CO-DYDRAMOL TABLETS 10/500MG
Active substance: PARACETAMOL
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SUMMARY 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
4.1
CLINICAL PARTICULARS
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: As an anti-tussive: Not recommended.
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 or any of the other excipients. Liver disease
4.4
Special warnings and precautions for use Dihydrocodeine may bring about histamine release, therefore it should not be given during an asthma attack and it should be administered with due care to persons liable to such attack. The dosage should be reduced in hypothyroidism and in renal insufficiency. Alcohol should be avoided. When dihydrocodeine is prescribed for chronic use, care should be taken to avoid unnecessary increase in dosage. Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater those with alcoholic liver disease. Do not exceed the recommended dose. Patients should be advised not to take other paracetamol-containing products concurrently. Keep out of reach of children. Prolonged use of high doses has produced morphine-like dependency. Avoid when there is a history of asthma, hepatic or renal impairment, or of drug abuse. 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 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.
Interactions with other Medicaments and other forms of Interaction
Additive CNS depression may occur with alcohol. An enhanced sedative effect may be seen in some patients taking tricyclic antidepressants, antipsychotics, anxiolytics and hypnotics. 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. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding. Dihydrocodeine should be used with caution in patients taking monoamine oxidase, CNS depressants or metoclopramide
4.6
Pregnancy and lactation
At normal therapeutic doses there is epidemiological evidence of the safety of paracetamol in pregnancy, but patients should follow the advice of their doctor regarding its use. Dihydrocodeine has been used for many years without apparent ill effects. It should be used with caution in late pregnancy as it may cause respiratory depression in the neonate. As with all medicines, use should be avoided during the first trimester Dihydrocodeine and paracetamol are excreted in breast milk in concentrations too low to be harmful to the breast fed infant
4.7.
Effects on Ability to Drive and Use Machines
Dihydrocodeine may cause vertigo which may affect the ability to drive or use machines
4.8.
Undesirable Effects Adverse effects of paracetamol are rare but hypersensitivity including skin urticaria and pruritus may occur. There have been reports of blood dyscrasias
rash,
including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
Dihydrocodeine may cause constipation, nausea, vomiting, drowsiness, headache or vertigo and these are relatively common if the dose is increased above 30mg. If constipation occurs it can be treated with a gentle laxative. Tolerance and dependence may occur with dihydrocodeine especially with prolonged dosage. There have been very rare occurrences of pancreatitis. Regular prolonged use of codeine/DHC is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is stopped. Prolonged use of painkillers for headaches can make them worse. 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 Johns 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 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
6.1
PHARMACEUTICAL PARTICULARS
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 25C. 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
30/08/2012
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
4.1
CLINICAL PARTICULARS
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: As an anti-tussive: Not recommended.
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 or any of the other excipients. Liver disease
4.4
Special warnings and precautions for use Dihydrocodeine may bring about histamine release, therefore it should not be given during an asthma attack and it should be administered with due care to persons liable to such attack. The dosage should be reduced in hypothyroidism and in renal insufficiency. Alcohol should be avoided. When dihydrocodeine is prescribed for chronic use, care should be taken to avoid unnecessary increase in dosage. Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater those with alcoholic liver disease. Do not exceed the recommended dose. Patients should be advised not to take other paracetamol-containing products concurrently. Keep out of reach of children. Prolonged use of high doses has produced morphine-like dependency. Avoid when there is a history of asthma, hepatic or renal impairment, or of drug abuse. 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 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.
Interactions with other Medicaments and other forms of Interaction
Additive CNS depression may occur with alcohol. An enhanced sedative effect may be seen in some patients taking tricyclic antidepressants, antipsychotics, anxiolytics and hypnotics. 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. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding. Dihydrocodeine should be used with caution in patients taking monoamine oxidase, CNS depressants or metoclopramide
4.6
Pregnancy and lactation
At normal therapeutic doses there is epidemiological evidence of the safety of paracetamol in pregnancy, but patients should follow the advice of their doctor regarding its use. Dihydrocodeine has been used for many years without apparent ill effects. It should be used with caution in late pregnancy as it may cause respiratory depression in the neonate. As with all medicines, use should be avoided during the first trimester Dihydrocodeine and paracetamol are excreted in breast milk in concentrations too low to be harmful to the breast fed infant
4.7.
Effects on Ability to Drive and Use Machines
Dihydrocodeine may cause vertigo which may affect the ability to drive or use machines
4.8.
Undesirable Effects Adverse effects of paracetamol are rare but hypersensitivity including skin urticaria and pruritus may occur. There have been reports of blood dyscrasias
rash,
including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
Dihydrocodeine may cause constipation, nausea, vomiting, drowsiness, headache or vertigo and these are relatively common if the dose is increased above 30mg. If constipation occurs it can be treated with a gentle laxative. Tolerance and dependence may occur with dihydrocodeine especially with prolonged dosage. There have been very rare occurrences of pancreatitis. Regular prolonged use of codeine/DHC is known to lead to addiction and tolerance. Symptoms of restlessness and irritability may result when treatment is stopped. Prolonged use of painkillers for headaches can make them worse. 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 Johns 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 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
6.1
PHARMACEUTICAL PARTICULARS
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 25C. 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
30/08/2012
Source: Medicines and Healthcare Products Regulatory Agency
Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.
