Unasyn

Unasyn

sultamicillin

ampicillin + sulbactam

Manufacturer:

Pfizer

Distributor:

DKSH
Full Prescribing Info
Contents
Sultamicillin: Sulbactam, ampicillin.
Description
Unasyn Tablet: Unasyn Tablet contains the tosylate salt equivalent to sultamicillin 375 mg which is a mutual prodrug of sulbactam and ampicillin yielding the equivalent of sulbactam 147 mg and ampicillin 220 mg; 750-mg tab contains ampicillin 440 mg and sulbactam 294 mg.
Each tablet also contains lactose, maize starch, sodium starch glycolate, hydroxypropylcellulose and magnesium stearate as excipients.
Unasyn Susp: After reconstitution, each 5-mL suspension contains 250 mg sultamicillin.
The suspension also contains sucrose, colloidal silica, dibasic sodium phosphate, monobasic sodium phosphate and cherry flavor as excipients.
Unasyn IM/IV: Each 750-mg vial contains sulbactam sodium 250 mg and ampicillin sodium 500 mg. Each 1.5-g vial contains sulbactam sodium 500 mg and ampicillin sodium 1000 mg. Each 3-g vial contains sulbactam sodium 1 g, ampicillin sodium 2 g.
Sultamicillin is a double ester in which ampicillin and the β-lactamase inhibitor sulbactam are linked via a methylene group. Sultamicillin is the oxymethylpenicillinate sulfone ester of ampicillin and has a molecular weight of 594.7.
Sulbactam sodium is a derivative of the basic penicillin nucleus. It is sodium penicillinate sulfone and has a molecular weight of 255.22. It is an off-white crystalline powder highly soluble in water.
Ampicillin sodium is derived from the penicillin nucleus, 6-aminopenicillanic acid. It is D(-)-α-aminobenzyl penicillin sodium salt and has a molecular weight of 371.39.
Action
Pharmacology: Pharmacodynamics: Biochemical studies with cell-free bacterial systems have shown sulbactam to be an irreversible inhibitor of most important β-lactamases that occur in penicillin-resistant organisms. It possesses significant antibacterial activity only against Neisseriaceae, Acinetobacter calcoaceticus, Bacteroides sp, Branhamella catarrhalis, Moraxella catarrhalis and Pseudomonas cepacia. The potential for sulbactam sodium's preventing the destruction of penicillins and cephalosporins by resistant organisms was confirmed in whole organism studies using resistant strains in which sulbactam sodium 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 β-lactam antibiotic alone.
The bactericidal component of Unasyn tablet is ampicillin which, like benzylpenicillin, acts against sensitive organisms during the stage of active multiplication by the inhibition of biosynthesis of cell wall mucopeptide.
Pharmacokinetics: Unasyn Tablet/Unasyn Susp: Following oral administration in humans, sultamicillin is hydrolysed 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 IV dose of sulbactam and ampicillin. Administration following food does not affect the systemic bioavailability of sultamicillin. Peak serum levels of ampicillin following sultamicillin are approximately twice those of an equal dose of oral ampicillin. Elimination half-lives are approximately 0.75 and 1 hr for sulbactam and ampicillin, respectively, in healthy volunteers, with 50-75% of each agent being excreted in the urine unchanged. 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.)
Unasyn IM/IV: Sulbactam sodium/ampicillin sodium IM/IV diffuses readily into most body tissues and fluids in the human. Penetration into brain and spinal fluid is low except when meninges are inflamed. High concentrations of sulbactam and ampicillin are achieved in the blood following IV or IM administration and both components have a half-life of approximately 1 hr. Most of the sulbactam/ampicillin IM/IV is excreted unchanged in the urine.
Microbiology: Sultamicillin is effective against a wide range of gram-positive and gram-negative bacteria including: Staphylococcus aureus and S. epidermidis (including penicillin-resistant and some methicillin-resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus sp; Haemophilus influenzae and H. parainfluenzae (both β-lactamase-positive and negative strains); Moraxella catarrhalis; anaerobes including Bacteroides fragilis and related species; Escherichia coli; Klebsiella sp; Proteus sp (both indole-positive and indole-negative); Enterobacter sp; Morganella morganii; Citrobacter sp; Neisseria meningitidis and Neisseria gonorrhoeae.
Indications/Uses
For infections caused by susceptible microorganisms. 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, bone and joint infections and gonococcal infections.
Unasyn Tablet/Unasyn Susp: Sultamicillin may also be indicated in patients requiring sulbactam/ampicillin therapy following initial treatment with sulbactam/ampicillin IM/IV.
Unasyn IM/IV: May also be administered perioperatively to reduce the incidence of postoperative wound infections in patients undergoing abdominal or pelvic surgery, in which peritoneal contamination may be present. In termination of pregnancy or caesarean section, sulbactam sodium/ampicillin sodium IM/IV may be used prophylactically to reduce postoperative sepsis.
Dosage/Direction for Use
Unasyn Tab: Adults (Including Elderly Patients): Recommended Dose: 375-750 mg twice daily.
In both adults and children, treatment is usually continued until 48 hrs 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.
Treatment of Uncomplicated Gonorrhoea: Sultamicillin can be given as a single oral dose of 2.25 g (six 375-mg tabs). Concomitant probenecid 1 g should be administered in order to prolong plasma concentrations of sulbactam and ampicillin.
Cases of gonorrhoea with a suspected lesion of syphilis should have darkfield examinations before receiving sultamicillin and monthly serological tests for a minimum of 4 months.
It is recommended that there be at least 10 days treatment for any infection caused by haemolytic Streptococci to prevent the occurrence of acute rheumatic fever or glomerulonephritis.
Children and Infants: The dosage for most infections in children weighing <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 ≥30 kg the usual adult dose should be given.
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 in such patients should be administered less frequently in accordance with usual practice for ampicillin. Unasyn IM/IV: Sulbactam sodium/ampicillin sodium IM/IV can be administered by either IV or IM routes. The following dilutions may be used: See Table 1.

