Emval
Emval Uses, Dosage, Side Effects, Food Interaction and all others data.
Emval is an L-valyl ester (prodrug) of ganciclovir, which after oral administration is rapidly converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2’-deoxyguanosine, which inhibits replication of herpes viruses in vitro and in vivo. Sensitive human viruses include human cytomegalovirus (HCMV), herpes simplex virus-1 and -2 (HSV-1 and HSV-2), human herpes virus 6, 7 and 8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) and hepatitis B virus.In CMV-infected cells ganciclovir is initially phosphorylated to ganciclovir mono-phosphate by the viral protein kinase, UL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolized intracellularly. This has been shown to occur in HSV- and HCMV-infected cells with half-lives of 18 and between 6 and 24 hours respectively after removal of extracellular ganciclovir. As phosphorylation is largely dependent on the viral kinase, the phosphorylation of ganciclovir occurs preferentially in virus-infected cells.The virustatic activity of ganciclovir is due to inhibition of viral DNA synthesis by: (a) competitive inhibition of incorporation of deoxyguanosine-triphosphate into DNA by viral DNA polymerase and (b) incorporation of ganciclovir triphosphate into viral DNA causing termination of, or very limited further viral DNA elongation. Typical antiviral IC 50 against CMV in vitro is in the range 0.08 μM (0.02 μg/ml) to 14 μM (3.5 μg/ml).The clinical antiviral effect of Emval has been demonstrated in the treatment of AIDS patients with newly diagnosed CMV retinitis (clinical trial WV15376). CMV shedding was decreased from 46% (32/69) of patients at study entry to 7% (4/55) of patients following 4 weeks of Emval treatment.
Emval is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases. After this, it (being an analogue of guanosine) gets incorporated into DNA and thus cannot be properly read by DNA polymerase. This results in the termination of the elongation of viral DNA.
| Trade Name | Emval |
| Availability | Prescription only |
| Generic | Valganciclovir |
| Valganciclovir Other Names | Valganciclovir |
| Related Drugs | valacyclovir, ganciclovir ophthalmic, ganciclovir, Valcyte, letermovir, cidofovir, foscarnet, Prevymis, Cytovene |
| Type | Tablet |
| Formula | C14H22N6O5 |
| Weight | Average: 354.3617 Monoisotopic: 354.165167844 |
| Protein binding | Plasma protein binding of ganciclovir is 1% to 2% over concentrations of 0.5 and 51 mg/mL. |
| Groups | Approved, Investigational |
| Therapeutic Class | Anti-viral drugs |
| Manufacturer | Emcure Pharmaceuticals Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Emval is used for the treatment of cytomegalovirus (CMV) retinitis in adult patients with acquired immunodeficiency syndrome (AIDS). Emval is used for the prevention of CMV disease in adult and pediatric solid organ transplant (SOT) patients who are at risk.
Emval is also used to associated treatment for these conditions: Cytomegalovirus (CMV) Infection, Cytomegalovirus Retinitis
How Emval works
Emval is a prodrug of ganciclovir that exists as a mixture of two diastereomers. After administration, these diastereomers are rapidly converted to ganciclovir by hepatic and intestinal esterases. In cytomegalovirus (CMV)-infected cells, ganciclovir is initially phosphorylated to the monophosphate form by viral protein kinase, then it is further phosphorylated via cellular kinases to produce the triphosphate form. This triphosphate form is slowly metabolized intracellularly. The phosphorylation is dependent upon the viral kinase and occurs preferentially in virus-infected cells. The virustatic activity of ganciclovir is due to the inhibition of viral DNA synthesis by ganciclovir triphosphate. Ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.
Dosage
Emval dosage
Standard Dosage: Emval is administered orally, and should be taken with food. Emval is rapidly and extensively converted into the active ingredient ganciclovir. The bioavailability of ganciclovir from Emval is up to 10-fold higher than from oral ganciclovir.The dosage and administration of Emval tablets or powder for oral solution as described below should be closely followed. The ganciclovir systemic exposure following administration of 900 mg Emval powder for oral solution is equivalent to a 900 mg Emval dose administered as two 450 mg tablets.An oral dosing dispenser with 25 mg graduations up to 500 mg is provided with the powder for oral solution. It is recommended that this dispenser is used to measure and administer the dose.
