Dihydrocodeine Tablets 30mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Dihydrocodeine Tablets BP 30mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Dihydrocodeine Tartrate BP 30.00mg
Excipient(s) with known effect:
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Oral Tablets
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Indicated for moderate to severe pain.
4.2 Posology and method of administration
Adults: One tablet every 4 to 6 hours when necessary, taken after food. Dosage should be reduced in older people.
Not recommended for children.
Chronic hepatic disease:
The dosage should be reduced.
Moderate to severe renal impairment:
The dosage should be reduced.
For concomitant illnesses/conditions where dose reduction may be appropriate see 4.4 Special Warnings and Precautions for Use.
4.3 Contraindications
Hypersensitivity to dihydrocodeine, or the other opioids analgesics or any of the excipients as listed in section 6.
Acute respiratory depression,
Obstructive airways disease,
Risk of paralytic ileus,
Head injury or raised intracranial pressure (in addition to the risk of respiratory depression and increased intracranial pressure may affect papillary and other responses vital for neurological assessment),
Acute alcoholism.
Severe hepatic dysfunction
Dihydrocodeine should not be given to comatose patients.
Dihydrocodeine is also contraindicated in acute diarrhoeal conditions such as ulcerative colitis or antibiotic associated colitis (e.g. pseudomembranous colitis) or diarrhoea caused by poisoning.
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.
Dosage should be reduced in the older people, in hypothyroidism, chronic hepatic disease and renal insufficiency.
Dihydrocodeine should be given in reduced doses or with caution to older or debilitated patients (see 4.2 Posology) and in patients with adrenocortical insufficiency, prostatic hyperplasia, urethral stricture, hypotension, shock, inflammatory or obstructive bowel disorders, myasthenia gravis, hypothyroidism or convulsive disorders It should be avoided or the dose reduced in patients with hepatic or renal impairment. However, these conditions should not necessarily be a deterrent to use in palliative care. Use in caution with a history of drug abuse.
Opioid analgesics should be avoided in patients with biliary tract disorders or used in conjunction with an antispasmodic.
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 codeine is considered essential then great care should be taken in patients taking MAOIs or within 14 days of stopping MAOIs (see section 4.5).
Alcohol should be avoided whilst under treatment with Dihydrocodeine.
Dihydrocodeine has a recognised abuse and addiction profile similar to other opioids. Tolerance to analgesic effects may develop upon repeated administration.
Discontinuation should be carried out gradually in patients who may have developed physical dependence, to avoid precipitating withdrawal symptoms.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose 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 “before taking” 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
Opiates reduce gastric emptying and may modify the absorption of concomitant administered drugs.
Alcohol: The hypotensive, sedative and respiratory depressive effects of alcohol may be enhanced; alcohol should be avoided.
Anaesthetics: concomitant administration of dihydrocodeine and anaesthetics may cause increased CNS depression and/or respiratory depression and/or hypotension.
Anti-arrhythmics: Dihydrocodeine may delay absorption of mexiletine. The analgesic activity of dihydrocodeine may be significantly impaired by quinidine which impairs codeine metabolism.
Antidepressants, anxiolytics, hypnotics and antipsychotics: Opiates potentiate the effects of CNS depressants, including anxiolytics (e.g.: chlordiazepoxide, diazepam), hypnotics, antipsychotics and tricyclic antidepressants.
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. Dihydrocodeine should be used with caution in patients taking monoamine oxidase inhibitors or within two weeks of such therapy.
Antihistamines: concomitant administration of dihydrocodeine and antihistamines with sedative properties may cause increased CNS depression and/or respiratory depression and/or hypotension.
Antidiarrhoeal and antiperistaltic agents (e.g. loperamide, kaolin): concurrent use may increase the risk of severe constipation.
Motility stimulants: Dihydrocodeine has an antagonistic effect on cisapride, metoclopramide and domperidone.
Sodium oxybate: concomitant administration of dihydrocodeine and sodium oxybate may cause increased CNS depression and/or respiratory depression and/or hypotension.
Ulcer-healing drugs: Cimetidine may inhibit the metabolism of dihydrocodeine resulting in increased plasma concentrations.
Interference with laboratory tests: Opioids may interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure.
4.6 Fertility, pregnancy and lactation
Pregnancy
A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine. Dihydrocodeine may cause respiratory depression in the neonate. Opioid analgesics may cause withdrawal effects in neonates of dependant mothers and gastric stasis during labour, increasing the risk of inhalation pneumonia.
Breastfeeding
It is not known if dihydrocodeine is excreted into breast milk and use should be avoided during breast-feeding unless the potential benefit outweighs the risk.
