Deadly medicines contamination in Pakistan

March 2013

More than 200 people died and around 1000 became seriously ill in Pakistan after taking contaminated cardiac medicines. WHO experts played a crucial role in the investigation.

Bleeding from the mouth and gastrointestinal tract, strange dark marks on the skin and extremely low levels of white blood cells and platelets – these were the symptoms of patients who began presenting to hospitals across the city of Lahore in early December 2011.

At first, doctors suspected they were facing a new outbreak of dengue fever. But they were baffled by reports of zero findings of the dengue mosquito larvae, and not all of the symptoms matched up with dengue. By mid-January, 25 people had died from this mysterious illness and hundreds more crowded emergency rooms throughout the city.

Immediate action

A team of doctors established a common link: these patients had all been taking locally-manufactured cardiovascular medication distributed free by the Punjab Institute of Cardiology in Lahore.

A pack of Isotab with one pill in an open hand

Suspecting an adverse reaction by drug overdose or contamination, the Punjab Secretary of Health immediately recalled five suspected drugs that had been distributed to around 46 000 patients. Preliminary testing was done in Pakistan, and then samples of these medicines were sent out to laboratories around the world.

Meanwhile, reports in the local media and online discussions started causing panic and many people stopped taking all medication. “The media reports emerging from Pakistan were picked up by WHO staff in Islamabad and Geneva. Despite some conflicting stories, it was obvious that Pakistan was facing a very serious health issue,” says Michael Deats, from WHO’s Department of Essential Medicines and Health Products.

Urgent request for WHO for experts

The Government of the Punjab made an urgent request for assistance from WHO for experts in pharmacology and medicines regulations.

"Many lives were saved once the contaminant was identified.”

Michael Deats, WHO

On 31 January, the United Kingdom Medicines and Healthcare Products Regulatory Agency announced that it had identified the contaminant. Large quantities of antiparasitic drug pyrimethamine were discovered in a batch of cardiovascular medication called Isotab. The drug had been manufactured by Efroze, a well-established manufacturer in Pakistan that makes both cardiovascular and antimalarial medications at its facility in Karachi.

At 14 times normal dosage levels, the pyrimethamine was causing severe folate deficiency, destroying the platelets in bone marrow and triggering heavy internal bleeding. Fortunately, high doses of calcium folinate can reverse the toxic effects of the overdose and the hospitals were able to start treating patients immediately.

WHO Drug Safety Alert issued

On 3 February, WHO issued a Drug Safety Alert to inform governments and pharmaceutical regulators around the world of the contamination.

On 6 February, Deats joined Mohamed Bin Shahna, from WHO’s Regional Office for the Eastern Mediterranean in Cairo and Khalid Bukhari from the WHO office in Islamabad, in Lahore. The WHO team embarked on an intensive tour of Lahore, Karachi and Islamabad visiting hospitals, laboratories, the Punjab Chief of Police, State Secretary of Health, senior government officials and pharmacy and manufacturers’ associations.

They visited the manufacturing site of Isotab where it was established that a 25kg drum of pyrimethamine had gone missing and had accidently been mixed into a batch of the cardiac medicine.

“We were very lucky that the entire batch of contaminated drugs was distributed from just one hospital and that it is one of the few in Lahore that uses electronic records so patients could be traced more easily. It was also fortunate that the contaminant was identified quickly and a cure was known and available immediately. Many lives were saved once the contaminant was identified,” says Deats.

Improving medicines regulation

A judicial enquiry held in 2012 found the manufacturer “criminally negligent” and called for a National Medicines Regulatory Authority to provide better oversight of local manufacturers. The Federal Government of Pakistan has since passed the laws to create this authority. WHO experts continue to work closely with the government to improve medicines regulation, including improving the quality of two drug-testing laboratories in Lahore and Karachi.