Valcyte (valganciclovir HCl)

Dosage of valganciclovir hydrochloride is expressed in terms of valganciclovir.

Valganciclovir hydrochloride is administered orally as tablets or an oral solution and should be given with food.

Adults should receive valganciclovir tablets (not the oral solution). Valganciclovir tablets should not be broken or crushed.

Valganciclovir oral solution is the preferred dosage form for pediatric patients. Valganciclovir tablets should be used in pediatric patients only if the calculated dose is within 10% of the tablet strength (i.e., a single 450-mg tablet may be used if the calculated dose is 405-495 mg). (See Pediatric Dosage under Dosage and Administration: Dosage.)

Patients receiving valganciclovir should be adequately hydrated.

Females of childbearing potential should be tested for pregnancy prior to initiation of valganciclovir. (See Pregnancy under Warnings/Precautions: Specific Populations, in Cautions.)

Because of the mutagenic and/or carcinogenic potential of valganciclovir, the tablets, powder for oral solution, and reconstituted oral solutions of the drug should be handled carefully according to guidelines issued for cytotoxic drugs. (See Handling and Disposal under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)

No formal drug interaction studies have been performed using valganciclovir. However, valganciclovir is rapidly and extensively converted to ganciclovir and interactions reported with ganciclovir are expected to occur in patients receiving valganciclovir.

Drug interaction studies with ganciclovir were performed in patients with normal renal function. In patients with renal impairment, concomitant use of valganciclovir and other drugs eliminated by renal excretion may result in increased concentrations of ganciclovir and the concomitant drug and such patients should be closely monitored for toxicity associated with ganciclovir and the concomitant drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Ganciclovir, Valganciclovir/Zidovudine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The magnitude of the toxic effects of both drugs are increased.

CLINICAL EFFECTS: Increased side effects, including hematologic and gastrointestinal toxicity.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: When possible, avoid this combination. Coadministration should be considered only if the potential benefits are judged to outweigh the risks. Dose reduction or interruption may be needed. Monitor with frequent complete blood counts with differential and platelet counts.

DISCUSSION: Patients receiving zidovudine and ganciclovir concurrently developed hematologic toxicity, including neutropenia and anemia, and gastrointestinal toxicity. Both ganciclovir and zidovudine have box warnings regarding hematologic toxicity. Granulocytopenia (neutropenia), anemia, thrombocytopenia, and pancytopenia have been reported. In a study in 12 patients, an oral dose of ganciclovir (1000 mg every 8 hours) administered concurrently with zidovudine (100 mg every 4 hours) decreased the mean steady state area-under-the-curve (AUC) of ganciclovir 17% and increased the zidovudine AUC 19%.

Ganciclovir,Valganciclovir/Imipenem-Cilastatin

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown, but may involve additive or synergistic effects on the seizure threshold.

CLINICAL EFFECTS: Concurrent use of imipenem-cilastatin with ganciclovir may result in generalized seizures.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of imipenem-cilastatin states that imipenem-cilastatin and ganciclovir should not be coadministered unless the potential benefits outweigh the risks of seizures.(1)

DISCUSSION: Generalized seizures have been reported in patients who received ganciclovir and imipenem-cilastatin.(1)

Ganciclovir; Valganciclovir/Maribavir

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Maribavir may inhibit pUL97 protein kinase which catalyzes the phosphorylation step required for activation of ganciclovir or valganciclovir.(1)

CLINICAL EFFECTS: Concurrent administration of maribavir with ganciclovir or valganciclovir may antagonize the antiviral activity of ganciclovir or valganciclovir, resulting in decreased clinical efficacy and/or virological failure of ganciclovir and valganciclovir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of maribavir states that the concurrent use of maribavir with ganciclovir or valganciclovir is not recommended.(1)

DISCUSSION: Ganciclovir and valganciclovir require activation via phosphorylation to the active form by human CMV pUL97 protein kinase.(2,3) The antiviral activity of maribavir is mediated by competitive inhibition of the protein kinase activity of pUL97 and may antagonize the antiviral activity of ganciclovir or valganciclovir.(1) In the setting of combination therapy, in vitro data suggests antagonistic activity when maribavir is coadministered with ganciclovir or valganciclovir.(4-7)

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

Selected Antiviral Agents/Cladribine Oral

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Antiviral agents may inhibit the intracellular phosphorylation of cladribine by competitive inhibition of intracellular kinases.(1-4)

CLINICAL EFFECTS: Concurrent administration of antiviral agents with cladribine may result in decreased clinical efficacy of cladribine.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation is not recommended.(1)

DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites.(1) Compounds phosphorylated by kinases linked to this monograph include: acyclovir, entecavir, ganciclovir, tenofovir, valacyclovir, and valganciclovir.

