Paracetamol clinical studies

The UK manufacturers report that in interaction clinical studies there was no evidence of clinically relevant interactions between letrozole and other commonly prescribed drugs, namely benzodiazepines such as diazepam, barbiturates, diclofenac, fiirosemide, ibuprofen, omeprazole, and paracetamol (acetaminophen). ... 

The absorption of raloxifene is reduced by colestyramine, and their concurrent use is not recommended. No clinically relevant changes in raloxifene pharmacokinetics occur with alumini-um/magnesium hydroxide, amoxicillin, ampicillin or calcium carbonate. Raloxifene does not alter digoxin or methylprednisolone levels. Oral antibacterials, antihistamines, aspirin, benzodiazepines, H2-receptor antagonists, ibuprofen or paracetamol (acetaminophen) were used in clinical studies without any obvious effect on raloxifene levels. Smoking does not appear to alter the efficacy of raloxifene. 

Animal studies have indicated a carcinogenic effect when paracetamol has been administered for prolonged periods in relatively high dosages. However, no clinical data are so far available to corroborate this. The matter cannot be dismissed entirely for the time being, in view of a report (68) of the development of chromosomal aberrations after prolonged use. 

In an early, double-blind, placebo-controlled study of the interaction between coumarin anticoagulants and paracetamol, there was a statistically significant lengthening of the prothrombin time (124). The effect, although statistically significant, was very small and was considered to be clinically unimportant. 

Studies in heaithy subjects found that gariic and hibiscus extracts did not affect the pharmacokinetics of single-dose paracetamol to a clinically relevant extent, although the clearance of paracetamol was increased by hibiscus extract. Similarly, single-dose studies in healthy subjects found that Kakkonto did not affect the pharmacokinetics of paracetamol, but animal studies found increased paracetamol levels. 

A study in 6 healthy subjects found that Zobo drink Hibiscus sabdariffa water extract), given 78 minutes before a single 1-g dose of paracetamol did not affect the absorption or AUC of paracetamol, but the total body clearance increased by 12%. This is not expected to be clinically significant. 

The modest pharmacokinetic interaction between the oral contraceptives and paracetamol appears to be established, but its clinical importance has not been directly studied. The clinical importance of the modest increased ethinylestradiol absorption is also uncertain, but likely to be minor. HRT appears not to interact with paracetamol. 

The changes described here appear to be small, and therefore unlikely to be clinically significant. Note that, it has been postulated, based on studies in animals, that propranolol may have a protective effect on paracetamol hepatic toxicity by inhibiting the oxidative metabolism of paracetamol to toxic metabolites. ... 

The findings from these studies suggest that neither lansoprazole nor omeprazole cause any clinically important changes in the pharmacokinetics of paracetamol. No special precautions appear to be needed on concurrent... 

Moreover, in response to one case-control study other clinicians running outpatient anticoagulant clinics have contended that they have not observed an interaction with paracetamol in their experience. ... 

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. 

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. 

Taken together, the results of these two studies suggest that these drugs may reduce the flu-like adverse effects of interferon, perhaps more so at lower doses of interferon. The clinical relevance of the measures of antiviral activity of interferon is uncertain, so the disparate effects found with paracetamol and prednisone are unclear. 

In a study in healthy subjects, rimantadine 100 mg twice daily was given for 13 days. On day 11, paracetamol 650 mg four times daily was started and continued for 8 days. The peak plasma levels and AUC of rimantadine were reduced by about 11% in the presence of paracetamol. This reduction is unlikely to be clinically relevant. 

Paracetamol No significant effect on the pharmacokinetics of paracetamol was found in one study but another small study found that the metabolism of paracetamol was reduced. Unlikely to be clinically significant. 36,37... 

A study in rheumatoid arthritis patients taking ciclosporin 2.5 mg/kg daily, found that creatinine clearances were reduced by 3.5% in those taking paracetamol 650 mg four times daily, but this was not considered to be clinically important. ... 

Observational studies In clinical trials, in the absence of premedication, the rates of infusion-related reactions have been higher with amphotericin B colloidal dispersion (ABCD) than with other forms of amphotericin B, including amphotericin B deoxy-cholate [7 ]. Data on pre-medication practices and infusion-related reactions in 170 patients (median age 37 years 52% men) who received 1230 infusions of ABCD (mean dose 2.8 mg/kg/day) have been captured in a multicenter, worldwide, observational registry [8 ]. Treatment was according to the site s standard treatment practice. Common pre-medications included glucocorticoids, antihistamines, paracetamol (acetaminophen), and metamizole. The overall rate of infusion-related reactions... 

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