For detoxification treatment of opioid addiction (heroin or other morphine-like drugs).2.
For maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.NOTEOutpatient maintenance and outpatient detoxification treatment may be provided only by Opioid Treatment Programs (OTPs) certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA).This does not preclude the maintenance treatment of a patient with concurrent opioid addiction who is hospitalized for conditions other than opioid addiction and who requires temporary maintenance during the critical period of his/her stay, or of a patient whose enrollment has been verified in a program which has been certified for maintenance treatment with methadone.
Methadone hydrochloride tablets for oral suspension is contraindicated in patients with a known hypersensitivity to methadone hydrochloride or any other ingredient in methadone hydrochloride tablets for oral suspension.
Methadone is contraindicated in any situation where opioids are contraindicated such as: patients with respiratory depression (in the absence of resuscitative equipment or in unmonitored settings), and in patients with acute bronchial asthma or hypercarbia.Methadone is contraindicated in any patient who has or is suspected of having a paralytic ileus.
Respiratory DepressionRespiratory depression is the chief hazard associated with methadone hydrochloride administration.
Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, in the short-term use setting.
These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration.Respiratory depression is of particular concern in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.Methadone should be administered with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, and central nervous system (CNS) depression or coma.
In these patients, even usual therapeutic doses of methadone may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.
Methadone should be used at the lowest effective dose and only under careful medical supervision.Cardiac Conduction EffectsThis information is intended to alert the prescriber to comprehensively evaluate the risks and benefits of methadone treatment.
The intent is not to deter the appropriate use of methadone in patients with a history of cardiac disease.Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval.
Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone.
These cases appear to be more commonly associated with, but not limited to, higher dose treatment (>200 mg/day).
Although most cases involve patients being treated for pain with large, multiple daily doses of methadone, cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
In most of the cases seen at typical maintenance doses, concomitant medications and/or clinical conditions such as hypokalemia were noted as contributing factors.
However, the evidence strongly suggests that methadone possesses the potential for adverse cardiac conduction effects in some patients.Methadone should be administered with particular caution to patients already at risk for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia).
Careful monitoring is recommended when using methadone in patients with a history of cardiac conduction abnormalities, those taking medications affecting cardiac conduction, and in other cases where history or physical exam suggest an increased risk of dysrhythmia.
QT prolongation has also been reported in patients with no prior cardiac history who have received high doses of methadone.
Patients developing QT prolongation while on methadone treatment should be evaluated for the presence of modifiable risk factors, such as concomitant medications with cardiac effects, drugs which might cause electrolyte abnormalities and drugs which might act as inhibitors of methadone metabolism.The potential risks of methadone, including the risk of life-threatening arrhythmias, should be weighed against the risks of discontinuing methadone treatment.
In the patient being treated for opiate dependence with methadone maintenance therapy, these risks include a very high likelihood of relapse to illicit drug use following methadone discontinuation.The use of methadone in patients already known to have a prolonged QT interval has not been systematically studied.
The potential risks of methadone should be weighed against the substantial morbidity and mortality associated with untreated opioid addiction.In using methadone an individualized benefit to risk assessment should be carried out and should include evaluation of patient presentation and complete medical history.
For patients judged to be at risk, careful monitoring of cardiovascular status, including evaluation of QT prolongation and dysrhythmias should be performed.Incomplete Cross-tolerance between Methadone and other OpioidsPatients tolerant to other opioids may be incompletely tolerant to methadone.
Incomplete cross-tolerance is of particular concern for patients tolerant to other mu-opioid agonists who are being converted to methadone, thus making determination of dosing during opioid conversion complex.
Deaths have been reported during conversion from chronic, high-dose treatment with other opioid agonists.
A high degree of "opioid tolerance" does not eliminate the possibility of methadone overdose, iatrogenic or otherwise.Misuse, Abuse, and Diversion of OpioidsMethadone is a mu-agonist opioid with an abuse liability similar to that of morphine and other opioid agonists and is a Schedule II controlled substance.
Methadone, like morphine and other opioids used for analgesia, has the potential for being abused and is subject to criminal diversion.Methadone can be abused in a manner similar to other opioid agonists, legal or illicit.
This should be considered when prescribing or dispensing methadone in situations where the clinician is concerned about an increased risk of misuse, abuse, or diversion.
Abuse of methadone poses a risk of overdose and death.
This risk is increased with concurrent abuse of methadone with alcohol and other substances.
In addition, parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.Interactions with other CNS DepressantsPatients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with methadone may experience respiratory depression, hypotension, profound sedation, or coma (see PRECAUTIONS).Interactions with Alcohol and Drugs of AbuseMethadone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.
Deaths associated with illicit use of methadone frequently have involved concomitant benzodiazepine abuse.Head Injury and Increased Intracranial PressureThe respiratory depressant effects of opioids and their capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure.
Furthermore, opioids produce effects which may obscure the clinical course of patients with head injuries.In such patients, methadone must be used with caution, and only if it is deemed essential.Acute Abdominal ConditionsThe administration of opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.Hypotensive EffectThe administration of methadone may result in severe hypotension in patients whose ability to maintain normal blood pressure is compromised (e.g., severe volume depletion).