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
Valtrex Side Effects, and Drug Interactions - Valacyclovir hydrochloride
Valtrex Side Effects, and Drug Interactions - Valacyclovir hydrochloride
SIDE EFFECTS
Frequently reported adverse events in clinical trials of VALTREX
are listed in Tables 2 and 3.
|
Table 2. Incidence (%) of Adverse Events in Herpes Zoster
Study Populations
|
|
Adverse Event
|
VALTREX 1 gram t.i.d. (n = 967)
|
Placebo (n = 195)
|
|
Nausea
|
15%
|
8%
|
|
Headache
|
14%
|
12%
|
|
Vomiting
|
6%
|
3%
|
|
Dizziness
|
3%
|
2%
|
|
Abdominal Pain
|
3%
|
2%
|
|
Table 3. Incidence (%) of Adverse Events in Genital Herpes
Study Populations
|
|
Adverse Event
|
Genital Herpes Treatment
|
Genital Herpes Suppression
|
|
VALTREX 1 gram b.i.d. (n = 1194)
|
VALTREX 500 mg b.i.d. (n = 1159)
|
Placebo (n = 439)
|
VALTREX 1 gram q.d. (n = 269)
|
VALTREX 500 mg q.d. (n = 266)
|
Placebo (n = 134)
|
|
|
|
Nausea
|
6%
|
5%
|
8%
|
11%
|
11%
|
8%
|
|
Headache
|
16%
|
15%
|
14%
|
35%
|
38%
|
34%
|
|
Vomiting
|
1%
|
<1%
|
<1%
|
3%
|
3%
|
2%
|
|
Dizziness
|
3%
|
2%
|
3%
|
4%
|
2%
|
1%
|
|
Abdominal Ppain
|
2%
|
1%
|
3%
|
11%
|
9%
|
6%
|
|
Dysmenorrhea
|
<1%
|
<1%
|
1%
|
8%
|
5%
|
4%
|
|
Arthralgia
|
<1%
|
<1%
|
<1%
|
6%
|
5%
|
4%
|
|
Depression
|
1%
|
0%
|
<1%
|
7%
|
5%
|
5%
|
In clinical studies for the treatment of cold sores, the adverse
events reported by patients receiving VALTREX (n = 609) or placebo (n = 609)
included headache (VALTREX 14%, placebo 10%) and dizziness (VALTREX 2%, placebo
1%).
Laboratory abnormalities reported in clinical trials of VALTREX
are listed in Table 4.
|
Table 4. Incidence (%) of Laboratory Abnormalities
in Herpes Zoster and Genital Herpes Study Populations
|
|
Herpes Zoster
|
Genital Herpes Treatment
|
Genital Herpes Suppression
|
|
Laboratory Abnormality
|
VALTREX 1 gram t.i.d.
|
Place-bo
|
VALTREX 1 gram b.i.d.
|
VALTREX 500 mg b.i.d.
|
Place-bo
|
VALTREX 1 gram q.d.
|
VALTREX 500 mg q.d.
|
Place-bo
|
|
Hemoglobin (<0.8 x LLN)
|
0.8%
|
0%
|
0.3%
|
0.2%
|
0%
|
0%
|
0.8%
|
0.8%
|
|
White blood cells (<0.75 x LLN)
|
1.3%
|
0.6%
|
0.7%
|
0.6%
|
0.2%
|
0.7%
|
0.8%
|
1.5%
|
|
Platelet count(<100,000/mm3)
|
1.0%
|
1.2%
|
0.3%
|
0.1%
|
0.7%
|
0.4%
|
1.1%
|
1.5%
|
|
AST (SGOT) (>2 x ULN)
|
1.0%
|
0%
|
1.0%
|
*
|
0.5%
|
4.1%
|
3.8%
|
3.0%
|
|
Serum creatinine (>1.5 x ULN)
|
0.2%
|
0%
|
0.7%
|
0%
|
0%
|
0%
|
0%
|
0%
|
|
*Data were not collected prospectively.
|
|
LLN = Lower limit of normal., ULN = Upper limit of normal.
|
In clinical studies for the treatment of cold sores, the frequencies
of abnormal ALT (>2 x ULN) were 1.8% for patients receiving VALTREX compared
with 0.8% for placebo. Other laboratory abnormalities (hemoglobin, white blood
cells, alkaline phosphatase, and serum creatinine) occurred with similar frequencies
in the 2 groups.
Observed During Clinical Practice
The following events have been identified during post-approval
use of VALTREX in clinical practice. 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 either their seriousness, frequency of
reporting, causal connection to VALTREX, or a combination of these factors.
General: Facial edema, hypertension, tachycardia.
Allergic: Acute hypersensitivity reactions
including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria.
