SULTAB 375

 

SULTAB 375

Sultamicillin Tosilate Tablets

 

COMPOSITION

Each film-coated tablet contains Sultamicillin Tosilate equivalent to Sultamicillin 375mg

 

DESCRIPTION

Sultamicillin is a mutual prodrug of sulbactam and ampicillin.

Sultamicillin is a double ester in which ampicillin and the beta-lactamase inhibitor sulbactam are linked via a methylene group. Chemically sultamicillin is the axymethylpenicillibate sulphone ester of ampicillin and has a molecular weight of 594.7

 

CLINICAL PARTICULARS

1. Therapeutic indications

Sultamicillin is indicate 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; intraabdominal infections and gonococcal infections. Sultamicillin may also be indicated in patients requiring sulbactam/ampicillin therapy following initial treatment with sulbactam/ampicillin IM/IV

 

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 gonorrhea, sulramicillin can be given as a single oral dose of 2.25 grams (six 375 mg tablets). Concomitant probenecid 1.0 gram should be administrated in order to prolong plasma concentrations of sulbactam and ampicillin.

Cases of gonorrhea 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 judgment. For children weighing 30kg 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 30ml/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 ampicillin.

 

3. Contraindications

The use of this combination is contraindicated in individuals with a history of an allergic reaction to any of the penicillin’s.

 

4. Special Warnings 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 cephalosporin’s. Before therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillin’s, cephalosporin’s, and other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted.

Serious anaphylactic reactions requires immediate emergency treatment with adrenaline. 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 no susceptible organisms, including fungi, is essential. Should super infection occur, the drug should be discontinued and/or appropriate therapy instituted.

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.

1. difficile produces toxins A and B which contribute to the development of CDAD. Hyper toxin producing strains of C. dificile 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.

Drug induced liver injury such as cholestasis hepatitis and jaundice have been associated with the use of ampicillin/ sulbactam. Patients should be advised to contract their doctor if signs and symptoms of hepatic disease develop. (see Section 3.7-Undesirable Effects).

Since infectious mononucleosis is viral in origin, sulbactam sodium/ampicillin sodium IM/IV should not be used in its treatment. A high percentage of patients with mononucleosis who received ampicillin have developed a skin rash. If is advisable to check periodically for organ system dysfunction during prolonged therapy; this includes renal, hepatic and hematopoiesis 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 condidered wen using sultamicillin in neonates, Tablets; Patients with rare hereditary problems of galactosse intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 

5. Interaction with Other Medicinal Products and Other Forms of Interaction

Allopurinol: The concurrent administration of allopurinol and ampicillin substantially increases the incidence of rashes in patients receiving both drugs as compared with patients receiving ampicillin alone.

Anticoagulants: Penicillin’s can produce alterations in platelet aggregation and coagulation tests. These effects may be additive with anticoagulants.

Bacteriostatic drugs (chloramphenicol, erythromycin, sulfonamides and tetracycline’s): Bacteriostatic drugs may interfere with the bactericidal effect of penicillin’s; 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.

Methotrexae; oncurrent use with penicillins has resulted in decreased clearance of methotrexate and in methotrexate toxicity, Patients should be closely monitored. Leucovorin dosage 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^TM. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone and estriol has been noted.

This may also occur with sulbactam sodium/ampicillin sodium IM/IV.

 

6. Fertility, pregnancy and Lactation User During 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

 Only if the potential benefit outweigh the potential risk.

Use During Lactation

The use of sultamicillin during lactation is not recommended. Low concentrations of ampicillin and sulbactom are exreted in the milk. This should be considered as the neonate may be exposed, particularly since renal function is not fully developed in neonates.

 

7. Undesirable Effects

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.

Immune System Disorders: Anaphylactic Shock, Anaphylactic reaction, Hypersensitivity.

Nervous, System Disorder: Dizziness, Somnolence, Sedation, Headache.

Respiratory, Thoracic and Mediastinal

Disorders: Dyspnoen.

Gastrointestinal Disorders: Enterocolitis, Melaena, Diarrhoea, Vomiting, Abdominal pain Dyspepsia, Nausea.

Skin and Subcutaneous Tissue Disorders: Angioedema, urticaria, dermatitis, Rash, Pruritus.

General Disorders and Administration Site Conditions: Fatigue, Malasie.

Adverse reactions associated with use of ampicillin alone may be observed with sultamicillin. Adverse reactions associated with the use of ampicillin and/or sulbactam/ampicillin IM/IV include:

Blood and Lymphatic System Disorders: Agranulocytosis; Hemolitic anaemia, Thrombocytopenic purpura, Thrombocytopenia, Leukopenia, Neutropenia., Eosinophilia, Anaemia. Nervous System Disorders: Convulsion. Gastrointestinal Disorders: Glossitis, Stomatitis, Tongue discoloration. Hepatobiliary Disorders: Cholestasis, Cholestasis hepatic, Bilirubinemia, Hepatic function abnormal, Joundice. Skin and Subcutaneonus Tissue Disorders: Toxic epidermal necrolysis, Stevens Johnson syndrome, Erythema multiforme, Dermatitis exfoliative.

Renal and Urinary Disorders: Tubulointerstitial nephritis.

Investigations: Platelet aggregation abnormal, Alanine aminotransferase increased, Aspartate aminotransferase increased.

 

8. Overdose

Limited information is available on the acute toxicity of ampicillin sodium and sulbactam sodium 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 CSF concrentrations of B-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.

 

PHARMACEUTICAL PARTICULARS

 

1.Shelf-life

24 Month

 

2.Storage Condition

Stored below 30°C in a dry place protected from light.

Keep out of reach of children.

 

3.Packing

Each pack of 10 tablets in a printed carton along with pack insert.