Consumer medicine information

Trimethoprim Viatris

Trimethoprim

BRAND INFORMATION

Brand name

Trimethoprim Viatris

Active ingredient

Trimethoprim

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Trimethoprim Viatris.

SUMMARY CMI

TRIMETHOPRIM VIATRIS

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 taking TRIMETHOPRIM VIATRIS?

TRIMETHOPRIM VIATRIS contains the active ingredient Trimethoprim. TRIMETHOPRIM VIATRIS is used to treat urinary tract infections caused by bacteria.
For more information, see Section 1. Why am I taking TRIMETHOPRIM VIATRIS? in the full CMI.

2. What should I know before I take TRIMETHOPRIM VIATRIS?

Do not use if you have ever had an allergic reaction to trimethoprim or any of the ingredients listed at the end of the CMI.
Talk to your doctor or pharmacist 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 take TRIMETHOPRIM VIATRIS? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with TRIMETHOPRIM VIATRIS 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 take TRIMETHOPRIM VIATRIS?

  • For adults and children over 12 years, the usual dose is one tablet daily. Elderly patients may need smaller doses.
  • For children 6 to 12 years, the usual dose is half a tablet daily.

More instructions can be found in Section 4. How do I take TRIMETHOPRIM VIATRIS? in the full CMI.

5. What should I know while using TRIMETHOPRIM VIATRIS?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using TRIMETHOPRIM VIATRIS.
  • Immediately stop taking TRIMETHOPRIM VIATRIS if a skin rash or any other allergic reaction occurs.
Things you should not do
  • Do not take any other medicines while you are taking TRIMETHOPRIM VIATRIS without first telling your doctor.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
Driving or using machines
  • Do not drive or operate machinery or tools until you know how TRIMETHOPRIM VIATRIS affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep your tablets in the original container they were provided in until it is time to take them.
  • Keep TRIMETHOPRIM VIATRIS below 30°C and protect from light.

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

6. Are there any side effects?

Speak to your doctor or pharmacist if you have any of these less serious side effects: nausea (feeling sick), vomiting, diarrhoea, sore tongue, stomach upset, dizziness, fainting, ringing, hissing, whistling, buzzing, or persisting noise in the ears, joint or muscle pain, nosebleeds, urticaria, skin rashes.
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: any type of skin rash which includes redness and itching, unusual bruising or bleeding, tiredness which may occur with headache, weight loss and yellowing of the eyes or skin, signs of frequent infections such as fever, chills, sore throat or mouth ulcers, swelling of the face, lips, mouth, tongue and throat, shortness of breath, wheezing or difficulty breathing, depression, hallucinations, confusion, nervousness, feeling anxious, blurred vision, redness of the eye, eye pain, increased sensitivity to light.
This is not a complete list of all possible side effects. 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

TRIMETHOPRIM VIATRIS

Active ingredient(s): trimethoprim

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I taking TRIMETHOPRIM VIATRIS?

TRIMETHOPRIM VIATRIS contains the active ingredient trimethoprim. TRIMETHOPRIM VIATRIS is an antibiotic.

TRIMETHOPRIM VIATRIS is used to treat urinary tract infections caused by bacteria. It works by stopping the growth of bacteria that are causing your infection.

Use TRIMETHOPRIM VIATRIS only as directed and consult a health care professional if pain or symptoms persist.

TRIMETHOPRIM VIATRIS will not work against infections caused by viruses, such as colds or flu.

Ask your doctor if you have any questions about why TRIMETHOPRIM VIATRIS has been prescribed for you.

Your doctor may have prescribed TRIMETHOPRIM VIATRIS for another reason.

2. What should I know before I take TRIMETHOPRIM VIATRIS?

Warnings

Do not use TRIMETHOPRIM VIATRIS if:

  • You are allergic to trimethoprim, any other antibiotics, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.
    Some of the symptoms of an allergic reaction to TRIMETHOPRIM VIATRIS may include red, itchy skin rashes, difficulty in breathing, swelling of the face, lips or throat or faintness.
  • It passed the expiry date (EXP.) printed on the pack.
  • The packaging is torn or shows signs of tampering.

