Methadone Dtf 1mg/Ml Oral Solution
1. NAME OF THE MEDICINAL PRODUCT
Methadone DTF 1mg/ml Oral Solution
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml contains 5mg Methadone Hydrochloride For full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM Oral Solution
4.1. Therapeutic indications
Methadone DTF 1mg/ml Oral Solution is used as part of the treatment of dependence on opioid drugs. It is administered in doses sufficient to suppress withdrawal symptoms.
4.2. Posology and method of administration
Methadone DTF 1mg/ml Oral Solution is usually administered orally in a single daily dose. The dose is adjusted according to the degree of dependence with the aim of gradual reduction. A typical dosage regimen is 10-20 mg daily initially, increased by 10-20mg daily until there are no signs of withdrawal or intoxication. Usual dose is 40-60 mg daily. After stabilisation which can often be achieved with doses of 40 mg, the dose is gradually decreased until total withdrawal is achieved.
Methadone DTF 1mg/ml Oral Solution is not recommended in children. Caution is required when repeating doses in the elderly and ill.
4.3. Contraindications
*Avoid in raised intracranial pressure or head injury - in addition to interfering with respiration, pupillary responses vital for neurological assessment may be affected.
* Respiratory depression, obstructive airways disease, concurrent administration with MAO inhibitors or within 2 weeks of discontinuation of treatment with them.
* Hypersensitivity to any of the product ingredients.
* Use during an acute asthma attack is not advisable.
* Obstetric use is not recommended during labour as the prolonged duration of action increases the risk of neonatal depression.
* Methadone is not suitable for use in children.
4.4. Special warnings and precautions for use
Precautions are similar to those for morphine salts.
Hypotension, hypothyroidism, asthma and decreased respiratory reserve; pregnancy and breast-feeding; may precipitate coma in hepatic impairment (but mainly such patients tolerate morphine well); reduce dose in renal impairment; elderly and debilitated; dependence (severe withdrawal symptoms if withdrawn abruptly); Methadone DTF 1mg/ml Oral Solution is 2U times the strength of Methadone Linctus. Methadone DTF 1mg/ml Oral Solution is intended for use for drug dependent persons. The product title includes the strength and prescriptions should be written accordingly. Methadone, even in low doses is a special hazard for children; non dependent adults are also at risk; dependent adults are at risk if tolerance is incorrectly assessed during induction.
Sunset Yellow (E110) may cause allergic reactions.
This medicinal product contains 2.21 g of sucrose per 5ml. This should be taken into account in patients with diabetes mellitus. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Cases of QT interval prolongation and torsades de pointes have been reported during treatment with methadone, particularly at high doses (>100mg/d). Methadone should be administered with caution to patients at risk for development of prolonged QT interval, e.g. in case of:
- history of cardiac conduction abnormalities,
- advanced heart disease or ischaemic heart disease,
- liver disease,
- family history of sudden death,
- electrolyte abnormalities, i.e. hypokalaemia, hypomagnesaemia,
- concomitant treatment with drugs that have a potential for QT-prolongation,
- concomitant treatment with drugs which may cause electrolyte abnormalities,
- concomitant treatment with cytochrome P450 CYP 3A4 inhibitors (see section 4.5).
In patients with recognised risk factors for QT-prolongation, or in case of concomitant treatment with drugs that have a potential for QT-prolongation, ECG monitoring is recommended prior to methadone treatment, with a further ECG test at dose stabilisation. ECG monitoring is recommended in patients without
recognised risk factors for QT-prolongation, before dose titration above 100mg/d and at seven days after titration.
4.5. Interaction with other medicinal products and other forms of interaction
Interactions are similar to other opioid analgesics:
Alcohol: enhanced sedative and hypotensive effect.
Antibacterials: rifampicin accelerates metabolism of methadone (reduced effect)
Antidepressants: CNS excitation or depression (hypertension or hypotension) if pethidine and possibly other opioid analgesics given to patients receiving MAOI’s (including moclobemide).
Antivirals : methadone possibly increases plasma concentration of zidovudine. Anxiolytics and hypnotics: enhanced sedative effects.
Ciprofloxacin: May cause profound sedation, confusion and respiratory depression.
Cisapride: possible antagonism of gastro-intestinal effects.
Domperidone andMetoclopramide : antagonism of gastro-intestinal effects. Mexiletine: methadone may delay the absorption of mexiletine.
Dopaminergics: hyperpyrexia and CNS toxicity reported with selegiline.
Ulcer healing drugs: cimetidine inhibits metabolism of opioid analgesics. Urinary acidifiers: may increase methadone elimination thereby reducing the plasma concentration : withdrawal symptoms may occur in some physically dependent patients.
Phenytoin or rifampicin: may increase methadone metabolism and precipitate withdrawal symptoms in physically dependent patients.
Opioid drugs: concurrent use with any of the following drugs may increase the risk of respiratoiy depression, codeine, co-proxamol, diamorphine, morphine, pentazocine and pethidine.
Opioid antagonists: antagonists such as naloxone, naltrexone and buprenorphine may precipitate serious withdrawal symptoms.
