Melatonin - Coumadin (Warfarin Sodium) Interaction

Interaction Details

Warfarin Sodium is classified as belonging to the following category: Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2. Also, other CYP1A2 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with drugs metabolized by the CYP1A2 enzyme might reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Interaction Rating

Likelihood of Occurrence

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.

Pharmacist Analysis

Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes.

Some studies suggest that melatonin might increase levels of drugs metabolized by CYP1A2. This is because melatonin may inhibit the activity of CYP1A2, leading to reduced metabolism of CYP1A2 substrates and increased serum levels of these drugs.

On the other hand, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin.

Overall, studies suggest that any inhibition of CYP1A2 by melatonin, when used at typical dosages, is likely to be very minor, and clinically significant drug interactions are thought to be unlikely.

There is some theoretical concern that melatonin may increase the risk of bleeding if used with drugs that have a 'blood-thinning' effect, like Coumadin, but it should be noted that the evidence on the potential interaction is limited and conflicting.

In isolated case reports, there have been some reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin), an anticoagulant. The mechanism of this interaction is not fully understood but melatonin is thought to have mild anticoagulant effects in some individuals.

Overall, the risk of an interaction between melatonin and blood-thinning drugs is relatively low bu it's always a good idea to talk to your healthcare provider before taking any new medications or supplements, including melatonin and Coumadin, to make sure they are safe and appropriate for you.

References

• Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191.
• Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134.
• Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31.

Interaction Details

Warfarin Sodium is classified as belonging to the following category: Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP2C19. Also, other CYP2C19 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2C19 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP2C19 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Interaction Rating

Likelihood of Occurrence

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.

Pharmacist Analysis

There is some theoretical concern that melatonin may increase the risk of bleeding if used with drugs that have a 'blood-thinning' effect, like Coumadin, but it should be noted that the evidence on the potential interaction is limited and conflicting.

In isolated case reports, there have been some reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin), an anticoagulant. The mechanism of this interaction is not fully understood but melatonin is thought to have mild anticoagulant effects in some individuals.

Overall, the risk of an interaction between melatonin and blood-thinning drugs is relatively low bu it's always a good idea to talk to your healthcare provider before taking any new medications or supplements, including melatonin and Coumadin, to make sure they are safe and appropriate for you.

References

• Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191.
• Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134.

Interaction Details

Warfarin Sodium is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

Pharmacist Analysis

There is some theoretical concern that melatonin may increase the risk of bleeding if used with drugs that have a 'blood-thinning' effect, like Coumadin, but it should be noted that the evidence on the potential interaction is limited and conflicting.

In isolated case reports, there have been some reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin), an anticoagulant. The mechanism of this interaction is not fully understood but melatonin is thought to have mild anticoagulant effects in some individuals.

Overall, the risk of an interaction between melatonin and blood-thinning drugs is relatively low bu it's always a good idea to talk to your healthcare provider before taking any new medications or supplements, including melatonin and Coumadin, to make sure they are safe and appropriate for you.

References

• Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31.

Interaction Details

Warfarin Sodium is classified as belonging to the following category: Anticoagulant/Antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There are isolated case reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin). The mechanism, if any, of this interaction is unknown. Taking melatonin orally seems to decrease coagulation activity within one hour of dosing in healthy men.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

Pharmacist Analysis

There is some theoretical concern that melatonin may increase the risk of bleeding if used with drugs that have a 'blood-thinning' effect, like Coumadin, but it should be noted that the evidence on the potential interaction is limited and conflicting.

In isolated case reports, there have been some reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin), an anticoagulant. The mechanism of this interaction is not fully understood but melatonin is thought to have mild anticoagulant effects in some individuals.

Overall, the risk of an interaction between melatonin and blood-thinning drugs is relatively low bu it's always a good idea to talk to your healthcare provider before taking any new medications or supplements, including melatonin and Coumadin, to make sure they are safe and appropriate for you.

References

• Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520.
• Wirtz, P. H., Spillmann, M., Bartschi, C., Ehlert, U., and von Kanel, R. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res 2008;44(2):127-133.
• U.S.Food and Drug Administration. Special Nutritionals Adverse Events Monitoring System: registered case reports.

Interaction Details

Warfarin Sodium is classified as belonging to the following category: Warfarin (Coumadin)

Theoretically, melatonin may have antiplatelet effects and may increase the risk of bleeding with warfarin.
Three cases of increased prothrombin time have been reported for patients aged 48-72 years who took melatonin orally in combination with warfarin. However, three cases of decreased prothrombin time have also been reported for patients aged 51-84 years who took melatonin orally in combination with warfarin. Until more is known, use melatonin cautiously in patients taking warfarin.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

Pharmacist Analysis

There is some theoretical concern that melatonin may increase the risk of bleeding if used with drugs that have a 'blood-thinning' effect, like Coumadin, but it should be noted that the evidence on the potential interaction is limited and conflicting.

In isolated case reports, there have been some reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin), an anticoagulant. The mechanism of this interaction is not fully understood but melatonin is thought to have mild anticoagulant effects in some individuals.

Overall, the risk of an interaction between melatonin and blood-thinning drugs is relatively low bu it's always a good idea to talk to your healthcare provider before taking any new medications or supplements, including melatonin and Coumadin, to make sure they are safe and appropriate for you.

References

• Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520.

Warfarin Sodium Overview

• Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

Melatonin - More Interactions

Melatonin interacts with 1425 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.