FDA label 3f607a9a-9b07-0a32-e054-00144ff8d46c

WARNING: LIFE-THREATENING RESPIRATORY DEPRESSION, LIFE-THREATENING QT PROLONGATION, ACCIDENTAL EXPOSURE, ABUSE POTENTIAL 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 [see Warnings and Precautions ( 5.1 )] . Proper dosing and titration are essential and methadone hydrochloride tablets for oral suspension 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 methadone hydrochloride tablets for oral suspension 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. Life-Threatening QT Prolongation QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred during treatment with methadone [see Warnings and Precautions ( 5.2 )] . 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 for changes in cardiac rhythm during initiation and titration of methadone hydrochloride tablets for oral suspension. Accidental Exposure Accidental ingestion of methadone hydrochloride tablets for oral suspension, especially in children, can result in fatal overdose of methadone [see Warnings and Precautions ( 5.3 )] . Abuse Potential Methadone hydrochloride tablets for oral suspension contain methadone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit [see Warnings and Precautions ( 5.4 )] . Routinely monitor all patients receiving methadone hydrochloride tablets for oral suspension for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence ( 9 )] . 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 [see Indications and Usage ( 1 )] . WARNING: LIFE-THREATENING RESPIRATORY DEPRESSION, LIFE-THREATENING QT PROLONGATION, ACCIDENTAL EXPOSURE, ABUSE POTENTIAL and TREATMENT FOR OPIOID ADDICTION See full prescribing information for complete boxed warning. Fatal respiratory depression may occur, with highest risk at initiation and with dose increases. Instruct patients on proper administration of methadone hydrochloride tablets for oral suspension to reduce the risk. ( 5.1 ) QT Interval prolongation and serious arrhythmia (torsades de pointes) have occurred with treatment with methadone. ( 5.2 ) Accidental ingestion of methadone hydrochloride tablets for oral suspension can result in fatal overdose of methadone, especially in children. ( 5.3 ) Methadone hydrochloride tablets for oral suspension contain methadone, a Schedule II controlled substance and can be abused and criminally diverted. ( 5.4 , 9 ) Methadone products, when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by certified opioid treatment programs as stipulated in 42 CFR 8.12. ( 1 )

5.3 Accidental Exposure Accidental ingestion of methadone hydrochloride tablets for oral suspension, especially in children, can result in a fatal overdose of methadone. Methadone hydrochloride tablets for oral suspension should be kept out of reach of children to prevent accidental ingestion.

5.4 Abuse Potential Methadone hydrochloride tablets for oral suspension 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. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

5.5 Elderly, Cachectic, and Debilitated Patients Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance compared to younger, healthier patients. Therefore, monitor such patients closely, particularly when initiating and titrating methadone hydrochloride tablets for oral suspension and when methadone hydrochloride tablets for oral suspension are given concomitantly with other drugs that depress respiration [see Warnings and Precautions ( 5.1 )] .

5.6 Use in Patients with Chronic Pulmonary Disease Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression, particularly when initiating therapy and titrating with methadone hydrochloride tablets for oral suspension, as in these patients, even usual therapeutic doses of methadone may decrease respiratory drive to the point of apnea [see Warnings and Precautions ( 5.1 )] .

6 ADVERSE REACTIONS The following adverse reactions have been identified during post-approval use of methadone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following serious adverse reactions and/or conditions are discussed elsewhere in the labeling: Respiratory Depression [see Warnings and Precautions ( 5.1 )] QT Prolongation [see Warnings and Precautions ( 5.2 )] Chronic Pulmonary Disease [see Warnings and Precautions ( 5.6 )] Interactions with CNS Depressants [see Warnings and Precautions ( 5.7 )] Hypotensive Effect [see Warnings and Precautions ( 5.8 )] Head Injuries and Increased Intracranial Pressure [see Warnings and Precautions ( 5.9 )] Gastrointestinal Effects [see Warnings and Precautions ( 5.10 )] Seizures [see Warnings and Precautions ( 5.11 )] The major hazards of methadone are respiratory depression and, to a lesser degree, systemic hypotension. Respiratory arrest, shock, cardiac arrest, and death have occurred. The most frequently observed adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. These effects seem to be more prominent in ambulatory patients and in those who are not suffering severe pain. In such individuals, lower doses are advisable. Other adverse reactions include the following: Body as a Whole: asthenia (weakness), edema, headache Cardiovascular: arrhythmias, bigeminal rhythms, bradycardia, cardiomyopathy, ECG abnormalities, extrasystoles, flushing, heart failure, hypotension, palpitations, phlebitis, QT interval prolongation, syncope, T-wave inversion, tachycardia, torsade de pointes, ventricular fibrillation, ventricular tachycardia Central Nervous System: agitation, confusion, disorientation, dysphoria, euphoria, insomnia, hallucinations, seizures, visual disturbances Endocrine: hypogonadism Gastrointestinal: abdominal pain, anorexia, biliary tract spasm, constipation, dry mouth, glossitis Hematologic: reversible thrombocytopenia has been described in opioid addicts with chronic hepatitis Metabolic: hypokalemia, hypomagnesemia, weight gain Musculoskeletal: decreased muscle mass and strength, osteoporosis and fractures Renal: antidiuretic effect, urinary retention or hesitancy Reproductive: amenorrhea, reduced libido and/or potency, reduced ejaculate volume, reduced seminal vesicle and prostate secretions, decreased sperm motility, abnormalities in sperm morphology Respiratory: pulmonary edema, respiratory depression Skin and Subcutaneous Tissue: pruritus, urticaria, other skin rashes, and rarely, hemorrhagic urticaria Hypersensitivity: Anaphylaxis has been reported with ingredients contained in methadone hydrochloride tablets for oral suspension. Advise patients how to recognize such a reaction and when to seek medical attention. Maintenance on a Stabilized Dose: During prolonged administration of methadone, as in a methadone maintenance treatment program, constipation and sweating often persist and hypogonadism, decreased serum testosterone and reproductive effects are thought to be related to chronic opioid use. Methadone Hydrochloride Tablets for Oral Suspension for the Detoxification and Maintenance Treatment of Opioid Dependence During the induction phase of methadone maintenance treatment, patients are being withdrawn from illicit opioids and may have opioid withdrawal symptoms. Monitor patients for signs and symptoms including: lacrimation, rhinorrhea, sneezing, yawning, excessive perspiration, goose-flesh, fever, chilling alternating with flushing, restlessness, irritability, weakness, anxiety, depression, dilated pupils, tremors, tachycardia, abdominal cramps, body aches, involuntary twitching and kicking movements, anorexia, nausea, vomiting, diarrhea, intestinal spasms, and weight loss and consider dose adjustment as indicated. Most common adverse reactions are: lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Mallinckrodt Inc. at 1-888-744-1414 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch