Methadone

Methadone hydrochloride tablets is indicated for the: Management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see WARNINGS AND PRECAUTIONS ( 5.1 )], reserve opioid analgesics, including methadone hydrochloride tablets, for use in patients for whom alternative analgesic treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. …

• Consider recommending or prescribing an opioid overdose reversal agent (e.g., naloxone, nalmefene) based on the patient’s risk factors for overdose
• Methadone hydrochloride tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks
• Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals
• Reserve titration to higher doses of methadone hydrochloride tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks
• Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with methadone hydrochloride tablets
• Consider this risk when selecting an initial dose and when making dose adjustments
• To convert to methadone hydrochloride tablets from another opioid, use available conversion factors to obtain estimated dose
• Titrate slowly with dose increases no more frequent than every 3 to 5 days. …

10 mg Tablets: White, round, biconvex tablets, scored on one side and debossed with “N” above the score and “128” below the score and plain on the other side. Tablets: 10 mg. ( 3 )

• The safety, effectiveness, and pharmacokinetics of methadone
• In pediatric patients below the age of 18 years have not been established

Clinical studies of methadone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. Elderly patients (aged 65 years or older) may have increased sensitivity to methadone. …

• Advise the patient to read the FDA-approved patient labeling (Medication Guide) Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store methadone hydrochloride tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home
• Inform patients that leaving methadone hydrochloride tablets unsecured can pose a deadly risk to others in the home [see WARNINGS AND PRECAUTIONS , DRUG ABUSE AND DEPENDENCE ]
• Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. …

• Methadone hydrochloride tablets are contraindicated in patients with: Significant respiratory depression [see WARNINGS AND PRECAUTIONS ]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS AND PRECAUTIONS ]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS AND PRECAUTIONS ]
• Hypersensitivity (e.g., anaphylaxis) to methadone [see ADVERSE REACTIONS ]. …

Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. The concomitant use of methadone hydrochloride tablets and CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors can increase the plasma concentration of methadone, resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of methadone hydrochloride tablets is achieved. …

Opioid Induced Hyperalgesia and Allodynia : Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation. ( 5.8) Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. Discontinue methadone hydrochloride tablets if serotonin syndrome is suspected. …

The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS ( 5.1 ) ] Life Threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS ( 5.2 ) ] QT Prolongation [see WARNINGS AND PRECAUTIONS ( 5.4 ) ] Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS ( 5.5 ) ] Interactions with Benzodiazepines and other CNS Depressants [see WARNINGS AND PRECAUTIONS ( 5.3 ) ] Opioid-Induced Hyperalgesia and Allodynia [see WARNINGS AND PRECAUTIONS ( 5.8 ) ] Serotonin Syndrome [see WARNINGS AND PRECAUTIONS ( 5.9 ) ] Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS ( 5.11 ) ] Severe Hy …

8.1 Pregnancy Risk Summary The majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone. …

Clinical Presentation Acute overdosage with methadone can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal-muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. …

9.1 Controlled Substance Methadone hydrochloride tablets contain methadone, a Schedule II controlled substance. 9.2 Abuse Methadone hydrochloride tablets contains methadone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see WARNINGS AND PRECAUTIONS ( 5.1 ) ] . …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.