imipenem/cilastatin

Imipenem inhibits bacterial cell wall synthesis.
Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary concentrations.
Imipenem resists the actions of many enzymes that degrade most other penicillins and penicillin-like anti-infectives.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Spectrum is broad.
Active against most gram-positive aerobic cocci:
- Streptococcus pneumoniae,
- Group A beta-hemolytic streptococci,
- Enterococcus,
- Staphylococcus aureus.
Active against many gram-negative bacillary organisms:
- Escherichia coli,
- Klebsiella,
- Acinetobacter,
- Proteus,
- Serratia,
- Pseudomonas aeruginosa.
Also displays activity against:
- Salmonella,
- Shigella,
- Neisseria gonorrhoeae,
- Numerous anaerobes.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: 70% excreted unchanged by the kidneys.

Half-Life: 1 hr (↑ in renal impairment).

Time/Action Profile ⬆ ⬇

( plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	6–8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Cross-sensitivity may occur with penicillins and cephalosporins.

Use Cautiously in:

Previous history of multiple hypersensitivity reactions;
Seizure disorders;
Renal impairment (↓ dose if CCr ≤90 mL/min);
OB: Safety not established in pregnancy;
Lactation: Use during breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children with CNS infections (↑ risk of seizures) or children <30 kg with renal impairment (safety and effectiveness not established);
Geri: Older adults may be at ↑ risk for adverse reactions due to age-related ↓ in renal function.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension

Derm: rash, pruritus, sweating, urticaria

GI: diarrhea, nausea, vomiting, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD)

Hemat: eosinophilia

Local: phlebitis at IV site

Neuro: dizziness, SEIZURES, somnolence

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), superinfection

Interactions ⬆ ⬇

Drug-drug:

Do not admix with aminoglycosides; inactivation may occur.
Probenecid↓ renal excretion and ↑ levels.
↑risk of seizures with ganciclovir or cyclosporine; avoid concurrent use with ganciclovir.
May ↓ valproate levels and ↑ risk of seizures.

Route/Dosage ⬆ ⬇

IV (Adults ): If infection is suspected or proven to be due to a susceptible bacterial species: 500 mg every 6 hr or 1 g every 8 hr; If infection is suspected or proven to be due to bacterial species with intermediate susceptibility: 1 g every 6 hr.
IV (Children ≥3 mo): 15–25 mg/kg every 6 hr; higher doses have been used in older children with cystic fibrosis.
IV (Children 4 wk–3 mo): 25 mg/kg every 6 hr.
IV (Children 1–4 wk): 25 mg/kg every 8 hr.
IV (Children <1 wk): 25 mg/kg every 12 hr.

Renal Impairment

IV (Adults ): If infection is suspected or proven to be due to a susceptible bacterial speciesCCr 60–89 mL/min: 400 mg every 6 hr or 500 mg every 6 hr; CCr 30–59 mL/min: 300 mg every 6 hr or 500 mg every 8 hr; CCr 15–29 mL/min: 200 mg every 6 hr or 500 mg every 12 hr; CCr <15 mL/min receiving hemodialysis: 200 mg every 6 hr or 500 mg every 12 hr; If infection is suspected or proven to be due to bacterial species with intermediate susceptibilityCCr 60–89 mL/min: 750 mg every 8 hr; CCr 30–59 mL/min: 500 mg every 6 hr; CCr 15–29 mL/min: 500 mg every 12 hr; CCr <15 mL/min receiving hemodialysis: 500 mg every 12 hr.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 250 mg imipenem/250 mg cilastatin; 500 mg imipenem/500 mg cilastatin

Assessment ⬆ ⬇

Monitor infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at baseline and throughout therapy.
Obtain a history before initiating therapy to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of sensitivity may still have an allergic response.
Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Have epinephrine, antihistamine, and resuscitative equipment close by. If hypersensitivity reaction occurs, immediately discontinue imipenem/cilastatin and treat as clinically indicated.
Monitor for CNS changes. If focal tremors, myoclonus, or seizures occur, evaluate, place on anticonvulsant other than valproic acid, and consider dose ↓ or discontinuing imipenem/cilastatin.
Monitor for diarrhea, abdominal cramping, fever, and bloody stools during and for several weeks after therapy. If CDAD is suspected or confirmed, discontinue imipenem/cilastatin and treat as clinically indicated.

Lab Test Considerations:

Obtain specimen for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
May transiently ↑ BUN, AST, ALT, LDH, alkaline phosphatase, bilirubin, and serum creatinine.
- May ↓ hemoglobin and hematocrit.
- May cause positive direct Coombs test.

Implementation ⬆ ⬇

IV Administration:

