DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Pimacef for Injection is a cephalosporin antibacterial indicated for the treatment of the following infections caused by susceptible strains of the designated microorganisms:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Pimacef for Injection and other antibacterial drugs, Pimacef for Injection should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. (1.6)
Pimacef for Injection is indicated in the treatment of pneumonia (moderate to severe) caused by susceptible strains of Streptococcus pneumoniae, including cases associated with concurrent bacteremia, Pseudomonas aeruginosa, Klebsiella pneumoniae, or Enterobacter species.
1.2 Empiric Therapy for Febrile Neutropenic Patients
Pimacef as monotherapy is indicated for empiric treatment of febrile neutropenic patients. In patients at high risk for severe infection, antimicrobial monotherapy may not be appropriate. Insufficient data exist to support the efficacy of Pimacef monotherapy in such patients [see Clinical Studies (14.1)].
1.3 Uncomplicated and Complicated Urinary Tract Infections (including pyelonephritis)
Pimacef is indicated in the treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by susceptible isolates of Escherichia coli or Klebsiella pneumoniae, when the infection is severe, or caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis, when the infection is mild to moderate, including cases associated with concurrent bacteremia with these bacteria.
1.4 Uncomplicated Skin and Skin Structure Infections
Pimacef is indicated in the treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus or Streptococcus pyogenes.
1.5 Complicated Intra-abdominal Infections (used in combination with metronidazole)
Pimacef is indicated in the treatment of complicated intra-abdominal infections (used in combination with metronidazole) in adults caused by susceptible isolates of Escherichia coli, viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, or Bacteroides fragilis [see Clinical Studies (14.2)].
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Pimacef for Injection and other antibacterial drugs, Pimacef for Injection should be used only to treat 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 AND ADMINISTRATION
Pediatric Patients (2 months to 16 years)
Recommended dosage in pediatric with CrCL greater than 60 mL/min. (2.2)
2.1 Dosage for Adults
The recommended adult dosages and routes of administration are outlined in Table 1 below for patients with creatinine clearance greater than 60 mL/min. Administer Pimacef for Injection intravenously over approximately 30 minutes.
2.2 Pediatric Patients
The maximum dose for pediatric patients should not exceed the recommended adult dose.
The usual recommended dosage in pediatric patients up to 40 kg in weight for durations as given above for adults is:
2.3 Dosage Adjustments in Patients with Renal Impairment
Adjust the dose of Pimacef for injection in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination. In these patients, the recommended initial dose of Pimacef for injection should be the same as in patients with CrCL greater than 60 mL/min except in patients undergoing hemodialysis. The recommended doses of Pimacef for injection in patients with renal impairment are presented in Table 2.
When only serum creatinine is available, the following formula 4 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:
Females: 0.85 × above value
In patients undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD), Pimacef for injection may be administered at the recommended doses at a dosage interval of every 48 hours.
In patients undergoing hemodialysis, approximately 68% of the total amount of Pimacef present in the body at the start of dialysis will be removed during a 3-hour dialysis period. The dosage of Pimacef for injection for hemodialysis patients is 1 g on Day 1 followed by 500 mg every 24 hours for the treatment of all infections except febrile neutropenia, which is 1 g every 24 hours.
Pimacef for Injection should be administered at the same time each day and following the completion of hemodialysis on hemodialysis days.
Data in pediatric patients with impaired renal function are not available; however, since Pimacef pharmacokinetics are similar in adults and pediatric patients [see Clinical Pharmacology (12.3)], changes in the dosing regimen proportional to those in adults are recommended for pediatric patients.
2.4 Preparation of Pimacef for Intravenous Infusion
2.5 Preparation for Intramuscular Administration
Constitute Pimacef for injection vials 0.5 gram, 1 gram and 2 grams with one of the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride, 5% Dextrose Injection, 0.5% or 1% Lidocaine Hydrochloride, or Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol. Refer to Table 3 below for the amount of diluent to be added to each vial.
