ADVERSE REACTIONS
Frequently reported adverse events in clinical trials of VALTREX in healthy patients are listed in Tables 4 and 5.
Table 4. 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 5. Incidence (%) of Adverse Events in Genital Herpes Study Populations |
Genital Herpes Treatment
|
Genital Herpes Suppression
|
|
Adverse Event
|
VALTREX
1 gram b.i.d.
(n = 1,194)
|
VALTREX
500 mg b.i.d.
(n = 1,159)
|
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 pain
|
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%
|
Laboratory abnormalities reported in clinical trials of VALTREX in otherwise healthy patients are listed in Table 6.
Table 6. 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
|
VALTREX1 gram b.i.d.
|
VALTREX500 mg b.i.d.
|
Place-bo
|
VALTREX
1 gram q.d.
|
VALTREX500 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.
Suppression of Genital Herpes in HIV-Infected Patients
In HIV-infected patients, frequently reported adverse events for VALTREX (500 mg twice daily; n = 194, median days on therapy = 172) and placebo (n = 99, median days on therapy = 59), respectively, included headache (13% vs. 8%), fatigue (8% vs. 5%), and rash (8% vs. 1%). Post-randomization laboratory abnormalities that were reported more frequently in valacyclovir subjects versus placebo included elevated alkaline phosphatase (4% vs. 2%), elevated ALT (14% vs. 10%), elevated AST (16% vs. 11%), decreased neutrophil counts (18% vs. 10%), and decreased platelet counts (3% vs. 0%).
Reduction of Transmission
In a clinical study for the reduction of transmission of genital herpes, the adverse events reported by patients receiving VALTREX 500 mg once daily (n = 743) or placebo once daily (n = 741) included headache (VALTREX 29%, placebo 26%), nasopharyngitis (VALTREX 16%, placebo 15%), and upper respiratory tract infection (VALTREX 9%, placebo 10%). In this 8-month study, there were no clinically significant changes from baseline laboratory parameters in subjects receiving VALTREX compared with placebo.
Cold Sores (Herpes Labialis)
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%). 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 connectionto 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, tremors (see PRECAUTIONS).
Eye
Visual abnormalities.
Gastrointestinal
Diarrhea.
Hepatobiliary Tract and Pancreas
Liver enzyme abnormalities, hepatitis.
Renal
Elevated creatinine, renal failure, renal pain (may be associated with renal failure).
Hematologic
Thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, TTP/HUS.
Skin
Erythema multiforme, rashes including photosensitivity, alopecia.
Renal Impairment
Renal failureand 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).
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