Consumer medicine information

Septrin Forte

Trimethoprim; Sulfamethoxazole

BRAND INFORMATION

Brand name

Septrin Forte

Active ingredient

Trimethoprim; Sulfamethoxazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Septrin Forte.

SUMMARY CMI

SEPTRIN Forte

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using SEPTRIN Forte?

SEPTRIN Forte contains the active ingredients trimethoprim and sulfamethoxazole. SEPTRIN Forte is used to treat a variety of bacterial infections, including bronchitis and infections of the ear, sinus, kidney, bladder, stomach, bowel, skin and wounds.

For more information, see Section 1. Why am I using SEPTRIN Forte? in the full CMI.

2. What should I know before I use SEPTRIN Forte?

Do not use if you have ever had an allergic reaction to trimethoprim and/ or sulfamethoxazole or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use SEPTRIN Forte? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SEPTRIN Forte and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use SEPTRIN Forte?

  • For adults and children over 12 years old the usual dose is one SEPTRIN Forte Tablet, twice a day.

More instructions can be found in Section 4. How do I use SEPTRIN Forte? in the full CMI.

5. What should I know while using SEPTRIN Forte?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using SEPTRIN Forte.
  • It is important that you drink plenty of fluids (water) while you are taking SEPTRIN Forte.
Things you should not do
  • Do not stop using SEPTRIN Forte just because you feel better.
  • It is important that you take the full course of SEPTRIN Forte prescribed by your doctor. This will reduce the risk of your infection recurring.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how SEPTRIN Forte affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
  • Alcohol may make you feel sick, vomit, or have stomach cramps, headaches and flushing.
Looking after your medicine
  • Keep your tablets below 30°C. Protect from light.
  • Keep your SEPTRIN Forte in the container it was supplied with.

For more information, see Section 5. What should I know while using SEPTRIN Forte? in the full CMI.

6. Are there any side effects?

Common side effects include nausea, vomiting, diarrhoea or other abdominal (gut) or stomach discomfort and inflammation of the mouth or tongue.

Serious side effects include any form of skin rash, severe fever, chills, sore throat, joint pains, cough or bruising, difficulty breathing or chest pains, severe, persistent diarrhoea, jaundice (yellowing of the skin), severe persistent headache, discolouration of urine.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

SEPTRIN Forte

Active ingredient(s): trimethoprim and sulfamethoxazole


Consumer Medicine Information (CMI)

This leaflet provides important information about using SEPTRIN Forte. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SEPTRIN Forte.

Where to find information in this leaflet:

1. Why am I using SEPTRIN Forte?
2. What should I know before I use SEPTRIN Forte?
3. What if I am taking other medicines?
4. How do I use SEPTRIN Forte?
5. What should I know while using SEPTRIN Forte?
6. Are there any side effects?
7. Product details

1. Why am I using SEPTRIN Forte?

SEPTRIN Forte contains the active ingredients trimethoprim and sulfamethoxazole. SEPTRIN Forte belongs to a group of medicines called "anti-infectives". They work in slightly different ways to stop the growth of bacteria causing the infection.

SEPTRIN Forte is used for the treatment of a variety of bacterial infections, including bronchitis and infections of the ear, sinus, kidney, bladder, stomach, bowel, skin and wounds.

2. What should I know before I use SEPTRIN Forte?

Warnings

Do not use SEPTRIN Forte if:

  • You are allergic to trimethoprim and/ or sulfamethoxazole, or any other sulfonamide (sulfur) antibiotic, or any of the ingredients listed at the end of this leaflet.
  • You have severe liver or kidney disease, any blood disorder or megaloblastic anaemia.
  • The child you are treating is under 3 months of age.
  • You have streptococcal Pharyngitis.
  • You are taking dofetilide, a medicine used to treat irregular heartbeats.
  • It passed the expiry date (EXP.) printed on the pack.
  • The packaging is torn or shows signs of tampering.

Always check the ingredients to make sure you can use this medicine.

Some of the symptoms of an allergic reaction to SEPTRIN Forte may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue which may cause difficulty in swallowing or breathing; rash, itching or hives, peeling of the skin.

Do not use SEPTRIN Forte to treat any other conditions unless advised by your doctor.

Do not give SEPTRIN Forte to anyone else, even if their symptoms seem similar to yours.