Parenteral drugs should be inspected visually for particulate matter before administration. If particulate matter is evident in reconstituted fluids, the drug solution should be discarded.
2.6 Compatibility and Stability
Intravenous Pimacef for Injection
Intravenous Infusion Compatibility
Pimacef for Injection vials are compatible at concentrations between 1 mg per mL and 40 mg per mL with the following intravenous infusion fluids: 0.9% Sodium Chloride Injection, 5% and 10% Dextrose Injection, M/6 Sodium Lactate Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringers and 5% Dextrose Injection, Normosol -R, and Normosol -M in 5% Dextrose Injection. These solutions may be stored up to 24 hours at controlled room temperature 20°C to 25°C (68°F to 77°F) or 7 days in a refrigerator 2°C to 8°C (36°F to 46°F).
Pimacef for Injection admixture compatibility information is summarized in Table 4.
Pimacef for Injection Admixture Incompatibility
Do not add solutions of Pimacef for injection, to solutions of ampicillin at a concentration greater than 40 mg per mL, or to metronidazole, vancomycin, gentamicin, tobramycin, netilmicin sulfate, or aminophylline because of potential interaction. However, if concurrent therapy with Pimacef for injection is indicated, each of these antibiotics can be administered separately.
Intramuscular Pimacef for Injection
Pimacef for injection constituted as directed is stable for 24 hours at controlled room temperature 20°C to 25°C (68°F to 77°F) or for 7 days in a refrigerator 2°C to 8°C (36°F to 46°F) with the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol, or 0.5% or 1% Lidocaine Hydrochloride.
Intramuscular and Intravenous Pimacef for Injection
As with other cephalosporins, the color of Pimacef powder, as well as its solutions tend to darken depending on storage conditions; however, when stored as recommended, the product potency is not adversely affected.
3 DOSAGE FORMS AND STRENGTHS
Pimacef for Injection, USP is a sterile white to pale yellow powder of Pimacef in single-dose vials for reconstitution and it is available in the following strengths:
Pimacef for injection, USP is a sterile powder of Pimacef in vials for reconstitution, available in the following strengths:
Pimacef for injection is contraindicated in patients who have shown immediate hypersensitivity reactions to Pimacef or the cephalosporin class of antibiotics, penicillins or other beta-lactam antibiotics.
Patients with known immediate hypersensitivity reactions to Pimacef or other cephalosporins, penicillins or other beta-lactam antibacterial drugs. (4)
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Before therapy with Pimacef for injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to Pimacef, cephalosporins, penicillins, or other beta-lactams. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Pimacef for injection occurs, discontinue the drug and institute appropriate supportive measures.
Serious adverse reactions have been reported including life-threatening or fatal occurrences of the following: encephalopathy, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus [see Adverse Reactions (6.2)]. Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. However, some cases of neurotoxicity occurred in patients receiving a dosage adjustment appropriate for their degree of renal impairment. In the majority of cases, symptoms of neurotoxicity were reversible and resolved after discontinuation of Pimacef and/or after hemodialysis. If neurotoxicity associated with Pimacef therapy occurs, discontinue Pimacef and institute appropriate supportive measures.
5.3 Clostridium difficile Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Pimacef, 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 antibacterial drug 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 antibacterial drug 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.
5.4 Development of Drug-Resistant Bacteria
Prescribing Pimacef for injection in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
As with other antimicrobials, prolonged use of Pimacef may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.
5.5 Drug/Laboratory Test Interactions
The administration of Pimacef may result in a false-positive reaction for glucose in the urine when using some methods (e.g. Clinitest tablets) [see Drug Interactions (7.1)].
Positive direct Coombs' tests have been reported during treatment with Pimacef. In patients who develop hemolytic anemia, discontinue the drug and institute appropriate therapy. Positive Coombs' test may be observed in newborns whose mothers have received cephalosporin antibiotics before parturition.