Treatment of cytomegalovirus (CMV) retinitis-
Adult patients
:
- Induction treatment of CMV retinitis: For patients with active CMV retinitis, the recommended dose is 900 mg twice a day for 21 days. Prolonged induction treatment may increase the risk of bone marrow toxicity
- Maintenance treatment of CMV retinitis: Following induction treatment, or in adult patients with inactive CMV retinitis, the recommended dose is 900 mg once daily. Patients whose retinitis worsens may repeat induction treatment. The duration of maintenance treatment should be determined on an individual basis.
Pediatric patients
: The safety and efficacy of Emval in the treatment of CMV retinitis have not been established in adequate and well-controlled clinical studies in pediatric patients.
Prevention of CMV disease in transplantation-
Adult patients
: For kidney transplant patients, the recommended dose is 900 mg once daily starting within 10 days post-transplantation and continuing until 200 days post-transplantation. For patients who have received a solid organ transplant other than kidney, the recommended dose is 900 mg once daily starting within 10 days post-transplantation and continuing until 100 days post-transplantation.
Pediatric patients
: In pediatric solid organ transplant patients from birth, who are at risk of developing CMV disease, the recommended once daily dose of Emval is based on body surface area (BSA) and creatinine clearance (ClCr) derived from Schwartz formula (ClCr), and is calculated using the equation below:Pediatric dose (mg)= 7 x BSA x ClCr. If the creatinine clearance exceeds 150 ml/min/1.73 m2, then a maximum value of 150 ml/min/1.73 m2
Side Effects
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
- Hematologic Toxicity
- Acute Renal Failure
- Impairment of Fertility
- Fetal Toxicity
- Mutagenesis and Carcinogenesis
Toxicity
It is expected that an overdose of valganciclovir could also possibly result in increased renal toxicity.
Interaction
In vivo drug-drug interaction studies were not conducted with valganciclovir. However, because valganciclovir is rapidly and extensively converted to ganciclovir, drug-drug interactions associated with ganciclovir will be expected for Emval. Drug-drug interaction studies with ganciclovir were conducted in patients with normal renal function. Following concomitant administration of Emval and other renally excreted drugs, patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug. Therefore, these patients should be closely monitored for toxicity of ganciclovir and the coadministered drug.
Food Interaction
- Take with food.
[Moderate] ADJUST DOSING INTERVAL: Food increases the bioavailability of ganciclovir from the prodrug, valganciclovir.
In 16 HIV-positive subjects, the administration of valganciclovir 875 mg once daily with a high-fat meal containing approximately 600 calories resulted in a 30% increase in the steady-state area under the plasma concentration-time curve (AUC) and a 14% increase in the peak plasma concentration (Cmax) of ganciclovir, with no delay in the time to reach peak plasma concentration (Tmax).
The mechanism is unknown.
MANAGEMENT: The manufacturer recommends that valganciclovir be taken with meals.
Emval Drug Interaction
Moderate: mycophenolate mofetil, mycophenolic acid, tacrolimusMinor: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimUnknown: aspirin, aspirin, meperidine, apixaban, arginine, furosemide, lithium, metoprolol, acetaminophen, acetaminophen, cyanocobalamin, cholecalciferol, phytonadione, cetirizine
Emval Disease Interaction
Major: hematologic toxicities, renal impairmentModerate: hepatic impairment
Volume of Distribution
- 0.703 ± 0.134 L/kg
Elimination Route
Emval is well absorbed from the gastrointestinal tract and the absolute bioavailability from valganciclovir tablets (following administration with food) is approximately 60%.
Half Life
Approximately 4.08 hours. Increased in patients with renal function impairment.
Clearance
- 3.07+/- 0.64 mL/min/kg [IV administration]
- 5.3 L/hr [Patient with creatinine clearance of 70.4 mL/min]
Elimination Route
The major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion.
Pregnancy & Breastfeeding use
Pregnancy: The safety of Emval for use in pregnant women has not been established. However, ganciclovir readily diffuses across the human placenta. The use of Emval should be avoided in pregnant women unless the benefit to the mother outweighs the potential risk to the fetus. Reprotoxicity studies have not been repeated with valganciclovir because of the rapid and extensive conversion to ganciclovir. In animal studies ganciclovir was associated with reproductive toxicity and teratogenicity (see section 3.3.4 Reproductive Toxicity). The safe use of Emval during labor and delivery has not been established.Lactation: Peri- and postnatal development has not been studied with valganciclovir or with ganciclovir but the possibility of ganciclovir being excreted in breast milk and causing serious adverse reactions in the nursing infant cannot be discounted. Human data are not available but animal data indicates that ganciclovir is excreted in the milk of lactating rats. Therefore, a decision should be made to discontinue the drug or discontinue nursing taking into consideration the potential benefit of Emval to the nursing mother.
