Primaxin I.M.

Antibacterial; fixed combination of imipenem (a carbapenem β-lactam antibiotic)2 4 5 6 148 196 197 198 and cilastatin1 35 (prevents renal metabolism of imipenem by dehydropeptidase I [DHP I]).1 2 101 113 125 137 140 141 145 148 196 198

Bone and Joint Infections

Treatment of serious bone and joint infections caused by susceptible Staphylococcus aureus (penicillinase-producing strains), S. epidermidis, Enterobacter, or Pseudomonas aeruginosa.1 146 164 167 182 256

Endocarditis

Treatment of endocarditis caused by susceptible S. aureus (penicillinase-producing strains).1 146 186 Not considered a preferred or alternative drug for staphylococcal endocarditis.a b

Should not be used for treatment of enterococcal endocarditis.103 198 199 210

Gynecologic Infections

Treatment of gynecologic infections (including mixed aerobic-anaerobic infections) caused by susceptible Enterococcus faecalis, S. aureus (penicillinase-producing strains), S. epidermidis, S. agalactiae (group B streptococci), Enterobacter, E. coli, Gardnerella vaginalis, Klebsiella, Proteus, Bacteroides (including B. fragilis), Bifidobacterium, Peptococcus, Peptostreptococcus, and Propionibacterium.1 146 176 178

Intra-abdominal Infections

Treatment of intra-abdominal infections (including mixed aerobic-anaerobic infections) caused by susceptible E. faecalis, S. aureus (penicillinase-producing strains), S. epidermidis, Citrobacter, Enterobacter, E. coli, Klebsiella, Morganella morganii, Proteus, Ps. aeruginosa, Bacteroides (including B. fragilis), Bifidobacterium, Clostridium, Eubacterium, Fusobacterium, Peptococcus, Peptostreptococcus, or Propionibacterium.1 164 172 179 256 .

Respiratory Tract Infections

Treatment of lower respiratory tract infections caused by susceptible S. aureus (penicillinase-producing strains), S. pneumoniae, Haemophilus influenzae, H. parainfluenzae, Acinetobacter, Enterobacter, E. coli, Klebsiella, or Serratia marcescens.1 164 167 170 172 183 256

Treatment of pneumonia and bronchitis (as an exacerbation of COPD) caused by susceptible S. pneumoniae.256 Indicated for polymicrobial infections when S. pneumoniae may be involved, but not usually indicated for monobacterial pneumococcal infections.1 Not considered a drug of first choice for empiric treatment of community-acquired pneumonia (CAP);147 193 usually reserved for use in patients with pneumonia who are at risk for Ps. aeruginosa and when anaerobes may be involved.147 193 261

Has been used for treatment of Legionella pneumophila† respiratory tract infections.152 154 171 215 Other anti-infectives (e.g., a macrolide or a fluoroquinolone with or without rifampin) generally preferred.76 261 304

Septicemia

Treatment of septicemia caused by susceptible E. faecalis, S. aureus (penicillinase-producing strains), Enterobacter, E. coli, Klebsiella, Ps. aeruginosa, Serratia, or Bacteroides (including B. fragilis).1 146 164 167 170 172 181 261

Skin and Skin Structure Infections

Treatment of serious skin and skin structure infections caused by susceptible S. aureus (penicillinase-producing strains), S. epidermidis, E. faecalis, Acinetobacter, Citrobacter, Enterobacter, E. coli, Klebsiella, M. morganii, P. vulgaris, P. rettgeri, Ps. aeruginosa, or Serratia.1 146 164 167 170 172 179 184

Treatment of serious skin and skin structure infections caused by susceptible Bacteroides (including B. fragilis), Fusobacterium, Peptococcus, or Peptostreptococcus.1 179 184

Urinary Tract Infections (UTIs)

Treatment of complicated and uncomplicated UTIs caused by susceptible E. faecalis, S. aureus (penicillinase-producing strains) , Enterobacter, E. coli, Klebsiella, M. morganii, P. vulgaris, Providencia rettgeri, or Ps. aeruginosa.1 146 158 164 167 168 170 172 173 180 261

Actinomycosis

Has been used for treatment of thoracic actinomycosis†.291 Not considered a drug of choice; penicillin G generally preferred for initial treatment of all forms of actinomycosis, including thoracic, abdominal, CNS, and cervicofacial infections.76 261 292

Bacillus Infections

Treatment of invasive infections caused by Bacillus cereus†.76 261 Vancomycin considered drug of choice; carbapenems (imipenem or meropenem) or clindamycin are alternatives.261

