Mydrox

Cefadroxil:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Mydrox (Cefadroxil) reviews

Mydrox (Cefadroxil) CAPSULES, USP

Rev. 01/16

Rx Only

To reduce the development of drug resistant bacteria and maintain the effectiveness of Mydrox (Cefadroxil) capsule and other antibacterial drugs, Mydrox (Cefadroxil) capsule should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Mydrox (Cefadroxil) is a semisynthetic cephalosporin antibiotic intended for oral administration. It is a white to yellowish-white crystalline powder. It is chemically designated as (6 R,7R)-7-[(R)-2-amino-2-(p-hydroxyphenyl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid monohydrate. It has the following structural formula:

C₁₆H₁₇N₃O₅S-H₂O M.W. 381.40

Mydrox (Cefadroxil) Capsules, USP contain the following inactive ingredients: black iron oxide, colloidal silicon dioxide, croscarmellose sodium, gelatin, lactose monohydrate, magnesium stearate, red iron oxide, and titanium dioxide.

It is chemically designated as (6 R,7R)-7-[(R)-2-amino-2-(p-hydroxyphenyl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate. It has the following structural formula:

CLINICAL PHARMACOLOGY

Mydrox is rapidly absorbed after oral administration. Following single doses of 500 mg 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 Mydrox (Cefadroxil) 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.

Microbiology

In vitro tests demonstrate that the cephalosporins are bactericidal because of their inhibition of cell-wall synthesis. Mydrox (Cefadroxil) has been shown to be active against the following organisms both in vitro and in clinical infections (see INDICATIONS AND USAGE ):

Beta-hemolytic streptococci

Staphylococci, including penicillinase-producing strains

Streptococcus ( Diplococcus ) pneumoniae

Escherichia coli

Proteus mirabilis

Klebsiella species

Moraxella ( Branhamella ) catarrhalis

Note: Most strains of Enterococcus faecalis (formerly Streptococcus faecalis) and Enterococcus faecium (formerly Streptococcus faecium) are resistant to Mydrox (Cefadroxil). It is not active against most strains of Enterobacter species, Morganella morganii (formerly Proteus morganii), and P. vulgaris. It has no activity against Pseudomonas species and Acinetobacter calcoaceticus (formerly Mima and Herellea species).

Susceptibility Tests:

Diffusion techniques

The use of antibiotic disk susceptibility test methods which measure zone diameter give an accurate estimation of antibiotic susceptibility. One such standard procedure1,3 which has been recommended for use with disks to test susceptibility of organisms to Mydrox (Cefadroxil) 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 Mydrox (Cefadroxil).

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:

Interpretive criteria for Enterobacteriaceae , and Staphylococcus spp.

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:

Dilution techniques

When using the CLSI agar dilution or broth dilution (including microdilution) method^2,3 or equivalent, the MIC values should be interpreted according to the following criteria:

Interpretive criteria for Enterobacteriaceae , and Staphylococcus spp.

As with standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard cephalothin powder should provide the following MIC values:

INDICATIONS AND USAGE

Mydrox (Cefadroxil) Capsules, USP are 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 E. coli, P. mirabilis, and Klebsiella species.

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

Pharyngitis and/or tonsillitis caused by Streptococcus pyogenes (Group A beta-hemolytic streptococci).

Note: Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Mydrox (Cefadroxil) is generally effective in the eradication of streptococci from the oropharynx. However, data establishing the efficacy of Mydrox (Cefadroxil) for the prophylaxis of subsequent rheumatic fever are not available.

Note: Culture and susceptibility tests should be initiated prior to and during therapy. Renal function studies should be performed when indicated.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Mydrox (Cefadroxil) Capsules, USP and other antibacterial drugs, Mydrox (Cefadroxil) Capsules, USP 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.

CONTRAINDICATIONS

Mydrox (Cefadroxil) capsules are contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

WARNINGS

BEFORE THERAPY WITH Mydrox (Cefadroxil) IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO Mydrox (Cefadroxil), 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 Mydrox (Cefadroxil) 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.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Mydrox (Cefadroxil), 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.

PRECAUTIONS

General

Mydrox should be used with caution in the presence of markedly impaired renal function (creatinine clearance rate of less than 50 mL/min/1.73 m²). (See DOSAGE AND ADMINISTRATION ). In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be made prior to and during therapy.

Prescribing Mydrox (Cefadroxil) 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.

Prolonged use of Mydrox (Cefadroxil) 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.

Mydrox (Cefadroxil) should be prescribed with caution in individuals with history of gastrointestinal disease particularly colitis.

Information for Patients

Patients should be counseled that antibacterial drugs including Mydrox (Cefadroxil) capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Mydrox (Cefadroxil) capsules are 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 Mydrox (Cefadroxil) capsules or other antibacterial drugs in 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.

