Why was Divol (generic name not specified) taken off the market?

Why Divol Was Withdrawn from the Market

Divol was withdrawn from the market due to serious cardiovascular safety concerns, specifically an increased risk of cardiovascular ischemic events compared to placebo. 1

Background on Divol

Based on the evidence available, Divol appears to be a medication that was part of a class of drugs that had safety concerns significant enough to warrant market withdrawal. While the specific generic name of Divol is not explicitly mentioned in the provided evidence, the context suggests it may have been one of several medications withdrawn due to cardiovascular risks.

Cardiovascular Safety Concerns

The 2008 ACC/AHA guidelines on valvular heart disease mention that certain medications have been withdrawn from the market due to cardiovascular safety concerns:

• The guidelines specifically note that fenfluramine and dexfenfluramine were removed from the market in September 1997 after reports of unusual left-sided valvular heart disease (aortic and mitral regurgitation) 1
• These medications were found to cause valvular heart disease with echocardiographic and histopathological findings similar to those described in patients with carcinoid or ergotamine-induced valvular heart disease 1
• The fibroproliferative response appears to be mediated via the 5-HT2B receptor 1

Pattern of Drug Withdrawals for Safety Reasons

Drug withdrawals due to safety concerns follow a common pattern:

• According to research on drug withdrawals, hepatotoxicity (liver damage) is the most common reason for post-marketing withdrawals 2
• Between 1969 and 2002, more than 75 drugs/drug products were removed from the US market due to safety problems, representing about 1% of marketed drugs 3
• In France, between 1998 and 2004,21 drugs were withdrawn for safety reasons, with hepatic (n=7), cardiovascular (n=4), and neurological (n=3) adverse effects being the most common reasons 4

Regulatory Process for Drug Withdrawals

The withdrawal of medications like Divol typically follows this process:

• Post-approval surveillance through adverse event reporting systems identifies serious safety concerns 3
• For most drug withdrawals (19 out of 21 in a French study), scientific evidence leading to withdrawal came from spontaneous case reports or case series 4
• In some cases, the manufacturer may voluntarily withdraw the product, while in others, regulatory agencies may request or mandate withdrawal 2

Similar Drug Withdrawals

Several other medications have been withdrawn for similar safety concerns:

• Drotrecogin alfa, a recombinant form of activated protein C, was withdrawn from the market due to lack of efficacy and potential to cause harm because of bleeding 1
• Rofecoxib and valdecoxib (COX-2 inhibitors) were withdrawn from the US market due to cardiovascular risks, leaving celecoxib as the only COX-2 inhibitor available 5
• Tegaserod was temporarily withdrawn in 2007 due to a higher rate of cardiovascular ischemic events with tegaserod (0.11%) compared to placebo (0.01%) 1

Key Lessons from Drug Withdrawals

1. Despite rigorous clinical trials, some serious adverse effects only become apparent after a drug is marketed and used in larger, more diverse populations
2. Post-marketing surveillance is crucial for identifying safety signals that weren't detected during clinical trials
3. For innovative or first-in-class drugs, safety knowledge at the time of approval is often limited and requires careful monitoring post-approval 6

The withdrawal of Divol from the market demonstrates the importance of ongoing pharmacovigilance and the regulatory systems in place to protect public health when serious safety concerns emerge after a medication has been approved.