Check with your doctor or pharmacist if you:

  • are allergic to any other medicines or any foods, dyes or preservatives.
  • have or have had, any medical conditions, especially the following:
    - folate deficiency.
    - kidney problems
    - liver problems.
    - porphyria.
    - any type of blood disorder.
    - take any medicines for any other condition.

If you have not told your doctor about any of the above, tell them before you start taking TRIMETHOPRIM VIATRIS.

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.

TRIMETHOPRIM VIATRIS is rated in Australia as a Category B3 drug for the use in pregnancy. Ask your doctor about the risks and benefits involved when using TRIMETHOPRIM VIATRIS during pregnancy.

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

TRIMETHOPRIM VIATRIS is able to pass into breast milk. There is a possibility that the breast-fed baby may be affected. Therefore, do not take TRIMETHOPRIM VIATRIS if you are breast-feeding or plan to breastfeed.

Paediatric use

  • TRIMETHOPRIM VIATRIS should not be administered to premature babies or infants under 4 months of age.
  • TRIMETHOPRIM VIATRIS is not recommended for use in children under the age of 6 years.
  • The safety and effectiveness of TRIMETHOPRIM VIATRIS in children under the age of 6 years has not been established.

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 be affected by TRIMETHOPRIM VIATRIS, or may affect how it works. These include:

  • pyrimethamine, a medicine used to prevent malaria
  • warfarin, a medicine used to prevent blood clots
  • coumarins
  • methotrexate, a medicine used to treat arthritis and some types of cancer
  • phenytoin, a medicine used to control epilepsy (fits or seizures)
  • digoxin, a medicine used to treat heart failure or to control a fast irregular heart beat
  • procainamide, a medicine used to correct an irregular heart beat or to slow an over active heart
  • zidovudine, zalcitabine or lamivudine; medicines used for certain viral infections
  • dapsone, a medicine used for leprosy or dermatitis herpetiformis
  • rifampicin, an antibiotic
  • ciclosporin, a medicine used to help prevent organ transplant rejection or to treat certain problems with the immune system
  • folate antagonists and anticonvulsants
  • repaglinide, used to treat diabetes
  • diuretics, also known as fluid or water tablets
  • bone marrow depressants
  • ACE inhibitors, medicines used to treat high blood pressure and some heart conditions
  • certain blood pressure medications that can increase potassium levels in the blood

The above medicines may either reduce the effectiveness of TRIMETHOPRIM VIATRIS, reduce its own effectiveness and/or react with TRIMETHOPRIM VIATRIS resulting in untoward or sometimes dangerous side effects.

This list is not exhaustive. Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking TRIMETHOPRIM VIATRIS.

Talk to your doctor about the need for additional contraception while taking TRIMETHOPRIM VIATRIS.

Some antibiotics may decrease the effectiveness of some birth control pills.

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

4. How do I take TRIMETHOPRIM VIATRIS? 

Follow all directions given to you by your doctor and pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist.

How much to take

  • Adults and children over 12 years:
    The usual dose is 1 tablet daily. Elderly patients and people with kidney problems may need smaller doses.
  • Children 6-12 years:
    The usual dose is ½ tablet daily.

Do not give TRIMETHOPRIM VIATRIS to children under the age of 6 years.

There is no information concerning the right dose for children under the age of 6 years.

Different people may respond differently to TRIMETHOPRIM VIATRIS, so your doctor may tell you to take a different dose.

Some people may need to take folate supplements while taking TRIMETHOPRIM VIATRIS. These people may include the elderly, people with folate deficiency and people taking certain medicines. Your doctor will tell you if this is necessary.

How to take TRIMETHOPRIM VIATRIS

Swallow the tablets whole with a glass of water.

TRIMETHOPRIM VIATRIS can be taken with or without food. Taking TRIMETHOPRIM VIATRIS with food will help reduce the chance of a stomach upset.

When to take TRIMETHOPRIM VIATRIS

  • TRIMETHOPRIM VIATRIS tablets are best taken before bedtime.
  • Keep taking TRIMETHOPRIM VIATRIS until you finish the pack, or for as long as your doctor recommends.
  • For most infections, TRIMETHOPRIM VIATRIS is usually taken for 7 days.
  • Do not stop taking TRIMETHOPRIM VIATRIS, even if you feel better after a few days, unless advised by your doctor.
  • Your infection may not clear completely if you stop taking your medicine too soon.

