1 NAME OF THE MEDICINAL PRODUCT

DHC CONTINUS 120 mg prolonged release tablets.

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Dihydrocodeine Tartrate 120 mg.

Excipient with known effect:

Lactose anhydrous 54 mg.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Prolonged release tablet.

White capsule-shaped tablet marked DHC 120.

4.1    Therapeutic indications

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

DHC CONTINUS 120 mg tablets are indicated for use in adults and children over 12 years of age.

4.2    Posology and method of administration

Posology

Adults and children over 12 years: The usual dose is one tablet 12-hourly.

Elderly: Dosage should be reduced.

Paediatric population

Children12 years or under: Not recommended.

Method of administration Oral.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1; severe respiratory depression with hypoxia; severe chronic obstructive lung disease; severe cor pulmonale; severe bronchial asthma; paralytic ileus; acute alcoholism. As dihydrocodeine may cause the release of histamine, it should not be given during an asthma attack.

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

4.4 Special warnings and precautions for use

Dihydrocodeine should be administered with caution to the elderly or patients with:

•    a history of opiate abuse or dependence

•    raised intracranial pressure or head injury

•    biliary tract disorders

•    prostatic hypertrophy

•    pancreatitis

•    impairment of hepatic function

•    severe renal dysfunction

•    constipation

•    an obstructive bowel disorder

•    respiratory depression with hypoxia

•    chronic obstructive lung disease

•    cor pulmonale

•    bronchial asthma

•    hypothyroidism

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 a recognised abuse and addiction profile similar to other agonist opioids. Dihydrocodeine may be sought and abused by people with latent or manifest addiction disorders. There is potential for development of psychological dependence (addiction) to opioid analgesics, including dihydrocodeine. The product should be used with particular care in patients with a history of alcohol and drug abuse.

Abuse of oral dosage forms by parenteral administration can be expected to result in serious adverse events, which may be fatal.

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.

Dihydrocodeine should be used with caution in patients taking monoamine oxidase inhibitors or within two weeks of such therapy.

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 potentially fatal dose of dihydrocodeine and may result in overdose effects (see section 4.9).

4.5 Interaction with other medicinal products and other forms of interaction

Dihydrocodeine should be used with caution in patients who are concurrently receiving other central nervous system depressants, including sedatives or hypnotics, phenothiazines, anxiolytics, anti-depressants, anti-psychotics, other tranquillisers and alcohol. Interactive effects may result in respiratory depression or sedation.

Interactive effects 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of dihydrocodeine in pregnant women. Dihydrocodeine should only be used during pregnancy and labour if considered essential 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.

Breastfeeding

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.

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 you have this medicine in your body over a specified limit unless you have a defence (called the ‘statutory defence’).

■    This defence applies when:

■    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.

■    Please note that it is still an offence to drive if you are unfit because of the medicine (i.e. your ability to drive is being affected).”

Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found here: https://www.gov.uk/drug-driving-law

Undesirable effects

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%.

Undesirable Effects	Common (> 1%)	Uncommon (< 1%)
Immune system disorders		Angioedema
Psychiatric disorders		Confusional state Drug dependence Hallucination Mood altered Dysphoria
Nervous system disorders	Somnolence	Convulsions Dizziness Headache Paraesthesia Sedation
Eye disorders		Blurred vision
Ear and labyrinth disorders		Vertigo
Vascular disorders		Hypotension Flushing
Respiratory, thoracic and mediastinal disorders		Dyspnoea Respiratory depression
Gastrointestinal disorders	Abdominal pain Constipation Dry mouth Nausea Vomiting	Diarrhoea Paralytic ileus
Hepato-biliary disorders		Biliary colic Hepatic enzymes increased
Skin and subcutaneous tissue disorders		Hyperhidrosis Pruritus Rash Urticaria
Renal and urinary disorders		Urinary retention Ureteric spasm
Reproductive system and breast disorders		Decreased libido
General disorders and administration site conditions		Asthenia Fatigue Malaise Withdrawal syndrome Drug tolerance

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 withdrawal symptoms may occur in the newborn of mothers undergoing treatment with dihydrocodeine (see section 4.6).

Reporting of 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.

4.9 Overdose

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.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

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.

5.2 Pharmacokinetic properties

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.

8 MARKETING AUTHORISATION NUMBER(S)

PL 16950/0021

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

01 September 1999

10 DATE OF REVISION OF THE TEXT

11/07/2016