Methadone Hcl (methadone HCl)

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Methadone hydrochloride may be administered orally as tablets, solution, concentrated solution, or dispersible tablets. Methadone also may be administered parenterally by IV, IM, or subcutaneous injection.

Abuse or misuse of methadone tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of methadone and can result in overdose and death. Preparations labeled for oral administration must not be injected.

Methadone also has been administered rectally+ and by epidural injection+.

No dosing information is available for this tab.

No dosing information is available for this tab.

Methadone is metabolized principally by the cytochrome P-450 (CYP) microsomal enzyme system, mainly by isoenzymes 3A4, 2B6, 2C19, 2C9 and 2D6.

Methadone appears to be a P-glycoprotein (P-gp) substrate, but pharmacokinetics are not substantially altered by P-gp inhibition.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Significant respiratory depression.

*Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.

*Known or suspected GI obstruction, including paralytic ileus.

*Hypersensitivity to methadone (e.g., anaphylaxis).

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Common adverse effects reported in adults receiving methadone include lightheadedness, dizziness, sedation, nausea, vomiting, and sweating.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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The manufacturers state that safety, efficacy, and pharmacokinetics of methadone in pediatric patients younger than 18 years of age have not been established.

Most 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. Based on findings from animal studies, advise pregnant females of the potential risk to a fetus.

Findings regarding specific major malformations, decreased fetal growth, premature birth and Sudden Infant Death Syndrome (SIDS) have been inconsistent. Children who were exposed to methadone in utero have been reported to demonstrate mild but persistent deficits in performance on psychometric and behavioral tests and visual abnormalities.

Untreated opioid addiction during pregnancy is associated with adverse obstetrical outcomes, including preeclampsia, fetal growth restriction, preterm birth, spontaneous abortion, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use and engagement in high-risk behaviors. Pregnant women involved in methadone maintenance programs have been reported to have improved prenatal care leading to reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs. Information is limited regarding dose and duration of methadone use during pregnancy, and most maternal exposure in these studies appears to occur after the first trimester of pregnancy.

In a double-blind, randomized controlled trial (Maternal Opioid Treatment: Human Experimental Research (MOTHER)), opioid withdrawal effects were assessed in neonates born to females who received methadone or buprenorphine treatment for opioid dependence during pregnancy. Enrollment in the study occurred at an average gestational age of 18.7 weeks. Prior to the end of pregnancy, 18% of methadone-treated women and 33% of buprenorphine-treated women discontinued treatment; outcomes were evaluated for the neonates whose mothers remained in treatment until delivery. No difference was observed between methadone- and buprenorphine-exposed neonates in the proportion of neonates requiring treatment for opioid withdrawal syndrome or the peak severity of the syndrome. Buprenorphine-exposed neonates required a lower total mean morphine sulfate dosage for treatment of withdrawal (1.1 versus 10.4 mg), had shorter hospital stays (10 versus 17.5 days), and shorter duration of treatment for withdrawal (4.1 versus 9.9 days) compared with methadone-exposed neonates. The groups did not differ in other outcome measures (head circumference, weight and length at birth, preterm birth, gestational age at delivery, and 1- and 5-minute Apgar scores) or in the rates of serious maternal or neonatal adverse events. The imbalance in treatment discontinuance rates between methadone- and buprenorphine-treated women complicate interpretation of the study findings.

Pharmacokinetic data from a limited number of pregnant females suggest that methadone clearance may be increased, trough plasma concentrations of the medication may be lower, and half-life of the medication may be decreased during the second and third trimesters of pregnancy compared with pharmacokinetic values determined for the same females postpartum or for nonpregnant opioid-dependent females. If methadone is used during pregnancy, dosage adjustment (i.e., increased dose or decreased dosing interval) may be necessary.

Methadone has been detected in umbilical cord plasma and amniotic fluid.

Opioid-dependent females on methadone maintenance therapy may require additional analgesia during labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Prolonged maternal use of opioid agonists during pregnancy can result in neonatal opioid withdrawal syndrome with manifestations of irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Females who require prolonged opioid agonist therapy during pregnancy should be advised of the risk of neonatal opioid withdrawal syndrome, and availability of appropriate treatment should be ensured. The onset, duration, and severity of the syndrome vary depending on the specific opioid agonist used, duration of use, timing and amount of last maternal use, and rate of drug elimination by the neonate. Withdrawal signs and symptoms should be closely monitored in a newborn and managed accordingly.

Methadone is distributed into human milk. Peak concentrations in milk reportedly occur approximately 4-5 hours after an oral dose of the medication. In 2 studies in 22 nursing females who were receiving methadone maintenance treatment, methadone was present in low concentrations (delivering approximately 2-3% of the maternal dose to the breast-fed infant) in milk, but no adverse effects on breast-fed infants were observed. Methadone has been detected in very low plasma concentrations in some infants whose mothers were receiving methadone. Cases of sedation and respiratory depression in infants exposed to methadone through breast milk have been reported rarely.

Breast-feeding has been associated with decreased severity of neonatal opiate withdrawal syndrome, decreased need for pharmacotherapy, and shorter hospital stays for the neonate. In individuals receiving methadone for opioid use disorder and considering breastfeeding, CDC recommends that breastfeeding be supported if there has been no return to drug use for >=90 days and there are no other contraindications; considered if there has been no return to drug use within 30-90 days; and discouraged if there is active substance use or a return to drug use within the last 30 days.

The manufacturers state that the benefits of breast-feeding should be considered along with the mother's clinical need for the medication and any potential adverse effects on the breast-fed infant from either the medication or the underlying maternal condition. Females who are receiving methadone and are breast-feeding or wish to breast-feed should be advised that the medication distributes into human milk, should be instructed to recognize respiratory depression and sedation in infants and to know when to seek medical care, and should be informed that nursing should be discontinued gradually (not abruptly) in order to prevent withdrawal in the infant.

Elderly patients (65 years of age or older) may have increased sensitivity to methadone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the primary risk for elderly patients treated with opioids and has occurred after large initial doses were administered to patients who were not opioid tolerant or when opioids were co-administered with other agents that depress respirations. Titrate the dosage of methadone slowly in geriatric patients and frequently reevaluate the patient for signs of CNS and respiratory depression.

Methadone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this medication may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.

Patients 65 years of age or older may have increased sensitivity to methadone. In general, use caution when selecting dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other medication therapy.

Respiratory depression is the main risk for geriatric patients treated with opioids and has occurred after administration of large initial doses in patients who were not opioid-tolerant or when opioids were co-administered with other medications that depress respiration. Titrate the dosage of methadone slowly in geriatric patients and frequently reevaluate the patient for signs of CNS and respiratory depression. Methadone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this medication may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; regular evaluation of renal function should occur.