 months postpartum had triamcinolone 40 mg injected into the first dorsal compartment of the wrist along with 2 mL of 1% lidocaine for de Quervain tenosynovitis. Twenty-four hours after the injection, the patient reported a 90% decrease in lactation as measured by breast pumping before and after the injection. She continued to pump her breasts and began taking fenugreek to stimulate lactation. Within 1 week, her milk supply increased by 50% and by 1 month after the injection, she was able to meet her infants breastfeeding needs.
A woman with idiopathic granulomatous mastitis received an injection of 40 mg of triamcinolone acetonide into erythematous areas of the affected breast. Her milk production decreased from the injected left breast. She had originally been able to express 60 mL on that side with an electric breast pump, and after the injection she was only able to express 10 mL. Her milk supply on the affected side recovered over the course of 2 weeks. Production on the unaffected right breast did not decrease.
来源:Drugs and Lactation Database (LactMed)
文献信息
Therapeutic Pyrazolyl Thienopyridines
申请人：Barrett D. Stephen
公开号：US20080090861A1
公开（公告）日：2008-04-17
The present invention provides for compounds of Formula I, and pharmaceutically acceptable salts thereof,
wherein R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, and R
7
have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as therapeutic agents in the treatment of TGFβ-mediated conditions, including cancer and fibrotic disorders. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.
The present invention provides for compounds of Formula I, and pharmaceutically acceptable salts thereof,
wherein R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, and R
7
have any of the values defined therefor in the specification, and pharmaceutically acceptable salts thereof, that are useful as therapeutic agents in the treatment of TGFβ-mediated conditions, including cancer and fibrotic disorders. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.
The invention features corticosteroids conjugated to either a charged group or a bulky group in a manner that resists in vivo cleavage, the resulting conjugate is a peripherally acting steroid with reduced activity in the central nervous system. The invention provides a method for treating a patient having an inflammatory disease by administering to the patient a corticosteroid conjugate.
