DIHYDROCODEINE TABLETS BP 30 MG - summary of medicine characteristics

Dihydrocodeine Tablets BP 30 mg

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Dihydrocodeine tartrate BP 30 mg per tablet.

Excipient with known effect: lactose

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet

Dihydrocodeine tablets BP 30 mg are presented as white normal convex tablets engraved with company logo on one face and A435 on the other face.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For the relief of moderate to severe pain in conditions where an alert patient is desired, eg sciatica, osteo-arthritis, chronic rheumatoid arthritis, arthritis of the spine, peripheral vascular disease, post-herpetic neuralgia, Paget’s disease, malignant disease and post-operative pain.

Because dihydrocodeine, in the recommended doses, causes little or no respiratory depression, its use in the treatment of post-operative pain may reduce the risk of chest complications.

4.2 Posology and method of administration

Posology

Adults and children over 12 years: One tablet every 4–6 hours or as recommended by the prescriber. Maximum dose in 24 hours 180mg (6 tablets).

Elderly: Dosage should be reduced in the elderly.

Paediatric population

Children aged 4–12 years: 0.5 to 1.0 mg/kg body-weight every 4–6 hours. A more suitable dosage form is recommended for this age group (e.g. elixir).

Children under 4 years: Not recommended.

The analgesic effect of this product is not materially enhanced by increasing the above dose: in severe cases the interval between doses should be reduced to obtain the requisite analgesic effect.

Method of administration

For oral use.

It is recommended that this product should be taken during or after food.

4.3 Contraindications

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

Respiratory depressionObstruc­tive airways disease

Diarrhoea due to pseudomembranous colitis

Risk of paralytic ileus.

Head injuries or conditions in which intracranial pressure is raised

Comatose patients

Acute alcoholism

4.4 Special warnings and precautions for use

Dihydrocodeine should be given in reduced doses or with caution to patients with asthma and decreased respiratory reserve. Avoid use during an acute asthma attack. Dihydrocodeine should be avoided, or the dose reduced in patients with hepatic or renal impairment.

Dihydrocodeine should be given in reduced doses or with caution to debilitated patients, adrenocortical insufficiency, prostatic hyperplasia, urethral stricture, hypotension, shock, inflammatory or obstructive bowel disorders, hypothyroidism or convulsive disorders.

However, these conditions should not necessarily be a deterrent to use in palliative care.

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

Concomitant use of Dihydrocodeine Tablets 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 Dihydrocodeine Tablets 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).

Use with caution in those with a history of drug abuse.

Alcohol should be avoided whilst under treatment with dihydrocodeine.

When dihydrocodeine is prescribed for chronic use the physician should take care to avoid any unnecessary increase in dosage, especially where there is a previous history of drug dependence and abuse.

Avoid abrupt withdrawal after long-term treatment.

Administration of pethidine and possibly other opioid analgesics to patients taking a monoamine oxidase inhibitor (MAOI) has been associated with very severe and sometimes fatal reactions. If the use of dihydrocodeine is considered essential then great care should be taken in patients taking MAOIs or within 14 days of stopping MAOIs. (See section 4.5).

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

The risk-benefit of continued use should be assessed regularly by the prescriber.

The leaflet will state in a prominent position in the “ What you need to know before you take Dihydrocodeine Tablets” section:

Do not take for longer than directed by your prescriber.

Taking dihydrocodeine regularly for a long time can lead to addiction, which might cause you to feel restless and irritable when you stop the tablets.

Taking a painkiller for headaches too often or for too long can make them worse.

The label will state (to be displayed prominently on outer pack – not boxed):

Do not take for longer than directed by your prescriber as taking dihydrocodeine regularly for a long time can lead to addiction.

4.5 Interaction with other medicinal products and other forms of interaction

Dihydrocodeine may cause the release of histamine; hence this product should not be administered during an asthmatic attack and should be administered with caution in patients with allergic disorders.

