Meta Information
ID:sustained-release-melatonin
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
major
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
null
Description:
Melatonin is the primary hormone that signals the brain to prepare for sleep; its administration must be timed to align with the desired sleep onset.
Actionable advice:
Melatonin should be taken 30 to 60 minutes before the intended bedtime for optimal effect.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Melatonin, primarily known for its use in treating insomnia and jetlag, has shown promising effects as a pain medication in chronic non-musculoskeletal pain conditions.
Label source:
PubMed: Melatonin for chronic back pain (the MOCHA trial): study protocol for a randomized, double-blind, placebo-controlled trial. (PMID 41250112)
Action type:
separate
Target id:
/environment/darkness
Target name:
A Dark Environment
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Darkness is the natural cue for endogenous melatonin release. Combining supplemental melatonin with a dark environment reinforces the sleep signal to the brain.
Actionable advice:
The sleep environment should be completely dark after taking melatonin to maximize its effectiveness.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The SCN-activated, light-inhibited production of melatonin conveys the message of darkness to the clock and induces night-state physiological functions, for example, sleep/wake blood pressure and metabolism.
Label source:
PubMed: British journal of pharmacology (2018)
Source url:
Exact phrase from label:
Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'.
Label source:
PubMed: Drug discovery today (2014)
Source url:
Exact phrase from label:
The midnight 2-hour dark period partially restored, but the evening melatonin pre-treatment completely restored the dLAN-induced disrupted neurobehaviours and associated gene expressions.
Label source:
PubMed: Scientific reports (2025)
Action type:
informational_none
Target id:
/environment/blue-light-exposure
Target name:
Blue Light Exposure (Screens, Lights)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
0
Description:
Exposure to light, especially in the blue spectrum, strongly suppresses the brain's production and release of melatonin, directly counteracting its sleep-promoting effects.
Actionable advice:
All screens and bright lights should be avoided for at least 1-2 hours before bed and especially after taking the dose.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In fact, there may be similarities between the widespread concern about vitamin D deficiency as a "sunlight deficiency" and reduced melatonin secretion as a result of "darkness deficiency" from overexposure to artificial blue light.
Label source:
PubMed: Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. (PMID 36235587)
Action type:
separate
Target id:
/intervention/fluvoxamine
Target name:
Fluvoxamine (Luvox)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Fluvoxamine is a potent inhibitor of CYP1A2, the primary enzyme that metabolizes melatonin, leading to a dramatic (up to 17-fold) increase in melatonin levels and risk of excessive sedation.
Actionable advice:
Melatonin should not be taken with fluvoxamine unless under strict medical supervision due to a major interaction.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Coadministration of fluvoxamine, on average, led to an 17-fold higher (P < .05) area under concentration-time curve (AUC) and a 12-fold higher (P < .01) serum peak concentration (Cmax) of melatonin.
Label source:
PubMed: Increased bioavailability of oral melatonin after fluvoxamine coadministration. (PMID 10668847)
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The effects of supplemental melatonin on fetal development are unknown, and its use is not established as safe during pregnancy.
Actionable advice:
Melatonin should be strictly avoided during pregnancy due to a lack of safety data.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Taking melatonin supplements during pregnancy has not been well studied.
Label source:
Anecdotal: MotherToBaby
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if supplemental melatonin passes into breast milk or what its effects might be on a nursing infant.
Actionable advice:
Melatonin should be strictly avoided while breastfeeding due to a lack of safety data.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Melatonin has no specific use during breastfeeding, and no data exist on the safety of maternal use of melatonin during breastfeeding.
Label source:
Anecdotal: LactMed
Action type:
avoid
Target id:
/class/cyp1a2-inhibitors
Target name:
CYP1A2 Inhibitors (e.g., Ciprofloxacin)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Medications that inhibit the CYP1A2 enzyme reduce the breakdown of melatonin, which can significantly increase its concentration and sedative effects.
