Medication: Zipod

Zipod uses

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Clinical trials
• Mg label
• Mg label
• Zipod reviews

DESCRIPTION

Zipod proxetil is an orally administered, extended spectrum, semi-synthetic antibiotic of the cephalosporin class. The chemical name is (RS)-1(isopropoxycarbonyloxy) ethyl (+)-(6R,7R)-7-[2-(2-amino-4-thiazolyl)-2-{(Z)methoxyimino} acetamido]-3-methoxymethyl-8-oxo-5-thia-1-azabicyclo [4.2.0]oct-2-ene-2-carboxylate.

Its empirical formula is C₂₁H₂₇N₅O₉S₂ and its structural formula is represented below:

The molecular weight of Zipod proxetil is 557.6.

Zipod proxetil is a prodrug; its active metabolite is Zipod. All doses of Zipod proxetil in this insert are expressed in terms of the active Zipod moiety. The drug is supplied as film-coated tablets.

Zipod Proxetil Tablets, USP contain Zipod proxetil equivalent to 100 mg or 200 mg of Zipod activity. Each film-coated tablet contains the following inactive ingredients: carboxymethylcellulose calcium, crospovidone, FD&C Yellow No. 6, hydroxypropyl cellulose, hypromellose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, talc and titanium dioxide.

Zipod Chemical Structure

CLINICAL PHARMACOLOGY

Absorption and Excretion

Zipod proxetil is a prodrug that is absorbed from the gastrointestinal tract and de-esterified to its active metabolite, Zipod. Following oral administration of 100 mg of Zipod proxetil to fasting subjects, approximately 50% of the administered Zipod dose was absorbed systemically. Over the recommended dosing range, approximately 29 to 33% of the administered Zipod dose was excreted unchanged in the urine in 12 hours. There is minimal metabolism of Zipod in vivo.

Effects of Food

The extent of absorption (mean AUC) and the mean peak plasma concentration increased when film-coated tablets were administered with food. Following a 200 mg tablet dose taken with food, the AUC was 21 to 33% higher than under fasting conditions, and the peak plasma concentration averaged 3.1 mcg/mL in fed subjects versus 2.6 mcg/mL in fasted subjects. Time to peak concentration was not significantly different between fed and fasted subjects.

When a 200 mg dose of the suspension was taken with food, the extent of absorption (mean AUC) and mean peak plasma concentration in fed subjects were not significantly different from fasted subjects, but the rate of absorption was slower with food (48% increase in T_max).

Pharmacokinetics of Zipod Proxetil Film-coated Tablets

Over the recommended dosing range, the rate and extent of Zipod absorption exhibited dose-dependency; dose-normalized C_max and AUC decreased by up to 32% with increasing dose. Over the recommended dosing range, the T_max was approximately 2 to 3 hours and the T_1/2 ranged from 2.09 to 2.84 hours. Mean C_max was 1.4 mcg/mL for the 100 mg dose, 2.3 mcg/mL for the 200 mg dose, and 3.9 mcg/mL for the 400 mg dose. In patients with normal renal function, neither accumulation nor significant changes in other pharmacokinetic parameters were noted following multiple oral doses of up to 400 mg Q 12 hours.

Distribution

Protein binding of Zipod ranges from 22 to 33% in serum and from 21 to 29% in plasma.

Skin Blister

Following multiple-dose administration every 12 hours for 5 days of 200 mg or 400 mg Zipod proxetil, the mean maximum Zipod concentration in skin blister fluid averaged 1.6 and 2.8 mcg/mL, respectively. Skin blister fluid Zipod levels at 12 hours after dosing averaged 0.2 and 0.4 mcg/mL for the 200 mg and 400 mg multiple-dose regimens, respectively.

Tonsil Tissue

Following a single, oral 100 mg Zipod proxetil film-coated tablet, the mean maximum Zipod concentration in tonsil tissue averaged 0.24 mcg/g at 4 hours post-dosing and 0.09 mcg/g at 7 hours post-dosing. Equilibrium was achieved between plasma and tonsil tissue within 4 hours of dosing. No detection of Zipod in tonsillar tissue was reported 12 hours after dosing. These results demonstrated that concentrations of Zipod exceeded the MIC₉₀ of S. pyogenes for at least 7 hours after dosing of 100 mg of Zipod proxetil.