4.7 Effects on ability to drive and use machines
Dihydrocodeine may cause drowsiness, dizziness, confusion, blurred vision or hallucinations. If affected, patients should not drive or operate
machinery. The effects are worse if the patient consumes alcohol while taking dihydrocodeine.
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
Common adverse drug reactions seen during therapy are constipation, nausea, vomiting, headache, somnolence, pruritus and rash. Other side effects are abdominal pain, paraesthesia, paralytic ileus.
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.
Tolerance and some of the most common side effects - drowsiness, nausea and vomiting and confusion - generally develop with long term use.
Prolonged use of a painkiller for headaches can make them worse.
Immune system disorders: maculopapular rash has been seen as part of a hypersensitivity syndrome associated with oral codeine phosphate; fever, splenomegaly and lymphadenopathy also occurred.
Endocrine disorders: hyperglycaemia
Metabolism and nutrition disorders: anorexia.
Psychiatric disorders: mental depression, hallucinations and nightmares, restlessness, confusion, mood changes, euphoria, dysphoria.
Nervous System disorders: convulsions (especially in infants and children), dizziness, drowsiness, headache, (prolonged use of a painkiller for headaches can make them worse). Raised intracranial pressure may occur in some patients.
Eye disorders: blurred or double vision or other changes in vision, miosis.
Ear and labyrinth disorders: vertigo.
Cardiac disorders: tachycardia, palpitations and bradycardia.
Vascular disorders: postural hypotension, facial flushing. Large doses produce hypotension.
Respiratory, thoracic and mediastinal disorders: Dyspnoea. Larger doses produce respiratory depression.
Gastrointestinal disorders: nausea, vomiting, constipation, dry mouth, stomach cramps, pancreatitis.
Hepatobiliary disorders: Biliary spasm (may be associated with altered liver enzyme values).
Skin and subcutaneous tissue disorders: allergic reactions, such as skin rash, pruritus, urticaria, sweating, facial oedema.
Musculoskeletal and connective tissue disorders: Uncontrolled muscle movements. Muscle rigidity may occur after high doses.
Renal and urinary disorders: urinary retention, difficulty with micturition, ureteric spasm, dysuria. An antidiuretic effect may also occur with codeine.
Reproductive system and breast disorders: sexual dysfunction, erectile dysfunction, decreased potency, decreased libido.
General disorders and administration site conditions: malaise, tiredness, hypothermia.
Dose-related increased post-operative pain has been reported following dental surgery.
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
The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.
Symptoms
Toxic doses vary considerably with the individual and regular users may tolerate large doses.
The triad of coma, pinpoint pupils and respiratory depression is considered indicative of opioid overdosage with dilation of the pupils occurring as hypoxia develops.
Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been coingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.
Other opioid overdose symptoms include hypothermia, confusion, convulsions, severe dizziness, severe drowsiness, nervousness or restlessness, hallucinations, slow heartbeat, circulatory failure, slow or troubled breathing, severe weakness, convulsions, especially in infants and children. Rhabdomyolysis, progressing to renal failure, has been reported in overdosage with opioids.
Management should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350mg or a child more than 5mg/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 4 hours after ingestion, or 8 hours if a sustained release preparation has been taken.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesics - Natural opium alkaloids ATC Code: N02A A08
Dihydrocodeine Tartrate is a potent analgesic with well defined anti-tussive properties.
5.2
Pharmacokinetic properties
Dihydrocodeine is well absorbed after oral administration. Peak plasma levels are attained approximately 1.6 - 1.8 hours after ingestion. The half-life is of the order of 3.5 hours. 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.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Starch (Maize)
Lactose
Polyvinylpyrrolidone Sodium Starch Glycollate Magnesium Stearate Colloidal Anhydrous Silica Purified Water
6.2 Incompatibilities
None stated.
6.3 Shelf life
Polypropylene containers: 36 months Blister Strips: 24 months
6.4
Special precautions for storage
Store in a dry place at or below 25°C. Keep container tightly closed.
6.5 Nature and contents of container
Polypropylene tamper evident containers. The polypropylene container may be presented in an outer cardboard carton: 1000, 500, 250, 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 10 tablets.
Blister Strips (composed of PVC film and aluminium foil): 100, 90, 80, 70, 60, 50, 40, 30, 28, 20, 10 tablets.
Bulk Supply to APS/Berk: Polyethylene lined polypropylene buckets with snap-on polypropylene lids: 5,000 or 15,000 tablets.
6.6 Special precautions for disposal
Nothing stated.
7 MARKETING AUTHORISATION HOLDER
Ranbaxy Ireland Ltd.,
Spafield, Cork Road,
Cashel, Co. Tipperary,
Ireland.
8 MARKETING AUTHORISATION NUMBER(S)
PL 06809/0059
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
27/11/2008
10 DATE OF REVISION OF THE TEXT
27/03/2015