Consumer medicine information

Resprim; Resprim Forte

Sulfamethoxazole; Trimethoprim

BRAND INFORMATION

Brand name

Resprim, Resprim Forte

Active ingredient

Sulfamethoxazole; Trimethoprim

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Resprim; Resprim Forte.

What is in this leaflet

This leaflet answers some common questions about Resprim.

It does not contain all of 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 Resprim against the benefits they expect it will have 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 Resprim is used for

Resprim contains the active ingredients sulfamethoxazole and trimethoprim, also known as co-trimoxazole.

Resprim is used to treat infections in different parts of the body caused by bacteria.

Resprim belongs to a group of medicines called antibiotics. There are many different types of medicines used to treat bacterial infections. Sulfamethoxazole in Resprim belongs to a group of medicines known as sulfonamides. Trimethoprim belongs to a group of medicines known as the benzylpyrimidines.

Resprim works by stopping the growth of the bacteria that is causing your infection.

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

Resprim has been prescribed for your current infection. Another infection later on may require a different medicine.

Your doctor may have prescribed Resprim for another reason.

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

Resprim is available only with a doctor's prescription.

Before you take Resprim

When you must not take it

Do not take Resprim if :

  • you have had an allergic reaction to trimethoprim, sulfamethoxazole or any other sulfonamide (sulfur) antibiotic, or any of the ingredients listed at the end of this leaflet
Some of the symptoms of an allergic reaction may include:
- shortness of breath
- wheezing or difficulty breathing
- swelling of the face, lips, tongue or other parts of the body
- rash, itching or hives, peeling of the skin.
  • 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

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

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 pregnant or intend to become pregnant.
    If Resprim is taken late in pregnancy, it may harm the baby.
    Your doctor will discuss the risks and benefits of taking Resprim during pregnancy.
  • you are breastfeeding or wish to breastfeed.
    Resprim passes into breast milk. Your doctor will discuss the risks and benefits of taking Resprim when breastfeeding.
  • you have any medical conditions, especially the following:
you are allergic to:
- diuretics (fluid tablets)
- medicines used to treat diabetes
- medicines for an overactive thyroid.
You may have an increased chance of being allergic to Resprim if you are allergic to these medicines.
  • any type of blood disorder (including porphyria and glucose-6-phosphate dehydrogenase deficiency)
  • liver or kidney disease
  • a hereditary disorder called phenylketonuria
  • epilepsy (fits or convulsions)
  • asthma
  • allergic disorders
  • rheumatoid arthritis
  • urinary obstruction.
  • folic acid deficiency

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

If you have not told your doctor about any of the above, tell him/her before you start taking Resprim.

Taking other medicines

Tell your doctor or pharmacist 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 and Resprim may interfere with each other. These include:

  • medicines used to treat diabetes, such as repaglinide, rosiglitazone, pioglitazone, glibenclamide, gliclazide, glipizide, chlorpropamide and tolbutamide
  • diuretics (fluid tablets)
  • phenytoin, a medicine used to treat epilepsy
  • pyrimethamine, a medicine used to prevent malaria
  • other 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, a medicine used to prevent blood clots
  • 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
  • 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.

These medicines may be affected by Resprim 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 and pharmacist have more information on medicines to be careful with or avoid while taking Resprim.

Use in very young children

Resprim should not be given to children under 12 years of age. Alternative dosage form of trimethoprim and sulfamethoxazole is available from other brands for children from 3 months to 12 years of age.

Use in People Over 65 Years

People over 65 years are more at risk of severe side effects when taking Resprim. The risk is greater if you have kidney or liver disease or are taking some types of other medicines, such as diuretics.

Use in People with HIV infection

People with HIV infection have been reported to get more side effects while being treated with Resprim than people without HIV.

How to take Resprim

Follow all directions given to you by your doctor or 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 for help.

How much to take

Take Resprim exactly as your doctor has prescribed. Your doctor will tell you how much Resprim to take each day.

The dose and length of time you have to take Resprim will depend on the type of infection you have.

The usual dose for adults and children over 12 years is one Resprim Forte tablet (or two Resprim tablets) twice a day.

How to take it

Swallow the tablets with a glass of water.

When to take it

Take Resprim after food. This will lessen the chance of a stomach upset.

How long to take it

Continue taking Resprim for as long as your doctor recommends.

Do not stop taking Resprim, 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 it

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 medicine as you would normally.

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

If you are not sure what to do, ask your doctor or pharmacist.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much Resprim. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Resprim, you may feel sick, vomit, feel dizzy, depressed or confused or have a headache.

Keep telephone numbers for these places handy.

If you are not sure what to do, contact your doctor or pharmacist.

While you are taking Resprim

Things you must do

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

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

If you become pregnant while taking Resprim, tell your doctor.

Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Drink plenty of fluids while you are taking Resprim. This will help to flush the medicine through your system.