Drug/Laboratory Test Interactions

Positive direct Coombs’ tests have been reported during treatment with the cephalosporin antibiotics. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs’ testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs’ test may be due to the drug.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies have been performed to determine carcinogenic potential. No genetic toxicity tests have been performed.

Pregnancy

Teratogenic Effects

Pregnancy Category B

Reproduction studies have been performed in mice and rats at doses up to 11 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Mydrox monohydrate. 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

Mydrox (Cefadroxil) has not been studied for use during labor and delivery. Treatment should only be given if clearly needed.

Nursing Mothers

Caution should be exercised when Mydrox monohydrate is administered to a nursing mother.

Pediatric Use

(See DOSAGE AND ADMINISTRATION .)

Geriatric Use

Of approximately 650 patients who received Mydrox (Cefadroxil) 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 1,000 patients who received Mydrox (Cefadroxil) 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 Mydrox (Cefadroxil) for the treatment of 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 Mydrox (Cefadroxil) has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Mydrox (Cefadroxil) is substantially excreted by the kidney, and dosage adjustment is indicated for patients with renal impairment (see DOSAGE AND ADMINISTRATION , Renal Impairment). 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.

ADVERSE REACTIONS

Gastrointestinal

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS ). Dyspepsia, nausea and vomiting have been reported rarely. Diarrhea has also occurred.

Hypersensitivity

Allergies (in the form of rash, urticaria, angioedema, and pruritus) have been observed. These reactions usually subsided upon discontinuation of the drug. Anaphylaxis has also been reported.

Other

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 Mydrox (Cefadroxil), 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, 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 DOSAGE AND ADMINISTRATION and OVERDOSAGE ). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

OVERDOSAGE

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.

DOSAGE AND ADMINISTRATION

Mydrox capsules are 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.

Adults

Urinary Tract Infections

For uncomplicated lower urinary tract infections (i.e., cystitis) the usual dosage is 1 or 2 g per day in a single (q.d.) or divided doses (b.i.d.).

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

Skin and Skin Structure Infections

For skin and skin structure infections the usual dosage is 1 g per day in single (q.d.) or divided doses (b.i.d.).

Pharyngitis and Tonsillitis

Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis - 1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.

Children

For urinary tract infections, the recommended daily dosage for children is 30 mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single dose or in equally divided doses every 12 hours. For other skin and skin structure infections, the recommended daily dosage is 30 mg/kg/day in equally divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal infections, a therapeutic dosage of Mydrox capsules should be administered for at least 10 days.

Renal Impairment

In patients with renal impairment, the dosage of Mydrox (Cefadroxil) monohydrate 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 Mydrox (Cefadroxil) capsules and the maintenance dose (based on the creatinine clearance rate [mL/min/1.73 m2]) 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.

HOW SUPPLIED

Mydrox (Cefadroxil) Capsules USP, 500 mg are available as opaque chocolate brown and white hard gelatin capsules, imprinted with “WEST-WARD 947” in bottles of 20, 50 and 100.

Store at 20° to 25°C (68° to 77°F).

Dispense in a tight container as defined in the USP using a child-resistant closure.

REFERENCES

• Clinical and Laboratory Standards Institute, Approved Standard, Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – Eleventh Edition, Vol. 32 (1): M02- A11, Wayne, PA, January, 2012.
  

• Clinical and Laboratory Standards Institute, Approved Standard: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard- Ninth Edition, Vol. 32 (2): M07- A9, Wayne, PA, January, 2012.
  

• Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. CLSI Document M100-S22, Vol.32, No.3, CLSI, Wayne, PA, January, 2012.

Distributed by:

West-Ward Pharmaceutical s Corp.

Eatontown, NJ 07724 - USA

Manufactured by:

Jazeera Pharmaceutical Industries (JPI)

Al- Kharj Road

P. O. Box 106229

Riyadh 11666

Saudi Arabia

An Affiliate of:

Hikma Pharmaceuticals LLC

P.O. Box 182400

Amman 11118

Jordan

Revised January 2016

Probenecid:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Mydrox (Probenecid) reviews

DESCRIPTION

Mydrox (Probenecid) is a uricosuric and renal tubular transport blocking agent.

The chemical name for Mydrox (Probenecid) is 4-[(dipropylamino) sulfonyl] benzoic acid (molecular weight 285.37). It has the following structural formula:

C₁₃H₁₉NO₄S

Mydrox (Probenecid), USP is a white or nearly white, fine, crystalline powder. Mydrox (Probenecid) is soluble in dilute alkali, in alcohol, in chloroform, and in acetone; it is practically insoluble in water and in dilute acids.

Each tablet for oral administration contains 500 mg of Mydrox (Probenecid) and the following inactive ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium carbonate, sodium lauryl sulfate, sodium starch glycolate, cornstarch, titanium dioxide, triacetin, FD&C Yellow #6, D&C Yellow #10, and FD&C Blue #2.

