Nu-Seals 300

Administrative change: update to amend the finished product manufacturers, Chanelle Medical, name and address.

Added text is underlined and deleted text is stroked through.

Section 6: Marketing Authorization Holder and Manufacturer

Nu-Seals 300mg is manufactured by Chanelle Medical Unlimited Company, Dublin Road, Loughrea, Co Galway, H62 FH90, Ireland.

This leaflet was last revised in June 2023 July 2024

*changes made to section 2 and 4.4 and 4.8 with the following text. remove text stroked through

Section 2 Qualitative and Quantitative composition

Each tablet contains:

Acetylsalicylic Acid (Aspirin) 300mg.

Excipients with known effect

Benzyl Alcohol 0.334mg per tablet

Section 4.4 Special warnings and Special precaution for Use

Nu-seals 300mg contains benzyl alcohol. High volumes should be used with caution and only if necessary, especially in patients with liver or kidney impairment because of the risk of benzyl alcohol accumulation and toxicity (metabolic acidosis). Benzyl alcohol may also cause allergic reactions.

Section 4.8 reporting of suspected adverse reactions

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.

*changes to section 2 - excipient warning (wording below)

Nu-Seals 300mg contains benzyl alcohol

This medicine contains 0.334 mg benzyl alcohol in each tablet.

Ask your doctor or pharmacist for advice if you have a liver or kidney disease. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”).

Benzyl alcohol may cause allergic reactions.

Minor change to section 4 reporting side effects - updated the ADR national reporting system details in line with Appendix V to the QRD Template.

Please see amendments below as tracked changes.

2. What you need to know before you take Nu-Seals 300mg

Other medicines and Nu-Seals 300mg

• Metamizole (substance to decrease pain and fever) may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells sticking together and forming a blood clot), when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose aspirin for cardioprotection.

Please see amendments as track changes below. 

4.5 Interation with Other Medicinal Proucts and Other Forms of Interaction

Metamizole may reduce the effect of acetylsalicylic acid on platelet aggregation, when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose aspirin for cardioprotection.

4.9 Overdose

Salicylate toxicity (> 100 mg/kg/day over 2 days may produce toxicity) may result from chronic, therapeutically acquired, intoxication, and from, potentially life-threatening, acute intoxications (overdose), ranging from accidental ingestions in children to incidental intoxications.

Chronic salicylate poisoning can be insidious as signs and symptoms are non-specific. Mild chronic salicylate intoxication, or salicylism, usually occurs only after repeated use of large doses. 

Symptoms

Common features include, dizziness, vomiting, nausea, dehydration, tinnitus, vertigo, deafness, sweating, headaches, confusion, warm extremities with bounding pulses, increased respiratory rate and hyperventilation.  Symptoms may be controlled by reducing the dosage. Tinnitus can occur at plasma concentrations of 150 to 300 micrograms/mL. More serious adverse events occur at concentrations above 300 micrograms/mL.

Some degree of acid base disturbance is present in most cases

The principle feature of acute intoxication is severe disturbance of the acid-base balance, which may vary with age and severity of intoxication. The most common presentation for a child is metabolic acidosis. The severity of poisoning cannot be estimated from plasma concentration alone. Absorption of acetylsalicylic acid can be delayed due to reduced gastric emptying, formation of concretions in the stomach, or as a result of ingestion of enteric-coated preparations. Management of acetylsalicylic acid intoxication is determined by its extent, stage and clinical symptoms and according standard poisoning management techniques. Predominant measures should be the accelerated excretion of the drug as well as the restoration of the electrolyte and acid-base metabolism.

Uncommon features include tachypnoea, diaphoresis, haematemesis, hyperpyrexia, hypoglycaemia, hyperglycaemia, increased ketone levels, hypokalaemia, hypernatraemia, hypoprothrombina, thrombocytopenia, increased INR/PTR, intravascular coagulation, dehydration, oliguria, renal failure,  GI bleeding, and non-cardiogenic pulmonary oedema, asphyxiation, respiratory arrest, dysarrhythmias, hypotension PT prolongation and cardiovascular arrest.

Toxic encephalopathy and Central nervous system features including confusion, disorientation, lethargy, coma, convulsions and toxic encephalopathy are less common in adults than in children.

Management

Gastric lavage or repeated administration of Give oral activated charcoal if an adult present within one hour of ingestion of more than 125 mg/kg. The plasma salicylate concentration should be measured for patients who have ingested >125mg/kg. However, the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. 

Urea and electrolytes, INR/PTR, blood pressure, ECG alteration and blood glucose should be monitored. Elimination is increased by urinary alkalisation, which is achieved by the administration of intravenous sodium bicarbonate. The urine pH should be monitored, and further intravenous sodium bicarbonate may be required to maintain urinary pH 7.5-8.5 (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.

4.3 Contra-indications

Hypoprothrombinaemia, haemophilia, haemorrhagic disease or a history of bleeding disorders, cerebral haemorrhage and active peptic ulceration.

Doses >100 mg/day during the third trimester of pregnancy.

