Actigrip Giorno e Notte (Acetaminophen,Diphenhydramine,Pseudoephedrine)

For the relief of symptoms associated with colds and flu; including relief of nasal congestion and congestion of mucous membranes of the upper respiratory tract, sneezing, runny nose, coughing, fever, headache, muscular aches and pains.

For oral use

Adults, the elderly and children aged 16 years and over:

Two tablets, up to four times daily, as required. Do not take more frequently than every four hours.

Children 10 to 15 years

One tablet, up to four times daily, as required. Do not take more frequently than every four hours. Not to be used for more than five days without the advice of a doctor. Parents or carers should seek medical attention if the child's condition deteriorates during treatment.

Children under 10 years

Actigrip Giorno e Notte (Acetaminophen,Diphenhydramine,Pseudoephedrine) Tablets are contraindicated in children under the age of 10 years.

Do not exceed the stated dose.

Known hypersensitivity to diphenhydramine, paracetamol, pseudoephedrine or to any of the excipients.

Concomitant use of other sympathomimetic agents including those given by other routes, beta-blockers and monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOI treatment

Cardiovascular disease including hypertension

Diabetes mellitus

Phaeochromocytoma

Hyperthyroidism

Closed angle glaucoma

Severe renal impairment

Not to be used in children under the age of 10 years.

As both diphenhydramine and pseudoephedrine have been associated with central nervous system adverse events , there is a possibility that the risk of experiencing such adverse events may be increased by use of the combination.

If any of the following occur, Actigrip Giorno e Notte (Acetaminophen,Diphenhydramine,Pseudoephedrine) Tablets should be stopped

- Hallucinations

- Restlessness

- Sleep disturbances

Use with caution in prostatic hypertrophy, urinary retention, susceptibility to angle-closure glaucoma, moderate renal impairment, hepatic disease or occlusive vascular disease.

The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

The product may cause drowsiness. This product should not be used to sedate a child.

The product labelling will contain the following advice:-

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.

Do not take with any paracetamol-containing products.

If symptoms persist, consult your doctor or pharmacist.

Keep out of the reach and sight of children

Do not use to sedate a child.

Ask a doctor before use if you suffer from a chronic or persistent cough, if you have asthma, are suffering from an acute asthma attack or where cough is accompanied by excessive secretions.

Actigrip Giorno e Notte (Acetaminophen,Diphenhydramine,Pseudoephedrine) may cause drowsiness. If patients are affected they should not drive or use machinery.

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, coma 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.

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 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 local centres and/or experts that provide advice on poisons and overdoses or a liver unit.

Diphenhydramine:

Symptoms of overdose may include drowsiness, hyperpyrexia and anticholinergic effects. With higher doses, and particularly in children, symptoms of CNS excitation include insomnia, nervousness, tremors and epileptiform convulsions. With massive overdose, coma or cardiovascular collapse may follow.

Treatment of overdosage should be symptomatic and supportive. Measures to promote gastric emptying (such as induced emesis or gastric lavage), and in cases of acute poisoning activated charcoal, may be useful.

Pseudoephedrine:

As with other sympathomimetic agents, symptoms of overdose include irritability, restlessness, tremor, convulsions, palpitations, hypertension and difficulty in micturition.

Necessary measures should be taken to maintain and support respiration and control convulsions. Gastric lavage should be performed if indicated. Catheterisation of the bladder may be necessary. If desired, the elimination of pseudoephedrine can be accelerated by acid diuresis or by dialysis.

ATC code: N02BE51. Diphenhydramine has a potent antihistaminic action although the actions most beneficial in influenza are its antitussive and to a lesser extent anticholinergic properties, which may alleviate mucus hypersecretion.

Paracetamol has central analgesic and antipyretic actions and pseudoephedrine is an indirectly acting sympathomimetic which has vasoconstrictor, bronchodilator and decongestant effects.

Diphenhydramine is well absorbed after oral administration with peak plasma levels at 2.5 hours and is subject to extensive first pass metabolism. The drug is 75% bound to plasma proteins, but binding decreases with chronic liver disease. Metabolism is by 2 successive N-demethylations followed by oxidation to a carboxylic acid. The terminal half life lies between 3.4 and 9.3 hours.

Paracetamol is rapidly and completely absorbed with peak plasma levels seen within 30 to 60 minutes. Less than 50% is protein bound and the drug is uniformly distributed throughout the body fluids. Paracetamol is eliminated by metabolism to inactive conjugates followed by urinary excretion. The half life is 2.75 - 3.25 hours.

Pseudoephedrine is rapidly absorbed, with peak serum levels after approximately 2.6 hours and onset of effect within about 30 minutes. It is well distributed throughout body fluids and tissues. Approximately 50% of the drug is excreted unchanged, the remainder undergoes metabolism to inactive metabolites. About 6% is converted to the active metabolite norpseudoephedrine.

The active ingredients of Actigrip Giorno e Notte (Acetaminophen,Diphenhydramine,Pseudoephedrine) tablets are well known constituents of medicinal products and their safety profile is well documented. The results of preclinical studies do not add anything of relevance for therapeutic purposes.

Not applicable.

No special requirements