Lung Tissue

Following a single, oral 200 mg Zipod proxetil film-coated tablet, the mean maximum Zipod concentration in lung tissue averaged 0.63 mcg/g at 3 hours post-dosing, 0.52 mcg/g at 6 hours postdosing, and 0.19 mcg/g at 12 hours post-dosing. The results of this study indicated that Zipod penetrated into lung tissue and produced sustained drug concentrations for at least 12 hours after dosing at levels that exceeded the MIC₉₀ for S. pneumoniae and H. influenzae.

CSF

Adequate data on CSF levels of Zipod are not available.

Effects of Decreased Renal Function

Elimination of Zipod is reduced in patients with moderate to severe renal impairment. (See PRECAUTIONS and DOSAGE AND ADMINISTRATION .) In subjects with mild impairment of renal function (50 to 80 mL/min creatinine clearance), the average plasma half-life of Zipod was 3.5 hours. In subjects with moderate (30 to 49 mL/min creatinine clearance) or severe renal impairment (5 to 29 mL/min creatinine clearance), the half-life increased to 5.9 and 9.8 hours, respectively. Approximately 23% of the administered dose was cleared from the body during a standard 3-hour hemodialysis procedure.

Effect of Hepatic Impairment (cirrhosis)

Absorption was somewhat diminished and elimination unchanged in patients with cirrhosis. The mean Zipod T_1/2 and renal clearance in cirrhotic patients were similar to those derived in studies of healthy subjects. Ascites did not appear to affect values in cirrhotic subjects. No dosage adjustment is recommended in this patient population.

Pharmacokinetics in Elderly Subjects

Elderly subjects do not require dosage adjustments unless they have diminished renal function. In healthy geriatric subjects, Zipod half-life in plasma averaged 4.2 hours (vs 3.3 in younger subjects) and urinary recovery averaged 21% after a 400 mg dose was administered every 12 hours. Other pharmacokinetic parameters (C_max, AUC, and T_max) were unchanged relative to those observed in healthy young subjects.

Microbiology

Mechanism of Action

Zipod is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Zipod has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Mechanism of Resistance

Resistance to Zipod is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins, and decreased permeability.

Zipod has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the Indications and Usage (1) section:

Gram-positive bacteria

Staphylococcus aureus (methicillin-susceptible strains, including those producing penicillinases)

Staphylococcus saprophyticus

Streptococcus pneumoniae (excluding penicillin-resistant isolates)

Streptococcus pyogenes

Gram-negative bacteria

Escherichia coli

Klebsiella pneumoniae

Proteus mirabilis

Haemophilus influenzae (including beta-lactamase producing isolates)

Moraxella catarrhalis

Neisseria gonorrhoeae (including penicillinase-producing isolates)

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Zipod. However, the efficacy of Zipod in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-positive bacteria

Streptococcus agalactiae

Streptococcus spp. (Groups C, F, G)

Gram-negative bacteria

Citrobacter diversus

Klebsiella oxytoca

Proteus vulgaris

Providencia rettgeri

Haemophilus parainfluenzae

Anaerobic Gram-positive bacteria

Peptostreptococcus magnus

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations. These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method.^{1 ,3} The MIC values should be interpreted according to criteria provided in Table 1.

Diffusion techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.^{2 ,3} This procedure uses paper disks impregnated with 10 mcg Zipod to test the susceptibility of microorganisms to Zipod. The disk diffusion interpretive criteria are provided in Table 1.

Table 1. Susceptibility Test Interpretive Criteria for Cefpodoxime²

Susceptibility of staphylococci to Zipod may be deduced from testing only penicillin and either cefoxitin or oxacillin.

A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration at the infection site necessary to inhibit growth of the pathogen. A report of Intermediate indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test.^{1 ,2,3} Standard Zipod powder should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 10 mcg disk, the criteria in Table 2 should be achieved.

