DRUGS & SUPPLEMENTS
Indications and Usage, Acute Bacterial Exacerbations of Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis: Secondary Bacterial Infections of Acute Bronchitis (1.4)Removed
Dosage and Administration, Dosage for I-M-Sure tablets: Secondary Bacterial Infections of Acute Bronchitis (2.2)Removed
1 INDICATIONS & USAGE
I-M-Sure tablet is a cephalosporin antibacterial drug indicated for the treatment of the following infections due to susceptible bacteria:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of I-M-Sure and other antibacterial drugs, I-M-Sure should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Cefuroxime axetiltablets are indicated for the treatment of adult patients and pediatric patients (13 years and older) with mild-to-moderate pharyngitis/tonsillitis caused by susceptible strains of Streptococcus pyogenes.
Limitations of Use
1.2 Acute Bacterial Otitis Media
I-M-Sure tablets are indicated for the treatment of pediatric patients with acute bacterial otitis media caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase–producing strains), Moraxella catarrhalis (including β-lactamase–producing strains), or Streptococcus pyogenes.
1.3 Acute Bacterial Maxillary Sinusitis
I-M-Sure tablets are indicated for the treatment of adult and pediatric patients (13 years and older) with mild-to-moderate acute bacterial maxillary sinusitis caused by susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae (non-β-lactamase–producing strains only).
Limitations of Use The effectiveness of I-M-Sure for sinus infections caused by β-lactamase–producing Haemophilus influenzae or Moraxella catarrhalis in patients with acute bacterial maxillary sinusitis was not established due to insufficient numbers of these isolates in the clinical trials .
1.4 Acute Bacterial Exacerbations of Chronic Bronchitis
I-M-Sure tablets are indicated for the treatment of adult patients and pediatric patients with mild-to-moderate acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae (β-lactamase–negative strains), or Haemophilus parainfluenzae (β-lactamase–negative strains).
1.5 Uncomplicated Skin and Skin-structure Infections
I-M-Sure tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated skin and skin-structure infections caused by susceptible strains of Staphylococcus aureus (including β-lactamase–producing strains) or Streptococcus pyogenes.
1.6 Uncomplicated Urinary Tract Infections
I-M-Sure tablets are indicated for the treatment of adult patients and pediatric patients with uncomplicated urinary tract infections caused by susceptible strains of Escherichia coli or Klebsiella pneumoniae.
1.7 Uncomplicated Gonorrhea
I-M-Sure tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated gonorrhea, urethral and endocervical, caused by penicillinase producing and non-penicillinase–producing susceptible strains of Neisseria gonorrhoeae and uncomplicated gonorrhea, rectal, in females, caused by non-penicillinase–producing susceptible strains of Neisseria gonorrhoeae.
1.8 Early Lyme Disease
I-M-Sure tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with early Lyme disease (erythema migrans) caused by susceptible strains of Borrelia burgdorferi.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of I-M-Sure and other antibacterial drugs, I-M-Sure 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.
2 DOSAGE & ADMINISTRATION
2.1 Important Administration Instructions
2.2 Dosage for I-M-Sure Tablets
Administer I-M-Sure tablets as described in the dosage guidelines table below with or without food.
Table 1. Adult Patients and Pediatric Patients Dosage Guidelines for I-M-Sure Tablets
a The safety and effectiveness of I-M-Sure administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established.
b When crushed, the tablet has a strong, persistent bitter taste. Therefore, patients who cannot swallow the tablet whole should receive the oral suspension.
2.5 Dosage in Patients with Impaired Renal Function
A dosage interval adjustment is required for patients whose creatinine clearance is <30 mL/min, as listed in Table 4 below, because cefuroxime is eliminated primarily by the kidney .
Table 4. Dosing in Adults with Renal Impairment
3 DOSAGE FORMS & STRENGTHS
I-M-Sure tablets, 250 mg of cefuroxime (as I-M-Sure), are blue, capsule-shaped, biconvex, film-coated tablets with “204” debossed on one side and plain on the other side
I-M-Sure Tablets, 500 mg of cefuroxime (as I-M-Sure), are blue, capsule-shaped, biconvex, film-coated tablets with 203” debossed on one side and plain on the other side.
