Valcyte

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• upset stomach
• vomiting
• stomach pain
• diarrhea
• shaking hands that you cannot control
• seizures
• decreased urination
• bloody urine
• sore throat, fever, chills, cough, or other signs of infection
• excessive tiredness
• pale skin
• yellowing of the skin or eyes
• headache
• dizziness
• confusion
• fast heartbeat
• difficulty falling asleep or staying asleep
• weakness
• shortness of breath
• unusual bleeding or bruising

See "Drug Precautions" for important information about serious side effects of Valcyte.

Common side effects of Valcyte in adults and children include:

• diarrhea
• nausea, vomiting
• fever
• shaky movements (tremors)
• low white cell, red cell and platelet cell counts in blood tests
• rejection of the transplanted organ (graft)

Other common side effects in children include:

• constipation
• high blood pressure
• cough and colds

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Valcyte. For more information, ask your doctor or pharmacist.

• Valcyte can affect your blood cells and bone marrow causing serious and life-threatening problems. Valcyte can lower the amount of your white blood cells, red blood cells, and platelets. Your doctor may do regular blood tests to check your blood cells while you are taking Valcyte . Based on these tests, your doctor may change your dose or tell you to stop taking Valcyte.
• Valcyte may cause cancer. Valcyte causes cancer in animals. It is not known if Valcyte causes cancer in people.
• Valcyte may cause birth defects. Valcyte causes birth defects in animals. It is not known if Valcyte causes birth defects in people. If you are pregnant, talk to your doctor before taking Valcyte.
  • Tell your doctor right away if you become pregnant while taking Valcyte .
  • If you are a female who can become pregnant, you should use effective birth control during treatment with Valcyte and for at least 30 days after treatment.
  • Men should use a condom during treatment with Valcyte , and for at least 90 days after treatment, if their female sexual partner can become pregnant. Talk to your doctor if you have questions about birth control.
• Valcyte may lower the amount of sperm in a man's body and cause fertility problems.
• Valcyte can affect your kidney, including serious problems such as kidney failure. Your doctor may do regular blood tests to check your kidney function while you are taking Valcyte. Your doctor may adjust your dose based on these tests.
• Valcyte changes into the medicine ganciclovir once it is in your body. Ganciclovir is also the active ingredient in Cytovene-IV and ganciclovir capsules. Do not take ganciclovir capsules or Cytovene-IV if you are taking Valcyte. The dose of medicine in Valcyte tablets and ganciclovir capsules is different. One tablet of Valcyte has more medicine than one capsule of ganciclovir. This means that one Valcyte tablet cannot be substituted for one ganciclovir capsule. You could overdose and become very sick if Valcyte is taken with ganciclovir capsules or Cytovene-IV. Talk to your doctor or pharmacist if you have questions about your medicine.

Do not take Valcyte tablets if you are:

• receiving hemodialysis. The use of ganciclovir capsules rather than Valcyte tablets is recommended.
• allergic to any of its ingredients or if you have ever had a serious allergic reaction to ganciclovir capsules or Cytovene-IV. Symptoms of an allergic reaction to Valcyte may include: sudden trouble breathing, wheezing, hives all over your body, swelling around your mouth, or feeling anxious.

Valcyte can cause seizures, sleepiness, dizziness, unsteady movements, and confusion. You should not drive a car or operate other dangerous machinery until you know how Valcyte affects you.

You should not use this medicine if you are allergic to valganciclovir or ganciclovir (Cytovene).

Valganciclovir (Valcyte) and ganciclovir (Cytovene) must never be taken together.

Your doctor may have switched you from ganciclovir (Cytovene) to valganciclovir (Valcyte). The strength of these two medications is different. A valganciclovir tablet contains more medicine than a ganciclovir capsule. You may not need to use as many valganciclovir tablets as you did ganciclovir capsules. Take only the number of valganciclovir tablets your doctor has prescribed.

To make sure valganciclovir is safe for you, tell your doctor if you have:

• kidney disease (or if you are on dialysis);

• a blood cell disorder (such as anemia or low levels of platelets in your blood); or

• if you are receiving radiation treatment or drugs that weaken your immune system (such as cancer medicine or steroids).