Table 2. Acceptable Quality Control Ranges for Cefpodoxime

ATCC® is a registered trademark of the American Type Culture Collection.

INDICATIONS AND USAGE

Zipod proxetil is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below.

Recommended dosages, durations of therapy, and applicable patient populations vary among these infections. Please see DOSAGE AND ADMINISTRATION for specific recommendations.

Acute otitis media caused by Streptococcus pneumoniae (excluding penicillin-resistant strains), Streptococcus pyogenes , Haemophilus influenzae (including beta-lactamase-producing strains), or Moraxella ( Branhamella ) catarrhalis (including beta-lactamase-producing strains).

Pharyngitis and/or tonsillitis caused by Streptococcus pyogenes.

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

Community-acquired pneumonia caused by S. pneumoniae or H. Influenzae (including beta-lactamase-producing strains).

Acute bacterial exacerbation of chronic bronchitis caused by S. pneumoniae , H. influenzae (non-beta-lactamase-producing strains only), or M. catarrhalis. Data are insufficient at this time to establish efficacy in patients with acute bacterial exacerbations of chronic bronchitis caused by beta-lactamase-producing strains of H. influenzae.

Acute, uncomplicated urethral and cervical gonorrhea caused by Neisseria gonorrhoeae (including penicillinase-producing strains).

Acute, uncomplicated ano -rectal infections in women due to Neisseria gonorrhoeae (including penicillinase-producing strains).

NOTE: The efficacy of Zipod in treating male patients with rectal infections caused by N. gonorrhoeae has not been established. Data do not support the use of Zipod proxetil in the treatment of pharyngeal infections due to N. gonorrhoeae in men or women.

Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains) or Streptococcus pyogenes. Abscesses should be surgically drained as clinically indicated.

NOTE: In clinical trials, successful treatment of uncomplicated skin and skin structure infections was dose-related. The effective therapeutic dose for skin infections was higher than those used in other recommended indications. (See DOSAGE AND ADMINISTRATION.)

Acute maxillary sinusitis caused by Haemophilus influenzae (including beta-lactamase-producing strains), Streptococcus pneumoniae , and Moraxella catarrhalis.

Uncomplicated urinary tract infections (cystitis) caused by Escherichia coli, Klebsiella pneumoniae , Proteus mirabilis, or Staphylococcus saprophyticus.

NOTE: In considering the use of Zipod proxetil in the treatment of cystitis, Zipod proxetil’s lower bacterial eradication rates should be weighed against the increased eradication rates and different safety profiles of some other classes of approved agents. (See CLINICAL STUDIES section.)

Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibility to Zipod. Therapy may be instituted while awaiting the results of these studies. Once these results become available, antimicrobial therapy should be adjusted accordingly.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Zipod Proxetil Tablets, USP and other antibacterial drugs, Zipod Proxetil Tablets, 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

Zipod proxetil is contraindicated in patients with a known allergy to Zipod or to the cephalosporin group of antibiotics.

WARNINGS

BEFORE THERAPY WITH Zipod PROXETIL IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO Zipod, OTHER CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF Zipod IS TO BE ADMINISTERED TO PENICILLIN SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS HYPERSENSITIVITY 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 Zipod PROXETIL OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINE, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Zipod proxetil tablets, USP, 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.

A concerted effort to monitor for C. difficile in cefpodoxime-treated patients with diarrhea was undertaken because of an increased incidence of diarrhea associated with C. difficile in early trials in normal subjects. C. difficile organisms or toxin was reported in 10% of the cefpodoxime-treated adult patients with diarrhea; however, no specific diagnosis of pseudomembranous colitis was made in these patients.

In post-marketing experience outside the United States, reports of pseudomembranous colitis associated with the use of Zipod proxetil have been received.

PRECAUTIONS

General

In patients with transient or persistent reduction in urinary output due to renal insufficiency, the total daily dose of Zipod proxetil should be reduced because high and prolonged serum antibiotic concentrations can occur in such individuals following usual doses. Zipod, like other cephalosporins, should be administered with caution to patients receiving concurrent treatment with potent diuretics.

