Ampicillin Sodium for Injection BP (Eugia Pharma) Product Monograph

Actions and Clinical Pharmacology

Ampicillin has a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria. It acts through the inhibition of cell wall mucopeptide biosynthesis during the stage of active multiplication.

Indications and Clinical Use

The treatment of infections due to susceptible gram negative organisms (including strains of shigellae, S. typhosa and other salmonellae, E. coli, H. influenzae, and P. mirabilis) and susceptible gram positive organisms (including streptococci, pneumococci, and non-beta-lactamase (penicillinase) producing staphylococci).

To reduce the development of drug-resistant bacteria and maintain the effectiveness of

Ampicillin Sodium for Injection BP and other antibacterial drugs, Ampicillin Sodium for Injection BP should be used only to treat 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.

Contraindications

A history of allergic reactions to penicillin or cephalosporins.

Warnings

Before therapy, inquiry as to past penicillin or other allergies is essential as reactions occur more frequently in hypersensitive persons. During therapy, if allergic or anaphylactic reactions occur, discontinue treatment and initiate usual measures, i.e. antihistamines, pressor amines or corticosteroids. During long-term therapy, renal, hepatic, and hematopoietic functions should be checked periodically. Candidiasis and other superinfections may occur, especially in debilitated and malnourished patients, or those with low resistance to infection due to corticosteroids, immunosuppressors or irradiation.

The passage of any penicillin from blood into brain is facilitated by inflamed meninges and during cardiopulmonary bypass. In the presence of such factors and particularly in the presence of renal failure when high serum concentrations can be attained, central nervous system adverse effects including myoclonus, convulsive seizures and depressed consciousness can be expected. Although this complication has not been reported with ampicillin, it should be anticipated.

Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported in association with beta-lactam treatment. When SCAR is suspected, Ampicillin Sodium for Injection BP should be discontinued and appropriate therapy and/or measures should be taken.

Precautions

General: A high percentage of patients with infectious mononucleosis or lymphatic leukemia who receive ampicillin develop a skin rash, and the drug should not be administered to such patients. In most cases, the rash is maculopapular, pruritic, and generalized. Prolonged use of antibiotics may promote overgrowth of nonsusceptible organisms. Should superinfections occur, appropriate measures should be taken.

Susceptibility/Resistance

Development of Drug Resistant Bacteria

Prescribing Ampicillin Sodium for Injection BP in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development of resistant organisms.

Drug Interactions

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. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or to hyperuricemia present in these patients. Ampicillin and aminoglycosides should not be reconstituted together due to the in vitro inactivation of the aminoglycosides by the ampicillin.

Drug/Laboratory Test Interactions: 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.

With high urine concentrations of ampicillin, false-positive urinary glucose reactions may occur if copper reduction methods are used. Therefore, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be employed.

Pregnancy: Animal studies with ampicillin have shown no teratogenic effects. 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.

Lactation: Ampicillin is excreted in trace amounts in human milk. Therefore, caution should be exercised when ampicillin is administered to a nursing mother.

Use in Elderly: There are no known specific precautions for the use of ampicillin in the elderly.

Adverse Reactions

Gastrointestinal Disturbances: glossitis, stomatitis, black “hairy” tongue, nausea, vomiting, diarrhea, enterocolitis and pseudomembranous colitis. (These reactions are usually associated with oral administration.)

Hypersensitivity Reactions: Erythematous maculopapular rashes have been reported fairly frequently; uriticaria, erythema multiforme, and a few cases of exfoliative dermatitis have been observed. Anaphylaxis is the most serious reaction usually associated with parenteral administration.

Note: Uriticaria, other skin rashes, and serum sickness like reactions may be controlled with antihistamines, and if necessary, systemic corticosteroids. Serious anaphylactic reactions require the immediate use of epinephrine, oxygen and i.v. corticosteroids. In cases of infectious mononucleosis, where ampicillin has been administered, an extremely high incidence of generalized rash has been reported.

Renal: Interstitial nephritis has been reported.

