This information is intended for use by health professionals
ParacetamolThe 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 daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.Medicinal products which induce hepatic microsomal enzymes, such as alcohol, barbiturates, monoamine oxidase inhibitors and tricyclic antidepressants, may increase the hepatotoxity of paracetamol, particularly after overdose
Phenylephrine hydrochlorideMonoamine oxidase inhibitors (including moclobemide): hypertensive interactions occur between sympathomimetic amines such as phenylephrine and monoamine oxidase inhibitors (see section 4.3).Sympathomimetic amines: concomitant use of phenylephrine with other sympathomimetic amines can increase the risk of cardiovascular side effects.. .Beta-blockers and other antihypertensives (including debrisoquine, guanethidine, reserpine, methyldopa): phenylephrine may reduce the efficacy of beta-blockers and antihypertensives. The risk of hypertension and other cardiovascular side effects may be increased. Tricyclic antidepressants (e.g. amitriptyline): may increase the risk of cardiovascular side effects with phenylephrine.Digoxin and cardiac glycosides: concomitant use of phenylephrine may increase the risk of irregular heartbeat or heart attack.
ParacetamolAdverse effects of paracetamol are rare, but hypersensitivity including skin rash may occur. There have been a few reports of blood dyscrasias including thrombocytopenia, leucopenia, pancytopenia, neutropenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Acute pancreatitis after ingestion of above normal amounts.
Phenylephrine hydrochlorideHigh blood pressure with headache, vomiting, probably only in overdosage. Rarely, palpitations. Also, rare reports of allergic reactions and occasionally urinary retention in males.
Reporting of suspected adverse reactionsReporting 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 national reporting system detailed in the label or leaflet.
ParacetamolLiver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).
Risk FactorsIf the patient:(a) Is on long-term treatment with carbamazepine, phenobarbitone, phenytoin, primadone, 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 depleted, e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12-48 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. ManagementImmediate 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 Nacetylcysteine, 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 24 hours from ingestion should be discussed with the NPIS or a liver unit.Phenylephrine hydrochlorideFeatures of severe overdosage of phenylephrine include haemodynamic changes and cardiovascular collapse with respiratory depression. Treatment includes early gastric lavage and symptomatic and supportive measures. Hypertensive effects may be treated with an i.v. alpha-receptor blocking agent.Phenylephrine overdose is likely to result in: nervousness, headache, dizziness, insomnia, increased blood pressure, nausea, vomiting, mydriasis, acute angle closure glaucoma (most likely to occur in those with closed angle glaucoma), tachycardia, palpitations, allergic reactions (e.g. rash, urticaria, allergic dermatitis), dysuria, urinary retention (most likely to occur in those with bladder outlet obstruction, such as prostatic hypertrophy). Additional symptoms may include, hypertension, and possibly reflex bradycardia. In severe cases confusion, hallucinations, seizures and arrhythmias may occur. However the amount required to produce serious phenylephrine toxicity would be greater than that required to cause paracetamol-related liver toxicity.Treatment should be as clinically appropriate. Severe hypertension may need to be treated with alpha blocking medicinal products such as phentolamine.
ATC CodeN02BE51 paracetamol, combinations excluding psycholepticsParacetamol: Paracetamol has both analgesic and antipyretic activity, which is believed to be mediated principally through its inhibition of prostaglandin synthesis within the central nervous system.Phenylephrine: phenylephrine is a post-synaptic alpha-receptor agonist with low cardioselective beta-receptor affinity and minimal central stimulant activity. It is a recognised decongestant and acts by vasoconstriction to reduce oedema and nasal swelling.