Check with your doctor if you:

  • Are allergic to trimethoprim, sulfamethoxazole or any other ingredient listed at the end of this information.
  • Are allergic to any other sulphonamide type antibiotics, any diuretics (medicines that increase the volume of your urine), or medicines for diabetes or an overactive thyroid gland.
  • Have ever had any type of liver, kidney or bladder complaint or disease (eg. hepatitis).
  • Have ever had any type of blood disorder (including porphyria and glucose-6-phosphate dehydrogenase deficiency).
  • Have asthma or an allergic disorder.
  • Have a folic acid vitamin deficiency.
  • Have phenylketonuria.
  • Suffer from alcoholism.
  • Suffer from rheumatoid arthritis.
  • Are being treated for epilepsy (fits).
  • Take any medicines for any other condition.
  • Have been diagnosed with AIDS.
    People with AIDS may not tolerate or respond to SEPTRIN in the same manner as someone who does not have AIDS. There may be an increase in the number and severity of side effects.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Paediatric Use

SEPTRIN Forte should not be used in premature babies nor during the first six weeks of life. It should probably not be given to infants less than 3 months of age.

Use in the Elderly

The use of SEPTRIN Forte in elderly patients, particularly those with a liver or kidney disease or those taking certain other medicines such as diuretics, carries an increased risk of severe adverse reactions.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with SEPTRIN Forte and affect how it works.

Below medicines may be affected by SEPTRIN Forte or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor will advise you.

  • Any malaria medicines (eg. pyrimethamine).
  • Any diabetes medicines suchas repaglinide, rosiglitazone, pioglitazone, glibenclamide, gliclazide, glipizide, chlorpropamide and tolbutamide.
  • Any diuretics (diuretics).
  • Any epilepsy (fits) medicines (eg. phenytoin, primidone and some barbiturates).
  • Any medicines used to treat infections such as rifampicin, dapsone and polymyxin.
  • Zidovudine, a medicine to treat HIV infection.
  • Ciclosporin, a medicine used to prevent organ transplant rejections or to treat certain problems with the immune system.
  • Warfarin, acenocoumarol, phenprocoumon, medicines used to thin the blood.
  • Medicines used to treat some heart conditions such as digoxin and amiodarone.
  • Amantadine, a medicine commonly used to treat the influenza virus and Parkinson's disease.
  • Memantine, a medicine used to treat Parkinson's disease.
  • Lamivudine, an antiretroviral medicine used to treat HIV/AIDS.
  • Urinary acidifiers (for kidney conditions) oral contraceptives ('the pill').
  • Sulfinpyrazone, a medicine used to treat gout.
  • Salicylates, medicines to treat conditions such as psoriasis or warts.
  • Medicines used to treat cancer such as paclitaxel, mercaptopurine and methotrexate.
  • Clozapine, a medicine used to treat schizophrenia.
  • Medicines used to treat overactive thyroid conditions.
  • Medicines used to treat depression such as imipramine, clomipramine, amitriptyline, dosulepin (dothiepin), doxepin, nortriptyline and trimipramine.
  • Immunosuppressant medicines such as azathioprine and methotrexate.
  • Medicines used to treat high blood pressure as well as a variety of heart and kidney conditions such as captopril, enalapril, lisinopril, fosinopril, perindopril, quinapril, ramipril, trandolapril, valsartan, telmisartan, irbesartan, candesartan, eprosartan, losartan, dofetilide and Olmesartan.
  • Procainamide.

Your doctor will have a complete list of the medicines that may cause problems when taken with SEPTRIN Forte.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SEPTRIN Forte.

4. How do I use SEPTRIN Forte?

How much to take

  • For adults and children over 12 years old the usual dose is one SEPTRIN Forte Tablet, twice a day.
  • Follow the instructions provided when SEPTRIN Forte was prescribed, including the number of days it should be taken.

Depending on the type of infection, and your overall health, your doctor may prescribe a different dose of SEPTRIN Forte.

How to take SEPTRIN Forte

SEPTRIN Forte Tablets should be taken with a glass of water.

Do not crush or chew the tablets.

If you forget to use SEPTRIN Forte

SEPTRIN Forte should be used regularly at the same time each day.

If you miss your dose at the usual time, if it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise take the dose that you have missed as soon as you remember, then go back to your normal schedule.

If you have forgotten to take more than one dose, contact your doctor or pharmacist.

Do not take a double dose to make up for the dose you missed.

If you use too much SEPTRIN Forte

If you think that you have used too much SEPTRIN Forte, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

If you take too much SEPTRIN Forte you may have the following symptoms: nausea, vomiting, dizziness, headache, depression and confusion. It is also possible that you will feel drowsy and you may lose consciousness.

