Valganciclovir
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| Systematic (IUPAC) name |
|
2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]-3-hydroxypropyl-(2S)-2-amino-3-methylbutanoate
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| Clinical data |
| Trade names |
Valcyte |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a605021 |
Pregnancy
category |
- US: C (Risk not ruled out)
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Routes of
administration |
Oral |
| Legal status |
| Legal status |
- UK: POM (Prescription only)
- US: ℞-only
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| Pharmacokinetic data |
| Bioavailability |
60% |
| Protein binding |
1–2% |
| Metabolism |
Hydrolysed to ganciclovir |
| Biological half-life |
4 hours |
| Excretion |
Renal |
| Identifiers |
| CAS Number |
175865-59-5 N |
| ATC code |
J05AB14 (WHO) |
| PubChem |
CID 64147 |
| IUPHAR/BPS |
4716 |
| DrugBank |
DB01610 Y |
| ChemSpider |
57721 Y |
| UNII |
GCU97FKN3R Y |
| ChEMBL |
CHEMBL1201314 N |
| NIAID ChemDB |
032967 |
| Chemical data |
| Formula |
C14H22N6O5 |
| Molar mass |
354.362 g/mol |
SMILES
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O=C(OCC(OCn1c2N\C(=N/C(=O)c2nc1)N)CO)[C@@H](N)C(C)C
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InChI
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InChI=1S/C14H22N6O5/c1-7(2)9(15)13(23)24-4-8(3-21)25-6-20-5-17-10-11(20)18-14(16)19-12(10)22/h5,7-9,21H,3-4,6,15H2,1-2H3,(H3,16,18,19,22)/t8?,9-/m0/s1 Y
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Key:WPVFJKSGQUFQAP-GKAPJAKFSA-N Y
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| NY (what is this?) (verify) |
Valganciclovir (Valcyte, manufactured by Hoffmann–La Roche, and also known as Cymeval, Valcyt, Valixa, Darilin, Rovalcyte, Patheon, and Syntex[1]) is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir.[2] After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[3]
Contents
- 1 Administration
- 2 Pharmacokinetics
- 3 Side effects
- 4 Alternative uses
- 5 Price and patent status
- 6 References
Administration
Orally, available in 450 mg tablets. For patients who have received a transplant, the recommended dose is 900 mg once daily, starting within 10 days of transplantation and continuing for 6 months post transplantation. HIV patients might initially need to take the dose 900 mg twice daily for the first 3 weeks.[4]
Pharmacokinetics
- Oral bioavailability is approximately 60%. Fatty foods significantly increase the bioavailability and the peak level in the serum.
- It takes about 2 hours to reach maximum concentrations in the serum.
- Valganciclovir is eliminated as ganciclovir in the urine, with a half-life of about 4 hours in people with normal kidney function.
- The mechanism of this drug is activation via a viral protein kinase HCMV UL97 and subsequent phosphorylation by cellular kinases. The phosphotransferase enzyme can likewise activate valganciclovir.
Side effects
- Blood: neutropenia, anemia, low platelets. Myelosuppression is one of the main side effects that may limit prolonged use of valganciclovir.
- Gastrointestinal: diarrhea, nausea, vomiting, abdominal pain.
- Central nervous system: fever, headache, insomnia, paresthesia, and peripheral neuropathy.
- Ocular: retinal detachment
Alternative uses
It has been proposed that valganciclovir could be used in the treatment of chronic fatigue syndrome. In an initial, open-label trial, 12 patients with elevated antibody titers to human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) and who had suffered with neurocognitive symptoms and debilitating fatigue consistent with chronic fatigue syndrome were administered valganciclovir for six months. "Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activities," accompanied in the same patients by falls in antibody titers to both viruses.[5] The results of a follow-up double-blind, placebo-controlled study of 30 patients[6] were ambiguous: overall scores on the Multidimensional Fatigue Inventory (MFS-20) were nominally higher in valganciclovir-treated patients vs. placebo, but the difference was not statistically significant; moreover, there were no differences in antibody titers between the two groups. However, in a secondary analysis, differences in several specific subscales of the score were significantly different between valganciclovir treatment and placebo.[6]
Continuous treatment of cytomegalovirus infections with valganciclovir in patients with glioblastoma multiforme has shown to increase 2-year survival to 90% in a trial of 25 patients.[7]
In a free preview of a Wednesday, March 4, 2015 online journal article from the New England Journal of Medicine, it was stated that,: "The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time." ... "Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.)."[8]
Price and patent status
Roche's Valcyte is protected by patent. However a generic version manufactured by Japanese-owned Indian company Daiichi-Ranbaxy was found by the District Court of New Jersey, USA not to infringe Roche's patent.[9] In November 2014, FDA approved generics by two manufacturers,[10] Endo and Dr. Reddy's. Endo's generic is already available throughout major pharmacies in the US.
