Co-Dydramol 10/500mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-Dydramol 10/500mg Tablets.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains: 10mg dihydrocodeine tartrate and 500mg paracetamol.
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Tablet.
White cylindrical biplane tablet with an approximate diameter of 12.7mm, embossed with logo reversed side scored and embossed “T2” on either side of a score line
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For relief of mild to moderate pain and pyrexia.
Also as a cough suppressant.
4.2 Posology and method of administration
Posology
Adults and children over 12 years.
Analgesia: Initially 1 or, if necessary 2 tablets every four to six hours. Maximum 8 tablets daily.
Antitussive: 1 tablet every four hours.
Older people
Dosage should be reduced in the older people.
Paediatric population
Children under 12years: Not recommended.
Method of administration
Tablets to be taken orally during or after meals.
4.3 Contraindications
• Hypersensitivity to paracetamol, codeine, dihydrocodeine, other opioids or to any of the excipients listed in section 6.1.
• .Diarrhoea caused by poisoning until the toxic material has been eliminated, or diarrhoea associated with pseudomembraneous colitis
• Respiratory depression
• Obstructive airway 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
• Do not give during an attack of asthma and should be administered with due care to persons liable to such attacks.
• Dosage should be reduced in the elderly in hypothyroidism (risk of depression and prolonged CNS depression is increased) in chronic hepatic disease and in renal insufficiency.
• Alcohol should be avoided whilst under treatment with these tablets. Inflammatory bowel disease - risk of toxic megacolon
• 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, eg 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
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
• Cyclizine
• Metoclopramide anddomperidone - 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
• Dihydrocodeine tartrate causes delayed absorption of Mexiletine, potential of hypnotics and sedatives and CNS excitation and hypertension by interacting with Monoamine-oxidase inhibitors (use only with extreme caution).
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.
• 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.
• Paracetamol interacts with Warfarin and Nicoumalone causing potentiation. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding. It is affected by cholestyramine causing reduced absorption and by metoclopramide causing potentiation. Interaction with metoclopramide or domperidone may increase the speed of paracetamol absorption.
• 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.
4.6 Fertility, pregnancy and lactation
Pregnancy
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 fetus, leading to withdrawal symptoms in the neonate. During labour opioids enter the fetal 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 may cross the placenta but is safe in therapeutic doses for short term use. Dihydrocodeine may potentially depress neonatal respiration and should therefore be avoided in the third trimester.
Breastfeeding
Paracetamol and dihydrocodeine are excreted in breast milk, but are not known to be harmful.
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 opioids in a breastfeeding woman.
4.7 Effects on ability to drive and use machines
Opioid analgesics can cause blurred vision and dizziness. Patients should make sure they are not affected before 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:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o 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 long-term 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. May cause liver damage in prolonged use.
• 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.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Paracetamol:
Symptoms: Pallor, nausea, vomiting, anorexia and abdominal pain in the first 24 hours. Liver damage may become apparent 12-24 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 early symptoms patients should be referred to hospital urgently for immediate medical attention. Any patient who has ingested 7.5g or more of paracetamol in the previous 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. Severe respiratory depression may occur.
Treatment: Treat respiratory depression or other life-threatening adverse effects first. Empty the stomach via gastric lavage or induction of emesis. This may be treated with opioid antagonist, Naloxone hydrochloride 0.4 mg to 2 mg subcutaneously, repeated as required at 2 or 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 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anilides ATC CODE: N02BE
Dihydrocodeine tartrate is a potent analgesic with well defined anti-tussive activity. Paracetamol has analgesic and anti-pyretic action.
5.2 Pharmacokinetic properties
Paracetamol is readily absorbed from the gastro intestinal-tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1-4 hours. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.
The pharmacokinetics of dihydrocodeine tartrate are thought to be similar to those of codeine, i.e. following gastrointestinal absorption plasma concentrations peak within 1 hour, metabolised in the liver and excreted almost entirely by the kidney as conjugates with glucuronic acid. The plasma half-life is likely to be between 3 and 4 hours after administration.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients Povidone
Stearic Acid
Croscarmellose Sodium Type 1 (AC-Di-Sol) Talc
Sodium Starch Glycollate Colloidal Silicon Dioxide
6.2 Incompatibilities
Not applicable
Shelf life
6.3
3 years
6.4 Special precautions for storage
Store in a dry place, below 20°C. Store in the original package in order protected from light.
6.5 Nature and contents of container
Plastic tub with a plastic tamper evident cap.
Co-Dydramol Tablets are available in packs of 25, 50, 100, 250, 500 and 1000s.
Not all pack sizes may be marketed
6.6 Special precautions for disposal and other handling
No special requirements for disposal. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Tillomed Laboratories Limited
3 Howard Road
Eaton Socon
St Neots
Cambridgeshire
PE19 8ET
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 11311/0521
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 19/07/1999 Date of latest renewal: 06/03/2009
10 DATE OF REVISION OF THE TEXT
26/02/2016