"Consumers and health care professionals will soon find updated labeling for extended-release and long-acting opioid pain relievers to help ensure their safe and appropriate use.
In addition to requiring new labeling on these prescript"...
Addiction, Abuse, and Misuse
Methadone hydrochloride tablets contain methadone, a Schedule II controlled substance. As an opioid, methadone hydrochloride tablets expose users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)]. As long-acting opioids such as methadone hydrochloride tablets have pharmacological effects over an extended period of time, there is a greater risk for overdose and death.
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed methadone hydrochloride tablets and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if the drug is misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing methadone hydrochloride tablets, and monitor all patients receiving methadone hydrochloride tablets for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol addiction or abuse) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the prescribing of methadone hydrochloride tablets for the proper management of pain in any given patient. Patients at increased risk may be prescribed long-acting opioids such as methadone hydrochloride tablets, but use in such patients necessitates intensive counseling about the risks and proper use of methadone hydrochloride tablets along with the intensive monitoring for signs of addiction, abuse, and misuse.
Abuse or misuse of methadone hydrochloride tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the methadone and can result in overdose and death [see Overdosage].
Opioid agonists such as methadone hydrochloride tablets are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing methadone hydrochloride tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. 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.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression has been reported with the use of long-acting opioids, even when used as recommended. Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of methadone hydrochloride tablets, the risk is greatest during the initiation of therapy or following a dose increase. The peak respiratory depressant effect of methadone occurs later, and persists longer than the peak analgesic effect, especially during the initial dosing period. Closely monitor patients for respiratory depression when initiating therapy with methadone hydrochloride tablets and following dose increases.
To reduce the risk of respiratory depression, proper dosing and titration of methadone hydrochloride tablets are essential [see Dosage and Administration]. Overestimating the methadone hydrochloride tablets dose when converting patients from another opioid product can result in fatal overdose with the first dose.
Accidental ingestion of even one dose of methadone hydrochloride tablets, especially by children, can result in respiratory depression and death due to overdose of methadone.
Life-Threatening QT Prolongation
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. In most patients on the lower doses typically used for maintenance, 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. The effects of methadone on the QT interval have been confirmed in in vivo laboratory studies, and methadone has been shown to inhibit cardiac potassium channels in in vitro studies.
Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. QT prolongation has also been reported in patients with no prior cardiac history who have received high doses of methadone.
Evaluate patients developing QT prolongation while on methadone treatment for the presence of modifiable risk factors, such as concomitant medications with cardiac effects, drugs that might cause electrolyte abnormalities, and drugs that might act as inhibitors of methadone metabolism.
Only initiate methadone hydrochloride tablets therapy for pain in patients for whom the anticipated benefit outweighs the risk of QT prolongation and development of dysrhythmias that have been reported with high doses of methadone.
The use of methadone in patients already known to have a prolonged QT interval has not been systematically studied.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of methadone hydrochloride tablets during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn [see Use in Specific Populations].
Interactions with Central Nervous System Depressants
Hypotension, profound sedation, coma, respiratory depression, and death may result if methadone hydrochloride tablets are used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids).
When considering the use of methadone hydrochloride tablets in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that cause CNS depression. If the decision to begin methadone hydrochloride tablets is made, start with methadone hydrochloride tablets 2.5 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant [see Drug Interactions].
Use in Elderly, Cachectic, and Debilitated Patients
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating methadone hydrochloride tablets and when methadone hydrochloride tablets are given concomitantly with other drugs that depress respiration [see Warnings and Precautions].
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 for respiratory depression, particularly when initiating therapy and titrating with methadone hydrochloride tablets, as in these patients, even usual therapeutic doses of methadone hydrochloride tablets may decrease respiratory drive to the point of apnea [see Warnings and Precautions]. Consider the use of alternative non-opioid analgesics in these patients if possible.
Methadone hydrochloride tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g. phenothiazines or general anesthetics) [see Drug Interactions (7.1)]. Monitor these patients for signs of hypotension after initiating or titrating the dose of methadone hydrochloride tablets.
Use in Patients with Head Injury or Increased Intracranial Pressure
Monitor patients taking methadone hydrochloride tablets who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with methadone hydrochloride tablets. Methadone hydrochloride tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury.
Avoid the use of methadone hydrochloride tablets in patients with impaired consciousness or coma.
Use in Patients with Gastrointestinal Conditions
Methadone hydrochloride tablets are contraindicated in patients with paralytic ileus. Avoid the use of methadone hydrochloride tablets in patients with other gastrointestinal obstruction.
The methadone in methadone hydrochloride tablets may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase.
Use in Patients with Convulsive or Seizure Disorders
The methadone in methadone hydrochloride tablets may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during methadone hydrochloride tablets therapy.
Avoidance of Withdrawal
Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including methadone hydrochloride tablets. In these patients, mixed agonists/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms [see Drug Interactions].
When discontinuing methadone hydrochloride tablets, gradually taper the dose [see Dosage and Administration]. Do not abruptly discontinue methadone hydrochloride tablets.
Driving and Operating Machinery
Methadone hydrochloride tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of methadone hydrochloride tablets and know how they will react to the medication.
Included as part of the WARNINGS
Last reviewed on RxList: 12/2/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Methadone Hydrochloride Information
Report Problems to the Food and Drug Administration
Chronic Pain/Back Pain
Find tips and advances in treatment.