Tablets: 250 mg and 500 mg
I-M-Sure is contraindicated in patients with a known hypersensitivity (e.g., anaphylaxis) to I-M-Sure or to other β-lactam antibacterial drugs (e.g., penicillins and cephalosporins).
Known hypersensitivity (e.g., anaphylaxis) to I-M-Sure or to other β-lactams (e.g., penicillins and cephalosporins).
5 WARNINGS AND PRECAUTIONS
5.1 Anaphylactic Reactions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on β-lactam antibacterials. These reactions are more likely to occur in individuals with a history of β-lactam 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. I-M-Sure is contraindicated in patients with a known hypersensitivity to I-M-Sure or other β-lactam antibacterial drugs . Before initiating therapy with I-M-Sure, inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue I-M-Sure and institute appropriate therapy.
5.2 Clostridium difficile-associated Diarrhea
Clostridium difficile-associated diarrhea has been reported with use of nearly all antibacterial agents, including I-M-Sure, 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 2 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.
5.3 Potential for Microbial Overgrowth
The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy.
5.4 Development of Drug-resistant Bacteria
Prescribing I-M-Sure either 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.
5.6 Interference with Glucose Tests
A false-positive result for glucose in the urine may occur with copper reduction tests, and a false-negative result for blood/plasma glucose may occur with ferricyanide tests in subjects receiving I-M-Sure .
The following serious and otherwise important adverse reaction is described in greater detail in the Warnings and Precautions section of the label:
The most common adverse reactions (≥3%) for I-M-Sure tablets are diarrhea, nausea/vomiting, Jarisch-Herxheimer reaction and vaginitis (early Lyme disease). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Multiple-dose Dosing Regimens with 7 to 10 Days’ Duration: In multiple-dose clinical trials, 912 subjects were treated with I-M-Sure (125 to 500 mg twice daily). It is noted that 125 mg twice daily is not an approved dosage. Twenty (2.2%) subjects discontinued medication due to adverse reactions. Seventeen (85%) of the 20 subjects who discontinued therapy did so because of gastrointestinal disturbances, including diarrhea, nausea, vomiting, and abdominal pain. The percentage of subjects treated with I-M-Sure who discontinued study drug because of adverse reactions was similar at daily doses of 1,000, 500, and 250 mg (2.3%, 2.1%, and 2.2%, respectively). However, the incidence of gastrointestinal adverse reactions increased with the higher recommended doses.
The adverse reactions in Table 5 are for subjects (n = 912) treated with I-M-Sure in multiple-dose clinical trials.
Table 5. Adverse Reactions (≥1%) after Multiple-dose Regimens with I-M-Sure Tablets
The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 912) treated with I-M-Sure in multiple-dose clinical trials.
Immune System Disorders: Hives, swollen tongue.
Metabolism and Nutrition Disorders: Anorexia.
Nervous System Disorders: Headache.
Cardiac Disorders: Chest pain.
Respiratory Disorders: Shortness of breath.
Gastrointestinal Disorders: Abdominal pain, abdominal cramps, flatulence, indigestion, mouth ulcers.
Skin and Subcutaneous Tissue Disorders: Rash, itch
Renal and Urinary Disorders: Dysuria.
Reproductive System and Breast Disorders: Vaginitis, vulvar itch.
General Disorders and Administration Site Conditions: Chills, sleepiness, thirst.
Investigations: Positive Coombs’ test.
Early Lyme Disease with 20-Day Regimen: Two multicenter trials assessed I-M-Sure tablets 500 mg twice daily for 20 days. The most common drug-related adverse experiences were diarrhea (10.6%), Jarisch-Herxheimer reaction (5.6%), and vaginitis (5.4%). Other adverse experiences occurred with frequencies comparable to those reported with 7 to 10 days’ dosing.
Single-dose Regimen for Uncomplicated Gonorrhea: In clinical trials using a single 1,000 mg dose of I-M-Sure, 1,061 subjects were treated for uncomplicated gonorrhea.
The adverse reactions in Table 6 were for subjects treated with a single dose of 1,000 mg I-M-Sure in US clinical trials.
Table 6. Adverse Reactions (≥1%) after Single-dose Regimen with 1,000-mg I-M-Sure Tablets for Uncomplicated Gonorrhea
The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 1,061) treated with a single dose of I-M-Sure 1,000 mg for uncomplicated gonorrhea in US clinical trials.
