No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Evaluation of the potential drug interaction of melatonin and warfarin: A case series
Abstract
Melatonin has the potential to interact with warfarin for many reasons. According to the Micromedex drug interaction database, melatonin has been associated with bleeding complications and reduced prothrombin time (PT) in four case reports of patients who received both melatonin and warfarin. However, there is no primary literature that supports this finding. The objective of this case series is to evaluate potential drug interactions between melatonin and warfarin. Ten adult patients, who admitted to Massachusetts General Hospital (MGH) (Boston, MA) between April 2011 and April 2012 and were treated with melatonin and warfarin concurrently, were evaluated. MGH is a 950-bed teaching hospital. Those 10 patients had changes in INR and PT. They are selected because they were not on any other medications that have major interactions with warfarin, did not receive other anticoagulants, chemotherapy, as needed or 1 dose of melatonin during their hospital stay. The Drug Interaction Probability Scale (DIPS) was used to evaluate the potential drug interaction, and the following outcomes were recorded for each patient: bleeding events, INR, PT, albumin, and LFTs. The 10 patients were 54 years old or older and the duration of concurrent administration of both medications ranged from 2 to 10 days. Melatonin dose was stable in all 10 patients while warfarin dose had changed (increased/ decreased) in some patients. Both INR and PT increased in most patients during concurrent administration of melatonin with warfarin and no bleeding events have been noted. By calculating DIPS score for each patient, we found that 6 patients experienced possible drug interaction, 2 had probable drug interaction, and 2 had doubtful drug interaction. LFTs and albumin were normal in most patients. In conclusion, concurrent use of melatonin and warfarin may result in INR and PT changes and affects coagulation activity. Monitoring INR and PT regularly is suggested when both medications are administered concurrently. � 2016, Zhengzhou University. All rights reserved.
... Ashy (2022) [36] Review Summarizing the consequences of COVID-19 infection on activity and function of coagulation. The effect of melatonin in this process. ...
... Of the few studies performed, there was a small cohort of 10 patients evaluated for potential melatonin-warfarin interaction at Massachusetts General Hospital in Boston. Noha Ashy and K.V. Stroff found increased measures of INR (international normalized ratio) and PT (prothrombin time) in patients that were administered both melatonin and warfarin [36]. Melatonin can also decrease the effectiveness of extended-release nifedipine for blood pressure control. ...
Background: Exogenous melatonin is commonly used to treat insomnia, other sleep problems, and numerous medical illnesses, including Alzheimer’s disease, autism spectrum disorder, and mild cognitive impairment in adults and children. There is evolving information regarding issues with the use of chronic melatonin. Methods: The present investigation was a narrative review. Results: Melatonin usage has risen dramatically in recent years. Many countries only allow melatonin prescriptions. In the United States (U.S.), it is classified as a dietary supplement accessible over the counter and can be derived from animals, microorganisms, or, most commonly, made synthetically. No regulatory agency oversees its manufacturing or sale in the U.S. melatonin concentration of marketed preparations varies widely between product labels and manufacturers. Melatonin’s ability to induce sleep is detectable. However, it is modest for most people. Sleep length appears to be less important in sustained-release preparations. The optimal dosage is unknown, and routinely used amounts vary substantially. Melatonin’s short-term negative effects are minimal, resolve at medicine cessation, and do not usually prevent usage overall. Much research on long-term melatonin administration has found no difference between exogenous melatonin and placebo in terms of long-term negative effects. Conclusion: Melatonin at low to moderate dosages (approximately 5–6 mg daily or less) appears safe. Long-term usage appears to benefit certain patient populations, such as those with autism spectrum disorder. Studies investigating potential benefits in reducing cognitive decline and increased longevity are ongoing. However, it is widely agreed that the long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation.
... Melatonin may have some minor medication interactions to keep in mind. There have been isolated case reports of increased effect of the anticoagulant drug warfarin (Coumadin) 52,53 . As well, there is some evidence that melatonin can increase seizure activity in children, possibly by inhibiting the effects of anticonvulsants 53,54 , though this effect has not been seen in adults. ...
Sleep disturbances are common among older adults, with approximately 50% reporting sleep difficulty at least a few nights per week. Frequently prescribed sedative-hypnotics such as benzodiazepines (BZDs) pose high risk of adverse events and hence safer alternatives are necessary. Melatonin regulates the brain's endogenous clock and it is the only human hormone available as a natural product in Canada. Clinical practice guidelines recommend against the use of melatonin for insomnia but do not stratify recommendations based on age, frailty or comorbidity. This article reviews the evidence for and efficacy of melatonin use specifically for older adults with insomnia symptoms. Melatonin demonstrates modest improvements in sleep parameters and has a low side effect profile and minimal drug-drug interactions. The available evidence is limited by small sample sizes, heterogeneity in dosage and formulation, with few older adult-specific studies. Based on the overall assessment of risk and potential benefit, despite lack of support from guidelines, melatonin seems to be a reasonable first-line option for the treatment of insomnia in older adults, especially those with frailty syndromes or multi-morbidity. In this article the evidence is presented to allow readers to decide for themselves.
... The authors concluded that the combined use of warfarin and melatonin leads to a change in PT and INR and influences the coagulation activity. They suggested that regular monitoring of PT and INR is recommended for those concurrently receiving both drugs [82]. ...
