The Story of Dydrogesterone in the US: A Commercial Decision
Contrary to the belief that dydrogesterone is banned, it was voluntarily withdrawn from the US market by its manufacturer, Solvay, in 1997 for commercial reasons. The drug, a synthetic progestin also known as Duphaston in many countries, was initially registered in the US in 1961 for treating conditions related to progesterone deficiency. However, Solvay eventually determined that the registered indications were no longer commercially viable, leading to its withdrawal. Similar commercial considerations also led to the drug's withdrawal from other markets, including the UK and Australia.
The FDA’s Official Ruling on the Withdrawal
In 2017, in response to a citizen petition, the FDA officially stated in the Federal Register that a review of its records found no evidence suggesting that dydrogesterone's withdrawal was due to safety or effectiveness issues. This clarification is significant as it confirms the commercial nature of the withdrawal and could potentially allow for the future approval of generic versions if a manufacturer decides to pursue it.
The Commercial Rationale Behind the Withdrawal
The decision to withdraw dydrogesterone was likely influenced by factors such as declining demand for its registered uses, increased competition from other treatments, and the manufacturer prioritizing more profitable products. The drug was also relatively inexpensive with limited new indications, making it less commercially appealing.
Comparison of Dydrogesterone with US-Approved Alternatives
Although dydrogesterone is unavailable in the US, several other progestin medications are used for similar conditions. The following table compares dydrogesterone with common US alternatives:
| Feature | Dydrogesterone (e.g., Duphaston) | Micronized Progesterone (e.g., Prometrium) | Medroxyprogesterone Acetate (MPA) (e.g., Provera) |
|---|---|---|---|
| Availability in US | No (withdrawn for commercial reasons) | Yes (FDA-approved) | Yes (FDA-approved) |
| Bioavailability | High oral bioavailability due to unique structure | Lower oral bioavailability; often formulated for vaginal or injectable use | Good oral bioavailability; often used for hormone therapy |
| Receptor Selectivity | Highly selective for progesterone receptors; minimal activity on other steroid receptors | Binds to progesterone receptors and is metabolized into other active steroids | Binds to progesterone, androgen, and glucocorticoid receptors; has other activities |
| Use in Early Pregnancy | Used worldwide for luteal phase support and threatened miscarriage | Standard of care in the US for luteal phase support | Use in pregnancy is generally not recommended |
| Effect on Ovulation | Does not inhibit ovulation at therapeutic doses | May inhibit ovulation depending on dosage and timing | Can suppress ovulation |
| Side Effect Profile | Generally well-tolerated, with side effects like headaches, nausea, and menstrual irregularities | Can cause drowsiness, vaginal discharge with vaginal formulations | Known to have more pronounced androgenic side effects |
The Path to Drug Discontinuation vs. FDA Ban
It is important to distinguish between a voluntary commercial withdrawal and a regulatory ban. A ban implies a regulatory body has deemed a drug unsafe or ineffective. Reasons for commercial withdrawal can include insufficient sales, market competition, changes in corporate strategy, or product line consolidation. Dydrogesterone's removal was a business decision, not an FDA ban for safety concerns, as confirmed by the 2017 FDA notice.
Conclusion: The True Reason Behind the Absence
Dydrogesterone's absence from the US market is due to a voluntary commercial withdrawal by its manufacturer decades ago, not an FDA ban for safety or effectiveness. While still used globally, US clinicians utilize other FDA-approved progestins for similar conditions. This case highlights the influence of market forces on drug availability. More information on the FDA's confirmation is available here.
