SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Meptid 100mg/ml Solution for injection

2. QUANTITATIVE AND QUALITATIVE COMPOSITION

Each 1 ml of solution contains 100mg of meptazinol (as hydrochloride).

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection.

Clear colourless solution free from particulate matter.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the treatment of moderate to severe pain, including post-operative pain, obstetric pain and the pain of renal colic.

4.2 Posology and method of administration

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. Children

Meptid injection has not been evaluated for use in children.

4.3 Contraindications

Patients with the following conditions:

-    known hypersensitivity to the active ingredient or to any of the excipients

-    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)

-    phaeochromocytoma (risk of pressor response to histamine release)

-    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 special 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.

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 Pregnancy and lactation

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 essentially by the physician.

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

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

System Organ Class	Very Common (> 1/10)	Uncommon (> 1/1,000 to < 1/100)
Nervous system disorders	dizziness, headache, vertigo, somnolence, drowsiness
Vascular disorders		hypotension
Respiratory, thoracic and mediastinal disorders		Respiratory depression
Gastrointestinal disorders	abdominal pain, constipation, diarrhoea, dyspepsia, nausea, vomiting
Skin and subcutaneous tissue disorders	Increased sweating, rash

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 table above.

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.

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.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Nervous System; 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 5 and a 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 intramuscular administration, meptazinol is rapidly absorbed and peak plasma levels are reached within 30 minutes. The plasma half-life is approximately 2 hours. The peak analgesic effect is seen within 30-60 minutes and lasts about 3-4 hours.

After intravenous administration, the onset of action is immediate, occurring within minutes, and lasts a minimum of one hour.

The major route of metabolism is via the glucuronidation pathway and excretion occurs mainly in the urine.

5.3 Preclinical safety data

Standard toxicity tests revealed no unexpected finding of clinical significance.

List of excipients

Glucose

Water for injections.

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

Do not store above 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

Single use only. Discard any unused contents.

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 THE AUTHORISATION

12/10/2005

10    DATE OF REVISION OF THE TEXT

19/06/2015