Valganciclovir

Unless your doctor tells you otherwise, continue your normal diet.

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if valganciclovir is excreted in human breast milk or if it will harm your nursing baby. The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking transmission of HIV.

Valganciclovir has caused birth defects in animal studies. Do not use valganciclovir without telling your doctor if you are pregnant.

Use birth control to prevent pregnancy, whether you are a man or a woman. Valganciclovir use by either parent may cause birth defects. A man taking valganciclovir should use a condom during treatment, and for at least 90 days after treatment ends.

Serious infections may occur during treatment with valganciclovir. Stop using this medicine and call your doctor right away if you have signs of infection such as: fever, chills, sore throat, weakness, cold or flu symptoms, painful mouth sores, pale skin, easy bruising or bleeding, dry cough, weight loss, or trouble breathing.

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

Valganciclovir may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Taking this medicine will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection. Avoid activities that may increase your risk of bleeding or injury.

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. valganciclovir is also used to prevent CMV disease in patients who have received an organ transplant (eg, heart, kidney, or kidney-pancreas transplant).

valganciclovir 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 valganciclovir will do as well as the risks of using it.

valganciclovir is available only with your doctor's prescription.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• blood in the urine or stools
• blurred vision
• chills
• cough
• dizziness
• fever
• headache
• hoarseness
• lower back or side pain
• nervousness
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• pounding in the ears
• seeing flashes or sparks of light
• seeing floating spots before the eyes
• shakiness in the legs, arms, hands, or feet
• shortness of breath
• slow or fast heartbeat
• sore throat
• trembling or shaking of the hands or feet
• troubled breathing
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness
• veil or curtain appearing across part of vision

• Changes in facial skin color
• confusion
• false beliefs
• fast or irregular breathing
• feeling, hearing, or seeing things that are not there
• hives, itching, and skin rash
• large, hive-like swellings on the eyelids, face, lips, mouth, or tongue
• puffiness or swelling of the eyelids or around the eyes
• runny or stuffy nose
• seizures
• tightness in the chest
• trouble thinking

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• diarrhea
• headache
• nausea and vomiting
• numbness, tingling, pain, or weakness of the hands or feet
• sleeplessness
• tingling, burning, or prickly sensations
• trouble with sleeping
• unsteadiness or awkwardness

• Agitation

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adult Patients

Induction Therapy of CMV Retinitis: In one randomized open-label controlled study, 160 patients with AIDS and newly diagnosed CMV retinitis were randomized to receive treatment with either Valganciclovir tablets (900 mg twice daily for 21 days, then 900 mg once daily for 7 days) or with intravenous ganciclovir solution (5 mg per kg twice daily for 21 days, then 5 mg per kg once daily for 7 days). Study participants were: male (91%), White (53%), Hispanic (31%), and Black (11%). The median age was 39 years, the median baseline HIV-1 RNA was 4.9 log10, and the median CD4 cell count was 23 cells/mm3. A determination of CMV retinitis progression by the masked review of retinal photographs taken at baseline and Week 4 was the primary outcome measurement of the 3-week induction therapy. Table 19

provides the outcomes at 4 weeks.

Maintenance Therapy of CMV Retinitis: No comparative clinical data are available on the efficacy of Valganciclovir tablets for the maintenance therapy of CMV retinitis because all patients in the CMV retinitis study received open-label Valganciclovir tablets after Week 4. However, the AUC for ganciclovir is similar following administration of 900 mg Valganciclovir tablets once daily and 5 mg per kg intravenous ganciclovir once daily. Although the ganciclovir Cmax is lower following Valganciclovir tablets administration compared to intravenous ganciclovir, it is higher than the Cmax obtained following oral ganciclovir administration. Therefore, use of Valganciclovir tablets as maintenance therapy is supported by a plasma concentration-time profile similar to that of two approved products for maintenance therapy of CMV retinitis.

Prevention of CMV Disease in Heart, Kidney, Kidney-Pancreas, or Liver Transplantation: A double blind, double-dummy active comparator study was conducted in 372 heart, liver, kidney, or kidney-pancreas transplant patients at high risk for CMV disease (D+/R-). Patients were randomized (2 Valganciclovir hydrochloride: 1 oral ganciclovir) to receive either Valganciclovir tablets (900 mg once daily) or oral ganciclovir (1000 mg three times a day) starting within 10 days of transplantation until Day 100 post-transplant. The proportion of patients who developed CMV disease, including CMV syndrome and/or tissue-invasive disease during the first 6 months post-transplant was similar between the Valganciclovir tablets arm (12.1%, N=239) and the oral ganciclovir arm (15.2%, N=125). However, in liver transplant patients, the incidence of tissue-invasive CMV disease was significantly higher in the Valganciclovir hydrochloride group compared with the ganciclovir group. These results are summarized in Table 20.

