Consumer medicine information

Alprim

Trimethoprim

BRAND INFORMATION

Brand name

Alprim

Active ingredient

Trimethoprim

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Alprim.

What is in this leaflet

This leaflet answers some common questions about ALPRIM.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking ALPRIM against the benefits expected for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What ALPRIM is used for

ALPRIM contains the active ingredient called trimethoprim which belongs to a group of medicines called antibiotics. ALPRIM is used to treat urinary tract infections caused by bacteria. It works by stopping the growth of the bacteria that is causing your infection.

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

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

Ask your doctor if you have any questions about why ALPRIM has been prescribed for you. Your doctor may have prescribed ALPRIM for another reason.

ALPRIM is available only with a doctor's prescription.

ALPRIM should not be administered to premature babies or infants under 4 months of age.

ALPRIM is not recommended for use in children under 6 years of age, as the safety and effectiveness of ALPRIM in this age group has not been established.

Before you take ALPRIM

When you must not take it

Do not take ALPRIM if you are allergic to any other medicines containing trimethoprim or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include red, itchy skin rashes, itching or hives; swelling of the face, lips, throat, or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath; faintness.

Do not take ALPRIM if you have:

  • a severe blood disorder or anaemia
  • severe kidney problems.

Do not take ALPRIM after the expiry date (EXP) printed on the pack. If you take this medicine after the expiry date, it may not work as well.

Do not take ALPRIM if the packaging is torn or shows signs of tampering or the tablets do not look quite right.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. ALPRIM is rated in Australia as a Category B3 drug for use in pregnancy. Ask your doctor about the risks and benefits of taking ALPRIM during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed.

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

Tell your doctor if you have, or have had, any medical conditions, especially the following:

  • folate deficiency
  • kidney problems
  • liver problems
  • porphyria
  • any type of blood disorder.

Your doctor may want to take special care if you have any of these conditions.

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

Taking other medicines

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

Some medicines may be affected by ALPRIM, or may affect how well 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
  • cyclosporine, a medicine used to help prevent organ transplant rejection or to treat certain problems with the immune system
  • repaglinide, used to treat diabetes
  • diuretics, also known as fluid or water tablets
  • 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
  • Folate antagonists and anticonvulsants

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. This list is not exhaustive. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking ALPRIM.

Talk to your doctor about the need for additional contraception while taking ALPRIM. Some antibiotics may decrease the effectiveness of some birth control pills.

Tell your doctor or pharmacist that you are taking ALPRIM before you start taking any other medicine.

How to take ALPRIM

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

For adults and children over 12 years, the usual dose is one tablet daily.

For children 6 to 12 years, the usual dose is half a tablet daily.

Do not give ALPRIM to children under the age of 6 years. There is no information concerning the right dose for children under the age of 6 years.

The elderly and people with kidney problems may need smaller doses.

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

Some people may need to take folate supplements while taking ALPRIM. 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 ALPRIM

Swallow the tablets whole with a glass of water.

When to take ALPRIM

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

ALPRIM tablets are best taken before bedtime.

How long to take ALPRIM for

Keep taking ALPRIM until you finish the pack, or for as long as your doctor recommends.

For most infections, ALPRIM is usually taken for 7 days.

Do not stop taking ALPRIM, 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 ALPRIM

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 missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

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 not sure what to do or have any questions, ask your doctor or pharmacist.

If you take too much ALPRIM (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much ALPRIM.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much ALPRIM, you may experience the following: nausea, vomiting, dizziness, headaches, confusion or mental depression.

While you are taking ALPRIM

Things you must do

Immediately stop taking ALPRIM if skin rash or any other allergic reaction occurs.

Before starting any new medicine, tell your doctor or pharmacist that you are taking ALPRIM.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking ALPRIM.

If you become pregnant while taking ALPRIM, tell your doctor immediately.

If your symptoms do not improve within a few days, or if they become worse, tell your doctor.

If you are taking ALPRIM 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 ALPRIM.

Things you must not do

Do not take any other medicines while you are taking ALPRIM without first telling your doctor.

Do not drive or operate machinery until you know how ALPRIM affects you.

Do not use ALPRIM to treat any other conditions unless your doctor tells you to.

Do not give ALPRIM to anyone else, even if they have the same condition as you.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking ALPRIM.

ALPRIM helps most people with urinary tract infections, but it may have unwanted side effects in some people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • epigastric distress
  • headache
  • stomach upset
  • nausea (feeling sick), vomiting
  • vomiting.
  • glossitis
  • diarrhoea.
  • sore tongue.
  • cough
  • difficult sleeping
  • dizziness, sleepiness, drowsiness
  • fainting
  • ringing, hissing, whistling, buzzing, or persisting noise in the ears
  • joint or muscle pain
  • nosebleeds

The above list includes the milder side effects of your medicine.

See your doctor immediately if you notice any of the following:

  • 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
  • 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.

The above list includes serious side effects which may require medical attention.

See your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • 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
  • pink or red itchy spots on the skin which may blister and progress to form raised, red, pale-centred marks
  • redness, blistering, peeling or loosening of skin; bleeding of the lips, eyes, mouth, nose and genitals
  • severe rash with skin peeling, fever, chills and aching muscles
  • blurred vision, redness of the eye, eye pain, increased sensitivity to light, uveitis (eye inflammation).

The side effects listed above are rare but serious and require urgent medical attention or hospitalisation.

Tell your doctor if you notice anything that is making you feel unwell.

This is not a complete list of all possible side effects.

Other side effects not listed above may also occur in some people.

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

After taking ALPRIM

Storage

Keep ALPRIM where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your tablets in a cool dry place where the temperature stays below 30°C and protect from light.

Do not store ALPRIM or any other medicine in the bathroom or near a sink.

Do not leave ALPRIM in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking ALPRIM, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

ALPRIM is a 9.5 mm white normal convex tablet marked "TM/300" on one side, "G" on the other.

Each pack contains 7 tablets.

Ingredients

The active ingredient in ALPRIM is trimethoprim.

Each ALPRIM tablet contains 300 mg of trimethoprim.

The tablets also contain the following inactive ingredients:

  • lactose monohydrate
  • povidone
  • sodium starch glycollate
  • purified talc
  • magnesium stearate.

ALPRIM tablets contain lactose and traces of sulfites and galactose.

Manufacturer

ALPRIM is made in Australia by:

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

Australian Registration Number:

ALPRIM 300 mg - AUST R 63518

This leaflet was prepared in December 2023.

ALPRIM_cmi\Dec23/00

Published by MIMS February 2024

BRAND INFORMATION

Brand name

Alprim

Active ingredient

Trimethoprim

Schedule

S4

 

1 Name of Medicine

Trimethoprim.

2 Qualitative and Quantitative Composition

Each Alprim 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

Alprim 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 Alprim 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 Alprim 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

Alprim 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 Alprim unless the plasma concentration of trimethoprim is monitored repeatedly during treatment.
Severe hepatic insufficiency.
Alprim 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 Alprim 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 Alprim 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 Alprim 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 reexposure 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

Alprim 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 63518 - Alprim 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