Structural Formula

CLINICAL PHARMACOLOGY

Mydrox (Probenecid) is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits.

Mydrox (Probenecid) inhibits the tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins.

Mydrox (Probenecid) also has been reported to inhibit the renal transport of many other compounds including aminohippuric acid (PAH), aminosalicylic acid (PAS), indomethacin, sodium iodomethamate and related iodinated organic acids, 17-ketosteroids, pantothenic acid, phenolsulfonphthalein (PSP), sulfonamides, and sulfonylureas. See also Drug Interactions.

Mydrox (Probenecid) decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals.

Mydrox (Probenecid) does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin.

INDICATIONS AND USAGE

Mydrox (Probenecid) tablets are indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis.

As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given.

CONTRAINDICATIONS

Hypersensitivity to Mydrox (Probenecid).

Children under 2 years of age.

Not recommended in persons with known blood dyscrasias or uric acid kidney stones.

Therapy with Mydrox (Probenecid) should not be started until an acute gouty attack has subsided.

WARNINGS

Exacerbation of gout following therapy with Mydrox may occur; in such cases colchicine or other appropriate therapy is advisable.

Mydrox (Probenecid) increases plasma concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported. If Mydrox (Probenecid) is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored.

In patients on Mydrox (Probenecid) the use of salicylates in either small or large doses is contraindicated because it antagonizes the uricosuric action of Mydrox (Probenecid). The biphasic action of salicylates in the renal tubules accounts for the so-called "paradoxical effect" of uricosuric agents. In patients on Mydrox (Probenecid) who require a mild analgesic agent the use of acetaminophen rather than small doses of salicylates would be preferred.

Rarely, severe allergic reactions and anaphylaxis have been reported with the use of Mydrox (Probenecid). Most of these have been reported to occur within several hours after readministration following prior usage of the drug.

The appearance of hypersensitivity reactions requires cessation of therapy with Mydrox (Probenecid).

Usage In Pregnancy

Mydrox (Probenecid) crosses the placental barrier and appears in cord blood. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against possible hazards.

PRECAUTIONS

General

Hematuria, renal colic, costovertebral pain, and formation of uric acid stones associated with the use of Mydrox in gouty patients may be prevented by alkalization of the urine and a liberal fluid intake. In these cases when alkali is administered, the acid-base balance of the patient should be watched.

Use with caution in patients with a history of peptic ulcer.

Mydrox (Probenecid) has been used in patients with some renal impairment, but dosage requirements may be increased. Mydrox (Probenecid) may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less. Because of its mechanism of action, Mydrox (Probenecid) is not recommended in conjunction with a penicillin in the presence of known renal impairment.

A reducing substance may appear in the urine of patients receiving Mydrox (Probenecid). This disappears with discontinuance of therapy. Suspected glycosuria should be confirmed by using a test specific for glucose.

Drug Interactions

When Mydrox (Probenecid) is used to elevate plasma concentrations of penicillin or other beta-lactams, or when such drugs are given to patients taking Mydrox (Probenecid) therapeutically, high plasma concentrations of the other drug may increase the incidence of adverse reactions associated with that drug. In the case of penicillin or other beta-lactams, psychic disturbances have been reported.

The use of salicylates antagonizes the uricosuric action of Mydrox (Probenecid). The uricosuric action of Mydrox (Probenecid) is also antagonized by pyrazinamide.

Mydrox (Probenecid) produces an insignificant increase in free sulfonamide plasma concentrations, but a significant increase in total sulfonamide plasma levels. Since Mydrox (Probenecid) decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when a sulfonamide and Mydrox (Probenecid) are coadministered for prolonged periods. Mydrox (Probenecid) may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycemia.

It has been reported that patients receiving Mydrox (Probenecid) require significantly less thiopental for induction of anesthesia. In addition, ketamine and thiopental anesthesia were significantly prolonged in rats receiving Mydrox (Probenecid).

The concomitant administration of Mydrox (Probenecid) increases the mean plasma elimination half-life of a number of drugs which can lead to increased plasma concentrations. These include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin. Although the clinical significance of this observation has not been established, a lower dosage of the drug may be required to produce a therapeutic effect, and increases in dosage of the drug in question should be made cautiously and in small increments when Mydrox (Probenecid) is being coadministrated. Although specific instances of toxicity due to this potential interaction have not been observed to date, physicians should be alert to this possibility.

Mydrox (Probenecid) given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric action of Mydrox (Probenecid), which probably is not significant under most circumstances.

In animals and in humans, Mydrox (Probenecid) has been reported to increase plasma concentrations of methotrexate.