Valganciclovir can cause birth defects. Do not use if you are pregnant, and tell your doctor right away if you become pregnant. You may need to have a negative pregnancy test before taking valganciclovir. Use effective birth control while you are taking valganciclovir and for at least 30 days after your treatment ends.

HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection. Valganciclovir will not prevent congenital (inherited) CMV in a newborn baby.

If a man fathers a child while using valganciclovir, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment. Continue using condoms for at least 90 days after you stop using valganciclovir.

This medication can affect fertility (your ability to have children), whether you are a man or a woman.

You should not breast-feed while you are taking valganciclovir. Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include urinating less than usual or not at all, swelling, weight gain, stomach pain, nausea, vomiting, signs of infection (fever, chills, sore throat, flu symptoms), or jaundice (yellowing of the skin or eyes).

• Your pharmacist can provide more information about valganciclovir.

• Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
• Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 6.01.

Date modified: October 13, 2017
Last reviewed: June 11, 2015

Absorption

Bioavailability

Valganciclovir, a prodrug of ganciclovir, is well absorbed from GI tract1 2 3 and metabolized by intestinal and hepatic esterases to ganciclovir.1 Systemic exposure to prodrug is transient and low.1 3

GI absorption of valganciclovir substantially greater than absorption of oral ganciclovir resulting in plasma ganciclovir concentrations comparable to those achieved with IV ganciclovir.1 2 4 6

Absolute bioavailability of ganciclovir approximately 60% when oral valganciclovir given with food.1 2 Time to peak ganciclovir concentrations 1–3 hours.1

Food

Administration of valganciclovir with a high-fat meal (approximately 600 calories, 31 g fat) increases AUC and peak plasma concentrations of ganciclovir at steady-state by 30 and 14%, respectively.1

Distribution

Extent

Ganciclovir crosses the placenta (based on an ex vivo human placental model).1 Not known whether ganciclovir or valganciclovir distributed into human milk.1

Plasma Protein Binding

Ganciclovir plasma protein binding 1–2%;1 protein binding of valganciclovir not determined because of rapid conversion to ganciclovir.1

Elimination

Metabolism

Valganciclovir rapidly hydrolyzed to ganciclovir; no other metabolites detected.1 Ganciclovir phosphorylated to ganciclovir phosphate in CMV-infected cells.1

Elimination Route

Major route of elimination of valganciclovir is renal excretion as ganciclovir by glomerular filtration and active tubular secretion.1

Half-life

Adults: Mean half-life of ganciclovir after oral administration of valganciclovir is approximately 4 hours in healthy or HIV-positive/CMV-positive adults (with or without retinitis) and 6.6–6.8 hours in adult heart, kidney, and kidney-pancreas transplant recipients.1

Children: Mean half-life of ganciclovir after oral administration of valganciclovir is 2.8–4.8 hours in pediatric solid organ transplant recipients 4 months through 11 years of age and 4.4–6 hours in pediatric solid organ transplant recipients ≥12 years of age.1 Clearance is influenced by BSA and renal function.1

Special Populations

Pharmacokinetics not evaluated in hepatic impairment.1

Half-life increased in renal impairment.1 2 Data from otherwise healthy adults with renal impairment indicate the mean half-life is about 22 hours if Clcr is 11–20 mL/minute and about 68 hours if Clcr is ≤10 mL/minute.1

Storage

Oral

25°C (may be exposed to 15–30°C).1

25°C (may be exposed to 15–30°C).1 After reconstitution, refrigerate at 2–8°C for up to 49 days.1 Do not freeze.1

Valganciclovir is used to treat symptoms of cytomegalovirus (CMV) retinitis, an infection in the eyes of people with acquired immunodeficiency syndrome (AIDS). Valganciclovir will not cure this eye infection, but it may help to keep the symptoms from becoming worse.

Valganciclovir 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 (eg, heart, kidney, or kidney-pancreas transplant).

This medicine may cause some serious side effects, including anemia and other blood problems. Before you begin treatment with valganciclovir, you and your doctor should talk about the benefit this medicine will do as well as the risks of using it.

