Summary of Product Characteristics (SmPC) - Paracetamol Hualan 1000 mg tablets
1 NAME OF THE MEDICINAL PRODUCT
Paracetamol Hualan 1000 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1000 mg of paracetamol.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
White, capsule shaped tablet engraved with a score line between “HY” and “1” on one side. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Symptomatic relief of occasional mild or moderate pain.
Febrile states.
Paracetamol Hualan 1000 mg Tablets are indicated in adults.
4.2 Posology and method of administration
Posology
Adults: Swallow one tablet every 6-8 hours, according to need. Do not exceed a dose of 4 tablets (equivalent to 4000 mg of Paracetamol) per 24 hours.
Patients with renal impairment: In case of renal failure, reduce the dose, depending on the degree of glomerular filtration according to the following chart:
| Glomerular filtration | Dose |
| 10-50 ml/min | 500 mg every 6 hours |
| <10 ml/min | 500 mg every 8 hours |
Due to the dose, this medication is not indicated for this group of patients. Patients with hepatic impairment: In the case of hepatic insufficiency, the dose should not exceed 2 g in 24 hours and the minimum interval between doses should be 8 hours (see section 4.4 special warnings and precautions for use).
The administration of high doses of paracetamol should be avoided for prolonged periods of time since the risk of liver damage is increased.
If the pain lasts more than 5 days, the fever lasts for more than 3 days or the pain or fever worsens or other symptoms appear, the clinical situation should be evaluated.
For the treatment of a sore throat, paracetamol should not be administered for more than 2 days in a row, without evaluating the clinical situation.
Paediatric population
Paracetamol Hualan 1000 mg Tablets should not be used in children and adolescents under 18 years.
Method of administration:
This medicine is administered orally.
The tablets should be taken with a glass of liquid, preferably water.
With the concomitant intake of paracetamol and foods, the absorption time of paracetamol increases, because the food decreases the motility and the time of gastrointestinal transit. For quick pain relief, take the medication without food, especially if it is high in carbohydrates.
4.3 Contraindications
Hypersensitivity to paracetamol or to any of the excipients of this medicine.
4.4 Special warnings and precautions for use
Contains paracetamol.
Do not use with any other paracetamol-containing products.
Underlying liver disease increases the risk or paracetamol related liver damage.
Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication.
Do not exceed the stated dose.
Patients should be advised to consult their doctor if their headaches become persistent.
Patients should be advised to consult a doctor if they suffer from non-serious arthritis and need to take painkillers every day.
Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.
Caution should be exercised in patients with glutathione depleted states, as the use of paracetamol may increase the risk of metabolic acidosis (refer also to section 4.9).
Use with caution in patients with glutathione depletion due to metabolic deficiencies.
If symptoms persists, medical advice must be sought.
Keep out of the sight and reach of children.
Pack Label:
Talk to a doctor at once if you take too much of this medicine even if you feel well. Do not take anything else containing paracetamol while taking this medicine.
Patient Information Leaflet:
Talk to a doctor at once if you take too much of this medicine even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage
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 daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see section 4.4).
4.6 Fertility, pregnancy and lactation
Pregnancy:
Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency
Breast-feeding:
Although maximum concentrations of 10 to 15 μg/ml (from 66.2 to 99.3 μmol/l) have been measured in maternal milk within 1 to 2 hours of the mother's ingestion of a single dose of 650 mg, paracetamol and its metabolites have not been detected in the urine of infants. The half-life in breast milk is from 1.35 to 3.5 hours. There have been no reports of adverse effects in children. Paracetamol can be used in women who are breast-feeding if the recommended dose is not exceeded. Caution should be exercised in the case of prolonged use.
4.7 Effects on ability to drive and use machines
Paracetamol Hualan 1000 mg Tablets has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive postmarketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class and frequency
The following convention has been utilised for the classification of the undesirable effects: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and very rare (<1/10,000), not known (cannot be estimated from available data).
Adverse event frequencies have been estimated from spontaneous reports received through post-marketing data
| Body system | Undesirable effect | Frequency |
| Blood and lymphatic system disorders | Thrombocytopenia Agranulocytosis | Very rare |
| Immune system disorders | Anaphylaxis Cutaneous hypersensitivity reactions including, among others, skin rashes and angiodema. Very rare cases of serious skin reactions have been reported. | Very rare |
| Metabolism and nutrition disorders | High anion gap metabolic acidosis | Not known |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm* | Very rare |
| Hepatobiliary disorders | Hepatic dysfunction | Very rare |
*There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
Description of selected adverse reactions
High anion gap metabolic acidosis
Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.
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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search MHRA Yellow Card in the Google Play or Apple App store.