Falsely high readings for theophylline have been reported in an in vitro study, using the Schack and Waxler technique, when therapeutic concentrations of theophylline and Mydrox (Probenecid) were added to human plasma.

ADVERSE REACTIONS

The following adverse reactions have been observed and within each category are listed in order of decreasing severity.

Central Nervous System: headache, dizziness.

Metabolic: precipitation of acute gouty arthritis.

Gastrointestinal: hepatic necrosis, vomiting, nausea, anorexia, sore gums.

Genitourinary: nephrotic syndrome, uric acid stones with or without hematuria, renal colic, costovertebral pain, urinary frequency.

Hypersensitivity: anaphylaxis, fever, urticaria, pruritus.

Hematologic: aplastic anemia, leukopenia, hemolytic anemia which in some patients could be related to genetic deficiency of glucose-6-phosphate dehydrogenase in red blood cells, anemia.

Integumentary: dermatitis, alopecia, flushing.

DOSAGE AND ADMINISTRATION

Gout

Therapy with Mydrox should not be started until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, Mydrox (Probenecid) may be continued without changing the dosage, and full therapeutic dosage of colchicine, or other appropriate therapy, should be given to control the acute attack.

The recommended adult dosage is 250 mg (1/2 Mydrox (Probenecid) tablet), twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter.

Some degree of renal impairment may be present in patients with gout. A daily dosage of 1000 mg may be adequate. However, if necessary, the daily dosage may be increased by 500 mg increments every 4 weeks within tolerance (and usually not above 2000 mg per day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not above 700 mg. As noted, Mydrox (Probenecid) may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less.

Gastric intolerance may be indicative of overdosage, and may be corrected by decreasing the dosage.

As uric acid tends to crystallize out of an acid urine, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily), or potassium citrate (7.5 g daily) to maintain an alkaline urine.

Alkalization of the urine is recommended until the serum urate level returns to normal limits and tophaceous deposits disappear, i.e., during the period when urinary excretion of uric acid is at a high level. Thereafter, alkalization of the urine and the usual restriction of purine-producing foods may be somewhat relaxed.

Mydrox (Probenecid) should be continued at the dosage that will maintain normal serum urate levels. When acute attacks have been absent for 6 months or more and serum urate levels remain within normal limits, the daily dosage may be decreased by 500 mg every 6 months. The maintenance dosage should not be reduced to the point where serum urate levels tend to rise.

Mydrox (Probenecid) and Penicillin Therapy (General)

Adults

The recommended dosage is 2000 mg ) daily in divided doses. This dosage should be reduced in older patients in whom renal impairment may be present.

Children

2–14 years of age:

Initial dose: 25 mg/kg body weight (or 0.7 g/square meter body surface).

Maintenance Dose: 40 mg/kg body weight (or 1.2 g/square meter body surface) per day, divided into 4 doses.

For children weighing more than 50 kg (110 lb) the adult dosage is recommended.

Mydrox (Probenecid) is contraindicated in children under 2 years of age.

The PSP excretion test may be used to determine the effectiveness of Mydrox (Probenecid) in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about one-fifth the normal rate when dosage of Mydrox (Probenecid) is adequate.

Penicillin Therapy *

In uncomplicated gonococcal infections in men and women (urethral, cervical, rectal), 1 g of Mydrox (Probenecid) should be given orally with 4.8 million units of aqueous procaine penicillin GSee package circulars of manufacturers for detailed information about CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS. (given IM), or 3 g of amoxicillin² (given orally), or 3.5 g of ampicillin² (given orally).

For further guidance, see CDC recommendations for definition of regimens of choice, alternative regimens, treatment of hypersensitive patients, and other aspects of therapy.

*Recommended by the Center for Disease Control, U.S. Department of Health and Human Services, Public Health Service (Morbidity and Mortality Weekly Report Supplement, Volume 34, Number 4S, October 18, 1985).

HOW SUPPLIED

Mydrox (Probenecid) Tablets, USP are available containing 500 mg of Mydrox (Probenecid), USP.

The tablets are capsule shaped, film-coated yellow, debossed with MYLAN 156 on one side, 500 on the other side. They are available as follows:

NDC 0378-0156-01

bottles of 100 tablets

Store at 20° to 25°C (68° to 77°F).

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505

REVISED MARCH 2006

PROB:R4AQ

PRINCIPAL DISPLAY PANEL - 500 mg

NDC 0378-0156-01

Mydrox (Probenecid)

Tablets, USP

500 mg

Rx only 100 Tablets

Each film-coated tablet contains:

Mydrox (Probenecid), USP 500 mg

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication

out of the reach of children.

Store at 20° to 25°C (68° to 77°F).

[See USP for Controlled Room

Temperature.]

Protect from light.

Usual Adult

Dosage: See accom-

panying prescribing information.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Mylan.com

RM0156A11