New Zealand - English - Medsafe (Medicines Safety Authority)
NEW ZEALAND DATA SHEET
Deprim oral suspension, sulfamethoxazole 200mg and trimethoprim 40mg per 5mL.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Deprim contains 200 mg Sulfamethoxazole and 40 mg trimethoprim per 5 mL.
Excipients with known effect:
For the full list of excipients, see section 6.1.
Deprim Suspension is a pink, raspberry flavoured suspension containing 200 mg Sulfamethoxazole
and 40 mg trimethoprim per 5 mL.
Deprim has a broad spectrum of antibacterial activity and may be indicated for the following:
Gastrointestinal tract infections:
Treatment of cholera as an adjunct to fluid and electrolyte replacement when the organism
has been shown to be sensitive in vitro
Treatment of Shigellosis (may be less effective in some parts of the world due to resistant
Treatment of travellers’ diarrhoea including gastroenteritis due to enterotoxigenic E. coli
Genital tract infections:
Treatment of gonorrhoea including oro-pharyngeal and ano-rectal infection
Treatment of chancroid (may be less effective in some parts of the world due to resistant
Treatment of ganuloma inguinale (venereum)
Urinary tract infections:
Treatment of acute uncomplicated urinary tract infections. It is recommended that initial episodes
of uncomplicated urinary tract infections be treated with a singleeffective antibacterial agent rather
than the combination.
Respiratory tract infections:
administration in otitis media
Treatment of acute exacerbations of chronic bronchitis
Treatment and prevention of Pneumocystis jirovecii
Treatment and prophylaxis of toxoplasmosis
Treatment of nocardosis
There are a number of other bacterial conditions caused by sensitive organisms for which treatment
with Deprim may be appropriate. The use of Deprim should be based on clinical experience and
local in vitro data.
Deprim should only be used where in the judgement of the physician the benefits of the treatment
outweigh any possible risks. Consideration should be given to the use of a single effective
The in vitro susceptibility of bacteria to antibiotics varies geographically and with time. The local
situation should always be considered when selecting antibiotic therapy.
Dose and method administration
Deprim should be administered at 12 hourly intervals, ideally after the morning and evening meals.
Maintenance of an adequate fluid intake is essential. Deprim may be used in children and in adults
who are unable to take co-trimoxazole tablets.
Deprim should be administered for at least 5 days or until the patient remains symptom free for at
least 2 days. If clinical improvement is not evident after 7 days therapy, the patient should be
For acute uncomplicated lower urinary tract infections short term therapy of 1-3 days has been
shown to be effective.
The following table indicates standard dosage:
Care is recommended because as a group, elderly patients are more susceptible to adverse reactions
and more likely to suffer serious effects as a result, particularly when complicating conditions exist
e.g. impaired kidney and/or liver functions and/or concomitant use of other medications.
Impaired renal function:
The dosage schedule used should reflect the creatinine clearance rate. The following table indicates
dosing schedule suitability for varying rates of renal impairment in adults and children aged over
12 years (no information is available for children under 12 years)
Measurements of plasma concentration of Sulfamethoxazole at intervals of 2 to 3 days are
recommended in samples obtained 12 hours after administration of Deprim. If the concentration of
the total Sulfamethoxazole exceeds 150 micrograms/mL then treatment should be interrupted until
the value falls below 120 micrograms/mL.
A higher dosage is recommended using 20 mg trimethoprim and 100 mf sulfamethoxazole (2.5 mL)
per kilogram bodyweight per day taken in two or more divided doses for 2 weeks. Peak plasma
levels of 5 mcg/mL are required.
Prevention for Adults: Use one of the following dosage schedules:
Standard dose (20 mL) daily 7 days per week
Standard dose (20 mL) 3 times per week on alternate days
Twice the standard dose (40 mL) per day in two divided doses three times per week on alternate
The total daily dose should not exceed 320 mg trimethoprim and 1600 mg sulfamethoxazole (40
Prevention for Children under 12 years of age: Use one of the following dose schedules for the
duration of the period at risk –
Standard dose taken in 2 divided doses 7 days per week
Standard dose taken in 2 divided doses three times per week on alternate days
Standard dose taken in 2 divided doses three times per week on consecutive days
Standard dosage taken as a single dose three times per week on consecutive days.
The total daily dose should not exceed 320 mg trimethoprim and 1600 mg sulfamethoxazole (40
For uncomplicated cases 40 mL every 12 hours for two days, or 50 mL followed by a further 50
mL eight hours later, or 100 mL once daily for three days. A single dose of 80 mL taken under
supervision can be used if patient compliance is not expected.
