Septrin 80mg/400mg Tablets
*Company:
AspenStatus:
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Updated on 19 January 2023
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- Document format updated
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Updated on 01 September 2021
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Updated on 01 September 2021
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- Change to section 2 - what you need to know - warnings and precautions
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Updated on 04 September 2020
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- Correction of spelling/typing errors
Updated on 31 July 2020
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- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 6.4 - Special precautions for storage
- Change to section 10 - Date of revision of the text
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Updated on 31 July 2020
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- Change to section 2 - what you need to know - warnings and precautions
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Updated on 30 April 2020
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Sulf,Trim_Tab_IE_S_400,80mg_v6.pdf
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- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 6.4 - Special precautions for storage
- Change to section 10 - Date of revision of the text
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Updated on 27 April 2020
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- XPIL Updated
Updated on 27 April 2020
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- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 18 January 2019
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Sulf,Trim_Tab_IE_P_400,80mg_v5.pdf
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- Change to Section 1 - what the product is
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 3 - dose and frequency
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 06 December 2018
File name
Sulf,Trim_Tab_IE_S_400,80mg_v5.pdf
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 10 - Date of revision of the text
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Updated on 18 June 2018
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- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.8 - Undesirable effects
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 10 - Date of revision of the text
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Updated on 18 June 2018
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Sulf,Trim_Tab_IE_P_400,80mg_v4.pdf
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- Change to section 1 - what the product is used for
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 3 - how to take/use
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 16 November 2017
Reasons for updating
- New SPC for new product
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Updated on 16 November 2017
Reasons for updating
- Change to section 3 - Pharmaceutical form
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 6.4 - Special precautions for storage
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 10 - Date of revision of the text
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3. PHARMACEUTICAL FORM
Tablet
White, round, biconvex tablets, debossed with “S2” on one side and scored on the other side.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
4.5 Interaction with other medicinal products and other forms of interaction
Repaglinide: trimethoprim may increase the exposure of repaglinide which may result in hypoglycaemia.
Folinic acid: folinic acid supplementation has been shown to interfere with the antimicrobial efficacy of trimethoprim-sulfamethoxazole. This has been observed in Pneumocystis jiroveci pneumonia prophylaxis and treatment.
Contraceptives: oral contraceptive failures have been reported with antibiotics. The mechanism of this effect has not been elucidated. Women on treatment with antibiotics should temporarily use a barrier method in addition to the oral contraceptive, or choose another method of contraception.
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: ANTIBACTERIALS FOR SYSTEMIC USE – SULFONAMIDES AND TRIMETHOPRIM – Combinations of sulphonamides and trimethoprim, incl. derivatives, ATC Code: J01EE0l
IMechanism of action
Sulfamethoxazole competitively inhibits the utilisation of para-aminobenzoic acid in the synthesis of dihydrofolate by the bacterial cell resulting in bacteriostasis. Trimethoprim reversibly inhibits bacterial dihydrofolate reductase (DHFR), an enzyme active in the folate metabolic pathway converting dihydrofolate to tetrahydrofolate. Depending on the conditions the effects may be bactericidal. Thus trimethoprim and sulfamethoxazole block two consecutive steps in the biosynthesis of purines and therefore nucleic acids essential to many bacteria. This action produces marked potentiation of activity in vitro between the two agents.
Trimethoprim binds to plasmodial DHFR but less tightly than to the bacterial enzyme. Its affinity for mammalian DHFR is some 50,000 times less for the corresponding bacterial enzyme.
Resistance
In vitro studies have shown that bacterial resistance can develop more slowly with both sulfamethoxazole and trimethoprim in combination that with either sulfamethoxazole or trimethoprim alone.
Resistance to sulfamethoxazole may occur by different mechanisms. Bacterial mutations cause an increase the concentration of PABA and thereby out-compete with sulfamethoxazole resulting in a reduction of the inhibitory effect on dihydropteroate synthetase enzyme. Another resistance mechanism is plasmid-mediated and results from production of an altered dihydropteroate synthetase enzyme, with reduced affinity for sulfamethoxazole compared to the wild-type enzyme.
