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
Raxar Side Effects, and Drug Interactions - Grepafloxacin
Raxar Side Effects, and Drug Interactions - Grepafloxacin
SIDE EFFECTS
Adverse reactions were assessed in clinical
trials involving approximately 2500 patients receiving single-dose
or multiple-dose regimens of grepafloxacin.
Multiple dose Regimens
Most of the adverse reactions reported in clinical
trials were transient in nature, mild to moderate in severity, and
required no treatment. Twenty
of 1069 patients (1.9%) receiving grepafloxacin 400 mg
daily and 50 of 925 patients (5.4%) receiving grepafloxacin 600
mg daily discontinued RAXAR
Tablets due to an adverse reaction
thought by the investigator to be drug-related.
Table 3 lists adverse events that occurred with frequencies of
1% or greater. These events were thought by the investigators to
be drug-related in patients treated with grepafloxacin in multiple
dose clinical
trials.
Table 3
Drug-related Adverse Reactions in Grepafloxacin Treated Patients
on Multiple dose Dosing
Regimens in Clinical Trials
|
Adverse Reaction
|
400 mg
daily (n=1069)
|
600 mg
daily (n=925)
|
|
Nausea
|
11.1 %
|
15.8 %
|
|
Taste perversion
|
9.0 %
|
17.8 %
|
|
Headache
|
4.6 %
|
4.9 %
|
|
Dizziness
|
4.3 %
|
5.4 %
|
|
Diarrhea
|
3.5 %
|
4.2 %
|
|
Vaginitis
|
3.3 %
|
1.4 %
|
|
Abdominal pain
|
2.2 %
|
2.1 %
|
|
Vomiting
|
1.7 %
|
5.7 %
|
|
Pruritus
|
1.6 %
|
1.2 %
|
|
Dyspepsia
|
1.5 %
|
3.1 %
|
|
Leukorrhea
|
1.4 %
|
0.0 %
|
|
Asthenia
|
1.4 %
|
2.3 %
|
|
Infection
|
1.3 %
|
0.4 %
|
|
Insomnia
|
1.3 %
|
2.1 %
|
|
Rash
|
1.1 %
|
1.9 %
|
|
Anorexia
|
0.8 %
|
1.8 %
|
|
Somnolence
|
1.0 %
|
1.5 %
|
|
Dry mouth
|
0.8 %
|
1.1 %
|
|
Photosensitivity reaction
|
0.7 %
|
1.8 %
|
|
Constipation
|
0.7 %
|
2.2 %
|
|
Pain
|
0.6 %
|
1.0 %
|
|
Nervousness
|
0.6 %
|
1.7 %
|
Additional drug-related events, occurring in multiple-dose clinical
trials at a rate of less
than 1% were:
Body as a Whole: Back pain,
body odor, chest
pain, chills, facial edema,
fever, malaise,
neck rigidity, pelvic
pain.
Cardiovascular System: Arrhythmia, hypotension,
palpitations, peripheral vascular
disorder, postural
hypotension, syncope,
tachycardia, vasodilatation.
Digestive System: Abnormal liver
function tests, abnormal
stools, cheilitis, dysphagia,
eructation, flatulence,
gastritis, gastrointestinal
disorder, gingivitis,
glossitis, increased appetite, melena,
mouth ulceration, oral
moniliasis, rectal disorder,
rectal hemorrhage,
stomatitis, tenesmus,
thirst, tongue discoloration,
tongue disorder, tongue
edema.
Hemic and Lymphatic System: Anemia, eosinophilia,
hypochromic, anemia, leukocytosis,
leukopenia, lymphadenopathy,
lymphocytosis, lymphoma like reaction,
prothrombin decreased,
prothrombin increased,
reticuloendothelial hyperplasia, thrombocytopenia,
thromboplastin
increased.
Metabolic and Nutritional System: Dehydration, edema,
electrolyte abnormality, gout,
hyperglycemia,
hyperlipidemia,
hypernatremia, hyperuricemia, increased alkaline
phosphatase, increased BUN, increased creatinine, increased gamma
glutamyl transpeptidase, increased SGOT, increased SGPT, peripheral
edema, weight
loss.
Musculoskeletal System: Arthralgia, myalgia.
Nervous System: Abnormal dreams, abnormal
gait, agitation, anxiety,
confusion, depression,
emotional lability, hallucinations, hyperkinesia, hypesthesia, hypokinesia,
paresthesia, speech
disorder, stupor, thinking
abnormal, tremor, vertigo.
Respiratory System: Asthma, atelectasis, bronchitis,
dyspnea, epistaxis, hemoptysis,
increased cough, laryngismus, pharyngitis,
pleural effusion, rhinitis,
sputum increased.
Skin and Appendages: Acne, alopecia,
dry skin, epidermal necrolysis,
exfoliative dermatitis,
fungal dermatitis,
herpes simplex, maculopapular
rash, skin
disorder, sweating, urticaria,
vesiculobullous rash.
Special Senses: Amblyopia, conjunctivitis,
deafness, dry eyes, ear
disorder, eye pain,
lacrimation disorder,
parosmia, photophobia,
taste loss, tinnitus.
Urogenital System: Albuminuria, balanitis, dysuria,
hematuria, impotence, polyuria,
urethral pain,
uricaciduria, urinary
frequency, urinary tract disorder, urination
impaired, urine abnormality,
vulvovaginal disorder.
