Methadone

Brands of Methadone Available in Kenya

 

Methadone Martindale Pharma , Martindale Pharmaceuticals

 


Methadone in Kenya: Brands,Prices,Availability,Where to Buy: Methadone Chemical Structure
Methadone Chemical Structure

MODE OF ACTION

Methadone hydrochloride is a μ agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown. Other NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.

INDICATIONS

  • For use in the treatment of opioid drug addiction (as a narcotic abstinence syndrome suppressant)
  • For the treatment of moderate to severe pain not responsive to non-narcotic analgesics.

DOSAGE AND ADMINISTRATION

Adults: Initially 10-20mg per day, increasing by 10-20mg per day until there are no signs of withdrawal or intoxication. The usual dose is 40-60mg per day. The dose is adjusted according to the degree of dependence with the aim of gradual reduction.

Elderly: In the case of elderly or ill patients repeated doses should only be given with extreme caution.

Children: Not recommended for children.

CONTRAINDICATIONS

  • Respiratory depression, obstructive airway disease. Use during an acute asthma attack is not recommended.
  • Acute alcoholism.
  • Concurrent administration with MAO inhibitors, including moclobemide, or within two weeks of discontinuation of treatment with them.
  • Patients dependent on non-opioid drugs.
  • Use during labour is not recommended, the prolonged duration of action increases the risk of neonatal depression.
  • Methadone is not suitable for children (serious risk of toxicity).
  • Hypersensitivity to the active substance or to any of the excipients .
  • Raised intracranial pressure  or head injury.
  • Phaeochromocytoma.
  • Risk of paralytic ileus (including drug induced gastrointestinal hypotonia).

DRUG INTERACTIONS

MAOI’s:

The concurrent use of MAOI’s is contraindicated as they may prolong and enhance the respiratory depressant effects of methadone.

CNS depressants:

Anaesthetics, hypnotics (including benzodiazepines, chloral hydrate and chlormethiazole), anxiolytics, sedatives, barbiturates, phenothiazines, some other major tranquillizers and tricyclic antidepressants may increase the general depressant effects of methadone when used concomitantly. Antipsychotics may enhance the sedative effects and hypotensive effects of methadone.

Methadone may increase desimipramine levels by up to a factor of two.

There are reports that antidepressant drugs (e.g. fluvoxamine and fluoxetine) may increase serum levels of methadone.

Other serotonergic drugs:

Methadone is a weak serotonin uptake inhibitor. There is an increased risk of serotonin syndrome when methadone is co-administered with other serotonergic drugs (e.g. SSRIs, SNRIs, TCAs, MAOIs, serotonergic anti-emetics, serotonergic anti-migraine drugs). This is not an exhaustive list.

Alcohol may enhance the sedative and hypotensive effects of methadone and increase respiratory depression.

Histamine H2 Antagonists:

Histamine H2 antagonists such as cimetidine, can reduce the protein binding of methadone resulting in increased opiate action.

Antibacterials

Rifampicin: Reduced plasma levels and increased urinary excretion of methadone can occur with concurrent administration of rifampicin. Adjustment of the dose of methadone may be necessary.

Ciprofloxacin: Plasma levels of methadone may increase with concurrent administration of ciprofloxacin due to inhibition of CYP 1A2 and CYP 3A4. Reduced serum concentrations of ciprofloxacin may occur. Concomitant use may lead to sedation, confusion and respiratory depression.

Erythromycin: Theoretically this may increase methadone levels due to decreased methadone metabolism.

Antifungals

Fluconazole, voricanozole and ketoconazole: May raise methadone levels, due to decreased methadone metabolism.

Anticonvulsants (Phenytoin, Phenobarbital, Carbamazepine and Primidone):

Induces methadone metabolism with the risk of precipitating withdrawal syndrome. Adjustment of the dose of methadone should be considered.

PH of urine:

Drugs that acidify or alkalinise the urine may have an effect on clearance of methadone as it is increased at acidic pH and decreased at alkaline pH.

Opioid agonist analgesics:

Additive CNS depression, respiratory depression and hypotension

Opioid antagonists:

Naloxone and naltrexone antagonises the analgesic, CNS and respiratory depressant effects of methadone and can rapidly precipitate withdrawal symptoms . Similarly buprenorphine and pentazocine may precipitate withdrawal symptoms.

Antiretroviral Agents such as Nevirapine, Efavirenz, Nelfinavir, Ritonavir, Abacavir:

Based on the known metabolism of methadone, these agents may decrease plasma concentrations of methadone by increasing its hepatic metabolism. Methadone may increase the plasma concentration of zidovudine. Narcotic withdrawal syndrome has been reported in patients treated with some retroviral agents and methadone concomitantly. Methadone maintained patients beginning antiretroviral therapy should be monitored for evidence of withdrawal and the methadone dose should be adjusted accordingly.

Cyclizine and other sedating antihistamines

May have additive psychoactive effects; antimuscarinic effects at high doses.

Other Drugs:

Methadone may have an effect on other drugs as a consequence of reduced gastro-intestinal motility.

Pregnancy Tests:

Methadone may interfere with the urine testing for pregnancy.

Cytochrome P450 3A4 inhibitors:

Methadone clearance is decreased when co-administered with drugs which inhibit CYP3A4 activity, such as some anti-HIV agents, macrolide antibiotics, cimetidine and azole antifungal agents (since the metabolism of methadone is mediated by the CYP3A4 isoenzyme).

St. John’s Wort:

May lower plasma concentrations of methadone.

Grapefruit Juice:

There are several anecdotal reports of raised methadone levels due to decreased methadone metabolism.