Infections and Infestations: Vaginal candidiasis.
Nervous System Disorders: Headache, dizziness, somnolence.
Cardiac Disorders: Tightness/pain in chest, tachycardia.
Gastrointestinal Disorders: Abdominal pain, dyspepsia.
Skin and Subcutaneous Tissue Disorders: Erythema, rash, pruritus.
Musculoskeletal and Connective Tissue Disorders: Muscle cramps, muscle stiffness, muscle spasm of neck, lockjaw-type reaction.
Renal and Urinary Disorders: Bleeding/pain in urethra, kidney pain.
Reproductive System and Breast Disorders:
Vaginal itch, vaginal discharge.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of I-M-Sure. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders
Hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia.
Pseudomembranous colitis .
Hepatic impairment including hepatitis and cholestasis, jaundice.
Immune System Disorders
Anaphylaxis, serum sickness-like reaction.
Increased prothrombin time.
Nervous System Disorders
Renal and Urinary Disorders
Skin and Subcutaneous Tissue Disorders
Angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria.
7 DRUG INTERACTIONS
7.1 Oral Contraceptives
I-M-Sure may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. Counsel patients to consider alternate supplementary (non-hormonal) contraceptive measures during treatment.
7.2 Drugs that Reduce Gastric Acidity
Drugs that reduce gastric acidity may result in a lower bioavailability of I-M-Sure compared with administration in the fasting state. Administration of drugs that reduce gastric acidity may negate the food effect of increased absorption of I-M-Sure when administered in the postprandial state. Administer I-M-Sure at least 1 hour before or 2 hours after administration of short-acting antacids. Histamine-2 antagonists and proton pump inhibitors should be avoided.
Concomitant administration of probenecid with I-M-Sure tablets increases serum concentrations of cefuroxime . Co-administration of probenecid with I-M-Sure is not recommended.
7.4 Drug/Laboratory Test Interactions
A false-positive reaction for glucose in the urine may occur with copper reduction tests (e.g., Benedict's or Fehling's solution), but not with enzyme-based tests for glycosuria. As a false-negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood/plasma glucose levels in patients receiving I-M-Sure. The presence of cefuroxime does not interfere with the assay of serum and urine creatinine by the alkaline picrate method.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, I-M-Sure should be used during pregnancy only if clearly needed.
Reproduction studies have been performed in mice at doses up to 3,200 mg/kg/day and in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to I-M-Sure.
8.3 Nursing Mothers
Because cefuroxime is excreted in human milk, caution should be exercised when I-M-Sure is administered to a nursing woman.
8.4 Pediatric Use
The safety and effectiveness of I-M-Sure have been established for pediatric patients aged 3 months to 12 years for acute bacterial maxillary sinusitis based upon its approval in adults. Use of I-M-Sure in pediatric patients is supported by pharmacokinetic and safety data in adults and pediatric patients, and by clinical and microbiological data from adequate and well-controlled trials of the treatment of acute bacterial maxillary sinusitis in adults and of acute otitis media with effusion in pediatric patients. It is also supported by postmarketing adverse events surveillance.
8.5 Geriatric Use
Of the total number of subjects who received I-M-Sure in 20 clinical trials, were aged 65 and older while 151 were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger adult subjects. Reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.
Cefuroxime is substantially excreted by the kidney, and the risk of adverse reactions 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.
8.6 Renal Impairment
Reducing the dosage of I-M-Sure is recommended for adult patients with severe renal impairment (creatinine clearance <30 mL/min) .
Overdosage of cephalosporins can cause cerebral irritation leading to convulsions or encephalopathy. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.
I-M-Sure tablets, USP contain cefuroxime as I-M-Sure. I-M-Sure is a semisynthetic, cephalosporin antibacterial drug for oral administration.
The chemical name of I-M-Sure (1-(acetyloxy) ethyl ester of cefuroxime) is (RS)-1 hydroxyethyl (6R,7R)-7-[2-(2-furyl)glyoxyl-amido]-3-(hydroxymethyl)-8-oxo-5-thia-1 azabicyclo[4.2.0]-oct-2-ene-2-carboxylate, 72-(Z)-(O-methyl-oxime), 1-acetate 3-carbamate. Its molecular formula is C20H22N4O10S, and it has a molecular weight of 510.48.