As with other antibiotics, prolonged use of Zipod proxetil may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient’s condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Prescribing Zipod Proxetil Tablets, USP 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 Zipod Proxetil Tablets, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Zipod Proxetil Tablets, USP 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 Zipod Proxetil Tablets, USP 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.

Drug Interactions

Antacids

Concomitant administration of high doses of antacids or H₂ blockers reduces peak plasma levels by 24% to 42% and the extent of absorption by 27% to 32%, respectively. The rate of absorption is not altered by these concomitant medications. Oral anti-cholinergics (e.g., propantheline) delay peak plasma levels (47% increase in T_max), but do not affect the extent of absorption (AUC).

Probenecid

As with other beta-lactam antibiotics, renal excretion of Zipod was inhibited by probenecid and resulted in an approximately 31% increase in AUC and 20% increase in peak Zipod plasma levels.

Nephrotoxic drugs

Although nephrotoxicity has not been noted when Zipod proxetil was given alone, close monitoring of renal function is advised when Zipod proxetil is administered concomitantly with compounds of known nephrotoxic potential.

Drug/Laboratory Test Interactions

Cephalosporins, including Zipod proxetil, are known to occasionally induce a positive direct Coombs’ test.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal carcinogenesis studies of Zipod proxetil have not been performed. Mutagenesis studies of Zipod, including the Ames test both with and without metabolic activation, the chromosome aberration test, the unscheduled DNA synthesis assay, mitotic recombination and gene conversion, the forward gene mutation assay and the in vivo micronucleus test, were all negative. No untoward effects on fertility or reproduction were noted when 100 mg/kg/day or less was administered orally to rats.

Pregnancy

Teratogenic Effects

Pregnancy Category B

Zipod proxetil was neither teratogenic nor embryocidal when administered to rats during organogenesis at doses up to 100 mg/kg/day or to rabbits at doses up to 30 mg/kg/day (1 to 2 times the human dose based on mg/m²).

There are, however, no adequate and well-controlled studies of Zipod proxetil use 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

Zipod proxetil has not been studied for use during labor and delivery. Treatment should only be given if clearly needed.

Nursing Mothers

Zipod is excreted in human milk. In a study of 3 lactating women, levels of Zipod in human milk were 0%, 2% and 6% of concomitant serum levels at 4 hours following a 200 mg oral dose of Zipod proxetil. At 6 hours post-dosing, levels were 0%, 9% and 16% of concomitant serum levels. Because of the potential for serious reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and efficacy in infants less than 2 months of age have not been established.

Geriatric Use

Of the 3338 patients in multiple-dose clinical studies of Zipod proxetil film-coated tablets, 521 (16%) were 65 and over, while 214 (6%) were 75 and over. No overall differences in effectiveness or safety were observed between the elderly and younger patients. In healthy geriatric subjects with normal renal function, Zipod half-life in plasma averaged 4.2 hours and urinary recovery averaged 21% after a 400 mg dose was given every 12 hours for 15 days. Other pharmacokinetic parameters were unchanged relative to those observed in healthy younger subjects.

Dose adjustment in elderly patients with normal renal function is not necessary.

ADVERSE REACTIONS

Clinical Trials

Film-coated Tablets

In clinical trials using multiple doses of Zipod proxetil filmcoated tablets, 4696 patients were treated with the recommended dosages of Zipod (100 to 400 mg Q 12 hours). There were no deaths or permanent disabilities thought related to drug toxicity. One-hundred twenty-nine (2.7%) patients discontinued medication due to adverse events thought possibly or probably related to drug toxicity. Ninety-three (52%) of the 178 patients who discontinued therapy (whether thought related to drug therapy or not) did so because of gastrointestinal disturbances, nausea, vomiting, or diarrhea. The percentage of Zipod proxetil-treated patients who discontinued study drug because of adverse events was significantly greater at a dose of 800 mg daily than at a dose of 400 mg daily or at a dose of 200 mg daily. Adverse events thought possibly or probably related to Zipod in multiple-dose clinical trials (N=4696 cefpodoxime-treated patients) were:

Incidence Greater Than 1%

Diarrhea or loose stools were dose-related: decreasing from 10.4% of patients receiving 800 mg per day to 5.7% for those receiving 200 mg per day. Of patients with diarrhea, 10% had C. difficile organism or toxin in the stool. (See WARNINGS.)