Many cephalosporins, including Pimacef, have been associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk, and exogenous vitamin K administered as indicated.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in the Warnings and Precautions section and below:
To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at-1-800-706-5575 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 clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials using multiple doses of Pimacef, 4137 patients were treated with the recommended dosages of Pimacef (500 mg to 2 g intravenous every 12 hours). There were no deaths or permanent disabilities thought related to drug toxicity. Sixty-four (1.5%) patients discontinued medication due to adverse reactions. Thirty-three (51%) of these 64 patients who discontinued therapy did so because of rash. The percentage of cefepime-treated patients who discontinued study drug because of drug-related adverse reactions was similar at daily doses of 500 mg, 1 g, and 2 g every 12 hours (0.8%, 1.1%, and 2%, respectively). However, the incidence of discontinuation due to rash increased with the higher recommended doses.
The following adverse reactions (Table 5) were identified in clinical trials conducted in North America (n=3125 cefepime-treated patients).
At the higher dose of 2 g every 8 hours, the incidence of adverse reactions was higher among the 795 patients who received this dose of Pimacef. They consisted of rash (4%), diarrhea (3%), nausea (2%), vomiting (1%), pruritus (1%), fever (1%), and headache (1%).
The following (Table 6) adverse laboratory changes, with Pimacef, were seen during clinical trials conducted in North America.
A similar safety profile was seen in clinical trials of pediatric patients
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Pimacef. 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.
In addition to the adverse reactions reported during the North American clinical trials with Pimacef, the following adverse reactions have been reported during worldwide postmarketing experience. Encephalopathy, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus have been reported. [see Warnings and Precautions (5.2)]
Anaphylaxis including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia, have been reported.
6.3 Cephalosporin-Class Adverse Reactions
In addition to the adverse reactions listed above that have been observed in patients treated with Pimacef, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterial drugs:
Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, hepatic dysfunction including cholestasis, and pancytopenia.
7 DRUG INTERACTIONS
7.1 Drug/Laboratory Test Interactions
The administration of Pimacef may result in a false-positive reaction for glucose in the urine with certain methods. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.
Monitor renal function if aminoglycosides are to be administered with Pimacef because of the increased potential of nephrotoxicity and ototoxicity of aminoglycoside antibacterial drugs.
Nephrotoxicity has been reported following concomitant administration of other cephalosporins with potent diuretics such as furosemide. Monitor renal function when Pimacef is concomitantly administered with potent diuretics.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category B
There are no adequate and well-controlled studies of Pimacef 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.
Pimacef was not teratogenic or embryocidal when administered during the period of organogenesis to rats at doses up to 1000 mg/kg/day (1.6 times the recommended maximum human dose calculated on a body surface area basis) or to mice at doses up to 1200 mg/kg (approximately equal to the recommended maximum human dose calculated on a body surface area basis) or to rabbits at a dose level of 100 mg/kg (0.3 times the recommended maximum human dose calculated on a body surface area basis).
8.2 Labor and Delivery
Pimacef has not been studied for use during labor and delivery. Treatment should only be given if clearly indicated.
8.3 Nursing Mothers
Pimacef is excreted in human breast milk. Caution should be exercised when Pimacef is administered to a nursing woman [see Clinical Pharmacology ].
8.4 Pediatric Use
The safety and effectiveness of Pimacef in the treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, pneumonia, and as empiric therapy for febrile neutropenic patients have been established in the age groups 2 months up to 16 years. Use of Pimacef in these age groups is supported by evidence from adequate and well-controlled studies of Pimacef in adults with additional pharmacokinetic and safety data from pediatric trials [see Clinical Pharmacology (12.3)].
Safety and effectiveness in pediatric patients below the age of 2 months have not been established. There are insufficient clinical data to support the use of Pimacef for injection in pediatric patients for the treatment of serious infections in the pediatric population where the suspected or proven pathogen is H. influenzae type b. In those patients in whom meningeal seeding from a distant infection site or in whom meningitis is suspected or documented, an alternate agent with demonstrated clinical efficacy in this setting should be used.