Mortality at six months was 3.7% (9/244) in the Valganciclovir hydrochloride group and 1.6% (2/126) in the oral ganciclovir group.

Prevention of CMV Disease in Kidney Transplantation: A double-blind, placebo-controlled study was conducted in 326 kidney transplant patients at high risk for CMV disease (D+/R-) to assess the efficacy and safety of extending Valganciclovir hydrochloride CMV prophylaxis from 100 to 200 days post-transplant. Patients were randomized (1:1) to receive Valganciclovir tablets (900 mg once daily) within 10 days of transplantation either until Day 200 post-transplant or until Day 100 post-transplant followed by 100 days of placebo. Extending CMV prophylaxis with Valganciclovir hydrochloride until Day 200 post-transplant demonstrated superiority in preventing CMV disease within the first 12 months post-transplant in high risk kidney transplant patients compared to the 100 day dosing regimen (primary endpoint). These results are summarized in Table 21.

The percentage of kidney transplant patients with CMV disease at 24 months post-transplant was 38.7% (63/163) for the 100 day dosing regimen and 21.3% (33/155) for the 200 day dosing regimen.

Pediatric Patients

Prevention of CMV in Pediatric Heart, Kidney, or Liver Transplantation: Sixty-three children, 4 months to 16 years of age, who had a solid organ transplant (kidney 33, liver 17, heart 12, and kidney/liver 1) and were at risk for developing CMV disease, were enrolled in an open-label, safety, and pharmacokinetic study of oral Valganciclovir hydrochloride (Valganciclovir for oral solution or tablets). Patients received Valganciclovir hydrochloride once daily within 10 days after transplant until a maximum of 100 days post-transplant. The daily doses of Valganciclovir hydrochloride were calculated at each study visit based on body surface area and a modified creatinine clearance [see Dosage and Administration (2.3)].

The pharmacokinetics of ganciclovir were similar across organ transplant types and age ranges. The mean daily ganciclovir exposures in pediatric patients were somewhat increased relative to those observed in adult solid organ transplant patients receiving Valganciclovir hydrochloride 900 mg once daily, but were within the range considered safe and effective in adults [see Clinical Pharmacology (12.3)]. No case of CMV syndrome or tissue-invasive CMV disease was reported within the first six months post-transplantation.

Pediatric use information for pediatric kidney transplant patients ages 4 months to 16 years and for pediatric heart transplant patients ages 1 to less than 4 months is approved for Roche Palo Alto LLC’s VALCYTE (Valganciclovir hydrochloride) tablets and oral solution. However, due to Roche Palo Alto LLC’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

1. Brion LP, Fleischman AR, McCarton C, Schwartz GJ. A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: noninvasive assessment of body composition and growth. J of Ped 1986: 109(4): 698-707.
2.  NIOSH [2014]. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings. By Connor T.H, MacKenzie BA, DeBord DG, Trout DB, O’Callaghan JP, Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-138 (Supersedes 2012-150).

NDC 65862-753-60
Rx only
Valganciclovir
Tablets USP
450 mg
DO NOT BREAK OR CRUSH TABLETS
AUROBINDO                             60 Tablets

• Valganciclovir HCl
• Valganciclovir Hydrochloride

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Oral:

Valcyte: 50 mg/mL (88 mL) [contains saccharin sodium, sodium benzoate; tutti-frutti flavor]

Generic: 50 mg/mL (88 mL)

Tablet, Oral:

Valcyte: 450 mg

Generic: 450 mg

Hypersensitivity (eg, anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to acyclovir or valacyclovir

Oral: Valganciclovir should be taken with meals. The preferred dosage form for pediatric patients is the oral solution; however, valganciclovir tablets may be used so long as the calculated dose is within 10% of the available tablet strength (450 mg).

Due to the carcinogenic and mutagenic potential, avoid direct contact with broken or crushed tablets, powder for oral solution, and oral solution. Consideration should be given to handling and disposal according to guidelines issued for antineoplastic drugs. However, there is no consensus on the need for these precautions.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, diarrhea, abdominal pain, or insomnia. Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), pale skin, confusion, loss of strength and energy, dark urine, jaundice, tremors, difficulty moving, rigidity, change in balance, hallucinations, depression, burning or numbness feeling, seizures, severe headache, severe dizziness, severe fatigue, swelling of arms or legs, or vision changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Older than 16 years:
Induction dose: 900 mg orally twice a day for 21 days
Maintenance dose: 900 mg orally once a day

Comments:
-The tablet formulation should be used, not the oral solution.
-The maintenance dose should be used after the induction dose or in patients with inactive CMV retinitis.

Use: For the treatment of CMV retinitis in patients with AIDS

Adults and adolescents older than 16 years:
Hemodialysis (CrCl less than 10 mL/min): Not recommended.

Comments: A reduced dose of ganciclovir is recommended; the manufacturer product information for ganciclovir should be consulted.