Incidence Less Than 1%: By body system in decreasing order

Clinical Studies

Adverse events thought possibly or probably related to Zipod proxetil that occurred in less than 1% of patients (N=4696)

Body – fungal infections, abdominal distention, malaise, fatigue, asthenia, fever, chest pain, back pain, chills, generalized pain, abnormal microbiological tests, moniliasis, abscess, allergic reaction, facial edema, bacterial infections, parasitic infections, localized edema, localized pain.

Cardiovascular – congestive heart failure, migraine, palpitations, vasodilation, hematoma, hypertension, hypotension.

Digestive – vomiting, dyspepsia, dry mouth, flatulence, decreased appetite, constipation, oral moniliasis, anorexia, eructation, gastritis, mouth ulcers, gastrointestinal disorders, rectal disorders, tongue disorders, tooth disorders, increased thirst, oral lesions, tenesmus, dry throat, toothache.

Hemic and Lymphatic – anemia.

Metabolic and Nutritional – dehydration, gout, peripheral edema, weight increase.

Musculo -skeletal – myalgia.

Nervous – dizziness, insomnia, somnolence, anxiety, shakiness, nervousness, cerebral infarction, change in dreams, impaired concentration, confusion, nightmares, paresthesia, vertigo.

Respiratory – asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dyspnea, pleural effusion, pneumonia, sinusitis.

Skin – urticaria, rash, pruritus non-application site, diaphoresis, maculopapular rash, fungal dermatitis, desquamation, dry skin non-application site, hair loss, vesiculobullous rash, sunburn.

Special Senses – taste alterations, eye irritation, taste loss, tinnitus.

Urogenital – hematuria, urinary tract infections, metrorrhagia, dysuria, urinary frequency, nocturia, penile infection, proteinuria, vaginal pain.

Film-coated Tablets

In clinical trials using a single dose of Zipod proxetil film-coated tablets, 509 patients were treated with the recommended dosage of Zipod (200 mg). There were no deaths or permanent disabilities thought related to drug toxicity in these studies.

Adverse events thought possibly or probably related to Zipod in single-dose clinical trials conducted in the United States were:

Incidence Greater Than 1%

Incidence Less Than 1%

Central Nervous System: Dizziness, headache, syncope.

Dermatologic: Rash.

Genital: Vaginitis.

Gastrointestinal: Abdominal pain.

Psychiatric: Anxiety.

Laboratory Changes

Significant laboratory changes that have been reported in adult and pediatric patients in clinical trials of Zipod proxetil, without regard to drug relationship, were:

Hepatic: Transient increases in AST, ALT (SGPT), GGT, alkaline phosphatase, bilirubin, and LDH.

Hematologic: Eosinophilia, leukocytosis, lymphocytosis, granulocytosis, basophilia, monocytosis, thrombocytosis, decreased hemoglobin, decreased hematocrit, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, thrombocythemia, positive Coombs’ test, and prolonged PT, and PTT.

Serum Chemistry: Hyperglycemia, hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, and hyponatremia.

Renal: Increases in BUN and creatinine.

Most of these abnormalities were transient and not clinically significant.

Post-marketing Experience

The following serious adverse experiences have been reported: allergic reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and serum sickness-like reactions, pseudomembranous colitis, bloody diarrhea with abdominal pain, ulcerative colitis, rectorrhagia with hypotension, anaphylactic shock, acute liver injury, in utero exposure with miscarriage, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis.

One death was attributed to pseudomembranous colitis and disseminated intravascular coagulation.

Cephalosporin Class Labeling

In addition to the adverse reactions listed above which have been observed in patients treated with Zipod proxetil, the following adverse reactions and altered laboratory tests have been reported for cephalosporin class antibiotics:

Adverse Reactions and Abnormal Laboratory Tests: Renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, serum sickness-like reaction, hemorrhage, agranulocytosis, and pancytopenia.

