Drug safety guidelines: are they effective?

Sir,

Paracetamol (acetaminophen) is the most extensively used over-the-counter analgesic and antipyretic agent. Over dosing of paracetamol can lead to hospital admissions.[12] In the United Kingdom, nearly 50% of drug poisoning occurs due to paracetamol over dosing and nearly 100-200 people die every year from it. The Toxic Exposure Surveillance System of the American Association of Poison Control Centers estimated that in 2004, 19,590 children aged less than 6 years experienced paracetamol poisoning.[3] Similar incidences are also reported in other countries like Denmark and Australia.[4]

There are multiple reasons for accidental occurrences of pediatric paracetamol poisoning such as public perception about its safe nature, easy availability in the market, lack of child proof packing at homes and dosing errors caused by pharmacists, parents and physicians.[5] In India, the data on paracetamol poisoning is not captured completely due to poor documentation. Based on the findings of a 10 year retrospective hospital-based study, about 0.32% cases of poisoning are due to acute paracetamol overdosing.[4]

The Drugs Controller General (DCGI), the apex drug regulatory authority in India, besides banning drugs, periodically issues drug safety guidelines and box warnings. In 2012, the DCGI issued safety guidelines and box warnings for paracetamol, nimesulide and statins.[6] On 4th April 2012, the DCGI sent letters to all the state drug controllers (SDCs) limiting the paracetamol content in prescription combination products and issuing box warning due to paracetamol's liver toxicity. The letter was issued based on the recommendation of the Drug Technical Advisory Board, the highest statutory authority on technical matters. In combination products, the paracetamol content is restricted to just 325 mg.[6]

In an attempt to find out the compliance to safety guidelines by the pharmaceutical companies, we did a survey at Sahaswan (Uttar Pradesh) in August 2013. The paracetamol combination products were examined for their paracetamol content and box warnings. Our findings showed that the paracetamol content was still in the range of 500 mg to 650 mg and was not restricted to 325 mg in spite of DCGI's notification and circular. Table 1 lists some of the findings.

Table 1

Paracetamol combination products in the market and manufactured after April 2012

It is unfortunate that the safety guidelines are ignored by the manufacturers and that the SDC fail to enforce the guidelines. The manufacturing falls under the jurisdiction of state Drugs Controller. In India, several paracetamol combination products are available for a number of indications such as cough and cold, pain, sprains etc. without a prescription.

Like other developing countries, in India, self-medication is rampant. There is every possibility that the patient may consume paracetamol from medications for different conditions such as fever, cough and cold, which may lead to overdosing. The excess dosing may also come from prescriptions and self-medication. The violation of the safety guidelines for paracetamol by the pharmaceutical companies puts the common people at high-risk for liver toxicity. The regulatory authorities need to be vigilant and ensure industries’ adherence to guidelines to protect the interests of the public.