DHC^® CONTINUS^® prolonged release tablets 60mg, 90 mg and 120 mg .

Dihydrocodeine Tartrate BP 60 mg, 90 mg and 120mg.

Prolonged release tablet.

White capsule-shaped tablet, 60 mg tablets are marked DHC 60, 90 mg tablets are marked DHC 90 and 120 mg tablets are marked DHC 120.

For the relief of severe pain in cancer and other chronic conditions.

Method of administration

Oral.

60 mg

Adults and children over 12 years: One or two tablets 12-hourly.

Elderly: Dosage should be reduced.

Children 12 years or under: Not recommended.

90 mg

Adults: One or two tablets 12-hourly.

Elderly: Dosage should be reduced.

Children: Not recommended for children.

120 mg

Adults: The usual dose is one tablet 12-hourly.

Elderly: Dosage should be reduced.

Children: Not recommended for children.

Hypersensitivity to dihydrocodeine or any of the tablet constituents; respiratory depression; obstructive airways disease; paralytic ileus; head injury; raised intracranial pressure; acute alcoholism. As dihydrocodeine may cause the release of histamine, it should not be given during an asthma attack and should be given with caution to asthmatics.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Dosage should be reduced in the elderly, in hypothyroidism, chronic hepatic disease and renal insufficiency.

Dihydrocodeine should be administered with caution to patients with a history of opioid abuse, biliary tract disorders, prostatic hypertrophy, pancreatitis, constipation, obstructive bowel disorder and severe cor pulmonale.

The patient may develop tolerance to the drug with chronic use and require progressively higher doses to maintain pain control. Prolonged use of this product may lead to physical dependence and a withdrawal syndrome may occur upon abrupt cessation of therapy. When a patient no longer requires therapy with dihydrocodeine, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

Dihydrocodeine has an abuse profile similar to other agonist opioids. DHC CONTINUS tablets may be sought and abused by people with latent or manifest addiction disorders. The product should be used with particular care in patients with a history of alcohol and drug abuse.

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.

DHC CONTINUS tablets must be swallowed whole, and not broken, chewed or crushed. The administration of broken, chewed or crushed tablets may lead to a rapid release and absorption of a potential overdose of dihydrocodeine (see Section 4.9).

Other central nervous system depressants, including sedatives or hypnotics, phenothiazines, other tranquillisers and alcohol, may result in respiratory depression or sedation. Dihydrocodeine should be used with caution in patients taking monoamine oxidase inhibitors or within two weeks of such therapy.

There are no or limited amount of data from the use of dihydrocodeine in pregnant women. Dihydrocodeine should not be used during pregnancy and labour due to the risk of neonatal respiratory depression. Infants born to mothers who have received opioids during pregnancy should be monitored for respiratory depression. Withdrawal symptoms may be observed in the newborn of mothers undergoing treatment with dihydrocodeine.

Dihydrocodeine has not been reported to be excreted in breast milk. However, it is advisable that dihydrocodeine only be administered to breast-feeding mothers if considered essential.

Dihydrocodeine may cause drowsiness and, if affected, patients should not drive or operate machinery.

The adverse experiences listed below are classified by body system according to their incidence (common or uncommon). Common adverse drug experiences have an incidence of 1% and uncommon adverse drug experiences have an incidence of < 1%.

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.

Paediatric population

Neonatal respiratory depression and withdrawl symptoms may occur in the newborn of mothers undergoing treatment with dihydrocodeine (see Section 4.6).

Acute overdosage 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 , which may in severe cases result in a fatal outcome.

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

In the case of massive overdosage, 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 IV 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 IV 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 overdosage, 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 overdosage. 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.

Additional/other considerations:

• 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. It may be reasonable to assume that late administration of activated charcoal may be beneficial for prolonged release preparations but there is no evidence to support this.

• DHC CONTINUS tablets will continue to release and add to the dihydrocodeine load for up to 12 hours after administration and the management of overdosage should be modified accordingly. Gastric contents may therefore need to be emptied, as this can be useful in removing unabsorbed drug, particularly when a prolonged release formulation has been taken.

Pharmacotherapeutic group: Natural opium alkaloids

ATC code: N02A A08

Dihydrocodeine is a semisynthetic narcotic analgesic with a potency between morphine and codeine. It acts on opioid receptors in the brain to reduce the patient's perception of pain and improve the psychological reaction to pain by reducing the associated anxiety.

Central Nervous System

The principal actions of therapeutic value of dihydrocodeine are analgesia and an antitussive effect (depression of the cough reflex by direct effect on the cough centre in the medulla). Antitussive effects may occur with doses lower than those usually required for analgesia.

Dihydrocodeine may produce respiratory depression by direct action on brain stem respiratory centres.

Gastrointestinal Tract and Other Smooth Muscle

Dihydrocodeine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm resulting in constipation.

Dihydrocodeine is well absorbed from the gastrointestinal tract following administration of DHC CONTINUS tablets and plasma levels are maintained throughout the twelve hour dosing interval.

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.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Lactose (anhydrous)

Hydroxyethylcellulose

Cetostearyl Alcohol

Magnesium Stearate

Purified Talc

Purified Water

None Known

Three years

Do not store above 25°C.

Polyethylene containers with polypropylene lids (56 tablets).

None Stated.

Napp Pharmaceuticals Limited

Cambridge Science Park

Milton Road

Cambridge

CB4 0GW

PL 16950/0019, 0020 and 0021

01 September 1999 / 5 March 2001

06 December 2010

POM

^® DHC, Continus, DHC Continus, NAPP and the NAPP device (logo) are Registered Trade Marks.

^© 2007 – 2010 Napp Pharmaceuticals Ltd.