Methadone and Methadose®

Brand name

  • Methadose®

Drug Class

Methadone is a synthetic opioid that is used as a pain reliever and for management of withdrawal symptoms in individuals with long term use of heroin or other opioids and pain killers.
Methadone was discovered in 1938 by two German scientists, Max Bockmühl and Gustav Ehrhart, who were attempting to find a gastrointestinal tract antispasmodic and analgesic which would be structurally dissimilar to morphine and be non-addictive. In 1947, Harris Isbell and his colleagues, who had been experimenting extensively with methadone, discovered that methadone was beneficial in the treatment of opiate-dependent patients.

Preparations

  • Methadone®  1mg/ml oral
  • Methadose® 10mg/1ml Oral Concentrate
  • Methadone tablets: 1 mg, 5mg, 10 mg, 25 mg

Indications

  • Treatment of opioid dependence
  • Treatment of chronic pain

What are the benefits of being on methadone program?

The benefits of methadone maintenance treatment fall into seven categories:

  1. reduction or cessation of opioids use, particularly intravenous
  2. reduction or cessation of other psychoactive substance use
  3. improved mental and physical health
    1. decreased incidence of concomitant infections such as endocarditis, osteomyelitis, and
      cellulitis, with consequently reduced need for hospitalization
    2. decreased emergency room visits for drug-related complications
    3. improved mental health outcomes
    4. improved hepatitis C (HCV) and HIV clinical parameters
    5. improved engagement with primary care
    6. improved nutrition and weight gain
    7. improved pregnancy outcomes
  4. decreased involvement with the criminal justice system
  5. improved living situations
  6. improved social and personal relationships
  7. improved vocational and employment opportunities
  8. patients who attain improved medical and social stability are much more likely to connect with social agencies to gain access to financial support; they are also more likely to be considered for educational and training programs which may be necessary for eventual employment

What happens if I miss a dose?

If you take methadone for pain: Take the missed dose as soon as you remember, then take your next dose 8 to 12 hours later.
If you take methadone for drug addiction: Take your missed dose the next day at the regular time. If you miss your doses for longer than 3 days in a row, call your doctor for instructions. You may need to restart at a lower dose.
Do not use extra medicine to make up a missed dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of this medicine can be fatal, especially in a child or other person using the medicine without a prescription.
Overdose symptoms may include slow breathing and heart rate, severe drowsiness, muscle weakness, cold and clammy skin, pinpoint pupils, and fainting.

Do not take Methadose and tell your doctor if:

  • you are allergic (hypersensitive) to methadone
  • you have severe breathing problems or a history of asthma or COPD
  • you are taking Monoamine Oxidase Inhibitors (MAOIs) used to treat depression
  • you have phaeochromoytoma, a tumour of the adrenal glands
  • you have a bowel disorder known as paralytic ileus
  • you have or have recently had a head injury
  • you have liver or kidney problems
  • you have problems with your gallbladder and bile duct
  • you have seizure or epilepsy
  • you are addicted to alcohol
  • you use benzodiazepines
  • you have low thyroid function (hypothyroid)
  • you have an enlarged prostate gland
  • you have a history of irregular heart beat
  • you have a history of heart disease
  • you have a family history of people dying suddenly without cause
  • you are pregnant or breast-feeding

Is it safe to drink alcohol while one is on methadone?

Alcohol use poses unique concerns in methadone maintenance patients. The risk of overdose is
increased, given the synergistic respiratory depressant effect alcohol has with methadone. In addition, alcohol interferes with the metabolism of methadone. In its early stages, problem drinking has the potential to induce hepatic enzymes which can accelerate methadone metabolism. At later stages, liver failure can precipitously reduce a patient’s tolerance to methadone. These complicated interactions underscore the need for physicians to appropriately screen and monitor for alcohol use disorders and provide intervention and treatment.

Is it safe to use Sedative-Hypnotics (Benzodiazepines and Z Drugs) while one is on methadone?

Like alcohol, these drugs have a synergistic respiratory depressant effect when used with methadone and may increase the risk of fatal overdose. Multidoctoring for sedative-hypnotics is common. It is the responsibility of the methadone prescriber to review PharmaNet profiles regularly. All psychoactive substances act through a final common end pathway in the brain and therefore sedative-hypnotics are relatively contraindicated in patients with addiction disorders.