4.4 Special Warnings and Special Precautions for Use

High doses of aspirin may precipitate acute haemolytic anaemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency.

4.6 Fertility, Pregnancy and Lactation

Low doses (up to 100 mg/day):

Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe.

Doses of 100-500 mg/day:

There is insufficient clinical experience regarding the use of doses above 100 mg/day up to 500 mg/day. Therefore, the recommendation below for doses of 500 mg/d and above apply also for this dose range.

Doses of 500 mg/day and above:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitor has been shown to results in increased pre- and post-implantation loss and embryo-foetal lethality.  In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, acetylsalicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

-cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

-renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

the mother and the neonate, at the end of pregnancy, to:

-possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

-inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.

4.8 Undesirable Effects

4.3 Contra-indications

Hypoprothrombinaemia, haemophilia, haemorrhagic disease or a history of bleeding disorders, cerebral haemorrhage and active peptic ulceration.

Doses >100 mg/day during the third trimester of pregnancy.

4.4 Special Warnings and Special Precautions for Use

High doses of aspirin may precipitate acute haemolytic anaemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency.

4.6 Fertility, Pregnancy and Lactation

Low doses (up to 100 mg/day):

Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe.

Doses of 100-500 mg/day:

There is insufficient clinical experience regarding the use of doses above 100 mg/day up to 500 mg/day. Therefore, the recommendation below for doses of 500 mg/d and above apply also for this dose range.

Doses of 500 mg/day and above:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitor has been shown to results in increased pre- and post-implantation loss and embryo-foetal lethality.  In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, acetylsalicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

-cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

-renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

the mother and the neonate, at the end of pregnancy, to:

-possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

-inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.

4.8 Undesirable Effects

4.3 Contraindications

Hypoprothrombinaemia, haemophilia, haemorrhagic disease or a history of bleeding disorders, cerebral haemorrhage and active peptic ulceration.

Doses >100 mg/day during the third trimester of pregnancy.

4.4 Special warnings and precautions for use

High doses of aspirin may precipitate acute haemolytic anaemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency.

4.6 Fertility, Pregnancy and Lactation

Pregnancy: 

Low doses (up to 100 mg/day):

Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe.

Doses of 100-500 mg/day:

There is insufficient clinical experience regarding the use of doses above 100 mg/day up to 500 mg/day. Therefore, the recommendation below for doses of 500 mg/d and above apply also for this dose range.

Doses of 500 mg/day and above:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitor has been shown to results in increased pre- and post-implantation loss and embryo-foetal lethality.  In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, acetylsalicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

-cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

-renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

the mother and the neonate, at the end of pregnancy, to:

-possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

-inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.

4.8 Undesirable effects

System Organ Class: Hepatobiliary disorders Undesirable Effect: Transaminase increased

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Changes are highlighted in red text below:

4.5       Interaction with Other Medicinal Products and Other Forms of Interaction

Salicylates inhibit the uricosuric effect of uricosuric drugs.

Antacids:  patients using enteric gastro-resistant coated aspirin should be advised against ingesting antacids simultaneously, to avoid premature drug release.

4.8       Undesirable Effects

¹May occur following chronic GI blood loss or acute haemorrhage

²May occur in various organ systems and may be fatal

³The special coating of Nu-Seals helps to reduce the incidence of side effects resulting from gastric irritation.

⁴Sometimes fatal, particularly in the elderly

¹The special coating of Nu-Seals helps to reduce the incidence of side effects resulting from gastric irritation.

²Sometimes fatal, particularly in the elderly

³May occur in various organ systems and may be fatal

⁴May occur following chronic GI blood loss or acute haemorrhage

4.9       Overdose

With the gastro-resistant enteric coated formulation, peak plasma levels may not occur for up to 12 hours.

5.1       Pharmacodynamic Properties

Nu-Seals 300 tablets have an gastro-resistant enteric coat sandwiched between a sealing coat and a top coat.  The gastro-resistant enteric coat is intended to resist gastric fluid whilst allowing disintegration in the intestinal fluid.

Changes to the Summary of Product Characteristics highlighted red text below:

4.2       Posology and Method of Administration

Undesirable effects may be minimised by using the lowest effective dose for the  shortest duration necessary to control symptoms (see section 4.4).  

4.3       Contraindications

Hypersensitivity to aspirin (e.g.- bronchospasm, rhinitis, urticaria), or to non-steroidal anti-inflammatory drugs or to any of the excipients listed in Section 6.1

4.4       Special warnings and precautions for use

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin or, selective serotonin-reuptake inhibitors or anti-platelet agents such as clopidogrel and dipyridamole  aspirin (see section 4.5).

Aspirin can reduce uric acid excretions and so should be used with care in patients with gout or a history of gout.

Patients with hypertension should be carefully monitored.

Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

4.5       Interaction with other medicinal products and other forms of interaction

Concomitant use of alcohol with aspirin may increase the risk of gastrointestinal bleeding.

Gold: risk of increased hepatotoxicity with aspirin.

Thiopental - Aspirin may potentiate the effects of thiopental anaesthesia.

Aspirin may enhance the effects of anticoagulants, antiplatelet agents and fibrinolytics leading to increased risk of bleeding.