I-M-Sure is in the amorphous form and has the following structural formula:
I-M-Sure tablets are film-coated and contain the equivalent of 250 or 500 mg of cefuroxime as I-M-Sure. I-M-Sure tablets contain the inactive ingredients microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, colloidal silicon dioxide, calcium stearate, calcium carbonate, crospovidone, hypromellose, titanium dioxide, propylene glycol, FD &C blue no.1 Aluminium lake.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
I-M-Sure is an antibacterial drug .
After oral administration, I-M-Sure is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to cefuroxime. Serum pharmacokinetic parameters for cefuroxime following administration of I-M-Sure tablets to adults are shown in Table 8.
Table 8.Pharmacokinetics of Cefuroxime Administered in the Postprandial State asCefuroxime Axetil Tablets to Adultsa
a Mean values of 12 healthy adult volunteers.
b Drug administered immediately after a meal.
Food Effect: Absorption of the tablet is greater when taken after food (absolute bioavailability increases from 37% to 52%). Despite this difference in absorption, the clinical and bacteriologic responses of subjects were independent of food intake at the time of tablet administration in 2 trials where this was assessed.
All pharmacokinetic and clinical effectiveness and safety trials in pediatric subjects using the suspension formulation were conducted in the fed state. No data are available on the absorption kinetics of the suspension formulation when administered to fasted pediatric subjects.
Lack of Bioequivalence: Oral suspension was not bioequivalent to tablets when tested in healthy adults. The tablet and oral suspension formulations are NOT substitutable on a milligram-per-milligram basis. The area under the curve for the suspension averaged 91% of that for the tablet, and the peak plasma concentration for the suspension averaged 71% of the peak plasma concentration of the tablets. Therefore, the safety and effectiveness of both the tablet and oral suspension formulations were established in separate clinical trials.
Cefuroxime is distributed throughout the extracellular fluids. Approximately 50% of serum cefuroxime is bound to protein.
The axetil moiety is metabolized to acetaldehyde and acetic acid.
Cefuroxime is excreted unchanged in the urine; in adults, approximately 50% of the administered dose is recovered in the urine within 12 hours. The pharmacokinetics of cefuroxime in pediatric subjects have not been studied. Until further data are available, the renal elimination of I-M-Sure established in adults should not be extrapolated to pediatric subjects.
Renal Impairment: In a trial of 28adults with normal renal function or severe renal impairment (creatinineclearance <30 mL/min), the elimination half-life was prolonged in relationto severity of renal impairment. Prolongation of the dosage interval isrecommended in adult patients with creatinine clearance <30 mL/min [seeDosage and Administration (2.5)].
Geriatric Patients: In a trial of 20elderly subjects (mean age = 83.9 years) having a mean creatinine clearance of34.9 mL/min, the mean serum elimination half-life was prolonged to 3.5 hours;however, despite the lower elimination of cefuroxime in geriatric patients,dosage adjustment based on age is not necessary .
Concomitant administration of probenecid withcefuroxime axetil tablets increases the cefuroxime area under the serumconcentration versus time curve and maximum serum concentration by 50% and 21%,respectively.
Mechanism of Action
I-M-Sure is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. I-M-Sure has activity in the presence of some β-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.
Mechanism of Resistance
Resistance to I-M-Sure is primarily through hydrolysis by β-lactamase, alteration of penicillin-binding proteins (PBPs), decreased permeability, and the presence of bacterial efflux pumps.
Susceptibility to I-M-Sure will vary with geography and time; local susceptibility data should be consulted, if available. Beta-lactamase-negative, ampicillin-resistant (BLNAR) isolates of H. influenzaeshould be considered resistant to I-M-Sure.
I-M-Sure has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections :
Staphylococcus aureus (methicillin-susceptible isolates only)
a Most extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to I-M-Sure.
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 break point for I-M-Sure of 1 mcg/mL. However, the efficacy of I-M-Sure in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.
