IMPORTANT SAFETY INFORMATION

WARNING: LIFE-THREATENING RESPIRATORY DEPRESSION, RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS, LIFE-THREATENING QT PROLONGATION, ACCIDENTAL INGESTION, ABUSE POTENTIAL, INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES and TREATMENT FOR OPIOID ADDICTION Life-Threatening Respiratory Depression Respiratory depression, including fatal cases, have been reported during initiation and conversion of patients to methadone, and even when the drug has been used as recommended and not misused or abused. Proper dosing and titration are essential and METHADOSE should only be prescribed by healthcare professionals who are knowledgeable in the use of methadone for detoxification and maintenance treatment of opioid addiction. Monitor for respiratory depression, especially during initiation of METHADOSE 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 initial dosing period. Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death. Reserve concomitant prescribing of benzodiazepines or other CNS depressants in patients in methadone treatment to those for whom alternatives to benzodiazepines or other CNS depressants are inadequate. Follow patients for signs and symptoms of respiratory depression and sedation. If the patient is visibly sedated, evaluate the cause of sedation and consider delaying or omitting daily methadone dosing. Life-Threatening QT Prolongation QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred during treatment with methadone. 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 METHADOSE. Accidental Ingestion Accidental ingestion of METHADOSE, especially by children, can result in fatal overdose of methadone. Misuse, Abuse, and Diversion of Opioids METHADOSE contains methadone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit. Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 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 P450 3A4, 2B6, 2C19, or 2C9 inducers may also result in an increase in methadone plasma concentration. Follow patients closely for respiratory depression and sedation, and consider dosage reduction with any changes of concomitant medications that can result in an increase in methadone levels. Conditions for Distribution and Use of Methadone Products for the Treatment of Opioid Addiction For detoxification and maintenance of opioid dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration.

CONTRAINDICATIONS

METHADOSE is contraindicated in patients with:

• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Hypersensitivity (e.g., anaphylaxis) to methadone or any other ingredient in METHADOSE.

WARNINGS AND PRECAUTIONS

• METHADOSE and METHADOSE Sugar-Free are for oral administration only. The preparation must not be injected. METHADOSE and METHADOSE Sugar-Free, if dispensed, should be packaged in child-resistant containers and kept out of reach of children to prevent accidental ingestion.
• Serious, life-threatening, or fatal respiratory depression has been reported with the use of methadone, even when used as recommended. Patients with chronic pulmonary disease, elderly, cachectic, or debilitated patients may be at increased risk. Monitor closely, especially during initiation and titration.
• Concomitant use of methadone and benzodiazepines or other CNS depressants increases the risk of adverse reactions including overdose and death. As a routine part of orientation to methadone treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, or alcohol.
• 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). 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. Monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction.
• Accidental ingestion of even one dose of METHADOSE, especially by children, can result in respiratory depression and death due to an overdose.
• METHADOSE contain methadone, an opioid agonist and a Schedule II controlled substance. Methadone can be abused in a manner similar to other opioid agonists, legal or illicit.
• Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy. Observe newborns for signs of NOWS and manage accordingly; NOWS may be life threatening if not recognized and treated in neonates.
• Concomitant use of METHADOSE with CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors, may increase plasma concentrations of methadone and use with CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers or discontinuation of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors in patients treated with METHADOSE may decrease methadone plasma concentrations.
• Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of METHADOSE with serotonergic drugs. Discontinue METHADOSE if serotonin syndrome is suspected.
• Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. If adrenal insufficiency is diagnosed, treat with physiologic replacement of corticosteroids and wean patient off of the opioid until adrenal function recovers.
• Methadone may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. Monitor during initiation and/or titration of methadone.
• Use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness may reduce respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Use of methadone should be avoided in patients with impaired consciousness or coma.
• METHADOSE is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus. The methadone in METHADOSE may cause spasm of the sphincter of Oddi.
• Methadone may increase frequency of seizures in patients with seizure disorders, and increase the risks of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control.
• Avoid use of METHADOSE with mixed agonist/antagonists or partial agonist analgesics due to risk of precipitation of withdrawal symptoms. When discontinuing METHADOSE, gradually taper the dosage.
• METHADOSE may impair the ability to perform potentially hazardous activities such as driving or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication.
• False positive urine drug screens for methadone have been reported for several drugs including diphenhydramine, doxylamine, clomipramine, chlorpromazine, thioridazine, quetiapine, and verapamil.

ADVERSE REACTIONS

The most frequently observed adverse reactions included lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. This is not a complete list of potential adverse events associated with methadone. Please see Full Prescribing Information for a complete list.

 

Description	Red, cherry flavored liquid concentrate
Generic Name	Methadone hydrochloride oral concentrate, USP
Dosage Strength	10 mg/mL
Identification Code	N/A
Rating	AA

ORDER INFORMATION

NDC #	Package Size	Case Quantity
0406-0527-10	1000 mL	4

For additional information on Methadose™ Oral Concentrate (Methadone Hydrochloride Oral Concentrate USP) 10 mg/mL, CII, call Customer Service at 1.800.325.8888 or Medical Information at 1.800.778.7898.

Code: 10004868
Revised: 8/2019