Ampicillin Sodium Injection IP 500mg (AMP-TAJ) Taj Pharma

1. COMPOSITION:
   (a) Ampicillin Sodium Injection IP 500mg (Amp-Taj) Taj Pharma
   1 vial contains 500mg of Ampicillin Sodium IP
   
   (b) Ampicillin Sodium Injection IP 1g (Amp-Taj) Taj Pharma
   1 vial contains 1000mg of Ampicillin Sodium IP

   c) Ampicillin Sodium Injection IP 2g (Amp-Taj) Taj Pharma
   1 vial contains 2000mg of Ampicillin Sodium IP

2. DOSAGE FORM:
   Dry Powder Injection
3. DESCRIPTION:
   Ampicillin for Injection the monosodium salt of [2S-[2α, 5α, 6β(S*)]]-6-[(aminophenylacetyl) amino]-3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid, is a synthetic penicillin. It is an antibacterial agent with a broad spectrum of bactericidal activity against both penicillin-susceptible Gram-positive organisms and many common Gram-negative pathogens.
4. PHARMACOLOGY:
   Ampicillin for Injection diffuses readily into most body tissues and fluids. However, penetration into the cerebrospinal fluid and brain occurs only when the meninges are inflamed. Ampicillin is excreted largely unchanged in the urine and its excretion can be delayed by concurrent administration of probenecid. Due to maturational changes in renal function,  ampicillin half-life  decreases  as postmenstrual age (a sum of gestational age and postnatal age) increases for infants with postnatal age of less than 28 days. The active form appears in the  bile  in higher  concentrations  than those  found in serum. Ampicillin is the least serum-bound of all the penicillins, averaging about 20% compared to approximately 60 to 90% for other penicillins. Ampicillin for Injection is well-tolerated by most patients and has been given in doses of 2 grams daily for many weeks without adverse reactions.

4.1 Microbiology

While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been demonstrated.

Antibacterial Activity

The following bacteria have been shown in in vitro studies to be susceptible to Ampicillin for Injection:

Gram-positive Bacteria

Hemolytic and nonhemolytic streptococci Streptococcus pneumoniae Nonpenicillinase-producing staphylococci Clostridium spp.

1. anthracis

Listeria  monocytogenes Most strains of enterococci. Gram-negative Bacteria

1. influenzae
2. gonorrhoeae
3. meningitidis Proteus mirabilis

Many strains of Salmonella, Shigella, and E. coli. AMPICILLIN does not resist destruction by penicillinase. Susceptibility Test Methods

Diffusion Techniques

Quantitative methods that require measurement of zone diameters provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure1,2 that has been recommended for use with disks to test the  susceptibility of microorganisms  to  ampicillin, uses the  10 mcg ampicillin disk. Interpretation involves correlation of the diameter obtained in the disk test with the minimum inhibitory concentration (MIC) for ampicillin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 10 mcg ampicillin disk should be  interpreted according to the criteria provided in Table 1.

Dilution Techniques

Quantitative methods that are used to determine minimum inhibitory concentrations (MICs) provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One suchstandardized procedures1,3 uses a standardized dilution method (broth or agar) or equivalent with ampicillin powder. The MIC values obtained should be interpreted according to the criteria provided in Table 1.

TABLE 1: SUSCEPTIBILITY TEST INTERPRETIVE CRITERIA

Non-meningitidis S. pneumoniae isolates may be considered susceptible to ampicillin if the isolate has a penicillin MIC of ≤ 0.06 mcg/mL.

Susceptibility of staphylococci to ampicillin may be deduced from testing only penicillin and either cefoxitin or oxacillin.

A report of “Susceptible”(S) indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in the blood. A report of “Intermediate” (I) indicates that the result should be considered equivocal, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of the drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major  discrepancies in interpretation. A report of “Resistant” (R) indicates that the pathogen is not likely to be inhibited if the  antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory control microorganisms1,2,3.

The 10 mcg ampicillin disk and the standard ampicillin powder should provide respectively the following zone diameters and MIC values in these laboratory test quality control strains:

TABLE 2: ACCEPTABLE QUALITY CONTROL RANGES

4.2 INDICATIONS:       
Ampicillin for Injection is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the following conditions:

Respiratory Tract Infections caused by Streptococcus pneumoniae, Staphylococcus aureus

(penicillinase and nonpenicillinase-producing), H. influenzae, and Group A beta-hemolytic streptococci.