Aspirin can interfere, to varying degrees, with some urine tests for catecholamines, dopa, glucose, ketones, hippuric acid, homogentisic acid, homovallinic acid, 17-hydroxycorticosteroids, 5-hydroxyindoleacetic acid, urine pregnancy tests and with some serum or plasma tests for albumin, barbiturates, calcium, propylthiouracil, tyrosine and uric acid

4.6       Fertility, Pregnancy and Lactation

Fertility:  Women attempting to conceive should not use any NSAID, including aspirin, because of the findings in a variety of animal models that indicate these agents block blastocyst implantation.

Pregnancy: Although clinical and epidemiological evidence suggests the safety of aspirin for use in pregnancy, cCaution should be exercised when considering use in pregnant patients.  With high doses there may be premature closure of the ductus arteriosus and possible kernicterus or persistent pulmonary hypertension in the newborn.  Analgesic doses of aspirin should be avoided during the last trimester of pregnancy.

Numerous malformations have been reported following maternal use of aspirin during pregnancy, however with the exception of a possible risk of gastroschisis, no specific pattern of malformations has been observed and a causative role for aspirin has not been proven.

4.8       Undesirable effects

4.8.1    Summary of the safety profile

The most commonly observed adverse events are gastrointestinal in nature

4.8.2 Tabulated list of adverse reactions

Undesirable effects are listed by MedDRA System Organ Classes.

Assessment of undesirable effects is based on the following frequency groupings:

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

 

 

	Undesirable Effect	Frequency
Gastrointestinal disorders1	Peptic ulcers2	Unknown
	GI Perforation2	Unknown
	GI Bleeding2	Unknown
	Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain,	Unknown
	Melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis, exacerbation of Crohn’s disease, gastritis	Unknown
Blood and lymphatic system disorders	Bleeding disorders	Unknown
	Haemorrhages and haematoma3	Unknown
	Anaemia4	Unknown
	Thrombocytopenia	Unknown
Immune system disorders	Hypersensitivity reactions including skin rashes, urticaria, angioedema, bronchospasm and anaphylaxis.  Bullous reactions including Stevens-Johnson and toxic epidermal necrolysis syndrome	Unknown
Nervous system disorders	Cerebral haemorrhage	Unknown
Ear and labyrinth disorders	Tinnitus	Unknown
Respiratory thoracic  and mediastinal disorders	Asthma, epistaxis, haemoptysis	Unknown
Skin and subcutaneous tissue disorders	Purpura, ecchymoses	Unknown
Renal and urinary disorders	Haematuria, urate kidney stones	Unknown
Investigations	Bleeding time prolonged	Unknown
Vascular disorders	Hypertension	Unknown
General disorders and administration site disorders	Oedema	Unknown
Cardiovascular	Cardiac failure,	Unknown

¹The special coating of Nu-Seals helps to reduce the incidence of side effects resulting from gastric irritation.

²Sometimes fatal, particularly in the elderly

³May occur in various organ systems and may be fatal

⁴May occur following chronic GI blood loss or acute haemorrhage

 

 

 

Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4 - Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. The special coating of Nu-Seals 75 helps to reduce the incidence of side effects resulting from gastric irritation.

 

Blood & lymphatic system: Aspirin prolongs bleeding time, and bleeding disorders, have occasionally been reported.  Haemorrhages and haematoma in various organ systems may result, and fatalities have occurred.  Anaemia may occur following chronic gastrointestinal blood loss or acute haemorrhage. Very rarely, a reduction in platelet count (thrombocytopenia) may occur.

 

Immune system: Hypersensitivity reactions include skin rashes, urticaria, angioedema, bronchospasm and rarely, anaphylaxis.

 

Nervous system: Cerebral haemorrhage

 

Ear & labyrinth: Tinnitus

 

Respiratory: Asthma (see section 4.4 Special warnings and precautions), epistaxis, haemoptysis

 

Skin & subcutaneous tissue: Purpura, ecchymoses (see also Immune System)

 

Renal & urinary: Haematuria, urate kidney stones.

 

Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.

 

Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

 

5.1       Pharmacodynamic properties

ATC code: N02B AB01A C06

 

Changes/amendments highlighted in red text below:

2 Qualitative and Quantitative Composition



Each tablet contains:



Acetylsalicylic Acid Ph.Eur. (Aspirin) 300mg.





Excipients: also includes trace amounts of Ponceau 4R (E124)



For a full list of excipients see section 6.1.





6.1 List of Excipients



Maize Starch

Hypromellose

Talc

Methacrylic acid – ethyl acrylate (1:1) copolymer dispersion 30 per cent

Emulsion silicone

Polyethylene glycol 3350

Propylene glycol

Benzyl alcohol

Emulsion silicone

Edible pPrinting ink containing Ponceau 4R (E124) shellac, iron oxide (E172), isopropyl alcohol, n-butyl alcohol, propylene glycol, ammonium hydroxide (E527) and simeticone

Each tablet contains:

Acetylsalicylic Acid Ph.Eur. (Aspirin) 300mg.