How Many Valtrex Can I Take in One Day

February 14, 2022 Post a Comment

Abstract

Valacyclovir given in a 5-twenty-four hour period regimen of 500 mg twice per day is effective as brusque-term treatment of episodes of recurrent genital herpes. This study compared the efficacy of a shorter, iii-day course (for 402 patients) with that of a 5-day course (for 398 patients) of valacyclovir for persons with frequent recurrence of symptoms. No significant differences were detected between the 2 dosing schedules for any of the end points measured. Median times to lesion healing, of pain duration, and of episode length for the v-twenty-four hours versus three-twenty-four hours treatment were 4.seven versus 4.iv days, ii.5 days versus two.9 days, and 4.4 days versus 4.3 days, respectively. The proportions of patients with aborted lesions were 26.six% and 25.four% in the v-day and 3-day groups, respectively. A 3-day grade of 500 mg of valacyclovir administered twice daily as episodic treatment of recurrent genital canker is equivalent to a 5-day course with regard to key markers of efficacy.

Genital canker is 1 of the most prevalent sexually transmitted diseases in the world today: ∼1 in 5 adults in the United States is seropositive for herpesvirus type ii (HSV-2) [1]. Although the disease itself is generally not life-threatening, it has significant morbidity and affect on patients' lives [2–4]. Presently, no cure is available for the condition, but treatment strategies are bachelor to alleviate the acute symptoms of a herpes outbreak or to suppress recurrences.

Orally administered antiviral therapy for genital herpes is prescribed either to convalesce the acute symptoms and signs of an outbreak (i.due east., episodic treatment) or to prevent the herpesvirus (HSV) reactivation and recurrent outbreaks (i.e., suppressive therapy). The specific aims of episodic treatment are to shorten the duration of the outbreak, reduce the severity of pain, and hasten lesion healing. Prompt treatment, starting within a few hours later the patient first detects symptoms of an outbreak, can halt the process of vesicular lesion evolution (i.due east, aborted lesions) [5, 6].

Valacyclovir, the l-valine ester of acyclovir, is widely used to treat genital herpes, both as episodic therapy administered twice daily and as suppressive therapy administered once daily. In controlled, randomized trials using lesion healing, pain, and HSV shedding as measures of clinical efficacy for v days, valacyclovir has been shown to be as effective as orally administered acyclovir (200 mg five times daily) as episodic handling for genital herpes recurrences [vii].

This double-blind, controlled study compared the efficacy and safety of a v-twenty-four hour period regimen of valacyclovir (500 mg b.i.d.) with a 3-day regimen of valacyclovir (500 mg b.i.d.) for the treatment of a single recurrent genital herpes episode. If a 3-day course of treatment is equivalent in efficacy to the 5-24-hour interval grade, then the reduced therapy duration could increase convenience to patients who prefer discreet, episodic medication regimens and could reduce the price of handling.

Patients and Methods

Study blueprint . This study was a randomized, double-blind comparing of the efficacy of valacyclovir administered orally for 5 days versus three days in the treatment of a single recurrent genital herpes episode in otherwise healthy adults. It was conducted at 48 medical centers, including 34 medical centers in the The states and 14 in Canada. The study protocol was approved by the institutional review board at each study site. A flow chart of the written report is shown in figure i.

Figure 1

Flow chart of participants and treatment completed in a comparative study of 3- and 5-day regimens of valacyclovir for the episodic handling of genital herpes.

Written informed consent was obtained from patients, who were then screened for eligibility on the ground of the findings of a medical history, physical examination, and claret testing. Patients enrolled in the study were given a three-twenty-four hour period supply of open-characterization valacyclovir (500 mg b.i.d.) and instructed to self-initiate handling no afterward than 24 h afterwards the beginning sign or symptom of a recurrence of their genital herpes. They were asked to return to the clinic within 24 h of initiating treatment. At this initial visit to the clinic for a treated recurrence, patients were stratified by sex and randomized into the 2 blinded treatment groups and provided with 2 additional days' worth of either valacyclovir (500 mg) or placebo.

Patients were asked to maintain a daily diary to tape data regarding lesion stages (prodromal, macule/papule, vesicle/pustule/ulcer, crust, or healed), pain severity (none, balmy, moderate, or astringent), adverse events, concomitant medications, and compliance with the study drug regimen. Patients were evaluated in the dispensary daily for 6 consecutive days and, if necessary, twice per week thereafter, until all lesions were healed and clinical symptoms were absent. Clinical assessments included review of the diary data and an assessment of lesion stages by the investigator. The investigator was permitted to override patient diary information that were inconsistent with clinical findings.