If you are taking Resprim for a long time, visit your doctor regularly so your progress can be checked. Your doctor may ask you to have regular tests to check your kidneys, liver or blood.

If you are taking Resprim for a long time, visit your doctor regularly so that they can check on your progress. You may need to have tests to check your blood, liver and kidneys.

If you have to have any blood tests, tell your doctor that you are taking Resprim. Resprim may affect the results of some tests.

Tell your doctor or pharmacist immediately if you get severe diarrhoea, even if it occurs several weeks after stopping Resprim. 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.

Things you must not do

Do not stop taking Resprim or change the dose without first checking with your doctor.

Do not let yourself run out of medicine over the weekend or on holidays.

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

Do not take Resprim to treat any other complaints unless your doctor tells you to.

Do not take any other medicines whether they require a prescription or not without first telling your doctor or consulting with a pharmacist.

Things to be careful of

Be careful driving or operating machinery until you know how Resprim affects you.

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

Be careful drinking alcohol while taking Resprim. Combining Resprim and alcohol can make you feel sick, vomit, or have stomach cramps, headaches and flushing. Your doctor may suggest you avoid alcohol while being treated with Resprim.

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

Use in people with HIV infection:
People with HIV infection may not respond to Resprim in the same way as people without HIV, and have been reported to get more side effects.

Side effects

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

While you are taking Resprim

Resprim treats infections in most people, 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.

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

If side effects do occur, they may be:

  • nausea, with or without vomiting
  • diarrhoea or other abdominal (gut) or stomach discomfort

These side effects are not usually serious or long lasting.

Tell your doctor if you notice these side effects and they worry you:

  • oral thrush (white, furry sore tongue and mouth)
  • vaginal thrush (sore and itchy vagina, vaginal discharge).

Your doctor will need to treat the thrush infection separately.

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

  • jaundice (yellowing of the eyes or skin)
  • severe or watery diarrhoea
  • any type of skin rash, peeling of the skin, severe itching or hives
  • fever, sore throat, lumps in the neck
  • cough, shortness of breath
  • severe persistent headache
  • discolouration of urine
  • swelling of the face and throat

These symptoms are usually rare but may be serious and need urgent medical attention.

Very rarely, people have died from complications due to certain severe skin, liver and blood reactions.

Elderly people, people with liver or kidney disease and people taking certain other medicines are more at risk of these severe reactions.

Other rare side effects include:

  • other allergic reactions
  • pins and needles in the hands & feet.
  • Loss of appetite, fits, headaches, depression, imagined sensations or nervousness
  • Increased or decreased urine production
  • Unsteadiness or dizziness
  • Sleeplessness, weakness, tiredness, increased sensitivity to light and stomach pains

If you experience any of these effects contact your doctor as soon as possible.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

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

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

After using Resprim

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

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

Do not store Resprim or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep Resprim 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.

Disposal

If your doctor tells you to stop taking Resprim, or your medicine has passed its expiry date, ask your pharmacist what to do with any that is left over.

Product description

What it looks like

Resprim tablets come in two strengths:

  • Resprim - round, white tablet marked 80|400 on one side and R on the other side
  • Resprim Forte - oblong, white tablet marked 160|800 on one side and RF on the other side.

Each blister pack contains 10 tablets.

Ingredients

The active ingredients in Resprim tablets are trimethoprim and sulfamethoxazole:

  • each Resprim tablet contains 80 mg of trimethoprim and 400 mg of sulfamethoxazole
  • each Resprim Forte tablet contains 160 mg of trimethoprim and 800 mg of sulfamethoxazole

Resprim and Resprim Forte tablets contain the following inactive ingredients:

  • povidone
  • docusate sodium
  • sodium starch glycollate
  • magnesium stearate.

Resprim and Resprim Forte tablets contain sulfites.

The tablets are gluten free.

Supplier

Resprim is supplied by:

Alphapharm Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:

Resprim - AUST R 17681

Resprim Forte - AUST R 17682

This leaflet was prepared in
December 2019.

Resprim_cmi\Dec19/00

Published by MIMS February 2020

BRAND INFORMATION

Brand name

Resprim, Resprim Forte

Active ingredient

Sulfamethoxazole; Trimethoprim

Schedule

S4

 

1 Name of Medicine

Sulfamethoxazole/trimethoprim.

6.7 Physicochemical Properties

Sulfamethoxazole is a white or almost white, odourless crystalline powder. It is practically insoluble in water, sparingly soluble in ethanol (96%), freely soluble in acetone, slightly soluble in chloroform and in ether. It dissolves in dilute solutions of sodium hydroxide. Melting point: 167°C to 172°C.
Trimethoprim is a white or yellowish white powder, odourless or almost odourless. It is very slightly soluble in water, slightly soluble in ethanol (96%), sparingly soluble in chloroform, practically insoluble in ether. Melting point: 199°C to 203°C.
Active ingredient: sulfamethoxazole. Chemical name: 4-amino-N- (5-methylisoxazol-3-yl) benzenesulphonamide. Molecular formula: C10H11N3O3S. Molecular weight: 253.3.
Active ingredient: trimethoprim. Chemical name: 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine. Molecular formula: C14H18N4O3. Molecular weight: 290.3.

