PADOLIEVE

Padolieve 500mg film coated tablets

Each film-coated tablet contains 500mg paracetamol.

For the full list of excipients, see section 6.1.

Film-coated tablet

White, caplet shaped, film-coated tablets with ‘P’, a bisect breakline and ‘500’ on one side and plain on the other side.

The tablet can be divided into equal doses.

Symptomatic treatment of mild to moderate pain and fever.

Posology

Adults (including the elderly)

The usual dose is 500mg to 1,000mg every 4 to 6hours as needed, to a maximum of 3g daily. Maximum single dose is 1,000mg.

The maximum daily dose must not be exceeded due to risk of serious hepatic damage (see sections 4.4 and 4.9).

Paediatric population (weighing 25‑50kg)

The recommended total daily dose of paracetamol is approximately 60mg/kg divided in 4 or 6 separate doses, or approximately 15mg/kg every 6hours or 10mg/kg every 4hours. Maximum daily dose must not be exceeded due to risk of serious hepatic damage (see sections 4.4 and 4.9).

Paediatric dosage should be based on body weight and a suitable dosage should be used. Information on the age of children within each weight group given below is for guidance only.

Care must be taken not to exceed the maximum number of doses in a 24hour period i.e. not more than 4doses in a 24hour period. Paracetamol should only be administered when clearly necessary and at the lowest efficacious dose.

Children and adolescents weighing 43‑50kg (about 12‑15years)

The usual dose is 500mg every 4hours as needed, up to a maximum of 4 tablets daily.

Children weighing 34‑43kg (about 11‑12years)

The usual dose is 500mg every 6hours as needed, up to a maximum of 4 tablets daily.

Children weighing 26‑34kg (about 8‑11years)

The usual dose is about ½ a tabletevery 4hours or one tablet every 6hours as needed, to a maximum of 3 tablets daily.

Children under 8years

Padolieve 500mg Film-coated tablets are not suitable for children under 8years of age, as the dosage strength is not suitable for this age group. However, there are appropriate dosage strengths and/or formulations available for this age group.

Impaired liver or kidney function

In patients with impaired hepatic or renal function or Gilbert’s syndrome, the dose must be reduced or the dosing interval prolonged (see section 4.4).

Patients with impaired renal function

Impaired renal function

In patients with renal insufficiency, the dose should be reduced:

These doses should not be repeated more frequently than every 4hours and not more than 4doses should be given in any 24hour period.

Maximum duration of continued use without medical advice: 3days

The lowest effective dose should be used for the shortest duration necessary.

Alcoholic patients: A maximum daily dose of 4 tablets per 24 hours must not be exceeded.

Method of administration

For oral use.

The tablet should be swallowed with a glass of water.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Padolieve 500mg Film-coated tablets are not suitable for use in children under 8years of age. However, there are appropriate dosage strengths and/or formulations available for this age.

Paracetamol should be used with caution in adults and adolescents weighing less than 50kg

Do not exceed the stated dose.

If high fever or signs of secondary infection occur or if symptoms persist for longer than 3days, a physician should be consulted.

In general, medicinal products containing paracetamol should only be taken for a few days without the advice of a physician or a dentist and not at high doses.

Patients should be advised not to take other paracetamol containing products concurrently.

Paracetamol should be used with caution in cases of dehydration and chronic malnutrition.

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment (see section 4.2) or severe haemolytic anaemia. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease. In patients with alcohol abuse the dose has to be reduced. The daily dose should not exceed 2grams in such cases.

Patient groups at increased risk of toxic liver effects

Elderly patients, infants, patients with chronic nutritional disorders, patients who are underweight, patients with liver or renal disease, patients taking excess alcohol or patients using medicines which are enzyme inducers are more likely to develop liver toxicity from paracetamol use. Even relatively small overdoses of paracetamol in these patients can cause serious liver toxicity which can be fatal (see sections 4.2 and 4.9).

Caution should be exercised when paracetamol is used in combination with CYP3A4 inducers or use of substances that induce liver enzymes, such as rifampicin, cimetidine or antiepileptics (e.g.glutetimmide, fenobarbital or carbamazepine).

Gilbert`s syndrome (Meulengracht`s disease)

Paracetamol is metabolized by enzymes which are deficient in some people with Gilbert's syndrome. Therefore, a subset of people with Gilbert's syndrome may have an increased risk of paracetamol toxicity.

Other notes:

Prolonged use of analgesics for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The diagnosis of medication overuse headache (MOH) should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.

In general terms, the habitual intake of analgesics particularly on combination of several pain-relieving active substances, may lead to permanent renal damage with the risk of renal failure. Therefore it must be avoided.

Abrupt discontinuation following long-term, high dose, incorrect use of analgesics may lead to headaches, fatigue, muscle pain, nervousness and autonomic symptoms. These withdrawal symptoms resolve within a few days. Until this time, further intake of analgesics must be avoided and not restarted without medical supervision.

Patients should be advised accordingly.