If you forget to take TRIMETHOPRIM VIATRIS

TRIMETHOPRIM VIATRIS should be used regularly at the same time each day. If you miss your dose at the usual time, take your dose as soon as you remember, and then go back to taking it as you would normally.

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

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

If you are unsure about whether to take your next dose, speak to your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you have taken too much TRIMETHOPRIM VIATRIS

If you think that you have taken too much TRIMETHOPRIM VIATRIS, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (Australia telephone 13 11 26) for advice, 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.

Also, report any other medicine or alcohol which has been taken.

If you take too much TRIMETHOPRIM VIATRIS you may have the following symptoms: nausea, vomiting, dizziness, headaches, confusion, and mental depression.

5. What should I know while using TRIMETHOPRIM VIATRIS?

Things you should do

  • Immediately stop taking TRIMETHOPRIM VIATRIS if a skin rash or any other allergic reaction occurs.
  • Use this medicine exactly as directed or as your doctor has prescribed.
  • Before starting any new medicine, tell your doctor or pharmacist that you are taking TRIMETHOPRIM.
  • If your symptoms do not improve within a few days or if they become worse, tell your doctor
  • If you have been taking TRIMETHOPRIM for a long time, visit your doctor regularly so that they can check on your progress.
  • You may need to have regular blood tests.
  • Always discuss with your doctor any problems or difficulties during or after taking TRIMETHOPRIM.

If you have been taking TRIMETHOPRIM VIATRIS for a long time, visit your doctor regularly so that they can check on your progress.

You may need to have regular blood tests.

Call your doctor straight away:

  • If you become pregnant while taking TRIMETHOPRIM VIATRIS, tell your doctor immediately.

Remind any doctor, dentist or pharmacist you visit that you are using TRIMETHOPRIM VIATRIS.

Things you should not do

  • Do not take any other medicines while you are taking TRIMETHOPRIM VIATRIS without first telling your doctor.
  • Do not use TRIMETHOPRIM to treat any other conditions unless your doctor tells you to.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how TRIMETHOPRIM VIATRIS affects you.

Drinking alcohol

Tell your doctor or pharmacist if you drink alcohol.

Looking after your medicine

  • Keep your medicine in the original container until it is time to take it.
  • Keep TRIMETHOPRIM VIATRIS below 30°C and protect from light. Follow the instructions in the carton on how to take care of your medicine properly.

Do not take TRIMETHOPRIM VIATRIS if the tablets do not look quite right.

Store TRIMETHOPRIM VIATRIS 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 can destroy some medicines.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

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 take TRIMETHOPRIM VIATRIS after the expiry date printed on the pack.

If you take this medicine after the expiry date, it may not work as well.

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.

Less serious side effects

Less serious side effectsWhat to do
  • headache
  • nausea (feeling sick), vomiting
  • diarrhoea
  • sore tongue
  • stomach upset
  • cough
  • dizziness, sleepiness, drowsiness
  • fainting
  • ringing, hissing, whistling, buzzing, or persisting noise in the ears
  • joint or muscle pain
  • nosebleeds
Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • any type of skin rash which includes itching and redness
  • unusual bruising or bleeding
  • tiredness which may occur together with headaches, sore mouth or tongue, weight loss or yellowing of the eyes or skin
  • signs of frequent infections such as fever, chills, sore throat or mouth ulcers
  • depression, hallucinations, confusion, nervousness, feeling anxious
  • signs of an allergic reaction such as itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath
  • blurred vision, redness of the eye, eye pain, increased sensitivity to light, uveitis (eye inflammation).
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.

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.

Check with your doctor as soon as possible if you have any problems while taking TRIMETHOPRIM VIATRIS even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

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.

7. Product details

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

What TRIMETHOPRIM VIATRIS contains

Active ingredient (main ingredient)Trimethoprim 300 mg each tablet
Other ingredients (inactive ingredients)Lactose monohydrate, povidone, sodium starch glycollate, purified talc, magnesium stearate.
Potential allergensLactose and traces of sulfites and galactose

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

What TRIMETHOPRIM VIATRIS looks like

TRIMETHOPRIM VIATRIS 300mg is a 9.5 mm white normal convex tablet marked "TM/300" on one side, "G" on the other (AUST R 338350).

