Why was rantidine stopped by the FDA

The generics industry is making headlines again because of contaminated drugs

After the antihypertensive agent valsartan, ranitidine is now also affected by recalls. The corresponding drugs, which are used against heartburn, among other things, are no longer available in Switzerland.

The generics manufacturer Sandoz advertises with the slogan “Trust connects, trust obliges”. The subsidiary of the Basel pharmaceutical company Novartis also emphasizes in advertisements in the “Schweizerische Ärztezeitung”, using the Swiss cross, that it has been selling “original Swiss generics since 1886”. Against this background, it is probably advisable for you to exercise the greatest possible caution in the marketing of your products. The company decided this week to temporarily stop supplying pharmacies and other customers worldwide with a drug that is important for them and many patients because of possible carcinogenic ingredients.

FDA determined

It is a generic based on the preparation Zantac from the French manufacturer Sanofi and is used against common ailments related to excessive acid production in the stomach. According to the Swiss package insert for the Sandoz product, this refers to gastric and duodenal ulcers as well as reflux disease (heartburn). Certain recurring digestive disorders are also treated with this drug.

In Switzerland, the affected tablets of the Sandoz brand Ranimed are only available upon presentation of a doctor's prescription. The same applies to the competitor product from the provider Mepha. Like the original Zantac, both preparations are based on the active ingredient ranitidine. The US health authority FDA announced on Friday last week that it had discovered the chemical N-nitrosodimethylamine (NDMA) in the ranitidine products it had examined. From animal experiments it is known that the chemical group of nitrosamines can trigger tumors in the liver and other organs. It is also suspected of causing cancer in humans.

NDMA hit the headlines last year when it was found that it had contaminated heart medication containing the active ingredient valsartan. Various generic manufacturers were also affected in this case. Variants of this antihypertensive agent were recalled in around thirty countries - including Switzerland - at the beginning of July 2018. A Chinese manufacturer of the active ingredient called Zhejiang Huahai Pharmaceuticals was identified as the source of the contamination.

Aggressive marketing methods

The fact that the active ingredients for generics are often produced in China today is explained by the strong cost pressure that prevails in this industry. Valsartan, as an original product with the brand name Diovan Novartis, brought in revenues in the billions for years, but after the loss of patent protection at the beginning of this decade, the pharmaceutical company's business suddenly shrunk. Copycat products are usually offered at a fraction of the price the original cost at the time. This forces the providers to market aggressively in order to achieve a satisfactory margin using high volumes.

In the latest report in connection with ranitidine, the FDA has neither ordered a recall nor named individual products or their manufacturers. She also explained that the concentrations of NDMA that were found in food were hardly ever found in the first samples. Nitrosamines are found in grilled meat, smoked fish and beer, among other things. The US company Valisure, which sells drugs over the Internet and boasts of rigorous tests for the products it offers, contradicts this representation. Company representatives say that levels have been reached that are very far above those that are permissible with the daily intake of NDMA.

Hardly any generics from Switzerland

In Switzerland, according to a notification that it sent out on Tuesday, the drug authority Swissmedic “stopped” the delivery of all ranitidine products as early as the end of August 2019. In addition to the tablets of the Sandoz brand Ranimed, those from Mepha and the injection solution Zantic from the British manufacturer GlaxoSmithKline are also affected.

Experience with valsartan suggests that suppliers from China or other emerging countries also worked improperly in the manufacture of the active ingredient for ranitidine. If this assumption is confirmed, the pressure on generic drug suppliers is likely to increase to take production back into their own hands. However, given the low prices that can be charged for imitation products, the incentives for this are very limited. In Switzerland, the pharmaceutical country, hardly any generics are produced - regardless of the Swiss cross in Sandoz advertising.