Interactions are hazardous: combined administration of these drugs should be avoided (or only undertaken with caution and appropriate monitoring).
Based on the known metabolism of methadone, nevirapine may decrease plasma concentrations of methadone by increasing its hepatic metabolism. Narcotic withdrawal syndrome has been reported in patients treated with nevirapine and methadone concomitantly. Methadone-maintained patients beginning nevirapine therapy should be monitored for evidence of withdrawal and methadone dose should be adjusted accordingly.
Cytochrome P450 3A4 inhibitors: methadone clearance is decreased when coadministered with drugs which inhibit P450 3A4 activity, such as some anti-HIV agents, macrolide antibiotics, cimetidine and azole antifungal agents (since the metabolism of methadone is mediated by the P450 3A4 isoenzyme).
In patients taking drugs affecting cardiac conduction, or drugs which may affect electrolyte balance there is a risk of cardiac event when methadone is taken concurrently.
Risk/benefit must be considered. Methadone is not recommended for use in labour because its prolonged duration of action increases the risk of neonatal respiratory depression. Methadone may cause gastric stasis and risk of inhalation pneumonia to the mother during labour.
Neonatal withdrawal and low birth-weight are immediate problems in the infants of women receiving methadone for the management of opioid addiction. Other effects including increased still births have been noted.
Methadone diffuses across the placenta and is excreted in breast milk.
4.7. Effects on ability to drive and use machines
Methadone may cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink. Blurred vision, dizziness, or nausea may occur which may affect the ability to drive or operate machinery.
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
• The medicine is likely to affect your ability to drive
• Do not drive until you know how the medicine affects you
• It is an offence to drive while under the influence of this medicine
• However, you would not be committing an offence (called ‘statutory defence’) if:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely
4.8. Undesirable effects
The most common side effects include nausea, vomiting, constipation and drowsiness. Larger doses cause respiratory depression and hypotension. Other side effects include difficulty with micturition, uretic or biliary spasm, dry mouth, sweating, headache, facial flushing, vertigo, bradycardia, palpitations, postural hypotension, hypothermia, hallucinations, mood changes, dependence miosis, urticaria and pruritis. Methadone effectively controls the symptoms of morphine withdrawal and dependence on methadone is easier to treat than dependance on morphine.
Cases of QT interval prolongation and torsade de pointes have been rarely reported.
Reporting of suspected adverse reactions
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 are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
4.9. Overdose
Overdose can cause varying degrees of coma, respiratory depression and pinpoint pupils. Pulmonary oedema after overdosage is a common cause of fatalities in addicts. The specific antidote naloxone is indicated if there is coma or bradypnea. Until naloxone is available and administered, artificial respiration is likely to be needed. Since naloxone is short-acting repeated injections are necessary according to the respiratory rate and depth of coma. Alternatively, it may be given by continuous intravenous infusion, the rate of administration being adjusted according to response.
Additional opioids legal or illegal are extremely dangerous and produce respiratory depression and death.
5. Pharmacological Properties
5.1. Pharmacodynamic Properties
Methadone, an opioid analgesic, binds with stereospecific receptors at many sites within the central nervous system to alter processes affecting both the perception of pain and the emotional response to pain.
5.2. Pharmacokinetic Properties
Methadone has a half life of 15-20 hours initially and the half life increases with continued administration. Protein binding is high. Onset of analgesic action is 3 0-60 minutes. Peak analgesic effect occurs after 90-120 minutes. Duration of analgesic action is 4-6 hours initially, increasing with repeated dosing due to accumulation of drug. Primary excretion is renal-rate increased in acidic urine. Secondary biliary excretion also occurs.
None Stated.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Glycerol (E422)
Sucrose Citric Acid
Sodium Benzoate (E211) Sunset Yellow (E110) Green S (E142)
Purified Water
6.2. Incompatibilities
Methadone hydrochloride and hydroxybenzoate preservatives are incompatible. Concurrent use of Methadone DTF 1mg/ml Oral Solution and syrups preserved with hydroxybenzoates is not recommended.
6.3. Shelf Life
24 months.
6.4. Special Precautions for Storage
Do not store above 25°C.
6.5. Nature and Contents of Container
30ml, 50ml, 100ml, 200ml, 300ml, 500ml, 1 litre and 2 litre type III amber glass bottle and tamper- evident screw cap with polyethylene terephthalate liner.
30ml, 50ml, 100ml, 200ml, 300ml, 500ml, 1 litre and 2 litre virgin HDPE bottle and PP tamper evident screw cap.
6.6. Special precautions for disposal and other handling of the product
Methadone Hydrochloride is a controlled drug under the Misuse of Drugs Act SI 12 of 1977
7. MARKETING AUTHORISATION HOLDER
Pinewood Laboratories Limited,
Ballymacarbry,
Clonmel,
Co. Tipperary,
Ireland
8. MARKETING AUTHORISATION NUMBER
PL 04917/0017
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28th June 1996
10 DATE OF REVISION OF THE TEXT
24/11/2014