Each pack contains 7 tablets.

Who distributes TRIMETHOPRIM VIATRIS

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in September 2024

TRIMETHOPRIM VIATRIS_cmi\Sep24/00

Published by MIMS November 2024

BRAND INFORMATION

Brand name

Trimethoprim Viatris

Active ingredient

Trimethoprim

Schedule

S4

 

1 Name of Medicine

Trimethoprim.

2 Qualitative and Quantitative Composition

Each Trimethoprim Viatris tablet contains trimethoprim 300 mg as the active ingredient.

Excipients with known effect.

Lactose and traces of sulfites and galactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Trimethoprim Viatris 300 mg tablets: 9.5 mm white, normal convex tablet marked TM/300 on one side, G on reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of acute urinary tract infections caused by sensitive organisms.

4.2 Dose and Method of Administration

Adults and children over 12 years.

One tablet daily for 7 days.

Children over 6 years.

Half a tablet daily for 7 days.

Children under 6 years.

There is no information available at present concerning the appropriate dose of trimethoprim in children under the age of 6 years.

Renal failure.

The use of trimethoprim in patients with creatinine clearance of less than 15 mL/minute is not recommended. If the creatinine clearance is between 15 and 30 mL/minute, a reduced dose should be considered.
In the treatment of acute urinary tract infection due to susceptible organisms it is not necessary to use trimethoprim for longer than 7 days.
To ensure maximal urinary concentration it may be advantageous to take the dose before bedtime. The dose may be taken with some food to minimise the possibility of gastrointestinal disturbance.

4.3 Contraindications

Trimethoprim should not be given to patients with a history of trimethoprim hypersensitivity.
Patients with severely impaired renal function (creatinine clearance less than 10 mL/min) should not be prescribed trimethoprim unless the plasma concentration of trimethoprim is monitored repeatedly during treatment.
Severe hepatic insufficiency.
Trimethoprim should not be given to patients with severe haematological disorders or documented megaloblastic anaemia due to folate deficiency.
Trimethoprim should not be administered to premature infants or children under 4 months of age.
Trimethoprim should not be administered to pregnant women and during the nursing period.

4.4 Special Warnings and Precautions for Use

Possible folate deficiency.

Care should be exercised in treating suspected folate deficient patients. Folate supplementation should be considered. Folinic acid (3-6 mg/day) as calcium folinate, may be administered without interfering with the antibacterial activity of trimethoprim, except in Enterococci infections.
Regular monthly blood counts are advisable when trimethoprim is given for long periods since there exists a possibility of symptomatic changes in haematological laboratory indices due to lack of available folate.

Electrolyte abnormalities.

Close monitoring of serum electrolytes is advised in patients at risk of hyperkalaemia. Elevations in serum potassium have been observed in some patients treated with trimethoprim. Patients at risk for the development of hyperkalaemia include older patients, those with renal insufficiency, poorly controlled diabetes mellitus, or those using concomitant potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, renin angiotensin system inhibitors (e.g. ACE inhibitors or renin angiotensin receptor blockers) or those taking other medicines that are known to increase serum potassium (e.g. heparin). If concomitant use of the above mentioned agent is deemed appropriate, monitoring of serum potassium is recommended (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

Skin rash.

Trimethoprim should be discontinued if a skin rash appears.

Porphyria.

Trimethoprim has been associated with acute attacks of porphyria and is considered unsafe in porphyria patients.
Trimethoprim has been noted to impair phenylalanine metabolism but this is of no significance in phenylketonuric patients on appropriate dietary restriction.
Rare incidents of serious hypersensitivity reactions have been reported in patients on trimethoprim therapy.
Rare incidents of trimethoprim interfering with haematopoiesis have been reported, especially when administered in large doses and/or for prolonged periods.
Monitoring of blood glucose is advised if co-administered with repaglinide (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use in hepatic impairment.

Trimethoprim should be used cautiously in patients with impaired hepatic function.

Use in renal impairment.

