Description
The Cathay Drug Co., Inc.
FORMULATION
Each vial contains:
Ampicillin (as sodium) …………………….. 250 mg
Sulbactam (as sodium) …………………… 125 mg
Each vial contains:
Ampicillin (as sodium) …………………….. 500 mg
Sulbactam (as sodium) …………………… 250 mg
Each vial contains:
Ampicillin (as sodium) …………………….. 1 g
Sulbactam (as sodium) …………………… 500 mg
Product Description
Ampicillin sodium/sulbactam sodium (Silgram) parenteral combination, is available as a white to off-white dry powder for reconstitution. Ampicillin sodium/Sulbactam sodium (Silgram) dry powder is freely soluble in aqueous diluents to yield pale yellow
Ampicillin sodium/Sulbactam sodium (Silgram) is an injectable antibacterial combination consisting of the semisynthetic antibiotic Ampicillin sodium and the beta-lactamase inhibitor Sulbactam sodium for intravenous and intramuscular administration. Ampicillin sodium is derived fromt eh penicillin nucleus, 6-aminopenicillinic acid. Chemically, it is monosodium (2S, 5R, 6R)-6-{®-2-amino-2-phenylacetamido}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylate and has a molecular weight of 371.39. Its chemical formula is C16H18N3NaO4S.
Ampicillin sodium
Sulbactam sodium
Sulbactam sodium is a derivative of the basic penicillin nucleus. Chemically, Sulbactam sodium is a sodium penicillinate sulfone; sodium (2S, 5R)-3,3-dimethyl-7-oxo–4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylate 4,4-dioxide. Its chemical formula is C8H10NNaO5S with a molecular weight of 255.22.
CLINICAL PHARMACOLOGY
Immediately after completions of a 15-minute intravenous infusion of Ampicillin sodium/Sulbactam sodium (Silgram), peak serum concentrations of ampicillin and sulbactam are obtained. Ampicillin serum levels are similar to those produced by the administration of equivalent amounts of ampicillin alone. The mean serum half-life of both drug is approximately 1 hour in healthy volunteers. Approximately 75 to 85% of both ampicillin and sulbactam are excreted unchanged in the urine during the first 8 hours after administration of Ampicillin sodium/Sulbactam sodium (Silgram) to individuals with normal renal function.
INDICATIONS
Ampicillin sodium/Sulbactam sodium (Silgram) is indicated in the treatment of the following:
- Community acquired pneumonia
- Upper urinary tract infections
- Intra-abdominal infections
- gynaecological infections
- skin and soft tissue infections
- prophylaxis to reduce the risk of infections following abdominal surgery
CONTRAINDICATIONS
The use of Ampicillin sodium/Sulbactam sodium (Silgram) is contraindicated individuals with a history of hypersensitivity to any of the active substances (ampicillin and sulbactam); to any other penicillin or to any of the excipients. It is also contraindicated in individuals with history of severe immediate hypersensitivity reaction (e.g. anaphylaxis to another beta lactam agent (e.g.cephalosporins, carbapanem or monobactam)
DOSAGE AND ADMINISTRATION
Ampicillin sodium/Sulbactam sodium (Silgram) may be administered by either the IV or the IM routes.
For IV administration, the dose can be given slow intravenous injection over at least 10-15 minutes or can also be delivered, in greater dilutions with 50 – 100 mL of a compatible diluent as an intravenous infusion over 15 – 30 minutes.
Ampicillin sodium/Sulbactam sodium (Silgram) may be administered by deep intramuscular injection.
Adult dosage
The recommended dose is 3 g to 12 g depending on the severity of the infection divided into equal single doses every six (6) hours.
Pediatric dosage
For pediatric patients who weighs 40 kg or more may receive the usual adult dosage.
For children over 2 years old – the recommended dose is 150 mg/kg/day (ampicillin 100 mg/kg/day + sulbactam 50 mg/kg/day). The therapeutic dosage should be given in three or four divided doses.
The intramuscular application should not be given in newborn infants, infants and toddlers (below 2 years old). Ampicillin sodium/Sulbactam sodium (Silgram) should be given exclusively by intravenous use according to the following indications:
- For newborn infants above the second living week, infants and toddlers till 2 years old the recommended dose is 150 mg/kg/day (ampicillin 100 mg/kg/day + sulbactam 50 mg/kg/day). The therapeutic dosage should be given in three or four divided doses.
- For newborn infants in the first living week, the recommended dose is 75 mg/kg/day (ampicillin 50 mg/kg/day + sulbactam 25 mg/kg/day). The therapeutic dosage should be given in two divided doses.