This medicine is available only with your doctor's prescription.

Adult Patients

Treatment of Cytomegalovirus (CMV) Retinitis: Valcyte is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) [see Clinical Studies (14.1)].

Prevention of CMV Disease: Valcyte is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]) [see Clinical Studies (14.1)].

Pediatric Patients

Prevention of CMV Disease: Valcyte is indicated for the prevention of CMV disease in kidney transplant patients (4 months to 16 years of age) and heart transplant patients (1 month to 16 years of age) at high risk [see Clinical Studies (14.2)].

Experience with Valcyte Tablets: An overdose of Valcyte could possibly result in increased renal toxicity [see Dosage and Administration (2.5), Use in Specific Populations (8.6)]. Because ganciclovir is dialyzable, dialysis may be useful in reducing serum concentrations in patients who have received an overdose of Valcyte [see Clinical Pharmacology (12.3)]. Adequate hydration should be maintained. The use of hematopoietic growth factors should be considered [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

Reports of adverse reactions after overdoses with valganciclovir, some with fatal outcomes, have been received from clinical trials and during post-marketing experience. The majority of patients experienced one or more of the following adverse events:

Hematological toxicity: myelosuppression including pancytopenia, medullary aplasia, leukopenia, neutropenia, granulocytopenia

Hepatotoxicity: hepatitis, liver function disorder

Renal toxicity: worsening of hematuria in a patient with pre-existing renal impairment, acute renal failure, elevated creatinine

Gastrointestinal toxicity: abdominal pain, diarrhea, vomiting

Neurotoxicity: generalized tremor, seizures

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. AU TGA pregnancy category: D US FDA pregnancy category: Not assigned. Comments: -Pregnant patients should be apprised of the potential harm to the fetus. -Maternal and embryo/fetal risk due to the mother's underlying condition should be considered. -Females of reproductive potential: Pregnancy testing recommended before starting this drug. Effective contraception is recommended during therapy and for at least 30 days after the last dose; local protocol should be consulted regarding contraception timing. -Males of reproductive potential: Barrier contraception should be used during therapy and for at least 90 days after the last dose. -Temporary or permanent female and male infertility may occur at recommended doses.

Animal studies have revealed evidence of embryolethality, fetotoxicity, and teratogenicity; effects included fetal resorptions, increased embryofetal mortality, fetal growth retardation, multiple fetal organs with structural abnormalities (including cleft palate, anophthalmia/microphthalmia, hydrocephalus, brachygnathia, aplastic organs [kidneys, pancreas]), hypoplasia of the testes and seminal vesicles in male offspring, and pathologic changes in the nonglandular region of the stomach. Ganciclovir (active metabolite) has been shown to be mutagenic in animal studies. There are no controlled data in human pregnancy. No human data available to establish presence/absence of drug-related risk. Using an ex vivo human placental cotyledon model, ganciclovir has been shown to cross the placenta, achieving fetal levels of 17% to 19% of maternal levels. The transfer was via passive diffusion and was not saturable (over concentration range 1 to 10 mg/mL). Most maternal CMV infections are asymptomatic or may be associated with a self-limited mononucleosis-like syndrome; however, CMV infections in immunocompromised patients may be symptomatic and may lead to significant maternal morbidity and mortality. CMV transmission to the fetus is due to maternal viremia and transplacental infection. Perinatal infection can occur from neonate exposure to CMV shedding in the genital tract. In infants with congenital CMV infection, about 10% are symptomatic at birth; mortality is about 10% in these infants and about 50% to 90% of symptomatic surviving neonates have significant morbidity (including mental retardation, sensorineural hearing loss, microcephaly, seizures, and other medical problems). Risk and severity of congenital CMV infection from primary maternal CMV infection may be greater than that from maternal reactivation of CMV infection. Pregnancy should be avoided in female patients and female partners of male patients using this drug. Females of reproductive potential should be advised to use effective contraception during and for at least 30 days after therapy. Males of reproductive potential should be advised to use barrier contraception during and for at least 90 days after therapy. Based on ganciclovir animal data, this drug may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females at recommended human doses. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.