8.5 Geriatric Use
Of the more than 6400 adults treated with Pimacef for injection in clinical studies, 35% were 65 years or older while 16% were 75 years or older. When geriatric patients received the usual recommended adult dose, clinical efficacy and safety were comparable to clinical efficacy and safety in non-geriatric adult patients.
Serious adverse events have occurred in geriatric patients with renal insufficiency given unadjusted doses of Pimacef, including life-threatening or fatal occurrences of the following: encephalopathy, myoclonus, and seizures [see Warnings and Precautions, Adverse Reactions (6.2)].
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored [see Clinical Pharmacology (12.3), Warnings and Precautions (5.2), Dosage and Administration (2.3)].
8.6 Renal Impairment
Adjust the dose of Pimacef for injection in patients with creatinine clearance less than or equal to 60 mL/min to compensate for the slower rate of renal elimination. [See Dosage Adjustments in Patients with Renal Impairment (2.3)]
Patients who receive an overdose should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis, not peritoneal dialysis, is recommended to aid in the removal of Pimacef from the body. Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and nonconvulsive status epilepticus [see Warnings and Precautions (5.2), Adverse Reactions (6.2), Dosage and Administration (2.3)].
Pimacef hydrochloride, USP is a semi-synthetic, cephalosporin antibacterial for parenteral administration. The chemical name is 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)-glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0] oct-2-en-3-yl]methyl]-1-methylpyrrolidinium chloride,72-(Z)-(O-methyloxime), monohydrochloride, monohydrate, which corresponds to the following structural formula:
Pimacef hydrochloride is a white to pale yellow powder. Pimacef hydrochloride contains the equivalent of not less than 825 mcg and not more than 911 mcg of Pimacef (C19H24N6O5S2) per mg, calculated on an anhydrous basis. It is highly soluble in water.
Pimacef for Injection, USP is supplied for intramuscular or intravenous administration in strengths equivalent to 500 mg, 1 g, and 2 g of Pimacef. Pimacef for injection, USP is a sterile, dry mixture of Pimacef hydrochloride and L-arginine. It contains the equivalent of not less than 90 percent and not more than 115 percent of the labeled amount of Pimacef (C19H24N6O5S2). The L-arginine, at an approximate concentration of 725 mg/g of Pimacef, is added to control the pH of the constituted solution at 4 to 6. Freshly constituted solutions of Pimacef for Injection, USP will range in color from pale yellow to amber.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Pimacef is a cephalosporin antibacterial drug [See Microbiology ].
Similar to other beta-lactam antimicrobial agents, the time that the unbound plasma concentration of Pimacef exceeds the MIC of the infecting organism has been shown to best correlate with efficacy in animal models of infection. However, the pharmacokinetic/pharmacodynamics relationship for Pimacef has not been evaluated in patients.
Pharmacokinetic parameters for Pimacef in healthy adult male volunteers following single 30-minute infusions (IV) of Pimacef 500 mg, 1 g, and 2 g are summarized in Table 7. Elimination of Pimacef is principally via renal excretion with an average (±SD) half-life of 2 (±0.3) hours and total body clearance of 120 (±8) mL/min in healthy volunteers. Pimacef pharmacokinetics are linear over the range 250 mg to 2 g. There is no evidence of accumulation in healthy adult male volunteers (n=7) receiving clinically relevant doses for a period of 9 days.
Pharmacokinetic parameters for Pimacef following a single intramuscular injection are summarized in Table 8. The pharmacokinetics of Pimacef are linear over the range of 500 mg to 2 g intramuscularly and do not vary with respect to treatment duration.
Following intramuscular (IM) administration, Pimacef is completely absorbed.
The average steady-state volume of distribution of Pimacef is 18 (±2) L. The serum protein binding of Pimacef is approximately 20% and is independent of its concentration in serum.
Pimacef is excreted in human milk at a concentration of 0.5 mcg/mL. A nursing infant consuming approximately 1000 mL of human milk per day would receive approximately 0.5 mg of Pimacef per day [see Use in Specific Populations (8.3)].
Concentrations of Pimacef achieved in specific tissues and body fluids are listed in Table 9.