Resistance to trimethoprim occurs through a plasmid-mediated mutation which results in production of an altered dihydrofolate reductase enzyme having a reduced affinity for trimethoprim compared to the wild-type enzyme.
Susceptibility testing breakpoints
5.2 Pharmacokinetic properties
Distribution
Approximately 66% of sulfamethoxazole in the plasma is protein bound. The concentration of active sulfamethoxazole in amniotic fluid, aqueous humour, bile, cerebrospinal fluid, middle ear fluid, sputum, synovial fluid and tissue (interstitial) fluid is of the order of 20-50% of the plasma concentration.
Biotransformation
Renal excretion of intact SMX accounts for 15-30% of the dose. This drug is more extensively metabolised than TMP, via acetylation, oxidation or glucuronidation. Over a 72 hour period, approximately 85% of the dose can be accounted for in the urine as unchanged drug plus the major (N4-acetylated) metabolite.
Special patient populations
Renal impairment
The elimination half-life of trimethoprim is increased by a factor of 1.5-3.0 when the creatinine clearance is less than 10 mL/minute. When the creatinine clearance falls below 30 mL/min the dosage of Septrin should be reduced (see section 4.2).
Hepatic impairment
Caution should be exercised when treating patients with severe hepatic impairment as there may be changes in the absorption and biotransformation of trimethoprim and sulfamethoxazole
Older patients
In older patients, a slight reduction in renal clearance of sulfamethoxazole but not trimethoprim has been observed.
Paediatric population
See special dosage regimen (see section 4.2).
6.4 Special precautions for storage
Do not store above 25°C.
Store in the original package in order to protect from light.
6.6 Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product
10. DATE OF REVISION OF THE TEXT
February 2015June 2016 October 2017
Updated on 14 November 2017
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PIL_9100_166.pdf
Reasons for updating
- New PIL for new product
Updated on 14 November 2017
Reasons for updating
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 6 - date of revision
Updated on 16 March 2015
Reasons for updating
- Change to section 3 - Pharmaceutical form
- Change to section 10 - Date of revision of the text
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3 PHARMACEUTICAL FORM
Tablet.
White, round, biconvex tablets, debossed with S2 on one side and scored on the other side. scored and coded 'GX Y2B'
10 DATE OF REVISION OF THE TEXT
February 2015 April 2014
Updated on 13 March 2015
Reasons for updating
- Change to further information section
- Change to date of revision
Updated on 10 April 2014
Reasons for updating
- Change to section 7 - Marketing authorisation holder
- Change to section 10 - Date of revision of the text
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7 MARKETING AUTHORISATION HOLDER
12/13 Exchange Place
I.F.S.C Dublin 1
3016 Lake Drive,
Citywest Business Campus
Dublin 24
10 DATE OF REVISION OF THE TEXT
July April 20143
Updated on 08 April 2014
Reasons for updating
- Change to date of revision
- Change to MA holder contact details
Updated on 07 August 2013
Reasons for updating
- Change to side-effects
- Change to date of revision
- Change to warnings or special precautions for use
Updated on 29 July 2013
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
- Correction of spelling/typing errors
- Change to section 4.4 - Special warnings and precautions for use
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Spelling error for trimethoprim and sulfamethoxazole corrected.
4.4 Special warnings and precautions for use
Fatalities, although very rare, have occurred due to severe reactions including fulminant Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract.
Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of Septrin. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment. If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, Septrin treatment should be discontinued (see 4.8 Undesirable Effects).
The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis. If the patient has developed SJS or TEN with the use of Septrin, Septrin must not be re-started in this patient at any time.
4.8 Undesirable effects
Skin and subcutaneous tissue disorders
Common: Skin rashes
Very rare: Photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (see section 4.4).
Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis),
Lyell’s syndrome carries a high mortality.
10 DATE OF REVISION OF THE TEXT
February 2011 July 2013
Updated on 02 July 2013
Reasons for updating
- Change to section 1 - Name of medicinal product
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 5.3 - Preclinical safety data
- Change to section 10 - Date of revision of the text
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1 NAME OF THE MEDICINAL PRODUCT
Septrin 80mg/400mg Forte Tablets.
