Action and Spectrum

Actions and spectrum: 

The antiviral valganciclovir drug used to treat cytomegalovirus (CMV) infections, which can occur in individuals with weakened immune systems. valganciclovir is a prodrug that is rapidly converted to its active form, ganciclovir, after oral administration.

Once activated, ganciclovir interferes with the viral DNA polymerase enzyme and inhibits viral replication. valganciclovir is effective against CMV infections that may occur in individuals who have undergone an organ transplant or individuals with HIV/AIDS. 

Drug Interaction

Adverse Reaction

Black Box Warning

Black Box Warning: 

valganciclovir does not have any black box warning. However, it has a boxed warning about hematologic toxicity, which can lead to neutropenia, anemia, and thrombocytopenia.

Patients taking valganciclovir should have their complete blood count (CBC) monitored regularly. valganciclovir can also cause renal impairment, and patients with pre-existing renal impairment should be used with caution. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

valganciclovir is contraindicated in patients with a known hypersensitivity to valganciclovir, ganciclovir, or any component of the formulation. It is also contraindicated in patients with severe leukopenia, neutropenia, or thrombocytopenia (less than 25,000 cells/mm3).  

Caution: 

• Renal impairment: In patients with renal impairment, it should be used with caution. Dose adjustments are required in such patients. 
• Hematologic toxicity: valganciclovir can cause bone marrow suppression, leading to anemia, neutropenia, and thrombocytopenia. The patients should be closely monitored for any signs of these side effects. 
• Hepatic impairment: valganciclovir should be used with caution in patients with hepatic impairment. Dose adjustments may be required in such patients. 
• Immunocompromised patients: valganciclovir should be used with caution in immunocompromised patients, i.e., HIV or receiving immunosuppressive therapy. 
• Pregnancy and lactation: valganciclovir should not be used during pregnancy unless the potential benefits outweigh the risks. It is also excreted in breast milk, and breastfeeding should be avoided while taking this medication. 
• Elderly patients: valganciclovir should be used with caution in elderly patients, as they may be more susceptible to its side effects.

Comorbidities: 

The antiviral valganciclovir medication that is primarily used to treat viral infections caused by cytomegalovirus (CMV). There are no specific comorbidities that preclude the use of valganciclovir.

However, caution should be exercised in patients with pre-existing renal impairment, neutropenia, or thrombocytopenia, as these conditions may be exacerbated by valganciclovir therapy.

In addition, valganciclovir may interact with other medications that are metabolized by the same liver enzymes, which may require dosage adjustments or close monitoring. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category Not Assigned 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

The antiviral valganciclovir drug used to treat cytomegalovirus (CMV) infection. It is a prodrug that is rapidly converted to ganciclovir in the body. Ganciclovir is a nucleoside analog that inhibits viral DNA synthesis by interfering with viral DNA polymerase. 

Once valganciclovir is administered orally, it is rapidly absorbed from the gastrointestinal tract, and its absorption is not significantly affected by food. valganciclovir is rapidly converted to ganciclovir, primarily by intestinal and hepatic esterases, and then enters systemic circulation. 

Ganciclovir has a low plasma protein binding of 1-2%. It is widely distributed throughout the body, with the highest concentrations found in the kidneys and liver. It can penetrate the blood-brain barrier and reach therapeutic concentrations in cerebrospinal fluid. 

Ganciclovir is phosphorylated by viral kinase and host cell kinases to its active form, ganciclovir triphosphate, which competes with deoxyguanosine triphosphate for incorporation into viral DNA, leading to inhibition of viral DNA synthesis. 

Ganciclovir is primarily eliminated by renal excretion. The half-life of ganciclovir is approximately 3 hours in individuals with normal renal function. Therefore, dose adjustment is required in patients with renal impairment.  

Pharmacodynamics: 

valganciclovir is a prodrug of ganciclovir, which means that it is converted to ganciclovir after oral administration. Ganciclovir is a synthetic nucleoside analog of guanosine and exerts its antiviral effect by inhibiting viral DNA synthesis.

It is phosphorylated by the viral protein kinase, UL97, and cellular kinases to form ganciclovir triphosphate (GCV-TP), which competitively inhibits the incorporation of deoxyguanosine triphosphate into viral DNA. The selective inhibition of viral DNA synthesis reduces the viral load and helps to control viral replication. 

valganciclovir has a high bioavailability of around 60% after oral administration and is rapidly converted to ganciclovir by hepatic and intestinal esterases. The drug achieves its peak plasma concentration within 1-3 hours and has a half-life of approximately 4 hours. valganciclovir is primarily eliminated in the urine, and the dose needs to be adjusted in patients with renal impairment.  

Pharmacokinetics: 

Absorption 

valganciclovir is rapidly converted to ganciclovir after oral administration. It is well absorbed from the gastrointestinal tract, with approximately 60% bioavailability. Food delays absorption but does not affect the extent of absorption. 

Distribution 

valganciclovir has a volume of distribution of 0.7 to 1.7 L/kg. It is widely distributed throughout the body, including the liver, kidneys, lungs, spleen, muscle, cerebrospinal fluid, and ocular tissues. 

Metabolism 

valganciclovir is rapidly and extensively converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is not extensively metabolized, but it is phosphorylated by viral and cellular kinases to form the active triphosphate form. 

Elimination and excretion 

valganciclovir is excreted by the kidneys through glomerular filtration and tubular secretion. Approximately 90% of the dose is excreted unchanged in the urine, and the remaining 10% is excreted in the feces. The elimination half-life of ganciclovir is about 2 to 4 hours, and it is prolonged in patients with renal impairment. 

Adminstartion

Administration: 

valganciclovir is available as oral tablets and is usually administered with food. The tablets should be administered whole and not crushed or chewed. The duration and dosage of treatment depend on the condition being treated, the patient’s age, weight, renal function, and other factors.

valganciclovir should be used with caution in patients with renal impairment, and the dosage should be adjusted accordingly. Patients should be advised to drink fluids while taking valganciclovir to prevent dehydration. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: valganciclovir 

Pronounced: [ val-gan-SYE-kloe-veer]  

Why do we use valganciclovir? 

valganciclovir is an antiviral drug that is primarily used to treat infections caused by cytomegalovirus (CMV), a common virus that can cause serious illness in people with weakened immune systems. In some cases, valganciclovir may be used off-label to treat viral pneumonia in children, particularly if the pneumonia is caused by a virus known as the human herpesvirus 6 (HHV-6). 

In some cases, viral pneumonia in children can be caused by the CMV, particularly in children who have weakened immune systems due to factors such as HIV infection, organ transplantation, or chemotherapy. In such cases, valganciclovir may be used to treat the underlying CMV infection and thereby help to alleviate the symptoms of viral pneumonia. 

It is important to note, however, that viral pneumonia in children can have a variety of causes, and the use of valganciclovir may not be appropriate or effective in all cases. The treatment of viral pneumonia should be tailored to the individual patient based on the underlying cause and other factors, and should be managed by a healthcare provider with expertise in the treatment of respiratory infections in children.