Dihydrocodeine Tablets 30mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Dihydrocodeine Tablets 30mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Dihydrocodeine Tartrate BP 30mg
3 PHARMACEUTICAL FORM
Dihydrocodeine Tablets are white, flat, circular tablets with a bevel edge and a break-line on one side for oral administration.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Dihydrocodeine is indicated for the relief of moderate to severe pain in all painful
conditions where an alert patient is required, e.g. Sciatica, osteoarthritis, chronic rheumatoid arthritis, arthritis of the spine, peripheral vascular disease, post herpetic neuralgia, Paget’s disease of the bone, malignant disease and post-operative pain.
4.2 Posology and method of administration
Dihydrocodeine tablets should be taken after food.
Adults: One tablet to be taken every four to six hours when necessary.
Elderly: Dosage should be reduced in the elderly.
Children under 12 years of age: Not recommended.
A maximum dose of not more than 6 tablets should be taken in any 24 hour period.
Dosage should be reduced in patients with hypothyroidism chronic hepatic disease and in patients with renal insufficiency.
4.3
Contraindications
Acute respiratory depression, obstructive airways disease; acute alcoholism;
raised intracranial pressure or head injury, as it can affect papillary responses vial for neurological assessment, and respiration; where there is a risk of paralytic ileus; hypersensitivity to the product. It is not indicated for acute abdomen.
4.4 Special warnings and precautions for use
Dihydrocodeine should not be taken during an attack of asthma, and should be administered with caution to patients liable to such attacks, as dihydrocodeine may bring about histamine releases. It should also be avoided in patients with decreased respiratory reserve.
Monoamine oxidase inhibitors including moclobemide should not be given with dihydrocodeine or other narcotic analgesics. Monoamine oxidase inhibitors should be stopped for at least two to three weeks before dihydrocodeine treatment is initiated.
The dosage should be reduced in the elderly or debilitated. The dosage should also be reduced or avoided in patients with chronic hepatic disease (may precipitate coma), and in renal insufficiency.
Caution should be exercised, or reduced doses given, in patients with hypotension, hypothyroidism, prostatic hypertrophy, convulsive disorders, shock, inflammatory or obstructive bowel disorders, myasthenia gravis, or adrenocortical insufficiency.
Prolonged administration may cause dependence, and severe withdrawal symptoms if it is withdrawn abruptly. Tolerance may develop in repeated use. Alcohol should be avoided during treatment with dihydrocodeine.
4.5 Interaction with other medicinal products and other forms of interaction
Alcohol: Enhanced sedative and hypotensive effect.
Anti-arrhythmics: Dihydrocodeine tartrate causes delayed absorption of mexiletine.
Anti-bacterial: Avoid opoid analgesics as premedication when patient is treated with ciprofloxacin as it reduces the plasma-ciprofloxacin concentration.
Anti-virals: The plasma concentration of dihydrocodeine is possible increased by ritonavir.
Anti-depressants: Monoamine oxidase inhibitors include moclobemide: The interaction can cause serious CNS excitation or depression (hypertension or hypotension). Dihydrocodeine should not be given concomitantly or till at least two weeks after discontinuing the treatment.
Tricyclics: Possible increased sedation.
Anti-psychotics: Enhanced sedative and hypotensive effect.
Anxiolytics and hyponotics and sedative: Enhanced sedative effect.
Cisapride: Possible antagonism of gastro-intestinal effects Cyclizine: May counteract the haemodynamic effects of opioids. Metoclopramide and Donperidone: Antagonism of gastro-intestinal effects. Ulcer-healing drugs: Cimetidine inhibits the metabolism of opioid analgesics.
4.6 Pregnancy and lactation
Inadequate evidence of safety in human pregnancy, but the drug has been used for many years without apparent ill consequences. Dihydrocodeine should only be administered during pregnancy and to nursing 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.
4.8 Undesirable effects
The most common side-effects are constipation, drowsiness, nausea and vomiting (particularly in the initial stages of treatment), headache, vertigo, urinary retention and ureteric and biliary spasm may occur. Constipation can be treated with a simple laxative.
Larger doses can produce respiratory depression and hypotension.
Other side-effects are dry mouth, sweating, headache, miosis, facial flushing, vertigo, bradycardia, tachycardia, palpitations, postural hypotension and hypothermia.
Patients have experienced hallucinations, mood changes, dysphoria, and decreased libido and potency. Skin reactions are rashes, urticaria and pruritis.
May cause dependence. Side-effects are more common when the dose exceeds 30mg.
4.9 Overdose
Opioids cause varying degrees of coma, respiratory depression, and pinpoint pupils. The specific antidote naloxone is indicated if there is coma or bradypnoea.
Respiratory depression is a major concern and it maybe treated by artificial ventilation or naloxone. Naloxone will immediately reverse the respiratory depression as well as antagonising the analgesic effect. Since naloxone has a shorter duration of action than many opioids, close monitoring and repeated injections are necessary according to the respiratory rate and depth of coma. Alternatively, it maybe given by continuous intravenous infusion, the rate of administration being adjusted according to response.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Dihydrocodeine Tartrate is used for the relief of mild to moderate pain. It has also been used as a cough suppressant.
Dihydrocodeine is a narcotic analgesic with similar but more addictive than codeine.
Dihydrocodeine possess some of the properties of naturally occurring or endogenous opioid peptides. Pharmacologically the opioid analgesics are broadly similar, dihydrocodeine is considered to produce its effects by action on specific opiate receptors in the central nervous system.
There are several types of opioid receptor, dihydrocodeine is thought to act mainly at the mu receptor which is distributed throughout the body especially at supra-spinal sites. It is at this receptor that dihydrocodeine is thought to exert its analgesic effect.
5.2 Pharmacokinetic properties
The pharmacokinetics of dihydrocodeine may be similar to those of codeine; they differ between subjects of normal renal function and those with chronic renal failure treated with haemodialysis. Dihydrocodeine is well absorbed from the gastrointestinal tract following oral administration and a small quantity is bound to plasma proteins.
Peak levels of plasma dihydrocodeine concentration are attained about one hour following ingestion. Plasma half-life has been reported to be between 3-4 hours after oral ingestion. The rate of absorption is independent of dose and oral bioavailability is only 20%, possibly because of substantial first-pass metabolism in the gut wall or liver.
Dihydrocodeine is metabolised in the liver by O- and N- demethylation to morphine, norcodeine and hydrocodone.
Dihydrocodeine and its metabolites are excreted entirely by the kidneys mainly as conjugates with glucuronic acid.
5.3 Preclinical safety data
Dihydrocodeine Tartrate has been in use for many years and has an established safety profile. Reproductive studies have been carried out in the hamster and they show that doses of 153mg/kg show abnormalities to the central nervous system and other developmental abnormalities. Oral toxicity has been studied in rats and the LD50 was found to be 250mg/kg.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize Starch
Polyvinylpyrrolidone
Lactose
Sodium Starch Glycollate Magnesium Stearate Colloidal Anhydrous Silica
6.2 Incompatibilities
None reported
6.3 Shelf life
Shelf-life of the unopened final container is one year
6.4 Special precautions for storage
In a dry place protected from light store at a temperature below 25°C.
6.5 Nature and contents of container
In securitainers of 25, 50, 100, 250, 500 and 1000 tablets.
6.6 Special precautions for disposal
No special requirements
7 MARKETING AUTHORISATION HOLDER
Consilient Health Ltd,
5th Floor, Beaux Lane House,
Mercer Street Lower,
Dublin 2,
Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 24837/0013
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/03/2009
10 DATE OF REVISION OF THE TEXT
06/03/2009