Oro-pharyngeal gonococcal infection: 20 mL three times a day for 7 days.
Ano-rectal gonorrhoea: The standard dosage recommendations for gonorrhoea are
20 mL twice daily for 7 days. If there is no evidence of healing after 7 days a further 7 days treatment
can be considered. However it should be kept in mind that failure to respond may indicate that the
disease is caused by a resistant organism.
20 mL twice daily for up to 2 weeks.
There is no consensus on the most appropriate dosage. Adult doses of 60 to 80 mL daily have been
There is no consensus on appropriate dosage for the treatment or prophylaxis of this disease. The
decision should be based on clinical experience. For prophylaxis, the dosages suggested for the
prevention of Pneumocystis jirovecii may be appropriate.
Hypersensitivity to trimethoprim, sulphonamides or co-trimoxazole
With a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or
Premature babies or full term infants in the neonatal period
Severe renal insufficiency where repeated measurements of the plasma concentration cannot be
Patients showing marked liver parenchymal damage
Patients with severe haematological disorders unless under careful supervision. Co-trimoxazole
has been given to patients receiving cytotoxic therapy with little or no additional effect on the
bone marrow or peripheral blood.
Special warnings and precautions for use
Sulfamethoxazole/trimethoprim-induced thrombocytopenia may be an immune-mediated disorder.
Fatalities, although rare, have occurred due to severe reactions including, Lyell syndrome (toxic
epidermal necrolysis), Stevens-Johnson syndrome, agranulocytosis,
fulminant hepatic necrosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the
There is an increased risk of severe adverse reactions in elderly patients or when complicating
conditions exist e.g. impaired kidney and/or liver function or concomitant use of other medicines.
Regular blood counts are advisable for patients receiving long term Deprim therapy to monitor any
asymptomatic changes in haematological properties that could develop from folate deficiency. Most
haematological disorders resulting from folate deficiency respond to administration of calcium
folinate or removal of Deprim treatment.
An adequate urinary output must be maintained at all times especially when malnutrition is
suspected. Urine samples should be inspected routinely to prevent the development of crystalluria.
The appearance of skin rashes, particularly in elderly patients, warrants the immediate removal of
Folate deficiency: A suitable folic acid supplement should be considered when treating elderly
patients, patients with suspected folate deficiencies, and patients receiving prolonged high doses of
A suitable folate supplement should be considered when treating elderly patients, patients with
suspected folate deficiencies, and patients receiving prolonged high doses of Deprim.
Trimethoprim impairs phenylalanine metabolism, but this has been demonstrated to be of no
clinical significance to phenylketonuric patients with appropriate dietary restrictions.
Deprim should be given with caution to patients with severe allergy or bronchial asthma.
Haemolysis may occur in glucose-6-phosphate dehydrogenase deficient (G-6-PD) patients.
Deprim should not be used in the treatment of streptococcal pharyngitis due to Group A beta-
haemolytic streptococci – penicillin is more effective in eradicating these organisms from the
The administration of Deprim to patients known or suspected to be at risk of acute porphyria should
exacerbation of porphyria.
Close monitoring of serum potassium is warranted in patients at risk of hyperkalaemia.
Interaction with other medicines and other forms of interaction
In elderly patients concurrently receiving diuretics, mainly thiazides, there appears to be an
increased risk of thrombocytopenia with or without purpura.
Occasional reports suggest that patients receiving pyrimethamine at doses in excess of 25 mg
weekly may develop megaloblastic anaemia should co-trimoxazole be prescribed concurrently.
In some situations, concomitant treatment with zidovudine may increase the risk of haematological
consideration should be
monitoring of haematological parameters.
Administration of Deprim 20 mL causes a 40% increase in lamivudine exposure because of the
trimethoprim content. Lamivudine has no effect on the pharmacokinetics of trimethoprim or
A reversible deterioration in renal function presented with increased levels of serum creatinine has
been observed in patients treated with Deprim and cyclosporin following renal transplantation.
Deprim has been shown to potentiate the anticoagulant activity of warfarin via stereo-selective
inhibition of its metabolism. Sulfamethoxazole may displace warfarin from plasma-albumin
protein-binding. Careful control of the anticoagulant therapy during treatment with Deprim is
Deprim prolongs the half-life of phenytoin and of co-administered could result in excessive
phenytoin effect. Close cmonitoring of the patient’s condition and serum phenytoin levels is
Interaction with sulphonylurea hypoglycaemic agents is uncommon but potentiation has been
Concurrent use of rifampicin and Deprim results in a shortening of the plasma half life of
trimethoprim after a period of about one week. This is ot thought to be of clinical significance.