Dosing

  • Maximum starting dose and only for heavy intravenous users is 30 mg daily
  • The time to peak plasma concentration and peak clinical effect is four hours (range of two to six hours).
  • The plasma half-life averages 24 to 36 hours at steady state, but ranges from four to 90 hours.
  • As a result of its long half-life, methadone may accumulate, leading to sedation and respiratory depression
  • It takes four to five days for methadone plasma levels to reach steady state after each dose change. So, it is recommended that dose to be increased by 5-10% no sooner than once every 5 days
  • Methadone is primarily excreted as an inactive metabolite (10% as unchanged methadone) primarily in urine and feces. Compromised renal function does not preclude the use of methadone, and the dosage does not need to be adjusted for patients on dialysis.
  • Elimination half-life is approximately 22 hours, but ranges from five hours to 130 hours.
  • If you miss three consecutive doses, your daily dose will be reduced to 50%
  • If you miss 5 consecutive doses, your daily dose will be reduced to 30 mg

Drug Interactions

Tell your doctor if you are taking any of the following medicines:

  • High doses of tricyclic antidepressants (TCAs) may interact with methadone and
    increase the risk of toxicity.
  • Concurrent use of benzodiazepines with methadone may increase the risk of respiratory depression.
  • Anti depressions such as: fluvoxamine, fluoxetine…
  • cimetidine
  • rifampicin
  • Phenytoin, carbamazepine, phenobarbital and primidone
  • Narcotic painkillers such as codeine and pentazocine
  • Naltrexone
  • Buprenorphine
  • HIV medications such as: nevirapine, efavirenz, abacavir and nelfinavir
  • Antibiotics such as: ciprofloxacin or macrolide antibiotics for example erythromycin
  • Anti-fungals such as: ketoconazole or fluconazole
  • John’s Wort – a herbal preparation for depression
  • Cyclizine, domperidone and metoclopramide used to treat nausea and vomiting
  • Mexiletine used to treat unusual heart rhythms.

Adverse Effects

Common (1% to 10%):

  • Edema
  • Nausea, vomiting
  • Constipation
  • Vertigo, fatigue
  • Euphoria, hallucinations
  • Weight gain
  • Miosis, dry eyes
  • Transient rash, sweating

 

Uncommon (0.1% to 1%):

  • Syncope, flushing, hypotension
  • Bradycardia, palpitations, QT interval prolongation, Torsades de pointes
  • Arrhythmias, bigeminal rhythms, cardiomyopathy, ECG abnormalities, extrasystoles, heart failure, phlebitis, QT interval prolongation, syncope, T-wave inversion, tachycardia, ventricular fibrillation, ventricular tachycardia
  • Dry mouth, glossitis
  • Abdominal pain, anorexia, biliary tract spasm
  • Asthenia, hypothermia
  • Agitation, dysphoria, insomnia, mood changes
  • Galactorrhea, dysmenorrhea, amenorrhea
  • Hypogonadism,
  • decreased serum testosterone
  • reduced libido and/or potency
  • reduced ejaculate volume
  • reduced seminal vesicle and prostate secretions
  • decreased sperm motility
  • abnormalities in sperm morphology
  • gynecomastia
  • adrenal insufficiency
  • increased prolactin concentrations
  • Urinary retention
  • Pulmonary edema
  • exacerbation of asthma
  • dry nose
  • respiratory depression
  • Pulmonary edema
  • Antidiuretic effect
  • lymphocytosis
  • Reversible thrombocytopenia
  • Hypokalemia, hypomagnesemia
  • Visual disturbances
  • Pruritus, urticaria
  • other skin rashes
  • Hemorrhagic urticaria
  • Bile duct dyskinesia

Driving and using machines

  • Methadose can severely affect your ability to drive or use machines as it may make you sleepy or dizzy
  • Review care plan with your doctor

Pregnancy and Breastfeeding

  • Methadone dose needs to be adjusted if you are pregnant or breastfeeding

Warning

  • Methadone metabolism is primarily a function of liver enzyme
    activity involving cytochrome P450 isoforms. There are many
    substances that interact by inducing, inhibiting or acting as a
    substrate for these enzymes. This can result in clinically significant
    drug interactions. Genetic, physiologic and environmental factors
    can also act on these enzymes, leading to a high degree of variation
    of individual methadone responsiveness.
  • Methadone is prone to misuse and capable of causing dependence, toxicity, overdose and death.
  • You should not use methadone if you have:
    • been taking Naltrexone over the past 5 days
    • severe asthma or breathing problems
    • blockage in your stomach or intestines.
    • some heart rhythm disorder
    • liver disorders
    • been taking specific psychiatric medications
    • long QT syndrome (in you or a family member);
    • a head injury
    • alcohol addiction
    • sedatives dependence such as diazepam, alprazolam, lorazepam, Ativan, Klonopin, Restoril, Tranxene, Versed, Xanax, and others
  • Children must not take this medicine.
  • If you take more of this medicine than you should, talk to a doctor or go to your nearest hospital straight away. Take the medicine pack with you.
  • If you forget a dose do not take it. Wait until the next dose is due and take only that amount
  • Do not take a double dose (two doses at the same time) to make up for a forgotten dose
  • take your daily doses as prescribed

Important note

This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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