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For IV administration, sulbactam sodium/ampicillin sodium IM/IV should be reconstituted with sterile water for injection or any compatible solution. (See Instructions for Use under Cautions for Usage.) To ensure complete dissolution, allow foaming to dissipate in order to visually inspect. The dose can be given by bolus injection over a minimum of 3 min or can be used in greater dilutions as an IV infusion over 15-30 min. Pfizer sulbactam sodium/ampicillin sodium parenteral may also be administered by deep IM injection; if pain is experienced, 0.5% sterile solution for injection of anhydrous lignocaine HCl may be used for reconstitution of the powder.
Adults: The usual dosage range of sulbactam sodium/ampicillin sodium IM/IV is 1.5-12 g/day in divided doses every 6 or 8 hrs up to a maximum daily dosage of sulbactam of 4 g. Less severe infections may be treated on an every 12-hr schedule. (See Table 2.)

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More or less frequent dosing may be indicated depending on the severity of the illness and the renal function of the patient. Treatment is usually continued until 48 hrs after pyrexia and other abnormal signs have resolved. Treatment is normally given for 5-14 days, but the treatment period may be extended or additional ampicillin may be administered in severely ill cases.
In treating patients on restricted sodium intake, it should be noted that 1500 mg of sulbactam sodium/ampicillin sodium IM/IV contains approximately 115 mg (5 mmol) of sodium.
For the prophylaxis of surgical infections, 1.5-3 g of sulbactam sodium/ampicillin sodium IM/IV should be given at induction of anesthesia, which allows sufficient time to achieve effective serum and tissue concentrations during the procedure.
The dose may be repeated every 6-8 hrs; administration is usually stopped 24 hrs after the majority of surgical procedures, unless a therapeutic course of sulbactam sodium/ampicillin sodium IM/IV is indicated.
In the treatment of uncomplicated gonorrhea, sulbactam sodium/ampicillin sodium IM/IV can be given as a single dose of 1.5 g. Concomitant probenecid 1 g orally should be administered in order to prolong plasma concentrations of sulbactam and ampicillin.
Children, Infants and Neonates: The dosage of sulbactam sodium/ampicillin sodium IM/IV for most infections in children, infants and neonates is 150-300 mg/kg/day (corresponding to sulbactam 50 mg/kg/day and ampicillin 100 mg/kg/day).
In children, infants and neonates, dosing is usually every 6 or 8 hrs in accordance with the usual practice for ampicillin.
In neonates during the 1st week of life (especially preterms), the recommended dose is 75 mg/kg/day (corresponding to 25 mg/kg/day sulbactam and 50 mg/kg/day ampicillin) in divided doses every 12 hrs.
Overdosage
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 CFS concentrations of β-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 enhance elimination of the drug from the body if overdosage occurs in patients with impaired renal function.
Contraindications
Individuals with a history of an allergic reaction to any of the penicillins.
Patients hypersensitive to sulbactam sodium/ampicillin sodium. This drug may cause hypersensitivity reaction and may be fatal. Stop using the drug and consult a doctor if rash, irritation or edema occurs.
Special Precautions
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 a 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 adrenaline. Oxygen, IV 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. Should superinfection occur, the drug should be discontinued and/or appropriate therapy instituted.
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.
Effects on the Ability to Drive or Operate Machinery: None known.
Use in Pregnancy & Lactation: 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.
Caution should be exercised when sultamicillin is administered to a nursing woman. 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.
Use in Children: 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.
Use In Pregnancy & Lactation
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.
Caution should be exercised when sultamicillin is administered to a nursing woman. 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.
Side Effects