When trimethoprim is administered simultaneously with drugs that form cations at physiological
pH, and are also partially 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 drugs.
Concomitant use of trimethoprim with digoxin has been shown to increase plasma digoxin levels
in a proportion of elderly patients.
Caution should be exercised in patients taking any other drugs that can cause hyperkalaemia.
Deprim may increase the free plasma levels of methotrexate.
If Deprim is considered appropriate therapy in patients receiving other anti-folate drugs such as
methotrexate, a folate supplement should be considered.
Fertility, pregnancy and lactation
Both trimethoprim and sulfamethoxazole cross the placenta and their safety in human pregnancy
has not been established.
malformations typical of folate antagonists. Studies have shown there may be an association
between exposure to folate antagonists and birth defects in humans. It is believed such teratogenic
effects may be prevented by adequate folate supplementation during pregnancy, however the use
of Deprim during pregnancy (especially in the first trimester) should be avoided unless the potential
benefit to the mother outweighs the potential risk to the foetus. Sulfamethoxazole competes with
bilirubin for binding to plasma albumin. As significantly maternally deprived drug levels persist for
several days in the new borm, there may be a risk of precipitating or exacerbating neonatal
administered to the mother near the time of delivery. The potential risk is particularly relevant in
infants at an increased risk of hyperbilirubinaemia e.g. those who are pre-term or with glucose-6-
phosphate dehyrogenase deficiency.
Sulfamethoxazole and trimethoprim are distributed in breast milk. Although levels are very low,
the risk of neonatal kernicterus and hypersensitivity exists, and administration of Deprim should be
avoided when the infant is at particular risk of hyperbilirubinaemia or is less than 8 weeks old.
Effect on ability to drive and use machines
Deprim is unlikely to have any effect on the patient’s ability to drive or handle machinery.
The frequency categories associated with the adverse events below are estimates.
For most events, suitable data for estimating incidence were not available. In addition, adverse
events may vary in their incidence depending on the indication. Data from large published clinical
trials were used to determine the frequency of very common to rare adverse events. Very rare
adverse events were primarily determined from post-marketing experience data and therefore refer
to reporting rate rather than a “true” frequency.
The following convention has been used for the classification of adverse events in terms of
frequency – Very common > 1/10, common >1/100 and < 1/10, uncommon > 1/1000 and < 1/100,
rare > 1/10,000 and < 1,000, very rare < 1/10,000.
Infections and Infestations
Common: Monilial overgrowth
Blood and lymphatic disorders
Very rare: Leucopenia, neutropenia, thrombocytopenia, granulocytosis, megaloblastic anaemia,
aplastic anaemia, haemolytic anaemia, methaemoglobinaemia, eosinophilia, purpura, haemolysis
in certain susceptible G-6-PD deficient patients
The majority of haematological changes are mild and reversible when treatment is stopped. Most
of the changes cause no clinical symptoms although they may become severe in isolated cases,
especially in the elderly, in those with hepatic or renal dysfunction or in those with poor folate
status. Fatalities have been recorded in at-risk patients and these patients should be observed
Immune system disorders
Very rare: Serum sickness, analphylaxis, allergic myocarditis, angioedema, drug fever, allergic
Metabolism and nutrition disorders
Very common: Hyperkalaemia
Very rare: Hypoglycaemia. Hyponatraemia, anorexia
Close supervision is recommended when co-trimoxazole is used in elderly patients or in patients
taking high doses of co-trimoxazole as these patients may be more susceptible to hyperkalaemia
Very rare: Depression, hallucinations
Nervous system disorders
Very rare: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, dizziness
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.
Respiratory, thoracic and mediastinal disorders
Very rare: Cough, shortness of breath, pulmonary infiltrates
Cough, shortness of breath and pulmonary infiltrates may be early indicators of respiratory
hypersensitivity which, while very rare, has been fatal.
Common: Nausea, diarrhoea
Very rare: Glossitis, stomatitis, pseudomembranous colitis, pancreatitis
Very rare: Elevation of serum transaminases, elevation of bilirubin levels, cholestatic jaundice,
Cholestatic jaundice and hepatic necrosis may be fatal.
Skin and subcutaneous tissue disorders
Common: Skin rashes
Very rare: Photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme,
Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis).
Lyell’s syndrome carries a high mortality.
