Principen

DESCRIPTION

Ampicillin trihydrate is a semisyntheticpenicillinderived from the basic penicillinnucleus, 6-aminopenicillanic acid. Ampicillin is designated chemically as (2S, 5R, 6R)-6-[(8)-2-Amino-2-phenylacetamido]-3,3-dimethyl-t-oxo-4-thia-1- azabicyclo[3.2.0] heptane-2-carboxylic acid. The chemical formula is C₁₆H₁₉N₃O₄S·3H₂O and its molecular weight is 403.45.

This is the anhydrous form of ampicillin. It is prepared as the trihydrate form attached to 3 water (H2O) molecules.

PRINCIPEN Capsules(Ampicillin Capsules USP) for oral administration provide ampicillin trihydrate equivalent to 250 mg and 500 mg ampicillin.

Inactive ingredients:black iron oxide, gelatin, FD&C Blue #1, FD&C Red #3, FD&C Red #40, lactose monohydrate, silica gel, and titanium dioxide.

PRINCIPEN for Oral Suspension(Ampicillin for oral suspension USP) provide, after constitution, ampicillin trihydrate equivalent to 125 mg and 250 mg ampicillin per 5 mL.

Inactive ingredients:antifoam AF emulsion, Atmos 300, colloidal silicon dioxide, FD&C Red #40, lecithin, natural and artificial flavors, sucrose, sodium citrate, sodium benzoate, and vanillin.

INDICATIONS

PRINCIPEN Capsules (Ampicillin Capsules) and PRINCIPEN for Oral Suspension (Ampicillin for Oral Suspension) are indicated in the treatment of infections caused by susceptible strains of the designated organism listed below;

Infections of the Genitourinary Tract Including Gonorrhea:E. coli, P. mirabilis, enterococci,志贺氏杆菌, S. typhosaand otherSalmonella, and nonpenicillinase-producingN. gononhoeae.

Infections of the Respiratory Tract:Nonpenicillinase-producingH. influenzaeand staphylococci, and streptococci includingstreptococcus pneumoniae.

Infections of the Gastrointestinal Tract:志贺氏杆菌, S. typhosaand otherSalmonella, E. coli, P. mirabilis, and enterococci.

Meningitis:O. Meningitides.

Bacteriologystudies to determine the causative organisms and their sensetivity to ampicillin should be performed. Therapy may be instituted prior to the results of susceptibility testing.

DOSAGE AND ADMINISTRATION

Adults and Children Weight Over 20 kg.

Forgenitourinaryorgastrointestinal tractinfections other thangonorrheain men and women, the usual dose is 500 mg qid in equally spaced doses; severe or chronic infections may require larger doses.

For the treatment of gonerrhea in both men and women, a single oral dose of 3.5 grams of ampicillin administered simultaneously with 1gramof probenecid is recommended. Physicians are cautioned to use no less than the above recommended dosage for the treatment of gonorrhea. Follow-up cultures should be obtained from the original site(s) of infection 7 to 14 days after therapy. In women, it is also desirable to obtain culture test-of-cure from both the endo-cervicaland anal canals. Prolonged intensive therapy is needed for complications such as proshtitis andepididymitis. For respiratory tract infections, the usual dose is 250 mg qid in equally spaced doses.

Children Weighing 20 kg or Less

For genitourinary orgastrointestinaltract infections, the usual dose is 100 mg/kg/day total, qid in equally divided and spaced doses. For respiratory infections, the usual dose is 50 mg/kg/day total, in equally divided and spaced doses three to four times daily. Doses for children should not exceed doses recommended for adults,

All Patients, Irrespective of Age and Weight

Larger doses may be required for severe or chronic infections. Although ampicillin is resistant to degradation bygastricacid, it should be administered at least one half-hour before or two hours after meals for maximal absorption. Except for the single dose regimen for gonorrhea referred to above, therapy should be continued for a minimum of 48 to 72 hours after the patient becomesasymptomaticor evidence at bacterial eradication has been obtained. In infections caused byhemolyticstrains of streptococci, a minimum of 10 days treatment is recommended to guard against the risk ofrheumatic feverof glomerulonephritis (seePRECAUTIONS—Laboratory Tests). In the treatment of chronic urinary or gastrointestinal infections, frequent bacteriologic and clinical appraisal is necessary during therapy and may be necessary for several months afterwards. Stubborn infections may require treatment for several weeks. Smaller doses than those indicated above should not be used.

HOW SUPPLIED

PRINCIPEN Capsules (Ampicillin Capsules USP):

250 mg/capsule:Size 2 capsule with a light gray body and scarlet cap. Printed in black ink with BRISTOL 7902 on both body and cap.

bottles of 100 NDC 0003-0122-50
bottles of 500 NDC 0003-0122-60
Unimatic, unit dose packs of 100 NDC 0003-0122-51

500 mg/capsule:Size 0 capsule with a light gray body and scarlet cap. Printed in black ink with BRISTOL 7093 on both body and cap.

bottles of 100 NDC 0003-0134-50
bottles of 500 NDC 0003-0134-60
Unimatic, unit dose packs of 100 NDC 0003-0134-51

PRINCIPEN for Oral Suspension (Ampicillin for Oral Suspension USP):

Ampicilin 125:当constituted as directed on the container label, a pleasant fruit-flavored suspension containing: 125 mg per 6 mL, In bottle sizes for preparation of

100 mL NDC 0003-0969-09
150 mL NDC 0003-0969-52
200 mL NOC 0003-0969-61

Ampicilin 260:当constituted as directed on the container label, a pleasant fruit-flavored suspension containing: 250 mg per 5 mL, In bottle sizes for preparation of

100 mL NDC 0003-0972-52
200 mL NDC 0003-0972-61

Storage

Capsules:Store at room temperature; avoid excessive heat; keep tightly closed.

Ampicilin for oral suspension:Store at room temperature; after constitution, discard unused portion after 7 days if kept at room temperature or after 14 days if refrigerated; keep bottles tightly closed.

ForRxonly

SIDE 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 penicillin and in those with a history ofallergy,asthma,hay fever, orurticaria.

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

Gastrointestinal:glositis, stamatitis, nausea, vomiting, enterocolitis,pseudomembranous colitis, and diarrhea. These reactions are usually associated with oral dosage forms of the drugs.

Hypersensitivity Reactions:An erythematous, mildlypruritic, maculopapular skin rash has been reported fairly frequently. The rash, which usually does not develop within the first week of therapy, may cover the entire body including the soles, palms, and oralmucosa. The eruption usually disappears in three to seven days.

Other hypersensitivity reactions that have been reported are: skin rash,pruritus, urticaria,erythema multiforme, and an occasional case of exfoliativedermatitis.Anaphylaxisis the most serious reaction experienced and has usually been associated with theparenteraldosage form of the drug

Note:Urticaria, other skin rashes, and serum sickness-like reactions may be controlled byantihistamines,如果有必要,系统性皮质类固醇。当ever 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 anaphylactoid reactions require emergency measures (see警告).

Liver:Moderate elevation in serum glutamic oxalaacetic transaminase (SGOT) has been noted, but the significance of this finding is unknown.

Hemic and Lymphatic Systems:Anemia,thrombocytopenia, thrombocytopenicpurpura,eosinophilia, leukapenia, and agranulacytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Other:Other adverse reactions that have been reported with the use at ampicillin arelaryngealstride and high fever. An occasional patient may complain ofsore口或ngue as with any oral penicillin preparation.

DRUG INTERACTIONS

当administered concurrently, the following drugs may interact with ampicillin.

Allopurinol:Increased possibility of skin rash, particularly in hyperuricemic patients may occur.

Bacteriostatic Antibiotics:Chloramphenicol, erythromycins,sulfonamides, or tetracyclines may interfere with the bactericidal effect of penicillins. This has been demonstrated in view, however, the clinical significance of this interaction is not well documented.

Oral Contraceptives:May be less effective and increased breakthrough bleeding may occur.

Probenecid:May decrease renal tubular secretion of ampicillin resulting in increased blood levels and/or ampicillin toxicity.

Drug/Laboratory Test Interaction

After treatment with ampicillin, a false-positive reaction for glucose in the urine may occur withcoppersulfate tests (Benedict's solution, Fehling's solution, or Clinitest tablets) but not with enzyme based tests such as Clinistix and Glucose Enzymatic Test Strip USP.

警告

严重的过敏症(ana和偶尔的致命的phylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral administration, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history at 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 who have experienced severe hypersensitivity reactions when treated with cephalosporins. Before initiating therapy with any 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 withepinephrine. Oxygen, intravenous steroids, and airway management, includingintubation, should also be administered as indicated.

Pseudomembranouscolitishas been reported with nearly allantibacterialagents, including ampicillin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normalflora的colonand may permit overgrowth of clostridia. Studies indicate that atoxinproduced byclostridium difficile, is one primary cause of "antibiotic-associated colitis". After the diagnosis of pseudomembranous colitis has bean established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective againstC. difficilecolitis.

PRECAUTIONS

General

Prolonged use of antibiotics may promote the overgrowth of nonsusceptible organisms, including fungi. Should superinfection occur, appropriate measures should be taken. Patients with gonorrhea who also havesyphilisshould be given additional appropriate parenteral penicillin treatment. Treatment with ampicillin does not preclude the need for surgical procedures, particularly in staphylococcal infections.

