VABOMERE SIDE EFFECTS

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in the Warnings and Precautions section:

• Hypersensitivity Reactions
• Seizure Potential
• Clostridioides difficile-associated Diarrhea
• Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid
• Thrombocytopenia
• Potential for Neuromotor Impairment
• Development of Drug-Resistant Bacteria
• Overgrowth of Nonsusceptible Organisms

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

VABOMERE was evaluated in a Phase 3 comparator-controlled clinical trial in cUTI, including pyelonephritis, whichincluded272 patientstreatedwithVABOMEREand273 patientstreated with the comparator piperacillin/tazobactam 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) every 8 hours. After a minimum of 15 doses of IV therapy, patients could be switched to oral levofloxacin (500 mg daily every 24 hours) to complete the treatment course. Mean duration of IV therapy was 8 days in both treatment groups. Mean duration of IV and oral therapy was 10 days; patients with baseline bacteremia could receive up to 14 days of treatment.

The mean age of patients treated with VABOMERE was 53 years (range 18 to 92 years), and 32% of patients were 65 years of age or older. Patients were predominantly female (66.5%) and White (93.4%). Most patients were enrolled in Europe (89.7%).

Serious Adverse Reactions And Adverse Reactions Leading To Discontinuation

Treatment was discontinued due to adverse reactions in 2.9% (8/272) of patients receiving VABOMERE and in 5.1% (14/273) of patients receiving piperacillin/tazobactam. Most common adverse reactions resulting in discontinuation of VABOMERE included hypersensitivity, 1.1% (3/272) and infusion-related reactions, 0.7% (2/272). Death occurred in 2 (0.7%) patients who received VABOMERE and in 2 (0.7%) patients who received piperacillin/tazobactam.

Common Adverse Reactions

The most frequently reported adverse reactions (3% or greater) in patients receiving VABOMERE in the Phase 3 cUTI trial were headache, phlebitis/infusion site reactions, and diarrhea. Table 3 provides adverse reactions occurring in 1% or greater of patients receiving VABOMERE in the Phase 1 cUTI trial.

Table 1: Adverse Reactions Occurring in 1% or Greater of Patients Receiving VABOMERE in the Phase 3 Clinical Trial in cUTI

Adverse Reactions Occurring In Less Than 1% Of Patients Receiving VABOMERE In The Phase 3 cUTI Trial

Blood and lymphatic system disorders:leukopenia

General disorders and administration site conditions:chest discomfort

Infections and infestations:pharyngitis, vulvovaginal candidiasis, oral candidiasis

Investigations:creatinine phosphokinase increase

Metabolism and nutrition disorders:decreased appetite, hyperkalemia, hyperglycemia, hypoglycemia

Nervous system disorders:dizziness, tremor, paresthesia, lethargy

Psychiatric disorders:hallucination, insomnia

Renal and urinary disorders: azotemia, renal impairment

Vascular disorders: deep vein thrombosis, hypotension, vascular pain

Other Adverse Reactions Associated With Meropenem

Additionally, adverse reactions reported with meropenem alone that were not reported in VABOMERE-treated patients in the Phase 3 clinical trial are listed below:

Blood and lymphatic system disorders: thrombocytosis, neutropenia, eosinophilia, thrombocytopenia, agranulocytosis, hemolytic anemia

Gastrointestinal disorders: abdominal pain

Hepatobiliary disorders: jaundice

Nervous system disorders: convulsions

Investigations: blood alkaline phosphatase increased, blood lactate dehydrogenase increased, blood bilirubin increased, blood creatinine increased, blood urea increased, blood thromboplastin decreased, prothrombin time decreased, Direct and Indirect Coombs test positive

Skin and subcutaneoustissue disorders: pruritus, toxic epidermal necrolysis, Stevens Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, erythema multiforme

Immune system disorders: angioedema

General disorders and administration site conditions: pain