Produktinformationen för Quramol 250 mg, 500 mg munsönderfallande tablett, MTnr 48241, 48242,
gäller vid det tillfälle då läkemedlet godkändes. Informationen kommer inte att uppdateras eftersom
läkemedlet inte marknadsförs i Sverige. Av samma anledning finns inte någon svensk
produktinformation.
Den engelska produktinformationen kommer dock att uppdateras för de produkter där Sverige är
referensland.
Om läkemedelsnamnet i följande produktinformation inte stämmer med namnet på dokumentet, beror
det på att läkemedlet i Sverige är godkänt under ett annat namn.
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SUMMARY OF PRODUCT CHARACTERISTICS
1.
NAME OF THE MEDICINAL PRODUCT
[Invented Name] 250 mg orodispersible tablets
[Invented Name] 500 mg orodispersible tablets
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
250 mg tablets: Each orodispersible tablet contains 250 mg paracetamol.
500 mg tablets: Each orodispersible tablet contains 500 mg paracetamol.
Excipient with known effect:
250 mg tablets: contains 11.2 mg aspartame (E951).
500 mg tablets: contains 22.4 mg aspartame (E951).
For the full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Orodispersible tablet.
250 mg tablets: White to off-white round, flat face radius edge tablets, diameter about 13 mm.
500 mg tablets: White to off-white round, flat face radius edge tablets, diameter about 17 mm.
4.
CLINICAL PARTICULARS
4.1
Therapeutic indications
Symptomatic treatment of mild to moderate pain and/or fever.
4.2
Posology and method of administration
Posology
Paediatric dosage should be based on body weight and suitable dosage form used. Information on the
age of children within each weight group given below is for guidance only.
Regular administration minimizes pain and fever oscillation. The recommended daily dose of
paracetamol is approximately 60 mg/kg/day divided in 4 or 6 doses, or approximately 15 mg/kg every
6 hours, or 10 mg/kg every 4 hours. The dose interval should always be at least 4 hours.
The maximum total daily dose is 60 mg/kg/day in children and 3000 mg/day in adults. Maximal daily
dose should not be exceeded due to risk of serious hepatic damage (see sections 4.4 and 4.9).
Paediatric population
17-25 kg (approximately 4-8 years):
26-32 kg (approximately 8-11 years):
33-43 kg (approximately 11-12 years):
44-50 kg (approximately 12 years):
Single dose (maximum daily dose)
250 mg (max. 1,000 mg per 24 hours)
250 mg (max. 1,500 mg per 24 hours)
500 mg (max. 2,000 mg per 24 hours)
500 mg (max. 2,500 mg per 24 hours)
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[Invented Name] 250 mg orodispersible tablets are not recommended in children below 4 years of age
or weighing less than 17 kg.
Adolescents (> 50 kg and over 12 years of age)
Single dose: 500 mg.
Maximum daily dose: 3,000 mg per 24 hours.
Adults
Single dose: 500 mg-1,000mg.
Maximum daily dose: 3,000 mg per 24 hours.
Impaired kidney function
In patients with renal insufficiency, the dose should be reduced:
Glomerular filtration rate
Maximum dose in adults
10-50 ml/min
500 mg every 6 hours
< 10 ml/min
500 mg every 8 hours
Impaired hepatic function
Paracetamol should be used with caution in the presence of hepatic insufficiency (see sections 4.3 and
4.4).
Elderly patients:
Dose adjustment is not required.
Chronic alcoholism:
Chronic alcohol consumption may lower the paracetamol toxicity threshold. In these patients, the
length of time between two doses should be a minimum of 8 hours. The total daily dose must not
exceed 2 g paracetamol.
In case of high fever or sign of infection for more than 3 days or in case of pain for more than 5
days the patient should be advised to contact a doctor.
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 of water.
The intake of paracetamol with food or drink does not affect the efficacy of the medicinal product.
4.3
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Severe hepatic insufficiency.
4.4
Special warnings and precautions for use
Caution is advised in the administration of paracetamol to patients with moderate and severe renal
insufficiency, mild to moderate hepatocellular insufficiency (including Gilbert’s syndrome), severe
hepatic insufficiency (Child-Pugh >9), acute hepatitis, concomitant treatment with medicinal products
affecting hepatic functions, glucose-6- phosphatedehydrogenase deficiency, haemolytic anaemia,
dehydration, alcohol abuse and chronic malnutrition.
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Patients should be advised not to take any other paracetamol-containing products concurrently due to
the risk of severe liver damage in case of overdose (see section 4.9).
If the pain persists for more than 5 days or the fever lasts for more than 3 days or gets worse a
physician should be consulted.
Alcoholic beverages should be avoided while taking this product because concomitant use of
paracetamol may cause liver damage. Paracetamol should be given with caution to patients with
alcohol dependence. In case of overdose, concomitant use of barbiturates, alcohol or other agents with
hepatotoxic effect will increase the risk of liver damage.