CNS Symptoms: Aggressive behavior; agitation;
ataxia; coma; confusion; decreased consciousness; dysarthria; encephalopathy;
mania; and psychosis, including auditory and visual hallucinations; seizures
(see PRECAUTIONS).
Eye: Visual abnormalities.
Gastrointestinal: Diarrhea.
Hepatobiliary Tract and Pancreas: Liver enzyme
abnormalities, hepatitis.
Renal: Elevated creatinine, renal failure.
Hematologic: Thrombocytopenia, aplastic
anemia, leukocytoclastic vasculitis. Skin: Erythema multiforme,
rashes including photosensitivity.
Renal Impairment: Renal failure and CNS
symptoms have been reported in patients with renal impairment who received VALTREX
or acyclovir at greater than the recommended dose. Dose reduction is recommended
in this patient population (see DOSAGE AND
ADMINISTRATION).
DRUG INTERACTIONS
See CLINICAL PHARMACOLOGY:
Pharmacokinetics.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
The data presented below include references to the steady-state acyclovir AUC
observed in humans treated with 1 gram VALTREX given orally 3 times a day to
treat herpes zoster. Plasma drug concentrations in animal studies are expressed
as multiples of human exposure to acyclovir (see CLINICAL
PHARMACOLOGY: Pharmacokinetics).
Valacyclovir was noncarcinogenic in lifetime carcinogenicity
bioassays at single daily doses (gavage) of up to 120 mg/kg/day for mice and
100 mg/kg/day for rats. There was no significant difference in the incidence
of tumors between treated and control animals, nor did valacyclovir shorten
the latency of tumors. Plasma concentrations of acyclovir were equivalent to
human levels in the mouse bioassay and 1.4 to 2.3 times human levels in the
rat bioassay.
Valacyclovir was tested in 5 genetic toxicity assays. An Ames
assay was negative in the absence or presence of metabolic activation. Also
negative were an in vitro cytogenetic study with human lymphocytes and a rat
cytogenetic study at a single oral dose of 3,000 mg/kg (8 to 9 times human plasma
levels).
In the mouse lymphoma assay, valacyclovir was not mutagenic
in the absence of metabolic activation. In the presence of metabolic activation
(76% to 88% conversion to acyclovir), valacyclovir was mutagenic.
Valacyclovir was not mutagenic in a mouse micronucleus assay
at 250 mg/kg but positive at 500 mg/kg (acyclovir concentrations 26 to 51 times
human plasma levels).
Valacyclovir did not impair fertility or reproduction in rats
at 200 mg/kg/day (6 times human plasma levels).
Pregnancy
Teratogenic Effects
Pregnancy Category B. Valacyclovir was not teratogenic in rats
or rabbits given 400 mg/kg (which results in exposures of 10 and 7 times human
plasma levels, respectively) during the period of major organogenesis.
There are no adequate and well-controlled studies of VALTREX
or ZOVIRAX in pregnant women. A prospective epidemiologic registry of acyclovir
use during pregnancy was established in 1984 and completed in April 1999. There
were 749 pregnancies followed in women exposed to systemic acyclovir during
the first trimester of pregnancy resulting in 756 outcomes. The occurrence rate
of birth defects approximates that found in the general population. However,
the small size of the registry is insufficient to evaluate the risk for less
common defects or to permit reliable or definitive conclusions regarding the
safety of acyclovir in pregnant women and their developing fetuses. VALTREX
should be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
Nursing Mothers
There is no experience with VALTREX. However, acyclovir concentrations
have been documented in breast milk in 2 women following oral administration
of ZOVIRAX and ranged from 0.6 to 4.1 times corresponding plasma levels. These
concentrations would potentially expose the nursing infant to a dose of acyclovir
as high as 0.3 mg/kg/day. VALTREX should be administered to a nursing mother
with caution and only when indicated.
Pediatric Use
Safety and effectiveness of VALTREX in pre-pubertal pediatric
patients have not been established.
Geriatric Use
Of the total number of subjects in clinical studies of VALTREX,
889 were 65 and over, and 350 were 75 and over. In a clinical study of herpes
zoster, the duration of pain after healing (post-herpetic neuralgia) was longer
in patients 65 and older compared with younger adults. Elderly patients are
more likely to have reduced renal function and require dose reduction. Elderly
patients are also more likely to have renal or CNS adverse events. With respect
to CNS adverse events observed during clinical practice, agitation, hallucinations,
confusion, delirium, and encephalopathy were reported more frequently in elderly
patients (see CLINICAL PHARMACOLOGY,
SIDE EFFECTS
: Observed During
Clinical Practice, and DOSAGE AND ADMINISTRATION).
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