Patients . Participants in this study were patients aged ⩾18 years who were otherwise healthy and who had a history of ⩾iv episodes of genital or perianal HSV outbreaks in the previous year or 2 episodes in the previous vi months. Confirmation of genital HSV infection was required for written report entry. Confirmation could be done by means of culture, direct antigen detection tests, Tzanck smears, immunofluorescence assays, or be means of a written confirmation past a primary-care doctor. Patients who received suppressive therapy with acyclovir during the 12 months before the report were eligible if they had experienced ⩾1 recurrence inside 3 months after discontinuation of therapy and within 3 months before study entry.

Patients were excluded if they were currently receiving probenecid, had received systemic antiviral treatment in the seven days earlier the beginning dose of the study drug, or had received an investigational drug or immunomodulatory handling in the 30 days before receiving the written report drug. Immunocompromised patients, those with known HIV infection, and those with renal damage (creatinine clearance, ⩽30 mL/min) or hepatic impairment (⩾five-fold increase in alanine transaminase level above the normal upper limit) were also excluded from the written report, equally were persons with a history of hypersensitivity to acyclovir. Other patients excluded from the study were pregnant women, nursing mothers, and sexually active women of childbearing age who were not using an constructive and acceptable method of contraception (i.e., oral contraceptives, diaphragm, condoms, or an intrauterine device).

Efficacy end points . The main end signal of the study was the time to lesion healing, which was measured as the number of days from initiation of therapy to reepithelialization of all lesions. Patients whose lesions aborted or who had clinical symptoms but who did non develop lesions were excluded from the analysis of the main end point.

The secondary stop point of this study was duration of pain, measured as the number of days from initiation of treatment or starting time of pain or discomfort (whichever was later) to the consummate cessation of pain. Other secondary end points included length of the episode and the occurrence of aborted lesions. The length of episode was measured as the number of days from initiation of treatment to complete resolution of all signs and symptoms. All patients, including those with aborted lesions, were included in this analysis. Patients whose lesions aborted were defined as those whose lesions did not progress beyond the macule/papule stag, or every bit those who had clinical symptoms, such as pain, only who did not develop lesions.

Statistical analysis . The intent-to-treat population was divers every bit all randomized patients. It was presumed that ∼30% of treated patients would not develop lesions and, thus, would not be included in the analysis of the primary cease point (i.e., time to lesion healing).

The distributions of times to lesion healing, cessation of pain, and cessation of all symptoms and signs were estimated past the Kaplan-Meier production-limit method. Equivalence in fourth dimension to lesion healing, duration of pain, and length of episode was assessed by a 95% CI for the Hodges-Lehman judge of the treatment difference. A difference of <20% from the median time to event for the 5-mean solar day regimen was not considered clinically significant. The 400 treated patients per report grouping provided µ80% power to establish equivalence.

Adventure ratios and 95% CIs were calculated for each time-to-issue end signal by apply of Cox's proportional hazard models, controlling for the patients' sex and the analysis heart. The validity of the proportional hazard model (the adventure ratio did not change with fourth dimension) was checked by plotting the log of the negative log of the survival distributions confronting time. The Cochran-Mantel-Haenszel test was used to examination for handling differences in proportions of patients with aborted lesions, adjusting for the patients' sex and analysis center.

Results

A total of 1170 patients were enrolled in the written report, of whom 800 were randomized to receive the 5-day regimen of valacyclovir (398 patients) or the three-mean solar day regimen of valacyclovir followed by placebo on days four and 5 of treatment (402 patients). The majority of the 370 patients enrolled but not randomized did not experience a genital herpes recurrence during the study menses. Of those randomized, 362 (91%) of 398 patients in the 5-day grouping and 359 (89%) of 402 patients in the 3-twenty-four hours grouping completed the report (figure 1). In each treatment grouping, the majority of patients who did not complete the written report (31 patients in the 5-24-hour interval grouping and 35 patients in the 3-day group) discontinued the study equally a result of a protocol violation. The other persons who did not complete the written report did not return for follow-up visits or voluntarily withdrew from participation.

Demographic and disease characteristics of randomized patients are presented in tabular array one. Compliance with dosing was high: 99% of patients were reported to have connected use of the study medication until the end of the dosing menstruum.

Table 1

Demographics and disease characteristics of randomized patients in a comparative study of three- and v-day regimens of valacyclovir for the episodic treatment of genital herpes.