Burkholderia Infections

Treatment of localized or septicemic melioidosis†,261 280 281 282 283 284 a potentially life-threatening disease caused by Burkholderia pseudomallei.280 282 283 A drug of choice.261 280 281 282 283 284 285 B. pseudomallei is difficult to eradicate (relapse of melioidosis is common).280 281 283 285

Alternative for treatment of glanders† caused by B. mallei.261

Alternative for treatment of infections caused by B. cepacia†.261

Campylobacter Infections

Treatment of systemic infections caused by Campylobacter fetus†;261 286 a drug of choice.261 286

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga canimorsus†.261

Optimum regimens for treatment of infections caused by Capnocytophaga have not been identified; some clinicians recommend use of penicillin G261 290 or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.261

Nocardia Infections

Treatment of infections caused by Nocardia†, including pulmonary nocardiosis caused by N. asteroides and primary cutaneous nocardiosis.261 293 294 295 Co-trimoxazole considered drug of first choice for Nocardia infections;76 147 261 alternatives include a sulfonamide (e.g., sulfisoxazole) with or without minocycline or amikacin; a tetracycline (e.g., doxycycline, minocycline); a carbapenem (imipenem or meropenem) with or without amikacin; amoxicillin and clavulanate; cycloserine; or linezolid.76 147 261

Rhodococcus Infections

Treatment of infections caused by Rhodococcus equi†; used in conjunction with vancomycin.261 Optimum regimens have not been identified;298 combination regimens usually are recommended, including vancomycin given with a fluoroquinolone, rifampin, a carbapenem (imipenem or meropenem), or amikacin.261 297 298 299

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.265 266 267 268 269 270 271 Used alone or in conjunction with other anti-infectives.268 269 271

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.14 Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.14

Storage

Parenteral

<25°C.1 256

Solutions and suspensions may darken (i.e., IV solutions may turn deep yellow or IM suspensions may turn light tan) with time;1 256 this color change does not indicate loss of potency.1 256 However, IV solutions of the drug should be discarded if they become brown.219

IV solutions prepared using 100 mL of 0.9% sodium chloride injection; 5 or 10% dextrose; 5% dextrose and 0.225, 0.45, or 0.9% sodium chloride; 0.15% potassium chloride in 5% dextrose; or 5 or 10% mannitol are stable for 4 hours at room temperature or 24 hours when refrigerated at 5°C.1

Reconstituted ADD-Vantage vials are stable for 4 hours at room temperature.1

IM suspensions prepared using lidocaine hydrochloride 1% injection (without epinephrine) should be used within 1 hour of reconstitution.256

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

• Fixed combination of imipenem monohydrate and the sodium salt of cilastatin.1 35 256 Imipenem is carbapenem antibiotic2 4 5 6 148 196 197 198 structurally and pharmacologically related to meropenem and ertapenem.1 2 3 Cilastatin is a specific and reversible inhibitor of dehydropeptidase I (DHP I).1 2 101 125 140 141 145 148 196 198 256

• Concomitant use of cilastatin prevents in vivo metabolism of imipenem by DHP I and results in urinary concentrations of active imipenem that are higher than could be obtained following use of the antibiotic alone.1 2 113 125 137 140 141 148 196 198 256

• Usually bactericidal in action.1 256

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1 256

• Spectrum of activity includes many gram-positive and -negative aerobic bacteria and some gram-positive and -negative anaerobic bacteria.1 256 Stable in the presence of a variety of β-lactamases (including penicillinases, cephalosporinases, and extended-spectrum β-lactamases).1 256

• Gram-positive aerobes: active in vitro and in clinical infections against Enterococcus faecalis, Staphylococcus aureus (including penicillinase-producing strains), S. epidermidis, Streptococcus agalactiae (group B streptococci), S. pneumoniae, and S. pyogenes (group A β-hemolytic streptococci).1 256 Also active in vitro against S, saprophyticus, groups C and G streptococci, viridans streptococci, Bacillus, Listeria monocytogenes, and Nocardia.1 256 Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.1 256

• Gram-negative aerobes: active in vitro and in clinical infections against Acinetobacter, Citrobacter, Enterobacter, Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, H. parainfluenzae, Klebsiella, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, and Serratia (including S. marcescens).1 256 Also active in vitro against Aeromonas hydrophila, Alcaligenes, Capnocytophaga, H. ducreyi, Neisseria gonorrhoeae, Pasteurella, and P. stuartii.1 256

• Anaerobes: active in vitro and in clinical infections against Bacteroides (including B. fragilis), Bifidobacterium, Clostridium, Eubacterium, Fusobacterium, Peptococcus, Peptostreptococcus, and Propionibacterium.1 256 Also active in vitro against Prevotella bivia, P. disiens, P. melaninogenica, and Veillonella.1

PRIMAXIN I.M. is indicated for the treatment of serious infections (listed below) of mild to moderate severity for which intramuscular therapy is appropriate. PRIMAXIN I.M. is not intended for the therapy of severe or life-threatening infections, including bacterial sepsis or endocarditis, or in instances of major physiological impairments such as shock.

