Ramelteon.pptx

Ramelteon.pptx

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  A seminar on RAMELTEON Presentedby : Dr. Debarshi Deka, House Surgeon IMS & SUM Hospital, Bhubaneswar Moderator: Dr. Krittika Agarwal, 2nd year Junior Resident IMS & SUM Hospital, Bhubaneswar
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  Overview ● INTRODUCTION ● MECHANISMOF ACTION ● PHARMACOKINETICS ● EFFICACY ● DOSAGE ● ADVERSE EFFECT ● CONTRAINDICATION ● SAFETY ● STORAGE CRITERIA
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  INTRODUCTION ● Ramelteon alsoknown as Rozerem is a melatonin receptor antagonist. ● It is used to treat sleep onset insomnia. ● It has no affinity for GABA receptor complex. ● Ramelteon was first described in 2002 and was approved for medical use in 2005. ● It is freely soluble in organic solvents such as methanol,ethanol etc. and is very soluble in water as well as in aqueous buffers from ph 3 and is taken orally.
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  MECHANISM OF ACTION ●Ramelteon has high affinity for melatonin MT1 and MT2 receptors in the brain and selectivity over the non human MT3 receptors. ● It affinity is 8-fold higher for the MT1 receptor over the MT2 receptor. ● It mimics the melatonin’s sleep-promoting properties.
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  Contd… ● The activityof ramelteon at the MT1 and MT2 receptors in the suprachiasmatic nucleus of the hypothalamus is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep–wake cycle.
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  PHARMACOKINETICS ● Ramelteon israpidly absorbed from GI tract and eliminated over a dose of 4- 64mg. ● Though its absorption is 84% but due to its extensive first pass metabolism it’s bioavailability is about only 2 % approximately. ● Due to its high lipophilicity it permeates more easily into tissues. ● The plasma protein binding of ramelteon is 82% independently of concentration. Ramelteon is primarily bound to albumin (70%). ● It is primarily metabolised through CYP1A2 pathway and eliminated primarily through urine and a very small amount in feces. ● It has a short eliminating half life of 1-2.6 hrs and due to this it doesn’t appear to result in accumulation when repeated once daily dosing.
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  EFFICACY ● According tostudies , Ramelteon 64 mg reduced latency to persistent sleep by 9.1 minutes and increased total sleep time by 11.1 minutes. ● Also a significant decrease in latency to persistent sleep (7.5 minutes) was found after administration of 8 mg ramelteon, but no statistically significant effect was found for the 16 mg dose. And total sleep time increased by 17.1 minutes with the 8 mg dose and by 13.4 minutes with the 16 mg dose. ● Efficacy may be reduced when ramelteon is used in combination with potent CYP enzyme inducers such as rifampin, since ramelteon concentrations may be decreased.
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  Contd.. ● No clinicallymeaningful interactions were found when coadministered with Omeprazole, Theophylline, Midazolam, Digoxin and Warfarin. ● There is not an effect on sleep architecture, ie, pattern of sleep stages and number of nightly awakenings, or on subjective sleep measures.
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  DOSAGE ● The recommendeddosage is 8 mg nightly and patients should be advised to take it within 30 minutes of going to bed. ● Again because of high lipophilicity ,fatty-food slows its absorption and for this reason patients should be advised not to take ramelteon within 1 hr of eating a high fat meal.
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  ADVERSE EFFECT ● Ramelteonhas not been shown to produce any dependence and has shown no potential for abuse, the withdrawal and rebound insomnia that is typical with GABA modulators. ● The most frequent adverse events leading to discontinuation were somnolence, dizziness,nausea,fatigue,headache and insomnia. There have been rare cases of anaphylactic reactions or abnormal thinking. ● The most common side effect of Ramelteon is Headache.
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  CONTRAINDICATIONS ● Ramelteon isnot given to patients taking Fluvoxamine (Luvox). As CYP1A2 inhibitors it has been shown to raise the serum Ramelteon approximately 70-fold, thus substantially increasing the risk of ramelteon-associated adverse events. ● Similarly, Ketoconazole increases the availability of ramelteon. The same was found for Fluconazole too. ● Again, as discussed earlier, concomitant use of a strong CYP enzyme inducer such as Rifampin may increase Ramelteon metabolism and reduce serum ramelteon, which might decrease its efficacy in some cases.
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  SAFETY & PRECAUTIONS Priorto the medication, as a precaution, patient should consult with the Doctor. ● This drug is not used in patients with severe hepatic impairment. ● It is also not recommended in patients with severe sleep apnea or severe chronic obstructive pulmonary. ● The drug should be used with caution, if at all, in nursing mothers and pregnant women.
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  Contd… ● Ramelteon hasbeen found sometimes to decrease blood cortisol and testosterone and to increase prolactin. Female patients should be monitored for the cessation of menses and galactorrhea, decreased libido, and fertility problems. ● If there present any breathing disorders like COPD.
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  STORAGE CRITERIA ● Ramelteonis to be stored at 77 degrees F(25 degrees C) away from light and moisture. ● Brief storage between 59-86 degrees F(15-30 degrees C) is permitted. ● The containers should be kept tightly closed when not in use.
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  References 1. Kaplan &Sadock’s SYNOPSIS OF PSYCHIATRY(12th ED)- by Robert Boland,MD and Marcia L. Verduin,MD -page 680 2. Owen RT (April 2006). "Ramelteon: profile of a new sleep-promoting medication". Drugs of Today. 42 (4): 255–263 3. "Rozerem- ramelteon tablet, film coated". DailyMed. 28 December 2018. Retrieved 13 April 2020 4. Uchikawa O, Fukatsu K, Tokunoh R, Kawada M, Matsumoto K, Imai Y, et al. (September 2002). "Synthesis of a novel series of tricyclic indan derivatives as melatonin receptor agonists". Journal of Medicinal Chemistry. 45 (19): 4222–4239 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC363 0951/#:~:text=Polysomnographic%20recordings%2 0showed%20that%2C%20compared,sleep%20time %20by%2011.1%20minutes.
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  THANK YOU