Single dose Regimens
In clinical trials,
patients were treated for uncomplicated gonorrhea using a single
dose of RAXAR 400 mg. There
were no deaths or permanent
disabilities in these studies.
Table 4 lists the adverse events which occurred with frequencies
of 1% or greater. These events were thought by the investigators
to be drug related in patients treated with RAXAR Tablets in single-dose
clinical trials.
Table 4
Drug-related Adverse Reactions in Grepafloxacin Treated Patients
on a Single dose Dosing
Regimen in Clinical Trials
|
Adverse Reaction
|
400 mg
daily (n=487)
|
|
Vaginitis
|
5.0%
|
|
Nausea
|
3.3%
|
|
Dizziness
|
2.1%
|
|
Vomiting
|
2.1%
|
|
Headache
|
1.8%
|
|
Leukorrhea
|
1.2%
|
|
Abdominal pain
|
1.2%
|
|
Diarrhea
|
1.2%
|
|
Pruritus
|
1.2%
|
|
Taste perversion
|
1.2%
|
Additional drug-related events occurring in single dose
clinical trials at
a rate of less than 1 were:
- Body as a Whole: Asthenia, chest
pain, chills, flu-like
syndrome, infection,
malaise.
- Cardiovascular System: Syncope, vasodilatation.
- Digestive System: Anorexia, constipation,
increased appetite, tenesmus.
- Hemic and Lymphatic System: Lymphadenopathy.
- Nervous System: Hyperkinesia, insomnia,
nervousness, somnolence.
- Respiratory System: Rhinitis.
- Skin and Appendages: Acne, rash,
sweating.
- Urogenital System: Balanitis.
Observed During Clinical Practice
In addition to adverse
reactions reported from clinical
trials the following events have been identified during post-approval
use of grepafloxacin formulations. Because they are reported voluntarily
from a population
of unknown size estimates of frequency
cannot be made. These events have been chosen for inclusion due
to a combination of their seriousness, frequency
of reporting, or potential
causal connection to grepafloxacin.
- Eye: Disturbances in vision.
- Non Site specific: Allergic reactions, including
anaphylactoid reaction/anaphylactic shock, angioedema,
laryngeal edema.
DRUG INTERACTIONS
Antacids, Sucralfate, Metal Cations, Multivitamins
Quinolones form chelates
with alkaline earth
and transition metal
cations. Administration of quinolones with antacids containing aluminum,
magnesium, or calcium,
with sucralfate, with metal cations such
as iron, or with multivitamins
containing iron or zinc,
or with formulations containing divalent
and trivalent cations such
as VIDEX (didanosine) chewable/buffered tablets or the pediatric
powder for oral solution,
may substantially interfere with the absorption of quinolones, resulting
in systemic concentrations
considerably lower than desired. These agents should not be taken
within 4 hours before or 4 hours after grepafloxacin administration.
Caffeine Theobromine
Grepafloxacin, like other quinolones, may inhibit the metabolism
of caffeine and theobromine. These stimulants are commonly found
in coffee and tea, respectively. In
some patients, this may lead
to reduced clearance, prolongation of plasma
half-life, and enhanced effects of caffeine
and theobromine.
Theophylline
Grepafloxacin is a competitive inhibitor
of the metabolism
of theophylline. Serum theophylline
concentrations increase when grepafloxacin is initiated in a patient
maintained on theophylline. When initiating a multi-day course
of grepafloxacin in a patient
maintained on theophylline, the theophylline maintenance dose
should be halved for the period
of concurrent use of grepafloxacin and monitoring of serum
theophylline concentrations
should be initiated as a guide
to further dosage adjustments.
Warfarin
In subjects receiving warfarin, no
significant change
in clotting time was
observed when grepafloxacin was coadministered. However, because
some quinolones have been reported to enhance the effects of warfarin
or its derivatives, prothrombin
time or other suitable
anticoagulation test should
be monitored closely if a quinolone
antimicrobial
is administered with warfarin or its derivatives.
Drugs Metabolized by Cytochrome P450 Enzymes
The drug interaction study
evaluating the effect
of grepafloxacin on theophylline indicates that grepafloxacin inhibits
theophylline metabolism,
which is mediated by CYP1A2. While no
clinical studies have
been conducted to evaluate the effect
of grepafloxacin on the metabolism
of C.P.A. substrates,
in vitro data suggest similar effects of grepafloxacin in
CYP3A4 mediated metabolism
and theophylline
metabolism. In addition,
other quinolones have been reported to decrease the CYP3A4-mediated
metabolism of cyclosporine.
Other drugs metabolized by C.P.A.
include terfenadine, astemizole, cisapride, midazolam, and triazolam.
The clinical relevance
of the potential effect
of grepafloxacin on the metabolism
of C.P.A. substrates
is not known. Patients receiving concurrent administration
of substrates of C.P.A.
were not excluded from clinical
trials of grepafloxacin.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
The concomitant
administration
of a nonsteroidal anti inflammatory
drug with a quinolone
may increase the risks of CNS
stimulation and
convulsions (see WARNINGS ).
Antidiabetic Agents
Disturbances of blood
glucose, including hyperglycemia
and hypoglycemia, have been reported in patients treated concomitantly
with quinolones and an antidiabetic
agent. Therefore, careful monitoring of blood
glucose is recommended
when these agents are coadministered.
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