Drug interactions paracetamol

There are few clinically significant drug interactions with paracetamol. 

The opioids (e.g. codeine, dextromethorphan), NSAIDs, aspirin and paracetamol found in many over-the-counter drugs have the potential for adverse drug interactions. For more details, see Over-the-Counter Drugs. 

The authors did not discuss the possible role of paracetamol, which was co-administered in a dosage of 4 g/day (see Paracetamol section under Drug-Drug Interactions in this monograph). 

Lau, A.H. Chang, C.W. Schlesinger, P.K. Evaluation of a potential drug interaction between sucralfate and aspirin. Clin.Pharmacol.Ther, 1986, 39, 151-155 [plasma pharmacokinetics extracted metabolites, salicylic acid, salicyluric acid a-phenylcinnamic acid (IS) gradient column temp 30] Mamolo, M.G. Vio, L. Maurich, V. Higb-pressure liquid chromatographic analysis of paracetamol, caffeine and acetylsalicylic acid in tablets. Salicylic acid quantitation. Farmaco.[Prat]., 1985, 40, 111— 123 [tablets simultaneous ac etcuninophen, caffeine, phenazone, salicylic acid]... 

Fattinger K, Frisullo R, Masche U, Braunschweig S, Meier PJ, Roos M. No clinically relevant drug interaction between paracetamol and phenprocoumcn based on a phar-macoepidemiological cohort study in medical inpatients. EurJ Clin Pharmacol (2002) 57, 863-7. 

How analytical methods deal with interferences is one of the more ad hoc aspects of method validation. There is a variety of approaches to studying interference, from adding arbitrary amounts of a single interferent in the absence of the analyte to establish the response of the instrument to that species, to multivariate methods in which several interferents are added in a statistical protocol to reveal both main and interaction effects. The first question that needs to be answered is to what extent interferences are expected and how likely they are to affect the measurement. In testing blood for glucose by an enzyme electrode, other electroactive species that may be present are ascorbic acid (vitamin C), uric acid, and paracetamol (if this drug has been taken). However, electroactive metals (e.g., copper and silver) are unlikely to be present in blood in great quantities. Potentiometric membrane electrode sensors (ion selective electrodes), of which the pH electrode is the... 

This is known as Michaelis-Menten or saturation kinetics. The processes that involve specific interactions between chemicals and proteins such as plasma protein binding, active excretion from the kidney or liver via transporters, and metabolism catalyzed by enzymes can be saturated. This is because there are a specific number of binding sites that can be fully occupied at higher doses. In some cases, cofactors are required, and their concentration may be limiting (see chap. 7 for salicylate, paracetamol toxicity). These all lead to an increase in the free concentration of the chemical. Some drugs, such as phenytoin, exhibit saturation of metabolism and therefore nonlinear kinetics at therapeutic doses. Alcohol metabolism is also saturated at even normal levels of intake. Under these circumstances, the rate of... 

Concomitant administration of paracetamol with other hepatotoxic drugs or drugs acting on liver microsomal enzymes enhances paracetamol toxicity. Other drugs that interact with paracetamol are metoclopramide, probenecid, and cholestyramine.81... 

Despite case reports of hepatotoxicity in patients taking enzyme inducers and paracetamol concomitantly, there is currently no good evidence that the interactions are clinically significant when recommended doses of paracetamol are used [5]. However, because of the theoretical basis and the potentially severe outcome, patients taking enzyme-inducing drugs are treated with N-acetylcysteine at a reduced threshold in the event of paracetamol overdose. 

Interactions. Rifampicin is a powerful enzyme inducer and speeds the metabolism of numerous drugs, including warfarin, steroid contraceptives, narcotic analgesics, oral antidiabetic agents, phenytoin and dapsone. Appropriate increase in dosage, and alternative methods of contraception, are required to compensate for increased drug metabolism (see also paracetamol overdose, p. 287). 

Many drugs are metabolized by a combination of routes and this can vary from individual to individual and depends on the dose of drug, the presence of interacting drugs and the state of the liver. Metabolism of aspirin and paracetamol are given as examples in Table 2.2 to illustrate this. 

When taken at the recommended dosage, there are few side effects with paracetamol and no major interactions with other drugs. 

Propantheline reduced the rate, but not the extent, of paracetamol absorption. This would be expected to reduce the rate of onset of analgesia. Other antimuscarinic drugs that delay gastric emptying would be expected to interact similarly. In one case, the diphenhydramine component of a paracetamol product delayed paracetamol absorption after an overdose, and complicated the evaluation of the risk of toxicity. 

Propantheline 30 mg intravenously delayed the peak serum levels of paracetamol 1.5 g in 6 convalescent patients from about 1 hour to 3 hours. Peak levels were lowered by about one-third, but the total amount of paracetamol absorbed was unchanged. This effect occurs because propantheline is an antimuscarinic drug that slows the rate at which the stomach empties, so that the rate of absorption in the gut is reduced. The practical consequence of this is likely to be that rapid pain relief with single doses of paracetamol may be delayed and reduced by antimuscarinics (see Table 18. r, (p.672), and Table 18.2 , (p.674) for a list) but this needs clinical confirmation. If the paracetamol is being taken in repeated doses over extended periods this seems unlikely to be an important interaction because the total amount absorbed is unchanged. 

A placebo-controlled, crossover study in 26 healthy subjects found that both intravenous granisetron 3 mg and tropisetron 5 mg blocked the analgesic effect of a single 1 oral dose of paracetamol given 90 minutes later. The pharmacokinetics of paracetamol were unaffected by the two drugs. The interaction was thought to involve the serotonergic system, see Mechanism, in Opioids + Antiemetics Ondansetron , p.l61. 

There was no pharmacokinetic interaction between argatroban and paracetamol, and no further change in coagulation parameters when both drugs were given together in a study. 

The rate and extent of paracetamol (acetaminophen) absorption are reduced by exenatide, even when the paracetamol is given up to four hours after the exenatide. The manufacturer therefore recommends that exenatide be used with caution with drugs that require rapid gastrointestinal absorption or drugs that require a threshold level for efficacy (such as the oral contraceptives and some antibacterials). Further study is necessary to establish the clinical relevance of any of these potential interactions. 

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