Ampicillin for Injection, USP (Sterimax) Product Monograph

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 FOR INJECTION, USP 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, ampicillinclass 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:

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 within 1 hour after reconstitution.

Pharmaceutical Information

Drug Substance:

Name: ampicillin sodium

Chemical Name: Sodium (2S, 5R, 6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate

Structural Formula:

Molecular Formula: C₁₆H₁₈NaN₃O₄S

Molecular Weight: 371.4 g/mol (anhydrous)

Description: Ampicillin sodium is a white to off-white crystalline powder. It is freely soluble, sparingly soluble in acetone practically insoluble in fatty oils and in liquid paraffin.

Composition: Each vial contains 250 mg, 500 mg, 1,000 mg, 2,000 mg or 10,000 mg of ampicillin base as the sodium salt. Each gram of ampicillin sodium for injection contains approximately 2.6 mEq of sodium.

Stability & Storage Recommendations: Store the dry powder at controlled room temperature not exceeding 25 °C.

Reconstituted Solutions: Use sterile water for injection as the only diluent.

Reconstituted solutions should be used within 1 hour when kept at controlled room temperature not exceeding 25 °C. Protect reconstituted solutions from freezing.

Reconstitution

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

Withdraw the entire contents and use within 1 hour 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 within 1 hour after reconstitution.

I.V. Infusion: Use sterile water for injection for initial dilution of the 1000 mg and 2000 mg vials, and reconstitute as follows:

Withdraw the entire contents and use within 1 hour after reconstitution.

Pharmacy Bulk Vial

Add 94 mL sterile Water for Injection. The resulting solution will contain 100 mg ampicillin activity per mL and is stable up to 1 hour at room temperature.

Dilute further within 1 hour with an appropriate IV solution to a final concentration as outlined in the following paragraph.

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:

Availability of Dosage Forms: AMPICILLIN FOR INJECTION, USP is supplied as a dry powder in vials containing: 250 mg, 500 mg, 1,000 mg, 2,000 mg or 10,000 mg of ampicillin base as the sodium salt.

Bibliography

1. 1. Ampicillin Sodium for Injection, USP, submission control number: 281284, Prescribing Information, Teva Canada Ltd. Apr 11, 2024