Actionable advice:
It is important to talk to a doctor before using melatonin with CYP1A2 inhibiting drugs, as the dose may need to be reduced.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When caffeine was coadministered the Cmax and AUC of melatonin were increased on average by 142% (P = 0.001, confidence interval on the difference 44, 80%) and 120% (P < 0.001, confidence interval on the difference 63, 178%), respectively.
Label source:
PubMed: British journal of clinical pharmacology (2003)
Source url:
Exact phrase from label:
The mean melatonin AUC and C(max) values were 4- to 5-fold higher in OC users than in non-OC users (P < .0001), whereas the weight-adjusted clearance was significantly lower in OC users (P < .0001).
Label source:
PubMed: Journal of clinical pharmacology (2008)
Action type:
adjust_with_prescriber
Target id:
/class/cyp1a2-inducers
Target name:
CYP1A2 Inducers (e.g., Carbamazepine, Smoking)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Substances that induce the CYP1A2 enzyme, such as tobacco smoke or certain anticonvulsants, accelerate the metabolism of melatonin, reducing its blood levels and effectiveness.
Actionable advice:
It is worth being aware that smoking or taking certain medications can reduce melatonin's effectiveness, potentially requiring a different dose.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Polycyclic aromatic hydrocarbons in cigarette smoke induce cytochrome P450(CYP)1A2, which is involved in the hepatic metabolism of melatonin (MT). This suggests that habitual smokers may have low serum MT levels during smoking compared with a non-smoking period.
Label source:
PubMed: European journal of clinical pharmacology (2005)
Source url:
Exact phrase from label:
Elevated CYP1A2 expression in liver was also found in the THS-exposed mice. Hypo-methylation of 7 CPG sites on the CYP1A2 promoter was identified, which accelerated the catabolism of melatonin.
Label source:
PubMed: Environmental pollution (Barking, Essex : 1987) (2021)
Source url:
Exact phrase from label:
Pharmacokinetics was affected by age, caffeine, smoking, oral contraceptives, feeding status, and fluvoxamine.
Label source:
PubMed: European journal of clinical pharmacology (2015)
Action type:
informational_none
Target id:
/class/benzodiazepines
Target name:
Benzodiazepines
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining melatonin with benzodiazepines can result in additive central nervous system depression, leading to excessive drowsiness, dizziness, and impaired coordination.
Actionable advice:
Extreme caution is warranted when combining melatonin with benzodiazepines, given the additive sedative effects.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The authors present a case of 16-year-old male intentionally overdosed on 900mg of melatonin (180 tablets) and 10 tablets of 0.5mg alprazolam. Admitted to the emergency department, he was extremely drowsy and minimally responsive with a Glasgow coma scale score of 8/15.
Label source:
PubMed: Sleep medicine: X (2024)
Source url:
Exact phrase from label:
Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo.
Label source:
PubMed: The Cochrane database of systematic reviews (2020)
Source url:
Exact phrase from label:
Administration of melatonin or temazepam significantly elevated subjective sleepiness levels, relative to placebo (P </= 0.05).
Label source:
PubMed: Journal of sleep research (2003)
Action type:
informational_none
Target id:
/class/cns-depressants
Target name:
Z-Drugs (e.g., Zolpidem, Zopiclone)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concurrent use of melatonin and Z-drugs can enhance sedative effects, increasing the risk of next-day drowsiness, cognitive impairment, and complex sleep behaviors.
Actionable advice:
Extreme caution is warranted when combining melatonin with Z-drugs, given the increased risk of drowsiness and impairment.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Zolpidem 20 mg plus melatonin 0 mg also enhanced daytime sleep (albeit nonsignificantly), but memory and vigilance were impaired (P < .05). Melatonin's sleep-promoting effects were not evident until the second nap.
Label source:
PubMed: Sleep (2005)
Source url:
Exact phrase from label:
Combining melatonin with low-dose zolpidem may promote daytime sleep without exacerbating performance impairments seen with high-dose zolpidem alone.
Label source:
PubMed: Sleep (2005)
Source url:
Exact phrase from label:
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability.