PRIMAXIN I.M. is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

1. Lower respiratory tract infections, including pneumonia and bronchitis as an exacerbation of COPD, caused by Streptococcus pneumoniae and Haemophilus influenzae.
2. Intra-abdominal infections, including acute gangrenous or perforated appendicitis and appendicitis with peritonitis, caused by Group D streptococcus including Enterococcus faecalis * ; Streptococcus viridans group * ; Escherichia coli; Klebsiella pneumoniae * ; Pseudomonas aeruginosa * ; Bacteroides species including B. fragilis, B. distasonis * , B. intermedius * and B. thetaiotaomicron * ; Fusobacterium species and Peptostreptococcus * species.
3. Skin and skin structure infections, including abscesses, cellulitis, infected skin ulcers and wound infections caused by Staphylococcus aureus including penicillinase-producing strains; Streptococcus pyogenes * ; Group D streptococcus including Enterococcus faecalis; Acinetobacter species * including A. calcoaceticus, * ; Citrobacter species * ; Escherichia coli; Enterobacter cloacae; Klebsiella pneumoniae * ; Pseudomonas aeruginosa * and Bacteroides species * including B. fragilis * .
4. Gynecologic infections, including postpartum endomyometritis, caused by Group D streptococcus including Enterococcus faecalis * ; Escherichia coli; Klebsiella pneumoniae * ; Bacteroides intermedius * ; and Peptostreptococcus species * .

As with other beta-lactam antibiotics, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with PRIMAXIN I.M. During therapy of Pseudomonas aeruginosa infections, periodic susceptibility testing should be done when clinically appropriate.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of PRIMAXIN I.M. and other antibacterial drugs, PRIMAXIN I.M. 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.

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 REACTIONS WHEN TREATED WITH ANOTHER BETA-LACTAM. BEFORE INITIATING THERAPY WITH PRIMAXIN I.M., CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OTHER BETA-LACTAMS, AND OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, PRIMAXIN SHOULD BE DISCONTINUED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, MAY ALSO BE ADMINISTERED AS INDICATED.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including PRIMAXIN, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis".

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis.

Lidocaine HCl  --Refer to the package circular for lidocaine HCl.

The acute intravenous toxicity of imipenem-cilastatin sodium in a ratio of 1:1 was studied in mice at doses of 751 to 1359 mg/kg. Following drug administration, ataxia was rapidly produced and clonic convulsions were noted in about 45 minutes. Deaths occurred within 4-56 minutes at all doses.

The acute intravenous toxicity of imipenem-cilastatin sodium was produced within 5-10 minutes in rats at doses of 771 to 1583 mg/kg. In all dosage groups, females had decreased activity, bradypnea and ptosis with clonic convulsions preceding death; in males, ptosis was seen at all dose levels while tremors and clonic convulsions were seen at all but the lowest dose (771 mg/kg). In another rat study, female rats showed ataxia, bradypnea and decreased activity in all but the lowest dose (550 mg/kg); deaths were preceded by clonic convulsions. Male rats showed tremors at all doses and clonic convulsions and ptosis were seen at the two highest doses (1130 and 1734 mg/kg). Deaths occurred between 6 and 88 minutes with doses of 771 to 1734 mg/kg.

In the case of overdosage, discontinue PRIMAXIN I.M., treat symptomatically, and institute supportive measures as required. Imipenem-cilastatin sodium is hemodialyzable. However, usefulness of this procedure in the overdosage setting is questionable.

1. National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically--Fourth Edition. Approved Standard NCCLS Document M7-A4, Vol. 17, No. 2 NCCLS, Villanova, PA, 1997.
2. National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests--Sixth Edition. Approved Standard NCCLS Document M2-A6, Vol. 17, No. 1 NCCLS, Villanova, PA, 1997.
3. National Committee for Clinical Laboratory Standards, Method for Antimicrobial Susceptibility Testing of Anaerobic Bacteria--Third Edition. Approved Standard NCCLS Document M11-A3, Vol. 13, No. 26 NCCLS, Vil-lanova, PA, 1993.

7632911  Issued August 2003

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