1. TRADE NAME OF MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Sultamicillin is a double ester in which ampicillin and the beta-lactamase
inhibitor sulbactam are linked via a methylene group. Chemically
Sultamicillin is the oxymethylpenicillinate sulphone ester of ampicillin and
has a molecular weight of 594.7.
3. PHARMACEUTICAL FORM
Sultamicillin is available as film-coated tablets containing the tosylate
salt equivalent to 375 mg sultamicillin which is a mutual prodrug of
sulbactam and ampicillin yielding the equivalent of 147 mg sulbactam and 220
Sultamicillin is also available as a powder for oral suspension
containing sultamicillin base that after reconstitution with water provides
250 mg sultamicillin per 5 ml.
4. CLINICAL PARTICULARS
4.1 Therapeutic Indications
Sultamicillin is indicated for infections caused by susceptible
micro-organisms. Typical indications are upper respiratory tract infections
including sinusitis, otitis media and tonsillitis; lower respiratory tract
infections including bacterial pneumonias and bronchitis; urinary tract
infections and pyelonephritis; skin and soft tissue infections and
Sultamicillin may also be indicated in patients requiring sulbactam/ampicillin
therapy following initial treatment with sulbactam/ampicillin IM/IV.
4.2 Posology and Method of Administration
The recommended dose of sultamicillin in adults (including elderly patients)
is 375-750 mg orally twice daily.
In both adults and children treatment is usually continued until 48 hours
after pyrexia and other abnormal signs have resolved. Treatment is normally
given for 5-14 days, but the treatment period may be extended if necessary.
In the treatment of uncomplicated gonorrhoea, sultamicillin can be given
as a single oral dose of 2.25 grams (six 375 mg tablets). Concomitant
probenecid 1.0 gram should be administered in order to prolong plasma
concentrations of sulbactam and ampicillin.
Cases of gonorrhoea with a suspected lesion of syphilis should have dark
field examinations before receiving sultamicillin and monthly serological
tests for a minimum of four months.
It is recommended that there be at least 10 days treatment for any
infection caused by hemolytic streptococci to prevent the occurrence of
acute rheumatic fever or glomerulonephritis.
Use in Children and Infants
The dosage for most infections in children weighing less than 30 kg is
sultamicillin 25-50 mg/kg/day orally in 2 divided doses depending on the
severity of the infection and the physician's judgement. For children
weighing 30 kg or more the usual adult dose should be given.
Use in Patients with Renal Impairment
In patients with severe impairment of renal function (creatinine clearance ≤
30 ml/min), the elimination kinetics of sulbactam and ampicillin are
similarly affected and hence the plasma ratio of one to the other will
remain constant. The dose of sultamicillin in such patients should be
administered less frequently in accordance with usual practice for
The use of this product is contraindicated in individuals with a history of
an allergic reaction to any of the penicillins.
4.4 Special Warning and Special Precautions for Use
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions
have been reported in patients on penicillin therapy including sultamicillin.
These reactions are more apt to occur in individuals with a history of
penicillin hypersensitivity and/or hypersensitivity reactions to multiple
allergens. There have been reports of individuals with a history of
penicillin hypersensitivity who have experienced severe reactions when
treated with cephalosporins. Before therapy with penicillin, careful inquiry
should be made concerning previous hypersensitivity reactions to penicillins,
cephalosporins, and other allergens. If an allergic reaction occurs, the
drug should be discontinued and the appropriate therapy instituted.
Serious anaphylactic reactions require immediate emergency treatment with
Oxygen, intravenous steroids, and airway management, including intubation,
should be administered as indicated.
As with any antibiotic preparation, constant observation for signs of
overgrowth of nonsusceptible organisms, including fungi, is essential.
occur, the drug should be discontinued and/or appropriate therapy
Clostridium difficile associated diarrhea (CDAD) has been reported
with use of nearly all antibacterial agents, including sultamicillin, and
may range in severity from mild diarrhea to fatal colitis. Treatment with
antibacterial agents alters the normal flora of the colon leading to
overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the
development of CDAD. Hypertoxin producing strains of C. difficile
cause increased morbidity and mortality, as these infections can be
refractory to antimicrobial therapy and may require colectomy. CDAD must be
considered in all patients who present with diarrhea following antibiotic
use. Careful medical history is necessary since CDAD has been reported to
occur over two months after the administration of antibacterial agents.
Since infectious mononucleosis is viral in origin, ampicillin should not
be used in the treatment. A high percentage of patients with mononucleosis
who receive ampicillin develop a skin rash.
It is advisable to check periodically for organ system dysfunction during
prolonged therapy; this includes renal, hepatic and hematopoietic systems.
The principal route of excretion of sulbactam and ampicillin following
oral administration of sultamicillin is via the urine. Because renal
function is not fully developed in neonates. this should be considered when
using sultamicillin in neonates.
Tablets: Patients with rare hereditary problems of galactose intolerance,
the Lapp lactase deficiency or glucose-galactose malabsorption should not
take this medicine.
Powder for Oral Suspension: Patients with rare hereditary problems of
fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase
insufficiency should not take this medicine.
4.5 Interaction with other Medicaments and Other Forms of Interaction
Allopurinol : The concurrent administration of allopurinol and
ampicillin increases substantially the incidence of rashes in patients
receiving both drugs as compared to patients receiving ampicillin alone.
Anticoagulants : Penicillins can produce alterations in platelet
aggregation and coagulation tests. These effects may be additive with
Bacteriostatic drugs (chloramphenicol, erythromycin, sulfonamides and
tetracyclines) : Bacteriostatic drugs may interfere with the
bactericidal effect of penicillins; it is best to avoid concurrent therapy.
Estrogen-containing oral contraceptives : There have been case
reports of reduced oral contraceptive effectiveness in women taking
ampicillin, resulting in unplanned pregnancy. Although the association is
weak, patients should be given the option to use an alternate or additional
method of contraception while taking ampicillin.
Methotrexate : Concurrent use with penicillins has resulted in
decreased clearance of methotrexate and a corresponding increase in
methotrexate toxicity. Patients should be closely monitored. Leucovorin
dosages may need to be increased and administered for longer periods of
Probenecid : Probenecid decreases renal tubular secretion of
ampicillin and sulbactam when used concurrently; this effect results in
increased and prolonged serum concentrations, prolonged elimination
half-life, and increased risk of toxicity.
Laboratory Test Interactions : False positive glycosuria may be
observed in urinalysis using Benedict reagent, Fehling reagent, and Clintest.
Following administration of ampicillin to pregnant women, a transient
decrease in plasma concentration of total conjugated estriol,
estriol-glucuronide, conjugated estrone and estradiol has been noted. This
effect may also occur with sulbactam sodium/ampicillin sodium IM/IV.