Clove

Eugenol, the primary active constituent of clove (70-90% of clove oil), inhibits platelet aggregation via inhibition of thromboxane synthesis and increased 12-HPETE formation. Eugenol was found to be more potent than aspirin in some in vitro assays. Combined with anticoagulants, additive bleeding risk exists. CYP2C9 inhibition by eugenol may also reduce warfarin clearance.

Monitor INR in patients on warfarin using clove supplements or clove oil. Report unusual bruising or bleeding. Discontinue clove oil supplementation at least 2 weeks before surgery. Culinary clove use at normal food amounts carries minimal risk.

Eugenol and acetyl eugenol from clove reversibly inhibit platelet aggregation by inhibiting thromboxane A2 formation and enhancing lipoxygenase products (12-HPETE). In vitro studies show eugenol is more potent than aspirin for some aggregation pathways. Combined with antiplatelet drugs, the additive inhibition of platelet function significantly raises bleeding risk.

Avoid combining high-dose clove or clove oil supplementation with antiplatelet medications unless medically supervised. Discontinue clove supplements 2 weeks before procedures. Monitor for signs of excessive bleeding.

In vitro studies using human liver microsomes demonstrate that eugenol is a strong inhibitor of CYP2C9 activity, with significant inhibition observed even at very low concentrations (IC50 <0.01 µM). This could increase plasma concentrations of CYP2C9 substrates including S-warfarin, phenytoin, and NSAIDs, heightening toxicity risk.

Monitor plasma levels or pharmacodynamic effects of CYP2C9-metabolized drugs in patients using medicinal clove preparations. Monitor INR for warfarin, phenytoin levels for epileptics, and blood pressure for losartan users. Effect at culinary doses is likely minimal.

Eugenol inhibits CYP2D6 activity in human liver microsomes in a concentration-dependent manner (IC50 ~11 µM). This can impair activation of prodrugs metabolized by CYP2D6 (e.g., codeine to morphine) or increase plasma levels of drugs cleared by this enzyme (e.g., metoprolol, haloperidol).

Use caution when combining clove oil or medicinal clove preparations with CYP2D6-metabolized drugs. For codeine, reduced analgesic effect may occur. For metoprolol or haloperidol, increased plasma levels may heighten cardiac or CNS side effects. Monitor clinically and adjust doses as needed.

Clove extract represses genes encoding hepatic gluconeogenic enzymes, with demonstrated blood glucose-lowering activity in animal studies. Eugenol affects blood sugar levels through multiple mechanisms. Additive hypoglycemic effects may occur when clove supplements are combined with antidiabetic medications.

Monitor blood glucose in diabetic patients who use therapeutic clove preparations. Patients should watch for hypoglycemic symptoms. Stop high-dose clove use at least 2 weeks before surgery as it may interfere with blood sugar control perioperatively.

Eugenol ingested at therapeutic doses has not been linked to liver injury, but high-dose clove oil overdose can cause severe hepatic injury through oxidative stress and mitochondrial dysfunction. Concurrent use with other hepatotoxic agents may compound liver stress.

Advise patients against using concentrated clove oil internally in large doses, particularly if on hepatotoxic medications. Monitor liver function tests with prolonged use of therapeutic clove preparations in patients on methotrexate or isoniazid. Culinary clove consumption is safe.