Intermittent Infusion: Reconstitute each 250- or 500-mg vial with 10 mL of D5W, D5/0.9% NaCl, 0.9% NaCl, or D5/0.45% NaCl and shake well. Diluent: Further dilute in 100 mL of D5W or 0.9% NaCl. Solution may range from clear to yellow in color. Infusion is stable for 4 hr at room temperature and 24 hr refrigerated. Concentration: 2.5–5 mg/mL.
Rate: Infuse doses ≤500 mg over 20–30 min. Infuse doses ≥750 mg over 40–60 min. Pedi: Infuse doses ≤500 mg over 15–30 min. Infuse doses >500 mg over 40–60 min.
- If rapid infusion causes nausea and vomiting, slow infusion.
Y-Site Compatibility:
- acyclovir
- amikacin
- aminocaproic acid
- anidulafungin
- argatroban
- arsenic trioxide
- ascorbic acid
- atracurium
- atropine
- benztropine
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftazidime/avibactam
- ceftolozane/tazobactam
- cefuroxime
- chloramphenicol
- cisatracurium
- cisplatin
- clindamycin
- cyanocobalamin
- cyclophosphamide
- cyclosporine
- cytarabine
- dactinomycin
- daunorubicin
- defibrotide
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxorubicin liposomal
- doxycycline
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- epoetin alfa
- eptifibatide
- eravacycline
- erythromycin
- esmolol
- etoposide
- famotidine
- fentanyl
- fludarabine
- fluorouracil
- folic acid
- foscarnet
- fosphenytoin
- furosemide
- gemtuzumab ozogamicin
- gentamicin
- glycopyrrolate
- granisetron
- heparin
- hydrocortisone
- hydromorphone
- idarubicin
- ifosfamide
- indomethacin
- insulin regular
- irinotecan
- isavuconazonium
- isoproterenol
- ketorolac
- labetalol
- leucovorin
- levofloxacin
- lidocaine
- linezolid
- magnesium sulfate
- melphalan
- meropenem
- meropenem/vaborbactam
- mesna
- methadone
- methotrexate
- methylprednisolone
- metoclopramide
- metoprolol
- metronidazole
- mitomycin
- mitoxantrone
- morphine
- multivitamins
- nafcillin
- naloxone
- nitroglycerin
- norepinephrine
- octreotide
- ondansetron
- oxacillin
- oxaliplatin
- oxytocin
- paclitaxel
- pamidronate
- pantoprazole
- pemetrexed
- penicillin G
- pentobarbital
- phentolamine
- phenylephrine
- phytonadione
- plazomicin
- potassium acetate
- potassium chloride
- propofol
- propranolol
- protamine
- remifentanil
- rituximab
- rocuronium
- sodium acetate
- succinylcholine
- sufentanil
- sulbactam/durlobactam
- tacrolimus
- tedizolid
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- trastuzumab
- vasopressin
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- alemtuzumab
- allopurinol
- amiodarone
- amphotericin B liposomal
- azathioprine
- blinatumomab
- ceftriaxone
- chlorpromazine
- dacarbazine
- dantrolene
- daptomycin
- diazepam
- diazoxide
- etoposide phosphate
- ganciclovir
- gemcitabine
- haloperidol
- lorazepam
- mannitol
- milrinone
- minocycline
- mycophenolate
- nalbuphine
- nicardipine
- palonosetron
- phenytoin
- prochlorperazine
- pyridoxine
- sargramostim
- sodium bicarbonate
- thiamine
- topotecan
- trimethoprim/sulfamethoxazole
- vecuronium

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider for signs of superinfection (black, furry overgrowth on tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy.
Caution patient to notify health care provider if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care provider. May occur up to several weeks after discontinuation of medication.
Advise patient to notify health care provider for history of stroke, seizure, or valproic acid use prior to initiating therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes ⬆ ⬇

Resolution of signs and symptoms of infection. Length of time for complete resolution depends on organism and site of infection.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

0006- Merck Sharp & Dohme LLC
- 0006-3516- PRIMAXIN IV
  - 0006-3516-59- 25 VIAL, SINGLE-DOSE in 1 TRAY (0006-3516-59) / 100 mL in 1 VIAL, SINGLE-DOSE

44567- WG Critical Care, LLC
- 44567-705- Imipenem and Cilastatin
  - 44567-705-10- 10 VIAL in 1 CARTON (44567-705-10) / 1 INJECTION, POWDER, FOR SOLUTION in 1 VIAL

52946- ACS Dobfar S.p.A
- 52946-0838-
  - 52946-0838-0- 20 kg in 1 BOX (52946-0838-0)

63323- Fresenius Kabi USA, LLC
- 63323-322- Imipenem and Cilastatin
  - 63323-322-25- 25 VIAL, SINGLE-DOSE in 1 CARTON (63323-322-25) / 20 mL in 1 VIAL, SINGLE-DOSE (63323-322-01)

63323- Fresenius Kabi USA, LLC
- 63323-322- Imipenem and Cilastatin
  - 63323-322-93- 25 VIAL, SINGLE-DOSE in 1 CARTON (63323-322-93) / 20 mL in 1 VIAL, SINGLE-DOSE (63323-322-21)

63323- Fresenius Kabi USA, LLC
- 63323-322- Imipenem and Cilastatin
  - 63323-322-94- 25 VIAL, SINGLE-DOSE in 1 CARTON (63323-322-94) / 20 mL in 1 VIAL, SINGLE-DOSE (63323-322-41)

63323- Fresenius Kabi USA, LLC
- 63323-349- Imipenem and Cilastatin
  - 63323-349-25- 25 VIAL, SINGLE-DOSE in 1 CARTON (63323-349-25) / 20 mL in 1 VIAL, SINGLE-DOSE (63323-349-01)

63323- Fresenius Kabi USA, LLC
- 63323-349- Imipenem and Cilastatin
  - 63323-349-93- 25 VIAL, SINGLE-DOSE in 1 CARTON (63323-349-93) / 20 mL in 1 VIAL, SINGLE-DOSE (63323-349-21)

63323- Fresenius Kabi USA, LLC
- 63323-349- Imipenem and Cilastatin
  - 63323-349-94- 25 VIAL, SINGLE-DOSE in 1 CARTON (63323-349-94) / 20 mL in 1 VIAL, SINGLE-DOSE (63323-349-41)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