In what could be a major crackdown on leading drug companies, the government has commenced a rationality review process on a long list of drug combinations that would force withdrawal of several high profile formulation brands from the markets.

The threatened combinations include amoxycillin-cloxacillin, ampicillin-cloxacillin and anti-asthmatics containing longer acting barbiturate phenobarbitone. In addition, persistence of nimuselide in anti-inflammatory/anti-analgesic preparations (normally with paracetamol) and leading cough preparations have been listed for rationality test.

Leading drug companies including Ranbaxy Labs, Cipla, Torrent, Unichem, Cadila, Aristo and Dr Reddy's Labs would be hit by the government action with the imminent ban on some of their high turnover brands.

An expert group constituted under the Drugs Technical advisory Board (DTAB), has begun the review process by asking the manufacturers individually as to why the combinations should not be prohibited in the wake of their losing out in scientific relevance. The companies have been directed to furnish the rationality data of the combinations within a month, sources said.

The move follows a directive from the Supreme Court, which has acted on a PIL (public interest litigation) from a Delhi-based non government organization (NGO).

Sources said the SC directive to the government was specific in regard to the particulars the companies must furnish.

With the move, leading amoxicillin-cloxacillin brands including Novaclox (Cipla), Tormoxin Plus (Torrent), Tresmox (Sarabhai), Hipenox (Cadila),Imox-clo (IPCA), Mytimox (Panacea) and Gardenal (Rhone-Poulenc) have come under the threat of ban.

In the ampicillin-cloxacillin segment, the prominent brands are Megapen (Aristo), Amplus (Jagsonpal), Clamp (Dr Reddy's), Remclox(American Remedies) and Baxin (Lyka Laboratories).

The sedative phenobarbitone which is capable of specific anti-convulsant action, if taken in toxic doses,would cause marked fall in blood pressure. This happens due to ganglionic blockade and vasomotor centre depression resulting in direct decrease in cardiac contractility. Phenobarbitone-paracetamol combinations are branded as Sumo(Alkem), Niap (American Remedies) and Nimsaid P (Sun Pharma).

Sources said the manufacturers of cough preparations like Benadryl (Parke Davis), Zedex (Wockhardt) and Dilosun (Glaxo) have also been asked to establish their rationale and toxicity acceptance.

The government usually acts on the prohibition or restriction of usage of a drug or combination of drugs as per the advice of the DTAB which is supported by a large pool of scientists and experts from the department of science & technology, the Indian Council of Medical Research, various laboratories under the CSIR and also from the corporate sector and medical profession.

The government also takes into account the recommendations made by the World Health Organization, although the WHO guidelines are not mandatory on any government. As and when harmfulness or unknown side-effects of established drugs and combinations surface, the government could intervene if the industry fails to undertake post-marketing surveillance (phase 4 clinical trial) of the products.