Renal and urinary disorders
Very rare: Impaired renal function (sometimes reported as renal failure), interstitial nephritis
Effects associated with P. Jirrovecii management
Very rare: Severe hypersensitivity reactions, rash, fever, neutropenia, thrmbocytopenis, raised liver
enzymes, hyperkalaemia, hyponatraemia, rhabdomyolysis.
At the high dosages used for PCP management severe hypersensitivity reactions have been
reported, necessitating cessation of therapy. If signs of bone marrow depression occur, the patient
should be given calcium folinate supplementation (5-10 mg/day). Severe hypersensitivity reactions
have been reported in PCP patients on re-exposure to co-trimoxazole, sometimes after a dosage
interval of a few days. Rhabdomyolysis has been reported in HIV positive patients receiving deprim
for prophylaxis or treatment of PCP.
Acute overdosage of co-trimoxazole commonly presents with nausea, vomiting, vertigo, dizziness,
mental and visual disturbances, diarrhoea, crystalluria, haematuria, and in severe cases, anuria.
Bone marrow depression has been reported in acute trimethoprim overdosage.
Chronic overdosage of co-trimoxazole may result in leucopenia, thrombocytopenia, and other blood
dyscrasias due to continual folic acid depletion.
Symptomatic treatments indicated for co-trimoxazole overdosage includes: emesis; gastrolavage;
forced diuresis of Sulfamethoxazole by alkalinisation of the urine; forced diuresis of trimethoprim
by acidification of the urine; haemodialysis; renal dialysis; specific treatment for significant
complications of blood dyscrasia or jaundice. Peritoneal dialysis is not effective. Ongoing
haematological assessment and monitoring of electrolytes is required in cases of overdosage. The
haematopoietic effects of trimethoprim may be countered by administration of calcium folinate 3-
6 mg by intramuscular injection for 5-7 days.
Sulfamethoxazole - a substituted sulphonamide, interferes with the synthesis of nucleic acids in
sensitive microorganisms by blocking the conversion of p-aminobenzoic acid to the co-enzyme
dihydrofolic acid, a reduced form of folic acid. In man, dihydrofolic acid is obtained from dietary
folic acid so sulphonamides do not affect human cells. Their action is primarily bacteriostatic
although they may be bactericidal where concentrations of thymine are low in the surrounding
medium. The sulphonamides have a broad spectrum of action but the development of widespread
resistance has greatly reduced their usefulness and susceptibility often varies widely even among
nominally sensitive pathogens.
Trimethoprim - a diaminopyrimidine antibiotic,is used for the treatment of infections due to
sensitive organisms. Trimethoprim is a dihydrofolate reductase inhibitor. It inhibits the conversion
of bacterial dihydrofolic acid to tetrahydrofolic acid which is necessary for the synthesis of certain
amino acids, purines, thymidine, and ultimately DNA synthesis. It acts in the same metabolic
pathway as the sulphonamides. The binding affinity of trimethoprim for bacterial dihydrofolate
reductase enzymes is estimated to be 50000 greater than for the corresponding mammalian enzyme
Because Sulfamethoxazole and trimethoprim act at consecutive points of the folate metabolic
pathway a potent synergy exists in vitro with an increase of up to about 10-fold in antibacterial
activity and a frequently bactericidal action where individually they are generally bacteriostatic.
The minimum inhibitory concentration (MIC) of each agent is reduced.
concentrations significantly lower than those attained in vivo following the administration of
recommended doses. Microorganisms that are sensitive include:
Brucella spp.; Citrobacter spp.; Enterobacter spp.; Escherichia coli (including enterotoxigenic
strains); Haemophilus ducreyi; Haemophilus influenzae (including ampicillin-resistant strains);
Klebsiella spp.; Legionella pneumophila; Morganella morganii (previously Proteus morganii);
Neisseria spp.; Proteus spp.; Providencia spp. (including previously Proteus rettgeri); Certain
Pseudomonas spp. (except P. aeroginosa ); Salmonella spp. (including S. typhi and paratyphi);
Serratia marcescens; Shigella spp.; Vibrio cholerae; Yersinia spp.
Listeria monocytogenes; Nocardia spp.; Staphylococcus aureus; Staphylococcus epidermidis and
saprophyticus; Streptococcus faecalis; Streptococcus pneumoniae; Streptococcus viridans.
Many strains of Bacteroides fragilis are sensitive. Some strains of Campylobacter fetus subspecies
jejuni, and Chlamydia (especially C. trachomatis) are sensitive without evidence of synergy. Some
varieties of non-tuberculous mycobacteria are sensitive to Sulfamethoxazole but not trimethoprim.
Mycoplasmas, Ureaplasma urealyticum, Mycobacterium tuberculosis and Treponema pallidum are
In vitro activity does not necessarily imply that clinical efficacy has been demonstrated and it should
be noted that satisfactory sensitivity testing is achieved only with recommended media free from
inhibitory substances especially thymidine and thymine.
Sulfamethoxazole and trimethoprim have very similar pharmacokinetic properties. The individual
pharmacokinetic profile of each agent is not altered in the presence of the other agent.
Sulfamethoxazole and trimethoprim are both rapidly and almost completely absorbed following
oral administration with or without food. Peak plasma levels of each agent are attained within 1-4
hours after ingestion and effective levels for antibacterial activity persist up to 24 hours after a
therapeutic dose. Steady state levels in adults are attained after dosing for 2-3 days. Plasma levels
are a function of dose for each agent.
Approximately 65% of the Sulfamethoxazole is bound to plasma proteins with a plasma half-life is
6-12 hours. It is prolonged in patients with severe renal impairment. Sulfamethoxazole diffuses
freely throughout the body tissues and may be detected in the urine, saliva, sweat, bile, in the
cerebrospinal, peritoneal, ocular and synovial fluids, and in pleural and other effusions. It crosses
the placenta into the foetal circulation and low concentrations have been detected in breast milk.
extravascular fluids represent only 20-50% of plasma levels. The apparent volume of distribution
is 20 litres. Sulfamethoxazole undergoes conjugation mainly in the liver, chiefly to the inactive N4-
acetyl derivative which represents about 15% of the total amount of Sulfamethoxazole in the blood.
Glucuronide conjugation also occurs but to a lesser extent. Elimination in the urine is dependent on
pH. About 80-100% of a dose is excreted in the urine of which about 60% is in the form of the
acetyl derivative with the remainder as unchanged drug and glucuronide. Sulfamethoxazole is also
oxidised to the hydroxylamine, a metabolite that has been implicated in adverse reactions to
Approximately 45% of trimethoprim is bound to plasma proteins. Trimethoprim is widely
distributed to various tissues and fluids including kidneys, liver, lung and bronchial secretions,
saliva, aqueous humour, prostatic tissue and fluid, and vaginal secretions. Concentrations in many
of these tissues are reported to be higher than serum concentrations but concentrations in the CSF
are about one-quarter to one-half of those in the blood. Trimethoprim readily crosses the placenta
and it appears in breast milk. The half-life is about 8-11 hours in adults and somewhat less in
children but is prolonged in severe renal impairment and in neonates whose renal function is
immature. Trimethoprim is a lipophilic weak base (pKa=7.3) which is relatively insoluble at
physiological pH and has an apparent volume of distribution of 130 litres. About 10-20% of
trimethoprim is metabolised in the liver mainly via the oxidation and hydroxylation pathways with
the principal metabolites being 1- and 3-oxides and the 3'- and 4'-hydroxy derivatives with some
metabolites being active. Small amounts are excreted in the faeces via the bile but most is excreted
in urine predominantly as unchanged drug. About 40-60% is excreted in urine within 24 hours.
Trimethoprim is removed from the blood by haemodialysis to some extent.
Both Sulfamethoxazole and trimethoprim are almost exclusively eliminated by renal excretion via
glomerular filtration and tubular secretion processes. Biliary excretion of each agent accounts for a
relatively minor amount of a therapeutic dose. In patients with severely impaired renal function
(creatinine clearance 15-30 mL/min) dosage adjustment is required.
Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction
List of excipients
Ponceau 4R (e124)
Raspberry flavour E_0026934
polysorbate 80, purified water q.s., syrup.
Other excipient, preservative
Sodium propyl hydroxybenzoate, Sodium methylhydroxybenzoate.
36 months from date of manufacture.
Special precautions for storage
Store at or below 25
Nature and contents of container
Packs of 100 mL.
Special precautions for disposal
No special requirements.
AFT Pharmaceuticals Ltd
PO Box 33-203
Phone: 0800 423 823
DATE OF FIRST APPROVAL
23 April 2009
DATE OF REVISION OF THE TEXT
SUMMARY TABLE OF CHANGES
Reformat consistent with new Medsafe Data Sheet
Update to remove the statement: "Deprim is well
tolerated at the recommended doses”, as per
Medsafe’s request dated 10 January 2019.