Laboratory Tests

In prolonged therapy, and particularly with high dosage regimens, periodic evaluation of the renal, hepatic, andhematopoieticsystems is recommended.

In streptococcal infections, therapy must be sufficient to eliminate the organism (10 days minimum); otherwise thesequelaeof streptococcal disease may occur. Cultures should be taken following completion of treatment to determine whether streptococci have been eradicated.

Cases of gonococcal infection with a suspectedlesionof syphilis should have darkfield examinations ruling out syphilis before receiving ampicillin. Patients who do not have suspected lesions of syphilis and are treated with ampicillin should have a follow- up serologic test for syphilis each month for four months to detect syphilis that may have been masked from treatment for gonorrhea.

Drug Interactions

SeeDRUG INTERACTIONSsection.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenesis,mutagenesis, or impairment of fertility in males or females.

Pregnancy

Teratogenic Eftects:Category B:Reproduction studies in animals have revealed no evidence of impaired fertility or harm to the fetus due to penicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, penicillin should be used during pregnancy only if clearly needed.

劳动和交付

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 contractians, 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 thatforcepsdelivery or other obstetrical intervention orresuscitation的newborn will be necessary.

Nursing Mothers

Ampicillin-class antibiotics are excreted in milk. Ampicillin used by nursing mothers may lead to sensitization of infants; therefore, a decision should be made whether to discontinue nursing or to discontinue ampicillin, taking into account the importance of the drug to the mother.

Pediatric Use

Penicillins are excreted primarily unchanged by the kidney, therefore, the incompletely developed renal functioning neonates and young infants will delay the excretion of penicillin. Administration to neonates and young infants should be limited to the lowest dosage compatible with an effective therapeutic regimen (seeDOSAGE AND ADMINISTRATION).

OVERDOSE

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 byhemodialysisbut not byperitoneal dialysis.

CONTRAINDICATIONS

A history of a previous hypersensitivity reaction to any of the penicillins is acontraindication. Ampicillin is also contraindicated in infections caused by penicillinase-producing organisms.

CLINICAL PHARMACOLOGY

Ampicillin is bactericidal at low concentrations and is clinically effective not only against thegram-positiveorganisms usually susceptible to penicillin G but also against a variety ofgram-negativeorganisms. It is stable in the presence of gastric acid and is well absorbed from the gastrointestinal tract. It diffuses readily into most body tissues and fluids; however, penetration into thecerebrospinal fluidand brain occurs only with meningeal inflammation. Ampicillin is excreted largely unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid which inhibits the renal tubular secretion of ampicillin. In blood serum, ampicillin is the least bound of all the penicillins; an average of about 20 percent of the drug is bound to plasma proteins as compared to 60 to 90 percent of the other penicillins. The administration of 500 mg dose of ampicillin capsules results in an average peak blood serum level of approximately 3.0 mcg/mL; the average peak serum level for the same dose of ampicillin for oral suspension is approximately 3.4 mcg/mL.

Microbiology

Whilein vitrostudies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in theINDICATIONS AND USAGEsection has not been documented.

Gram-Positive:strains of alpha- and beta-hemolytic streptococci,Streptococcus pneumoniae, those strains of staphylococci, which do not produce penicillinase,Clostridium sp., Bacillus anthracis, Corynebacterium xeroses, and most strains of enteracocci.

Gram-Negative:Hemophilus influenzae; Neisseria gonorrhoaeandN. Meningitides;Proteus mirabilis, and many strains of Salmonella (includingS. typhosa),志贺氏杆菌, andEscherichia coli.

Note:Ampicillin is inactivated by penicillinase and therefore is ineffective against penicillinase-producing organisms including certain strains at staphylococci,Pseudomonas aeruginosa, P. Vulgaris, Klebsiella pneumoniae, Enterobacter aerogenes, and some strains ofE. coli. Ampicillin is not active againstRickettsia,Mycoplasma, and "largeviruses" (Miyagawanella).

Testing for Susceptibility:The invading organism should be cultured and its susceptibility demonstrated as a guide to therapy. If the Kirby-Bauer method ofdiscsusceptibility is used, a 10 mcg ampicillin disc should be used to determine the relativein vitrosusceptibility.

PATIENT INFORMATION

1. The patient should inform the physician of any history of sensitivity to allergens, including previous hypersensitivity reactions to penicillins and cephalosporins (see警告).

2. The patient should discontinue ampicillin and contact the physician immediately if any side effect occurs (see警告).

3.氨苄青霉素与完整的玻璃应采取(8oz) of water, one-half hour before or two hours after meals.

4. Diabetic patients should consult with the physician before changing diet or dosage ofdiabetesmedication (seePRECAUTIONS—Drug/Laboratory Test Interactions).