4.9 Overdose
Symptoms of overdose include dizziness, vomiting, loss of appetite, jaundice, abdominal pain, and kidney and liver failure. If an overdose has been ingested, the patient should be treated promptly in a medical centre even if there are no significant symptoms or signs because, although these may cause death, they often do not manifest immediately after ingestion, but after the third day. Death may occur from liver necrosis. Also, acute renal failure may appear.
The overdose of paracetamol is evaluated in four phases, which begin at the time of ingestion of the overdose:
PHASE I (12-24 hours): nausea, vomiting, diaphoresis and anorexia;
PHASE II (24-48 hours): clinical improvement; AST, ALT, bilirubin and prothrombin levels begin to rise
PHASE III (72-96 hours): peak of hepatotoxicity; 20,000 values may appear for the AST
PHASE IV (7-8 days): recovery
Hepatotoxicity may appear. The minimum toxic dose is 6 g in adults and more than 100 mg/Kg in children. Doses greater than 20-25 g are potentially fatal. Symptoms of hepatotoxicity include nausea, vomiting, anorexia, malaise, diaphoresis, abdominal pain and diarrhoea. Hepatotoxicity does not manifest until 48-72 hours after ingestion. If the ingested dose was greater than 150 mg/Kg or the amount ingested cannot be determined, a serum paracetamol sample should be obtained at 4 hours after ingestion. In the event that hepatotoxicity occurs, perform a liver function study and repeat the study at 24-hour intervals. Liver failure may lead to encephalopathy, coma and death.
Plasma levels of paracetamol higher than 300 μg/ml, found at 4 hours after ingestion, have been associated with liver damage in 90% of patients. This begins to occur when plasma levels of paracetamol at 4 hours are greater than 120 μg/ml or greater than 30 μg/ml at 12 hours after ingestion.
Chronic ingestion of doses greater than 4 g/day may result in transient hepatotoxicity. The kidneys may suffer tubular necrosis, and the myocardium may be injured.
Treatment:
In all cases gastric aspiration and lavage will be carried out, preferably within 4 hours after ingestion.
There is a specific antidote for the toxicity produced by paracetamol: the N-acetylcysteine that can be administered intravenously or orally.
Intravenous route:
300 mg/Kg of N-acetylcysteine (equivalent to 1.5 ml/Kg of 20% aqueous solution, pH: 6.5) are recommended, administered via intravenous route for a period of 15 minutes or 20 hours, according to the following scheme:
- 1.
Adults
Attack dose: 150 mg/Kg (equivalent to 0.75 ml/Kg of 20% aqueous solution of N-acetylcysteine, pH: 6.5), administered slowly intravenously or diluted in 200 ml of 5% dextrose, for a duration of 15 minutes.
Maintenance dose:
- a) Initially, 50 mg/Kg (equivalent to 0.25 ml/Kg of 20% aqueous solution of N-acetylcysteine, pH: 6.5) will be administered in 500 ml of 5% dextrose in slow infusion for 4 hours.
- b) Subsequently, 100 mg/Kg (equivalent to 0.50 ml / Kg of 20% aqueous solution of N-acetylcysteine, pH: 6.5) will be administered in 1000 ml of 5% dextrose in slow infusion for 16 hours.
- 2.
Children
For children, the volume of the 5% dextrose solution for infusion should be adjusted based on the age and weight of the child, to avoid pulmonary vascular congestion.
The effectiveness of the antidote is maximum if it is administered before the expiration of 8 hours after the poisoning; decreases progressively from the eighth hour, and is ineffective after 15 hours of intoxication.
The administration of the aqueous solution of N-acetylcysteine at 20% may be interrupted when the results of the blood test show blood levels of paracetamol lower than 200 μg/ml.
Adverse effects of N-acetylcysteine IV: exceptionally, rashes and anaphylaxis have been observed, generally in the interval between 15 minutes and 1 hour from the beginning of the infusion.
Oral route:
The antidote N-acetylcysteine must be administered within 10 hours after overdose.
Adults
The recommended dose of antidote for adults is:
- an initial dose of 140 mg/Kg of body weight
- 17 doses of 70 mg/Kg of body weight, one every 4 hours
Each dose should be diluted to 5% with a cola drink, grape juice, orange juice or water, before being administered, due to its unpleasant odor and its irritating or sclerosing properties. If the dose is vomited within 1 hour after administration, it should be repeated.
If necessary, the antidote (diluted with water) can be administered by duodenal intubation.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: other analgesics and antipyretics. Anilides: Paracetamol.
ATC code: N02BE01.
Paracetamol is an analgesic that also has antipyretic properties.