5. What should I know while using SEPTRIN Forte?

Things you should do

It is important that you drink plenty of fluids (water) while you are taking SEPTRIN Forte.

Tell your doctor that you are taking SEPTRIN Forte before you have any blood tests.

If you are taking SEPTRIN Forte over a long period, or you have kidney problems, your doctor may ask you to undergo regular blood and urine tests.

Call your doctor straight away if you:

  • If you become pregnant while taking SEPTRIN Forte
  • If you fell the tablets is not helping your condition
  • You get severe diarrhoea, even if it occurs several weeks after stopping SEPTRIN Forte

Do not take any diarrhoea medicine without checking with your doctor.

Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care.

Remind any doctor, dentist or pharmacist you visit that you are using SEPTRIN Forte.

Things you should not do

  • Do not stop using SEPTRIN Forte just because you feel better.

It is important that you take the full course of SEPTRIN Forte prescribed by your doctor. This will reduce the risk of your infection recurring.

Things to be careful of

Sometimes use of this medicine allows other bacteria and fungi which are not sensitive to SEPTRIN Forte to grow. If other infections such as thrush occur while you are taking SEPTRIN Forte tell your doctor.

Your skin may burn more easily while you are taking SEPTRIN Forte. If outdoors, wear protective clothing or use a SPF 30+ sunscreen.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SEPTRIN Forte affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may make you feel sick, vomit, or have stomach cramps, headaches and flushing. Your doctor may suggest you avoid alcohol while being treated with SEPTRIN Forte.

Looking after your medicine

  • Keep your tablets below 30°C. Protect from light.
  • Keep your SEPTRIN Forte in the container it was supplied with.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Heat and dampness may affect this medicine.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • Nausea.
  • Vomiting.
  • Diarrhoea or other abdominal (gut) or stomach discomfort.
  • Inflammation of the mouth or tongue.
  • Oral thrush (white, furry sore tongue and mouth).
  • Vaginal thrush (sore and itchy vagina, vaginal discharge).
Speak to your doctor if you have any of these less serious side effects and they worry you.
Your doctor will need to treat the thrush infection separately.

Serious side effects

Serious side effectsWhat to do
  • Any form of skin rash
    The rash may indicate that you are allergic to SEPTRIN Forte. In very rare circumstances, patients have died from complications that may arise from certain severe allergic reactions.
  • Severe fever, chills, sore throat, joint pains, cough or bruising.
  • Difficulty breathing or chest pains.
  • Severe, persistent diarrhoea. This is particularly important if there is any blood or mucus present. It is possible for this reaction to only become apparent several weeks after taking SEPTRIN Forte.
  • Jaundice (yellowing of the skin), which is related to the function of your liver.
  • Severe persistent headache.
  • Discolouration of urine.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
Other rare side effectsWhat to do
  • Various other allergic side effects,
  • Pins and needles in the hands and feet.
  • Ringing in the ears.
  • Diarrhoea.
  • Loss of appetite.
  • Kidney damage.
  • Fits.
  • Headaches, depression, imagined sensations (hallucinations).
  • Nervousness.
  • An increase or decrease in urine production.
  • Unsteadiness.
  • Dizziness, sleeplessness, weakness, tiredness.
  • Increased sensitivity to light.
  • Respiratory toxicity (Acute Respiratory Distress Syndrome).
  • Stomach pains.
  • Uveitis (eye inflammation)
Contact your doctor as soon as possible if you have any of these rare side effects

Ask your doctor or pharmacist if you don't understand anything in this list.

Various effects on the blood, particularly in the elderly, have been attributed to the use of SEPTRIN Forte. In very rare circumstances, patients have died from some of these effects.

Having a blood test may be able to detect these effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What SEPTRIN Forte contains

Active ingredient
(main ingredient)
160 mg of trimethoprim
800 mg sulfamethoxazole
Other ingredients
(inactive ingredients)
povidone
docusate sodium
sodium starch glycollate
magnesium stearate

Do not take this medicine if you are allergic to any of these ingredients.

What SEPTRIN Forte looks like

SEPTRIN Forte Tablets are white, elliptical, biconvex, and embossed “SEPTRIN FORTE” on the upper face and the bottom face is plain and scored along the shorter axis. They are supplied in blister packs of 10 tablets.

(Aust R 10998).

Who distributes SEPTRIN Forte

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in November 2023.