Trimethoprim may cause a significant, reversible increase in serum creatinine. It is unclear if this represent inhibition of tubular secretion of creatinine or genuine renal dysfunction. It should not be given in severe impairment unless blood concentrations can be monitored.
Monitoring of renal function and serum electrolytes should be considered particularly with longer term use.
Trimethoprim should only be initiated and used in dialysis patients under close supervision from specialists in both infectious disease and renal medicine.
Trimethoprim should be used cautiously in patients with impaired renal function.

Use in the elderly.

Care should be exercised in treating elderly patients.
Elderly people may be more susceptible and a lower dose may be advisable. If there is evidence of folic acid deficiency, calcium folinate should be administered and response checked by haematologic monitoring. It may be necessary to discontinue trimethoprim.

Paediatric use.

See Section 4.2 Dose and Method of Administration.
Particular care should be exercised in the haematological monitoring of children on long term therapy.

Effects on laboratory tests.

Regular monthly blood counts are advisable when trimethoprim is given for long periods since there exists a possibility of symptomatic changes in haematological laboratory indices due to lack of available folate.
Trimethoprim may cause depression of haemopoiesis.
Trimethoprim may interfere with the Jaffe alkaline picrate reaction assay for creatinine, resulting in overestimations of normal values.
Trimethoprim interferes with assays for serum methotrexate when dihydrofolate reductase from Lactobacillus casei is used in the assay.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There is the possibility of megaloblastic anaemia developing in patients prescribed trimethoprim whilst taking pyrimethamine for malarial prophylaxis.

Warfarin and other coumarins.

Trimethoprim may potentiate the anticoagulant activity of warfarin and other coumarins though the precise mechanism is unclear. Careful control of anticoagulant therapy during treatment with trimethoprim is advisable.

Phenytoin, digoxin, procainamide.

Trimethoprim may increase serum concentrations and potentiate the effect of phenytoin, digoxin and procainamide. Close monitoring of the patient's condition and serum levels is advisable.

Zidovudine, zalcitabine, lamivudine.

Trimethoprim has been reported to reduce the renal excretion and increase blood concentrations of zidovudine, zalcitabine and lamivudine.

Dapsone.

Trimethoprim and dapsone increase each other's serum concentration when given concomitantly.

Repaglinide.

Trimethoprim may enhance the hypoglycaemic effects of repaglinide.

Rifampicin.

Rifampicin may decrease the trimethoprim concentration.

Ciclosporin.

An increased risk of nephrotoxicity has been reported with use of trimethoprim or co-trimoxazole and ciclosporin.

Medicines that form cations.

When trimethoprim is administered simultaneously with medicines that form cations at physiological pH, and are also partly excreted by active renal secretion (e.g. procainamide, amantadine), there is the possibility of competitive inhibition of this process which may lead to an increase in plasma concentration of one or both of the medicines.

Diuretics.

In patients given trimethoprim who were also receiving diuretics, hyponatraemia has been reported. In elderly patients taking diuretics, particularly thiazides, there is an increased incidence of thrombocytopenia with purpura.

Folate antagonists and anticonvulsants.

Trimethoprim may induce folate deficiency in patients predisposed to folate deficiency such as those receiving concomitant folate antagonists or anticonvulsants.

Bone marrow depressants.

Use of trimethoprim with other depressants of bone marrow function may increase the likelihood of myelosuppression or bone marrow aplasia and there may be a particular risk of megaloblastic anaemia if it is given with other folate inhibitors, such as pyrimethamine or methotrexate.
Cytotoxic agents such as azathioprine, mercaptopurine and methotrexate increase the risk of haematologic toxicity when given with trimethoprim.
If trimethoprim is considered appropriate therapy in patients receiving other anti-folate drugs such as methotrexate, a folate supplement should be considered (see Section 4.4 Special Warnings and Precautions for Use).
Cases of pancytopenia have been reported in patients taking trimethoprim in combination with methotrexate. Most of these patients were on long term methotrexate therapy, and/or predisposed to folate deficiency, and none of them were reported to have received a prophylactic folinic acid supplement (see Section 4.4 Special Warnings and Precautions for Use).

ACE inhibitors.