Unasyn Tablet: Sultamicillin is generally well tolerated. The majority of side effects observed were of mild or moderate severity and were normally tolerated with continued treatment.
Body as a Whole: Allergic reaction, anaphylactic shock and anaphylactoid reaction.
Central and Peripheral Nervous System Disorder: Dizziness
Gastrointestinal System Disorders: The most frequently observed side effect was diarrhea/loose stools. Nausea, vomiting, epigastric distress, melena and abdominal pain/cramps have been observed. As with other ampicillin-class antibiotics, enterocolitis and pseudomembranous colitis rarely may occur.
Respiratory System Disorder: Dyspnea.
Skin/Skin Structures: Rash and itching were infrequently observed, along with angioedema, dermatitis and urticaria.
Miscellaneous: Drowsiness/sedation, fatigue/malaise and headache have been rarely observed.
Adverse reactions associated with the use of ampicillin alone may be observed with sultamicillin.
Unasyn IM/IV: As with other parenteral antibiotics, the principal side effect observed is injection site pain, especially associated with the IM route of administration. A small number of patients may develop phlebitis or an injection site reaction after IM administration.
Blood and Lymphatic System Disorders: Anemia, hemolytic anemia, thrombocytopenia, eosinophilia and leukopenia have been reported during therapy with sulbactam sodium/ampicillin sodium. These reactions are reversible on discontinuation of therapy and are believed to be sensitivity reactions.
Gastrointestinal System Disorders: Nausea, vomiting, diarrhea, enterocolitis and pseudomembranous colitis.
Hepatobiliary Disorders: Bilirubinemia, abnormal hepatic function and jaundice.
Immune System Disorders: Anaphylactoid reaction and anaphylactic shock.
Investigations: Transient elevations of ALT (SGPT) and AST (SGOT) transaminases.
Nervous System Disorders: Rare reports of convulsions.
Renal and Urinary System Disorders: Rare reports of interstitial nephritis.
Skin and Subcutaneous Tissue Disorders: Rash, itching, other skin reactions, rare reports of Stevens-Johnson syndrome, epidermal necrolysis and erythema multiforme.
Adverse reactions associated with the use of ampicillin alone may be observed with sulbactam sodium/ampicillin sodium IM/IV.
Drug Interactions
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 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 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's reagent, Fehling's reagent and Clinitest. 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.
Unasyn IM/IV: Aminoglycosides: Mixing ampicillin with aminoglycosides in vitro has resulted in substantial mutual inactivation; if these groups of antibacterials are to be administered concurrently, they should be administered at separate sites at least 1 hr apart (see Incompatibilities).
Bacteriostatic Drugs (Chloramphenicol, Erythromycin, Sulfonamides and Tetracyclines): Bacteriostatic drugs may interfere with the bactericidal effect of penicillins; it is best to avoid concurrent therapy.
Incompatibilities: Sulbactam sodium/ampicillin sodium IM/IV and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.
Caution For Usage
Unasyn IM/IV: Instructions for Use: Sulbactam sodium is incompatible with most IV solutions, but ampicillin sodium and hence, sulbactam sodium/ampicillin sodium IM/IV is less stable in solutions containing dextrose or other carbohydrates, and should not be mixed with blood products or protein hydrosylates. Ampicillin and hence, sulbactam sodium/ampicillin sodium IM/IV is incompatible with aminoglycosides and should not be physically mixed in the same container (see Dosage and Administration). The concentrated solution for IM administration should be used within 1 hr of reconstitution. Time periods for use in different diluents for IV infusion are as follows: See Table 3.

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MIMS Class
ATC Classification
J01CR01 - ampicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.
J01CR04 - sultamicillin ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.
FC tab/susp: D; Inj: S
Presentation/Packing
Unasyn Tablet: FC tab 375 mg x 10 x 10's. 750 mg x 2 x 4's.
Unasyn Susp: Susp 250 mg/5 mL x 60 mL.
Unasyn IM/IV: Powd for inj 750 mg (vial, dry powd for reconstitution) x 1's. 1.5 g x 1's. 3 g x 1's.
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