Efficacy . In the intent-to-care for assay, the median time to lesion healing (table 2) was 4.vii days in the valacyclovir 5-twenty-four hour period group (292 developed lesions) and iv.4 days in the 3-24-hour interval group (299 developed lesions). The Kaplan-Meier plot for lesion healing is illustrated in figure ii. No significant differences in fourth dimension to lesion healing were noted between treatment groups by either method of assay.

Tabular array 2

Median time to event efficacy stop points, with Hodges-Lehman estimates of handling differences and 95% CIs for differences, in a comparative study of 3- and v-twenty-four hours regimens of valacyclovir for the episodic treatment of genital herpes.

Figure 2

Time to lesion healing in a comparative study of three- and 5-twenty-four hours regimens of valacyclovir for the episodic treatment of genital herpes. Hazard ratio, 0.95; 95% CI, 0.81–one.13; P = .59.

The elapsing of hurting and length of episodes were similar in both treatment groups, with no pregnant differences between persons who received the five-solar day and 3-day dosing regimens for either end point (table 2). To satisfy the proportional run a risk assumption, the patients' sex was included in the Cox model every bit a stratification variable for duration of pain and every bit a covariate for length of episode. In men, the median elapsing of hurting was 2.0 days for the valacyclovir 5-24-hour interval group and two.4 days for the valacyclovir 3-day group. The difference in duration of pain was non statistically significant (P = .2563). Because the 95% CI is 20% of the 5-day group'due south median duration of pain, the 2 regimens are considered to be equivalent. Women experienced a longer duration of hurting, with a median duration of ii.nine days for the valacyclovir 5-day group and 3.0 days for the valacyclovir iii-day group. (P = .0773; table 3). For length of episode, the issue of the patients' sex in the Cox proportional adventure model was statistically significant (adventure ratio, 0.81; 95% confidence limits, 0.70, 0.95).

Table 3

Median duration of pain for persons enrolled in a comparative study of iii- and 5-twenty-four hours regimens of valacyclovir for the episodic handling of genital herpes.

Prevention of lesion progression beyond the macule/papule phase (i.e., progression to aborted lesions) was reported past ∼26% of patients. No differences were detected between the valacyclovir 5-day and valacyclovir 3-day handling groups (26.half dozen% vs. 25.four%, respectively), every bit shown past an RR of one.04 and 95% confidence limits of 0.83 and 1.32.

Prophylactic . Adverse events that occurred during the study catamenia were similar between handling groups. The most common agin events reported in the 5- and iii-day treatment groups were headache (in 10% of patients), nausea (in four%), diarrhea (in 4% and 2%, respectively), and fatigue (in 1% and 2%, respectively).

Discussion

The results of this study indicate that a shorter iii-24-hour interval course of valacyclovir is as effective as a five-solar day course for the episodic treatment of recurrent genital herpes, with median durations to result end points similar to those for trials described elsewhere [v–7]. The previously recommended v-24-hour interval valacyclovir treatment regimen is based on the results of two controlled trials in immunocompetent patients with recurrent genital canker [five, 6]. The clinical footing of testing a 3-24-hour interval valacyclovir regimen for episodic treatment of recurrent genital canker was the previous viral shedding data from a study of 5-24-hour interval courses of valacyclovir (500 mg b.i.d.) [5]. For HSV culture–positive patients who received a 5-day regimen of valacyclovir, the median fourth dimension to cessation of viral shedding was 2 days. Thus, it was theorized that maximum event of valacyclovir on HSV is doable within the first three days of treatment, which is consistent with the mode of activeness of acyclovir in inhibiting virus replication. Virologic evidence of iii- and 5-24-hour interval equivalence can be inferred on the footing of a similar trial in Europe [8], in which 531 patients with recurrent genital herpes were randomized to receive valacyclovir (500 mg b.i.d.) for either 3 or 5 days. The median times to abeyance of viral shedding for patients with a positive HSV culture result immediately before starting treatment for 3 or 5 days were like (1.7 vs. one.8 days, respectively), which replicates before findings [5].

The results of our study demonstrate that a shorter 3-day handling class with valacyclovir is clinically equivalent to a 5-day course for the episodic treatment of recurrent genital canker. In this written report, a trend toward longer duration of pain was seen in men who received the shorter course of therapy. Although virtually statistically meaning, the magnitude of the departure is small and almost certainly non clinically relevant. In clinical situations in which patients exhibit hurting as well every bit other clinical testify of delayed healing after receiving iii days of therapy, an additional 2 days of therapy may prove to be benign. In addition to the convenience of a shorter course of handling, a 3-solar day regimen has the benefit of a 40% decrease in the amount of drug and may result in a forty% reduction in the drug price of a prescription. Whether the patient or insurance company sees a full 40% reduction in prescription price would involve tablet quantity, prescription fees, and other aspects of filling a prescription.

