Science knows no country, because knowledge belongs to humanity & is the torch which eliminates the world (Louis Pasteur)

1. Carcinogenic (NDMA) Contamination in Ranitidine (Zantac etc.); A Ringing Bell catching Momentum
Roohi B. Obaid: Pharmaceutical Professional of Quality & Regulatory Sciences, Alumni University of
Karachi, International Forum for Regulators, CDER-US-FDA & HPFB-Health Canada.
roohibanoobaid@gmail.com. Karachi the 24 Sep 2019
Stomach produces acid to help in digestion of food but excess amount of the acid produces pain and ulcers.
The drug Ranitidine (Zantac) helps in its reduction and called as an antacid due to its property of neutralizing
the acids available in stomach. It is a freely available drug extensively used by the consumers since early 80s
all around the world. Ranitidine is included in the essential medicine list of World Health Organization
(WHO) as the most effective and safe medicine. Roughly 25 to 50,000 prescriptions are generated here in
Pakistan on daily basis and is the most prescribing drug like rest of the world. It is used to treat heartburn,
sour stomach and gastro-esophageal reflux disease. Tablet of 150 mg is available on fast moving shelves
under and over the counter of our pharmacies and stores.
A semi volatile chemical Nitroso dimethyl amine (NDMA) discovered in late 70s is known as an
environmental contaminant. It is found in water, food (meats, dairy products & vegetables) and later on
referred as potent carcinogen. United States Food and Drug Administration (US-FDA) concluded and
announced a permissible intake limit of NDMA i.e. 96 ng/day. It means that long term exposure to levels
above it may have potential to increase the risk of cancer. NDMA was identified last year in specific supply
of a raw material “valsartan” used to manufacture an anti-hypertensive drug product. It ended up in stop
distribution and a huge recall all around. Other follow on products (Losartan & Irbesartan) and impurities of
the same chemical family “N-Nitrosamine” Nitroso diethyl amine (NDEA), Nitroso methyl aminobutyric acid
(NMBA), Dimethyl Formamide (DMF) further expanded and balloon the global recalls that are continued.
2.5 mg NDMA was found in 150 mg tablet of ranitidine (FDA approved analytical method of Gas
Chromatography/ Mass Spectroscopy - GC/MS was used) which is 26000 times greater than the permissible
limit, if taken one tablet per day. The typical recommended dose for peptic ulcer disease in adults is 150 mg
twice daily for 4 - 8 weeks followed by maintenance dose of 150 mg once daily. In this way, 5 mg NDMA is
consumed per day that is total 280 mg if used for 8 weeks. It can reach exposure of up to 1 Gm in a year
which is alarming. Studies published in peer review scientific literatures reveal the existence of dangerous
levels of NDMA in the urine of those who had taken ranitidine (Teng Zeng & William A. Mitch, Mar 2016).
News broke on September 13, 2019 that Zantac/ Ranitidine exposed consumers to dangerous levels of
NDMA. Global health regulators responded with a coordinated alarm immediately. Canada stopped further
distribution until evidence is provided to demonstrate that the available product does not contain NDMA
above the acceptable limit. Germany, Switzerland and Austria have initiated recall of ranitidine based drugs.
Finland has withdrawn drugs from its pharmacies. On the other hand, Sandoz, unit of Novartis have stopped
its worldwide distribution.
As a matter of reality and truth, we (private and public sector) have yet failed to test and quantify NDMA
from products available in market. We have to be responsibly responsive in putting efforts to accomplish the
task. Furthermore, data, information, knowledge and experience strongly suggest to go back and to develop a
strategy to screen out the products for such impurities. This is indeed our responsibility and commitment to
public health that requires nothing but collaborative working among academia, industry and testing
laboratories. It will help in increasing the worthy contribution to science.