Primaxin Drug Information
Generic name: IMIPENEM AND CILASTATIN SODIUM
Uses of Primaxin
Lower Respiratory Tract Infections PRIMAXIN for intravenous use is indicated for the treatment of lower respiratory tract infections caused by susceptible strains of Staphylococcus aureus (penicillinase-producing isolates), Acinetobacter species, Enterobacter species, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella species, Serratia marcescens.
Urinary Tract
Infections (complicated and uncomplicated) PRIMAXIN is indicated for the treatment of urinary tract infections (complicated and uncomplicated) caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa.
Intra-Abdominal Infections PRIMAXIN is indicated for the treatment of intra-abdominal infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus species, Pseudomonas aeruginosa, Bifidobacterium species, Clostridium species, Eubacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species, Bacteroides species including B. fragilis, Fusobacterium species.
Gynecologic Infections PRIMAXIN is indicated for the treatment of gynecologic infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Streptococcus agalactiae (Group B streptococci), Enterobacter species, Escherichia coli, Gardnerella vaginalis, Klebsiella species, Proteus species, Bifidobacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species, Bacteroides species including B. fragilis.
Bone and Joint Infections PRIMAXIN is indicated for the treatment of bone and joint infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Enterobacter species, Pseudomonas aeruginosa.
Limitations of Use PRIMAXIN is not indicated in patients with meningitis because safety and efficacy have not been established. PRIMAXIN is not recommended in pediatric patients with CNS infections because of the risk of seizures. PRIMAXIN is not recommended in pediatric patients less than 30 kg with impaired renal function, as no data are available.
Periodic assessment of organ system functions, including renal, hepatic and hematopoietic, is advisable during prolonged therapy.
Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of PRIMAXIN and other antibacterial drugs, PRIMAXIN 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.
Dosage & Administration of Primaxin
Dosage in Adults For Intravenous Injection Only
The dosage of PRIMAXIN in adult patients should be based on suspected or confirmed pathogen susceptibility as shown in Table 1 below. The dosage recommendations for PRIMAXIN represent the quantity of imipenem to be administered. An equivalent amount of cilastatin is also present in the solution.
These doses should be used for patients with creatinine clearance of greater than or equal to 90 mL/min. A reduction in dose must be made for patients with creatinine clearance less than 90 mL/min as shown in Table 3. Recommend that the maximum total daily dosage not exceed 4 g/day.
Administer 500 mg by intravenous infusion over 20 to 30 minutes. Administer 1000 mg by intravenous infusion over 40 to 60 minutes. Table 1: Dosage of PRIMAXIN in Adult Patients with Creatinine Clearance Greater than or Equal to 90 mL/min If the infection is suspected or proven to be due to bacterial species with intermediate susceptibility 1000 mg every 6 hours
Dosage in Pediatric Patients PRIMAXIN is not recommended in pediatric patients with CNS infections because of the risk of seizures. PRIMAXIN is not recommended in pediatric patients <30 kg with renal impairment, as no data are available. Based on studies in adults, the maximum total daily dose in pediatric patients should not exceed 4 g/day.
The recommended dosage for pediatric patients with non-CNS infections is shown in Table 2 below: Table 2: Recommended PRIMAXIN Dosage in Pediatric Patients for Non-CNS Infections
Dosage in Adult Patients with Renal Impairment Patients with creatinine clearance less than 90 mL/min require dosage reduction of PRIMAXIN as indicated in Table 3. The serum creatinine should represent a steady state of renal function. Patients with creatinine clearance less than 15 mL/min should not receive PRIMAXIN unless hemodialysis is instituted within 48 hours.
There is inadequate information to recommend usage of PRIMAXIN for patients undergoing peritoneal dialysis.
Dosage in Hemodialysis Patients
When treating patients with creatinine clearances of less than 15 mL/min who are undergoing hemodialysis, use the dosage recommendations for patients with creatinine clearances of less than 30 to greater than or equal to 15 mL/min in Table 3 above. Both imipenem and cilastatin are cleared from the circulation during hemodialysis. The patient should receive PRIMAXIN after hemodialysis and at intervals timed from the end of that hemodialysis session.
Dialysis patients, especially those with background CNS disease, should be carefully monitored; for patients on hemodialysis, PRIMAXIN is recommended only when the benefit outweighs the potential risk of seizures.
Reconstitution and Preparation of PRIMAXIN Solution for Intravenous Administration PRIMAXIN Vials Do not use diluents containing benzyl alcohol to reconstitute PRIMAXIN for administration to neonates because it has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Contents of the vials must be reconstituted by adding approximately 10 mL of the appropriate diluent to the vial.