Drugs affecting gastric emptying:

Domperidone and metoclopramide may increase the speed of onset but not the extent of methadone absorption by reversing the delayed gastric emptying associated with opioids. Conversely, methadone may antagonise the effect of domperidone/metoclopramide on gastro-intestinal activity.

Antiarrhythmics:

Methadone delays the absorption of mexiletine.

Methadone and QT interval prolongation:

In patients taking drugs affecting cardiac conduction, or drugs which may affect electrolyte balance there is a risk of cardiac events when methadone is taken concurrently.

Centrally acting alpha-adrenergic blockers

There is an increased risk of hypotension, cognitive effects and ECG changes (including PR interval and QT interval prolongation) when methadone is co-administered with centrally acting alpha-adrenergic blockers (lofexidine and clonidine).

Sedative medicines such as benzodiazepines or related drugs:

The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited.

ADVERSE EFFECTS

Blood and lymphatic system disorders

Not known

Reversible thrombocytopenia has been reported in opioid-dependent patients with chronic hepatitis.

Metabolism and nutrition disorders

Common

Fluid retention

Not known

Anorexia, hypokalaemia, hypomagnesaemia

Psychiatric disorders

Common

Euphoria, hallucinations

Uncommon

Dysphoria, dependence, agitation, insomnia, disorientation, reduced libido

Nervous system disorders

Common

Sedation

Uncommon

Headache, syncope

Eye disorders

Common

Blurred vision, miosis, dry eyes

Not known

Nystagmus, Strabismus, visual acuity reduced

Ear and labyrinth disorders

Common

Vertigo

Cardiac disorders

Rare

Bradycardia, palpitations, cases of prolonged QT interval and torsade de pointes have been reported, especially with high doses of methadone.

Vascular disorders

Uncommon

Facial flush, hypotension

Respiratory, thoracic and mediastinal disorders

Uncommon

Pulmonary oedema, exacerbation of asthma, dry nose, respiratory depression particularly with large doses,

Gastrointestinal disorders

Very common

Nausea, vomiting

Common

Constipation

Uncommon

Xerostomia, glossitis

Hepatobiliary disorders

Uncommon

Bile duct dyskinesia

Skin and subcutaneous tissue disorders

Common

Transient rash, sweating

Uncommon

Pruritis, urticaria, other rash and in very uncommon cases bleeding urticaria

Endocrine disorders

Not known

Raised prolactin levels with long-term administration
Hypoadrenalism, Hypogonadism
Hypoglycaemia

Renal and urinary disorders

Uncommon

Urinary retention, anti-diuretic effect

Reproductive system and breast disorders

Uncommon

Reduced potency, galactorrhoea, dysmenorrhoea and amenorrhoea

General disorders and administration site conditions

Common

Fatigue, drowsiness

Uncommon

Oedema of the lower extremities, asthenia, oedema, hypothermia

Reporting of suspected adverse reactions:

The PPB Department of Pharmacovigilance was set up with a vision to develop, implement and continuously upgrade an appropriate system for detecting, reporting and monitoring adverse drug reactions (ADRs) and other relevant problems with medicines in Kenya. The department strives to ensure the safety and efficacy of pharmaceutical products in Kenya.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals/ Patients are encouraged to report any suspected adverse reactions via Pharmacovigilance Yellow Form, pv@pharmacyboardkenya.org or clicking below button:

 

SPECIAL WARNINGS

Addiction/tolerance/dependence

Methadone is a drug of addiction and is controlled under the Narcotic Drugs and Psychotropic Substances (Control ) Act (Schedule 1). It has a long half-life and can therefore accumulate. A single dose which will relieve symptoms may, if repeated on a daily basis, lead to accumulation and possible death.

Tolerance and dependence may occur as with morphine.

Methadone can produce drowsiness and reduce consciousness although tolerance to these effects can occur after repeated use.

Withdrawal

Abrupt cessation of treatment can lead to withdrawal symptoms which, although similar to those with morphine, are less intense but more prolonged. Withdrawal of treatment should therefore be gradual.

Respiratory depression

Due to the slow accumulation of methadone in the tissues, respiratory depression may not be fully apparent for a week or two. Asthma may be exacerbated due to histamine release. Concomitant treatment with other agents with CNS depressant activity is not advised due to the potential for CNS and respiratory depression.

Hepatic disorders

Caution as methadone may precipitate porto-systemic encephalopathy in patients with severe liver damage.

As with other opioids, methadone may cause troublesome constipation, which is particularly dangerous in patients with severe hepatic impairment, and measures to avoid constipation should be initiated early


Methadone in Kenya

Methadone in Kenya

Clinical | Pharmacokinetic data


Pregnancy Category: C
Routes of Administration: By mouth, intravenous, insufflation, sublingual, rectal
Bioavailability: 15-20% subcutaneous, 100% intravenous , 41–99% (by mouth)
Protein Binding: 85–90%
Metabolosim: Liver (CYP3A4, CYP2B6 and CYP2D6-mediated)
Onset of Action: Rapid
Elimination Half life: 15 to 55 hours
Excretion: Urine, faeces

Legal Status | Dosage forms & Strengths


Prescription Category:
Prescription only Medicine (POM) , ℞-only
Narcotic Drugs and Psychotropic Substances (Control ) Act Schedule:
This is a controlled Schedule 1 Drug ,Narcotic Drugs and Psychotropic Substances (Control ) Act
Dosage Forms | Strengths:
Tablets | Oral solution

Drug Indentifiers:

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References/ Citation:




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