For the treatment of acute pelvic inflammatory disease, may receive a dosage of 3 g (2 g of Ampicillin plus 1 g of Sulbactam) every 6 hours in conjunction with doxycycline (100 mg every 12 hours administered IV or orally). The parenteral regimen may be discontinued 24 hours after clinical improvement. However, oral doxycycline should be continued to complete 14 days therapy.
Use in the elderly: Ampicillin sodium/Sulbactam sodium injection may be administered in the elderly in the usual dosages with no special precautions.
Prophylaxis of surgical infections: 1.5 g – 3 g Ampicillin sodium/Sulbactam sodium injection should be given at induction of anesthesia, which allows time to achieve effective serum and tissue concentrations during the procedure. In case of long-term surgery another dose in 3 – 4 hours may be administered. Administration of Ampicillin sodium/Sulbactam sodium is usually stopped 24 hours after the majority of surgical procedures unless a therapeutic overdose is indicated.
Use in patients with renal impairment
In patients with renal impairment (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 whatever the renal function is. The dose of Ampicillin sodium/Sulbactam sodium in such patients should be administered less frequently in accordance with the usual practice for ampicillin.
Recommended dosages for patients with impaired renal function
| Creatinine clearance (mL/min) | Dose interval |
| >30 | 6 to 8 hours |
| 15 to 30 | 12 hours |
| 5 to 14 | 24 hours |
| < 5 | 48 hours |
Sulbactam sodium and ampicillin sodium are both eliminated from the blood stream to an equal extent by hemodialysis treatment. Ampicillin sodium/Sulbactam sodium should therefore be administered immediately after dialysis and then 48 hour intervals until the following dialysis treatment.
Duration of use: the duration of treatment depends on the course of the illness. The duration of treatment is generally 5 to 14 days depending on the severity of the infection. In severe cases, treatment may be continued for a prolonged period. The treatment should be continued for another 48 hours after the fever and other symptoms of the disease subsided.
DIRECTION FOR USE
For intravenous and Intramuscular administration, the following dilutions may be used:
| Strength/Vial | Volume of Diluent to be added | Withdrawal volume |
| 375 mg | 0.8 mL | 1.0 mL |
| 750 mg | 1.6 mL | 2.0 mL |
| 1.5 g | 3.2 mL | 4.0 mL |
- For 250 mg/125 mg: Dissolve contents of the vial by adding 0.8 mL of Sterile Water for Injection. Final volume is 1 mL.
- For 500 mg/250 mg: Dissolve contents of the vial by adding 1.6 mL of Sterile Water for Injection. Final volume is 2 mL.
- For 1 g/500 mg: Dissolve contents of the vial by adding 3.2 mL of Sterile Water for Injection. Final volume is 4 mL.
Note: Concentrated solution (375 mg/mL), must be administered within one hour after preparation.
For deep intramuscular administration, Silgram may be reconstituted with 0.5% Lidocaine hydrochloride injection if pain is experienced.
For intravenous administration, Silgram may be reconstituted with sterile water for injection or any of the compatible diluents described below. Solution should be allowed to stand after reconstitution to allow any foaming to dissipate in order to permit visual inspection for complete dissolution.
An appropriate volume should then be immediately diluted with a suitable parenteral diluent to yield solutions containing 3 to 45 mg (Silgram) per mL (2 to 30 mg Ampicillin/ 1 to 15 mg Sulbactam per mL).
Maximum Concentration
| Diluent | (mg/mL) (Ampicillin/Sulbactam) | Use Periods |
| Sterile Water for Injection | 45 (30/15)
45 (30/15) 30 (20/10) |
8hours at 25°C
48 hours at 4°C 72 hours at 4°C |
| 0.9% Sodium Chloride Injection | 45 (30/15)
45 (30/15) 30 (20/10) |
8hours at 25°C
8 hours at 4°C 72 hours at 4°C |
| 5% Dextrose Injection | 30 (20/10)
30 (20/10) 3 (2/1) |
2 hours at 25°C
4 hours at 4°C 4 hours at 25°C |
| Lactated Ringer’s Injection | 45 (30/15)
45 (30/15) |
8hours at 25°C
24 hours at 4°C |
| M/6 Sodium Lactate Injection | 45 (30/15)
45 (30/15) |
8hours at 25°C
8 hours at 4°C |
| 5%Dextrose in 0.45% Saline | 3 (2/1)
15 (10/5) |
4 hours at 25°C
4 hours at 4°C |
WARNINGS AND PRECAUTIONS
Serious and occasionally fatal hypersensitivity (anaphylactic), penicillin hypersensitivity and/or hypersensitivity reactions to multiple allergens.
Careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins and other allergens. If an allergic reaction occurs, Ampicillin sodium/Sulbactam sodium (Silgram) should be discontinued and the appropriate therapy instituted.
Serious anaphylactoid reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids and airway management including intubation should be administered as indicated.
General: A high percentage of patients with mononucleosis who receive ampicillin develop skin rash. Thus, Ampicillin class antibiotics should not be administered to patients with mononucleosis.
Periodic assessment of organ system functions, including renal, hepatic and hematopoietic function is advisable during prolonged therapy (more than 14 days). The monitoring is very important in neonates, and in other pediatric patients.
In patients treated with Ampicillin sodium/Sulbactam sodium (Silgram) 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.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
During treatment with Ampicillin sodium/Sulbactam sodium, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.
Administration of ampicillin may reduce the efficacy of oral contracetptives. Supplemental non-hormonal contraceptive measures may be required.
Antibiotic-associated colitis has been reported with nearly all antibacterial agents including Ampicillin sodium/Sulbactam sodium and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, Ampicillin sodium/Sulbactam sodium should be immediately discontinued, a physician be consulted, and an appropriate therapy initiated. Anti-peristatic drugs are contraindicated in this situation.
Ampicillin sodium/Sulbactam sodium 1g/500 mg: this medicinal product contains 5 mmol (115 mg) of sodium/vial of powder for solution for injection or infusion. To be taken into consideration for patients on controlled sodium diet.
DRUG INTERACTIONS
Effects of other medicinal products: Acetylsalicylic acid, indomethacin and phenylbutazone decrease excretion of penicillins.
Other antibiotics or chemotherapeutic agents
Ampicillin sodium/ Sulbactam sodium should not be combined with bacteriostatic chemotherapeutics or antibiotics such as tetracyclines, erythromycin, sulphonamides or chloramphenicol due to the possibility of reduced effectiveness.
Ampicillin sodium / Sulbactam sodium (Sllgram) and aminoglycosides should not be reconstituted together due to the in vitro inactivation of aminoglycosides by the ampicillin component of Ampicillin sodium / Sulbactam sodium (Silgram). If concomitant treatment is necessary the two substances should be administered at different sites at a time interval of at least one hour.
Allopurinol
The concurrent use of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with Ampicillin sodium /Sulbactam sodium (Silgram) and allopurinol administered concurrently.
Anticoagulants
The changes in platelet aggregation and prothrombin time observed with parenterally administered penicillins may be increased on simultaneous administration of anticoagulants.
Methotrexate
The concurrent administration of methotrexate and penicillins resulted in reduced methotrexate clearance and consequentially in methotrexate toxicity. These patients should be closely monitored and the increased and prolonged administration of Leucovorin should be considered.
Probenecid
Probenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with Ampicillin sodium / Sulbactam sodium (Silgram) may result in increased and prolonged blood levels of ampicillin and sulbactam.
Hormonal contraceptives
During treatment with aminopenicillins, the reliability of the contraceptive effect of hormonal contraceptives (“the pill”) may be compromised in rare cases. It is therefore recommended to additionally use non-hormonal methods of contraception.
Influence of laboratory tests
A high concentration of ampicillin in urines may result in false positive values of glucosuria. The use of glucose tests based on enzymatic glucose oxidase reactions is recommended.
ADVERSE EFFECTS
The following undesirable effects have been observed and reported during treatment with ampicillin sodium I sulbactam sodium with the following frequencies: Very common (:?1110); common (k1/100 to <1/10); uncommon (21/1,000 to 51/100); rare 1/10,000 to 51/1,000); very rare (51/10,000), not known (cannot be estimated from the available data)
The most common undesirable effects are pain at the injection site, phlebitis, nausea, vomiting, meteorism and diarrhea. For severe and persistent diarrhea, the possibility of potentially fatal antibiotic-associated pseudomembranous colitis should be considered. In these cases, Ampicillin sodium/ Sulbactam sodium should therefore be discontinued immediately and a suitable therapy (e.g. oral vancomycin 4 x 250 mg daily) instituted. Drugs that inhibit peristalsis are contraindicated.
Infections and infestations
Not known: Overgrowth of non- sensitive organisms
Blood and lymphatic system disorders
Very rare: Hematocytological changes such as reversible and hemolytic anemia, thrombocytopenia, eosinophilia and leucopenia. Impairment of blood coagulation. Immune system disorders
Rare: Hypersensitivity reactions like urticaria, fever, maculopaputar eruptions are possible. If such symptoms occur, the drug should be discontinued and the doctor consulted. An immediate reaction in the form of urticaria generally indicates a true penicillin allergy and requires discontinuation of the treatment.