Label source:
PubMed: Pharmacological reviews (2018)
Action type:
informational_none
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
moderate
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
0
Description:
Alcohol is a central nervous system depressant that can amplify the sedative effects of melatonin. It also disrupts sleep architecture in the later part of the night, negating melatonin's benefits.
Actionable advice:
Alcohol should not be consumed for at least 4 hours before taking melatonin.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
studies found that in nonalcoholics who occasionally use alcohol, both high and low doses of alcohol initially improve sleep, although high alcohol doses can result in sleep disturbances during the second half of the nocturnal sleep period.
Label source:
PubMed: Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism (2001)
Source url:
Exact phrase from label:
As a rhythm regulator, melatonin exerts a wide range of different effects: circadian rhythm regulation, thermoregulation, sleep induction, antioxidant, immunomodulatory, and anti-stress ones. This review presents from a chronobiological perspective the impact of melatonin on alcohol intoxication in terms of mental disorders, sleep and inflammation, hepatic injury, and mitochondrial function.
Label source:
PubMed: Chronobiology international (2021)
Source url:
Exact phrase from label:
Following a single acute alcohol intake, changes in biological rhythms are dose-dependent, reflected in the melatonin and cortisol secretions, and the core body temperature (CBT) rhythms.
Label source:
PubMed: Progress in neuro-psychopharmacology & biological psychiatry (2020)
Action type:
separate
Target id:
/condition/diabetes-mellitus
Target name:
Diabetes Mellitus
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Melatonin can influence glucose metabolism and insulin sensitivity, potentially affecting blood sugar control, especially when taken in the evening close to meals.
Actionable advice:
Blood glucose levels are best monitored closely when starting or stopping melatonin for those with diabetes.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women.
Label source:
PubMed: Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. (PMID 11298086)
Action type:
monitor
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its potential effects on blood glucose and insulin sensitivity, melatonin may alter the effectiveness of medications used to manage diabetes.
Actionable advice:
It is a good idea to consult a doctor and monitor blood sugar carefully when taking melatonin with diabetes medications.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our results show that melatonin reduces insulin sensitivity in human AT during the evening. These results may partly explain the previous studies showing a decrease in glucose tolerance after oral melatonin administration in the evening or when eating late when endogenous melatonin is present.
Label source:
PubMed: Journal of pineal research (2024)
Source url:
Exact phrase from label:
Melatonin administration impaired glucose tolerance. When administered in the morning, melatonin significantly increased the incremental area under the curve (AUC) and maximum concentration (Cmax) of plasma glucose following OGTT by 186% and 21%, respectively, as compared to placebo; while in the evening, melatonin significantly increased glucose AUC and Cmax by 54% and 27%, respectively.
Label source:
PubMed: Sleep (2014)
Action type:
monitor
Target id:
/condition/seizure-disorder
Target name:
Seizure Disorder / Epilepsy
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There are conflicting reports, but some evidence suggests melatonin may alter neurotransmitter activity in a way that could lower the seizure threshold in susceptible individuals.
Actionable advice:
Melatonin is best avoided by those with a history of seizures, unless approved by a neurologist.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In the present communication we present evidence, based on magnetoencephalographic (MEG) brain measurements, that melatonin may exert proconvulsive activity in humans as well.
Label source:
PubMed: The International journal of neuroscience (1992)
Source url:
Exact phrase from label:
Experimental studies point to a possibility that endogenous melatonin may possess proconvulsive activity. Moreover, some scarce clinical data seem to express this view; however, a limited number of patients were included. The anticonvulsant activity of exogenous melatonin may involve GABA-mediated inhibition, while endogenous melatonin may act as a proconvulsant due to a decrease in the brain dopaminergic transmission.
Label source:
PubMed: International journal of molecular sciences (2024)
Source url:
Exact phrase from label:
On the other hand, melatonin has been shown to induce electroencephalographic abnormalities in patients with temporal lobe epilepsy and increase seizure activity in neurologically disabled children.