Severe COVID-19 is associated with the dynamic changes in coagulation parameters. Coagulopathy is considered as a major extra-pulmonary risk factor for severity and mortality of COVID-19; patients with elevated levels of coagulation biomarkers have poorer in-hospital outcomes. Oxidative stress, alterations in the activity of cytochrome P450 enzymes, development of the cytokine storm and inflammation, endothelial dysfunction, angiotensin-converting enzyme 2 (ACE2) enzyme malfunction and renin–angiotensin system (RAS) imbalance are among other mechanisms suggested to be involved in the coagulopathy induced by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The activity and function of coagulation factors are reported to have a circadian component. Melatonin, a multipotential neurohormone secreted by the pineal gland exclusively at night, regulates the cytokine system and the coagulation cascade in infections such as those caused by coronaviruses. Herein, we review the mechanisms and beneficial effects of melatonin against coagulopathy induced by SARS-CoV-2 infection.
... Beyond such contrasting findings, a more pertinent problem faced by passengers with cardiovascular conditions is the time dosing of their medications, especially with abrupt changes in time zones, meals, and wakefulness in transcontinental flights. 22 Certain nonprescription sleep supplements (such as melatonin) consumed by passengers for sleep adjustment have also been observed to interfere or interact with cardiovascular medications, 28,29 and dose titration of the implicated cardiac medications may be required to maintain optimal effects. Some (such as temazepam, zaleplon, etc) may also have direct effects on the cardiovascular system, 30 and discontinuation or avoidance of such pharmacological sleep aids should be strongly advised. ...
The exponential growth of commercial flights has resulted in a sharp rise of air travellers over the last 2 decades, including passengers with a wide range of cardiovascular conditions. Notwithstanding the ongoing COVID-19 pandemic that had set back the aviation industry for the next 1 to 2 years, air travel is expected to rebound fully by 2023-2024. Guidelines and evidence-based recommendations for safe air travel in this group vary, and physicians often encounter situations where opinions and assessments on fitness for flights are sought. This article aims to provide an overview of the stressors of commercial passenger flights with an impact on cardiovascular health for the general cardiologist and family practitioner, when assessing the suitability of such patients for flying fitness.
... Melatonin, a signaling molecule for circadian rhythms, plays an important role in many biological processes (Dahm et al. 2006, Kostovski et al. 2011. It was suggested that endogenous melatonin may also produce antithrombotic, antioxidant and antiinflammatory activity (Carrillo-Vico et al. 2005, Claustrat et al. 2005, Dahm et al. 2006, Ashy and Shroff 2016. Depend on its wide effects, melatonin could be expected to regulate hemostatic events and the effects of melatonin on hemostasis are relatively poorly studied (Kostovski et al. 2011). ...
Cardiovascular diseases (CVDs) are the leading causes of death and illness worldwide. While there have been advancements in the treatment of CVDs using medication and medical procedures, these conventional methods have limited effectiveness in halting the progression of heart diseases to complete heart failure. However, in recent years, the hormone melatonin has shown promise as a protective agent for the heart. Melatonin, which is secreted by the pineal gland and regulates our sleep–wake cycle, plays a role in various biological processes including oxidative stress, mitochondrial function, and cell death. The Sirtuin (Sirt) family of proteins has gained attention for their involvement in many cellular functions related to heart health. It has been well established that melatonin activates the Sirt signaling pathways, leading to several beneficial effects on the heart. These include preserving mitochondrial function, reducing oxidative stress, decreasing inflammation, preventing cell death, and regulating autophagy in cardiac cells. Therefore, melatonin could play crucial roles in ameliorating various cardiovascular pathologies, such as sepsis, drug toxicity-induced myocardial injury, myocardial ischemia–reperfusion injury, hypertension, heart failure, and diabetic cardiomyopathy. These effects may be partly attributed to the modulation of different Sirt family members by melatonin. This review summarizes the existing body of literature highlighting the cardioprotective effects of melatonin, specifically the ones including modulation of Sirt signaling pathways. Also, we discuss the potential use of melatonin-Sirt interactions as a forthcoming therapeutic target for managing and preventing CVDs.
Graphical Abstract
The unprecedented pandemic of COVID-19 swept millions of lives in a short period, yet its menace continues among its survivors in the form of post-COVID syndrome. An exponentially growing number of COVID-19 survivors suffer from cognitive impairment, with compelling evidence of a trajectory of accelerated aging and neurodegeneration. The novel and enigmatic nature of this yet-to-unfold pathology demands extensive research seeking answers for both the molecular underpinnings and potential therapeutic targets. Ferroptosis, an iron-dependent cell death, is a strongly proposed underlying mechanism in post-COVID-19 aging and neurodegeneration discourse. COVID-19 incites neuroinflammation, iron dysregulation, reactive oxygen species (ROS) accumulation, antioxidant system repression, renin-angiotensin system (RAS) disruption, and clock gene alteration. These events pave the way for ferroptosis, which shows its signature in COVID-19, premature aging, and neurodegenerative disorders. In the search for a treatment, melatonin shines as a promising ferroptosis inhibitor with its repeatedly reported safety and tolerability. According to various studies, melatonin has proven efficacy in attenuating the severity of certain COVID-19 manifestations, validating its reputation as an anti-viral compound. Melatonin has well-documented anti-aging properties and combating neurodegenerative-related pathologies. Melatonin can block the leading events of ferroptosis since it is an efficient anti-inflammatory, iron chelator, antioxidant, angiotensin II antagonist, and clock gene regulator. Therefore, we propose ferroptosis as the culprit behind the post-COVID-19 trajectory of aging and neurodegeneration and melatonin, a well-fitting ferroptosis inhibitor, as a potential treatment.
ResearchGate has not been able to resolve any references for this publication.