Staphylococcus epidermidis (methicillin-susceptible isolates only)
Staphylococcus saprophyticus (methicillin-susceptible isolates only)
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility tests for antimicrobial drug products used in local hospitals and practice areas 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 MICs. These MICs provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth or agar).1,2 The MIC values should be interpreted according to criteria provided in Table 10.2,3
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.4 This procedure uses paper disks impregnated with 30 mcg I-M-Sure to test the susceptibility of microorganisms to I-M-Sure. The disk diffusion interpretive criteria are provided in Table 10.3
Table 10. Susceptibility Test Interpretive Criteria for I-M-Sure
a For Enterobacteriaceae, Haemophilus spp., and Moraxella catarrhalis, susceptibility interpretive criteria are based on a dose of 500 mg every 12 hours in patients with normal renal function.
b Haemophilus spp. includes only isolates of H. influenzaeand H. parainfluenzae.
Susceptibility of staphylococci to cefuroxime may be deduced from testing only penicillin and 485 either cefoxitin or oxacillin.
Susceptibility of Streptococcus pyogenes may be deduced from testing penicillin.3
A report of “Susceptible” indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. 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 drug is not likely to inhibit growth of the pathogen if the antimicrobial drug 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.1,2,4 The QC ranges for MIC and disk diffusion testing using the 30-mcg disk are provided in Table 11.3
Table 11. Acceptable Quality Control (QC) Ranges for I-M-Sure
ATCC = American Type Culture Collection.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility
Although lifetime studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic activity was found for I-M-Sure in a battery of bacterial mutation tests. Positive results were obtained in an in vitro chromosome aberration assay; however, negative results were found in an in vivo micronucleus test at doses up to 1.5 g/kg. Reproduction studies in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on body surface area) have revealed no impairment of fertility.
14 CLINICAL STUDIES
14.1 Acute Bacterial Maxillary Sinusitis
One adequate and well-controlled trial was performed in subjects with acute bacterial maxillary sinusitis. In this trial, each subject had a maxillary sinus aspirate collected by sinus puncture before treatment was initiated for presumptive acute bacterial sinusitis. All subjects had radiographic and clinical evidence of acute maxillary sinusitis. In the trial, the clinical effectiveness of I-M-Sure in treating acute maxillary sinusitis was comparable to an oral antimicrobial agent containing a specific β-lactamase inhibitor. However, microbiology data demonstrated I-M-Sure to be effective in treating acute bacterial maxillary sinusitis due only to Streptococcus pneumoniae or non-β-lactamase–producing Haemophilus influenzae. Insufficient numbers of β-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis isolates were obtained in this trial to adequately evaluate the effectiveness of I-M-Sure in treating acute bacterial maxillary sinusitis due to, these 2 organisms.
This trial randomized 317 adult subjects,132 subjects in the U.S and 185 subjects in South America.
Table 12 shows the results of the intent-to-treat analysis.
Table12. Clinical Effectiveness of I-M-Sure Tablets in the Treatment ofAcute Bacterial Maxillary Sinusitis
a 95% confidence interval around thesuccess difference [-0.08, +0.32]
b 95% confidence interval around thesuccess difference [-0.10, +0.16].
c Control was an antibacterial drugcontaining a β-lactamase inhibitor.
In this trial and in a supporting maxillary puncture trial, 15 evaluable subjects had non β-lactamase–producing Haemophilus influenzae as the identified pathogen. Of these, 67% (10/15) had this pathogen eradicated. Eighteen (18) evaluable subjects had Streptococcus pneumoniae as the identified pathogen. Of these, 83% (15/18) had this pathogen eradicated.
14.2 Early Lyme Disease
Two adequate and well-controlled trials were performed in subjects with early Lyme disease. All subjects presented with physician-documented erythema migrans, with or without systemic manifestations of infection. Subjects were assessed at 1 month posttreatment for success in treating early Lyme disease (Part I) and at 1 year posttreatment for success in preventing the progression to the sequelae of late Lyme disease (Part II).
A total of 355 adult subjects (181 treated with I-M-Sure and 174 treated with doxycycline) were randomized in the 2 trials, with diagnosis of early Lyme disease confirmed in 79% (281/355). The clinical diagnosis of early Lyme disease in these subjects was validated by 1) blinded expert reading of photographs, when available, of the pretreatment erythema migrans skin lesion, and 2) serologic confirmation (using enzyme-linked immunosorbent assay [ELISA] and immunoblot assay [“Western” blot]) of the presence of antibodies specific to Borrelia burgdorferi, the etiologic agent of Lyme disease. The efficacy data in Table 14 are specific to this “validated” patient subset, while the safety data below reflect the entire patient population for the 2 trials. Clinical data for evaluable subjects in the “validated” patient subset are shown in Table 13.