The price of a four-month course of valganciclovir from Roche is about US$8,500 in high-income countries, $6,000 in India. However, the valganciclovir patent was rejected by the Indian Patent Office[11] in 2010, although Roche may appeal the rejection.
References
- ^ Drugs.about list of names for valganciclovir
- ^ Sugawara M, Huang W, Fei YJ, et al. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000;89(6):781-9.
- ^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
- ^ electronic Medicines Compendium
- ^ Kogelnik AM; Loomis K; Hoegh-Petersen M; Rosso F; Hischier C; Montoya JG (Dec 2006). "Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue.". J Clin Virol 37 (Suppl 1): S33–8. doi:10.1016/S1386-6532(06)70009-9. PMID 17276366.
- ^ a b Montoya JG; Kogelnik AM; Bhangoo M; Lunn MR; Flamand L; Merrihew LE; Watt T; Kubo JT; Paik J; Desai M (Dec 2013). "Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome". J Med Virol 85 (12): 2101–9. doi:10.1002/jmv.23713. PMID 23959519.
- ^ Survival in Patients with Glioblastoma Receiving Valganciclovir
- ^ Kimberlin, DW, Jester, PM, Sánchez, PJ, Ahmed, A, Arav-Boger, R, Michaels, MG, for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group; et al. (March 5, 2015). "Valganciclovir for Symptomatic Congenital Cytomegalovirus Disease". New England Journal of Medicine. doi:10.1056/NEJMoa1404599. Retrieved March 4, 2015.
- ^ US Court rules Ranbaxy's generic valganciclovir does not infringe Roche's Valcyte patent
- ^ http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/drugandbiologicapprovalreports/andagenericdrugapprovals/ucm422394.htm.
- ^ Valganciclovir rejected by the Indian Patent Office
- Kogelnik AM et al. Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. J Clin Virol. 2006;37(S1):S33-S38.
- Paltiel AD et al. Preevaluation of clinical trial data: the case of preemptive cytomegalovirus therapy in patients with human immunodeficiency virus. Clin Infect Dis. 2001;32(5):783-93.
- Pescovitz MD et al. Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother. 2000;44(10):2811-5.
- Reusser P. Antiviral therapy: current options and challenges. Schweiz Med Wochenschr. 2000;130(4):101-12.
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DNA virus antivirals (primarily J05, also S01AD and D06BB)
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| Baltimore I |
| Herpesvirus |
DNA-synthesis
inhibitor |
| TK activated |
| Purine analogue |
- guanine (Aciclovir#/Valaciclovir
- Ganciclovir/Valganciclovir
- Penciclovir/Famciclovir)
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| Pyrimidine analogue |
- uridine (Idoxuridine
- Trifluridine (+tipiracil)
- Edoxudine)
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| Not TK activated |
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| Other |
- Docosanol
- early protein (Fomivirsen)
- Tromantadine
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| HPV/MC |
- Imiquimod/Resiquimod
- Podophyllotoxin
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| Vaccinia |
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| Poxviridae |
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| Hepatitis B (VII) |
- Nucleoside analogues/NARTIs: Entecavir
- Lamivudine
- Telbivudine
- Clevudine
- Nucleotide analogues/NtRTIs: Adefovir
- Tenofovir
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| Multiple/general |
| Nucleic acid inhibitors |
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| Interferon |
- Interferon alfa 2b
- Peginterferon alfa-2a
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| Multiple/unknown |
- Ribavirin#/Taribavirin†
- Moroxydine
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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