Melatonin - Luvox (Fluvoxamine) Interaction

Interaction Details

Fluvoxamine is classified as belonging to the following category: Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.

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

References

• Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254.
• Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85..

Interaction Details

Fluvoxamine 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.

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

Fluvoxamine is classified as belonging to the following category: Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, melatonin might increase levels of drugs metabolized by CYP2D6.
Laboratory research suggests that certain lots of melatonin inhibit CYP2D6. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2D6 enzyme 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 evidence to suggest that melatonin may inhibit the activity of the CYP2D6 enzyme (a type of metabolizing enzyme).

CYP2D6 is responsible for metabolizing many drugs, including some antidepressants, antipsychotics, and beta blockers. When this enzyme is inhibited, it can lead to increased levels of these drugs in the body, which can cause side effects or toxicity.

Studies are conflicting as some have shown that melatonin can inhibit CYP2D6 while others have found no significant effect of melatonin on CYP2D6 activity.

Overall, the potential interaction between melatonin and drugs metabolized by CYP2D6 is still unclear and may depend on factors such as the dose of melatonin, the specific drug being metabolized, and individual differences in metabolism.

It is always recommended to consult with a healthcare provider before taking any new supplements or medications, especially if you are taking other medications or have underlying health conditions.

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

Fluvoxamine is classified as belonging to the following category: Fluvoxamine (Luvox)

Theoretically, taking fluvoxamine with melatonin might increase levels of melatonin.
Fluvoxamine can significantly increase melatonin levels. In some cases, fluvoxamine might increase bioavailability of exogenously administered melatonin by up to 20 times. Some researchers think this might be a beneficial interaction and be potentially useful for cases of refractory insomnia. However, this interaction might also cause unwanted excessive drowsiness and possibly other adverse effects. Fluvoxamine is known to increase endogenous melatonin secretion. It seems to increase serum levels of exogenously administered melatonin possibly by decreasing melatonin metabolism by inhibiting cytochrome P450 (CYP450) 1A2 and 2C19 or by inhibiting melatonin elimination. This effect has been found in healthy people taking fluvoxamine 50-75 mg and melatonin 5 mg.

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.

References

• Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
• von Bahr C, Ursing C, Yasui N, et al. Fluvoxamine but not citalopram increases serum melatonin in healthy subjects – an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 2000;56:123-7.
• Grozinger M, Hartter S, Wang X, et al. Fluvoxamine strongly inhibits melatonin metabolism in a patient with low-amplitude melatonin profile. Arch Gen Psychiatry 2000 Aug;57:812-3.
• Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
• Sunami E, Usuda K, Nishiyama Y, et al. A preliminary study of fluvoxamine maleate on depressive state and serum melatonin levels in patients after cerebral infarction. Intern Med. 2012;51(10):1187-93.

Fluvoxamine Overview

• Fluvoxamine is used to treat obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over) and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). Fluvoxamine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

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.