Valtrex References

10: Transplantation. 2005 Feb 15;79(3):317-24.

valacyclovir - Valtrex for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection.

Reischig T, Jindra P, Mares J, Cechura M, Svecova M, Hes O, Opatrny K Jr, Treska V.

Department of Internal Medicine I, Charles University Hospital, Pilsen, Czech Republic.

BACKGROUND: Both oral ganciclovir and valacyclovir - Valtrex decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir - Valtrex has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir - Valtrex in the prophylaxis of CMV disease after renal transplantation. METHODS: A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir - Valtrex (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy. RESULTS: No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively. CONCLUSIONS: valacyclovir - Valtrex and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. valacyclovir - Valtrex is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy.

11: Expert Opin Investig Drugs. 2005 Feb;14(2):135-61.

Agents and strategies in development for improved management of herpes simplex virus infection and disease.

Kleymann G.

The quiet pandemic of herpes simplex virus (HSV) infections has plagued humanity since ancient times, causing mucocutaneous infection such as herpes labialis and herpes genitalis. Disease symptoms often interfere with every-day activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immuno-compromised patient population. After infection the virus persists for life in neurons of the host in a latent form, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. So far, vaccines, ILs, IFNs, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or non-specific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir - Valtrex, penciclovir and famciclovir as the first choice of treatment. The recently discovered inhibitors of the HSV helicase-primase are the most potent development candidates today. These antiviral agents act by a novel mechanism of action and display low resistance rates in vitro and superior efficacy in animal models. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease.

12: Skin Therapy Lett. 2005 Feb;10(1):1-4.

valacyclovir - Valtrex for the management of herpes viral infections.

Chakrabarty A, Anderson NJ, Beutner R, Tyring SK.

Solano Research, Davis, CA, USA.

The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types 1-3, they establish permanent residence within our nervous system and reactivate during periods of stress, trauma, and/or other precipitating factors. To date, there is no cure for herpes viral infections but antivirals can attenuate the symptoms and duration of episodic outbreaks. Prophylactic therapy can suppress recurrences. The first antiviral with selective activity against virus-infected cells is considered to be acyclovir. Our article will highlight the clinical indications of the current generation, valacyclovir - Valtrex, which is a prodrug of acyclovir. We consider valacyclovir - Valtrex as a second-generation antiviral, having taken into account the initial selectivity and safety profile of its progenitor, acyclovir.

13: Rev Med Suisse. 2005 Jan 12;1(2):134, 136-9.

Infectious diseases in the ambulatory care setting

Zanetti G.

Service des maladies infectieuses, et Division autonome de medecine, preventive hospitaliere, CHUV, 1011 Lausanne. Giorgio.Zanetti@chuv.hospvd.ch

Hot topics in infectiology mainly include emerging diseases, particularly those caused by antibiotic-resistant bacteria. Prudent use of antibiotics is therefore mandatory. Among new classes of antibiotics for outpatients therapy are linezolid (for resistant, Gram-positive bacterial, and telithromycine (for treatment of respiratory tract infections). This review also addresses the following topics: short course of doxycycline for treatment of early Lyme disease in adults, recommendations against the widespread use of fluoroquinolones for community-acquired pneumonia, prevention of Herpes simplex type 2 transmission with valacyclovir - Valtrex, management of acute, symptomatic hepatitis C, and the absence of an established link between vaccines and chronic diseases.

14: Cutis. 2005 Jan;75(1):33-6.

A case of Kaposi varicelliform eruption in Darier-White disease.

Donnelly AA, Butler R, Miller CH.

Branch Medical Clinic Everett, Washington, USA.

Darier-White disease (DWD), otherwise known as keratosis follicularis, is a rare disorder of keratinization of the epidermis, mucous membranes, and nails. It is autosomal dominant in transmission. Patients with DWD are prone to frequent superinfection including the rare complication of Kaposi varicelliform eruption. It is postulated that a defect in cell-mediated immunity may contribute to this predisposition.

15: Med Monatsschr Pharm. 2005 Jan;28(1):30.

How contagious is herpes?

Farber I.

Institut fur Virologie und Antivirale Therapie, Universitatsklinikum Jena, Winzerlaer Str. 10, 07740 Jena.

16: Anesth Analg. 2004 Dec;99(6):1760-2, table of contents.

Epidural blood patch and acute varicella.

Martin DP, Bergman BD, Berger IH.

Department of Anesthesiology, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905, USA.

We present the case of a 38-yr-old woman who required an epidural blood patch in the context of acute varicella (chickenpox). The unique risks in this case include the possible triggering of central nervous system complications after the introduction of viremic blood into the epidural or intrathecal space. However, the risk was believed to be acceptable because the patient was receiving antiviral coverage. She enjoyed complete relief of her headache but experienced transient back and leg pain. Leptomeningeal irritation caused by acute varicella infection may put patients at increased risk for pain after epidural blood patch.