4.2 Posology and method of administration
For severe infections and septicemia:
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Tablets |
Adult Suspension |
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Three |
15ml twice daily |
4.4 Special warnings and precautions for use
Particular care is always advisable when treating elderly patients because, as a group, they are more susceptible to adverse reactions and more likely to suffer serious effects as a result particularly when complicating conditions exist, e.g. impaired kidney and/or liver function and/or concomitant use of other drugs.
Septrin should be given with caution to patients with severe allergy or bronchial asthma.
Administration of trimethoprium/ sulfametoxazole 160mg/800mg (co-trimoxazole) causes a 40% increase in lamivudine exposure because of the trimethoprium component. Lamivudine has no effect on the pharmacokinetics of trimethoprium or sulfametoxazole.
5.3 Preclinical safety data
Reproductive toxicology: At doses generally in excess of the recommended human therapeutic dose, trimethoprium and sulfametoxazole have been reported to cause cleft palate and other foetal abnormalities in rats, finding typical of a folate antagonist. Effects with trimethoprium were preventable by co-administration of dietary folate. In rabbits, folate loss was seen at doses of trimethoprim in excess of human therapeutic doses.
10 DATE OF REVISION OF THE TEXT
February 2011
Updated on 30 January 2013
Reasons for updating
- Improved electronic presentation
Updated on 11 January 2013
Reasons for updating
- Improved electronic presentation
Legal category:Product subject to medical prescription which may not be renewed (A)
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Updated on 27 May 2011
Reasons for updating
- Change to marketing authorisation holder
Updated on 05 May 2011
Reasons for updating
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 10 - Date of revision of the text
- SPC retired pending re-submission
Legal category:Product subject to medical prescription which may not be renewed (A)
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Product ownership changed from GSK to Aspen
Updated on 28 October 2008
Reasons for updating
- Correction of spelling/typing errors
Legal category:Product subject to medical prescription which may not be renewed (A)
Updated on 12 September 2008
Reasons for updating
- Change to side-effects
Updated on 11 September 2008
Reasons for updating
- Change to section 4.8 - Undesirable effects
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The following text has been added to section 4.8 of the
Eye disorders:
Very rare: Uveitis
Updated on 07 April 2008
Reasons for updating
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 5.1 - Pharmacodynamic properties
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5.1 Pharmacodynamic Properties
Updated on 12 July 2007
Reasons for updating
- Improved electronic presentation
Updated on 12 June 2007
Reasons for updating
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
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4.3 Contraindications
4.4 Special Warnings and Special Precautions for Use
Regular monthly blood counts are advisable when Septrin is given for long periods, or to folate deficient patients or to the elderly, since there exists a possibility of asymptomatic changes in haematological laboratory indices due to lack of available folate. These changes may be reversed by administration of folinic acid (5 to 10 mg/day) without interfering with the antibacterial activity.
In glucose-6-phosphate dehydrogenase deficient (G-6-PD) patients haemolysis may occur.
Septrin should be given with caution to patients with severe allergy or bronchial asthma.
Septrin should not be used in the treatment of streptococcal pharyngitis due to Group A beta-haemolytic streptococci; eradication of these organisms from the oropharynx is less effective than with penicillin.
Trimethoprim has been noted to impair phenylalanine metabolism but this is of no significance in phenylketonuric patients on appropriate dietary restriction.
The administration of Septrin to patients known or suspected to be at risk of acute porphyria should be avoided. Both trimethoprim and sulphonamides (although not specifically sulfamethoxazole) have been associated with clinical exacerbation of porphyria.
Close monitoring of serum potassium and sodium is warranted in patients at risk of hyperkalaemia. and hyponatraemia.
Except under careful supervision Septrin should not be given to patients with serious haematological disorders (see Adverse Reactions). Septrin has been given to patients receiving cytotoxic therapy with little or no additional effect on the bone marrow or peripheral blood.
4.8 Undesirable Effects
As Septrin contains trimethoprim and a sulphonamide the type and frequency of adverse reactions associated with such compounds are expected to be consistent with extensive historical experience.
Data from large published clinical trials were used to determine the frequency of very common to rare adverse events. Very rare adverse events were primarily determined from post-marketing experience data and therefore refer to reporting rate rather than a "true" frequency. In addition, adverse events may vary in their incidence depending on the indication.
