Cinnamon

Cassia cinnamon contains high levels of coumarin (~5 mg/tsp) which has intrinsic anticoagulant properties. Cinnamaldehyde and cinnamon oil also inhibit CYP2C9 (the primary enzyme metabolising S-warfarin), reducing warfarin clearance and increasing plasma INR. A fatal bleeding case was documented when cinnamon was combined with dabigatran in an 80-year-old patient with atrial fibrillation.

Avoid concurrent use of cinnamon supplements with warfarin or DOACs. If patients insist on using cinnamon, Ceylon cinnamon (Cinnamomum verum) has lower coumarin content. Monitor INR closely if Cassia cinnamon supplements are used. Advise patients against self-medicating with high-dose cinnamon preparations.

Cinnamon enhances insulin sensitivity, stimulates GLUT4 translocation, and inhibits alpha-glucosidase activity, lowering post-prandial blood glucose. Combined with antidiabetic medications, this additive hypoglycemic effect may precipitate hypoglycaemia. An animal study showed cinnamon may increase pioglitazone absorption via CYP2C9 modulation.

Monitor blood glucose more frequently when patients on antidiabetic medications begin cinnamon supplementation. Warn patients that cinnamon is not a substitute for prescribed antidiabetic therapy. Dose adjustment of diabetes medications may be needed. Educate patients on signs of hypoglycaemia.

Coumarin found in cinnamon (especially Cassia) affects CYP3A4 activity, potentially slowing the metabolism of CYP3A4-dependent calcium channel blockers. Increased plasma levels of these drugs could cause excessive blood pressure lowering, peripheral oedema, and reflex tachycardia.

Monitor blood pressure more closely when patients on calcium channel blockers add cinnamon supplements. Be especially cautious with high-dose cinnamon preparations. If symptoms of CCB toxicity arise (oedema, flushing, dizziness), reduce or discontinue cinnamon supplementation.

Cinnamaldehyde, a primary volatile compound in cinnamon, has been shown to inhibit CYP2A6 (Drug Metabolism & Disposition, April 2016), the primary enzyme responsible for nicotine metabolism. This may slow nicotine clearance from the body, theoretically increasing nicotine plasma levels and its cardiovascular and CNS effects.

Clinically significant interaction at culinary doses is unlikely. At supplemental doses of cinnamon oil or extract, inform patients on nicotine replacement therapy of this theoretical interaction. Monitor for signs of nicotine excess (nausea, palpitations, headache) if high-dose cinnamon is used concurrently.

Supplemental doses of Cassia cinnamon (high coumarin content) have been associated with hepatotoxicity in case reports. Coumarin is a known hepatotoxin at high doses. Combined with other hepatotoxic medications, the liver burden increases, raising the risk of drug-induced liver injury (DILI). Ceylon cinnamon carries lower risk due to trace coumarin.

Advise against concurrent use of high-dose Cassia cinnamon supplements with known hepatotoxic drugs. Baseline and periodic liver function tests (ALT, AST) are recommended. Inform patients that Cassia cinnamon supplements (not culinary use) are associated with liver toxicity at high doses. Prefer Ceylon cinnamon if supplementation is desired.

Coumarin compounds in cinnamon have demonstrated in vitro inhibition of CYP2D6. This enzyme metabolises metoprolol, codeine (bioactivation), tramadol, and several antipsychotics. Inhibition may increase plasma levels of CYP2D6-metabolised drugs, reducing prodrug activation (codeine to morphine) or increasing parent drug accumulation.

Clinically significant interaction at food doses is unlikely. At supplemental cinnamon doses, monitor patients on narrow-therapeutic-index CYP2D6 substrates. For codeine or tramadol users, cinnamon supplementation may theoretically reduce analgesic efficacy. At supplemental doses, consider alternative analgesics if needed.