The depressant effects of opioid analgesics are enhanced by other CNS depressants such as:

Sedatives such as benzodiazepines or related drugs – increased 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).

Alcohol – enhanced hypotensive, sedative effect and respiratory depression.

Anaesthetics – may increase anaesthetic and sedative effect.

Sedating antihistamines – may enhance the CNS depressive effects when taken with opioids.

Anxiolytics or hypnotics – may enhance CNS depressive effects when taken with opioids.

Tricyclic antidepressants – may enhance CNS depressive effects when taken with opioids.

Antipsychotics – enhanced hypotensive, sedative effect.

MAOIs taken with pethidine have been associated with severe CNS excitation or depression (including hypertension or hypotension). Although this has not been documented with dihydrocodeine, it is possible that a similar interaction may occur and therefore the use of dihydrocodeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation.

Administration with moclobemide may cause CNS excitation or depression (hypertension or hypotension).

Cimetidine may inhibit the metabolism of dihydrocodeine, resulting in increased plasma concentrations.

Cimetidine may inhibit the metabolism of opioids.

Concomitant use of dihydrocodeine and ritonavir should be avoided due to the risk of toxicity.

Dihydrocodeine may delay absorption of mexiletine.

Dihydrocodeine may antagonise the gastrointestinal effects of metoclopramide and domperidone.

Cyclizine may counteract the haemodynamic benefits of opioids.

4.6 Fertility, pregnancy and lactation

Pregnancy

Whilst there is no adequate evidence of safety in human pregnancy, dihydrocodeine has been widely used without apparent ill-effect for many years and studies in animals have not yet demonstrated any hazard. The administration of opioid analgesics during labour may cause respiratory depression in the new-born infant, therefore administration should be avoided during the later stages of pregnancy. Babies born to opioid-dependant mothers may suffer withdrawal symptoms.

Breast-feeding

Dihydrocodeine passes into breast milk in very small amounts which are probably insignificant, however, it is recommended that administration should be avoided if the mother is breast feeding.

4.7 Effects on ability to drive and use machines

Dihydrocodeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.

May cause drowsiness, paraesthesia, dizziness, vertigo, muscle rigidity, visual disturbances, confusion and hallucinations, if affected, do 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

Immune system disorders

Allergic reactions such as hives, itching, skin rashes, swelling of face, dyspnoea and difficulty in breathing.

Metabolism and nutrition disorders

Anorexia.

Psychiatric disorders

Mental depression, hallucinations, restlessness, confusion, mood changes, euphoria, dysphoria.

Nervous system disorders

Paraesthesia, convulsions, uncontrolled muscular movements, tremors, dizziness, headache.

Eye disorders

Miosis, visual disturbances.

Ear and labyrinth disorders

Vertigo.

Cardiac disorders

Bradycardia, tachycardia, palpitations, syncope.

Vascular disorders

Hypotension, facial flushing.

Respiratory, thoracic and mediastinal disorders

Respiratory depression.

Gastrointestinal disorders

Nausea and vomiting, constipation, dry mouth, abdominal pain.

Hepatobiliary disorders

Biliary spasm which may be associated with alterations in liver enzyme values.

Skin and subcutaneous tissue disorders

Urticaria, pruritis, sweating.

Musculoskeletal, connective tissue and bone disorders

Muscle rigidity has been reported after high doses especially respiratory muscles.

Renal and urinary disorders

Difficulty with micturition, urinary retention, ureteric spasm, dysuria.

Reproductive system and breast disorders Sexual dysfunction.

General disorders and administration site conditions

Oedema, drowsiness, malaise.

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

The effects in overdose will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms

Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large. Symptoms resulting from overdose are, pinpoint pupils, nausea and vomiting are common.. Hypotension and tachycardia are possible but unlikely.

Management

This should include general symptomatic and supportive measures including monitoring of vital signs until stable. Consider activated charcoal if an adult presents

within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg..

Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

For reversal of post-operative opioid depression, dosage of naloxone must be carefully titrated to avoid interference with post-operative pain or causing other adverse effects; hypertension and tachycardia, sometimes resulting in left ventricular failure and pulmonary oedema has resulted following naloxone administration in these circumstances especially in cardiac patients. Initial doses of as low as 0.5mcg/kg of body-weight have been recommended. Supportive measures such as intravenous fluids and vasopressor drugs may be required.

Patients should be monitored continuously while administrating additional naloxone as needed.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics, Natural opium alkaloids, ATC code N02AA08

Dihydrocodeine tartrate is an analgesic with uses similar to those of morphine but is less potent.

Dihydrocodeine is an opioid (narcotic analgesic) which binds with stereospecific receptors located at many sites within the central nervous system.

It alters processes affecting both the perception and emotional response to pain.

The exact site and mechanism of action is unknown.

However it is thought to affect the release of various neurotransmitters from afferent nerves sensitive to painful stimuli and maybe partially responsible for the analgesic effect.

Multiple subtypes of opioid receptors have been proposed, each responsible for various therapeutic and/or side effects of opioid drugs. Action of dihydrocodeine may therefore depend upon its binding affinity for each type of receptor and on whether it acts as a full agonist or a partial agonist or is inactive at each type of receptor. At least two types of receptors (mu and kappa) are known to be responsible for the analgesic action. Sigma, a third type may not mediate analgesia; action at this receptor may produce the subjective and psychomimetic effects characteristic of other opioid analgesics such as pentazocine, butorphanol and nalbuphine.

Dihydrocodeine also has an antidiarroheal action, it acts locally and probably centrally to alter the intestinal motility.

It has anti-tussive action due to suppression of the cough reflex by a direct action probably in the medulla or pons.

Dihydrocodeine is also a suppressant of the narcotic abstinence syndrome and acts as a substitute for other opioid drugs.

When administered orally it prevents or attenuates the withdrawal symptoms during detoxification. The resulting withdrawal symptoms which may occur when the substituted opioid is discontinued are less severe.

Dihydrocodeine is much less potent as an analgesic as compared with morphine and has only mild sedative effect.

5.2 Pharmacokinetic properties

Absorption and Distribution

Dihydrocodeine is well absorbed from the gastro-intestinal tract following oral administration and a small quantity is bound to plasma proteins.

Peak levels of plasmalevels occur 1.6 – 1.8 hours after ingestion.

Plasma half-life has been reported to be 34 hours after oral ingestion.

Dihydrocodeine is metabolised in the liver by 0– and N-demethylation.

Biotransformation

After oral administration the bioavailability of the drug is approximately 20%, indicating that the pre-systemic metabolism plays a substantial role in reducing the bioavailability of dihydrocodeine.

Elimination

Dihydrocodeine is excreted in the urine as unchanged drug and metabolites. The mean elimination half-life ranges between 3.5 – 5 hours.

5.3 Preclinical safety data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose BP

Maize starch BP

Pregelatinised maize starch BP

Sodium starch glycollate BP

Stearic acid BP

Magnesium stearate BP

6.2 Incompati­bilities

Not applicable.

6.3

3 years

6.4 Special precautions for storage

Store in the original package in order to protect from light and moisture.

6.5 Nature and contents of container

The product is packed in opaque plastic containers composed of either, high density polypropylene or high density polyethylene with caps composed of high density polyethylene in pack sizes of 28, 30, 42, 50, 56, 84, 100, 112, 250, 500 and 1000 tablets.

Blister packs of aluminium /opaque PVC. It is subsequently packed in printed boxboard cartons in pack sizes of 28, 30, 42, 56, 84, 100 and 112 tablets.

6.6 Special precautions for disposal

No special requirements for handling.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Crescent Pharma Ltd

Units 3 and 4

Quidhampton Business Units

Polhampton Lane

Overton

Hampshire

RG25 3ED

United Kingdom