Ototoxicity: Ampicillin may be ototoxic when given i.v. in very high doses.

Hepatic: A mild transitory elevation of serum glutamic oxaloacetic transaminase (SGOT) in individuals receiving large (2 to 4 times recommended dose) and often repeated i.m. injections.

Evidence indicates that serum glutamic oxaloacetic transaminase (SGOT) is released at the site of i.m. injection of sodium ampicillin and that the presence of the enzyme in the blood does not necessarily indicate liver involvement.

Hematologic Disturbances: Anemia, thrombocytopenia, thrombocytopenic purpura, hemorrhagic diathesis, eosinophilia, leukopenia and agranulocytosis have been reported rarely in association with ampicillin therapy. These reactions are usually reversible on discontinuation of the drug and are believed to be hypersensitivity phenomena.

Symptoms and Treatment of Overdosage

The treatment of overdosage would likely be needed only in patients with severely impaired renal function. In case of overdosage, 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 by peritoneal dialysis.

Dosage and Administration

Dosage:

Infections of the ear, nose, throat and lower respiratory tract: Adults: 250 to 500 mg every 6 hours. Children: 25 to 50 mg/kg/day in equally divided doses at 6-hour intervals. Infections of gastrointestinal tract and of the genitourinary tract: Adults: 500 mg every 6 hours. Children: 50 mg/kg/day in equally divided doses at 6-hour intervals.

Larger doses may be required for stubborn or severe infections. The children’s dosages are intended for individuals whose weights will not result in calculated dosage greater than that recommended for adults.

In the treatment of chronic urinary tract and intestinal tract infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used; higher doses may be needed at times. 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.

Treatment 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 betahemolytic streptococci. In gonorrhea therapy, serologic tests for syphilis should be performed initially and monthly for 3 months.

Administration:

Instruction for inserting the needle into the rubber stopper:

In order to avoid a coring phenomenon of the plug, when inserting the needle into the rubber stopper, it is recommended to use a needle of outside diameter less than or equal to 0.8 mm for the reconstitution of the product. Needle should be inserted only at the center of the rubber stopper, in vertical direction.

IM/Direct IV Use: Entire contents should be withdrawn and the dose injected over a period of 3-5 minutes.

IV Infusion: Entire contents should be withdrawn and the dose injected over a period of at least 10-15 minutes.

CAUTION: More rapid administration may result is convulsive seizures. The solution must be used immediately after reconstitution.

Pharmaceutical Information

Drug Substance

Stability & Storage Recommendations

Store the dry powder at room temperature (15°C to 25°C).

Reconstituted Solutions: Use sterile water for injection as the only diluent. Reconstituted solutions should be used immediately after reconstitution.

Reconstitution

I.M. Use: Using sterile water for injection, reconstitute as follows:

Withdraw the entire contents and use immediately after reconstitution.

Direct I.V. Use: Use sterile water for injection, reconstitute as follows:

For direct intravenous administration, the product should be diluted to a concentration of 50 mg/mL with Sterile Water for Injection and administered by slow injection (three to four minutes).

Withdraw the entire contents and use immediately after reconstitution.

I.V. Infusion: Use sterile water for injection for initial dilution of the 1 g and 2 g vials, and reconstitute as follows:

Withdraw the entire contents and use immediately after reconstitution.

Parenteral Products: Stability studies on ampicillin sodium, at concentrations of 2 mg/mL and 30 mg/mL in various i.v. solutions, indicate the drug will lose less than 10% activity at room temperature (22°C) for the time periods stated when the drug is added to the following infusion fluids:

Isotonic sodium chloride: (30 mg/mL) 8 hours

5% dextrose in water: (2 mg/mL) 0 hours

5% dextrose in 0.4% sodium chloride solution: (2 mg/mL) 0 hours

Availability of Dosage Forms:

REFERENCES:

1. 1. AMPICILLIN SODIUM FOR INJECTION, USP (Powder for Solution, 250 mg, 500 mg, 1000 mg or 2000 mg), submission control number 234483, Prescribing Information, Teva Canada Limited, February 14, 2020.