"The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
Dotarem is a gadolinium-based"...
The following are discussed in greater detail in other sections of labeling:
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Seizure Potential [see WARNINGS AND PRECAUTIONS]
- Interaction with Valproic Acid [see WARNINGS AND PRECAUTIONS]
- Clostridium difficile – Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
- Development of Drug-Resistant Bacteria [see WARNINGS AND PRECAUTIONS]
- Overgrowth of Nonsusceptible Organisms [see WARNINGS AND PRECAUTIONS]
- Laboratory Tests [see WARNINGS AND PRECAUTIONS]
- Patients with Renal Impairment [see WARNINGS AND PRECAUTIONS]
- Dialysis [see WARNINGS AND PRECAUTIONS]
- Potential for Neuromotor Impairment [see WARNINGS AND PRECAUTIONS]
Adverse Reactions From Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reactions 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.
During clinical investigations, 2904 immunocompetent adult patients were treated for non-CNS infections with MERREM I.V. (500 mg or 1000 mg every 8 hours). Deaths in 5 patients were assessed as possibly related to meropenem; 36 (1.2%) patients had meropenem discontinued because of adverse events. Many patients in these trials were severely ill and had multiple background diseases, physiological impairments and were receiving multiple other drug therapies. In the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with MERREM I.V.
The following adverse reaction frequencies were derived from the clinical trials in the 2904 patients treated with MERREM I.V.
Local Adverse Reactions
Local adverse reactions that were reported irrespective of the relationship to therapy with MERREM I.V. were as follows:
Systemic Adverse Reactions
Systemic adverse reactions that were reported irrespective of the relationship to MERREM I.V. occurring in greater than 1.0% of the patients were diarrhea (4.8%), nausea/vomiting (3.6%), headache (2.3%), rash (1.9%), sepsis (1.6%), constipation (1.4%), apnea (1.3%), shock (1.2%), and pruritus (1.2%).
Additional systemic adverse reactions that were reported irrespective of relationship to therapy with MERREM I.V. and occurring in less than or equal to 1.0% but greater than 0.1% of the patients are listed below within each body system in order of decreasing frequency:
Body as a Whole: pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement, chills, pelvic pain
Metabolic/Nutritional: peripheral edema, hypoxia
Skin and Appendages: urticaria, sweating, skin ulcer
Adverse Laboratory Changes
Adverse laboratory changes that were reported irrespective of relationship to MERREM I.V. and occurring in greater than 0.2% of the patients were as follows:
Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased WBC, shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia
Renal: increased creatinine and increased BUN
NOTE: For patients with varying degrees of renal impairment, the incidence of heart failure, kidney failure, seizure and shock reported irrespective of relationship to MERREM I.V., increased in patients with moderately severe renal impairment (creatinine clearance > 10 to 26 mL/min) [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, Use In Specific Populations and CLINICAL PHARMACOLOGY].
Urinalysis: presence of red blood cells
Complicated Skin and Skin Structure Infections
In a study of complicated skin and skin structure infections, the adverse reactions were similar to those listed above. The most common adverse events occurring in > 5% of the patients were: headache (7.8%), nausea (7.8%), constipation (7.0%), diarrhea (7.0%), anemia (5.5%), and pain (5.1%). Adverse events with an incidence of > 1%, and not listed above, include: pharyngitis, accidental injury, gastrointestinal disorder, hypoglycemia, peripheral vascular disorder, and pneumonia.
Clinical Adverse Reactions
MERREM I.V. was studied in 515 pediatric patients ( ≥ 3 months to < 13 years of age) with serious bacterial infections (excluding meningitis, see next section) at dosages of 10 to 20 mg/kg every 8 hours. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to MERREM I.V. and their rates of occurrence as follows:
Nausea and Vomiting 0.8%
MERREM I.V. was studied in 321 pediatric patients ( > 3 months to < 17 years of age) with meningitis at a dosage of 40 mg/kg every 8 hours. The types of clinical adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to MERREM I.V. and their rates of occurrence as follows:
Rash (mostly diaper area moniliasis) 3.1%
Oral Moniliasis 1.9%
In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents (either cefotaxime or ceftriaxone). In the MERREM I.V. treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm.
Adverse Laboratory Changes
Laboratory changes seen in the pediatric studies, including the meningitis studies, were similar to those reported in the adult studies.
There is no experience in pediatric patients with renal impairment.
The following adverse reactions have been identified during post-approval use of MERREM I.V. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions section of this product label and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity. Hematologic -agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia. Skin-toxic epidermal necrolysis, Stevens-Johnson Syndrome, angioedema, and erythema multiforme.
Read the Merrem I.V. (meropenem) Side Effects Center for a complete guide to possible side effects
Probenecid competes with meropenem for active tubular secretion, resulting in increased plasma concentrations of meropenem. Co-administration of probenecid with meropenem is 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. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid. If administration of MERREM I.V. is necessary, then supplemental anti-convulsant therapy should be considered [see WARNINGS AND PRECAUTIONS].
Read the Merrem I.V. Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 12/30/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Merrem I.V. Information
Merrem I.V. - User Reviews
Merrem I.V. User Reviews
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