Published by MIMS January 2024

BRAND INFORMATION

Brand name

Septrin Forte

Active ingredient

Trimethoprim; Sulfamethoxazole

Schedule

S4

 

1 Name of Medicine

Trimethoprim/sulfamethoxazole.

2 Qualitative and Quantitative Composition

Each Septrin Forte tablet contains 160 mg trimethoprim and 800 mg sulfamethoxazole.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Septrin Forte tablets are white, elliptical, biconvex, and embossed "Septrin Forte" on the upper face and the bottom face is plain and scored along the shorter axis.

4 Clinical Particulars

4.1 Therapeutic Indications

Upper and lower respiratory tract infections; renal and urinary tract infections; genital tract infections; gastrointestinal tract infections; skin and wound infections; septicaemias, and other infections caused by sensitive organisms.

4.2 Dose and Method of Administration

In the majority of acute infections, Septrin Forte should be given for at least 5 days or until the patient has been symptom free for 2 days.

Dosage.

Adults and children over 12 years of age.

Standard dosage: One Septrin Forte tablet every twelve hours.

Treatment of Pneumocystis jirovecii pneumonitis.

The recommended dosage for patients with documented Pneumocystis jirovecii pneumonitis is 20 mg/kg trimethoprim and 100 mg/kg sulfamethoxazole per 24 hours given in equally divided doses every 6 hours for 14 days. The aim is to obtain peak plasma or serum levels of > 5 microgram/mL (see Section 4.8 Adverse Effects (Undesirable Effects)).
Attention should be paid to the folate status of the patient should treatment be prolonged.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use.

Children under 12 years.

(See Section 4.3 Contraindications).
Alternative dosage form is available from other brands for use in children under 12 years of age.

Dosage in patients with reduced renal function.

The following dosage regimens have been published for the administration of Septrin Forte to patients with reduced kidney function. See Table 1.

4.3 Contraindications

Septrin Forte should not be given to patients with a history of sulphonamide or trimethoprim hypersensitivity.
Marked liver parenchymal damage, blood dyscrasias, megaloblastic bone marrow or severe renal insufficiency characterised by creatinine clearance < 15 mL/min (see Section 4.2 Dose and Method of Administration).
Septrin Forte should not be given to premature babies nor during the first six weeks of life, because of the risk of producing kernicterus. It should probably not be given to infants less than 3 months of age.
Septrin Forte should not be used in the treatment of streptococcal pharyngitis. Clinical studies have documented that patients with Group A Beta-haemolytic streptococcal tonsillopharyngitis have a greater incidence of bacteriologic failure when treated with Septrin Forte than do those patients treated with penicillin as evidenced by failure to eradicate this organism from the tonsillopharyngeal area.
Septrin Forte must not be given in combination with dofetilide (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Use in treatment of Pneumocystis jirovecii pneumonitis in patients with acquired immunodeficiency syndrome (AIDS).

Because of their unique immune dysfunction, AIDS patients may not tolerate or respond to Septrin Forte in the same manner as non-AIDS patients. The incidence of side effects, particularly rash, fever, and leukopenia, with Septrin Forte therapy in AIDS patients who are being treated for Pneumocystis jirovecii pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of Septrin Forte in non-AIDS patients.

Use in glucose-6-phosphate dehydrogenase deficiency.

In individuals with glucose-6-phosphate dehydrogenase deficiency haemolysis may occur. This may be dose related. Trimethoprim/sulfamethoxazole should not be given to patients with a glucose-6-phosphate dehydrogenase deficiency unless absolutely essential, and then only in minimal doses.

Pseudomembranous colitis.

The use of Septrin Forte can lead in very rare instances to the development of severe colitis as a result of colonisation with Clostridium difficile, a toxin producing organism. The colitis, which may or may not be accompanied by the formation of a pseudomembrane in the colon, can be fatal. If significant diarrhoea occurs (this may, however, begin up to several weeks after the cessation of antibiotic therapy) trimethoprim/sulfamethoxazole should be discontinued. This may be sufficient treatment in the early stages although colestyramine orally may help by binding the toxin in the colonic lumen. However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered.
Drugs which delay peristalsis (e.g. opiates and diphenoxylate with atropine, Lomotil) may prolong and/or worsen the condition and should not be used.
Fluids, electrolytes, and protein replacement therapy should be provided when indicated.
Even if an organism is sensitive to trimethoprim, if it is not sensitive to sulfamethoxazole the combination should not be used, to avoid unnecessary exposure to the potential side effects of the sulphonamide component.

Serious adverse reactions.

