McKenna's Pharmacology for Nursing, 2e

C H A P T E R 1 6  Anti-inflammatory, antiarthritis and related agents 251

(aspirin may mask Reye’s syndrome in children); and for the relief of musculoskeletal pain associated with arth­ ritis (see Table 16.2). Pharmacokinetics Paracetamol is rapidly absorbed from the GI tract, reaching peak levels in 30 minutes to 2 hours. It is extensively metabolised in the liver and excreted in the urine, with a half-life of about 2 hours. Caution should be used in people with hepatic or renal impairment, which could interfere with metabolism and excretion of the drug, leading to toxic levels. Paracetamol crosses the placenta and enters breast milk; it should be used cau- tiously during pregnancy or breastfeeding because of the potential adverse effects on the fetus or neonate. Contraindications and cautions Paracetamol is contraindicated in the presence of allergy to paracetamol. It should be used cautiously in preg- nancy or breastfeeding and in hepatic dysfunction or chronic alcoholism because of associated toxic effects on the liver. Adverse effects Adverse effects associated with paracetamol use include headache, haemolytic anaemia, renal dysfunction, skin rash and fever. Hepatotoxicity is a potentially fatal adverse effect that is usually associated with chronic use and overdose, and is related to direct toxic effects on the liver. The dose that could prove toxic varies with the age of the person, other drugs that the person Prototype summary: Paracetamol Indications: Treatment of mild to moderate pain, fever, or signs and symptoms of the common cold or flu; musculoskeletal pain associated with arthritis and rheumatic disorders. Actions: Acts directly on the hypothalamus to cause vasodilation and sweating, which will reduce fever; mechanism of action as an analgesic is not understood. Pharmacokinetics: Route Onset Peak Duration Oral Varies 0.5–2 hours 3–6 hours T 1/2 : 1 to 3 hours; metabolised in the liver and excreted in the urine. Adverse effects: Rash, fever, chest pain, liver toxicity and failure, bone marrow suppression.

might be taking and the underlying hepatic function of that person. When overdose occurs, acetylcysteine can be used as an antidote. Life support measures may also be necessary. Clinically important drug–drug interactions There is an increased risk of bleeding with oral anti­ coagulants because of effects on the liver; of toxicity with chronic ethanol ingestion because of toxic effects on the liver; and of hepatotoxicity with barbiturates, carbamazepine, hydantoins, rifampicin or sulfinpyra- zone. These combinations should be avoided, but if they must be used, appropriate dose adjustment should be made and the person should be monitored closely.

■■ BOX 16.6  Withdrawal of Paradex and Capadex (in New Zealand)— DEXTROPROPOXYPHENE AND PARACETAMOL COMBINATION

In December 2009 the Medicines Adverse Reactions Committee (MARC) reviewed the benefits and risk of dextropropoxyphene-containing medicines. 1 The MARC assessed the published literature; adverse reactions reported in New Zealand (NZ) and internationally; NZ Poisons Centre data, the results of a Paradex utilisation study conducted in New Zealand in 2007. The MARC also considered reviews conducted by other medicine regulators. After analysis and discussion of the available data the MARC concluded there is evidence that: • These medicines are no more effective than maximum recommended doses of paracetamol alone. • These medicines have the potential to cause more adverse reactions than paracetamol used at recommended doses. • These medicines are more dangerous than other simple analgesics in overdose, particularly when combined with alcohol. Deaths have occurred in association with dextropropoxyphene use in NZ. • Deaths related to dextropropoxyphene overdose have occurred within 1 hour of ingestion and before medical intervention could be obtained. Prescribing restrictions introduced in 2006 have failed to ensure that these medicines were only used in people for whom the benefits are likely to outweigh the risks. Overall the risks of these medicines exceed their benefits. Therefore, in the interests of public safety, the MARC has recommended that Capadex and Paradex be withdrawn from New Zealand. 1 www.medsafe.govt.nz/profs/PUArticles/Dextropropoxyphene%20- %20review%20concludes%20risk-benefit%20balance%20 unfavourable.htm Source: MEDSAFE – NZ Medicines and Medical Devices Safety Authority (2010)