Valganciclovir hydrochloride
[CAS# 175865-59-5]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antiviral drugs
• Name: Valganciclovir hydrochloride
• Synonyms: [2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]-3-hydroxypropyl] (2S)-2-amino-3-methylbutanoate hydrochloride
• Molecular Formula: C₁₄H₂₂N₆O₅^.HCl
• Molecular Weight: 390.83
• CAS Registry Number: 175865-59-5
• EC Number: 641-360-4
• SMILES: CC(C)[C@@H](C(=O)OCC(CO)OCN1C=NC2=C1N=C(NC2=O)N)N.Cl

Properties

• Solubility: 10 mM (DMSO) (Expl.)

Safety Data

• Hazard Symbols: GHS08 Danger
• Hazard Statements: H340-H350-H351-H360-H360fd-H372
• Precautionary Statements: P203-P260-P264-P270-P280-P318-P319-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	1A	H360
Germ cell mutagenicity	Muta.	1A	H340
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Carcinogenicity	Carc.	1A	H350
Carcinogenicity	Carc.	2	H351
Germ cell mutagenicity	Muta.	1B	H340

Discovory and Applicatios

Valganciclovir hydrochloride is an antiviral medication that is primarily used in the treatment and prevention of cytomegalovirus (CMV) infections. It is an ester prodrug of ganciclovir, a well-known antiviral agent that inhibits the replication of CMV by targeting viral DNA polymerase. Valganciclovir hydrochloride itself is not active until it is converted into ganciclovir through hydrolysis in the body, which allows it to exert its therapeutic effects.

The development of valganciclovir hydrochloride followed the recognition that ganciclovir, while effective against CMV, had limitations in terms of its oral bioavailability. Ganciclovir has poor absorption when taken orally, which reduces its clinical usefulness for long-term therapy or prevention of CMV infections. Valganciclovir was introduced as a solution to this problem, as it has better oral bioavailability, allowing for more efficient delivery and reducing the need for intravenous administration.

Valganciclovir hydrochloride is primarily used in patients with weakened immune systems, such as those undergoing organ transplantation, where CMV infections can cause severe complications. It is also employed for the prevention and treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). CMV retinitis is a sight-threatening infection of the retina that can lead to blindness if not properly treated.

The drug is commonly prescribed for the prevention of CMV infection and disease in transplant patients, including those who have received kidney, liver, heart, or bone marrow transplants. It is also indicated for the treatment of CMV disease, particularly in immunocompromised patients. For example, valganciclovir is used in the treatment of CMV infections in HIV-positive individuals, where it helps to prevent or treat CMV-related complications such as retinitis.

Valganciclovir hydrochloride works by inhibiting the replication of CMV through the same mechanism as ganciclovir. After being converted into ganciclovir, the drug is incorporated into the viral DNA during replication, where it causes chain termination, effectively halting the virus's ability to multiply. This mechanism makes valganciclovir a potent agent for controlling CMV infections.

The drug is typically administered orally, though it is also available in an intravenous formulation for patients who cannot take oral medications. The oral form of valganciclovir hydrochloride is often preferred because it is more convenient and allows for outpatient management of patients.

As with other antiviral medications, valganciclovir hydrochloride can cause side effects. The most common adverse effects include gastrointestinal disturbances such as nausea, vomiting, and diarrhea. It can also lead to hematologic side effects, including neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). These side effects may require monitoring of blood counts during treatment. Additionally, valganciclovir hydrochloride can cause renal toxicity, particularly in patients with pre-existing kidney conditions, and dose adjustments may be necessary in such cases.

Valganciclovir hydrochloride is contraindicated in pregnant women due to its potential teratogenic effects, and its use is generally avoided in the first trimester unless absolutely necessary. The drug is also contraindicated in patients with known hypersensitivity to ganciclovir or valganciclovir.

In summary, valganciclovir hydrochloride is an important antiviral medication used to prevent and treat CMV infections in immunocompromised patients, particularly those undergoing organ transplantation or suffering from AIDS. Its superior oral bioavailability compared to ganciclovir has made it a valuable option for the management of CMV-related complications. However, like all medications, it is associated with potential side effects, and careful monitoring is required during treatment.

References

2024. Valacyclovir or valganciclovir for cytomegalovirus prophylaxis: A randomized controlled trial in adult and pediatric kidney transplant recipients. *Journal of Clinical Virology*, 168.
DOI: 10.1016/j.jcv.2024.105678

2024. Cytomegalovirus Antiviral Resistance Among Kidney Transplant Recipients in a Phase 3 Trial of Letermovir vs Valganciclovir Prophylaxis. *The Journal of Infectious Diseases*, 230(1).
DOI: 10.1093/infdis/jiae287

1999. Pharmacokinetics of Valganciclovir and Ganciclovir Following Multiple Oral Dosages of Valganciclovir in HIV- and CMV-Seropositive Volunteers. *Clinical Pharmacokinetics*, 37(2).
DOI: 10.2165/00003088-199937020-00005