Fatalities, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), fulminant hepatic necrosis, agranulocytosis, aplastic anaemia and other blood dyscrasias.

Hypersensitivity and allergic reactions.

The trimethoprim/sulfamethoxazole should be discontinued if a skin rash appears. Clinical signs such as rash, sore throat, fever, arthralgia, cough, shortness of breath, pallor, purpura or jaundice may be early indications of serious reactions.
An adequate urinary output should be maintained at all times. Evidence of crystalluria in vivo is rare, although sulfonamide crystals have been noted in cooled urine from treated patients. In patients suffering from malnutrition this risk may be increased.
As with other sulfonamide preparations, critical appraisal of benefit versus risk should be made in patients with liver damage, renal damage, urinary obstruction, blood dyscrasias, allergies or bronchial asthma.
Pulmonary infiltrates reported in the context of eosinophilic or allergic alveolitis may manifest through symptoms such as cough or shortness of breath. Should such symptoms appear or unexpectedly worsen, the patient should be re-evaluated and discontinuation of trimethoprim/sulfamethoxazole therapy considered.

Long-term treatment.

If trimethoprim/sulfamethoxazole is given over a prolonged period, regular blood counts are required. If a significant reduction in count of any formed blood element is noted, Septrin Forte should be discontinued.
As with all medicines containing sulfonamides, caution is advisable in patients with porphyria or thyroid dysfunction.
Patients who are "slow acetylators" may be more prone to idiosyncratic reactions to sulfonamides.

Electrolyte abnormalities.

Close monitoring of serum potassium and renal function is warranted in patients receiving high-dose trimethoprim/sulfamethoxazole, as used in patients with Pneumocystis jirovecii pneumonia, or in patients receiving standard-dose trimethoprim/sulfamethoxazole with underlying disorders of potassium metabolism or renal insufficiency, or who are receiving drugs which induce hyperkalaemia (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Severe and symptomatic hyponatremia can occur in patients receiving Septrin Forte, particularly for the treatment of P. jirovecii pneumonia.
Evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications.
Sulfonamides, including trimethoprim/sulfamethoxazole, may induce diuresis, particularly in patients with oedema of cardiac origin.
Cross sensitivity is known to occur amongst sulfonamides (see Section 4.3 Contraindications).
Except under careful supervision, trimethoprim/sulfamethoxazole should not be given to patients with serious haematological disorders. Trimethoprim/sulfamethoxazole has been given to patients receiving cytotoxic therapy.
Because of possible interference with folate metabolism, regular blood counts are advisable in patients on long-term therapy, in those who are predisposed to folate deficiency (i.e. the elderly, chronically alcoholics and rheumatoid arthritis), in malabsorption syndromes, malnutrition states, or during the treatment of epilepsy with anticonvulsant medicines such as phenytoin, primidone or barbiturates. Changes indicative of folic acid impairment have, in certain specific situations, been reversed by folinic acid therapy.
Urine analysis and renal function tests should be performed during long-term therapy, particularly in patients with reduced renal function.
Special care should be exercised in treating elderly or suspected folate-deficient patients; folate supplementation should be considered.
The possibility of superinfection with a non-sensitive organism should be borne in mind.
Trimethoprim has been noted to impair phenylalanine metabolism in some patients.

Use in renal impairment.

In patients with renal impairment, a reduced or less frequent dosage is recommended in order to avoid accumulation of trimethoprim in the blood. Non-ionic diffusion is the main factor in the renal handling of trimethoprim, and as renal failure advances, trimethoprim excretion decreases. See the special dosage table for use in renal impairment. Patients with severe renal impairment who are receiving Septrin Forte should be closely monitored for symptoms and signs of toxicity such as nausea, vomiting and hyperkalaemia. Trimethoprim/sulfamethoxazole should be given with caution to patients with impaired renal function and to those with underlying disorders such as: possible folate deficiency; hypoglycaemia; electrolyte abnormalities (hyperkalaemia).

Patients on peritoneal dialysis.

Peritoneal dialysis results in minimal clearance of administered trimethoprim and sulfamethoxazole. Use of trimethoprim and sulfamethoxazole in patients receiving peritoneal dialysis is not recommended.

Respiratory toxicity.

Very rare, severe cases of respiratory toxicity, sometimes progressing to Acute Respiratory Distress Syndrome (ARDS), have been reported during Septrin treatment. The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological signs of pulmonary infiltrates, and deterioration in pulmonary function may be preliminary signs of ARDS. In such circumstances, Septrin should be discontinued and appropriate treatment given.