Data suggest that Pimacef does cross the inflamed blood-brain barrier. The clinical relevance of these data is uncertain at this time.
Metabolism and Excretion
Pimacef is metabolized to N-methylpyrrolidine (NMP) which is rapidly converted to the N-oxide (NMP-N-oxide). Urinary recovery of unchanged Pimacef accounts for approximately 85% of the administered dose. Less than 1% of the administered dose is recovered from urine as NMP, 6.8% as NMP-N-oxide, and 2.5% as an epimer of Pimacef. Because renal excretion is a significant pathway of elimination, patients with renal dysfunction and patients undergoing hemodialysis require dosage adjustment [see Dosage and Administration (2.3)].
Patients with Renal impairment
Pimacef pharmacokinetics have been investigated in patients with various degrees of renal impairment (n=30). The average half-life in patients requiring hemodialysis was 13.5 (±2.7) hours and in patients requiring continuous peritoneal dialysis was 19 (±2) hours. Pimacef total body clearance decreased proportionally with creatinine clearance in patients with abnormal renal function, which serves as the basis for dosage adjustment recommendations in this group of patients [see Dosage and Administration (2.3)].
Patients with Hepatic impairment
The pharmacokinetics of Pimacef were unaltered in patients with hepatic impairment who received a single 1 g dose (n=11).
Pimacef pharmacokinetics have been investigated in elderly (65 years of age and older) men (n=12) and women (n=12) whose mean (SD) creatinine clearance was 74 (±15) mL/min. There appeared to be a decrease in Pimacef total body clearance as a function of creatinine clearance. Therefore, dosage administration of Pimacef in the elderly should be adjusted as appropriate if the patient's creatinine clearance is 60 mL/min or less [see Dosage and Administration (2.3)].
Pimacef pharmacokinetics have been evaluated in pediatric patients from 2 months to 11 years of age following single and multiple doses on every 8 hours (n=29) and every 12 hours (n=13) schedules. Following a single intravenous dose, total body clearance and the steady-state volume of distribution averaged 3.3 (±1) mL/min/kg and 0.3 (±0.1) L/kg, respectively. The urinary recovery of unchanged Pimacef was 60.4 (±30.4)% of the administered dose, and the average renal clearance was 2 (±1.1) mL/min/kg. There were no significant effects of age or gender (25 male vs. 17 female) on total body clearance or volume of distribution, corrected for body weight. No accumulation was seen when Pimacef was given at 50 mg per kg every 12 hours (n=13), while Cmax, AUC, and t½ were increased about 15% at steady state after 50 mg per kg every 8 hours. The exposure to Pimacef following a 50 mg per kg intravenous dose in a pediatric patient is comparable to that in an adult treated with a 2 g intravenous dose. The absolute bioavailability of Pimacef after an intramuscular dose of 50 mg per kg was 82.3 (±15)% in eight patients.
Mechanism of Action
Pimacef is a bactericidal drug that acts by inhibition of bacterial cell wall synthesis. Pimacef has a broad spectrum of in vitro activity that encompasses a wide range of Gram-positive and Gram-negative bacteria. Within bacterial cells, the molecular targets of Pimacef are the penicillin binding proteins (PBP).
Pimacef has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the Indications and Usage section (1).
Staphylococcus aureus (methicillin-susceptible isolates only)
Viridans group streptococci
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Pimacef against isolates of similar genus or organism group. However, the efficacy of Pimacef in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.
Staphylococcus epidermidis (methicillin-susceptible isolates only)
NOTE: Most isolates of enterococci, e.g., Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to Pimacef.
Acinetobacter calcoaceticus subsp. lwoffii
NOTE: Pimacef is inactive against many isolates of Stenotrophomonas maltophilia.
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial drugs 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 for treatment.
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method 1,2 (broth and/or agar). The MIC should be interpreted according to criteria provided in Table 10.
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates 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 discs impregnated with 30 mcg Pimacef to test the susceptibility of microorganisms to Pimacef. The disk diffusion interpretive criteria are provided in Table 10.
