Co-Dydramol Tablets Bp
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-Dydramol Tablets BP 10/500mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 10mg Dihydrocodeine Tartrate and 500mg Paracetamol.
3 PHARMACEUTICAL FORM
White uncoated tablets.
White, circular, flat bevelled-edge uncoated tablets impressed with the word “C” and the identifying letters “CT” on either side of a central division line on one face. Nominal diameter 12.5mm.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Analgesic for the relief of mild to moderate pain.
4.2 Posology and method of administration
Posology
It is recommended that this product should be taken during or after meals. Adults and children over 12 years:
Initially one or, if necessary, two tablets every 4 hours to a maximum of 8 tablets daily.
Children under 12 years: Not recommended.
Elderly: Dosage should be reduced in the elderly.
Method of Administration For oral administration.
4.3 Contraindications
• Known hypersensitivity to paracetamol, dihydrocodeine, other opioids or other constituents in the tablets.
• Diarrhoea caused by poisoning until the toxic material has been eliminated, or diarrhoea associated with pseudomembranous colitis.
• Respiratory depression.
• Obstructive airways disease.
4.4 Special warnings and precautions for use
Co-dydramol should be used with caution in patients with:
• hepatic function impairment (avoid if severe) and those with non-cirrhotic alcoholic liver disease. The hazards of overdose are greater in those with alcoholic liver disease.
• Prolonged use of co-dydramol may cause hepatic necrosis.
• renal function impairment
• hypothyroidism (risk of respiratory depression and prolonged CNS depression is increased)
• inflammatory bowel disease - risk of toxic megacolon
• Opioids should not be administered during an asthma attack
• convulsions - may be induced or exacerbated
• drug abuse, dependence (including alcoholism), enhanced instability, suicidal ideation or attempts - predisposed to drug abuse
• head injuries or conditions where intracranial pressure is raised
• gall bladder disease or gall stones - opioids may cause biliary contraction
• gastro-intestinal surgery - use with caution after recent GI surgery as opioids may alter GI motility
• prostatic hypertrophy or recent urinary tract surgery
• adrenocortical insufficiency, e.g. Addison’s Disease
• hypotension and shock
• myasthenia gravis
• phaeochromocytoma - opioids may stimulate catecholamine release by inducing the release of endogenous histamine
Where analgesics are used long-term (>3 months) with administration every two days or more frequently, headache may develop or worsen. Headache induced by overuse of analgesics (MOH medication-overuse headache) should not be treated by dose increase. In such cases, the use of analgesics should be discontinued in consultation with the doctor.
Label Warnings:
Do not take with any other paracetamol-containing products.
Immediate medical advice should be sought in the event of an overdose, even
if you feel well, because of the risk of delayed, serious liver damage.
or if leaflet present:
Immediate medical advice should be sought in the event of an overdose, even
if you feel well.
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
Paracetamol can interact with the following:
• Drugs which alter gastric emptying time (e.g. cimetidine, ethyl alcohol, oral steroid contraceptives). These drugs reduce or delay peak paracetamol blood levels.
• Metoclopramide or domperidone increases the speed of absorption of paracetamol.
• Colestyramine reduces paracetamol absorption.
• Drugs which interfere with the metabolism of paracetamol by competition with metabolic pathways or substrates e.g. anticonvulsants (phenytoin), hepatic enzyme inducers, alcohol, barbiturates, tricyclic antidepressants. A poor diet (low protein) may also have a similar effect on the risk of serious paracetamol toxicity to hepatic enzyme inducers. Patients who have taken barbiturates, tricyclic antidepressants and alcohol may show diminished ability to metabolise large doses of paracetamol, the plasma half-life of which may be prolonged.
• The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding.
• Alcohol can increase the hepatotoxicity of paracetamol overdosage and may have contributed to the acute pancreatitis reported in one patient who had taken an overdosage of paracetamol.
Dihydrocodeine can interact with the following:
• CNS depressants - enhanced sedative and/or hypotensive effect with alcohol, anaesthetics, hypnotics, anxiolytics, antipsychotics, hydroxyzine, tricyclic antidepressants
• Antibacterials, e.g. ciprofloxacin, - avoid premedication with opioids as reduced plasma ciprofloxacin concentration
• MAOIs - use only with extreme caution
• Cyclizine
• Mexiletine - delayed absorption
• Metoclopramide and domperidone - antagonise GI effects
• Cisapride - possible antagonism of GI effects
• Dopaminergics (e.g. selegiline) - possible risk of hyperpyrexia and CNS toxicity. This risk is greater with pethidine but with other opioids the risk is uncertain
• Ulcer healing drugs - cimetidine inhibits the metabolism of opioid analgesics.
• Anticholinergics (e.g. atropine) - risk of severe constipation which may lead to paralytic illness, and/or urinary retention
• Antidiarrhoeal drugs (e.g. loperamide, kaolin) - increased risk of severe constipation
• Antihypertensive drugs (e.g. guanethidine, diuretics) - enhanced hypotensive effect
• Opioid antagonists (e.g. buprenorphine, naltrexone, naloxone)
• Neuromuscular blocking agents - additive respiratory depressant effects
4.6 Fertility, pregnancy and lactation
Epidemiological studies in human pregnancy have shown no effects due to paracetamol used in the recommended dosage. However, paracetamol should be avoided in pregnancy unless considered essential by the physician.
Risk benefit must be considered because opioid analgesics cross the placenta. Studies in animals have shown opioids to cause delayed ossification in mice and increased resorption in rats.