Use in the elderly.

The use of Septrin Forte in elderly patients carries an increased risk of severe adverse reactions. In rare instances fatalities have occurred. The risk of severe adverse reactions is particularly greater when complicating conditions exist, e.g. impaired kidney and/or liver function, or concomitant use of other medicines. Severe skin reactions, or generalised bone marrow suppression (see Section 4.8 Adverse Effects (Undesirable Effects)) or a specific decrease in platelets (with or without purpura) are the most frequently reported severe adverse reactions in elderly patients. In those concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. Appropriate dosage adjustments should be made for patients with impaired kidney function (see Section 4.2 Dose and Method of Administration).
In view of the increased risk of severe adverse reactions in the elderly, consideration should be given to whether Septrin Forte is the antibacterial of choice in this age group.

Paediatric use.

No data available.

Effects on laboratory tests.

Septrin Forte, specifically the trimethoprim component, can interfere with a serum methotrexate assay as determined by the competitive binding protein technique (CBPA) when a bacterial dihydrofolate reductase is used as the binding protein. No interference occurs, however, if methotrexate is measured by a radioimmunoassay (RIA).
The presence of trimethoprim and sulfamethoxazole may also interfere with the Jaffe alkaline picrate reaction assay for creatinine resulting in over-estimations of about 10% in the range of normal values.
The Lactobacillus casei serum folate assay and the L. leishmanii serum vitamin B12 assay are affected by Septrin Forte.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Trimethoprim is an inhibitor of the organic cation transporter 2 (OCT2), and a weak inhibitor of CYP2C8. Sulfamethoxazole is a weak inhibitor of CYP2C9.
Systemic exposure to drugs transported by OCT2 may increase when co-administered with trimethoprim/sulfamethoxazole. Examples include dofetilide, amantadine, memantine and lamivudine. See Tables 2 and 3.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Sulfonamides may cross the placenta and cause jaundice and haemolytic anaemia in the newborn. Sulfonamides may cause kernicterus in babies during the first month of life by displacing bilirubin from plasma albumin. Sulfonamides should therefore be avoided as far as possible during the last month of pregnancy (see Section 5.2 Pharmacokinetic Properties). Trimethoprim may interfere with folic acid metabolism and animal experiments have shown that administration of very high doses of trimethoprim during organ development may give rise to birth defects typical of folic acid antagonism. Two large observational studies have suggested a 2 to 3.5-fold increased risk of spontaneous abortion in women treated with trimethoprim alone and in combination with sulfamethoxazole during the first trimester compared to either no exposure to antibiotics or to exposure to penicillins. Septrin Forte should only be used during pregnancy if the potential benefit justifies the potential risk to the foetus. If a trimethoprim/sulfonamide combination is given during pregnancy, or if the patient becomes pregnant while taking this drug, folic acid supplementation may be requires. The patient should be appropriately counselled.
Both trimethoprim and sulfamethoxazole are excreted in breast milk at concentrations comparable or somewhat lower than that in the blood.
Although the quantity of trimethoprim/sulfamethoxazole ingested by a breast-fed infant is small, it is recommended that the possible risks should be balanced against the expected therapeutic effect (see Section 5.2 Pharmacokinetic Properties). Consideration should be made of the infant's age (see Section 4.3 Contraindications). A folate supplement may be considered with prolonged high dose of trimethoprim/sulfamethoxazole.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash (including maculopapular), pruritus and urticaria).
Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anaemia and other blood dyscrasias (see Section 4.4 Special Warnings and Precautions for Use).

Haematologic.

Agranulocytosis, aplastic anaemia, thrombocytopenia, leukopenia, neutropenia, haemolytic anaemia, autoimmune anaemia, megaloblastic anaemia, hypoprothrombinaemia, methaemoglobinaemia, eosinophilia, purpura, bone marrow depression, granulocytopenia and pancytopenia. Haematological changes have been observed particularly in the elderly. The great majority of these changes were mild, asymptomatic, and proved reversible on withdrawal of the drug which was, in some instances, necessary before therapy could be completed.
High doses of trimethoprim as used in patients with Pneumocystis jirovecii pneumonia induces progressive but reversible increase in serum potassium concentration in a substantial number of patients. Even treatment with recommended doses may cause hyperkalaemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalaemia are given concomitantly.
Cases of hyponatraemia have also been reported.

Allergic reactions.