Concomitant use of medicines known to increase serum potassium, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and potassium sparing diuretics, potassium supplements, potassium containing salt substitutes, renin-angiotensin system inhibitors (e.g. ACE inhibitors or renin angiotensin receptor blockers) and other potassium increasing substances (e.g. heparin) may result in severe hyperkalaemia. Monitoring of potassium should be undertaken as appropriate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
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.
Trimethoprim is contraindicated in pregnant women, premature infants or infants during the first few weeks of life. If trimethoprim is given during pregnancy, folic acid supplementation may be required.
 Trimethoprim is excreted in human milk. When trimethoprim is administered to a nursing mother, alternative arrangements should be made for feeding the infant.

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 a part of its registration.

4.8 Adverse Effects (Undesirable Effects)

The adverse effects encountered most often with trimethoprim are rash and pruritus. Other adverse effects reported involved the gastrointestinal and haematopoietic systems.

Dermatologic reactions.

Rash, pruritus and exfoliative dermatitis.
Rarely: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
At the recommended dose of 300 mg daily, the incidence of rash is 7.9%. These rashes were maculopapular, morbilliform, pruritic and generally mild to moderate, appearing 7 to 14 days after the initiation of therapy.
Common: urticaria, skin rashes.
Very rare: photosensitivity, fixed drug eruption, erythema nodosum, bullous dermatitis, purpura, angioedema, exfoliative dermatitis, erythema multiforme, Stevens-Johnsons syndrome, toxic epidermal necrolysis.
Unknown: pruritus.
Lyell's syndrome (toxic epidermal necrolysis) carries a high mortality.

Infections and infestations.

Common: Monilial overgrowth.

Gastrointestinal reactions.

Epigastric distress, nausea, vomiting and glossitis.
Common: diarrhoea.
Very rare: constipation, stomatitis, pseudomembranous colitis, pancreatitis.
Unknown: sore mouth.

Haematologic reactions.

Thrombocytopenia, leukopenia, neutropenia, megaloblastic anaemia and methaemoglobinaemia.
Although an effect on folate metabolism is possible, interference with haematopoiesis occurs rarely at the recommended dosage. If any such change is seen, calcium folinate may be administered. Elderly patients may be more susceptible and a lower dosage may be advisable.
Very rare: pancytopenia, bone marrow depression, agranulocytosis, aplastic anaemia, haemolytic anaemia, eosinophilia, purpura, haemolysis.
Unknown: hyperkalaemia (particularly in the elderly and in HIV patients).

Metabolism and nutritional disorders.

Hyperkalaemia, hyponatraemia.
Very rare: hypoglycaemia, anorexia.
Close supervision is recommended when trimethoprim is used in elderly patients, patients with renal impairment or patients taking high doses as these patients may be more susceptible to hyperkalaemia and hyponatraemia.

Psychiatric disorders.

Very rare: depression, hallucinations, confusional states, agitation, anxiety, abnormal behaviour, insomnia and nightmares.

Nervous system disorders.

Common: headache.
Very rare: dyskinesias, aseptic meningitis, tremor, ataxia, dizziness, lethargy, syncope, paraesthesia, convulsions, peripheral neuritis, vertigo, tinnitus.
Aseptic meningitis was rapidly reversible on withdrawal of the drug, but recurred in a number of cases on re-exposure to either co-trimoxazole or to trimethoprim alone or trimethoprim-containing agents.

Eye disorders.

Very rare: uveitis.

Respiratory, thoracic and mediastinal disorders.

Very rare: cough, shortness of breath, wheeze, epistaxis.

Musculoskeletal and connective tissue disorders.

Very rare: arthralgia and myalgia.

Renal and urinary disorders.

Very rare: impaired renal function (sometimes reported as renal failure), haematuria.
Unknown: Raised serum creatinine and blood urea nitrogen levels. It is not known however, whether this represents inhibition of creatinine tubular secretion or genuine renal dysfunction.

Immune system disorders.

Anaphylaxis and anaphylactoid reactions, hypersensitivity, angioedema, drug fever, allergic vasculitis.
Very rare: hypersensitivity, drug fever, allergic vasculitis resembling Henoch-Schoenlein purpura, periarteritis nodosa, systemic lupus erythematosus.

Miscellaneous reactions.

Fever, elevation of serum transaminases and bilirubin, increases in BUN and serum creatinine levels, abdominal cramps, stomatitis, cholestatic jaundice, hepatic necrosis.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

Acute.