Regular use during pregnancy may cause physical dependence in the foetus, leading to withdrawal symptoms in the neonate. During labour opioids enter the foetal circulation and may cause respiratory depression in the neonate. Administration should be avoided during the late stages of labour and during the delivery of a premature infant.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding, however some opioids are distributed in breast milk in small amounts and it is advisable to avoid administration of opioids in a breastfeeding woman.
4.7 Effects on ability to drive and use machines
Opioid analgesics can impair mental function and can cause blurred vision and dizziness. Patients should make sure they are not affected before driving or operating 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
At the recommended dosage, paracetamol may cause the following side
effects:
• Allergic reactions - rare but may include skin rash, drug fever, mucosal lesions.
• Effects on CNS - drowsiness, impaired mental functions
• Effects on GI system - Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year, and liver damage has been reported after daily ingestion of excessive amounts for shorter periods. Acute pancreatitis has been reported. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were longterm users of paracetamol, nor was the control of their disease improved after paracetamol withdrawal.
• Effects on CVS - toxic myocarditis.
• Effects on blood - methaemoglobinaemia, neutropenia, pancytopenia, leukopenia, thrombocytopenic purpura, haemolytic anaemia and agranulocytosis.
• Effects on GU system - Nephrotoxicity following therapeutic doses of paracetamol is uncommon, but papillary necrosis has been reported after prolonged administration.
• Other effects - Most reports of adverse reactions to paracetamol relate to overdosage with the drug.
Adverse effects of opioid treatment which have been reported include:
• Allergic reactions (may be caused by histamine release) - including rash, urticaria, difficulty breathing, increased sweating, redness or flushed face.
• Effects on CNS - confusion, drowsiness, vertigo, dizziness, changes in mood, hallucinations, CNS excitation (restlessness/excitement), convulsions, mental depression, headache, trouble sleeping, or nightmares, raised intracranial pressure, tolerance or dependence.
• Effects on GI system - constipation, GI irritation, biliary spasm, nausea, vomiting, loss of appetite, dry mouth, paralytic ileus or toxic megacolon.
• Effects on CVS - bradycardia, palpitations, hypotension.
• Effects on sensory system - blurred or double vision.
• Effects on GU system - ureteral spasm, antidiuretic effect.
• Other effects - trembling, unusual tiredness or weakness, malaise, miosis, hypothermia.
• Effects of withdrawal - abrupt withdrawal precipitates a withdrawal syndrome. Symptoms may include tremor, insomnia, nausea, vomiting, sweating and increase in heart rate, respiratory rate and blood pressure. NOTE - tolerance diminishes rapidly after withdrawal so a previously tolerated dose may prove fatal.
• Regularly 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.
4.9 Overdose
Paracetamol:
Symptoms: Pallor, nausea, vomiting, anorexia and abdominal pain in the first 24 hours. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias have been reported.
Liver damage is likely in adults who have taken 10g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.
Treatment: Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any patient who had ingested around 7.5g or more of paracetamol in the preceding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N-acetylcysteine which may have a beneficial effect up to at least 48 hours after the overdose, may be required. General supportive measures must be available.
Opioids:
Symptoms: cold clammy skin, confusion, convulsions, severe drowsiness, tiredness, low blood pressure, pinpoint pupils of eyes, slow heart beat and respiratory rate coma.
Treatment: Treat respiratory depression or other life-threatening adverse effects first. Empty the stomach via gastric lavage or induction of emesis.
The opioid antagonist naloxone (0.4-2mg subcutaneous) can be given and repeated at 2-3 minute intervals to a maximum of 10mg. Naloxone may also be given by intramuscular injection or intravenous infusion. The patient should be monitored as the duration of opioid analgesic may exceed that of the antagonist.
5.1 Pharmacodynamic properties
Dihydrocodeine tartrate is an opioid analgesic.
Paracetamol has analgesic and antipyretic properties.
5.2 Pharmacokinetic properties
Dihydrocodeine is absorbed from the gastrointestinal tract. Dihydrocodeine is metabolised by O- and N-demethylation in the liver to morphine, norcodeine and other metabolites. It is excreted almost entirely by the kidney, mainly as conjugates with glucoric acid.
Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 10-60 minutes after ingestion. Paracetamol is distributed into most body tissues. It crosses the placenta and is present in breast milk. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as the glucoronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. A minor hydroxylated metabolite which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdosage and cause tissue damage. The elimination half-life varies from about 1-3 hours.
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
Also contains: pregelatinised maize starch, maize starch, colloidal silicon dioxide, stearic acid, water.
6.2 Incompatibilities
None known
6.3 Shelf life
Shelf-life
Three years from the date of manufacture.
Shelf-life after dilution/reconstitution Not applicable.
Shelf-life after first opening Not applicable.
6.4 Special precautions for storage
Store below 25°C in a dry place. Protect from light.
6.5 Nature and contents of container
Child-resistant blister pack: (i) 250pm white rigid PVC (ii) 9pm soft aluminium/ 35g/m2 glassine paper. Compliant with BS8404.
Pack sizes: 30, 100.
PE tablet container with a child-resistant PP closure. Compliant with ISO8317. Pack sizes: 30, 100.
PP tablet container with or without polyfoam wad or polyethylene ullage filler and a PE closure for supply to nursing homes.
Pack sizes: 500, 1000.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Actavis UK Limited (Trading style: Actavis)
Whiddon Valley BARNSTAPLE N Devon EX32 8NS
8 MARKETING AUTHORISATION NUMBER(S)
PL 00142/0384
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
26/01/1994 / 11/03/2009
10 DATE OF REVISION OF THE TEXT
23/07/2014