SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Meptid 200mg Film-Coated Tablets

2.    QUANTITATIVE AND QUALITATIVE COMPOSITION

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

For a 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    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the short term treatment of moderate pain.

4.2    Posology and method of administration Adults

200mg 3-6 hourly as required. Usually one tablet 4 hourly.

The adult dosage schedule can be used in the elderly.

Children

Meptid Tablets have 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).

-    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

Clinical studies have indicated absence of clinically significant respiratory depression but caution should be exercised in patients already severely compromised. A reduced dose may therefore be appropriate.

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.

Safety in long term use is not known, therefore it is recommended that this drug be used in the treatment of moderate pain, for short periods of time. Repeated administration of opioid analgesics may cause dependence and tolerance (severe withdrawal symptoms if withdrawn abruptly).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.

Sunset yellow FCF (E 110) can cause allergic-type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.

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 gastro-intestinal 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, unless considered essential by the physician.

Meptazinol 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

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

Meptid Tablets are subject to hepatic first pass metabolism which prevents systemic concentrations of the drug reaching levels achieved by parenteral administration.

Recommended treatment includes supportive therapy and naloxone if required.

Gut decontamination may be considered within an hour of a substantial overdose provided the airway can be protected and the benefit outweighs the risk.

In the unlikely event of overdose producing respiratory depression, naloxone is the treatment of choice. Naloxone has a short duration of action in comparison with meptazinol. Repeated administration or administration by continuous intravenous infusion may be considered necessary. The effects are only partially reversed by naloxone.

5 PHARMACOLOGICAL PROPERTIES

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 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 findings of clinical significance.

6.1 List of excipients

Tablet Core:

Microcrystalline cellulose Polacrillin potassium Magnesium Stearate

Tablet Coating:

Opadry 06B230000 orange containing:

Hypromellose (E464)

Macrogol 400 Sunset yellow (E110)

Titanium dioxide (E171)

Erythrosine (E127)

6.2    Incompatibilities

Not applicable.

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

Glass bottles containing 50 or 100 tablets, or

Cartons containing PVC blister packs of 6, 28, 56, 100 or 112 tablets. 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 16973/0017

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

17 December 1992/11 October 2005

10    DATE OF REVISION OF THE TEXT

18/06/2015