Amoxicillin
FDA Label NDC 16590-401

Formulations of amoxicillin for oral suspension, USP contain amoxicillin, a semisynthetic antibiotic, an analog of ampicillin, with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Chemically, it is (2S,5R,6R)-6-[(R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate. It may be represented structurally as:

Chemical Structure Image (Amoxicillin Os Structure)

Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. The effect of food on the absorption of amoxicillin from the suspension of amoxicillin has been partially investigated. The 400 mg formulation has been studied only when administered at the start of a light meal. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. The half-life of amoxicillin is 61.3 minutes. Most of the amoxicillin is excreted unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid. In blood serum, amoxicillin is approximately 20%  protein-bound.
 
Orally administered doses of amoxicillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels 1 to 2 hours after administration in the range of 1.5 mcg/mL to 3 mcg/mL and 3.5 mcg/mL to 5 mcg/mL, respectively.
 
Detectable serum levels are observed up to 8 hours after an orally administered dose of amoxicillin. Following a 1 gram dose and utilizing a special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid. Approximately 60%  of an orally administered dose of amoxicillin is excreted in the urine within 6 to 8 hours.

Amoxicillin is similar to ampicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide. Amoxicillin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and other antibacterial drugs, amoxicillin 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.
 
Amoxicillin is indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) strains of the designated microorganisms in the conditions listed below:

Infections of the ear, nose, and throat – due to Streptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Infections of the genitourinary tract – due to E. coli, P. mirabilis, or E. faecalis.

Infections of the skin and skin structure – due to Streptococcus spp. (α- and β-hemolytic strains only), Staphylococcus spp., or E. coli.

Infections of the lower respiratory tract – due to Streptococcus spp. (α- and β-hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Gonorrhea, acute uncomplicated (ano-genital and urethral infections) – due to N. gonorrhoeae (males and females).

A history of allergic reaction to any of the penicillins is a contraindication.

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) 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 LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH AMOXICILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AMOXICILLIN SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC 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 amoxicillin, 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.
 
C. 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.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur, amoxicillin should be discontinued and appropriate therapy instituted.
 
A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis.
 
Prescribing amoxicillin 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.

It should be recognized that in the treatment of chronic urinary tract infections, frequent bacteriological and clinical appraisals are necessary. Smaller doses than those recommended above should not be used. Even 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. Except for gonorrhea, 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. It is recommended that there be at least 10 days’ treatment for any infection caused by Streptococcus pyogenes to prevent the occurrence of acute rheumatic fever.

Amoxicillin may be taken every 8 hours or every 12 hours, depending on the strength of the product prescribed.
 
Patients should be counseled that antibacterial drugs, including amoxicillin, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amoxicillin 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 amoxicillin 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 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

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

All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with amoxicillin should have a follow-up serologic test for syphilis after 3 months.

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.
 
Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.
 
In common with other antibiotics, amoxicillin may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST^®, Benedict’s Solution, or Fehling’s Solution. Since this effect may also occur with amoxicillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX^®) be used.
 
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. This effect may also occur with amoxicillin.

Long-term studies in animals have not been performed to evaluate carcinogenic potential. Studies to detect mutagenic potential of amoxicillin alone have not been conducted; however, the following information is available from tests on a 4:1 mixture of amoxicillin and potassium clavulanate. Amoxicillin and clavulanic acid mixture was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and clavulanic acid mixture was weakly positive in the mouse lymphoma assay, but the trend toward increased mutation frequencies in this assay occurred at doses that were also associated with decreased cell survival. Amoxicillin and clavulanic acid mixture was negative in the mouse micronucleus test, and in the dominant lethal assay in mice. Potassium clavulanate alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test, and was negative in each of these assays. In a multi-generation reproduction study in rats, no impairment of fertility or other adverse reproductive effects were seen at doses up to 500 mg/kg (approximately 3 times the human dose in mg/m²).

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 amoxicillin 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.

Penicillins have been shown to be excreted in human milk. Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin is administered to a nursing woman.

Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of amoxicillin should be modified in pediatric patients 12 weeks or younger (≤3 months). (See DOSAGE AND ADMINISTRATION: Neonates and Infants.)

An analysis of clinical studies of amoxicillin was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. Of the 1,811 subjects treated with capsules of amoxicillin, 85% were less than 60 years old, 15% were ≥61 years old and 7% were ≥71 years old. This analysis and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

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 penicillins:

Mucocutaneous candidiasis.

Nausea, vomiting, diarrhea, black hairy tongue, and hemorrhagic/pseudomembranous colitis.
 
Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See WARNINGS.)

Anaphylaxis (See WARNINGS.)
 
Serum sickness–like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis and urticaria have been reported.

NOTE:  These hypersensitivity reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, amoxicillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to amoxicillin therapy.

A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported.

Crystalluria has also been reported (see OVERDOSAGE).

Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported rarely.

Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

In clinical trials using combination therapy with amoxicillin plus clarithromycin and lansoprazole, and amoxicillin plus lansoprazole, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with amoxicillin, clarithromycin, or lansoprazole.

* Dosing for infections caused by less susceptible organisms should follow the recommendations for severe infections.
+The children's dosage is intended for individuals whose weight is less that 40 kg or more should be dosed according to the adult recommendations.

After reconstitution, the required amount of suspension should be placed directly on the child’s tongue for swallowing. Alternate means of administration are to add the required amount of suspension to formula, milk, fruit juice, water, ginger ale, or cold drinks. These preparations should then be taken immediately. To be certain the child is receiving full dosage, such preparations should be consumed in entirety.
 
All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS: Laboratory Tests.)
 
Larger doses may be required for stubborn or severe infections.

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Patients with a glomerular filtration rate of 10 to 30 mL/min. should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a less than 10 mL/min. glomerular filtration rate should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.
 
Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

There are currently no dosing recommendations for pediatric patients with impaired renal function.

Prepare suspension at time of dispensing as follows: Tap bottle until all powder flows freely. Add approximately 1/3 of the total amount of water for reconstitution (see table below) and shake vigorously to wet powder. Add remainder of the water and again shake vigorously.

                                             200 mg/5 mL
                                                                                           Amount of Water
   Bottle Size                                                                  Required for Reconstitution
     50 mL                                                                                       35 mL
     75 mL                                                                                       52 mL
   100 mL                                                                                       69 mL

Each teaspoonful (5 mL) will contain 200 mg amoxicillin.
 
                                            400 mg/5 mL

                                                                                          Amount of Water
   Bottle Size                                                                  Required for Reconstitution
     50 mL                                                                                       35 mL
     75 mL                                                                                       52 mL
   100 mL                                                                                       69 mL

Each teaspoonful (5 mL) will contain 400 mg amoxicillin.

NOTE:  SHAKE ORAL SUSPENSION WELL BEFORE USING. Keep bottle tightly closed. Any unused portion of the reconstituted suspension must be discarded after 14 days. Refrigeration preferable, but not required.

Amoxicillin for Oral Suspension, USP: Each 5 mL of reconstituted bubble-gum-flavored pink suspension contains 200 or 400 mg amoxicillin as the trihydrate.

                                             200 mg/5 mL
 
                  50 mL bottle                                               NDC 65862-070-50
                  75 mL bottle                                               NDC 65862-070-75
                100 mL bottle                                               NDC 65862-070-01

                                             400 mg/5 mL
 
                  50 mL bottle                                               NDC 65862-071-50
                  75 mL bottle                                               NDC 65862-071-75
                100 mL bottle                                               NDC 65862-071-01

Store dry powder at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].