Interference with laboratory tests

Paracetamol may affect phosphotungstic uric acid tests and blood sugar tests by glucose-oxydase-peroxidase.

Pregnancy

Epidemiological data from the use of oral therapeutic doses of paracetamol indicate no undesirable effects on the pregnancy or on the health of the foetus/newborn infant. Prospective data on pregnancies exposed to overdoses did not show an increase in malformation risk. Reproductive studies with the oral route did not show any malformation or foetotoxic effects.

Consequently under normal conditions of use, paracetamol can be used during pregnancy, after a benefit-risk assessment. During pregnancy paracetamol should not be taken for long periods, at high doses or in combination with other medicinal products, as safety of use in such cases is not established.

Lactation

After oral use, paracetamol is excreted into breast milk in small quantities. No undesirable effects on nursing infants have been reported. Therapeutic doses of this medicinal product may be used during breast-feeding.

Padolieve has no or negligible influence on the ability to drive and use machines.

At therapeutic doses few undesirable effects occur. However, in rare or very rare occasions the following undesirable effects have been reported. Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: 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).

Paracetamol has been widely used and reports of adverse reactions are rare, and are generally associated with overdose.

Nephrotoxic effects are uncommon and have not been reported in association with therapeutic doses, except after prolonged administration.

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Immediate medical attention is required in the event of an overdose even if there are no significant early symptoms.

There is a risk of poisoning, particularly in elderly subjects, in young children, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition. Overdosing may be fatal in these cases.

Liver 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). It is considered that excess quantities of toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

Symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor, and abdominal pain or patients maybe asymptomatic.

Overdose of paracetamol in a single administration in adults or in children causes liver cell necrosis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy which may lead to coma and death. Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with increased prothrombin levels that may appear 12 to 48 hours after administration.

Some patients may be at increased risk of liver damage from paracetamol toxicity.

Risk Factors include: If the patient;

a. Is on long-term treatment with carbamazepine, phenobarbitone, 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 depleted e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia

Emergency Procedure:

Immediate transfer to hospital

Blood sampling to determine initial paracetamol plasma concentration

Gastric lavage

IV (or oral if possible) administration of the antidote N-acetylcysteine as soon as possible in accordance with National treatment guidelines.

Symptomatic treatment should be implemented.

Pharmacotherapeutic group: Other analgesics and antipyretics, Anilides, ATC code: N02BE01

Paracetamol is an antipyretic and analgesic. Paracetamol produces antipyresis through action on the hypothalamic heat-regulation centre and analgesia by elevation of the pain threshold. Paracetamol has analgesic and antipyretic actions similar to acetylsalicylic acid, but it has no useful anti-inflammatory properties.

Paracetamol produces its analgesic effect from the inhibition of prostaglandin synthesis. Prostaglandins appear sensitise pain receptors to mechanical stimulation or to other chemical mediators. Paracetamol lowers body temperature in patients with fever but rarely lowers normal body temperature. This again is due to the inhibition of synthesis and release of prostaglandins. The drug also acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow.

Paracetamol is generally well tolerated by patients hypersensitive to acetylsalicylic acid.

Absorption

Paracetamol is rapidly and almost completely absorbed from the alimentary tract. Peak plasma concentrations occur after 30minutes to 2hours following oral dosing.

Distribution

The volume of distribution of paracetamol is approximately 1L/Kg body weight. Plasma protein binding is negligible at usual therapeutic concentrations, although this is dose dependant.

Metabolism

Paracetamol is metabolised in the liver and excreted in the urine mainly as glucoronide and sulphate conjugates with about 10% as glutathione conjugates.

Elimination

Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1‑4hours.

In animal experiments regarding acute, subchronic and chronic toxicity of paracetamol in rats and mice, gastro-intestinal lesions, blood count changes, degeneration of liver and renal parenchyma, even necroses were observed. The causes for these changes were attributed to the mechanism of action on the one hand and on the other to the metabolism of paracetamol. Extensive investigations showed no evidence of a relevant genotoxic risk of paracetamol at therapeutic, i.e. non-toxic, doses.

Long-term studies in rats and mice yielded no evidence on relevant tumorigenic effects at non-hepatotoxic dosages of paracetamol.

Paracetamol passes through the placenta.

Tablet core:

Starch, pregelatinised

Maize starch

Povidone K-30

Stearic acid

Talc

Film-coating:

Opadry White (Y‑1‑7000) includes:

Titanium dioxide (E171)

Macrogol 400

Hypromellose 5cP

Not applicable.

Clear PVC/aluminium foil blister strips packed into cardboard cartons

White HDPE bottles and a PP screw closure

10, 12, 20, 24, 30, 50, 60 and100 film-coated tablets for blisters,

30 and 100film-coated tablets for HDPE bottles

Not all pack sizes may be marketed.

Stasisport Pharma N.V.

Square Marie Curie 50

1070 Anderlecht

Belgium

September 2016

No special requirements. Any unused product or waste should be disposed of in accordance with local requirements.