Label source:
PubMed: Pharmacological reports : PR (2011)
Action type:
avoid
Target id:
/class/anticonvulsants
Target name:
Anticonvulsant Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Melatonin may potentially reduce the efficacy of anticonvulsant drugs by lowering the seizure threshold. Additionally, some anticonvulsants induce enzymes that break down melatonin faster.
Actionable advice:
It is important to talk to a neurologist before taking melatonin while on medication for a seizure disorder.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our results suggest that nocturnal activation of hippocampal Mel(1b) receptors depresses GABA(A) receptor function in the hippocampus and enhances seizure susceptibility.
Label source:
PubMed: Epilepsia (2005)
Source url:
Exact phrase from label:
Specific actions within the hippocampus may mean that patients with temporal lobe epilepsy are particularly susceptible to the endogenous expression of melatonin via inhibitory actions on dopaminergic activity reducing seizure thresholds.
Label source:
PubMed: Medical hypotheses (2011)
Source url:
Exact phrase from label:
Melatonin (50 mg/kg; 60 min before the test) significantly raised the electroconvulsive threshold in mice.
Label source:
PubMed: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (1999)
Action type:
informational_none
Target id:
/condition/autoimmune-disease
Target name:
Autoimmune Conditions
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Melatonin has immunostimulatory properties, which could theoretically exacerbate the underlying pathology of autoimmune diseases like rheumatoid arthritis or lupus.
Actionable advice:
It is important to talk to a doctor before using melatonin with an autoimmune condition.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Melatonin possesses anti-inflammatory and immune-modulative properties in animal and clinical trials.
Label source:
PubMed: Efficacy and Safety of Melatonin as an Adjunctive Therapy on Clinical, Biochemical, and Quality of Life in Patients with Ulcerative Colitis. (PMID 34567156)
Action type:
informational_none
Target id:
/class/immunosuppressants
Target name:
Immunosuppressant Medications
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Melatonin's immune-stimulating effects may counteract the intended action of immunosuppressant drugs, such as those used after an organ transplant.
Actionable advice:
Melatonin is best avoided by those taking immunosuppressant drugs, as it may interfere with their action.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation.
Label source:
PubMed: International journal of molecular sciences (2013)
Source url:
Exact phrase from label:
Estrogens, melatonin and chronic stress (inducing decreased adrenal glucocorticoid release over a long time) strongly modulate the NEI system and stimulate the immune response. The vitamin D endocrine system is regarded as a potential immunosuppressive factor. Consequently, estrogens (especially in patients affected by B-cell-driven immunity) and melatonin should be avoided, and glucocorticoids (as replacement therapy) and vitamin D are allowed in the treatment of autoimmunity.
Label source:
PubMed: Arthritis research & therapy (2009)
Source url:
Exact phrase from label:
Additionally, the use of Panax ginseng, green tea, Schisandra sphenanthera and melatonin in patients receiving tacrolimus is highly controversial.
Label source:
PubMed: Pharmaceutics (2022)
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The liver is responsible for metabolizing melatonin. Impaired liver function can lead to higher and more prolonged levels of melatonin, increasing the risk of side effects.
Actionable advice:
Melatonin is best used with caution and under medical guidance in those with liver disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
A high hepatic extraction ratio was calculated, suggesting prominent first pass hepatic metabolism and reduced bioavailability for orally administered melatonin.
Label source:
PubMed: The Journal of clinical endocrinology and metabolism (1985)
Source url:
Exact phrase from label:
Liver is the organ that high concentration of melatonin (N-acetyl-5-methoxytryptamine) accumulates, and it is the sole organ where circulating melatonin is metabolized.
Label source:
PubMed: Journal of cellular physiology (2018)
Source url:
Exact phrase from label:
The pathophysiology of these disturbances is not fully understood but is believed to be linked to impaired hepatic melatonin metabolism.
