meropenem/vaborbactam

Inhibits bacterial cell wall synthesis. Addition of vaborbactam protects meropenem from being degraded by certain serine beta-lactamases, such as Klebsiella pneumoniae carbapenemase.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Active against the following gram-negative pathogens:
- Escherichia coli,
- Enterobacter cloacae,
- Klebsiella pneumoniae.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Meropenem undergoes hydrolysis; vaborbactam is not metabolized. Both meropenem and vaborbactam are primarily excreted by the kidneys (40–60% of meropenem and 75–95% of vaborbactam excreted unchanged in the urine).

Half-Life: Meropenem: 1.22 hr; Vaborbactam: 1.68 hr.

Time/Action Profile ⬆ ⬇

( plasma concentrations)

ROUTE		ONSET		PEAK		DURATION
IV		rapid		end of infusion		8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to any of the carbapenems (ertapenem, imipenem, meropenem);
Anaphylactic reactions to other beta-lactams (cross-sensitivity may occur);
OB: Pregnancy.

Use Cautiously in:

Renal impairment (↑ risk of thrombocytopenia and seizures; ↓ dose if eGFR <50 mL/min/1.73 m²);
History of seizures, brain lesions, or meningitis;
Rep: Women of reproductive potential;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be at ↑ risk for adverse reactions due to age-related ↓ in renal function.

Adv. Reactions/Side Effects ⬆ ⬇

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

Local: infusion site reactions, phlebitis

MS: RHABDOMYOLYSIS

Neuro: delirium, headache, paresthesias, SEIZURES

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

Probenecid↓ renal excretion of meropenem and ↑ its levels; concurrent use not recommended.
May ↓ valproate levels and ↑ risk of seizures; concurrent use not recommended.
May ↓ levels and effectiveness of hormonal contraceptives.

Route/Dosage ⬆ ⬇

IV (Adults ): 4 g (meropenem 2 g/vaborbactam 2 g) every 8 hr for up to 14 days.

Renal Impairment

IV (Adults ): eGFR 30–49 mL/min/1.73 m²: 2 g (meropenem 1 g/vaborbactam 1 g) every 8 hr for up to 14 days; eGFR 15–29 mL/min/1.73 m²: 2 g (meropenem 1 g/vaborbactam 1 g) every 12 hr for up to 14 days; eGFR <15 mL/min/1.73 m²: 1 g (meropenem 0.5 g/vaborbactam 0.5 g) every 12 hr for up to 14 days.

Availability ⬆ ⬇

Powder for injection: 2 g/vial (1 g meropenem/1 g vaborbactam)

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
Obtain a history before initiating therapy to determine previous use of and reactions to penicillins.
Monitor for diarrhea, abdominal pain, fever, and bloody stools. If CDAD suspected, discontinue meropenem/vaborbactam and treat as clinically indicated. May begin up to several weeks following cessation of therapy.
Observe for anaphylaxis (rash, pruritus, laryngeal edema, wheezing). If symptoms occur, immediately discontinue therapy and provide appropriate medical care. Have epinephrine, an antihistamine, and resuscitative equipment close by.
Assess for severe cutaneous adverse reactions, including SJS, TEN, and DRESS, during therapy. If rash or other signs and symptoms suggestive of these reactions occur, immediately discontinue meropenem/vaborbactam, treat as indicated, and consider alternate therapy.
Assess for history of CNS disorders, including seizures. If focal tremors, myoclonus, or seizures occur, place patient on anticonvulsant therapy as needed and assess need to ↓ meropenem/vaborbactam dose or discontinue.
Monitor for signs and symptoms of rhabdomyolysis. If signs of symptoms occur, discontinue therapy and treat as indicated.
Assess injection site for phlebitis, pain, and swelling periodically during administration.

Lab Test Considerations:

Obtain specimens for culture and sensitivity prior to initiating therapy. 1st dose may be given before receiving results.
- May ↑ AST and ALT.
- May cause hypokalemia, leukopenia and azotemia.

Implementation ⬆ ⬇

Intermittent Infusion: Reconstitution: Reconstitute each vial with 20 mL of 0.9% NaCl. Mix gently to dissolve.Diluent: Dilute further in 250 mL to 1000 mL of 0.9% NaCl. Concentration: 2–16 mg/mL. Solution is clear to light yellow; do not infuse solution if discolored or contains particulate. Infusion must be completed within 4 hr if stored at room temperature or 22 hr if refrigerated.
Rate: Infuse over 3 hr.
Y-Site Compatibility:
- amikacin
- ampicillin/sulbactam
- azithromycin
- aztreonam
- bumetanide
- calcium gluconate
- cefazolin
- cefepime
- cefiderocol
- ceftazidime
- ceftazidime/avibactam
- ceftolozane/tazobactam
- ceftriaxone
- cefuroxime
- cisatracurium
- dexamethasone
- dexmedetomidine
- digoxin
- diltiazem
- dopamine
- doxycycline
- epinephrine
- eptifibatide
- ertapenem
- esmolol
- esomeprazole
- famotidine
- fentanyl
- fosphenytoin
- furosemide
- gentamicin
- heparin
- hydrocortisone
- hydromorphone
- imipenem/cilastatin
- insulin, regular
- labetalol
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- mesna
- methylprednisolone
- metoclopramide
- metronidazole
- micafungin
- milrinone
- morphine
- naloxone
- nitroglycerin
- norepinephrine
- octreotide
- pantoprazole
- penicillin G potassium
- phenylephrine
- piperacillin/tazobactam
- plazomicin
- potassium chloride
- potassium phosphates
- rocuronium
- sodium bicarbonate
- sodium phosphates
- sulbactam/durlobactam
- tedizolid
- tigecycline
- tobramycin
- vancomycin
- vasopressin
- vecuronium
Y-Site Incompatibility:
- albumin
- amiodarone
- anidulafungin
- calcium chloride
- caspofungin
- ceftaroline
- ciprofloxacin
- daptomycin
- diphenhydramine
- dobutamine
- eravacycline
- isavuconazonium
- midazolam
- nicardipine
- ondansetron
- phenytoin

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to report signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) and rash or other symptoms of 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 promptly if signs and symptoms of rhabdomyolysis (muscle pain or weakness, dark urine) occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep: Advise women of reproductive potential to use nonhormonal contraceptive and notify health care provider if pregnancy is planned or suspected or if breastfeeding. Monitor breastfed infant for thrush and diarrhea.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