Bacterial Meningitis caused by E. coli, Group B streptococci, and other Gram-negative bacteria (Listeria monocytogenes, N. meningitidis). The addition of an aminoglycoside with ampicillin may increase its effectiveness against Gram-negative bacteria.

Septicemia and Endocarditis caused by susceptible Gram-positive organisms including Streptococcus spp., penicillin G-susceptible staphylococci, and enterococci. Gram-negative sepsis caused by E. coli, Proteus mirabilis and Salmonella spp. responds to ampicillin. Endocarditis due to enterococcal strains usually respond to intravenous therapy. The addition of an aminoglycoside  may  enhance  the effectiveness of ampicillin when treating streptococcal endocarditis.

Urinary Tract Infections caused by sensitive strains of E. coli and Proteus mirabilis.

Gastrointestinal Infections caused by Salmonella typhi(typhoid fever), other Salmonella spp., and

Shigella spp. (dysentery) usually respond to oral or intravenous therapy.

Bacteriology studies to determine the causative  organisms  and their susceptibility to  ampicillin should be performed. Therapy may be instituted prior to  obtaining  results of susceptibility testing. It is advisable to reserve the  parenteral form of this  drug  for moderately severe and severe infections  and for patients who are unable to take the oral forms. A change to oral ampicillin may be made as soon as appropriate.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ampicillin for Injection and  other  antibacterial  drugs, Ampicillin for Injection should be  used only to  treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Indicated surgical procedures should be performed.

4.3 DOSAGE AND ADMINISTRATION:
This insert is for a Pharmacy Bulk Package and is intended for preparing IV admixtures only. Dosage recommendations for intramuscular or direct intravenous injection are for informational purposes only.

Infections of the respiratory tract and soft tissues.

Patients weighing 40 kg (88 lbs) or more: 250 mg to 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 25 to 50 mg/kg/day in equally divided doses at 6-to 8-hour intervals.

Infections of the gastrointestinal and genitourinary tracts (including those caused by Neisseria gonorrhoeae in females).

Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6-to 8-hour intervals.

In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.

Urethritis in males due to N. gonorrhoeae.

Adults – Two doses of 500 mg each at an interval of 8 to 12 hours. Treatment may be repeated if necessary or extended if required.

In the treatment of complications of gonorrheal urethritis, such as  prostatitis  and epididymitis, prolonged and intensive therapy is recommended. Cases of  gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months.

The doses for the preceding infections may be given by either the intramuscular or intravenous route. A change to oral ampicillin may be made when appropriate.

Bacterial Meningitis

Adults and children – 150 to 200 mg/kg/day in equally divided doses every 3 to 4 hours. (Treatment may be initiated with intravenous drip therapy and continued with intramuscular injections.) The  doses for other infections may be given by either the intravenous or intramuscular route.

Neonates (less than or equal to 28 days of postnatal age) – Dosage should be based on Gestational age and Postnatal age according to Table 3.

TABLE 3: Dosage in Neonates (less than or equal to 28 days of postnatal age) for Bacterial Meningitis and Septicemia:

Septicemia

Adults and children – 150 to 200 mg/kg/day. Start with intravenous administration for at least three days and continue with the intramuscular route every 3 to 4 hours.

Neonates (less than or equal to 28 days of postnatal age) – Dosage should be based on Gestational age and Postnatal age according to Table 3 (above).

Treatment of all infections should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. A minimum of 10 days treatment is recommended for  any  infection caused by  Group A  beta-hemolytic  streptococci  to help prevent the occurrence of acute rheumatic fever or acute glomerulonephritis.

4.4 CONTRAINDICATIONS:     
A history of a previous hypersensitivity reaction to any of the penicillins is a contraindication.

4.5 WARNINGS:          
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy.

Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been well-documented reports of individuals with a history of penicillin hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating 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 appropriate therapy instituted.

Serious anaphylactoid reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ampicillin for injection, 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. 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.

4.6 PRECAUTIONS:     
General

The possibility of superinfections with mycotic organisms or bacterial pathogens should be kept in mind during therapy. In such cases, discontinue the drug and substitute appropriate treatment.

A high percentage (43 to 100 percent) of patients with infectious mononucleosis who receive ampicillin develop a skin rash.

Typically, the rash appears 7 to 10 days after the start of oral ampicillin therapy and remains for a few days to a week after the drug is discontinued. In most cases, the rash is maculopapular, pruritic, and generalized. Therefore, the administration of ampicillin is not recommended in patients with mononucleosis. It is not known whether these patients are truly allergic to ampicillin.