Variations of color within this range do not affect the potency of the product. The reconstituted suspension must not be administered by direct Intravenous Infusion After reconstitution, shake vial well and transfer the resulting suspension to 100 mL of an appropriate infusion solution before administering by intravenous infusion. Repeat transfer of the resulting suspension with an additional 10 mL of infusion solution to ensure complete transfer of vial contents to the infusion solution.
Agitate the resulting mixture until clear. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard unused portion of the infusion solution where applicable.
Storage of Reconstituted Solutions Vials (After Reconstitution) PRIMAXIN, as supplied in single dose vials and reconstituted with the appropriate diluents, maintains satisfactory potency for 4 hours at room temperature or for 24 hours under refrigeration (5°C). Do not freeze solutions of PRIMAXIN.
Incompatibility and Compatibility of PRIMAXIN with other Antibacterial Drugs Do not mix PRIMAXIN with, or physically add to, other antibacterial drugs. PRIMAXIN may be administered concomitantly with other antibacterial drugs, such as aminoglycosides.
| Suspected or Proven Pathogen Susceptibility | Dosage of PRIMAXIN |
|---|---|
| If the infection is suspected or proven to be due to a susceptible bacterial species | 500 mg every 6 hours OR 1000 mg every 8 hours |
| If the infection is suspected or proven to be due to bacterial species with intermediate susceptibility [see Microbiology (12.4) ] | 1000 mg every 6 hours |
| Age | Dose (mg/kg) Doses less than or equal to 500 mg should be given by intravenous infusion over 20 to 30 minutes, Doses greater than 500 mg should be given by intravenous infusion over 40 to 60 minutes Recommend that the maximum total daily dosage not exceed 4g/day | Frequency (hours) |
|---|---|---|
| Greater than or equal to 3 Months of Age | ||
| 15-25 mg/kg | Every 6 hours | |
| Less than or equal to 3 months of age (Greater than or equal to 1,500 g body weight) | ||
| 4 weeks to 3 months of age | 25 mg/kg | Every 6 hours |
| 1 to 4 weeks of age | 25 mg/kg | Every 8 hours |
| Less than 1 week of age | 25 mg/kg | Every 12 hours |
| Males: | (weight in kg) × (140-age in years) |
| (72) × serum creatinine (mg/100 mL) | |
| Females: | (0.85) × (value calculated for males) |
| Creatinine clearance (mL/min) | ||||
|---|---|---|---|---|
| Greater than or equal to 90 | Less than 90 to greater than or equal to 60 | Less than 60 to greater than or equal to 30 | Less than 30 to greater than or equal to 15 | |
| Dosage of PRIMAXIN Administer doses less than or equal to 500 mg by intravenous infusion over 20 to 30 minutes. Discard unused portion of the infusion solution., Administer doses greater than 500 mg by intravenous infusion over 40 to 60 minutes. In patients who develop nausea during the infusion, the rate of infusion may be slowed. If the infection is suspected or proven to be due to a susceptible bacterial species: | 500 mg every 6 hours | 400 mg every 6 hours | 300 mg every 6 hours | 200 mg every 6 hours |
| OR | ||||
| 1000 mg every 8 hours | 500 mg every 6 hours | 500 mg every 8 hours | 500 mg every 12 hours | |
| Dosage of PRIMAXIN, If the infection is suspected or proven to be due to bacterial species with intermediate susceptibility [see Microbiology (12.4) ]: | 1000 mg every 6 hours | 750 mg every 8 hours | 500 mg every 6 hours | 500 mg every 12 hours |
Side Effects of Primaxin
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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Patients During clinical investigations 1,723 patients were treated with PRIMAXIN. Table 4 shows the incidence of adverse reactions reported during the clinical investigations of adult patients treated with PRIMAXIN.