Signs of acute overdosage with trimethoprim may appear following ingestion of 1 g or more of the drug and include nausea, vomiting, dizziness, headaches, mental depression, confusion and bone marrow depression (see Section 4.9 Overdose, Chronic).

Treatment.

General supportive measures and the use of activated charcoal (where physicochemical appropriate) have generally been seen as acceptable recommendations. Acidification of the urine will increase renal elimination of trimethoprim. Peritoneal dialysis is not effective and haemodialysis only moderately effective in eliminating the drug.

Chronic.

Use of trimethoprim at high doses and/or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia and/or megaloblastic anaemia. If signs of bone marrow depression occur, trimethoprim should be discontinued and the patient should be given folinic acid as calcium folinate, 3 to 6 mg intramuscularly daily for three days, or as required to restore normal haematopoiesis.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Trimethoprim is a synthetic antibacterial.
Trimethoprim blocks the formation of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the enzyme dihydrofolate reductase. Its affinity for the bacterial dihydrofolate reductase enzyme is much stronger than for the corresponding mammalian enzyme. Thus, trimethoprim selectively interferes with bacterial biosynthesis of nucleic acids and proteins.
Trimethoprim is an active in vitro against the common urinary tract pathogens.
Representative minimum inhibitory concentrations (MIC) for trimethoprim in susceptible organisms are shown in Table 1.
It is not active against Pseudomonas spp.
Normal vaginal and faecal flora are the source of most pathogens causing urinary tract infections. It is therefore relevant to consider the suppressive effect of trimethoprim at these sites.
Concentrations of trimethoprim in vaginal secretions are consistently greater than those found simultaneously in the serum, being typically 1.6 times the concentration of simultaneously obtained serum samples.
Sufficient trimethoprim is excreted in the faeces to markedly reduce or eliminate trimethoprim susceptible organisms from the faecal flora.
In vitro resistance develops rapidly when susceptible bacteria are passed through increasing concentrations of the drug. However, following clinical use there have been conflicting reports on the development of resistance to trimethoprim when used alone. The possibility of increasing resistance to trimethoprim cannot at present be ruled out. Generally, resistance is more likely to occur in hospital than in domiciliary use. Plasmid mediated as well as chromosomal resistance to trimethoprim have been reported.
Microbiology, susceptibility tests.

Dilution or diffusion techniques.

Either quantitative (MIC) or breakpoint should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Immediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applications in body sites where the drug is physiologically concentrated or in situations where high dosage of the drug is used. This category also provides a buffer zone, which prevents small-uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable; other therapy should be selected.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Trimethoprim is rapidly absorbed following oral administration.

Distribution.

Approximately 44% of the drug is protein bound in the blood.

Metabolism.

Time to peak concentration in the circulation occur about 0.6 to 4 hours after an oral dose. Food decreases the area under the plasma concentration-time curve by approximately 20%. The half-life of trimethoprim ranges from 8 to 12 hours in the presence of normal renal function.

Excretion.

In subjects receiving a single dose of 100 mg trimethoprim, the urinary concentration ranged from 30 to 160 microgram/mL, zero to 4 hours after the dose, and from 18 to 90 microgram/mL 8 to 24 hours after the dose. Increasing the dose of trimethoprim to 200 mg will double the urinary concentration.
Elimination is delayed in patients with renal insufficiency. The use of trimethoprim in patients with a creatinine clearance of less than 15 mL/minute is not recommended.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Trimethoprim Viatris tablets contain the following inactive ingredients: lactose monohydrate, povidone, sodium starch glycollate, purified talc and magnesium stearate.

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.

6.5 Nature and Contents of Container

Container type: PVC/PVDC/Al blister pack of 7 tablets.

Australian register of therapeutic goods (ARTG).

AUST R 338350 - Trimethoprim Viatris trimethoprim 300 mg tablet blister pack.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

5-(3,4,5-trimethoxybenzyl)-pyrimidine-2, 4-diamine.
Structural formula:
Molecular formula: C14H18N4O3.
Molecular weight: 290.3.

CAS number.

738-70-5.
Melting point about 200°C. Solubility 1:2500 of water, 1:300 in ethanol (96%), 1:55 of chloroform and 1:80 of methyl alcohol.
It is a white, or yellowish-white powder, odourless or almost odourless. Practically insoluble in ether.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes