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The effects of CNS depressants (including other opioid analgesics, tranquilisers, sedative hypnotics and alcohol) may be potentiated by codeine. When such therapy is contemplated, the dose of one or both agents should be reduced.

Concurrent use of MAO inhibitors or tricyclic antidepressants with codeine may increase the effect of either the antidepressant or codeine.

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Interaction with other medicinal products and other forms of interaction<>Buy Codeine Painkiller Online

  The effects of CNS depressants (including other opioid analgesics, tranquilisers, sedative hypnotics and alcohol) may be potentiated by codeine. When such therapy is contemplated, the dose of one or both agents should be reduced. Concurrent use of MAO inhibitors or tricyclic antidepressants with codeine may increase the effect of either the antidepressant or codeine. Concurrent use of anticholinergics and codeine may produce paralytic ileus. Isoniazid may increase the risk of hepatotoxicity with therapeutic doses of paracetamol. Antiepileptics, such as carbamazepine, phenobarbital, phenytoin and primidone can reduce the effects of paracetamol and increase the risk of hepatotoxicity. Paracetamol may increase the elimination half-life of chloramphenicol. Oral contraceptives may increase its rate of clearance. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

 Fertility, pregnancy and lactation<>Buy Codeine Painkiller Online

  Pregnancy Codeine There is inadequate evidence of the safety of codeine in human pregnancy. Animal studies with codeine do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Paracetamol There is epidemiological evidence for the safety of paracetamol. Animal studies with paracetamol do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Paracetamol can be used during pregnancy if clinically needed however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency. Co-codamol As a precautionary measure, it is preferable to avoid the use of co-codamol during pregnancy. Breast-feeding Paracetamol Paracetamol is excreted in breast milk but not in a clinically significant amount. Codeine Codeine should not be used during breastfeeding (see section 4.3). At normal therapeutic doses codeine and its active metabolite may be present in breast milk at very low doses and is unlikely to adversely affect the breast fed infant. However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolite, morphine, may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant, which may be fatal. Fertility There are no data on the effects of co-codamol on human fertility. Fertility was unaffected following paracetamol or codeine treatment in animal studies (see section 5.3).
4.7 Effects on ability to drive and use machines
Patients should be advised not to drive or operate machinery if affected by dizziness or sedation.
4.8 Undesirable effects
• Regular prolonged use of codeine 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. The information below lists reported adverse reactions, ranked using the following frequency classification: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Blood and the lymphatic system Not known: blood dyscrasias including thrombocytopenia and agranulocytosis Immune system disorders Not known: anaphylactic shock, angioedema, allergic reactions (hypersensitivity) including skin rash Hepatobiliary disorders Not known: cytolytic hepatitis, which may lead to acute hepatic failure Nervous system disorders Not known: dizziness, light-headedness, confusion, drowsiness Ear and labyrinth disorders Not known: ototoxicity leading to sensorineural hearing loss. Gastrointestinal disorders Not known: pancreatitis, constipation, nausea, vomiting Skin and subcutaneous tissue disorders Very rare cases of serious skin reactions have been reported. Renal and urinary disorders Not known: urinary retention  

Reporting of suspected adverse reactions <>Buy Codeine Painkiller Online

  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 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<>Buy Codeine Painkiller Online

  If the patient: • is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John’s Wort or other drugs that induce liver enzymes, or • regularly consumes ethanol in excess of recommended amounts, or • is likely to be glutathione depleted e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.  

Symptoms <>Buy Codeine Painkiller Online

  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, gastrointestinal bleeding 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.  

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  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 paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine 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 a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with the National Poisons Information Service (NPIS) or a liver unit. Codeine The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.  

Symptoms <>Buy Codeine Painkiller Online

  Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.  

Management<>Buy Codeine Painkiller Online

  This should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350mg or a child more than 5mg/kg. Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Paracetamol, combinations excl. Psycholeptics Paracetamol is an analgesic which acts peripherally, probably by blocking impulse generation at the bradykinin sensitive chemo-receptors which evoke pain. Although it is a prostaglandin synthetase inhibitor, the synthetase system in the CNS rather than the periphery appears to be more sensitive to it. This may explain paracetamol’s lack of appreciable anti-inflammatory activity. Paracetamol also exhibits antipyretic activity. Codeine is a centrally acting weak analgesic. Codeine exerts its effects through µ opioid receptors, although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.

5.2 Pharmacokinetic properties<>Buy Codeine Painkiller Online

  Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Concentration in plasma reaches a peak in 30-60 minutes. Plasma half-life is 1-4 hours. Paracetamol is relatively uniformly distributed throughout most body fluids, plasma protein binding is variable. Codeine phosphate is well absorbed after oral administration and is widely distributed. About 86% is excreted in the urine in 24 hours; 40-70% if free or conjugated morphine, 5-15% is free or conjugated norcodeine. The bioavailabilities of paracetamol and codeine, when given as the combination, are similar to those when they are given separately.
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.
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