Vabomere

Name: Vabomere

Cautions for Vabomere

Contraindications

Known hypersensitivity to the components of meropenem and vaborbactam or anaphylactic reactions to beta-lactams.1

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions were reported in patients treated with meropenem and vaborbactam in the clinical trials. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving therapy with beta-lactam antibacterial drugs. 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 antibacterial drug.1

Before initiating therapy with meropenem and vaborbactam, it is important to inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactam antibacterial drugs, and other allergens. If an allergic reaction to meropenem and vaborbactam occurs, discontinue the drug immediately.1

Seizure Potential

Seizures and other adverse central nervous system (CNS) experiences have been reported during treatment with meropenem, which is a component of meropenem and vaborbactam. These experiences have occurred most commonly in patients with CNS disorders (e.g., brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function.1

Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity. Continue anti-convulsant therapy in patients with known seizure disorders. If focal tremors, myoclonus, or seizures occur, evaluate neurologically, place on anti-convulsant therapy if not already instituted, and reexamine the dosage of meropenem and vaborbactam to determine whether it should be decreased or discontinued.1

Clostridium difficile-associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including meropenem and vaborbactam, 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.1

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing isolates 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.1

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.1

Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid

The concomitant use of meropenem and vaborbactam and valproic acid or divalproex sodium is generally not recommended. Case reports in the literature have shown that co-administration of carbapenems, including meropenem, 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.1

Consider administration of antibacterial drugs other than carbapenems to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. If administration of meropenem and vaborbactam is necessary, consider supplemental anticonvulsant therapy.1

Thrombocytopenia

In patients with renal impairment, thrombocytopenia has been observed in patients treated with meropenem, but no clinical bleeding has been reported.1

Potential for Neuromotor Impairment

Alert patients receiving meropenem and vaborbactam on an outpatient basis regarding adverse reactions such as seizures, delirium, headaches and/or paresthesias that could interfere with mental alertness and/or cause motor impairment. Until it is reasonably well established that meropenem and vaborbactam is well tolerated, advise patients not to operate machinery or motorized vehicles.1

Development of Drug-resistant Bacteria

Prescribing meropenem and vaborbactam in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of drug-resistant bacteria.1

Overgrowth of Nonsusceptible Organisms

As with other antibacterial drugs, prolonged use of meropenem and vaborbactam may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient is essential. If superinfection does occur during therapy, appropriate measures should be taken.1

Specific Populations

Pregnancy

Fetal malformations were observed in vaborbactam-treated rabbits, therefore advise pregnant women of the potential risks to the fetus. There are insufficient human data to establish whether there is a drug-associated risk of major birth defects or miscarriages with meropenem and vaborbactam, meropenem, or vaborbactam in pregnant women.1

Malformations (supernumerary lung lobes, interventricular septal defect) were observed in offspring from pregnant rabbits administered intravenous vaborbactam during the period of organogenesis at doses approximately equivalent to or above the maximum recommended human dose (MRHD) based on plasma AUC comparison. The clinical relevance of the malformations is uncertain. No similar malformations or fetal toxicity were observed in offspring from pregnant rats administered intravenous vaborbactam during organogenesis or from late pregnancy and through lactation at a dose equivalent to approximately 1.6 times the MRHD based on body surface area comparison.1

No fetal toxicity or malformations were observed in pregnant rats and cynomolgus monkeys administered intravenous meropenem during organogenesis at doses up to 1.6 and 1.2 times the MRHD based on body surface area comparison, respectively. In rats administered intravenous meropenem in late pregnancy and during the lactation period, there were no adverse effects on offspring at doses equivalent to approximately 1.6 times the MRHD based on body surface area comparison.1

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.1

Animal Data for Meropenem: Reproductive studies have been performed with meropenem in rats at doses of up to 1000 mg/kg/day and in cynomolgus monkeys at doses of up to 360 mg/kg/day (on the basis of body surface area comparisons, approximately 1.6 times and 1.2 times higher, respectively, than the MRHD of 2 grams every 8 hours). These studies revealed no evidence of harm to the fetus due to meropenem, although there were slight changes in fetal body weight at doses of 250 mg/kg/day (equivalent to approximately 0.4 times the MRHD of 2 grams every 8 hours based on body surface area comparison) and above in rats. In a published study, meropenem administered to pregnant rats from Gestation Day 6 to Gestation Day 17, was associated with mild maternal weight loss at all doses, but did not produce malformations or fetal toxicity. The no-observed-adverse-effect-level (NOAEL) for fetal toxicity in this study was considered to be the high dose of 750 mg/kg/day (equivalent to approximately 1.2 times the MRHD based on body surface area comparison). In a peri-postnatal study in rats described in the published literature, intravenous meropenem was administered to dams from Gestation Day 17 until Postpartum Day 21. There were no adverse effects in the dams and no adverse effects in the first generation offspring (including developmental, behavioral, and functional assessments and reproductive parameters) except that female offspring exhibited lowered body weights which continued during gestation and nursing of the second generation offspring. Second generation offspring showed no meropenem-related effects. The NOAEL value was considered to be 1000 mg/kg/day (approximately 1.6 times the MRHD based on body surface area comparisons).1

