Q. 1. Now the drug market is flooded with Paracetamol and Methionine combinations. As compared to Paracetamol, does this combination have better efficacy and safety; and can it be used safely in the management of pyrexia associated with liver diseases?
R. Selvan,
Deepam Hospital,
230, Gandhiji Road,
Erode - 638 002, India.
A. Paracetamolleads to its hepatotoxic effect through depletion of hepatocyte glutathione concentration. Methionine is useful in treating paracetamol toxicity as it helps in restoring hepatocyte glutathione levels(1-3). This is the theoretical basis of adding methionine to paracetamol to prevent its toxicity if an over- dose occurs [paracetamol is the commonest drug incriminated in drug overdose in UK and USA](4).
There are no published studies in English literature comparing the
efficacy of this combination with that of paracetamol. Neither is there any hard evidence in humans that this combination will cause less problem of overdose related toxicity(4). Safety of methionine is not studied widely. Dietary supplementation with methionine has caused reduced folate concentration and other metabolic changes. Methionine is metabolized to homocysteine and vice-versa in a methylation cycle and raised levels of homocysteine have been associated with peripheral vascular disease,
ischemic heart disease, stroke and coagulation
some suggestion that methionine may have a
role in promoting carcinogenesis(4,5). Safety
of this combination in patients with liver disease is also questionable as large
doses of methionine in patients with liver disease have precipitated hepatic encephalopathy(4).
Fortunately for us the maket is still not "flooded" with paracetamol-methionine
combination and we have many preparations having paracetamol alone also available to choose from. In fact marketing of such combination drug raises issues involving rationality, cost and ethics. In India paracetamol
toxicity is extremely rare(6). Hence, to prevent such rare adverse consequences, tonnes of methionine (and paracetamol combination) will be unnecessarily prescribed to millions of people at a cost even four to six times that of paracetamol(3 ).
Jagdish Chandra,
Professor of Pediatrics,
Kalawati Saran Children's Hospital,
Lady Hardinge Medical College,
New Delhi, 110001, India.
1.
Mitchell DB, Acosta D, Bruckner JV. Role of glutathione depletion in cytotoxicity of acetaminophen in primary culture system of rat hepatocyte. Toxicology 1985; 37: '127-135.
2.
Xavier P, Romiro J, Gomez Lachon MJ, Fabra R, Trullenque R, Castell JV. Intracellular glutathione in human hepatocytes incubated with s-adenosyl L-methionine and GSH-depleting drug. Toxicology 1991; 293-302.
3. Vale JA, Meredith TI, Goulding R. Treatment of acetaminopliem poisoning. The use of oral methionine. Arch Intern Med 1981;141:394-396.
4.
Jones AL, Hayes PC, Proudfoot AT, Vale JA, Prescott LF. Should methionine be added to every paracetamol tablet? 1997; 315: 301-304.
5.
Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ureland PM, Sahper AG. Prospective
study of serum total homocyteine concentration and risk of stroke in
middle aged British men. Lancet 1995:346: 1395-1398.
6.
Seha SK, Kale R. Adding methionine to every paracetamol tablet. BMJ 1998; 316: 473-474.
|