17: Clin Infect Dis. 2004 Nov 1;39 Suppl 5:S258-66.

Efficacy and safety of valacyclovir - Valtrex for the suppression and episodic treatment of herpes simplex virus in patients with HIV.

Warren T, Harris J, Brennan CA.

Westover Heights Clinic, 2330 NW Flanders, Ste. 207, Portland, OR 97210, USA.

Three randomized controlled trials of valacyclovir - Valtrex for the management of recurrences of genital herpes in HIV-infected persons were conducted between 1991 and 2002. One study evaluated episodic therapy for the treatment of genital herpes, and 2 studies evaluated continuous suppressive therapy. valacyclovir - Valtrex at 1000 mg twice daily for 5 days was comparable to acyclovir at 200 mg 5 times daily in accelerating healing of a single episode of genital herpes (hazard ratio, 1.0; 95% confidence interval [CI], 0.8-1.2; P=.89). valacyclovir - Valtrex at 500 mg twice daily was effective in preventing or delaying recurrences of genital herpes compared with placebo (hazard ratio, 0.20; 95% CI, 0.13-0.30; P<.001) and with valacyclovir - Valtrex at 1000 mg once daily (hazard ratio, 0.56; 95% CI, 0.40-0.80; P=.001), in 6-month and 48-week studies, respectively. The safety profile of valacyclovir - Valtrex was similar to that of acyclovir. valacyclovir - Valtrex is well tolerated, safe, and effective for the treatment and suppression of recurrent genital herpes in human immunodeficiency virus-infected persons.

18: J Biopharm Stat. 2004 Nov;14(4):869-80.

Assessing bioequivalence using genomic data.

Chow SC, Shao J, Li L.

National Health Research Institutes, Taiwan.

For approval of a generic drug product, the assessment of bioequivalence in drug absorption is usually considered as a surrogate for evaluation of drug efficacy and safety in clinical studies. For some drug products, the United States Food and Drug Administration indicates that the assessment of similarity between dissolution profiles may be used as a surrogate for assessment of bioequivalence. Along this line, we propose assessing bioequivalence using genomic data collected from the same individuals, assuming that there is an established relationship between pharmacokinetic and genomic data. Because there may be a bias in the prediction of pharmacokinetic data using genomic data and the variations in these two types of data are different, we propose to assess bioequivalence based on sensitivity analysis of prediction bias and variation difference within some predetermined limits. Our methods are derived for average, population, and individual bioequivalence.

19: J Fam Pract. 2004 Nov;53(11):864-7.

Steroid is effective for vestibular neuritis, valacyclovir - Valtrex is not.

Methylprednisolone, starting at 100 mg/d and tapering to 10 mg over 3 weeks, is an effective treatment for vestibular neuritis. valacyclovir - Valtrex (Valtrex) is not effective.

20: J Pharmacol Exp Ther. 2004 Nov;311(2):659-67. Epub 2004 Jun 29.

Pharmacokinetics of novel dipeptide ester prodrugs of acyclovir after oral administration: intestinal absorption and liver metabolism.

Anand BS, Katragadda S, Mitra AK.

School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA.

The amino acid prodrug of acyclovir (ACV), valacyclovir - Valtrex (VACV), is an effective antiherpetic drug. Systemic availability of ACV in humans is 3 to 5 times higher after oral administration of VACV. Enhanced bioavailability of VACV has been attributed to its carrier-mediated intestinal absorption via hPEPT1 peptide transporter followed by rapid and complete conversion to ACV. An earlier report suggested that the dipeptide ester prodrugs of ACV possess high affinity toward the intestinal oligopeptide transporter hPEPT1 and therefore seem to be promising candidates in the treatment of oral herpes virus infections. In the present study, we have examined the bioavailability of a series of dipeptide prodrugs of ACV after oral administration in Sprague-Dawley rats with cannulated jugular and portal veins. The area under plasma-concentration time curves expressed as minutes microgram milliliter(-1) for total concentration of VACV (208.4 +/- 41.2), and the dipeptide prodrugs Gly-Val-ACV (GVACV) (416.1 +/- 140.9), Val-Val-ACV (VVACV) (147.7 +/- 89.3), and Val-Tyr-ACV (VYACV) (180.7 +/- 81.2) were significantly higher than that of ACV (21.2 +/- 5.2) upon intestinal absorption. Interestingly, the bioavailability of ACV after administration of GVACV was approximately 2-fold higher than VACV. There was significant metabolism by hepatic first pass effect of the dipeptide prodrugs as evident by the higher levels of ACV obtained after systemic absorption compared with intestinal absorption of GVACV and VVACV. The dipeptide prodrugs of ACV exhibited higher systemic availability of regenerated ACV upon oral administration and thus seem to be promising drug candidates in treatment of genital herpes infections.