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Proper dosing and titration are essential and Methadone Hydrochloride should only be prescribed by healthcare professionals who are knowledgeable in the use of methadone for detoxification and maintenance treatment of opioid addiction.

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Monitor for respiratory depression, especially during initiation of Methadone Hydrochloride or following a dose increase. The peak respiratory depressant effect of methadone occurs later, and persists longer than the peak pharmacologic effect, especially during the prostate volume normal ml dosing period see WARNINGS.

Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction for changes in cardiac rhythm during initiation and titration of Methadone Hydrochloride see WARNINGS.

Methadone Powder

Interactions with Drugs Affecting Cytochrome P Isoenzymes The concomitant use of Methadone Hydrochloride with all cytochrome P 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression.

In addition, discontinuation of concomitantly used cytochrome P prostate volume normal ml 2B6, 2C19, or 2C9 inducers may also result in an increase in methadone plasma concentration.

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Methadone Powder Description Methadone Hydrochloride Powder, an opioid agonist, is for oral administration only and is used in the preparation of a liquid by dissolving the powder in an appropriate vehicle. This product is for prescription drug compounding only.

Methadone hydrochloride is chemically described as 3-heptanone,6- dimethylamino -4,4-diphenyl- hydrochloride. Methadone hydrochloride is a white, essentially odorless, bitter-tasting crystalline powder. It is very soluble in water, soluble in isopropanol and in chloroform, and practically insoluble in ether and in glycerine. Methadone hydrochloride has a melting point of °C, a pKa of 8.

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Its structural formula is: Methadone Powder - Clinical Pharmacology Mechanism of Action Methadone hydrochloride is a mu-agonist; a synthetic opioid analgesic with multiple actions quantitatively similar to those of morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. The principal actions of therapeutic value are analgesia and detoxification or maintenance in opioid addiction.

The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. When administered orally, methadone is approximately one-half as prostate volume normal ml as when given parenterally. Oral administration results in a delay of the onset, a lowering of the peak, and an increase in the duration of analgesic effect.

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Pharmacodynamics Effects on the Central Nervous System Methadone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. Methadone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic e.

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Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Some NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.

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Effects on the Gastrointestinal Tract and Other Smooth Muscle Methadone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm, resulting in constipation.

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Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase. Effects on the Cardiovascular System Methadone produces peripheral vasodilation, which may result in orthostatic hypotension or syncope.

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They also stimulate prolactin, growth hormone GH secretion, and pancreatic secretion of insulin and glucagon. Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility.

Cytoreductive radical prostatectomy in metastatic prostate cancer: does it really make sense? World J Urol. No improvement noted in overall or cause-specific survival for men presenting with metastatic prostate cancer over a year period.

The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models.

The clinical significance of these findings is unknown.

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Overall, the effects of opioids appear to be modestly immunosuppressive. Concentration—Adverse Reaction Relationships There is a relationship between increasing [drug substance] plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression.

In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions.

Dose proportionality of methadone pharmacokinetics is not known. Effect of food on the bioavailability of methadone has not been evaluated.

Distribution Methadone is a lipophilic drug and the steady-state volume of Prostatitis és prosztata és kezelése ranges between 1. Methadone is secreted in saliva, breast milk, amniotic fluid and umbilical cord plasma.

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Metabolism Methadone is primarily metabolized by N-demethylation to an inactive metabolite, 2-ethylidene-1, 5-dimethyl-3,3-diphenylpyrrolidene EDDP. Excretion The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion.

Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged between 1.

Since methadone is lipophilic, it has been known to persist in the liver and other tissues. The slow release from the liver and other tissues may prolong the duration of methadone action despite low plasma concentrations. Specific Populations Use During Pregnancy The disposition of oral methadone has been studied in approximately 30 pregnant patients in the second and third trimesters.

Elimination of methadone was significantly changed in pregnancy.

Total body clearance of methadone was increased in pregnant patients compared to the same patients postpartum or to non-pregnant opioid-dependent women. The terminal half-life of methadone is decreased during second and third trimesters.

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The decrease in plasma half-life and increased clearance of methadone resulting in lower methadone trough levels during pregnancy can lead to withdrawal symptoms in some pregnant patients.