Methadone Hydrochloride

Methadone is used to treat addiction to opioids (such as heroin) as part of an approved treatment program. Methadone belongs to a class of drugs known as opioid (narcotic) analgesics. It helps prevent withdrawal symptoms caused by stopping other opioids.

Methadone may also be used to treat severe pain. Do not use methadone to relieve pain that is mild or that will go away in a few days. Methadone is not for occasional ("as needed") use.

Methadone is available under the following different brand and other names: Methadose, and Dolophine.

Adult Dosage Forms & Strengths

Injectable solution: Schedule II

• 10mg/mL

Tablet: Schedule II

• 5mg
• 10mg
• 40mg (pediatric)

Dispersible tablet: Schedule II

• 40mg

Oral solution: Schedule II

• 5mg/5mL
• 10mg/5mL

Oral concentrate solution: Schedule II

• 10mg/mL

Dosage Considerations -- Should Be Given As Follows:

For Adults with Chronic Severe Pain

Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Opioid-naive patients: 2.5 mg taken orally once every 8-12 hours; titrate slowly with dose increases no more frequent than every 3-5 days

Opioid-tolerant patients

• Discontinue all other around-the-clock opioids
• Substantial inter-patient variability, see prescribing information for guidance

Opioid-tolerant definition

• Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
• Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day oral morphine, 25 mcg/hour transdermal fentanyl, 30 mg/day oral oxycodone, 8 mg/day oral hydromorphone, 25 mg/day oral oxymorphone, or an equianalgesic dose of another opioid

Limitations of use

• Use of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
• Not indicated for acute pain or as an as needed analgesic

Detoxification

20-30 mg taken orally once daily or minimum dosage necessary to suppress withdrawal; may be titrated to 40 mg/day in divided doses and continued for 2-3 days, then decreased 20% daily as tolerated

Dosing Modifications

Renal impairment (CrCl less than 10mL/min): 50-75% of normal dose

Hepatic impairment: Not recommended in severe liver disease

Dosing Considerations

Conversion from oral to parenteral: Parenteral-to-oral ratio, 1:2 (5 mg parenteral = 10 mg taken orally)

To convert to methadone from another opioid, use available conversion factors to obtain estimated dose

Do not abruptly discontinue methadone in a physically dependent patient

Pediatric

Pain (Off-label)

0.7 mg/kg/day orally/subcutaneously/intravenously(IV)/intramuscularly (IM) divided once every 6 hours as needed; not to exceed 10 mg/dose

Opiate Withdrawal (Off-label)

Neonates: 0.05-0.2 mg/kg taken orally once every 12-24 hours; reduce dose by 10-20% per week over 4-6 weeks; adjust tapering on signs and symptoms of withdrawal

Geriatric

Pain

2.5 mg orally or intramuscularly (IM) once every 8-12 hours; titrate slowly with dose increases no more frequent than every 3-5 days

Detoxification

20-30 mg taken orally once daily or minimum dosage necessary to suppress withdrawal; may be titrated to 40 mg/day in divided doses and continued for 2-3 days, then decreased 20% daily as tolerated

Side effects of methadone include:

• Agitation
• Anticholinergic effects (dry mouth, palpitation, fast heart rate)
• Cardiac arrest
• Chest pain
• Coma
• Constipation
• Dizziness
• Drowsiness
• Feeling uneasy
• Euphoria
• Heart attack (myocardial infarction)
• Itching and hives
• Lightheadedness or fainting
• Mental clouding or depression
• Nausea
• Nervousness
• Respiratory arrest
• Respiratory/circulatory depression
• Restlessness
• Seizures
• Severe cardiac arrhythmias
• Shock
• Slow heart rate
• Sweating, flushing, warmness of face/neck/throat
• Urinary retention, urinating less than usual
• Visual disturbances
• Vomiting
• Weakness