Animal Data for Vaborbactam: In a rat embryo-fetal toxicology study, intravenous administration of vaborbactam during Gestation Days 6–17 showed no evidence of maternal or embryofetal toxicity at doses up to 1000 mg/kg, which is equivalent to approximately 1.6 times the MRHD based on body surface area comparisons. In the rabbit, intravenous administration of vaborbactam during Gestation Days 7–19 at doses up to 1000 mg/kg/day (approximately 5 times the MRHD based on AUC exposure comparison) was not associated with maternal toxicity or fetal weight loss. A low incidence of malformations occurred in the 300 mg/kg/day mid-dose group (two fetuses from different litters with interventricular septal defects, one fetus with a fused right lung lobe and one fetus with a supernumerary lung lobe), and in the 1000 mg/kg/day high-dose group (two fetuses from different litters with supernumerary lobes). The NOAEL was considered to be 100 mg/kg/day which is equivalent to 0.3 times the MRHD based on plasma AUC exposure comparison and 6-times the MRHD based on maximum plasma concentration (C max) comparison. The clinical relevance of the malformations is uncertain. Vaborbactam C max values may have influenced malformations in the rabbit study, and the recommended 3-hour infusion time for clinical administration of vaborbactam is associated with lower plasma C max values than the 30-minute infusions in rabbits. In a peri-postnatal study in rats, vaborbactam administered intravenously to pregnant dams from Gestation Day 6 to Lactation Day 20 caused no adverse effects on the dams, or in first and second generation offspring. The NOAEL was considered to be 1000 mg/kg/day (equivalent to approximately 1.6 times the MRHD based on body surface area comparison).1

Lactation

Meropenem has been reported to be excreted in human milk. It is unknown whether vaborbactam is excreted in human milk. No information is available on the effects of meropenem and vaborbactam on the breast-fed child or on milk production.1

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for meropenem and vaborbactam and any potential adverse effects on the breast-fed child from meropenem and vaborbactam or from the underlying maternal condition.1

Pediatric Use

The safety and effectiveness of meropenem and vaborbactam in pediatric patients (younger than 18 years of age) has not been established. Studies of meropenem and vaborbactam have not been conducted in patients younger than 18 years of age.1

Geriatric Use

Of the 272 patients treated with meropenem and vaborbactam in the Phase 3 cUTI trial, 48 (18%) patients were 65 years of age and older, while 39 (14%) patients were 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.1

Meropenem, a component of meropenem and vaborbactam, is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.1

Population pharmacokinetic (PK) analysis found no clinically relevant change in pharmacokinetic parameters in elderly patients. No dosage adjustment based on age is required. Dosage adjustment for elderly patients should be based on renal function.1

Renal Impairment

Pharmacokinetic studies conducted with meropenem and vaborbactam in subjects with renal impairment have shown that the plasma exposures of both meropenem and vaborbactam increased with decreasing renal function. Dosage adjustment for meropenem and vaborbactam is recommended in patients with renal impairment (eGFR less than 50 mL/min/1.73m 2).1

For patients with changing renal function, monitor serum creatinine concentrations and eGFR at least daily and adjust the dosage of meropenem and vaborbactam accordingly. Meropenem and vaborbactam are removed by hemodialysis. Following a single dose of meropenem and vaborbactam, vaborbactam exposure was substantially greater when meropenem and vaborbactam was administered after hemodialysis than before hemodialysis.1

Common Adverse Effects

The most frequently reported adverse reactions occurring in ≥3% of patients treated with meropenem and vaborbactam were headache, phlebitis/infusion site reactions, and diarrhea.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Meropenem And Vaborbactam

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For Injection, for IV infusion

2 g (1 g of meropenem and 1 g of vaborbactam)

Vabomere

The Medicines Company

Uses of Vabomere

  • It is used to treat a urinary tract infection (UTI).

What are some things I need to know or do while I take Vabomere?

  • Tell all of your health care providers that you take Vabomere. This includes your doctors, nurses, pharmacists, and dentists.
  • Very bad and sometimes deadly allergic side effects have rarely happened with drugs like this one. Talk with the doctor.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
  • Do not use longer than you have been told. A second infection may happen.
  • If you are 65 or older, use Vabomere with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is this medicine (Vabomere) best taken?

Use Vabomere as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Seizures.
  • Stiff muscles, shakiness, or muscle movements that are not normal.
  • A burning, numbness, or tingling feeling that is not normal.
  • Feeling confused.
  • It is common to have diarrhea when taking this medicine. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking Vabomere or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

What are some other side effects of Vabomere?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Headache.
  • Irritation where this medicine is given.
  • Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If OVERDOSE is suspected

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.

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