Paracetamol, safety

Buckley, N.A. and Srinivasan, J. (2002) Should a lower treatment line be used when treating paracetamol poisoning in patients with chronic alcoholism a case for. Drug Safety, 25 (9), 619-624. 

These include drugs, pesticides, environmental pollutants, industrial chemicals, and food additives about which we need to know much, particularly concerning their safety. Of particular importance, therefore, is the ability to predict, understand, and treat toxicity as shown by examples such as paracetamol hepa to toxicity (see chap. 7). 

Various forms of hepatotoxicity, sometimes involving jaundice or mimicking biliary tract disease, have been reported by the UK Committee on Safety of Medicines (8). In most, but not all, cases the drug had been taken with paracetamol. In some cases, rechallenge caused hepatotoxicity within a few hours, and an immunologi-cally based mechanism has been suggested. 

The dosage of mefenamic acid that is used in preterm infants to induce closure of patent ductus arteriosus must not exceed 2 mg/kg/day in three divided doses, to avoid the danger of renal insufficiency (SEDA-19, 97). The promotion of mefenamic acid in Pakistan for fever in children, as a drug of unsurpassed efficacy compared to [paracetamol] in fever control and better tolerance , has been criticized by the Medical Lobby for Appropriate Marketing. In fact, there have been no controlled comparisons of mefenamic acid with a reference drug or placebo, and its safety and efficacy have not been established in children (SEDA-19, 97). 

The safety profile of over-the-counter naproxen has been adequately evaluated, and the incidence of adverse events was similar to the incidence with placebo, ibuprofen, and paracetamol. There were no serious adverse reactions in these studies (SEDA-20, 93). 

As the debate developed, the safety of paracetamol and its combination with aspirin, which had only come to the fore on a large scale as phenacetin disappeared, also came to be questioned. The difficulty in assigning specific roles to the various analgesics is partly related to the use of drug combinations but largely because of the prolonged time over which the disorder develops. 

The renal safety of aspirin used as single ingredient is easier to evaluate. From the seven case-control studies, only 3 showed an increased risk. All 3 suffered from the same ingredient bias as previously mentioned for paracetamol. In contrast however, both observational studies reported a robust, slightly decreased, odds ratio for the use of aspirin (Figure 1). In both studies, calculated odds ratio s were based on hundreds of regular users of aspirin [41, 42]. 

Intrinsic safety - Some drugs are intrinsically and obviously safer than others at therapeutic doses. Compare, e.g., the adverse reactions produced by paracetamol and any cytotoxic drug. 

Fig. 26.2 First page of a EDQM safety data sheet of paracetamol [17]...

EDQM. Reference Substances. Safety Data Sheet Paracetamol crs, revision date 07 Mar 2014. www.edqm.eu/site/Databases-10.html... 

Sinatra RS, Jahr JS, Reynolds LW Viscusi ER, Groudine SB, Payen-Champenois C. The analgesic efficacy and safety of single and repeated administration of intravenous paracetamol (acetaminophen) 1 g for the treatment of postoperative pain following orthopedic surgery. Anesthesiology 2005 102 822-831. 

In the late nineteenth century, the emergence of an industry using aniline-based dyes prompted chemists to look for medicines based on aniline (phenylamine). First on the scene was acetanilide, but its toxic side effects saw it being rapidly replaced by phenacetin. Phenacetin remained a widely used painkiller until after World War II, but concern about its safety saw it being replaced on the market by paracetamol during the 1960s. As it happens, both acetanilide and phenacetin owe their effects as drugs to the fact that they are metabolized into paracetamol in the body. 

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