Study Grouping Members

Participating investigators included the post-obit persons: Fred Aoki, Winnipeg, Manitoba; Karl Beutner, Vallejo, CA; Ronald Castellanos, Fort Myers, FL; Robert Cesarec, Wauwatosa, WI; Scott Clark, Longmont, CO; Loretta Davis, Augusta, GA; Francisco Diaz-Mitoma, Ottawa, Ontario; Frank Dunlap, Tucson, AZ; Kenneth Fife, Indianapolis, IN; Gumaro Garza, McAllen, TX; Harold Guy, San Diego, CA; David Haase, Halifax, Nova Scotia; H. Hunter Handsfield, Seattle, WA; John Imig, Bedrock, CO; Terry Jones, Bryan, TX; Terrance Kurtz, Des Moines, IA; William Lang, San Francisco, CA; Marking Lebwohl, New York, NY; Peter Leone, Raleigh, NC; Lisa Marr, Portland, OR; Kim Papp, Waterloo, Ontario; John Pickens, Memphis, TN; Gerald Pierone, Vero Beach, FL; Michel Poisson, Montreal, Quebec; Donald Poretz, Annandale, VA; Jerold Powers, Scottsdale, AZ; Kuljeet Rai, San Jose, CA; Howard Reisman, Roswell, GA; Michael Reitano, New York, NY; Dennis Riff, Anaheim, CA; Jason Rivers, Vancouver, British Columbia; Barbara Romanowski, Edmonton, Alberta; Jeff Rosen, Coral Gables, FL; Bob Roth, Chico, CA; Stephen Sacks, Vancouver, British Columbia; John Sellors, Hamilton, Ontario; Steve Precipitous, Nashville, TN; Neil Shear, Toronto, Ontario; Gary Sibbald, Mississauga, Ontario; Susan Skalsky, E Brunswick, NJ; Malcolm Sperling, Fountain Valley, CA; Claude Saint Pierre, Sherbrooke, Quebec; Dale Terrell, Saint Louis, MO; Sylvie Trottier, Sainte Foy, Quebec; Stephen Tyring, Nassau Bay, TX; Anna Wald, Seattle, WA; David Whiting, Dallas, TX; and Kurt Williams, Saskatoon, Saskatchewan.

Acknowledgments

Nosotros thank Mike Colopy for performing statistical analysis.

References

, , , et al.

Canker simplex virus type two in the United States, 1976 to 1994

N Engl J Med

1997

, vol.

337

(pg.

1105

eleven

)

, , , et al.

Impact of suppressive antiviral therapy on the health related quality of life of patients with recurrent genital herpes infection

Sex Transm Infect

1999

, vol.

(pg.

398

402

)

, , .

Recurrence rates in genital canker after symptomatic commencement-episode infection

Ann Intern Med

1994

, vol.

121

(pg.

847

)

, .

Herpes simplex type 2 infections—an update

Adv Intern Med

2000

, vol.

(pg.

175

208

)

, , , et al.

A large-calibration, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic handling of recurrent canker genitalis

Arch Intern Med

1996

, vol.

156

(pg.

1729

)

, , , et al.

A randomized placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital canker infections

Arch Dermatol

1998

, vol.

134

(pg.

185

)

, , , et al.

Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double-blind clinical trial

Genitourin Med

1997

, vol.

(pg.

110

)

, , .

Virological bear witness that valaciclovir aborts genital herpes simplex virus lesions [abstruse 106]. In: Plan and abstracts of STIs at the Millennium: Past, Nowadays, and Future (Baltimore)

Medical Order for the Study of Venereal Diseases/American Sexually Transmitted Diseases Association (MSSVD/ASTDA)

2000

, vol.

Members of the study group are listed at the end of the text.

Financial back up: Glaxo Wellcome (protocol HS2A4004).

Presented in part: Eighth International Congress on Infectious Diseases, Boston, May 1998 (abstract 22.012).

millerlamonegre.blogspot.com

Source: https://academic.oup.com/cid/article/34/7/958/316764

Miller Lamonegre

How Many Valtrex Can I Take in One Day

Abstract

Patients and Methods

Results

Discussion

Study Grouping Members

Acknowledgments

References

Post a Comment for "How Many Valtrex Can I Take in One Day"