Skin and systemic reactions may occur. Stevens-Johnson syndrome, fixed drug reaction, morbilliform rash, erythema and toxic epidermal necrolysis (Lyell's syndrome) have been reported.
The following have been reported rarely; eosinophilic or allergic alveolitis, anaphylaxis, allergic myocarditis, exfoliative dermatitis, angioedema, erythema multiforme, drug fever, chills, drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schoenlein purpura, serum sickness-like syndrome, generalised allergic reactions, photosensitivity, conjunctival and scleral injection. In addition, polyarteritis nodosa and systemic lupus erythematosus have been reported.

Congenital disorders and pregnancy, puerperium and perinatal conditions.

Spontaneous abortion.

Gastrointestinal.

Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, isolated cases of vanishing bile duct syndrome, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhoea, anorexia, moniliasis. Jaundice has occurred rarely and has usually been mild and transient, frequently occurring in patients with a past history of infectious hepatitis.

General disorders and administration site conditions.

Venous pain and phlebitis.

Genitourinary.

Renal failure, impaired renal function, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, and crystalluria.

Neurologic.

Aseptic meningitis, meningitis-like symptoms, convulsions, neuropathy (including peripheral neuritis and paraesthesia), ataxia, vertigo, tinnitus, headache, uveitis and vasculitis cerebral.

Psychiatric.

Hallucinations, depression, apathy, nervousness.

Endocrine.

The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycaemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycaemia have occurred rarely in patients receiving sulfonamides. Cases of hypoglycaemia in non-diabetic patients treated with trimethoprim/sulfamethoxazole are rarely seen, usually occurring after a few days of therapy. Patients with renal dysfunction, liver disease, malnutrition or those receiving high doses of trimethoprim/sulfamethoxazole, are particularly at risk.

Musculoskeletal.

Arthralgia, myalgia and isolated cases of rhabdomyolysis.

Respiratory.

Pulmonary infiltrates, pulmonary vasculitis.

Vascular disorders.

Vasculitis, necrotising vasculitis, granulomatosis with polyangiitis.

Eye disorders.

Very rare: uveitis.

Miscellaneous.

Weakness, fatigue, insomnia, fungal infections such as candidiasis, retinal vasculitis.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems and to also contact Arrotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

Symptoms.

Acute.

The amount of a single dose of Septrin Forte that is either associated with symptoms of overdosage or is likely to be life-threatening has not been reported. Signs and symptoms of overdosage reported with sulphonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness, and unconsciousness. Pyrexia, haematuria and crystalluria may be noted. Blood dyscrasias and jaundice are potential late manifestations of overdosage.
Signs of acute overdosage with trimethoprim include nausea, vomiting, dizziness, headache, mental depression, confusion, and bone marrow depression.

Chronic.

Use of Septrin Forte at high doses and/or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia and/or megaloblastic anaemia. Other blood dyscrasias may occur due to folinic acid deficiency.

Treatment.

Acute.

Treatment of overdose should consist of general supportive measures. General principles of treatment include the prevention of further absorption, forcing of oral fluids, and the administration of intravenous fluids if urine output is low and renal function is normal. Alkalinisation of the urine may aid the elimination of the sulfamethoxazole component of trimethoprim/sulfamethoxazole but may decrease the elimination of the trimethoprim component. The patient should be monitored with blood counts and appropriate blood chemistries including electrolytes. If a significant blood dyscrasia or jaundice occurs, specific therapy should be instituted for these complications. On cessation of therapy calcium folinate, 3 mg to 6 mg intramuscularly for five to seven days may be given to counteract the effects of trimethoprim on haematopoiesis. Peritoneal dialysis is not effective, and haemodialysis is only moderately effective in eliminating trimethoprim and sulfamethoxazole.

Chronic.

If signs of bone marrow depression occur, the patient should be given leucovorin 5 to 15 mg daily until normal haematopoiesis is restored.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Combinations of sulfonamides and trimethoprim, incl. derivatives, ATC code: J01 EE01.

Mechanism of action.

Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus, trimethoprim and sulfamethoxazole block two consecutive steps in the biosynthesis of nucleic acids and proteins essential to bacteria.

Microbiology.

