Cefadroxil (Cefadroxil/cefadroxil hemihydrate) USP (hemihydrate) is a semisynthetic cephalosporin antibiotic intended for oral administration. It is white to off-white crystalline powder. It is slightly soluble in water and it is acid-stable. It is chemically designated as 5-Thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, 7-[[amino (4-hydroxyphenyl) acetyl] amino]-3- methyl-8-oxo-, hemihydrate, [6R-[6α, 7β (R*)]]-. It has the formula CHNOS•½ HO and the molecular weight of 372.39. It has the following structural formula:

Each film coated tablet for oral administration contains Cefadroxil (Cefadroxil/cefadroxil hemihydrate) hemihydrate equivalent to 1 gram Cefadroxil (Cefadroxil/cefadroxil hemihydrate) . In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, monosodium citrate, polyethylene glycol, talc and titanium dioxide.

Each capsule for oral administration contains Cefadroxil (Cefadroxil/cefadroxil hemihydrate) hemihydrate equivalent to 500 mg Cefadroxil (Cefadroxil/cefadroxil hemihydrate) . In addition, each capsule contains the following inactive ingredients: magnesium stearate and pregelatinized starch.

The capsule shell also contains D&C yellow no. 10, FD&C blue no. 1, FD&C red no. 40, gelatin and titanium dioxide.

The imprinting ink also contains D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C blue no. 2 aluminum lake, FD&C red no. 40 aluminum lake, pharmaceutical glaze, propylene glycol and synthetic black iron oxide.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) is rapidly absorbed after oral administration. Following single doses of 500 and 1000 mg, average peak serum concentrations were approximately 16 and 28 mcg/mL, respectively. Measurable levels were present 12 hours after administration. Over 90% of the drug is excreted unchanged in the urine within 24 hours. Peak urine concentrations are approximately 1800 mcg/mL during the period following a single 500 mg oral dose. Increases in dosage generally produce a proportionate increase in Cefadroxil (Cefadroxil/cefadroxil hemihydrate) urinary concentration. The urine antibiotic concentration, following a 1-g dose, was maintained well above the MIC of susceptible urinary pathogens for 20 to 22 hours.

Beta-hemolytic streptococci
Staphylococci
Streptococcus (Diplococcus) pneumoniae
Escherichia coli
Proteus mirabilis
Klebsiella
Moraxella (Branhamella) catarrhalis
The use of antibiotic disk susceptibility test methods which measure zone diameter give an accurate estimation of antibiotic susceptibility. One such standard procedure which has been recommended for use with disks to test susceptibility of organisms to Cefadroxil (Cefadroxil/cefadroxil hemihydrate) uses the cephalosporin class (cephalothin) disk. Interpretation involves the correlation of the diameters obtained in the disk test with the minimum inhibitory concentration (MIC) for Cefadroxil (Cefadroxil/cefadroxil hemihydrate) .

Reports from the laboratory giving results of the standard single-disk susceptibility test with a 30 mcg cephalothin disk should be interpreted according to the following criteria:

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of “intermediate susceptibility” suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissue and fluids (e.g., urine) in which high antibiotic levels are attained. A report of “Resistant” indicates that achievable concentrations of the antibiotic are unlikely to be inhibitory and other therapy should be selected.

Standardized procedures require the use of laboratory control organisms. The 30 mcg cephalothin disk should give the following zone diameters:

When using the NCCLS agar dilution or broth dilution (including microdilution) method or equivalent, a bacterial isolate may be considered susceptible if the MIC (minimum inhibitory concentration) value for cephalothin is 8 mcg/mL or less. Organisms are considered resistant if the MIC is 32 mcg/mL or greater. Organisms with an MIC value of less than 32 mcg/mL but greater than 8 mcg/mL are intermediate.

As with standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard cephalothin powder should give MIC values in the range of 0.12 mcg/mL and 0.5 mcg/mL for ATCC 29213. For ATCC 25922, the MIC range should be between 4 mcg/mL and 16 mcg/mL. For ATCC 29212, the MIC range should be between 8 and 32 mcg/mL.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefadroxil (Cefadroxil/cefadroxil hemihydrate) Tablets and Cefadroxil (Cefadroxil/cefadroxil hemihydrate) Capsules and other antibacterial drugs, Cefadroxil (Cefadroxil/cefadroxil hemihydrate) Tablets and Cefadroxil (Cefadroxil/cefadroxil hemihydrate) capsules 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.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) is indicated for the treatment of patients with infection caused by susceptible strains of the designated organisms in the following diseases:

Urinary tract infections caused by and species.

Skin and skin structure infections caused by staphylococci and/or streptococci.

Pharyngitis and/or tonsillitis caused by (Group A beta-hemolytic Streptococci).

Renal function studies should be performed when indicated.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

BEFORE THERAPY WITH Cefadroxil (Cefadroxil/cefadroxil hemihydrate) IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO Cefadroxil (Cefadroxil/cefadroxil hemihydrate) , CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-SENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.

IF AN ALLERGIC REACTION TO Cefadroxil (Cefadroxil/cefadroxil hemihydrate) OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by is a primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug effective against .