Prescribing ampicillin for injection in the absence of a 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 ampicillin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When ampicillin is prescribed to treat a bacterial infection, patients should be told that although it is 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 ampicillin 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 antibiotics, 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 antibiotic. If this occurs, patients should contact their physician as soon as possible.

Laboratory Tests

As with any potent drug, periodic assessment of organ system function, including renal, hepatic, and hematopoietic, should be made during prolonged therapy.

Transient elevation of serum transaminase has been observed following administration of ampicillin. The significance of this finding is not known.

Drug Interactions

The concurrent administration of allopurinol and ampicillin increases substantially the incidence of skin rashes in patients receiving both drugs as compared to  patients  receiving  ampicillin alone. It is not known whether this potentiation of ampicillin rashes is  due  to  allopurinol or the  hyperuricemia present in these patients.

Drug/Laboratory Test Interactions

With high urine concentrations of ampicillin, false-positive glucose reactions may occur if Clinitest, Benedict’s Solution, or Fehling’s Solution are used. Therefore, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix or Tes-Tape) be used.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

No long-term animal studies have been conducted with this drug.

Pregnancy Category B

Reproduction studies have been performed in laboratory animals at doses several times the human dose and have revealed no evidence of adverse  effects due  to  ampicillin. There are, however, no  adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Oral ampicillin-class antibiotics are poorly absorbed during labor. Studies in guinea pigs showed that intravenous administration of ampicillin slightly decreased the  uterine  tone  and  frequency of contractions, but moderately increased the height and duration of contractions. However, it is not known whether use of these drugs in humans during  labor  or  delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.

Nursing Mothers

Ampicillin is excreted in trace amounts in human milk. Therefore, caution should be exercised when ampicillin-class antibiotics are administered to a nursing woman.

Pediatric Use

Guidelines for the administration of these drugs to children, including neonates are presented in DOSAGE AND ADMINISTRATION section.

4.7 UNDESIRABLE EFFECTS:
As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever, or urticaria.

The following adverse reactions have been reported as associated with the use of ampicillin:

Gastrointestinal

Glossitis, stomatitis, black “hairy” tongue, nausea, vomiting, enterocolitis, pseudomembranous colitis, and diarrhea. (These reactions are usually associated with oral dosage forms.)

Hypersensitivity Reactions

Skin rashes and urticaria have been reported frequently. A few cases of exfoliative dermatitis and erythema multiforme have been reported. Anaphylaxis is the most serious reaction experienced and has usually been associated with the parenteral dosage form.

Note: Urticaria, other skin rashes, and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, ampicillin should be discontinued, unless, in the opinion of the physician, the condition being treated is life- threatening and amenable only to  ampicillin therapy. Serious anaphylactic  reactions require the immediate use of epinephrine, oxygen, and intravenous steroids.

Liver – A moderate rise in serum glutamic  oxaloacetic  transaminase  (SGOT) has  been noted, particularly in infants, but the significance of this finding is unknown. Mild transitory SGOT elevations have been observed in individuals receiving larger (two to four times) than usual and oft-repeated intramuscular injections. Evidence indicates that glutamic oxaloacetic  transaminase  (GOT) is released at the site of intramuscular injection of ampicillin sodium and  that the  presence  of  increased amounts  of this enzyme in the blood does not necessarily indicate liver involvement.

Hemic and Lymphatic Systems – Anemia, thrombocytopenia, thrombocytopenic  purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with the penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Central Nervous System – Seizures

4.8 OVERDOSAGE:     
In cases of overdose, discontinue medication, treat symptomatically, and institute  supportive  measures as required. In patients with renal function impairment, ampicillin-class antibiotics can be removed by hemodialysis but not peritoneal dialysis.

5. SHELF-LIFE:
   2 years
6. STORAGE AND HANDLING INSTRUCTIONS:
   Store intact vials at 20°C to 25°C (68°F to 77°F).

Solutions for IM or direct IV should be used within 1 hour.

Stability of parenteral admixture in NS at 25°C (77°F) is 8 hours (concentrations up to 30 mg/mL) and at 4°C (39°F) is 24 hours (concentration of 30 mg/mL) or 48 hours (concentrations up to 20 mg/mL). Protect from freezing.

6.1 PACKING INFORMATION:
Type I glass vial with rubber stopper containing 500mg/1000mg of ampicillin.

Pack of 1 vial.

7. MANUFACTURED IN INDIA BY:
   TAJ PHARMACEUTICALS LTD;
   Survey No. 622/2/1/4, Dedhrota, Himatnagar-Vijapur Highway, Dist-Sabarkantha, 383220, Gujarat.