A report of Susceptible (S) 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 (I) 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 the 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 (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the infection site; other therapy should be selected.
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 Pimacef powder should provide the following range of MIC values noted in Table 11. For the diffusion technique using the 30 mcg disc, the criteria in Table 11 should be achieved.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No animal carcinogenicity studies have been conducted with Pimacef. In chromosomal aberration studies, Pimacef was positive for clastogenicity in primary human lymphocytes, but negative in Chinese hamster ovary cells. In other in vitro assays (bacterial and mammalian cell mutation, DNA repair in primary rat hepatocytes, and sister chromatid exchange in human lymphocytes), Pimacef was negative for genotoxic effects. Moreover, in vivo assessments of Pimacef in mice (2 chromosomal aberration and 2 micronucleus studies) were negative for clastogenicity. No untoward effects on fertility were observed in rats when Pimacef was administered subcutaneously at doses up to 1000 mg/kg/day (1.6 times the recommended maximum human dose calculated on a body surface area basis).
14 CLINICAL STUDIES
14.1 Febrile Neutropenic Patients
The safety and efficacy of empiric Pimacef monotherapy of febrile neutropenic patients have been assessed in two multicenter, randomized trials comparing Pimacef monotherapy to ceftazidime monotherapy (at a dose of 2 g intravenously every 8 hours). These studies comprised 317 evaluable patients. Table 12 describes the characteristics of the evaluable patient population.
Table 13 describes the clinical response rates observed. For all outcome measures, Pimacef was therapeutically equivalent to ceftazidime.
Insufficient data exist to support the efficacy of Pimacef monotherapy in patients at high risk for severe infection (including patients with a history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy, or with severe or prolonged neutropenia). No data are available in patients with septic shock.
14.2 Complicated Intra-abdominal Infections
Patients hospitalized with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter trial comparing the combination of Pimacef (2 g every 12 hours) plus intravenous metronidazole (500 mg every 6 hours) versus imipenem/cilastatin (500 mg every 6 hours) for a maximum duration of 14 days of therapy. The study was designed to demonstrate equivalence of the two therapies. The primary analyses were conducted on the population consisting of those with a surgically confirmed complicated infection, at least one pathogen isolated pretreatment, at least 5 days of treatment, and a 4 to 6 week follow-up assessment for cured patients. Subjects in the imipenem/cilastatin arm had higher APACHE II scores at baseline. The treatment groups were otherwise generally comparable with regard to their pretreatment characteristics. The overall clinical cure rate among the primary analysis patients was 81% (51 cured/63 evaluable patients) in the Pimacef plus metronidazole group and 66% (62/94) in the imipenem/cilastatin group. The observed differences in efficacy may have been due to a greater proportion of patients with high APACHE II scores in the imipenem/cilastatin group.
16 HOW SUPPLIED/STORAGE AND HANDLING
Pimacef for injection, USP is supplied as follows: Pimacef for Injection, USP in the dry state, is a white to pale yellow powder. Constituted solution of Pimacef for Injection, USP can range in color from pale yellow to amber.
Storage and Handling
Pimacef for injection, USP in the dry state should be stored at 2° to 25° C (36° to 77° F) and protected from light.
17 PATIENT COUNSELING INFORMATION
Mfg. by: Mfg. for:
Hospira Healthcare India Pvt. Ltd. Apotex Corp.
Irungattukottai - 602 105, India Weston, FL 33326
for Injection, USP
For IV or IM Use
Carton NDC 60505-0834-0 60505-0834-4
for Injection, USP
For IV Use
Carton NDC 60505-0681-0 60505-0681-4
Pimacef 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.
Pimacef 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.
Pimacef 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.
Pimacef 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.
Pimacef 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 Pimacef?
Depending on the reaction of the Pimacef after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Pimacef 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 Pimacef 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 Pimacef, 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 Pimacef 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.
The information was verified by Dr. Arunabha Ray, MD Pharmacology