Severe acute hypersensitivity reactions can appear such as: facial edema, swelling of the tongue, swelling of the larynx narrowing of the airways, severe skin reactions such as erythema exsudativum multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis (Lyell’s syndrome), tachycardia, dyspnea, drug fever, eosinophilia, serum sickness, hemolytic anemia, allergic vasculitis and nephritis, hypotension, anaphylactoid reaction, anaphylactic shock.
On occurrence of these signs, immediate medical assistance may be necessary.
Skin fungi and penicillin can share antigenic properties, so that hypersensitivity reactions as seen after a second contact may occur even on the first administration of a penicillin in a person currently or previously suffering from a fungal skin infection.
Nervous system disorders
Uncommon: Vertigo and headache. Neurotoxic reactions (cramps) in events of meningitis or epilepsy, particularly after administration of high doses and impaired renal function respectively.
Gastrointestinal disorders
Common: Nausea, vomiting, meteorism and diarrhea can occur. If severe and persistent diarrhea occurs, the possibility of antibiotic- related pseudomernbranous colitis should be considered, which can be life-treating. Therefore in these cases .Ampicillin sodium! Sulbactam sodium should be discontinued immediately and a suitable therapy (e.g. oral vancomycin 250 mg four times daily) instituted. Peristalsis inhibiting drugs are contraindicated.
Hepatobiliary disorders
Very rare: Transient and reversible increase in transaminases (SGOT [ALT]. SGPT [AST], bilirubinemia, abnormal liver function tests, jaundice
Skin and subcutaneous tissue disorders
Uncommon: Rash, pruritus and other cutaneous reactions. The typical, measles-like ampicillin rash (ampicillin- associated exanthema) that occurs 5 to 11 days after the start of the treatment, does not necessarily preclude subsequent treatment with penicillin derivatives.
Musculoskeletal and connective tissue disorders
Very rare: Transient and minor increase of creatine phosphokinase (CPK)
Renal and urinary disorders
Rare: Interstitial Nephritis, crystalluria by high intravenous dosage.
General disorders and administration site conditions
Very common: Intramuscular injection may be followed by pain at the injection site. Common: Intravenous administration may be followed by phlebitis or pain at the injection site.
Diarrhea
Rare: As with other parenteral antibiotics, pain at the injection site particularly in connection with an intravenous administration was reported as primary side effects. In some patients phlebitis or reactions in the area of the injection site may occur.
Asthenia, sleepiness.
Adverse reactions usually associated with ampicillin alone may also occasionally occur with ampicillin/sulbactam: Arthralgia, stomatitis, black tongue discoloration, agranulocytosis, hereditary angioneurotic edema, exfoliative dermatitis and erythema multiforme as well as the occurrence of an anaphylactic shock with a penicillin-hypersensitivity.
OVERDOSE
Only limited experience is available for the acute toxicity of ampicillin sodiumisulbactam sodium. Overdose may induce symptoms corresponding to the undesirable effect profile of Ampicillin sodium/ Sulbactam sodium. In such cases, these described undesirable effects may possibly be observed more frequently and in a more severe form. In very high doses, beta- lactam antibiotics can induce cerebral (epileptic) seizures. Since ampicillin and sulbactam can be removed by hemodialysis, in the event of overdose, higher elimination can be achieved by hemodialysis in patients with renal impairment.
TREATMENT
Sedation with diazepam for seizures resulting from overdose.
AVAILABILITY
Silgram 250 mg/ 125 mg Sterile Powder for Injection IM/ IV —Type III Clear Glass Vial with rubber stopper and aluminum seal (Box of l’s)
Silgram 500 mg/ 250 mg Sterile Powder for Injection IM/ IV —Type III Clear Glass Vial with rubber stopper and aluminum seal (Box of l’s)
Silgram 1 g/ 500 mg Sterile Powder for Injection IM/ IV — Type III Clear Glass Vial with rubber stopperand aluminum seal (Box of l’s)
STORAGE
Store at temperatures not exceeding 30°C.
Marketing Authorization Holder
THE CATHAY DRUG CO., INC.
2/F Vernida I Condominium, 120 Amorsolo St., Legaspi Village, Makati City
Manufacturer
YSS LABORATORIES CO., INC.
1133 United Nations Ave., Paco, Manila
Date of revision: July 3, 2019
Reviews
There are no reviews yet.