Methadone (Dolophine) Warnings, Risks, and Complications

RISK OF MISUSE, ABUSE, AND OPIATE ADDICTION: Patients taking methadone can develop a drug dependence on opiate drugs, even when they take methadone at the prescribed medication dosage. The risk of developing an addiction is higher if you take methadone for reasons other than prescribed, at higher doses, or more frequently than prescribed. Misuse and abuse of methadone can lead to opioid overdose and death. People who have a personal or family history of drug abuse or other mental illness are at greater risk of methadone abuse. 

Your doctor will prescribe the lowest dose of methadone for the shortest time possible to control your pain. Before you begin treatment, your provider will go over how to use methadone safely. This is a requirement under the FDA’s Risk Evaluation and Mitigation Strategy (REMS) program to reduce illicit opioid use and addiction.

RESPIRATORY DEPRESSION: Methadone can cause irregular, slow, or shallow breathing at any time during treatment, but especially when you first start taking it and after the dose is increased. This can lead to respiratory arrest and death. Accidental ingestion of even one methadone tablet by a child can be fatal. 

Alcohol and certain other medications like sedatives, anti-anxiety medicines, benzodiazepines, muscle relaxants, and other opioids can also cause slowed breathing. Concomitant use of these medications with methadone can result in profound sedation, CNS depression, and slowed breathing. The risk is higher in older adults (age 65 and above), people with chronic obstructive pulmonary disease (COPD) and other respiratory conditions, and those taking high doses of methadone.

Learn to recognize the signs and symptoms of breathing problems (slow or shallow breathing, bluish toes or fingers) and seek emergency medical care if they develop.

LIFE-THREATENING ARRHYTHMIAS: There are reports of life-threatening QT prolongation and other cardiac arrhythmias, such as torsades de pointes, after taking methadone. Risk factors include taking high doses of methadone, hypokalemia (low serum potassium levels), hypomagnesemia (low serum magnesium levels), concomitant use of diuretics (water pills), history of cardiac arrhythmias, and taking other medications that can also cause QT prolongation. Your doctor may avoid prescribing methadone if you are at a high risk of these potentially life-threatening heart problems.

NEONATAL OPIOID WITHDRAWAL SYNDROME: The use of opioids by pregnant women can lead to opioid dependence in the baby. This can result in withdrawal effects after the baby is born and stops receiving opioids through the mother. The condition is called neonatal opioid withdrawal syndrome. It can be life-threatening if not recognized and treated in time. 

Tell your healthcare providers if you have used methadone during pregnancy. Signs and symptoms of NOWS can include high-pitched crying, poor feeding, fussiness, irritability, trembling, abnormal sleep, and seizures. Be vigilant for these symptoms in your baby and seek immediate medical help if they occur. Likewise, breastfeeding women should be aware that the medicine can pass into breast milk. They should carefully monitor the baby for any unusual signs and symptoms. Breast milk will need to be weaned slowly to prevent withdrawal.

DRUG INTERACTIONS: Taking methadone with certain other medications, such as benzodiazepines, non-benzodiazepine anti-anxiety medications, sedatives, hypnotics, tranquilizers, muscle relaxants, antipsychotics, other opioids, alcohol, and other drugs that depress the central nervous system can lead to profound sedation, respiratory depression, coma, and death. 

Concomitant use of methadone and serotonergic drugs can result in a life-threatening condition called serotonin syndrome due to too much serotonin in the central nervous system. 

Give your doctor a full list of all your medications, including prescription drugs, over-the-counter medications, dietary supplements, and herbal products, before starting methadone treatment to lower the risk of dangerous drug interactions.

ADRENAL INSUFFICIENCY: Opioid medications, including methadone, can lead to a fall in hormone levels made by the adrenal glands in the body, especially with long-term use. Signs and symptoms of adrenal insufficiency may include nausea, vomiting, dizziness, tiredness, weakness, and loss of appetite. Tell your healthcare professional if you experience any of these symptoms. You may need to be treated with corticosteroids for replacement.

SEVERE HYPOTENSION: Patients taking methadone can develop severe hypotension (low blood pressure), including postural hypotension or orthostatic hypotension (fall in blood pressure when going from a sitting or lying position to standing). The risk of low blood pressure is higher in older adults (age 65 years and above), people who are dehydrated, and people taking other medications that also cause low blood pressure. 

Tell your doctor if you develop dizziness, lightheadedness, or fainting when going from lying or sitting to standing. Get up slowly out of bed to prevent falls.

RISKS IN PEOPLE WITH CERTAIN MEDICAL CONDITIONS: Methadone treatment can lead to worsening of certain medical conditions such as increased intracranial pressure, brain tumors, gastrointestinal obstruction including paralytic ileus, and seizure disorders. Give your doctor a complete medical history before starting methadone treatment for pain control or methadone maintenance treatment for opioid use disorders to prevent opioid cravings.

OPIOID OVERDOSE: Too much methadone in the body can be fatal. A methadone overdose can occur even at the recommended doses and cause death if it is not recognized and treated in time. In children, accidental ingestion of even one tablet of methadone can be fatal. The risk of an overdose is higher if you take higher doses or more frequent doses of methadone than prescribed. Older adults and people with a history of substance abuse or previous opioid overdose are at higher risk. Methadone overdose symptoms include slowed breathing, slow heartbeat, severe drowsiness, cold or clammy skin, and unresponsiveness. 

Store methadone safely out of reach of children, visitors, and pets. Call 911 right away if you think an overdose has occurred. Talk to your doctor about having a medication called naloxone (Narcan) to prevent the dangerous effects of an overdose.

LIFE-THREATENING WITHDRAWAL SYMPTOMS: Suddenly stopping methadone after long-term use can lead to life-threatening withdrawal effects. Symptoms may include yawning, sweating, chills, restlessness, irritability, anxiety, runny nose, wide pupils, uncontrolled pain, and suicidal thoughts. Do not change your dose or stop taking methadone without talking to your doctor first. Your doctor will tell you how to slowly lower your dose to prevent withdrawal effects.

EXTREME DROWSINESS: Methadone can cause severe drowsiness and a decreased ability to think, react, and focus. Alcohol and certain other medications like sedatives, anti-anxiety medicines, benzodiazepines, and muscle relaxants can make these side effects worse. The risk of extreme drowsiness is higher in older adults (age 65 years and older).

Give your doctor a complete list of your medications to avoid interactions and severe side effects. Avoid drinking alcohol while taking methadone. Do not drive or do other activities that require your full attention until you know how methadone affects you. 

LABORATORY TESTS: Methadone can result in false positive results on urine tests. Tell laboratory personnel you are on methadone before any lab tests.