REMEDEINE FORTE TABLETS, CO-DYDRAMOL 30/500 MG TABLETS - summary of medicine characteristics

1 Name of the medicinal product

REMEDEINE FORTE tablets

Co-Dydramol 30/500mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Tablet containing paracetamol 500 mg and dihydrocodeine tartrate BP 30 mg

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet

White to off-white, circular, flat faced tablet with a bevelled edge. The tablet is

PD

engraved 30 on one side.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the treatment of severe pain where there is a higher analgesic requirement (higher than tablets of 500/20 mg).

4.2 Posology and method of administration

Posology

Adults

1 or 2 tablets every four to six hours when necessary to a maximum of 8 tablets in 24 hours.

Elderly

One tablet every 4 – 6 hours increasing to two tablets every 4 – 6 hours if required and tolerated. Do not exceed eight tablets in any 24 – hour period.

Paediatric population

Children 16 to 18 years

1 or 2 tablets every six hours when necessary to a maximum of 8 tablets in 24 hours.

Children 12 to 15 years

1 tablet every six hours when necessary to a maximum of 4 tablets in 24 hours.

Children under 12 years

Not recommended.

Method of administration

For oral use.

This medicine should, if possible, be taken during or after meals.

4.3 Contraindications

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

Respiratory depression.

Obstructive airways disease.

4.4 Special warnings and precautions for use

This medicine should be given with caution in patients with allergic disorders and should not be given during an attack of asthma. Caution should also be observed if there is marked impairment of liver function, advanced kidney disease and in chronic alcoholics.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs:

Concomitant use of this medicine and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe this medicine concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).

Do not exceed the recommended dose.

Patients should be advised not to take other paracetamol-containing products concurrently.

Dosage should be reduced in the elderly, in hypothyroidism and in chronic hepatic disease. An overdose can cause hepatic necrosis.

Dihydrocodeine should be used with caution in patients taking monoamine oxidase inhibitors and should be avoided in those patients with raised intracranial pressure or head injury.

Use with caution in patients with prostatic hypertrophy since dihydrocodeine may cause urinary retention.

The risk-benefit of continued use should be assessed regularly by the prescriber, and in particular the prescriber should take care to avoid any unnecessary increase in dosage especially where there is evidence of a previous history of drug dependence or abuse.

4.5 Interaction with other medicinal products and other forms of interaction

Additive Central Nervous System (CNS) depression may occur with alcohol, and other CNS depressants such as anxiolytics, anti-depressants, hypnotics and antipsychotics.

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 (see section 4.4).

The rate of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption of paracetamol may be reduced by cholestyramine.

The anti-coagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding.

4.6 Fertility, pregnancy and lactation

Pregnancy

Epidemiological studies in human pregnancy have shown no effects due to paracetamol or dihydrocodeine. However, both drugs should be avoided during pregnancy unless considered essential by the physician.

A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should beused at the lowest effective dose for the shortest possible time and at the lowest possible frequency

Breastfeeding

Paracetamol is excreted in breast milk but not in a clinically significant amount.

Available published data do not contraindicate breast feeding

4.7 Effects on ability to drive and use machines

Dihydrocodeine may cause drowsiness and, if affected, patients should not 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: – The medicine has been prescribed to treat a medical or dental problem and – You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and

It was not affecting your ability to drive safely.

4.8 Undesirable effects

Constipation, if it occurs, is readily treated with a mild laxative.

Other side-effects of dihydrocodeine which may occur in a few patients, are nausea, vomiting, headache, vertigo, giddiness, urinary retention, pruritus, sedation, dysphoria, hallucinations and allergic reactions including skin rashes.

Adverse effects of paracetamol are rare but hypersensitivity reactions including skin rash, blood dyscrasias, acute pancreatitis have been reported. Very rare cases of serious skin reactions have been reported.

Dependence may occur. Regular prolonged use of dihydrocodeine is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is then stopped.

Prolonged use of a painkiller for headaches can make them worse.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Paracetamol

Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk factors

If the patient

a) Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

or

b) Regularly consumes ethanol in excess of recommended amounts.

or

c) Is likely to be glutathione depleted e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Management

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see British National Formulary (BNF) overdose section.

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be discussed with the National Poisons Information Service (NPIS) or a liver unit.

Dihydrocodeine

Symptoms

Acute overdose with dihydrocodeine can be manifested by somnolence progressing to stupor or coma, miotic pupils, rhabdomyolysis, non-cardiac pulmonary oedema, bradycardia, hypotension and respiratory depression or apnoea.

Management

Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation.

In the case of massive overdose, administer naloxone intravenously (0.4 to 2 mg for an adult and 0.01 mg/kg body weight for children) if the patient is in a coma or respiratory depression is present. Repeat the dose at 2 minute intervals if there is no response, or by an infusion. An infusion of 60% of the initial dose per hour is a useful starting point. A solution of 10 mg made up in 50 ml dextrose will produce 200 micrograms/ml for infusion using an Intravenous pump (dose adjusted to the clinical response). Infusions are not a substitute for frequent review of the patient’s clinical state. Intramuscular naloxone is an alternative in the event that Intravenous access is not possible.

As the duration of action of naloxone is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. Naloxone is a competitive antagonist and large doses (4 mg) may be required in seriously poisoned patients. For less severe overdose, administer naloxone 0.2 mg intravenously followed by increments of 0.1 mg every 2 minutes if required.

Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to dihydrocodeine overdose. Naloxone should be administered cautiously to persons who are known, or suspected, to be physically dependent on dihydrocodeine. In such cases, an abrupt or complete reversal of opioid effects may precipitate pain and an acute withdrawal syndrome.

Consider activated charcoal (50 g for adults, 10–15 g for children), if a substantial amount has been ingested within 1 hour, provided the airway can be protected.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics, Opioids in combination with non-opioid analgesics, ATC code: N02AJ01

Paracetamol is an effective analgesic possessing a remarkably low level of side effects. Its broad clinical utility has been extensively reported, and it now largely replaces aspirin for routine use. Paracetamol is well tolerated; having a bland effect on gastric mucosa, unlike aspirin, it neither exacerbates symptoms of peptic ulcer nor precipitates bleeding.

Dihydrocodeine tartrate has been widely used for a number of years as a powerful analgesic. In addition the compound exhibits well-defined anti-tussive activity.

Fortifying paracetamol with dihydrocodeine tartrate provides an effective combination of drugs for the treatment of severe pain.

5.2 Pharmacokinetic properties

Dihydrocodeine is well absorbed from the gastrointestinal tract. Like other phenanthrene derivatives, dihydrocodeine is mainly metabolised in the liver with the resultant metabolites being excreted mainly in the urine. Metabolism of dihydrocodeine includes O-demethylation, N-demethylation and 6-keto reduction.

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine as the glucuronide and sulphate conjugates.

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Magnesium stearate Ph Eur

Starch maize special Ph Eur

6.2 Incompatibilities

None known.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 30°C

Keep the container in the outer carton in order to protect from moisture.

6.5 Nature and contents of container

1. Polypropylene container with polyethylene lid containing 56 or 112 tablets.

2. Polyethylene container with polypropylene lid containing 56 or 112 tablets

3. High density polyethylene container with polypropylene cap with EPE liner containing 56 or 112 tablets

4. Blister packs containing 2, 8, 12, 28, 56, 112, 200 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements for disposal. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Crescent Pharma Limited

Units 3 & 4

Quidhampton Business Units

Polhampton Lane

Overton

Hampshire

RG25 3ED

8 MARKETING AUTHORISATION NUMBER(S)

PL 20416/0257