Trimethoprim/sulfamethoxazole is effective against a wide range of Gram-negative and Gram-positive organisms, including: E. coli, Neisseria, Salmonella, Klebsiella, Enterobacter, Shigella, Vibrio cholerae, Bordetella pertussis, Streptococcus, Staphylococcus, Pneumococcus. Trimethoprim/sulfamethoxazole is usually active against the problem organisms Haemophilus influenzae and Proteus.
Trimethoprim/sulfamethoxazole is also active against the protozoan Pneumocystis jirovecii (see special dosage instructions).
Trimethoprim/sulfamethoxazole is not active against Mycobacterium tuberculosis and Treponema pallidum. Pseudomonas aeruginosa is frequently insensitive. See Table 4.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Trimethoprim/sulfamethoxazole is rapidly absorbed on oral administration reaching peak blood levels after 1 to 4 hours, which correspond to those achieved when each component is given alone. The mean serum half-lives of trimethoprim and sulfamethoxazole are 10 hours and 8 - 10 hours, respectively.

Distribution.

The volume of distribution of trimethoprim is about 130 litres and that of sulfamethoxazole is about 20 litres. At the above concentrations, about 42 - 45% of trimethoprim and 66% of sulfamethoxazole is bound to plasma proteins. The free forms of trimethoprim and sulfamethoxazole are considered to be the therapeutically active forms.
Studies in both animals and man have shown that diffusion of trimethoprim/sulfamethoxazole into the tissue is good. Large amounts of trimethoprim and smaller amounts of sulfamethoxazole pass from the bloodstream into the interstitial fluid and other extravascular body fluids.
In humans, trimethoprim and sulfamethoxazole were detected in the foetal placenta, umbilical cord blood, amniotic fluid and foetal tissues (liver, lung), indicating placental transfer of both drugs (see Section 4.6 Fertility, Pregnancy and Lactation).

Metabolism.

Approximately 50 - 70% of the trimethoprim dose and 10-30% are excreted unchanged. The principal trimethoprim metabolites are 1- and 3-oxides and the 3'- and 4'- hydroxyl derivatives; some metabolites are active.
Sulfamethoxazole is metabolised in the liver, predominantly by N4-acetylation and to a lesser extent by glucuronide conjugation; the metabolites are inactive.

Excretion.

The elimination half-lives of the two components are very similar (a mean of 10 hours for trimethoprim and 11 hours for sulfamethoxazole).
Both substances, as well as their metabolites, are eliminated almost entirely by the kidneys through both glomerular filtration and tubular secretion, giving urine concentrations of both active substances considerably higher than the concentration in the blood. Around two thirds of the trimethoprim dose and one quarter of the sulfamethoxazole dose are excreted unchanged into the urine. The total plasma clearance of trimethoprim equals 1.9 mL/min/kg. The total plasma clearance of sulfamethoxazole equals 0.32 mL/min/kg. A small part of the substances is eliminated via the faeces.

Pharmacokinetics in special populations.

Children and adolescents.

In children aged 1 to 9 years the total plasma clearance of trimethoprim is around three-fold larger than in adults. As a consequence the half-life of trimethoprim in children is less than half of that observed in adults. Similar observations have been made for sulfamethoxazole (see Section 4.2 Dose and Method of Administration).

Hepatic impairment.

The pharmacokinetics of trimethoprim and sulfamethoxazole in patients with moderate or severe hepatic impairment are not significantly different from those observed in healthy subjects. [See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)] for advice and experience of use in patients with impaired liver function.

Patients with cystic fibrosis.

The renal clearance of trimethoprim and the metabolic clearance of sulfamethoxazole are increased in patients with cystic fibrosis. Consequently, the total plasma clearance is increased and the elimination half-life is decreased for both drugs.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Magnesium stearate, docusate sodium (0.8 mg per tablet), sodium starch glycollate, povidone.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Protect from light.

6.5 Nature and Contents of Container

Septrin Forte tablets: Trimethoprim 160 mg and sulfamethoxazole 800 mg, white elliptical, biconvex tablet embossed "Septrin Forte" on the upper face. Bottom face plain and scored along the shorter axis. 2* or 10 tablets in blister pack PVC/PVDC/Al or 100 tablets in bottle*.
* Currently not marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Trimethoprim is a white to light yellow, odourless, bitter compound.
Sulfamethoxazole is an almost white, odourless, tasteless compound.

Chemical structure.


Chemical Name: 2,4-diamino-5-(3,4,5,trimethoxybenzyl)-pyrimidine.
Molecular Formula: C14H18N4O3.
Molecular Weight: 290.3 g/mol.

CAS number.

738-70-5.
Chemical Name: N1-(5-methyl-3-isoxazolyl) sulphanilamide.
Molecular Formula: C10H11N3O3S.
Molecular Weight: 253.28 g/mol.

CAS number.

723-46-6.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes