Do We Really Need Hepato-protectors?

There are some notorious high-selling ‘drugs’, classified in the Indonesian MIMS as hepato-protectors, while almost the rest of the world is devoid of it. It is also strange that they actually belong to dietary supplements (DS), a class of remedies that is by definition a non-drug (previously named ‘quasi drugs’) and therefore were without any controlled clinical trial to prove its efficacy as an effective medicine called drug. As we all know, the flood of supplements into our country (and the rest of the world) began in the mid 90's, made easy by a controversial Act of the United States called Dietary Supplement Health Education Act (DSHEA), 1993. This act had opened the door for all such remedies to enter the world, unproven by studies - normally required for all drugs to be marketed - or sometimes only ‘proven’ by mere cultural use. Therefore food supplements ( FS, a term used in Europe) ought not to be mixed in a compendium for drugs like MIMS, because doctors and pharmacists can’t differentiate unproven remedies from effective drugs. One could find a difference of registration code numbers. Regulation, in fact, requires that DS are clearly marked, but who bothers reading it or even understand the meaning? Therefore, the ‘education’ part of the Act should stipulate that the sale of FS must be coupled with adequate information to the public. Among others, it has to be clearly stated that the use of FS is no guarantee of a cure and that the user should decide for themselves whether it offers them a personal benefit. DS may also not claim a ‘disease claim’ on the label, but may only claim a ‘health claim’. This rule is often violated in developing countries, but the difference between disease and health may be subtle and debatable.

Isoprinosine™ (generic name, methisoprinol) was in the Indonesian market long before the above Act. When Isoprinosine’s registration dossier was assessed by the Indonesian National Drug Evaluation Committee it was unanimously rejected without hesitation. No proof of efficacy could be shown in the clinical trial study report done in the United States. These were widely publicized by the FDA and were known to us and therefore the fledgling was (prematurely) dead and the drug company was shut down (Isoprinosine was the only product of Newport Pharm. Int. Inc. USA, initially distributed by PT Wigo)

Despite of the negative recommendation of the Evaluation Committee, the Director General of POM issued a marketing approval under protest of the Committee. Even when the ‘drug’ was subsequently reevaluated because of registration renewal requirements of POM - every 5 years – and the change of ownership (acquisition of PT Dupa by PT Darya Varia) no new data were available and therefore marketing status should be withdrawn. However the ‘drug’ managed to stay happily in Indonesia until today with a ‘valid’ registration number.

Hepato-protectors (and Nootropics) are officially not included in the formal nomenclature of drug classes; it is not found in official books, obviously it has been newly created to suit a drug that doesn’t work. What should a hepato-protector do? Protect the liver against what and when, and for how long? Obviously, the name had its origin from animal studies, by which a chemical is experimented in rats whereby the compound is given (orally or parenterally) and followed by a challenger (usually a toxic compound). When it can be proven that the treated rats recover more favorably than the placebo-treated group, then the chemical could be said to protect the rat against a toxic stuff. If the primary outcome of the study happens to be observed in the liver, then it would be a perfect marketable name for a class of drugs to be called a liver-protector to trap the doctor into prescribing it. However, such an experiment can’t be found or is done in a human setting, because we can’t give a drug to a human for years to prevent a disease of the liver. It would be very unpredictable when that disease will be attacking the person (mostly none at all), and therefore if such a study should be done it would be impossible to perform. This would also be the difficulty to study a drug that could be proven to shorten wake-up time of a CNS depressant poisoning, for the simple reason that duration of a coma in a poisoned patient can’t be predicted from neither the dose of the poison or the depth of the coma. These two variables are all patient-specific, so that each person reacts in a haphazard manner when wake-up time is measured as the primary variable of the clinical trial. Simple observational, comparative outcome studies may bring more conclusive results. Such finding taught us not to give stimulants (amphetamines or caffeine) to poisoned patients in coma, resulting in dramatically reduced death rates from 25% to 2 % (1970’s) by just watching and caring.

Dozens of ineffective drugs like this have the lucky fate to have a long half-life in our country: Adona, ATP, Ketosteril, Neo-Minophagen, Fosfomycin IV, Anti-catarrhact eye drops, and many more. POM still refused to withdraw the drug(s) from the market, causing the truth being defeated by politics. This provokes for any quackery remedy to find their market share in our beloved country. Is it not reasonable then that patients go abroad for their flu? There is seemingly a lost of trust in our health system, inflicting hordes of people seeking refuge in other countries, a substantial loss for us, but a windfall of a few billion dollars annually to others’ benefit.

We will be waiting for our Health Minister to take immediate action, because doesn’t POM has the prime responsibility to protect the public from malicious drug-sellers? On top of all that, it also has created a stark conflict among doctors, an obvious reason for the organizers of this meeting to include this presentation with giving me a provocative title.

Let me close this writing with a fitting paraphrase from Shakespeare, an advice given by Polonius to his son Laertes, in Hamlet:

‘Those drugs thou hast, and their adoption tried,
Grapple them to thy soul with hoops of steel;
But do not dull thy palm with entertainment
Of each new-hatch’d unfledged remedy.’