Ranitidine Recalls Begin In Europe As Regulators Take Action
Executive Summary
OTC products are among the first to be recalled in Europe following the discovery of a human carcinogen in ranitidine-based drugs.With investigations underway worldwide, regulators across Europe are split into two camps: immediate action or wait and see.
Germany, Switzerland and Austria are the first European countries to initiate recalls of ranitidine-based drugs after tests showed that certain products contained N-nitrosodimethylamine, a probable human carcinogen.
With a Europe-wide review of ranitidine underway at the European Medicines Agency, national regulators in the DACH region are overseeing company-led recalls of OTC and prescription formulations of the drug as a precautionary measure.
The NDMA contamination has been linked by regulators to ranitidine produced by Indian API manufacturer Saraca Laboratories. However, there are indications that the problem may not be limited to Saraca, according to Germany’s drug agency BfArM.
EMA Kicks Off Investigation
EMA is working alongside the US Food and Drug Administration to find the cause of adulteration of histamine-2 blocker (H2) drugs containing ranitidine with NDMA, the same contaminant that led to worldwide recalls over the past year of hundreds of prescription drugs indicated for blood pressure and heart failure (Also see "Contamination In Common OTC Antacid Adds To FDA's API Impurity Concerns" - HBW Insight, 15 Sep, 2019.)
NMDA is present in some foods and in water supplies but is not expected to cause harm when ingested in very low levels.
EMA says is evaluating the data to assess whether patients using ranitidine are at any risk from NDMA and will provide information about this as soon as it is available.
At the same time, EMA’s human medicines committee, CHMP, is working on guidance for marketing authorization holders on avoiding nitrosamine impurities in drugs.
Germany is the only European country to date to recall OTC products containing ranitidine: Hexal’s Ranitic 75mg and 1 A Pharma’s Ranitidin 75.
Both Hexal and 1A Pharma said they were recalling certain batches of product at the pharmacy level “as a precaution”, insisting that the drugs presented no acute risk to consumers.
Higher strength ranitidine drugs (150mg and 300mg) sold on prescription have also been recalled in Germany, marketed by Mylan, Teva’s Ratiopharm, AbZ-Pharma and Betapharm Arzneimittel.
Company-led recalls for prescription generics marketed by Hexal and 1A Pharma have been initiated in Austria, while SwissMedic is overseeing recalls by Sandoz and Mepha Pharma in Switzerland. As a precautionary measure, SwissMedic said it had stopped distribution in the country of “all ranitidine preparations.”
Ranitidine is available widely across Europe as an OTC drug for the short-term relief of acid reflux and/or heartburn at a maximum does of 75mg. A dose of 150mg is permitted without a prescription in handful of countries, including Sweden and Poland.
While BfArM, SwissMedic and Austria’s BASG have had cause to act quickly, regulators elsewhere in the region have adopted a wait and see approach.
The UK’s Medicines and Healthcare products Regulatory Agency told HBW Insight that it was aware of the EMA review but had no information to suggest ranitidine drugs on sale in the country posed a risk to patients.
“We are not aware of any specific information that would indicate that there is any risk to patients and are not currently initiating any product recalls,” an MHRA spokesperson said. “We are monitoring the issue, continue to liaise with our European counterparts and will take appropriate action if necessary.”
On the continent, Dutch medicines regulator MEB said it was not yet known whether the contamination issue affected products on sale in the Netherlands. “Until there is sufficient clarity about the situation in the Netherlands, it is still too early to give advice to patients and consumers,” commented the agency, which is working in tandem with manufacturers to investigate.
Norway’s drug regulator Statens legemiddelverk said it was monitoring the situation closely but said it would not advise patients to stop taking ranitidine until more was known about the health risks of contamination. Meanwhile, Spain’s AEMPS has told healthcare professional and consumers that there is no need to discontinue ranitidine use. The risk to patients was very low, the agency said.
Outside the region, Singapore’s drug regulator HSA has recalled a number of ranitidine drugs – including GSK’s Zantac at doses of 150mg – after finding trace elements of NDMA “above the internationally acceptable level.”
Australia’s TGA said the contamination issue may affect “multiple products” sold in the country and has begun testing select batches of ranitidine.