Document: spc-doc_PL 05146-0006 change

• spc-doc_PL 05146-0006
• spc-doc_PL 44704-0001

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol 250 mg Orodispersible Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each orodispersible tablet contains 250 mg paracetamol.

Contains 11.2 mg aspartame (E951)

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Orodispersible tablet.

White to off-white round, flat face radius edge tablets

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For use in children from the age of four and adolescents only. Symptomatic treatment of mild to moderate pain and/or fever.

4.2 Posology and method of administration

Posology:

Doses depend on body weight and age; a single dose ranges from 10 to 15 mg/kg body weight (=b.w.) to a maximum of 60 mg/kg b.w. for total daily dose (also see section 4.4).

Paracetamol orodispersible tablet is not recommended in children below 4 years of age (17 kg).

Method of administration:

The tablet should be placed in the mouth where it melts on the tongue so it can be easily swallowed. Alternatively, to facilitate the intake, the tablet can be swallowed with a glass of water or, especially in younger children, dispersed in a spoonful or a teaspoonful of water.

The intake of paracetamol with food or drink does not affect the efficacy of the medicinal product.

Instructions for use:

-    The specific dose interval depends on the symptoms and the maximum daily dose. It should, however, preferably never fall below 6 hours and in no case fall below 4 hours.

-    In cases of severe renal insufficiency (creatinine clearance lower than 10 ml/min.) the minimum interval between 2 administrations should be 8 hours.

-    Depending on the reoccurrence of symptoms (fever and/or pain), repeated administration is allowed.

4.3 Contraindications

Paracetamol 250 mg orodispersible tablets are contraindicated in patients with hypersensitivity to paracetamol or any of the excipients.

4.4 Special warnings and precautions for use

The total dose of paracetamol should not exceed:

-    60 mg/kg/day for children weighing less than 40 kg;

-    3g daily for children and adolescents weighing more than 40 kg.

The recommended dose should not be exceeded.

Prolonged or frequent use is discouraged. Paracetamol should be used with caution in the presence of hepatic or renal dysfunction and in case of dehydration or chronic malnutrition.

Taking multiple daily doses in one administration can severely damage the liver; in such case unconsciousness does not occur. However, medical assistance should be sought immediately (see section 4.9).

Caution is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with noncirrhotic alcoholic liver disease. Caution should be exercised in cases of chronic alcoholism. The daily dose should not exceed 2 grams in such case.

Gilbert’s syndrome (Meulengracht’s disease).

In cases of high fever, signs of a secondary infection, or persistence of the symptoms for more than three days, medical advice should be sought.

Long-term use of analgesics, especially combinations of various analgesic agents, has the potential to cause permanent renal damage including the risk of renal failure (analgesics nephropathy).

Abrupt discontinuation of long-term use of high-dosed analgesics, taken not as directed, may cause headache, tiredness, muscular pain, nervousness and vegetative symptoms. The withdrawal symptoms subside within a few days. In the meantime do not restart use of the analgesic and do not start a new therapy without medical advice.

In children treated with 60 mg/kg daily of paracetamol, the combination with another antipyretic is not justified except in the case of ineffectiveness.

Paracetamol contains aspartame, which is a source of phenylalanine. The phenylalanine in the tablets may be harmful to people with phenylketonuria.

If symptoms persist, a doctor should be consulted.

4.5 Interaction with other medicinal products and other forms of interaction

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; occasional doses have no significant effect.

Use of substances that induce liver enzymes, such as barbiturates, can increase the hepatotoxicity of paracetamol overdose due to increased and more rapid formation of toxic metabolites.

Caution should be taken in case of concomitant use of enzyme inducing substances (see section 4.9).

Probenecide blocks the binding of paracetamol to glucuronic acid reducing paracetamol clearance by a factor of about 2. If probenecide is taken concurrently the paracetamol dose should be reduced.

Salicylamide may prolong the elimination t1/2 of paracetamol.

Ethyl alcohol potentiates paracetamol toxicity, possibly by inducing hepatic production of paracetamol-derived hepatotoxic products.

Isoniazid reduces the paracetamol clearance, with possible potentiation of its action and/or toxicity, by inhibition of its metabolism in the liver.

Paracetamol may decrease the bioavailability of lamotrigine, with possible reduction of its effect, due to a possible induction of its metabolism in the liver

Interference with laboratory tests

Paracetamol may affect phosphotungstate uric acid tests and blood sugar tests by glucose-oxydase-peroxydase.

4.6 Pregnancy and lactation

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.Reproductive studies did not show any malformation or foetotoxic effects.

