Melatonin - Valium (Diazepam) Interaction

Interaction Details

Diazepam is classified as belonging to the following category: Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.

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

Melatonin can interact with drugs that cause sedation or CNS depression, such as benzodiazepines, opioids, and alcohol, leading to additive effects (i.e., additive sedation and drowsiness effects).

This interaction can increase drowsiness and impair cognitive and motor functions, which may be unsafe for activities that require alertness and concentration, such as driving or operating heavy machinery.

However, if you are using melatonin solely for sleep at night, the interaction is generally not of significant concern.

Nevertheless, it is advisable to consult with a healthcare provider before taking melatonin with other medications, especially those that affect the central nervous system.

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

Diazepam 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

Diazepam 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.

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

Diazepam 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

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

Diazepam is classified as belonging to the following category: Anticonvulsants

Theoretically, melatonin may reduce the effects of anticonvulsants. Some clinical research suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological impairment.

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..

Diazepam Overview

• Diazepam is used to relieve anxiety and to control agitation caused by alcohol withdrawal. It is also used along with other medications to control muscle spasms and spasticity caused by certain neurological disorders such as cerebral palsy (condition that causes difficulty with movement and balance), paraplegia (inability to move parts of the body), athetosis (abnormal muscle contractions), and stiff-man syndrome (a rare disorder with muscle rigidity and stiffness). Diazepam is also used along with other medications to control seizures. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain.

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.