Chemical structure.


CAS number.

Sulfamethoxazole: 723-46-6.
Trimethoprim: 738-70-5.

2 Qualitative and Quantitative Composition

Each Resprim tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim as the active ingredients.
Each Resprim Forte tablet contains 800 mg of sulfamethoxazole and 160 mg of trimethoprim as the active ingredients.
Resprim and Resprim Forte tablets contain sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Resprim.

Sulfamethoxazole 400 mg with trimethoprim 80 mg tablet: white, scored, marked 80/400 on one side, R on reverse.

Resprim Forte.

Sulfamethoxazole 800 mg with trimethoprim 160 mg tablet: white, biconvex, elongated, marked 160/800 on one side, RF on reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

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, 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.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.3 Contraindications

Trimethoprim/sulfamethoxazole is contraindicated in patients showing 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).
Trimethoprim/sulfamethoxazole should not be given to patients with a history of hypersensitivity to the active ingredients or the excipients, or other sulfonamides.
Trimethoprim/sulfamethoxazole 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.
Trimethoprim/sulfamethoxazole should not be used in the treatment of streptococcal pharyngitis. Clinical studies have documented that patients with group A β-haemolytic (Sp.) streptococcal tonsillopharyngitis have a greater incidence of bacteriologic failure when treated with trimethoprim/sulfamethoxazole than do those patients treated with penicillin as evidenced by failure to eradicate this organism from the tonsillopharyngeal area.
Trimethoprim/sulfamethoxazole 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 affected patients may not tolerate or respond to trimethoprim/sulfamethoxazole in the same manner as non-AIDS affected patients. The incidence of side effects, particularly rash, fever and leucopenia, with trimethoprim/sulfamethoxazole therapy in AIDS affected 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 trimethoprim/sulfamethoxazole in non-AIDS affected patients.

Use in glucose-6-phosphate dehydrogenase deficiency.

In glucose-6-phosphate dehydrogenase deficient individuals, 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 Resprim 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 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 sulfonamide 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), 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, Resprim 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 Resprim, 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 Resprim 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.

Use in the elderly.

The use of trimethoprim/sulfamethoxazole in elderly patients carries an increased risk of severe adverse effects. In rare instances, fatalities have occurred. The risk of severe adverse effects 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 effects in the elderly, consideration should be given to whether trimethoprim/sulfamethoxazole is the antibacterial of choice in this age group.

Paediatric use.

No data available.

Effects on laboratory tests.

Two laboratory procedures, namely the Lactobacillus casei serum folate assay and the L. leishmanii serum vitamin B12 assay are affected by trimethoprim/sulfamethoxazole.
Trimethoprim/sulfamethoxazole, 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 overestimations of about 10% in the range of normal values.

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 coadministered 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. Resprim 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 required. 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 breastfed 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.

4.8 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-Schonlein 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 nondiabetic 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.

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

4.2 Dose and Method of Administration

In acute infections, trimethoprim/sulfamethoxazole should be given for at least 5 days or until the patient has been symptom free for 2 days.

Adults and children over 12 years.

Standard dosage.

2 Resprim tablets or 1 Resprim Forte tablet every 12 hours.

For severe infections.

3 Resprim tablets or 1½ Resprim Forte tablets every 12 hours. This is the maximum daily dosage.
The recommended dose 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 six hours for 14 days.
Attention should be paid to the folate status of the patient should treatment be prolonged.

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.

Patients with reduced renal function.

The following dosage regimens are based on published information for the administration of trimethoprim/sulfamethoxazole to patients with reduced renal function (see Table 1).

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.

4.9 Overdose

Acute.

Symptoms.

The amount of a single dose of trimethoprim/sulfamethoxazole 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 sulfonamides 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.

Treatment.

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.

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

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Resprim and Resprim Forte tablets contain the following inactive ingredients: povidone, docusate sodium, sodium starch glycollate, 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

Resprim.

Blister pack (Al/PVC/PVDC) of 10* tablets. Blister pack (Al/PVC/PVDC) of 20 and 30 tablets for hospital only; Bottle (HDPE) of 10, 20 and 30 tablets.

Resprim Forte.

Blister pack (Al/PVC/PVDC) of 10* and 100 tablets for hospital only; Bottle (HDPE) of 4, 10 and 500 tablets.
Some pack sizes and/or pack types may not be marketed.
* Currently marketed in Australia.

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.

Summary Table of Changes