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The following convention has been used for the classification of adverse events in terms of frequency: |
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Very common 1/10, |
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common 1/100 and <1/10, |
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uncommon 1/1000 and <1/100, |
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rare 1/10,000 and <1/1000, |
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very rare <1/10,000. |
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Infections and Infestations |
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Common: |
Monilial overgrowth. |
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Blood and lymphatic system disorders |
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Very rare: |
Leucopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastic anaemia, aplastic anaemia, haemolytic anaemia, methaemoglobinaemia, eosinophilia, purpura, haemolysis in certain susceptible G-6-PD deficient patients. |
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Immune system disorders |
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Very rare: |
Serum sickness, anaphylaxis, allergic myocarditis, angioedema, drug fever, allergic vasculitis resembling Henoch-Schoenlein purpura, periarteritis nodosa, systemic lupus erythematosus. |
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Metabolism and nutrition disorders |
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Very common: |
Hyperkalaemia |
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Very rare: |
Hypoglycaemia, hyponatraemia, anorexia |
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Psychiatric disorders |
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Very rare: |
Depression, hallucinations |
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Nervous system disorders |
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Common: |
Headache |
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Very rare: |
Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, dizziness |
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Aseptic meningitis was rapidly reversible on withdrawal of the drug, but recurred in a number of cases on re-exposure to either Septrin or to trimethoprim alone. |
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Respiratory, thoracic and mediastinal disorders |
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Very rare: |
Cough, shortness of breath, pulmonary infiltrates |
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Cough, shortness of breath and pulmonary infiltrates may be early indicators of respiratory hypersensitivity which, while very rare, has been fatal. |
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Gastrointestinal disorders |
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Common: |
Nausea, diarrhoea |
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Uncommon: |
Vomiting |
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Very rare: |
Glossitis, stomatitis, pseudomembranous colitis, pancreatitis |
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Hepatobiliary disorders |
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Very rare: |
Cholestatic jaundice, hepatic necrosis |
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Cholestatic jaundice and hepatic necrosis may be fatal. |
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Oral: |
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Very rare: |
Elevation of serum transaminases, elevation of bilirubin levels |
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Skin and subcutaneous tissue disorders |
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Common: |
Skin rashes |
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Very rare: |
Photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, Stevens-Johnson syndrome, Lyells syndrome (toxic epidermal necrolysis) |
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Lyells syndrome carries a high mortality. |
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Musculoskeletal and connective tissue disorders |
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Very rare: |
Arthralgia, myalgia |
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Renal and urinary disorders |
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Very rare: |
Impaired renal function (sometimes reported as renal failure), interstitial nephritis |
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Effects associated with Pneumocystis jiroveci (carinii) pneumonitis (PJP) management |
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Very rare: |
Severe hypersensitivity reactions, rash, fever, neutropenia, thrombocytopenia, raised liver enzymes, rhabdomyolysis |
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At the high dosages used for PJP management severe hypersensitivity reactions have been reported, necessitating cessation of therapy. If signs of bone marrow depression occur, the patient should be given calcium folinate supplementation (5 to 10 mg/day). Severe hypersensitivity reactions have been reported in PJP patients on re-exposure to trimethoprim-sulfamethoxazole, sometimes after a dosage interval of a few days. Rhabdomyolysis has been reported in HIV positive patients receiving Septrinfor prophylaxis or treatment of PJP. |
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Very rare: |
Hyperkalaemia, hyponatraemia |
Updated on 01 June 2006
Reasons for updating
- Improved electronic presentation
Updated on 23 May 2006
Reasons for updating
- Change to section 1 - Name of medicinal product
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 6.4 - Special precautions for storage
- Change to section 6.5 - Nature and contents of container
- Change to section 9 - Date of renewal of authorisation
Legal category:Product subject to medical prescription which may not be renewed (A)
Updated on 23 May 2006
Reasons for updating
- Improved electronic presentation
Updated on 12 October 2004
Reasons for updating
- New PIL for medicines.ie
Updated on 09 August 2004
Reasons for updating
- Improved electronic presentation
Legal category:Product subject to medical prescription which may not be renewed (A)
Updated on 01 July 2003
Reasons for updating
- New SPC for medicines.ie
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