Consequently under normal conditions of use, paracetamol can be used throughout the duration of pregnancy, after a benefit-risk assessment.

Lactation:

Paracetamol is excreted in breast milk but not in a clinically significant amount. No negative effects on infants have been reported. Paracetamol may be used by breastfeeding women as long as the recommended dosage is not exceeded. In case of long term use caution should be exercised.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

At therapeutic doses few undesirable effects occur.

Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10.000, <1/1000), very rare (<1/10,000), not known (cannot be estimated from available data).

Blood and lymphatic system disorders

Rare: agranulocytosis (after prolonged administration), thrombocytopenia, thrombocytopenic purpura, leucopenia, haemolytic anemia

Very rare: pancytopenia

Immune system disorders

Rare: allergies (excluding angioedema)

Very rare: hypersensitivity reaction (angioedema, difficulty in breathing, sweating, nausea, hypotension, shock, anaphylaxis) requiring discontinuation of treatment

Metabolism and nutrition disorders Very rare: hypoglycemia

Psychiatric disorders

Rare: depression, confusion, hallucinations

Nervous system disorders Rare: tremor, headache

Eye disorders

Rare: abnormal vision

Cardiac disorders Rare: oedema

Respiratory, thoracic and mediastinal disorders

Very rare: bronchospasm in patients who are sensitive for aspirin and other NSAIDs (analgetic asthma)

Gastrointestinal disorders

Rare: haemorrhage, abdominal pain, diarrhoea, nausea, vomiting Hepatobiliary disorders

Rare: abnormal hepatic function, hepatic failure, hepatic necrosis, jaundice Very rare: hepatotoxicity

An amount of 6 grams of paracetamol may already lead to hepatic damage (in children: more than 140 mg/kg); larger amounts cause irreversible hepatic necrosis. Hepatic damage after chronic use of 3-4 grams of paracetamol daily has been reported.

Skin and subcutaneous tissue disorders Rare: pruritus, rash, sweating, purpura, urticaria Very rare: exanthema, serious skin reactions

Not known: acute generalised exanthematous pustulosis, toxic necrolysis, drug-induced dermatosis, Stevens-Johnson-Syndrome

Renal and urinary disorders

Very rare: sterile pyuria (cloudy urine) and renal side effects (severe renal function disorder, interstitial nephritis, hematuria, enuresis)

General disorders and administration site conditions

Rare: dizziness (excluding vertigo), malaise, pyrexia, sedation, drug interaction NOS

Injury, poisoning and procedural complications Rare: overdose and poisoning

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 Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

4.9 Overdose

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

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, 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 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 local overdose 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 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 24 h from ingestion should be discussed with the NPIS or a liver unit.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group:other analgesics and antipyretics; anilides; ATC code: N02BE01

Paracetamol has both analgesic and antipyretic effects. However, it does not have an anti-inflammatory effect.

5.2 Pharmacokinetic properties

Absorption

After oral administration paracetamol is rapidly and almost completely absorbed. Peak plasma concentrations are reached after 30 minutes to 2 hours.

Distribution

The volume of distribution of paracetamol is approximately 1 L/kg bodyweight. At therapeutic doses protein binding is negligible.

Metabolism

In adults paracetamol is conjugated in the liver with glucuronic acid (~60%), sulphate (~35%) and cystein (~3%). In neonates and children <12 years sulphate conjugation is the main elimination route and glucuronidation is lower than in adults. Total elimination in children is comparable to that in adults, due to an increased capacity for sulphate conjugation.

Elimination

Paracetamol is excreted in urine, predominantly as the glucuronide and the sulphate conjugate, and approximately 5% unchanged. The elimination half life varies between 1 and 4 hours.

Physiopathological Variations

Renal Insufficiency: In cases of severe renal insufficiency (creatinine clearance lower than 10 ml/min) the elimination of paracetamol and its metabolites is delayed.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to those already included in other sections of the SmPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Ethylcellulose Mannitol (E421)

Microcrystalline cellulose (E460)

Crospovidone Type B Aspartame (E951)

Magnesium stearate (E572)

Strawberry flabour (contains amongst others, maltodextrine, arabic gum (E414))

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

2 years

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of container

PVC/PVdC or PCTFE/PVC blisters in a cardboard box, 12 or 20 tablets per box.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7    MARKETING AUTHORISATION HOLDER

Eurand S.p.A.

Via Martin Luther King 13

20060 Pessano con Bornago - Milano

Italy

8    MARKETING AUTHORISATION NUMBER(S)

PL 05146/006

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

31/05/2014

10    DATE OF REVISION OF THE TEXT

05/08/2013