Prescribing Cefadroxil (Cefadroxil/cefadroxil hemihydrate) Tablets and Cefadroxil (Cefadroxil/cefadroxil hemihydrate) Capsules 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.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) should be used with caution in the presence of markedly impaired renal function (creatinine clearance rate of less than 50 mL/min/1.73 M) (See ). In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be made prior to and during therapy.

Prolonged use of Cefadroxil (Cefadroxil/cefadroxil hemihydrate) may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) should be prescribed with caution in individuals with history of gastrointestinal disease, particularly colitis.

Of approximately 650 patients who received Cefadroxil (Cefadroxil/cefadroxil hemihydrate) for the treatment of urinary tract infections in three clinical trials, 28% were 60 years and older, while 16% were 70 years and older. Of approximately 1000 patients who received Cefadroxil (Cefadroxil/cefadroxil hemihydrate) for the treatment of skin and skin structure infection in 14 clinical trials, 12% were 60 years and older while 4% were 70 years and over. No overall differences in safety were observed between the elderly patients in these studies and younger patients. Clinical studies of Cefadroxil (Cefadroxil/cefadroxil hemihydrate) for the treatment for pharyngitis or tonsillitis did not include sufficient numbers of patients 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience with Cefadroxil (Cefadroxil/cefadroxil hemihydrate) has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) is substantially excreted by the kidney, and dosage adjustment is indicated for patients with renal impairment (see ). 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.

Other reactions have included hepatic dysfunction including cholestasis and elevations in serum transaminase, genital pruritus, genital moniliasis, vaginitis, moderate transient neutropenia, fever. Agranulocytosis, thrombocytopenia,idiosyncratic hepatic failure, erythema multiforme, Stevens-Johnson syndrome, serum sickness, and arthralgia have been rarely reported.

In addition to the adverse reactions listed above which have been observed in patients treated with Cefadroxil (Cefadroxil/cefadroxil hemihydrate) , the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics:

Toxic epidermal necrolysis, abdominal pain, superinfection, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, prolonged prothrombin time, positive Coombs’ test, increased BUN, increased creatinine, elevated alkaline phosphatase, elevated aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT), elevated bilirubin, elevated LDH, eosinophilia, pancytopenia, neutropenia.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment, when the dosage was not reduced (see and ). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

A study of children under six years of age suggested that ingestion of less than 250 mg/kg of cephalosporins is not associated with significant outcomes. No action is required other than general support and observation. For amounts greater than 250 mg/kg, induce gastric emptying.

In five anuric patients, it was demonstrated that an average of 63% of a 1 g oral dose is extracted from the body during a 6 to 8 hour hemodialysis session.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) is acid-stable and may be administered orally without regard to meals. Administration with food may be helpful in diminishing potential gastrointestinal complaints occasionally associated with oral cephalosporin therapy.

Urinary Tract Infections:
For all other urinary tract infections the usual dosage is 2 g per day in divided doses (b.i.d).

Pharyngitis and Tonsillitis:
Cefadroxil (Cefadroxil/cefadroxil hemihydrate) oral suspension may be more suitable for pediatric patients.

In patients with renal impairment, the dosage of Cefadroxil (Cefadroxil/cefadroxil hemihydrate) should be adjusted according to creatinine clearance rates to prevent drug accumulation. The following schedule is suggested. In adults, the initial dose is 1000 mg of Cefadroxil (Cefadroxil/cefadroxil hemihydrate) and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 M]) is 500 mg at the time intervals listed below.

Patients with creatinine clearance rates over 50 mL/min may be treated as if they were patients having normal renal function.

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) tablets contain Cefadroxil (Cefadroxil/cefadroxil hemihydrate) hemihydrate equivalent to 1 gram of Cefadroxil (Cefadroxil/cefadroxil hemihydrate) and are supplied as follows:

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) 1 gram Tablets: white, oblong, biconvex film-coated tablets, debossed on one side with ‘CF 512’ and scored on the other side.

(50s) NDC 63304-512-50

(100s) NDC 63304-512-01

(unit-dose 100s) NDC 63304-512-80

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) capsules contain Cefadroxil (Cefadroxil/cefadroxil hemihydrate) hemihydrate equivalent to 500 mg of Cefadroxil (Cefadroxil/cefadroxil hemihydrate) and are supplied as follows:

Cefadroxil (Cefadroxil/cefadroxil hemihydrate) 500 mg Capsules: white opaque body and brown opaque cap imprinted with ‘C’ on the cap and ‘582’ on the body.

(50s) NDC 63304-582-50

(100s) NDC 63304-582-01

Dispense in a tight container as defined in the USP.

Store at 20 - 25° C (68 - 77° F). (See USP Controlled Room Temperature).

1. National Committee for Clinical Laboratory Standards, Approved Standard, , 4th Edition, Vol. 10(7): M2-A4, Villanova, PA, April, 1990.

2. National Committee for Clinical Laboratory Standards, Approved Standard: , 2nd Edition, Vol. 10(8): M7-A2, Villanova, PA, April, 1990.

Manufactured for:

Ranbaxy Pharmaceuticals Inc.

Jacksonville, FL 32216 USA

by: Ranbaxy Laboratories Ltd.

New Delhi - 110 019, India

March 2007