MEPTID INJECTION 100 MG / ML - summary of medicine characteristics

Meptid 100mg/ml Solution for injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 200mg of meptazinol (as hydrochloride).

Excipient with known effect

Each tablet contains 2.15 mg of sunset yellow FCF (E 110).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet.

Oval, biconvex, orange, film coated tablets. The tablets are engraved “MPL 023” on one side.

4.1 Therapeutic indications

Meptid Tablets are indicated for the short term treatment of moderate pain.

4.2 Posology and method of administration

Prior to starting treatment with opioids, a discussion should be held with patients to put in place a strategy for ending treatment with meptazinol in order to minimise the risk of addiction and drug withdrawal syndrome (see section 4.4).

Posology

Adults

Intramuscular dosage: 75–100mg Meptid. The injection may be repeated 2–4 hourly as required. For obstetric pain a dose of 100–150mg should be used according to weight. This dose should approximate 2mg/kg.

Intravenous dosage: 50–100mg Meptid by slow intravenous injection. The injection may be repeated 2–4 hourly as required. If vomiting occurs, a suitable antiemetic should be given.

Epidural/intrat­hecal use: This formulation is not suitable for these routes.

Elderly

The adult dosage schedule can be used in the elderly.

Paediatric population

No data are available.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with the following conditions:

– acute alcoholism and where there is a risk of paralytic ileus

– raised intracranial pressure or head injury (in addition to interfering with respiration, affect pupillary responses vital for neurological assessment).

– acute respiratory depression

– during an asthma attack

– patients on monoamine-oxidase inhibitors (MAOIs) and for 14 days after discontinuing an MAOI (see section 4.5)

4.4 Special warnings and precautions for use

Caution should be exercised in patients whose respiratory system is already compromised.

Patients with moderate to severe renal impairment should be given a reduced dose as the effect in these patients may be prolonged and increased. Cerebral sensitivity may also be increased. Patients with hepatic impairment should be given a reduced dose as opioid analgesics may precipitate coma in these patients.

Since safety in long term use is not known, it is recommended that this drug be used in the treatment of acute pain only, apart from appropriate therapy in malignant conditions.

Repeated administration of opioid analgesics may cause dependence and tolerance (severe withdrawal symptoms if withdrawn abruptly).

Safety for use in myocardial infarction has not been established.

Meptazinol should also be used with caution in patients with the following conditions: hypotension, hypothyroidism, asthma (avoid during an attack), prostatic hypertrophy and convulsive disorders.

Drug dependence, tolerance and potential for abuse

For all patients, prolonged use of this product may lead to drug dependence (addiction), even at

therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression).

Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.

A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.

Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.

Patients should be closely monitored for signs of misuse, abuse, or addiction.

The clinical need for analgesic treatment should be reviewed regularly.

Drug withdrawal syndrome

Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with meptazinol.

Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.

The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

If women take this drug during pregnancy, there is a risk that their newborn infants will experience

neonatal withdrawal syndrome.

Hyperalgesia

Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality. Symptoms of hyperalgesia may resolve with a reduction of opioid dose.

4.5 Interaction with other medicinal products and other forms of interaction

The following undesirable effects could occur as a result of possible interaction with meptazinol hydrochloride.

Antidepressants: CNS excitation or depression manifesting as hypertension or hypotension may occur if meptazinol is administered to patients receiving MAOIs (including moclobemide). Avoid concomitant use for 14 days after an MAOI is discontinued (see section 4.3). Possible increased sedation if meptazinol is used with tricyclic antidepressants.

Antipsychotics: enhanced sedative and hypotensive effect.

Antivirals: avoid concomitant use with ritonavir as plasma concentration of meptazinol may be increased.

Alcohol: enhanced sedative and hypotensive effect.

Quinolones (ciprofloxacin): Avoid premedication with meptazinol as a reduced plasma ciprofloxacin concentration may be experienced.

Anxiolytics and hypnotics: enhanced sedative effect.

Drugs used in nausea and vomiting: Concomitant use of metoclopramide or domperidone may result in antagonism of gastrointestinal side-effects.