Contraindication
Emval is contraindicated in patients with known hypersensitivity to valganciclovir, ganciclovir or to any of the excipients.
Special Warning
Pediatric Use: A higher risk of hematological cytopenias in neonates and infants warrants careful monitoring of blood counts in these age groups. Monitoring of liver function abnormalities, renal function and gastrointestinal fluid loss is also recommended in pediatric patients.Geriatric Use: Safety and efficacy have not been established in this patient populationRenal Impairment: In patients with impaired renal function, dosage adjustments based on creatinine clearance are required.Hepatic Impairment: Safety and efficacy have not been established in this patient population
Storage Condition
Store Emval tablets at 20°C to 25°C; excursions are permitted to 15°C to 30°C
Innovators Monograph
You find simplified version here Emval
FAQ
What is Emval used for?
Emval is used to treat cytomegalovirus retinitis (eye infection that can cause blindness) in people who have acquired immunodeficiency syndrome (AIDS).
How safe Emval is?
Emval is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation.
What are the side effects of Emval?
Emval may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- diarrhea
- nausea
- vomiting
- pain, tenderness, or swelling of the abdomen
- eye pain
- constipation
- headache
- weight loss
- back, joint, or muscle pain
- mouth ulcers
- depression
- anxiety
When should I take Emval?
Emval should be taken twice a day for 21 days and, whenever possible, taken with food.
How do I take Emval?
Take Emval with food. Drink plenty of liquids while you are taking Emval.Emval tablets are for adults or children, but Emval liquid is only for children. Adults should not use the oral solution or the dose may not be correct.
Is Emval safe during pregnancy?
Do not take Emval if you are pregnant or plan to become pregnant.You will need to take a pregnancy test before you start treatment and use effective birth control during your treatment and for 30 days after your final dose.
How do you take Emval?
The manufacturer recommends avoiding breastfeeding during Emval use because of the risk of infant drug toxicity, neonates with CMV infections are often treated directly with Emval.
Can you take Emval with food?
Emval should be administered with or immediately after a meal. This will make it easier for your body to absorb the medication.
Is Emval safe during breastfeeding?
the manufacturer recommends avoiding breastfeeding during Emval use because of the risk of infant drug toxicity, neonates with CMV infections are often treated directly with Emval.
Can you overdose on Emval ?
You could overdose and become very sick if Emval is taken with ganciclovir capsules or Cytovene-IV. Talk to your doctor or pharmacist if you have questions about your medicine.
Can I drive after taking Emval?
After taking Emval do not drive or use any tools or machines if you feel dizzy, tired, shaky or confused while taking this medicine.
How long does Emval stay in your system?
Emval only active in your body for a short period of time after it's taken. On its own, its half-life is approximately 30 minutes. Oonce Emval has converted into acyclovir, it has a half-life of 2.5 to 3.3 hours in people with normal renal function.
Is Emval an antiviral?
Emval is an antiviral. It is used to treat infections caused by viruses.This medicine is also used to prevent CMV disease in patients who have received an organ transplant .
Is Emval cytotoxic?
bnrand is classed as a cytotoxic medicine and will therefore require special handling. These medications are often identified by a purple label and the nurses/pharmacists at your hospital/pharmacy will also identify them for you.
Can I crush Emval?
Do not break or crush Emval.Avoid contact with your skin or eyes. If you come in contact with the contents of the tablet or oral solution, wash your skin well with soap and water or rinse your eyes well with plain water.
Is Emval an immunosuppressant?
No, Emval is not an immunosuppressant.Emval is often prescribed to people taking immunosuppressants after a transplant to prevent a CMV infection.
How long can you take Emval?
The usual dose Emval is two tablets taken twice a day for 21 days . Do not take this dose for more than 21 days unless your doctor tells you to, as this may increase your risk of possible side effects.
Is Emval an antibiotic?
Emval is an antiviral drug. It works by preventing viral cells from multiplying in your body.
Is Emval a prodrug?
Emval an oral prodrug that is rapidly converted to ganciclovir, also plays a major role in the treatment and prevention of CMV infections in immunocompromised hosts.
How many days should I take Emval?
Emval comes as a tablet to take by mouth. It is usually taken every 8 hours (three times a day) for 7 days to treat shingles. To treat genital herpes it is usually taken twice a day for 5 days.
