Each Film-Coated Tablet contains: Sultamicillin (as Tosylate) 750 mg.
Sultamicillin is a prodrug ampicillin and the beta-lactamase inhibitor sulbactam; it consists of the two compounds linked chemically as a double ester. During absorption from the gastrointestinal tract it is hydrolyzed, releasing equimolar quantities of ampicillin and sulbactam.
Pharmacology: Pharmacodynamics: Biochemical studies with cell-free bacterial systems have shown sulbactam to be an irreversible inhibitor of most important beta-lactamases that occur in penicillin-resistant organisms. While sulbactam antibacterial activity is mainly limited to Neisseriaceae, the potential for sulbactam in preventing the destruction of penicillins and cephalosporins by resistant organisms was confirmed in whole-organism studies using resistant strains, in which sulbactam exhibited marked synergistic effects with penicillins and cephalosporins. Since sulbactam also binds to some penicillin-binding proteins, some sensitive strains are rendered more susceptible to the combination than to the beta-lactam antibiotic alone. The bactericidal component of this product is ampicillin which, like benzyl penicillin, acts against sensitive organisms during the stage of active multiplication by the inhibition of biosynthesis of cell wall mucopeptide.
Sultamicillin is effective against a wide range of gram-positive and gram-negative bacteria including: Staphylococcus aureus and Staphylococcus epidermidis (including penicillin-resistant and some methicillin resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus species; Haemophilus influenzae and H. parainfluenzae (both beta-lactamase-positive and negative strains); Moraxella catarrhalis; anaerobes including Bacteroides fragilis and related species; Escherichia coli; Klebsiella species; Proteus species (both indole-positive and indole-negative); Enterobacter species; Morganella morganii; Citrobacter species; Neisseria meningitidis and Neisseria gonorrhoeae.
Pharmacokinetics: Following oral administration in humans, sultamicillin is hydrolyzed during absorption to provide sulbactam and ampicillin in a 1:1 molar ratio in the systemic circulation. The bioavailability of an oral dose is 80% of an equal intravenous dose of sulbactam and ampicillin. Administration following food does not affect the systemic bioavailability of sultamicillin. Peak serum levels of ampicillin, following administration of sultamicillin, are approximately twice those of an equal dose of oral ampicillin. Elimination half-lives are approximately 0.75 and 1 hour for sulbactam and ampicillin, respectively, in healthy volunteers, with 50-75% of each agent being excreted unchanged in the urine. Elimination half-lives are increased in the elderly and in patients with renal dysfunction.
Probenecid decreases the renal tubular secretion of both ampicillin and sulbactam. Concurrent use of probenecid with sultamicillin results in increased and prolonged blood levels of ampicillin and sulbactam (see INTERACTIONS).
Sultamicillin is used in the treatment of infections where beta-lactamase-producing organisms might occur including uncomplicated gonorrhea, otitis media, respiratory-tract and urinary-tract infections.
The usual dose is 375 mg to 750 mg twice daily or as prescribed by the physician.
Limited information is available on the acute toxicity of ampicillin and sulbactam in humans. Overdosage of the drug would be expected to produce manifestations that are principally extensions of the adverse reactions reported with the drug. The fact that high cerebrospinal fluid (CSF) concentrations of beta-lactam antibiotics may cause neurologic effects, including seizures, should be considered. Because ampicillin and sulbactam are both removed from the circulation by hemodialysis, these procedures may enhance elimination of the drug from the body if overdosage occurs in patients with impaired renal function.
The use of sultamicillin is contraindicated in individuals with a history of an allergic reaction to any of the penicillins.
Hypersensitivity: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. 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 a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, SULTAMIN should be discontinued and the appropriate therapy instituted.
Hepatotoxicity: Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of SULTAMIN. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
Severe Cutaneous Adverse Reactions: Sultamicillin may cause severe skin reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), dermatitis exfoliative, erythema multiforme, and acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash they should be monitored closely and Sultamicillin discontinued if lesions progress. (See CONTRAINDICATIONS and ADVERSE REACTIONS.)
Clostridium difficile-Associated Diarrhea: 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.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
General: A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash. Thus, ampicillin class antibiotics should not be administered to patients with mononucleosis. In patients treated with sultamicillin the possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.
Prescribing sultamicillin in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Information for Patients: Patients should be counseled that antibacterial drugs including sultamicillin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When sultamicillin is prescribed to treat a bacterial infection, patients should be told that although its common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by sultamicillin or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibacterial, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible.
Patients known to be hypersensitive to penicillin should be given an antibacterial of another class. Care is necessary if very high doses are given, especially if renal function is poor.
Use in Pregnancy: Animal reproduction studies have revealed no evidence of impaired fertility or harm to the fetus due to sultamicillin. Sulbactam crosses the placental barrier. However, safety for use in human pregnancy has not been established. Therefore, sultamicillin should be used during pregnancy only if the potential benefits outweigh the potential risk.
Use in Lactation: The use of sultamicillin during the lactation is not recommended. Low concentrations of ampicillin and sulbactam are excreted in the milk. This should be considered as the neonate may be exposed, particularly since renal function is not fully developed in neonates.
Sultamicillin is generally well tolerated. The majority of side effects observed were of mild or moderate severity and were normally tolerated with continued treatment.
Infections and infestations:
Pseudomembranous colitis, Candida infection.
Blood and Lymphatic System Disorders:
Immune System Disorders:
Anaphylactic shock, anaphylactic reaction, hypersensitivity.
Nervous System Disorders:
Dizziness, somnolence, sedation, headache.
Respiratory, Thoracic and Mediastinal Disorders:
Enterocolitis, melena, diarrhea, vomiting, abdominal pain, dyspepsia, nausea, stomatitis, dysgeusia, tongue discoloration.
Jaundice, hepatic function abnormal.
Skin and Subcutaneous Tissue Disorders:
Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema, urticaria, dermatitis, rash, pruritus.
Musculoskeletal and Connective Tissue Disorder:
General Disorders and Administration Site Conditions:
Alanine aminotransferase increased, aspartate aminotransferase increased.
Adverse reactions associated with the use of ampicillin alone may be observed with sultamicillin.
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 anticoagulants.
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 decrease 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 time.
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 Clinitest. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucoronide, conjugated estrone and estradiol has been noted.
Store at temperatures not exceeding 30°C.
J01CR04 - sultamicillin ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.
FC tab 750 mg (white to off-white, oblong shaped, biconvex, plain on one side and bisected on the other side) x 50's.