Label source:
PubMed: Scientifica (2016)
Action type:
informational_none
Target id:
/intervention/caffeine
Target name:
Caffeine
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
8
Hours after target:
0
Description:
Caffeine is a stimulant that promotes wakefulness by blocking adenosine receptors, directly opposing the sleep-promoting action of melatonin.
Actionable advice:
Caffeine is best avoided for at least 8 hours before taking melatonin.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified.
Label source:
PubMed: Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. (PMID 21734299)
Action type:
separate
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Melatonin may have mild antiplatelet effects, which could theoretically increase the risk of bleeding when combined with blood-thinning medications.
Actionable advice:
It is a good idea to talk to a doctor before using melatonin while taking blood-thinning medications.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.
Label source:
PubMed: Melatonin for the prevention and treatment of jet lag. (PMID 12076414)
Action type:
informational_none
Target id:
/class/antihypertensives
Target name:
Antihypertensive Medications
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Melatonin can cause a small reduction in blood pressure, which may have an additive effect when taken with medications designed to lower blood pressure.
Actionable advice:
It is a good idea to check blood pressure if melatonin is started while on blood pressure medication.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Melatonin treatment reduced nocturnal systolic BP significantly from 136+/-9 to 130+/-10 mm Hg (P=.011), and diastolic BP from 72+/-11 to 69+/-9 mm Hg (P=.002), whereas placebo had no effect on nocturnal BP.
Label source:
PubMed: The American journal of medicine (2006)
Source url:
Exact phrase from label:
A few studies noted adverse events relating to endocrine (e.g. reproductive parameters, glucose metabolism) and cardiovascular (e.g. blood pressure, heart rate) function, which appear to be influenced by dosage, dose timing and potential interactions with antihypertensive drugs.
Label source:
PubMed: Complementary therapies in medicine (2019)
Action type:
monitor
Target id:
/class/estrogens
Target name:
Oral Contraceptives / Estrogen Therapy
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Estrogen-containing medications can inhibit the enzymes that break down melatonin, potentially increasing its levels and sedative effects.
Actionable advice:
Hormonal contraceptives may increase melatonin's effects; a lower dose may be needed.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results implicate intestinal CYP1A1, and possibly CYP2C19, as the loci of EE drug interactions with highly extracted drugs like MEL.
Label source:
PubMed: Drug metabolism and disposition: the biological fate of chemicals (2009)
Source url:
Exact phrase from label:
17-Ethinhyloestradiol appeared not to suppress the 6-hydroxylation of melatonin but inhibited the sulphation of 6-hydroxymelatonin, but this is unlikely to result in an interaction following therapeutic intake of the steroid.
Label source:
PubMed: Physiology & behavior (2014)
Source url:
Exact phrase from label:
Our results suggest that estrogen modulates the nocturnal synthesis of melatonin in the pineal gland in peripubertal female rats. The effects of estrogen on melatonin synthesis appeared to be mediated by the modulation of NAT activity.
Label source:
PubMed: Journal of pineal research (1998)
Action type:
informational_none
Target id:
/class/beta-blockers
Target name:
Beta-Blocker Medications
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain beta-blockers (e.g., atenolol, propranolol) are known to suppress the body's natural nighttime production of melatonin, which can lead to sleep disturbances.
Actionable advice:
If you experience sleep issues on a beta-blocker, melatonin supplementation may help, but discuss with your doctor first.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Therefore, we tested whether nightly melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers.
Label source:
PubMed: Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. (PMID 23024438)
Action type:
informational_none
Target id:
/class/nsaids
Target name:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Evening use of NSAIDs, particularly indomethacin, can suppress the body's natural production of melatonin by inhibiting prostaglandins involved in its synthesis.
Actionable advice:
If taking NSAIDs in the evening, be aware they may interfere with your body's natural sleep signals.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because the
published safety data on neonatal outcomes involved mostly preterm infants, the generalizability
of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is
uncertain.
Label source:
Action type:
informational_none
Derived From
melatonin
Provenance Note
Interactions duplicated from 'melatonin'. Sustained-release melatonin; same interactions.