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 ADMINISTRATIONsection.

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. Linear IgA bullous dermatosis has 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 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

To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx, LLC at 1- 800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 infusion 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 1.

TABLE 1: 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 1 (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.

DIRECTIONS FOR USE

Use only freshly prepared solutions. Intramuscular and intravenous injections should be administered within one hour after preparation since the potency may decrease significantly after this period.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

For Intramuscular Use – Dissolve contents of a vial with the amount of Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP, listed in the table below:

While Ampicillin for Injection, USP, 1 g and 2 g, are primarily for intravenous use, they may be administered intramuscularly when the 250 mg or 500 mg vials are unavailable. In such instances, dissolve in 3.5 or 6.8 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP, respectively. The resulting solution will provide a concentration of 250 mg per mL.  

For Direct Intravenous Use – Add 5 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP to the 250 mg and 500 mg vials and administer slowly over a 3- to 5- minute period. Ampicillin for Injection, USP, 1 g or 2 g may also be given by direct intravenous administration. Dissolve in 7.4 or 14.8 mL Sterile Water for Injection, USP, or Bacteriostatic Water for Injection, USP, respectively, and administer slowly over at least 10 to 15 minutes. CAUTION: More rapid administration may result in convulsive seizures.

For Administration by Intravenous Drip – Reconstitute as directed above (For Direct Intravenous Use) prior to diluting with Intravenous Solution. Stability studies on ampicillin sodium at several concentrations in various intravenous solutions indicate the drug will lose less than 10% activity at the temperatures noted for the time periods stated.

Only those solutions listed above should be used for the intravenous infusion of Ampicillin for Injection, USP. The concentrations should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of ampicillin is administered before the drug loses its stability in the solution in use.