A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Merrem I.V. Side Effects, and Drug Interactions - Meropenem
Merrem I.V. Side Effects, and Drug Interactions - Meropenem
SIDE EFFECTS
Adult Patients
During clinical investigations, 2904 immunocompetent adult
patients were treated for infections outside the CNS with MERREM I.V. (500mg
or 1000 mg q 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:
|
Inflammation at the injection site
|
2.4%
|
|
Injection site reaction
|
0.9%
|
|
Phlebitis/thrombophlebitis
|
0.8%
|
|
Pain at the injection site
|
0.4%
|
|
Edema at the injection site
|
0.2%
|
Systemic Adverse Reactions
Systemic adverse clinical 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 adverse systemic clinical 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: Bleeding events were
seen as follows: gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis
(0.2%), hemoperitoneum (0.2%), summing to 1.2%.
Body as a Whole
pain, abdominal pain, chest pain, fever, back pain, abdominal
enlargement, chills, pelvic pain
Cardiovascular
heart failure, heart arrest, tachycardia, hypertension, myocardial
infarction, pulmonary embolus, bradycardia, hypotension, syncope
Digestive System
oral moniliasis, anorexia, cholestatic jaundice/jaundice, flatulence,
ileus, hepatic failure, dyspepsia, intestinal obstruction
Hemic/Lymphatic
anemia, hypochromic anemia, hypervolemia
Metabolic/Nutritional
peripheral edema, hypoxia
Nervous System
insomnia, agitation/delirium, confusion, dizziness, seizure
(see PRECAUTIONS), nervousness, paresthesia,
hallucinations, somnolence, anxiety, depression, asthenia
Respiratory
respiratory disorder, dyspnea, pleural effusion, asthma, cough
increased, lung edema
Skin and Appendages
urticaria, sweating, skin ulcer
Urogenital System
dysuria, kidney failure, vaginal moniliasis, urinary incontinence
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:
Hepatic
increased SGPT (ALT), SGOT (AST), alkaline phosphatase, LDH,
and bilirubin 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).
Urinalysis
presence of urine red blood cells
Pediatric Patients
Clinical Adverse Reactions
MERREM I.V. was studied in 515 pediatric patients (³
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:
|
Diarrhea
|
3.5%
|
|
Rash
|
1.6%
|
|
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
8hours. 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:
|
Diarrhea
|
4.7%
|
|
Rash (mostly diaper area moniliasis)
|
3.1%
|
|
Oral Moniliasis
|
1.9%
|
|
Glossitis
|
1.0%
|
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 abnormalities seen in the pediatric-aged patients
in both the pediatric and the meningitis studies are similar to those reported
in adult patients.
There is no experience in pediatric patients with renal impairment.
Post-marketing Experience
Worldwide post-marketing adverse events not previously listed
in the 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. Skin - toxic epidermal
necrolysis, Stevens-Johnson Syndrome, angioedema, and erythema multiform.
DRUG INTERACTIONS
Probenecid competes with meropenem for active tubular secretion
and thus inhibits the renal excretion of meropenem. This led to statistically
significant increases in the elimination half-life (38%) and in the extent of
systemic exposure (56%). Therefore, the coadministration of probenecid with
meropenem is not recommended.
There is evidence that meropenem may reduce serum levels of
valproic acid to subtherapeutic levels (therapeutic range considered to be 50
to 100 µg/mL total valproate).
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