Ulcer healing drugs: cimetidine may inhibit metabolism of meptazinol resulting in increased plasma concentration.

4.6 Fertility, pregnancy and lactation

Pregnancy

Reproduction studies in animals have shown no evidence of teratogenic effect. No experience is available in human beings. Meptazinol should not be used during pregnancy (apart from labour) unless considered essential by the physician.

Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate.

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.

Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available.

Breast-feeding

Administration to nursing women is not recommended as meptazinol may be secreted in breast milk and may cause respiratory depression in the infant.

Meptid Injection should not be given to lactating women unless considered essential by the physician.

4.7 Effects on ability to drive and use machines

Since dizziness and occasionally drowsiness have been reported, patients should be cautioned against driving or operating machinery until it is established that they do not become dizzy or drowsy whilst taking meptazinol.

4.8 Undesirable effects

For very rare reports of psychiatric disorders (hallucination, confusion, depression), causal relationship with the use of meptazinol has not been established and therefore omitted from the above table.

Reactions not already stated which are attributable to opioid analgesics include difficulty with micturition, ureteric or biliary spasm, dry mouth, facial flushing, bradycardia, tachycardia, palpitations, hypothermia, dysphoria, mood changes, miosis, decreased libido or potency, urticaria and pruritus.

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, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Overdose with Meptid Injection has not been reported. Large doses, including seven times the recommended therapeutic dose, have been given in balanced and total intravenous anaesthesia without significant respiratory depressant effects.

In the event of cardiovascular and respiratory collapse, normal resuscitative procedures should be employed. Respiratory depression caused by overdosage with meptazinol may only be partially reversed with therapeutic doses of naloxone. Naloxone has a short duration of action in comparison with meptazinol. Repeated administration or administration by continuous intravenous infusion may be considered necessary.

Patients should be informed of the signs and symptoms of overdose and to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Opioids, Other Opioids, ATC Code: N02AX

Meptid (meptazinol) is a centrally acting analgesic belonging to the hexahydroazepine series, which has demonstrated mixed agonist and antagonist activity at opioid receptors.

Receptor binding studies have shown that although meptazinol displays only a low affinity for 8 and K opioid receptor sites, it has a somewhat higher affinity for the subpopulation of p sites. These binding sites also display a high affinity for the endogenous opioid peptides, and are thought to be responsible for, among other things, analgesia, but not for the mediation of respiratory depression. A component of its analgesic action is also attributable, in mice at least, to an effect on central cholinergic transmission. In this respect it differs from all conventional analgesic drugs which have been examined.

5.2 Pharmacokinetic properties

After oral administration, meptazinol is rapidly absorbed and peak plasma levels are reached within 90 minutes. The plasma elimination half-life is variable (1.4–4 hours). The peak analgesic effect is seen within 30–60 minutes and lasts about 3–4 hours.

The drug is rapidly metabolised to the glucuronide, and mostly excreted in the urine.

5.3 Preclinical safety data

Standard toxicity tests revealed no unexpected finding of clinical significance.

6.1 List of excipients

Tablet Core:

Microcrystalline cellulose, Polacrillin potassium, Magnesium Stearate

Tablet Coating:

Hypromellose (E 464)

Macrogol 400

Sunset yellow FCF (E 110)

Titanium dioxide (E 171)

Erythrosine (E 127)

6.2 Incompatibilities

Meptid injection should not be mixed with other drugs in the same infusion solution or in the same syringe. Meptid injection is an acidic solution of the hydrochloride salt of meptazinol and is therefore pharmaceutically incompatible with injection solutions known to be strongly basic (for example thiopentone) as precipitation of the meptazinol base may occur.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store below 25 C.

6.5 Nature and contents of container

1 ml clear glass ampoules. The glass complies with the requirements of the European Pharmacopoeia Type I. The ampoules will be packed in cartons of 10.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Almirall, S.A.

Ronda General Mitre 151

08022 Barcelona

Spain

8 MARKETING AUTHORISATION NUMBER(S)

PL 16973/0018

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

12/10/2005