In general, habitual intake of analgesics, particularly a combination of several analgesic substances,
can lead to permanent renal damage with the risk of renal failure (analgesic nephropathy).
There is a possible risk of metabolic acidosis associated with paracetamol use in patients with
additional risk factors such as malnutrition or sepsis like inflammatory response.
[Invented Name] contains aspartame, which is a source of phenylalanine. The phenylalanine in the
tablets may be harmful to people with phenylketonuria.
4.5
Interaction with other medicinal products and other forms of interaction
Probenecid inhibits the binding of paracetamol to glucuronic acid, thus leading to a reduction in
paracetamol clearance by a factor of approximately 2. In patients concurrently taking probenecid, the
paracetamol dose should be reduced.
Use of substances that induce liver enzymes, such as carbamazepine, phenytoin, phenobarbital,
rifampicin and St John’s wort (Hypericum perforatum) can increase the hepatotoxicity of paracetamol
due to increased and more rapid formation of toxic metabolites. Therefore, caution should be taken in
case of concomitant use of enzyme inducing substances.
Zidovudine inhibits paracetamol metabolism and vice versa, which may add to the toxicity of both.
Repeated paracetamol intake for longer than one week enhances the effects of anticoagulants,
particularly warfarin. Therefore long-term administration of paracetamol in patients who are being
treated with anticoagulants should only take place under medicinal supervision. The effect may occur
already at daily doses of 1.5-2 g for 5-7 days. If paracetamol is used in doses at > 2 g daily, INR
values (International Normalized Ratio) should be monitored. Occasional paracetamol intake has no
significant effects on bleeding tendency.
Concurrent intake of medicinal products that accelerate gastric emptying, such as metoclopramide or
domperidone, accelerates the absorption and onset of effect of paracetamol.
Cholestyramine reduces absorption of paracetamol, and should therefore not be administered within
an hour following paracetamol administration.
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Isoniazid may affect the pharmacokinetics of paracetamol with possible potentiation of liver toxicity.
Concurrent intake of medicines that slow gastric emptying can delay the absorption and onset of
effect of paracetamol.
Paracetamol may affect the pharmacokinetics of chloramphenicol. Monitoring of chloramphenicol
plasma levels is recommended if combining paracetamol with chloramphenicol injection treatment.
Ethyl alcohol potentiates paracetamol toxicity, possibly by inducing hepatic production of
paracetamol-derived hepatotoxic products.
Effects on laboratory tests
Intake of paracetamol can affect tests for uric acid using phosphotungstic acid and blood sugar tests
using glucose-oxidase-peroxidase.
4.6
Fertility, pregnancy and lactation
Pregnancy
Epidemiological studies concerning the use of oral therapeutic doses of paracetamol have shown no
adverse effects on human pregnancy or on the foetus or newborn. Paracetamol may be used at
therapeutic doses during pregnancy after consideration has been given to the benefit versus risk ratio.
During pregnancy, paracetamol should not be taken for a long period, at high doses or in combination
with other medicinal products, as safety of use has not been established in such cases.
Breast-feeding
Low levels of paracetamol are excreted in human milk. No undesirable effects on breastfed infants
have been reported. Paracetamol can be used during breast-feeding as long as the recommended
dosage is not exceeded. In case of long term use caution should be exercised.
Fertility
There are no concerns about effects on fertility due to paracetamol treatment.
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
Adverse effects are rare at common therapeutic doses.
Liver damage has rarely been described when paracetamol has been used at therapeutic doses, but in
patients with a history of liver damage or using paracetamol combined with some other agent
damaging the liver (such as alcohol) the risk of liver damage must be taken into consideration.
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as:
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).
Frequency
Rare
(≥1/10,00
0-<
1/1,000)
System
Blood and lymphatic system
disorders
Immune system disorders
Psychiatric disorders
Nervous system disorders
Eye disorders
Gastrointestinal disorders
Hepatobiliary disorders
Symptoms
Platelet disorders, stem cell disorders, agranulocytosis,
leucopenia, thrombocytopenia,
haemolytic anaemia, pancytopenia
Allergies (excluding angioedema)
Depression NOS, confusion, hallucinations
Tremor NOS, headache NOS
Abnormal vision
Haemorrhage NOS, abdominal pain NOS, diarrhoea
NOS, nausea, vomiting
Abnormal hepatic function, hepatic failure, hepatic
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Very Rare
(< 10,000)
Skin and subcutaneous tissue
disorders
General disorders and
administration site conditions
Immune system disorders
Metabolism and nutrition
disorders
Respiratory, thoracic and
mediastinal disorders
Not known
necrosis, jaundice
Pruritus, rash, angioedema, urticaria, sweating, purpura
Oedema, hyperthermia
Anaphylactic shock, hypersensitivity reaction (requiring
discontinuation of treatment)
Hypoglycemia
Bronchospasm
Hepatobiliary disorders
Hepatotoxicity
Renal and urinary disorders
General disorders and
administration site conditions
Sterile pyuria (cloudy urine) and renal side effects
Dizziness (excluding vertigo), malaise, sedation, drug
interaction NOS
Skin and subcutaneous tissue
disorders
Stevens-Johnson syndrome, toxic epidermal necrolysis
Interstitial nephritis has been reported incidentally after prolonged use of high doses. Some cases of
erythema multiforme, edema of the larynx, anemia, liver alteration and hepatitis, renal alteration
(severe renal impairment, haematuria, anuresis) and vertigo have been reported.