Table 13. Clinical Effectiveness of I-M-Sure Tablets Compared with Doxycycline in the Treatment of Early Lyme Disease
a 95% confidence interval around the satisfactory difference for Part I (-0.08, +0.05).
b 95% confidence interval around the satisfactory difference for Part II (-0.13, +0.07).
c n’s include subjects assessed as unsatisfactory clinical outcomes (failure + recurrence) in Part I (cefuroxime axetil - 11 [5 failure, 6 recurrence]; doxycycline - 8 [6 failure, 2 recurrence]).
d Satisfactory clinical outcome includes cure + improvement (Part I) and success + 560 improvement (Part II).
I-M-Sure and doxycycline were effective in prevention of the development of sequelae of late Lyme disease.
While the incidence of drug-related gastrointestinal adverse reactions was similar in the 2 treatment groups (cefuroxime axetil - 13%; doxycycline - 11%), the incidence of drug-related diarrhea was higher in the I-M-Sure arm versus the doxycycline arm (11% versus 3%, respectively).
1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. 2015. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
2. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing for Infrequently Isolated or Fastidious Bacteria: Approved Guidelines - Second Edition. 2010. CLSI document M45-A2, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement. 2015. CLSI document M100S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
4. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. 2015. CLSI document M02-A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
16 HOW SUPPLIED/STORAGE AND HANDLING
I-M-Sure Tablets, USP: I-M-Sure tablets,
250 mg of cefuroxime (as I-M-Sure), are blue, capsule-shaped, biconvex, film-coated tablets with “204” debossed on one side and plain on the other side as follows:
20 Tablets/Bottle NDC 67877-215-20
60 Tablets/Bottle NDC 67877-215-60
100 Tablets/Bottle NDC 67877-215-01
30 Tablets (3x10 Unit-dose Tablets) NDC 67877-215-84
I-M-Sure Tablets, 500 mg of cefuroxime (as I-M-Sure), are blue, capsule-shaped, biconvex, film-coated tablets with “203” debossed on one side and plain on the other side as follows:
20 Tablets/Bottle NDC 67877-216-20
60 Tablets/Bottle NDC 67877-216-60
100 Tablets/Bottle NDC 67877-216-01
30 Tablets (3x10 Unit-dose Tablets) NDC 67877-216-84
Store at 20° to 25°C (68° to 77°F). . Replace cap securely after each Use.
17 PATIENT COUNSELING INFORMATION
Inform patients that I-M-Sure is a cephalosporin that can cause allergic reactions in some individuals .
Clostridium difficile -associated Diarrhea
Inform patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, 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 their last dose of the antibacterial. If this occurs, advise patients to contact their physician as soon as possible.
Instruct patients to swallow the tablet whole, without crushing the tablet. Patients who cannot swallow the tablet whole should receive the oral suspension.
Inform patients that antibacterial drugs, including I-M-Sure, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When I-M-Sure is prescribed to treat a bacterial infection, inform patients 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 I-M-Sure or other antibacterial drugs in the future.
Alkem Laboratories Limited
ALKEM HOUSE, Lower Parel,
Mumbai - 400 013, INDIA
Ascend Laboratories, LLC
Parsipanny, NJ 07054
AXETIL TABLETS, USP
AXETIL TABLETS, USP
I-M-Sure 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.
I-M-Sure 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.
I-M-Sure 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.
I-M-Sure 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.
I-M-Sure 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.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming I-M-Sure?
Depending on the reaction of the I-M-Sure after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider I-M-Sure 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.Is I-M-Sure addictive or habit forming?
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.
Reviewsdrugs.com conducted a study on I-M-Sure, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of I-M-Sure consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
Visitor reported side effectsNo survey data has been collected yet
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
Visitor reported dosesNo survey data has been collected yet
Visitor reported time for resultsNo survey data has been collected yet
Visitor reported administrationNo survey data has been collected yet
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The information was verified by Dr. Arunabha Ray, MD Pharmacology