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`

`

`® Bactrim™ Roche®
`strong Sterile Co-trimoxazole Solution B.P.
`Antibacterial Agent
`For intravenous infusion only
`
`Action
`‘Bactrim’ (trimethoprim and sulfamethoxazole) blocks two consecutive
`steps in the biosynthesis of nucleic acids and proteins essential to many
`bacteria (Figure 1). Sulfamethoxazole inhibits bacterial synthesis of
`dihydrofolic acid by competing with para-aminobenzoic acid. Trimethoprim
`blocks the production of tetrahydrofolic acid from dihydrofolic acid by
`reversibly inhibiting the required enzyme, dihydrofolate reductase.
`
`FIGURE 1
`
`Dihydrofolic acid
`synthetase
`
`Dihydrofolic acid
`reductase
`
`TMP • Trimethoprim
`SMZ • Sulfamethoxazole
`
`SMZ
`
`>
`
`TMP
`
`DNA
`
`Para-aminobenzoic acid
`Dihydropteridin
`
`> Dihydrofolic
`acid
`
`Tetrahydrofolic
`acid
`
`^ / Synthesis
`of
`Purines
`
`RNA
`
`The effect of the dual consecutive action is to reduce the minimum
`inhibitory concentration of each agent (synergism) and to convert a
`bacteriostatic action to a bactericidal action.
`
`Indications
`‘Bactrim’ (trimethoprim and sulfamethoxazole) is indicated in the treatment
`of the following infections when associated with the gram-positive and
`gram-negative organisms listed in Table I.
`— Upper and lower respiratory tract infections (particularly chronic
`bronchitis and including acute and chronic otitis media).
`— Acute, recurrent, and chronic urinary tract infections.
`— Genital tract infections (uncomplicated gonococcal urethritis).
`— Gastrointestinal tract infections.
`— Skin and soft tissue infections.
`‘Bactrim’ is also indicated in the treatment of Pneumocystis carinii
`pneumonitis.
`
`Table I
`List of susceptible organisms
`Streptococcus pyogenes
`Streptococcus viridans
`Staphylococcus aureus
`Staphylococcus albus
`DIplococcus pneumoniae
`Haemophilus influenzae
`Neisseria gonorrheae
`Escherichia coli
`
`Klebsiella spp.
`Enterobacter (Aerobacter) aerogenes
`Proteus mirabilis
`Proteus vulgaris
`Salmonella typhi
`Salmonella paratyphi
`Salmonella typhimurlum
`Salmonella enteritidls
`Shigella spp.
`
`‘Bactrim’ for Infusion is indicated in the treatment of serious systemic
`infections such as meningitis and septicemia caused by susceptible
`organisms as well as in the treatment of Pneumocystis carinii pneumonitis,
`when oral administration is not practical.
`‘Bactrim’ is not indicated in infections associated with Pseudomonas,
`Mycopiasma, or viruses.
`Contraindications
`‘Bactrim’ is contraindicated in patients with evidence of known hyper­
`sensitivity to trimethoprim or sulfonamides, marked liver parenchymal
`damage, blood dyscrasias, or marked renal impairment when measure­
`ments of drug concentrations cannot be done (See Precautions).
`‘Bactrim’ should not be given to premature neonates or infants less than
`two months of age (See Precautions). It is contraindicated in pregnancy
`and during the nursing period. If pregnancy cannot be excluded, the
`possible risks should be balanced against the expected therapeutic
`effect.
`
`Precautions
`General
`As with other sulfonamide preparations, critical appraisal of benefit versus
`risk should be done in patients with liver or renal damage, urinary
`obstruction, blood dyscrasias, allergies or bronchial asthma. The possi­
`bility of superinfection with a non-sensitive organism should be borne
`in mind.
`If ‘Bactrim’ for Infusion is administered on an emergency basis to neonatal
`infants, a potential complication in this age group is kernicterus.
`In patients with renal impairment, a reduced or less frequent dosage is
`recommended in order to avoid accumulation of trimethoprim and
`sulfamethoxazole in the blood. For such patients, serum drug concentra­
`tion measurements are necessary. ‘Bactrim’ should not be used when the
`creatinine serum concentration is above 2 mg/dl in order to avoid possible
`permanent impairment of renal function. 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, chronic alcoholics and rheumatoid arthritis), in malabsorption
`syndromes, in malnutrition states, or during the treatment of epilepsy with
`anticonvulsant drugs such as phenytoin, primidone or barbiturates.
`Changes indicative of folic acid impairment have, in certain specific
`situations, been reversed by folinic acid therapy.
`Drug Interactions
`PABA or its derivatives antagonize sulfamethoxazole. Increased sulfa­
`methoxazole blood concentrations may occur in patients who are also
`receiving urinary acidifiers, oral anticoagulants or sulfonylurea hypo-
`glycemics, phenylbutazone, oxyphenbutazone, indomethacin, sulfin­
`pyrazone or salicylates.
`Adverse Reactions
`Hematological changes have been observed in some patients, particularly
`the elderly. The great majority of these changes were mild, asymptomatic,
`and proved reversible on withdrawal of the drug. The reported changes
`were primarily neutropenia and thrombocytopenia.