Paracetamol (Acetaminophen) + Herbal medicines - Drug Interactions

Studies in healthy subjects found that garlic and hibiscus extractsdid not affect pharmacokinetics of single-dose paracetamol toa clinically relevant extent, although clearance of paracetamolwas increased by hibiscus extract. Similarly, single-dose studies inhealthy subjects found that Kakkonto did not affect pharmacokinetics of paracetamol, but animal studies found increased paracetamol levels.

Clinical evidence,mechanism, importance and management

A study in 16 healthy subjects found that use of an aged garlic extract (approximately equivalent to 6 to 7 cloves of garlic daily) for 3 months had little effect on metabolism of a single 1-g oral dose of paracetamol. There was a very slight increase in glucuronidation after long-term use of garlic, and some evidence that sulfate conjugation was enhanced, but no effect on oxidative metabolism (See reference number 1). No clinically significant interaction would therefore be expected if paracetamol is taken with garlic.

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 absorption or AUC of paracetamol, but total body clearance increased by 12 % (See reference number 2). This is not expected to be clinically significant.

A study in 6 healthy subjects found that 5 g of Kakkonto extract,a Chinese herbal medicine containing extracts of Puerariae, Ephedrae, Zingiberis, Cinnamomi, Glycyrrhizae, Paeoniae and Zizphi spp. had no effects on pharmacokinetics of a single 12-mg/kg dose of paracetamol. A further study in 19 healthy subjects found that 1.25 g of Kakkonto had no effect on pharmacokinetics of paracetamol 150mg (from a preparation also containing salicylamide, caffeine and promethazine methylene disalicylate). Because in animal studies high doses of Kakkonto for 7 days were found to significantly increase serum levels of paracetamol, authors concluded that further investigations were required to assess safety and efficacy of concurrent use (See reference number 3).

Gwilt PR,Lear CL, Tempero MA, Birt DD, Grandjean AC, Ruddon RW, Nagel DL. The effectof garlic extract on human metabolism of acetaminophen. Cancer Epidemiol Biomarkers Prev (1994) 3, 155–60.

Kolawole JA,Maduenyi A. Effect of Zobo drink (Hibiscus sabdariffa water extract) on thepharmacokinetics of acetaminophen in human volunteers. Eur J Drug Metab Pharmacokinet (2004) 29, 25–9.

Qi J,Toyoshima A, Honda Y, Mineshita S. Pharmacokinetic study on acetaminophen: interaction with a Chinese medicine. J Med Dent Sci (1997) 44, 31–5.