4.9
Overdose
There is a risk of poisoning, particularly in elderly subjects, 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). In addition,
hepatic injury following repeated supratherapeutic ingestions may occur at any dose above the daily
recommended dose even in subjects without known risk factors.
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.
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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 or even
36 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. The mode of
administration of N-acetylcysteine should be considered individually taking into account the
consciousness of the patient and his/her tendency to vomit. Intravenous N-acetylcysteine should be
given 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. If oral antidote is given, it should be
noticed that activated charcoal also adsorbs the antidote. 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. It is used for the relief of mild to moderate
pain and for fever. The primary mechanism of action may be the inhibition of prostaglandins
synthesis. Paracetamol produces peripheral vasodilatation yielding increased blood flow through the
skin, perspiration and heat loss. The analgesic effect starts within 30 minutes, with maximum effect
within 1 to 2 hours and lasts up to 4 to 5 hours. The antipyretic effect starts within 30 to 60 minutes.
The maximum antipyretic effect is between 2 to 3 hours and the effect lasts up to 8 hours.
Unlike acetyl salicylic acid, paracetamol does not cause gastrointestinal irritation and is well tolerated
by patients. Thrombocyte aggregation and bleeding time are generally not affected by paracetamol.
Patients with hypersensitivity to acetyl salicylic acid generally tolerate paracetamol.
5.2
Pharmacokinetic properties
Absorption
After oral administration paracetamol is rapidly and almost completely absorbed with a bioavailability
of 80-88%. Peak plasma concentrations are reached after 30 to 60 minutes.
Distribution
The volume of distribution of paracetamol is approximately 1 l/kg bodyweight. Blood, plasma and
saliva concentrations are comparable. At therapeutic doses protein binding is negligible.
Biotransformation
Most of the paracetamol dose is metabolized in the liver to nontoxic sulphate and glucuronide
conjugates. A small part of the dose is metabolized to a reactive, potentially toxic intermediate
product that binds to liver glutathione and forms nontoxic cysteine and mercaptopurine derivatives
excreted via the kidneys. At therapeutic doses sulphate/glucuronide reactions are not saturated but
high overdoses (of 140 mg/kg or more) saturate these reactions. In such cases, the amount of reactive
intermediate product may deplete liver glutathione reserves, and the toxic metabolite will bind to liver
cell proteins causing liver cell necrosis.
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Elimination
Elimination is mainly in the urine. 90% of the absorbed amount is renally excreted within 24 hours,
mainly as glucuronides (60–80%) and sulphate conjugates (20–30%). Less than 5% is eliminated in
unchanged form. The elimination half-life of paracetamol after oral and i.v. administration is 1.5-3
hours in adults.
Renal insufficiency
In cases of severe renal insufficiency (creatinine clearance lower than 10 ml/min) the elimination of
paracetamol and its metabolites is delayed.
Elderly patients
Conjugation is unchanged in this patient group.
Paediatric patients
In neonates and children <12 years sulphate conjugation is the main elimination route and
glucuronidation is lower than in adults. Therefore, severe liver damage caused by paracetamol would
seem to be rarer in children than in adults. Total elimination in children is comparable to that in
adults, due to an increased capacity for sulphate conjugation. The elimination half-life of paracetamol
is 2-2.5 hours in children.
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 (E470b)
Strawberry flavour (contains among others, maltodextrine, arabic gum [E414], triethyl citrate)
6.2
Incompatibilities
Not applicable.
6.3
Shelf life
3 years.
6.4
Special precautions for storage
Do not store above 30C.
6.5
Nature and contents of container
250 mg tablets: PVC/PVdC/paper/polyester/aluminium foil or PVC/PVdC/aluminium foil , 12 and 24
tablets
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500 mg tablets: PVC/PVdC/paper/polyester/aluminium foil or PVC/PVdC/aluminium foil blisters, 12,
18 and 24 tablets
Not all pack sizes may be marketed.
6.6
Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
7.
MARKETING AUTHORISATION HOLDER
Orion Corporation
Orionintie 1
FI-02200 Espoo
Finland
8.
MARKETING AUTHORISATION NUMBER(S)
<[To be completed nationally]>
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
<[To be completed nationally]>
10.
DATE OF REVISION OF THE TEXT
17.1.2014
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