FDA approves an update to the drug label for Soltamox (tamoxifen citrate, oral solution) - Drug Information Update

The US Food and Drug Administration has approved a labeling change for Soltamox (tamoxifen citrate, oral solution), reverting to two months of contraception following cessation of tamoxifen.

The history and rationale of contraception duration in the tamoxifen label is as follows:

• In September 2017, FDA issued a draft guidance, “Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations Guidance for Industry”.  The 2017 draft guidance recommended contraception be based on embryo-fetal development and genotoxicity data. The recommended duration of contraception for genotoxic drugs was mainly based on adverse embryo-fetal effects, including malformations, observed in offspring of mice treated with cyclophosphamide (a classic mutagenic drug) at various stages of follicular growth. The rationale for the longer waiting period was to allow for additional elimination of potentially damaged follicles and oocytes prior to conception. However, no new clinical data on tamoxifen supported the recommendation for 9 months of contraception post treatment.  
• On September 25, 2018, FDA approved a label update for Soltamox to conform with the draft guidance recommending nine months of contraception, from two months, following cessation of tamoxifen. Prior to September 25, 2018, the Soltamox label had recommended 2 months of contraception following cessation of tamoxifen.
• FDA re-evaluated genotoxicity data, post-marketing reports, and published literature and found that tamoxifen was genotoxic in non-human studies, and results were inconclusive in human studies. The available data from post-marketing reports and published literature from women who became pregnant 2-9 months after their last dose of tamoxifen have not identified a drug-associated risk of major birth defects or adverse maternal or fetal outcomes. Based on current available evidence, FDA is modifying its recommendation for Soltamox to revert to the prior labeling recommendation that patients receive 2 months of contraception following cessation of tamoxifen. The labeling recommendations will be re-evaluated in the future should additional pregnancy outcome data become available. 

Soltamox is approved for multiple indications:

• For treatment of adult patients with estrogen receptor-positive metastatic breast cancer 
• For adjuvant treatment of adult patients with early stage estrogen receptor-positive breast cancer 
• To reduce risk of invasive breast cancer following breast surgery and radiation in adult women with ductal carcinoma in situ (DCIS) 
• To reduce the incidence of breast cancer in adult women at high risk 

The most common adverse reactions reported in patients who received tamoxifen were hot flashes, mood disturbances, vaginal discharge, vaginal bleeding, nausea, and fluid retention.

To view full prescribing information, please visit: Soltamox.