Table 5: Additional Adverse Laboratory Changes The following adverse laboratory changes were reported during clinical trials: Hepatic: Increased alanine aminotransferase (ALT or SGPT), aspartate aminotransferase (AST or SGOT), alkaline phosphatase, bilirubin, and lactate dehydrogenase (LDH) Hemic: Increased eosinophils, positive Coombs test, increased WBC, increased platelets, decreased hemoglobin and hematocrit, increased monocytes, abnormal prothrombin time, increased lymphocytes, increased basophils Electrolytes: Decreased serum sodium, increased potassium, increased chloride Renal: Increased BUN, creatinine Urinalysis: Presence of urine protein, urine red blood cells, urine white blood cells, urine casts, urine bilirubin, and urine urobilinogen. Pediatric Patients Table 6: Incidence (%) Adverse reactions that occurred in >1% of PRIMAXIN-treated pediatric patients (greater than or equal to 3 months of age) of Adverse Reactions Reported During Clinical Investigations of Pediatric Patients Greater Than or Equal to 3 Months of Age Treated with PRIMAXIN Table 7: Incidence (%) Adverse reactions that occurred in >1% of PRIMAXIN-treated pediatric patients (neonates to 3 months of age) of Adverse Reactions Reported During Clinical Investigations of Pediatric Patients Neonates to 3 Months of Age Treated with PRIMAXIN Adverse Laboratory Changes The following adverse laboratory changes were reported in studies of 178 pediatric patients 3 months of age: increased AST (SGOT), decreased hemoglobin/hematocrit, increased platelets, increased eosinophils, increased ALT (SGPT), increased urine protein, decreased neutrophils. The following adverse laboratory changes were reported in studies of 135 patients (neonates to 3 months of age): increased eosinophils, increased AST (SGPT), increased serum creatinine, increased/decreased platelet count, increased/decreased bilirubin, increased ALT (SGPT), increased alkaline phosphatase, increased/decreased hematocrit.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of PRIMAXIN. 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. Table 8: Adverse Reactions Identified During Post Approval Use of PRIMAXIN Adverse Laboratory Changes Adverse laboratory changes reported since the drug was marketed were: Hematologic: agranulocytosis.
Examination of published literature and spontaneous adverse reactions reports suggested a similar spectrum of adverse reactions in adult and pediatric patients.
| Body System | Adverse Reactions | Frequency (%) |
|---|---|---|
| Local Administration site | Phlebitis/thrombophlebitis | 3.1% |
| Pain at the injection site | 0.7% | |
| Erythema at the injection site | 0.4% | |
| Vein induration | 0.2% | |
| Gastrointestinal | Nausea | 2.0% |
| Diarrhea | 1.8% | |
| Vomiting | 1.5% | |
| Skin | Rash | 0.9% |
| Pruritus | 0.3% | |
| Urticaria | 0.2% | |
| Vascular | Hypotension | 0.4% |
| Body as a Whole | Fever | 0.5% |
| Nervous system | Seizures | 0.4% |
| Dizziness | 0.3% | |
| Somnolence | 0.2% |
| Body System | Adverse Reactions |
|---|---|
| Gastrointestinal | Pseudomembranous Colitis (the onset of Pseudomembranous colitis symptoms), Hemorrhagic Colitis |
| Gastroenteritis | |
| Abdominal Pain | |
| Glossitis | |
| Tongue Papillar | |
| Hypertrophy | |
| Heartburn | |
| Pharyngeal Pain | |
| Increased Salivation | |
| CNS | Encephalopathy |
| Confusion | |
| Myoclonus | |
| Paresthesia | |
| Vertigo | |
| Headache | |
| Special Senses | Hearing Loss |
| Tinnitus | |
| Respiratory | Chest Discomfort |
| Dyspnea | |
| Hyperventilation | |
| Thoracic Spine Pain | |
| Cardiovascular | Palpitations |
| Tachycardia | |
| Skin | Erythema Multiforme |
| Angioneurotic Edema | |
| Flushing | |
| Cyanosis | |
| Hyperhidrosis | |
| Skin Texture Changes | |
| Candidiasis | |
| Pruritus Vulvae | |
| Local Administration site | Infused vein infection |
| Body as a Whole | Polyarthralgia |
| Asthenia/Weakness | |
| Renal | Oliguria/Anuria |
| Polyuria |
| Body System | Adverse Reactions | Frequency (%) |
|---|---|---|
| Local Administration Site | Phlebitis | 2.2% |
| Intravenous Site Irritation | 1.1% | |
| Gastrointestinal | Diarrhea | 3.9% |
| Gastroenteritis | 1.1% | |
| Vomiting | 1.1% | |
| Skin | Rash | 2.2% |
| Renal | Urine Discoloration | 1.1% |
| Body System | Adverse Reactions | Frequency (%) |
|---|---|---|
| Gastrointestinal | Diarrhea | 3% |
| CNS | Convulsions | 5.9% |
| Cardiovascular | Tachycardia | 1.5% |
| Skin | Rash | 1.5% |
| Body as a Whole | Oral Candidiasis | 1.5% |
| Renal | Oliguria/Anuria | 2.2% |
| Body System | Adverse Reactions |
|---|---|
| Gastrointestinal | Hepatitis (including fulminant hepatitis) |
| Hepatic failure | |
| Jaundice | |
| Staining of the teeth and/or tongue | |
| Hematologic | Pancytopenia |
| Bone marrow depression | |
| Thrombocytopenia | |
| Neutropenia | |
| Leukopenia | |
| Hemolytic anemia | |
| CNS | Tremor |
| Psychic disturbances including hallucinations | |
| Dyskinesia | |
| Agitation | |
| Special Senses | Taste perversion |
| Skin | Stevens-Johnson syndrome |
| Toxic epidermal necrolysis | |
| Body as a whole | Drug fever |
| Renal | Acute renal failure |
| Urine discoloration |
Warnings & Cautions for Primaxin
Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam.
