Co-Dydramol Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-dydramol Tablets 10/500mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains dihydrocodeine tartrate BP 10mg and paracetamol BP 500mg.
3 PHARMACEUTICAL FORM
Tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Recommended as an analgesic and as an anti-tussive.
4.2 Posology and method of administration
Co-dydramol tablets should, if possible, be taken during or after meals.
The dosage may have to be reduced in elderly patients. See also sub-section 4.4 Special Warnings and Special Precautions for Use.
As an analgesic:
Adults and children over 12 1 tablet every 4 hours; this may increase if
years: necessary to 2 tablets 4 times daily.
Children under 12 years: Not recommended.
As an anti-tussive:
Adults and children over 12 1 tablet every 4 hours.
years:
Children under 12 years: Not recommended.
4.3 Contraindications
Respiratory depression, obstructive airways disease, allergic disorders, or during an attack of asthma, or hypersensitivity to paracetamol, dihydrocodeine tartrate, other opioids or any of the other excipients.
Liver disease
• Diarrhoea caused by poisoning until the toxic material has been eliminated, or diarrhoea associated with pseudomembraneous colitis
4.4 Special warnings and precautions for use
The risk benefit of continued use should be assessed regularly by the prescriber.
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 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, 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
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 should be advised not to take other paracetamol-containing products concurrently. Keep out of reach of children.
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 taking the tablets.
Taking a painkiller for headaches too often or for too long can make them worse.
The label will state (prominently on outer pack, but not in a box:)
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
Ritonavir may increase the plasma concentration of dihydrocodeine.
Dihydrocodeine may delay the absorption of mexiletine if taken concomitantly.
Concomitant use of regular paracetamol and imatinib should be restricted or avoided.
Paracetamol can interact with the following:
• Drugs which alter gastric emptying time (eg 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 eg 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, eg ciprofloxacin, - avoid premedication with opioids as reduced plasma ciprofloxacin concentration
• 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
Cyclizine
• Mexiletine - delayed absorption
• Metoclopramide and domperidone - antagonise GI effects
• Cisapride - possible antagonism of GI effects
• Dopaminergics (eg 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 (eg atropine) - risk of severe constipation which may lead to paralytic illness, and/or urinary retention
• Antidiarrhoeal drugs (eg loperamide, kaolin) - increased risk of severe constipation
• Antihypertensive drugs (eg guanethidine, diuretics) - enhanced hypotensive effect
• Opioid antagonists (eg 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 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 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 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.
4.8 Undesirable effects
At the recommended dosage, paracetamol may cause the following side effects:
• Allergic reactions - rare but may include skin rash, urticaria, pruritis, 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, thrombocytopenia, 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.
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
4.9 Overdose
Paracetamol
Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below)
Risk factors
If the patient
a) is on long term treatment with carbamazepine, phenobarbital, phenytoin, Primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes or
b) Regularly consumes ethanol in excess of recommended amounts, or
c) Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. 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, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Management
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. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetycysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be suitable alternative for remote areas, outside hospital. Management of patients who present serious hepatic dysfunction beyond 24 h from ingestion should be discussed with the NPIS or a liver unit.
Dihydrocodeine
The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs
Symptoms
Acute overdosage with dihydrocodeine can be manifested by somnolence progressing to stupor or coma, miotic pupils, rhabdomyolysis, non-cardiac pulmonary oedema, bradycardia, hypotension and respiratory depression or apnoea
Management
Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation
In the case of massive overdosage, administer naloxone intravenously (0.4 to 2 mg for an adult and 0.01 mg/kg body weight for children) if the patient is in a coma or respiratory depression is present. Repeat the dose at 2 minute intervals if there is no response, or by an infusion. An infusion of 60% of the initial dose per hour is a useful starting point. A solution of 10 mg made up in 50 ml dextrose will produce 200 micrograms/ml for infusion using an IV pump (dose adjusted to the clinical response). Infusions are not a substitute for frequent review of the patient's clinical state. Intramuscular naloxone is an alternative in the event that IV access is not possible
As the duration of action of naloxone is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. Naloxone is a competitive antagonist and large doses (4 mg) may be required in seriously poisoned patients. For less severe overdosage, administer naloxone 0.2 mg intravenously followed by increments of 0.1 mg every 2 minutes if required
Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to dihydrocodeine overdosage. Naloxone should be administered cautiously to persons who are known, or suspected, to be physically dependent on dihydrocodeine. In such cases, an abrupt or complete reversal of opioid effects may precipitate pain and an acute withdrawal syndrome
Consider activated charcoal (50 g for adults, 10-15 g for children), if an adult presents within 1 hour of ingestion of more than 420mg or a child more than 3mg/kg
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Paracetamol has analgesic and antipyretic effects. It is only a weak inhibitor of prostaglandin biosynthesis, although there is some evidence to suggest that it may be more effective against enzymes in the CNS than those in the periphery. This fact may partly account for its ability to reduce fever (a central action) and to induce analgesia. Dihydrocodeine is a centrally acting analgesic which produces its effects by its action at opioid binding sites within the CNS.
5.2 Pharmacokinetic properties
Co-dydramol Tablets contain 1 part dihydrocodeine tartrate to 50 parts of paracetamol. The pharmacokinetics of the 2 components are given below.
Peak plasma concentrations are achieved after an oral dose in approximately 1/2 to 2 hours. The plasma half-life is reported to be around 3 to 5 hours. Codeine is metabolised in the liver and excreted via the kidneys mainly as conjugates with glucuronic acid.
Paracetamol is also absorbed from the gastrointestinal tract and distributed into most body tissues. Peak plasma concentrations occur around 10 to 60 minutes after an oral dose. The elimination half-life is about 1 to 3 hours. Paracetamol is metabolised in the liver and excreted in urine as the glucuronide and sulphate conjugates. A small amount (less than 5%) is excreted as unchanged active.
5.3 Preclinical safety data
There are no preclinical safety data of relevance to the prescriber.
6.1 List of excipients
Maize starch, polyvinylpyrrolidone, stearic acid, sodium starch glycollate, colloidal silicon dioxide and talc.
6.2 Incompatibilities
None known.
6.3 Shelf life
12 months.
6.4 Special precautions for storage
Store below 25°C. Protect from light.
6.5 Nature and contents of container
Securitainers, pack sizes 25, 50, 100, 250, 500 and 1,000.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Ennogen Pharma Limited Unit G4,
Riverside Industrial Estate,
Riverside Way,
Dartford DA1 5BS UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 40147/0020
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/03/2009
10 DATE OF REVISION OF THE TEXT
17/10/13