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| Clinical data | |
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| Trade names | Valcyte, Valcip, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a605021 |
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| Pregnancy category | |
| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 60% |
| Protein binding | 1–2% |
| Metabolism | Hydrolysed toganciclovir |
| Eliminationhalf-life | 4 hours |
| Excretion | Kidney |
| Identifiers | |
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| DrugBank |
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| UNII | |
| KEGG | |
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| NIAID ChemDB | |
| PDB ligand | |
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| Chemical and physical data | |
| Formula | C14H22N6O5 |
| Molar mass | 354.367 g·mol−1 |
| 3D model (JSmol) | |
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Valganciclovir, sold under the brand nameValcyte among others, is anantiviral medication used to treatcytomegalovirus (CMV) infection in those withHIV/AIDS or followingorgan transplant.[3] It is often used long term as it only suppresses rather than cures the infection.[3] Valganciclovir is taken by mouth.[3]
Common side effects includeabdominal pain, headaches, trouble sleeping, nausea, fever, andlow blood cell counts.[3] Other side effects may includeinfertility andkidney problems.[3] When used duringpregnancy, it causes birth defects in some animals.[3] Valganciclovir is theL-valylester ofganciclovir and works when broken down into ganciclovir by theintestine andliver.[3]
Valganciclovir was approved for medical use in 2001.[4] It is on theWorld Health Organization's List of Essential Medicines.[5] In 2017, ageneric version was approved.[6]
Valganciclovir is commonly used for treatment ofcytomegalovirus (CMV)retinitis (eye infection may cause blindness) in people who have acquiredimmunodeficiency syndrome (AIDS).[7] Valganciclovir is also used to prevent cytomegalovirus disease in people who have received a heart, kidney, or kidney-pancreas transplant and who have a chance of getting CMV disease.[7] Overall, valganciclovir works by preventing the spread of CMV disease or slowing the growth of CMV.[citation needed]
Valganciclovir is used for the prevention of CMV disease in people following kidney transplant (4 months to 16 years of age) and heart transplant (1 month to 16 years of age) at high risk.[2]
Valganciclovir is commonly associated with vomiting, abdominal pain, diarrhea, and headache.[2] Other side effects include fever,trouble sleeping,peripheral neuropathy, andretinal detachment.[2]
Of note, the FDA issued severalblack box warnings concerning potential severe toxicities. These include:
While not studied in people, it can be assumed that interactions will be similar as those withganciclovir, since valganciclovir is converted into ganciclovir in the body.[2]Zidovudine may decrease the concentration of ganciclovir, and together the drugs can causeanemia andneutropenia.[2]Probenecid can increase the concentration of ganciclovir, which could increase the chances of ganciclovir toxicity.[2] People with kidney problems could have an increase in bothmycophenolate mofetil and ganciclovir concentrations when both drugs are taken together.[2] Ganciclovir can also increase the concentration ofdidanosine.[2]
Valganciclovir is a prodrug forganciclovir, which is a synthetic analog of 2′-deoxy-guanosine. Its structure is the same as ganciclovir, except for the addition of a L-valyl ester at the 5' end of the incompletedeoxyribose ring. The valine increases both the absorption of the drug in the intestines, as well as the bioavailability of the drug once it is absorbed. The L-valyl ester is cleaved byesterases in the intestines and the liver, leaving ganciclovir to be absorbed by the virus-infected cells.[8]
Ganciclovir is firstphosphorylated to ganciclovir monophosphate by a viral thymidine kinase encoded by the cytomegalovirus (CMV) upon infection.[9] Human cellular kinases further phosphorylate the molecule to create ganciclovir diphosphate, then ganciclovir triphosphate.[9] These kinases are present in 10-fold greater concentrations in CMV orherpes simplex virus (HSV)-infected cells compared to uninfected human cells, allowing ganciclovir triphosphate to concentrate in infected cells.[9]
Ganciclovir triphosphate is a competitive inhibitor ofdeoxyguanosine triphosphate (dGTP).[9] It is incorporated into viral DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. Ganciclovir triphosphate serves as a poor substrate for chain elongation. Once incorporated into viral DNA due to its structure similarity to dGTP, chain termination occurs once a single nucleotide is added to the distal hydroxyl group of the incomplete deoxyribose ring of ganciclovir.[10]
The synthesis of valganciclovir has been reviewed. Many routes use ganciclovir as a starting material.[11]
Roche's Valcyte is protected bypatent. However a generic version manufactured by Japanese-owned Indian companyDaiichi-Ranbaxy was found by theDistrict Court of New Jersey, USA not to infringe Roche's patent.[12]In November 2014, FDA approved generics by two manufacturers.[13]
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 theIndian Patent Office[14] in 2010, although Roche mayappeal the rejection.[needs update]
Also known as Cymeval, Valcyt, Valixa, Darilin, Rovalcyte, Patheon, and Syntex.[15]
