Imipenem and cilastatin

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

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

• Cilastatin and Imipenem
• Imipemide
• Imipenem/Cilastatin
• Primaxin I.M. [DSC]

There are no dosage adjustments provided in the manufacturer's labeling.

Applies to cilastatin / imipenem: powder for solution

Along with its needed effects, cilastatin / imipenem may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking cilastatin / imipenem:

• Confusion
• convulsions (seizures)
• dizziness
• pain at place of injection
• skin rash, hives, itching, fever, or wheezing
• tremors

• Dizziness
• increased sweating
• nausea or vomiting
• unusual tiredness or weakness

• Fever
• severe abdominal or stomach cramps and pain
• watery and severe diarrhea, which may also be bloody (these side effects may also occur up to several weeks after you stop receiving this medicine)

Some side effects of cilastatin / imipenem may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• nausea and vomiting

500 mg IV every 6 hours or 1 g IV every 6 to 8 hours (based on imipenem content), depending on the nature and severity of the infection
Maximum dose: 50 mg/kg/day or 4 g/day, whichever is less
Duration: 14 days, depending on the nature and severity of the infection

250 mg IV every 6 hours or 500 mg to 1 g IV every 6 to 8 hours (based on imipenem content), depending on the nature and severity of the infection
Maximum dose: 50 mg/kg/day or 4 g/day, whichever is less
Duration: 14 days, depending on the nature and severity of the infection

IV: 250 mg IV every 6 hours or 500 mg to 1 g IV every 6 to 8 hours (based on imipenem content), depending on the nature and severity of the infection
Maximum dose: 50 mg/kg/day or 4 g/day, whichever is less
Duration: 7 to 14 days, depending on the nature and severity of the infection

IM:
Mild to moderate infections: 750 mg IM every 12 hours
Maximum dose: 1500 mg/day

250 mg IV every 6 hours or 500 mg to 1 g IV every 6 to 8 hours (based on imipenem content), depending on the nature and severity of the infection
Initial empiric treatment with broad-spectrum coverage according to the hospital's and/or ICU's antibiogram is recommended if multidrug-resistant organisms are suspected.

Maximum dose: 50 mg/kg/day or 4 g/day, whichever is less
Duration: If the causative organism is not Pseudomonas aeruginosa, the duration of treatment should be as short as clinically possible (e.g., as little as 7 days) to reduce the risk of superinfections with resistant organisms.

IV: 250 mg IV every 6 hours or 500 mg to 1 g IV every 6 to 8 hours (based on imipenem content), depending on the nature and severity of the infection
Maximum dose: 50 mg/kg/day or 4 g/day, whichever is less
Duration: 7 to 10 days, or for 3 days after acute inflammation resolves, depending on the nature and severity of the infection
For more severe infections, such as diabetic soft tissue infections, 14 to 21 days of therapy may be required.

IM:
Mild to moderate infections: 500 to 750 mg IM every 12 hours (based on imipenem content), depending on the nature and severity of the infection
Maximum dose: 1500 mg/day

IV:
Non-CNS infections: (based on imipenem content)
Less than 7 days, less than 1500 g: 20 to 25 mg/kg IV every 12 hours
Less than 7 days, 1500 g or more: 25 mg/kg IV every 12 hours
1 to 4 weeks, less than 1200 g: 25 mg/kg IV every 12 hours
1 to 4 weeks, 1200 g or more: 25 mg/kg IV every 8 hours
4 weeks to 3 months: 25 mg/kg IV every 6 hours
3 months or older: 15 to 25 mg/kg IV every 6 hours

Maximum dose: 2 g/day for fully susceptible organisms and 4 g/day for moderately susceptible organisms

IM: Safety and efficacy of IM imipenem-cilastatin have not been established in pediatric patients below the age of 12 years.

IM imipenem-cilastatin is contraindicated in patients with severe shock or heart block due to the lidocaine diluent.

Serious and occasionally fatal hypersensitivity reactions have been reported with antibiotics. The drug should be discontinued immediately at the first appearance of a skin rash or other signs of hypersensitivity. Severe, acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures including oxygen, IV fluids, antihistamines, corticosteroids, cardiovascular support and airway management as clinically indicated.

Imipenem-cilastatin has been associated with seizures and other CNS side effects such as confusion, most commonly in patients with CNS disorders such as brain lesions, history of seizures, bacterial meningitis, or renal impairment. Recommended dosages should not be exceeded, especially in patients with risk factors. IV imipenem-cilastatin is not recommended in pediatric patients with CNS infections due to the risk of seizures. Neurologic evaluation, anticonvulsant therapy, and imipenem dosage adjustment or discontinuation are recommended for patients who experience tremors, myoclonus or seizures.

Clostridium difficile associated diarrhea (CDAD) has been reported with almost all antibiotics and may potentially be life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea following imipenem-cilastatin therapy. Mild cases generally improve with discontinuation of the drug, while severe cases may require supportive therapy and treatment with an antimicrobial agent effective against C difficile. Hypertoxin producing strains of C difficile cause increased morbidity and mortality; these infections can be resistant to antimicrobial treatment and may necessitate colectomy.

Renal, hepatic, and hematopoietic monitoring is recommended periodically during prolonged therapy.

Imipenem-cilastatin should not be physically mixed with other antibiotics.

Moderate accumulation of cilastatin may occur after multiple doses of IV imipenem-cilastatin in neonates. The safety of this accumulation is unknown.

Safety and efficacy of IM imipenem-cilastatin have not been established in pediatric patients less than 12 years.