The exact mechanism of action of paracetamol is unknown, although it is known to act at the level of the Central Nervous System and, to a lesser degree, blocking the generation of painful impulses at the peripheral level.
It is believed that paracetamol increases the pain threshold by inhibiting the synthesis of prostaglandins, by blocking cyclooxygenases in the Central Nervous System (specifically COX-3). However, paracetamol does not significantly inhibit cyclooxygenases in peripheral tissues.
Paracetamol stimulates the activity of descending serotonergic pathways that block the transmission of nociceptive signals to the spinal cord from peripheral tissues. In this sense, some experimental data indicate that the administration of antagonists of different subtypes of serotonergic receptors administered intra-spinally are capable of nullifying the antinociceptive effect of paracetamol.
The anti-thermal action is related to the inhibition of the synthesis of PGE1 in the hypothalamus, the physiological coordinating organ of the thermoregulation process.
5.2 Pharmacokinetic properties
Orally, the bioavailability of paracetamol is 75-85%. It is widely and quickly absorbed; the maximum plasma concentrations are reached, depending on the pharmaceutical form, with a time of 0.5 to 2 hours. The degree of binding to plasma proteins is 10%. The time it takes to achieve the maximum effect is 1 to 3 hours, and the duration of the action is 3 to 4 hours. The metabolism of paracetamol undergoes a hepatic first-pass effect, following a linear kinetics. However, this linearity disappears when doses higher than 2 g are administered. The paracetamol it is metabolized mainly in the liver (90-95%), being eliminated mainly in urine as a conjugate with glucuronic acid, and in a smaller proportion with sulfuric acid and cysteine; less than 5% is excreted unaltered. The elimination half-life is 1.5-3 hours (it increases in case of overdose and in patients with hepatic insufficiency, the elderly and children). High doses can saturate the usual mechanisms of hepatic metabolism, which leads to the use of alternative metabolic pathways that give rise to hepatotoxic and possibly nephrotoxic metabolites, due to glutathione depletion.
Physiopathological variations:
Renal insufficiency: in case of severe renal insufficiency (creatinine clearance less than 10 ml/min) the elimination of paracetamol and its metabolites is delayed.
Elderly patients: the ability to conjugate is not modified. An increase in the elimination half-life of paracetamol has been observed.
5.3 Preclinical safety data
Paracetamol, at therapeutic doses, does not present toxic effects and only at very high doses causes centrilobular hepatic necrosis in animals and man. Also, at very high dose levels, paracetamol causes methemoglobinaemia and oxidative haemolysis in dogs and cats and very rarely in humans.
In studies of chronic, sub-chronic and acute toxicity, carried out with rats and mice, gastrointestinal lesions, changes in the blood count, degeneration of the liver and renal parenchyma, including necrosis, have been observed. On the one hand, the causes of these changes have been attributed to the mechanism of action and, on the other hand, to the metabolism of paracetamol. It has also been seen in humans, that the metabolites seem to produce the toxic effects and the corresponding changes in the organs. In addition, very rare cases of reversible chronic aggressive hepatitis have been described during prolonged use (e.g. 1 year) with therapeutic doses. In the case of subtoxic doses, signs of intoxication may appear after 3 weeks of treatment. Therefore, paracetamol should not be taken for long periods of time nor at high doses.
Additional investigations showed no evidence of a relevant genotoxic risk of paracetamol at therapeutic doses, i.e. at non-toxic doses.
Long-term studies in rats and mice produced no evidence of tumors with non-hepatotoxic paracetamol doses.
Fertility: studies of chronic toxicity in animals show that high doses of paracetamol produce testicular atrophy and inhibition of spermatogenesis; the importance of this fact for its use in humans is unknown.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Povidone K30
Pregelatinised Starch
Stearic Acid
Magnesium Stearate
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Pack
type
Material Proposed
Shelf life
PVC sheet and PVC/Al composite film 48 months Blister
PVC sheet and polyester/Al composite film 48 months
HDPE pots with Polyolefin lids with PE
foam liner
24 months Pots
HDPE pots with Polyolefin lids laminated
extruded PE foam liner
24 months
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Pack type
Material Pack sizes
PVC sheet and PVC/Al composite film
Blister
PVC sheet and polyester/Al composite film
8, 10, 12, 15, 16, 20, 24, 28, 30, 32, 40, 50, 56, 60, 84, 90
HDPE pots with Polyolefin lids with PE foam
liner
Pots
HDPE pots with Polyolefin lids laminated
extruded PE foam liner
100
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
ualan Pharmaceuticals Limited
16/17 College Green
Dublin 2
Dublin
D02 V078
Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 52104/0003
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
21/02/2023
10 DATE OF REVISION OF THE TEXT
04/03/2025