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Severe Interactions of methadone include:
  • alvimopan
  • eliglustat
  • itraconazole
  • ketoconazole
  • rasagiline
  • selegiline
• Methadone has serious interactions with at least 59 different drugs.
• Methadone has moderate interactions with at least 315 different drugs.
• Mild Interactions of methadone include:
  • azithromycin
  • brimonidine
  • dextroamphetamine
  • eucalyptus
  • lidocaine
  • naloxone
  • octreotide
  • octreotide (antidote)
  • pazopanib
  • ruxolitinib
  • sage
  • ziconotide
  • zidovudine

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Detoxification and maintenance of dependence

• 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

Addiction, abuse, and misuse

• Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
• Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

Life-threatening respiratory depression

• Serious, life-threatening, or fatal respiratory depression may occur
• Monitor for respiratory depression, especially during initiation or following a dose increase
• Instruct patients to swallow tablet/capsule whole; crushing, chewing, snorting, injecting or dissolving can cause rapid release and absorption of a potentially fatal dose

Accidental exposure

• Accidental of even 1 dose, especially by children, can result in a fatal overdose

Neonatal opioid withdrawal syndrome

• Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
• Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
• 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
• 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

This medication contains methadone. Do not take Methadose or Dolophine if you are allergic to methadone or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

Hypersensitivity to methadone or formulation components; acute abdominal condition, toxin-mediated diarrhea, pseudomembranous colitis, respiratory depression; concurrent use of selegiline, known or suspected paralytic ileus, asthma (acute), significant respiratory impairment

Acute pain or postoperative pain; pain that is mild or not expected to persist

Effects of Drug Abuse

Methadone has a high risk for abuse. It can also cause severe, possibly fatal, breathing problems and heartbeat problems. These problems are more likely to happen when this medication is first started, or when you are switching from another opioid to methadone, or when the dose is increased. Breathing problems from methadone may not happen right away after taking a dose. Most heartbeat problems have happened in people using large doses of methadone for pain relief, but this problem can also occur in people taking smaller doses to treat opioid addiction. Do not increase your dose or take this medication more often than directed. Get medical help right away if you notice unusual slow/shallow breathing, fast/irregular heartbeat, severe dizziness, or fainting.

Short-Term Effects

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.

Methadone may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

Long-Term Effects

There are no long-term effects from the use of methadone.

Cautions

Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present.

Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (e.g., major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary.

Serious, life-threatening, or fatal respiratory depression reported.

Accidental exposure reported, including fatalities.

Interactions with CNS depressants (e.g., alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension; deaths reported due to methadone abuse in conjunction with benzodiazepines.

Monitor for hypotension during dose initiation and titration.

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.

Risk of QT interval prolongation at high doses.

Use caution in cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease, head injury, prostatic hyperplasia, urethral stricture, hepatic impairment, thyroid dysfunction, increased intracranial pressure, prostatic hypertrophy, adrenal insufficiency, history of depression or suicidal tendencies, renal function impairment, seizures with epilepsy, urethral stricture, patients who are morbidly obese, or urinary tract surgery.

May cause CNS depression; use caution in performing tasks, which require mental alertness.

Not recommended to treat abdominal conditions; may obscure diagnosis or clinical course of patients with acute abdominal conditions.

Pregnancy and Lactation with Methadone Hydrochloride

During pregnancy, use methadone with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. Before using this medication, women of childbearing age should talk with their doctor(s) about the risks and benefits. Pregnancy may affect the amount of this drug in your body, so tell your doctor if you are pregnant or if you plan to become pregnant. During pregnancy, this medication should be used only when clearly needed. It may slightly increase the risk of birth defects if used during the first two months of pregnancy. Also, using it for a long time or in high doses near the expected delivery date may harm the unborn baby. To lessen the risk, take the smallest effective dose for the shortest possible time. Babies born to mothers who use this drug for a long time may develop severe (possibly fatal) withdrawal symptoms. Tell the doctor right away if you notice any symptoms in your newborn baby such as slow/shallow breathing, irritability, shaking, persistent crying, vomiting, diarrhea, poor feeding, or difficulty gaining weight.

Methadone is excreted in breast milk; use caution if breastfeeding. Tell the doctor immediately if your baby develops unusual sleepiness, difficulty feeding, or trouble breathing. Consult your doctor before breastfeeding or if you plan to stop breast-feeding.