Milk Thistle (Silybum marianum)

Traditional texts describe the preparations below, and where those texts give specific amounts, the amounts are quoted here as part of that record. This is a record of historical practice, not a dosage recommendation - the figures are what the sources say, not what HerbMate tells you to take. Amounts, potency, and safe use vary enormously by preparation, plant part, and person.

Chlorzoxazone

Milk thistle does not appear to affect the pharmacokinetics of chlorzoxazone.

Ranitidine

Silymarin, a major constituent of milk thistle, does not appear to affect the pharmackinetics of single-dose ranitidine.

Caffeine

Milk thistle does not appear to affect the pharmacokinetics of caffeine.

Pyrazinamide

The interaction between milk thistle and pyrazinamide is based on experimental evidence only.

Protease inhibitors

Although some studies have found that milk thistle slightly lowers indinavir levels, it appears that this is a time-dependent effect rather than a drug interaction, since it also occurred in a control group in one study. The balance of evidence suggests that no important pharmacokinetic interaction occurs. In vitro studies suggest that silibinin does not affect the pharmacokinetics of ritonavir. Milk thistle 175 mg three times daily (Thisilyn; Nature’s Way, standardised for 80% silymarin content) for 3 weeks caused a 9% reduction in the AUC of indinavir and a 25% reduction in its trough plasma level after four doses of indinavir 800 mg every 8 hours, but only the value for the trough level reached statistical significance. The authors suggested that the effect on the trough level could represent a time-dependent effect of indinavir pharmacokinetics, as the plasma levels without milk thistle were found to be similarly lowered after a washout phase. In another similar study, in 10 healthy subjects, milk thistle standardised for silymarin 160 mg (General Nutrition Corp.) three times daily for 13 days and then with indinavir 800 mg every 8 hours for 4 doses did not cause any statistically significant changes in the indinavir pharmacokinetics (6% reduction in AUC and 32% reduction in minimum level). In yet another similar study, in 8 healthy subjects, milk thistle capsules (standardised for silymarins 456 mg; Kare and Hope Ltd.), three times daily for 28 days, had no effect on the pharmacokinetics of indinavir 800 mg every 8 hours for four doses when compared with 6 subjects in a control group not receiving milk thistle extract. Both the control and indinavir group had a lower indinavir AUC after the second and third time of administration compared with the first, and this decline was greater in the control group. A meta-analysis of these 3 studies showed no effect of milk thistle on indinavir levels.

Digoxin

Milk thistle does not appear to affect the pharmacokinetics of digoxin. In a study, 16 healthy subjects were given a single 400-microgram dose of digoxin before and on the last day of a 14-day course of a milk thistle extract (standardised to 80% silymarin) 300mg three times daily. No statistically significant changes in the pharmacokinetics of digoxin were found, although there was a trend towards a minor 10% reduction in the AUC of digoxin.

Rosuvastatin

Silymarin, a major constituent of milk thistle, does not appear to affect the pharmackinetics of single-dose rosuvastatin. In a randomised study, 8 healthy subjects were given silymarin (Legalon) 140mg three times daily for 5 days. On day 4 they were given a single 10-mg oral dose of rosuvastatin. Silymarin did not significantly affect the pharmacokinetics of rosuvastatin.

Food

No interactions found.

Irinotecan

Milk thistle does not appear to affect the pharmacokinetics of irinotecan.

Herbal medicines

No interactions found.

Benzodiazepines

Milk thistle does not appear to affect the pharmacokinetics of midazolam.

Text

In vitro studies have suggested that milk thistle may interact with a number of drugs by inhibiting their metabolism by various cytochrome P450 isoenzymes or affecting their transport by P-glycoprotein. However, in vivo studies suggest that any such inhibition is unlikely to be clinically relevant. Milk thistle may raise the levels of a hepatotoxic metabolite of pyrazinamide.

Nifedipine

Milk thistle does not appear to alter the haemodynamic effects of nifedipine. In a study in 16 healthy subjects, silymarin 280 mg was given 10 hours, and 90 minutes, before a 10-mg dose of nifedipine. Silymarin increased the AUC of nifedipine by about 10% and reduced its maximum serum levels by about 30%, but these effects varied greatly between subjects. Silymarin did not alter the haemodynamic effects of nifedipine. One capsule of the product used in this study (Legalon) contains 173 to 186mg dry extract from milk thistle fruits, equivalent to silymarin 140 mg calculated as silibinin.

Metronidazole

Silymarin (the active constituent of milk thistle) modestly reduces metronidazole levels.

These entries keep the wording of the reference they come from, and three phrases mean three different things. "No interactions found" means the source looked for reports of that pairing and found none. "No data found" means nothing has been published either way. "Based on experimental evidence only" means the effect has been seen in a laboratory or animal study but not in people - a reason for caution, not a report of harm.