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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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Routes of administration | By mouth |
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Pharmacokinetic data | |
Bioavailability | 60% |
Protein binding | 1–2% |
Metabolism | Hydrolysed to ganciclovir |
Elimination half-life | 4 hours |
Excretion | Kidney |
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Chemical and physical data | |
Formula | C14H22N6O5 |
Molar mass | 354.367 g·mol−1 |
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Valganciclovir, sold under the brand name Valcyte among others, is an antiviral medication used to treat cytomegalovirus (CMV) infection in those with HIV/AIDS or following organ 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 include abdominal pain, headaches, trouble sleeping, nausea, fever, and low blood cell counts. [3] Other side effects may include infertility and kidney problems. [3] When used during pregnancy, it causes birth defects in some animals. [3] Valganciclovir is the L-valyl ester of ganciclovir and works when broken down into ganciclovir by the intestine and liver. [3]
Valganciclovir was approved for medical use in 2001. [4] It is on the World Health Organization's List of Essential Medicines. [5] In 2017, a generic version was approved. [6]
Valganciclovir is commonly used for treatment of cytomegalovirus (CMV) retinitis (eye infection may cause blindness) in people who have acquired immunodeficiency 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, and retinal detachment. [2]
Of note, the FDA issued several black box warnings concerning potential severe toxicities. These include:
While not studied in people, it can be assumed that interactions will be similar as those with ganciclovir, since valganciclovir is converted into ganciclovir in the body. [2] Zidovudine may decrease the concentration of ganciclovir, and together the drugs can cause anemia and neutropenia. [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 both mycophenolate mofetil and ganciclovir concentrations when both drugs are taken together. [2] Ganciclovir can also increase the concentration of didanosine. [2]
Valganciclovir is a prodrug for ganciclovir, 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 incomplete deoxyribose 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 by esterases in the intestines and the liver, leaving ganciclovir to be absorbed by the virus-infected cells. [8]
Ganciclovir is first phosphorylated 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 or herpes 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 of deoxyguanosine 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 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. [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 the Indian Patent Office [14] in 2010, although Roche may appeal the rejection.[ needs update ]
Also known as Cymeval, Valcyt, Valixa, Darilin, Rovalcyte, Patheon, and Syntex. [15]
Aciclovir, also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following transplant and severe complications of Epstein–Barr virus infection. It can be taken by mouth, applied as a cream, or injected.
Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet.
Valaciclovir, also spelled valacyclovir, is an antiviral medication used to treat outbreaks of herpes simplex or herpes zoster (shingles). It is also used to prevent cytomegalovirus following a kidney transplant in high risk cases. It is taken by mouth.
Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure. It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir, and elvitegravir/cobicistat/emtricitabine/tenofovir. It does not cure HIV/AIDS or hepatitis B. It is available by mouth as a tablet or powder.
Cidofovir, brand name Vistide, is a topical or injectable antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis in people with AIDS.
Entecavir, sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus infection. In those with both HIV/AIDS and hepatitis B virus antiretroviral medication should also be used. Entecavir is taken by mouth as a tablet or solution.
Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections.
Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, including 15-40% of those with AIDS.
Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate analog DNA polymerase inhibitor. Foscarnet is the conjugate base of a chemical compound with the formula HO2CPO3H2 (Trisodium phosphonoformate).
Penciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections. It is a nucleoside analogue which exhibits low toxicity and good selectivity. Because penciclovir is absorbed poorly when given orally it is more often used as a topical treatment. It is the active ingredient in the cold sore medications Denavir, Vectavir and Fenivir. Famciclovir is a prodrug of penciclovir with improved oral bioavailability.
Human betaherpesvirus 5, also called human cytomegalovirus (HCMV,HHV-5), is a species of virus in the genus Cytomegalovirus, which in turn is a member of the viral family known as Herpesviridae or herpesviruses. It is also commonly called CMV. Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals. CMV is a double-stranded DNA virus.
Maribavir, sold under the brand name Livtencity, is an antiviral medication that is used to treat post-transplant cytomegalovirus (CMV). Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.
Blueberry muffin baby, also known as extramedullary hematopoiesis, describes a newborn baby with multiple purpura, associated with several non-cancerous and cancerous conditions in which extra blood is produced in the skin. The bumps range from 1-7 mm, do not blanch and have a tendency to occur on the head, neck and trunk. They often fade by three to six weeks after birth, leaving brownish marks. When due to a cancer, the bumps tend to be fewer, firmer and larger.
Cytomegalovirus esophagitis is a form of esophagitis associated with cytomegalovirus. Symptoms include dysphagia, upper abdominal pain, diarrhea, nausea, vomiting, and sometimes hematemesis. This condition occurs in the setting of patients with a weakened immune system who are susceptible to both infections by CMV and the manifestation of symptoms. A large majority of patient that have CMV Esophagitis are diagnosed with HIV. Another significant segment of the population have weakened immune systems through transplant surgery, diabetes, or due to medication. Diagnosis is done primarily by endoscopy with biopsy, as CMV Esophagitis has a distinctive pathology pattern of linear ulcers.
Cytomegalovirus colitis is an inflammation of the colon.
Letermovir is an antiviral drug for the treatment of cytomegalovirus (CMV) infections. It has been tested in CMV infected patients with allogeneic stem cell transplants and may also be useful for other patients with a compromised immune system such as those with organ transplants or HIV infections. The drug was initially developed by the anti-infective division at Bayer, which became AiCuris Anti-infective Cures AG through a spin-out and progressed the development to end of Phase 2 before the project was sold to Merck & Co for Phase 3 development and approval.
Brincidofovir, sold under the brand name Tembexa, is an antiviral drug used to treat smallpox. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.
Lobucavir is an antiviral drug that shows broad-spectrum activity against herpesviruses, hepatitis B and other hepadnaviruses, HIV/AIDS and cytomegalovirus. It initially demonstrated positive results in human clinical trials against hepatitis B with minimal adverse effects but was discontinued from further development following the discovery of increased risk of cancer associated with long-term use in mice. Although this carcinogenic risk is present in other antiviral drugs, such as zidovudine and ganciclovir that have been approved for clinical use, development was halted by Bristol-Myers Squibb, its manufacturer.
Cecilia Söderberg-Nauclér, born 1967, is a Swedish immunologist who is Professor of Microbial Pathogenesis at the Karolinska Institute. In 2013, she demonstrated that a simple antiviral could improve the life expectancy of glioblastoma disease. During the COVID-19 pandemic in Sweden, Söderberg-Nauclér on several occasions strongly criticized the Swedish response to SARS-CoV-2, claiming that they were leading the country into a catastrophe, and demanded that the Swedish state epidemiologist should resign.
GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 were both found to be effective in vitro against feline coronavirus strains responsible for feline infectious peritonitis (FIP), a lethal systemic disease affecting domestic cats. Remdesivir was never tested in cats, but GS-441524 has been found to be effective treatment for FIP.