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

In acute rodent toxicity studies, a single 5 g/kg oral dose produced no adverse effects.

In the event of serious toxic reaction from overdosage, hemodialysis or peritoneal dialysis may aid in the removal of Zipod from the body, particularly if renal function is compromised.

The toxic symptoms following an overdose of beta-lactam antibiotics may include nausea, vomiting, epigastric distress, and diarrhea.

DOSAGE AND ADMINISTRATION

Film-coated Tablets

Zipod Proxetil Tablets, USP should be administered orally with food to enhance absorption. (See CLINICAL PHARMACOLOGY.)

The recommended dosages, durations of treatment, and applicable patient population are as described in the following chart:

Adults and Adolescents

Patients with Renal Dysfunction

For patients with severe renal impairment, the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.

When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to estimate creatinine clearance (mL/min). For this estimate to be valid, the serum creatinine level should represent a steady state of renal function.

Patients with Cirrhosis

Zipod pharmacokinetics in cirrhotic patients (with or without ascites) are similar to those in healthy subjects. Dose adjustment is not necessary in this population.

HOW SUPPLIED

Zipod Proxetil Tablets, USP are available in the following strengths (cefpodoxime equivalent), colors, and sizes:

100 mg, (light orange, film-coated, elliptical, embossed with SZ 438)

Bottles of 20 NDC 0781-5438-20

Bottles of 100 NDC 0781-5438-01

200 mg, (light orange, film-coated, oblong, embossed with SZ 439)

Bottles of 20 NDC 0781-5439-20

Bottles of 100 NDC 0781-5439-01

Store at 20° to 25°C (68° to 77°F).

Replace cap securely after each opening.

REFERENCES

• Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-third Informational Supplement, CLSI document M100-S23. CLSI document M100-S23, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2013.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Eleventh Edition CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.

CLINICAL TRIALS

Cystitis

In two double-blind, 2:1 randomized, comparative trials performed in adults in the United States, Zipod proxetil was compared to other beta-lactam antibiotics. In these studies, the following bacterial eradication rates were obtained at 5 to 9 days after therapy:

In these studies, clinical cure rates and bacterial eradication rates for Zipod proxetil were comparable to the comparator agents; however, the clinical cure rates and bacteriologic eradication rates were lower than those observed with some other classes of approved agents for cystitis.

Acute Otitis Media Studies

In controlled studies of acute otitis media performed in the United States, where significant rates of beta-lactamase-producing organisms were found, Zipod proxetil was compared to cefixime. In these studies, using very strict evaluability criteria and microbiologic and clinical response criteria at the 4 to 21 day post-therapy follow-up, the following presumptive bacterial eradication/clinical success outcomes (cured and improved) were obtained.

07-2014M

46143253

Manufactured in Austria by Sandoz GmbH

for Sandoz Inc., Princeton, NJ 08540

100 mg Label

NDC 0781-5438-01

Cefpodoxime

Proxetil

Tablets, USP

100 mg*

Rx only

100 Tablets

SANDOZ

Zipod Proxetil 100 mg Label

200 mg Label

NDC 0781-5439-01

Cefpodoxime

Proxetil

Tablets, USP

200 mg*

Rx only

100 Tablets

SANDOZ

Zipod Proxetil 200 mg Label

Zipod pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.

• Cefpodoxime

Zipod available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.

• Syrup; Oral; Cefpodoxime 100 mg / 5 ml
• Syrup; Oral; Cefpodoxime 50 mg / 5 ml
• Tablets, Dispersible; Oral; Cefpodoxime 100 mg
• Tablets, Dispersible; Oral; Cefpodoxime 50 mg
• Tablets; Oral; Cefpodoxime 200 mg

Zipod destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.

• Human:
• Cephalosporins third-generation

Zipod Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.

• J01DD13 - Cefpodoxime

Zipod pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.

• FDC

Frequently asked Questions

Depending on the reaction of the Zipod after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Zipod not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology