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Moderate to severe pain non-responsive to non-narcotic drugs (FDA Approved)[1]
Detoxification and treatment of opioid use disorder as part of medication-assisted treatment (FDA Approved)[1]
Treatment of neonatal abstinence syndrome (Not FDA Approved, Class C Drug)[2]

Indication 1: Moderate to Severe Pain Non-responsive to Non-narcotic Drugs

Methadone is FDA approved for use in moderate to severe pain that has not responded to non-opioid medications or as an alternative if the pain is unresponsive to other opioid drugs. Methadone is an analgesic used in cancer patients or other terminally ill patients and in chronic pain pathologies. Before starting methadone for noncancer chronic pain, the patient should undergo an evaluation of risk factors that can lead to drug misuse or diversion and establish that benefit of therapy overweighs the harms. The evaluation should include psychosocial reasons for underlying chronic pain like comorbid psychiatric disorders and social support issues.[1][3] Buy Methadone Physeptone online in Australia

Methadone is an alternative in treating patients with opioid tolerance as they may not respond to traditional analgesic regimens. In such patients, methadone dosages are adjusted or combined with other opioids as adjuvant treatments to enhance response to analgesic interventions.[3][4]

Methadone is a commonly prescribed drug to treat severe, cancer-related, or neuropathic pain in pediatric populations.[5] However, in pediatric populations, the use of opioid medications for analgesia is considered off-label due to scant clinical data to elaborate on the harms versus benefits in this population.[6] Buy Methadone Physeptone online in Australia

Indication 2: Detoxification and Treatment of Opioid Use Disorder as Part of Medication-assisted treatment

Methadone and buprenorphine are FDA approved to treat opioid use disorder as part of federally regulated opioid treatment programs. Methadone prescriptions are for detoxification and maintenance therapy. Methadone is a useful agent for opioid withdrawal symptoms such as tachycardia, diaphoresis, nausea, vomiting, diarrhea, etc. Abstinence rates from opioid use are better when patients undergo long-term versus short-term methadone treatment. Methadone has been shown to improve retention in treatment and detoxification programs and has shown improvement in mortality rates for opioid abusers.[3] Clinicians must evaluate the availability of methadone in pharmacies when referring patients to such programs, as licensing and availability can vary significantly across states.[3][7] Buy Methadone Physeptone online in Australia

Indication 3: Treatment of Neonatal Abstinence Syndrome

Neonatal abstinence syndrome (NAS) can be due to a variety of substance abuse during pregnancy, such as alcohol, tobacco, and opioids, all of which can cross the placenta to affect the neonate. Typically treatment is supportive for neonates with milder cases. Pharmacologic intervention is employed when there are moderate to severe signs of withdrawal in neonates (e.g., seizures) and often involves using methadone to treat signs of NAS.[2] Although used to treat opioid withdrawal symptoms in neonates, using methadone for this indication is not FDA-approved. Comparisons have been made in some studies using morphine or buprenorphine as alternatives to treating NAS. Methadone showed better efficacy in treating NAS compared to morphine.[8] However, studies show buprenorphine may be more efficacious in improving neonatal outcomes, including birth weight and length of stay in the hospital, compared to methadone.[2][9] Buy Methadone Physeptone online in Australia

Mechanism of Action

Methadone is a synthetic opioid and full agonist at the μ-opioid receptor and induces other opioid receptors. The μ-opioid receptors, located in the CNS (e.g., brainstem, locus coeruleus, periaqueductal gray matter) and parts of the gastrointestinal tract, act to modulate various neurochemical activities involved in analgesia, euphoria, and sedation. Activation of the μ-receptors by methadone activates the same pathways. It induces downstream effects via G-protein signaling, including inhibition of neuronal transmission of pain afferents from the spinal cord, producing analgesic effects, and receptor internalization and recycling, contributing to less opioid tolerance in patients.[10][11] Buy Methadone Physeptone online in Australia

Methadone is also a non-competitive antagonist to the N-methyl-d-aspartate (NMDA) receptor, possibly further adding to its benefits for neuropathic pain.[6][10][12] When using methadone to treat opioid addiction, the clinician titrates the methadone to a higher daily dose that prevents withdrawal signs and causes narcotic blockade to prevent euphoria from other shorter-acting opioids. Due to the longer half-life of methadone (8 to 60 hours), the withdrawal time-course and symptoms are less severe.[10][11][13]

Administration

Methadone is available as a lipophilic hydrochloride salt in oral, IM, IV, subcutaneous, epidural, and intrathecal formulations.[14][15] Different dosing and formulations depend on the purpose of use, but oral formulations in either tablet or concentrated syrup form are the most commonly used. A general guideline for dosing regimens is listed. Buy Methadone Physeptone online in Australia

Pain management:
- Opioid-naive: Oral, 2.5 mg every eight hours with incremental dose increase if needed about once every week.[15]
- Opioid-Tolerant: Oral, 10 mg of methadone is approximately equivalent to a 15 mg dose of oral morphine. Follow dosing charts for equivalent dosing and conversion factors tailored to the individual patient.[15]
Opioid use disorder:
- General: Oral dosing starts at 30 to 40 mg/day and is titrated upwards by 10 to 20 mg/week to an optimal of 80 to 150 mg/day.[13] Long-term treatment is optimal if it lasts for at least 14 months.[7]
- Pregnancy: Continue maintenance treatment in women who are pregnant and have opioid use disorder. Consider treating with buprenorphine instead due to less sedation on the neonate.[16] Buy Methadone Physeptone online in Australia
Opioid withdrawal:
- Adults: Oral dosing starts at 10 to 20 mg and is increased by 10 mg increments until the withdrawal symptoms are controlled, usually about 40 mg. Stabilize dosing for 2 to 3 days and then reduce dose by 10 to 20% daily and monitor for withdrawal symptoms.
- Neonates: Oral, 0.05 to 0.1 mg/kg every 6 hours until withdrawal symptoms stabilize. Then reduce the dose by 10 to 20% daily and continue serial monitoring of withdrawal symptoms [2]. Buy Methadone Physeptone online in Australia