Before initiating therapy with PRIMAXIN, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens. If an allergic reaction to PRIMAXIN occurs, discontinue the drug immediately. Serious anaphylactic reactions require immediate emergency treatment as clinically indicated.
Seizure Potential Seizures and other
CNS adverse experiences, such as confusional states and myoclonic activity, have been reported during treatment with PRIMAXIN, especially when recommended dosages were exceeded. These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) and/or compromised renal function. However, there have been reports of CNS adverse experiences in patients who had no recognized or documented underlying CNS disorder or compromised renal function.
Anticonvulsant therapy should be continued in patients with known seizure disorders. If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of PRIMAXIN re-examined to determine whether it should be decreased, or the antibacterial drug discontinued.
Increased Seizure Potential Due to Interaction with Valproic Acid Case reports in the literature have shown that co-administration of carbapenems, including PRIMAXIN, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction.
The concomitant use of PRIMAXIN and valproic acid/divalproex sodium is generally not recommended. Antibacterials other than carbapenems should be considered to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of PRIMAXIN is necessary, supplemental anti-convulsant therapy should be considered.
Close adherence to the recommended dosage and dosage schedules is urged, especially in patients with known factors that predispose to convulsive activity.
Clostridioides difficile -Associated Diarrhea (CDAD)
Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including PRIMAXIN, 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, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Development of Drug-Resistant Bacteria As with other antibacterial drugs, prolonged use of PRIMAXIN may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Prescribing PRIMAXIN 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.
Drug Interactions with Primaxin
Ganciclovir
Generalized seizures have been reported in patients who received ganciclovir and PRIMAXIN. These drugs should not be used concomitantly with PRIMAXIN unless the potential benefits outweigh the risks.
Probenecid
Concomitant administration of PRIMAXIN and probenecid results in increases in the plasma level and half-life of imipenem. Therefore, it is not recommended that probenecid be given concomitantly with PRIMAXIN.
Valproic Acid
Case reports in the literature have shown that co-administration of carbapenems, including PRIMAXIN, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid.
The concomitant use of PRIMAXIN and valproic acid/divalproex sodium is generally not recommended. Antibacterials other than carbapenems should be considered to treat infections in patients whose seizures are well-controlled on valproic acid or divalproex sodium.
Pregnancy Safety for Primaxin
Pregnancy Risk Summary Available data from a small number of postmarketing cases with PRIMAXIN use in pregnancy are not sufficient to identify any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Developmental toxicity studies with imipenem and cilastatin sodium (alone or in combination) administered to mice, rats, rabbits, and monkeys at doses 0.4 to 2.9 times the recommended human dose (RHD), (based on body surface area), showed no drug-induced fetal malformations. Embryofetal development studies with imipenem/cilastatin administered to cynomolgus monkeys at doses similar to the RHD (based on body surface area) showed an increase in embryonic loss (see Data ).
The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies within the general population.
Data Animal Data Reproductive toxicity studies with imipenem and cilastatin (alone or in combination) administered to mice, rats, and rabbits showed no evidence of effects on embryofetal (mice, rats and rabbits) or pre/postnatal (rats) development. Imipenem/cilastatin was administered intravenously to mice at doses up to 320 mg/kg/day (GD 6 to 15). The higher dose is approximately equal to the RHD (based on body surface area).
Imipenem/cilastatin administered intravenously to pregnant cynomolgus monkeys during organogenesis at 100 mg/kg/day, approximately 0.6 times the RHD (based on body surface area), at an infusion rate mimicking human clinical use, was not associated with fetal malformations, but there was an increase in embryonic loss relative to controls. Imipenem/cilastatin administered to pregnant cynomolgus monkeys during organogenesis at 40 mg/kg/day by bolus intravenous injection caused significant maternal toxicity including death and embryofetal loss.
Pediatric Use of Primaxin
Pediatric Use Use of PRIMAXIN in pediatric patients is supported by evidence from adequate and well-controlled trials of PRIMAXIN in adults and clinical studies in pediatric patients. PRIMAXIN is not recommended in pediatric patients with CNS infections because of the risk of seizures. PRIMAXIN is not recommended in pediatric patients less than 30 kg with renal impairment, as no data are available.
Contraindications for Primaxin
PRIMAXIN is contraindicated in patients who have shown hypersensitivity to any component of this product. Known hypersensitivity to any component of PRIMAXIN
Overdosage Information for Primaxin
In the case of overdosage, discontinue PRIMAXIN, treat symptomatically, and institute supportive measures as required. PRIMAXIN is hemodialyzable.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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