Selected Antivirals/Talimogene Laherparepvec

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus (HSV-1) which has been modified to express human GM-CSF.(1)

CLINICAL EFFECTS: Administration of antiviral agents with activity against HSV-1 may interfere with the effectiveness of talimogene laherparepvec.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concomitant use when possible. Talimogene laherparepvec is a live, attenuated herpes simplex virus (HSV-1) which is injected into cancerous lesions where it replicates and produces GM-CSF, leading to lysis of tumors. It is sensitive to antiherpetic agents such as acyclovir, valacyclovir and famciclovir and so administration of these antivirals may impair talimogene laherparepvec effectiveness.(1)

DISCUSSION: Agents that inhibit herpes simplex virus activity may impair the ability of talimogene laherparepvec to replicate and produce GM-CSF in tumors. The impact of concurrent antiviral and talimogene laherparepvec therapy has not been studied; patients requiring antiviral prophylaxis or treatment with acyclovir, valacyclovir and famciclovir were excluded from clinical trials.(1) Agents linked to this monograph are systemic formulations of acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, valacyclovir and valganciclovir.

Selected Myelosuppressive Agents/Clozapine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2)

CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal.

PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia.

PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent absolute neutrophil count (ANC) monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. The U.S. Food and Drug Administration (FDA) recommends that prescribers monitor patients' ANC according to the monitoring frequencies described in the prescribing information. Severe neutropenia remains a serious, potentially fatal risk that is greatest in the first several months of clozapine treatment. ANC monitoring can help identify neutropenia early to allow for timely intervention.(1-2) Australia, Canada, and U.K.: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing. For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(2)

DISCUSSION: Concurrent use of clozapine and selected myelosuppressive agents may require more frequent ANC monitoring or consideration of treatment alternatives secondary to neutropenic episodes. Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26)

Selected Myelosuppressive Agents/Deferiprone

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1)

CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal.

PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2)

PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1)

DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3)

Selected Myelosuppressive Agents/Dipyrone

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use of dipyrone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1-29)

CLINICAL EFFECTS: Concurrent use of dipyrone with agents that cause bone marrow depression, including myelosuppressives, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding. Undetected severe neutropenia or agranulocytosis may be fatal.(1-29)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of dipyrone and myelosuppressive agents should be avoided. The European Medicines Agency states dipyrone is contraindicated in patients with a prior medical history of dipyrone-induced agranulocytosis (or from other pyrazolones/pyrazolidines), impaired bone marrow function or diseases of the hematopoietic system.(3) International labeling for dipyrone and methotrexate state that co-administration may increase the hematotoxicity of methotrexate, especially in elderly patients, and therefore should be avoided.(1-2) The European Medicines Agency advises if agranulocytosis is suspected with dipyrone, a complete blood count (including differential blood count) should be performed immediately, and treatment must be stopped while waiting for the results. If confirmed, treatment must not be reintroduced.(1-3)

DISCUSSION: A retrospective cohort study analyzed new users of dipyrone (n=444,972), non-steroidal anti-inflammatory drugs (n=3,814,367) which served as a reference cohort, and opioids-paracetamol (n=3,129,221) which was the negative control. During continuous treatment over a median of 37-40 days, 26 cases of hospitalized agranulocytosis occurred. With the assumption that agranulocytosis onset was 7 days prior to admission, the hazard ratio of agranulocytosis associated with dipyrone was 4.40 [0.90-21.57] compared to NSAIDs and 2.45 [0.68-8.83] compared to opioid-paracetamol. HR of neutropenia from dipyrone was 2.98 [1.57-5.65] compared to NSAIDs and not statistically significant compared to opioids-paracetamol. In a sensitivity analysis assuming that the onset of agranulocytosis was the date of hospitalization, the HR of dipyrone-induced agranulocytosis was 7.20 [95% confidence interval: 1.92-26.99] compared to NSAIDs and 3.31 [1.17-9.34] compared to opioids-paracetamol. Agranulocytosis was very rare but more than 4 times more common with dipyrone than other analgesics.(4) In a review of 1,448 reports of agranulocytosis attributed to dipyrone, patients with fatal outcomes were older and more often had also received methotrexate compared to those with non-fatal outcomes (odds ratio: 5.18; 95% confidence interval: 3.06-8.78).(5) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(2,6-26)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Selected Antivirals/Vusolimogene Oderparepvec

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Vusolimogene oderparepvec is a genetically modified herpes simplex virus type 1 (HSV-1) oncolytic viral therapy.(1)

CLINICAL EFFECTS: Administration of antiviral agents with activity against HSV-1 may interfere with the effectiveness of vusolimogene oderparepvec.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving systemic antiviral treatment for herpetic infection should delay vusolimogene oderparepvec for 72 hours after completing antiviral therapy.(1)

DISCUSSION: Agents that inhibit herpes simplex virus activity may impair the ability of vusolimogene oderparepvec to replicate in tumors.(1) Antiviral agents with activity against HSV-1 include: acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, valacyclovir, and valganciclovir.

Selected Nephrotoxic Agents/Tenofovir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Tenofovir and other nephrotoxic agents may result in additive or synergistic effects on renal function and increase nephrotoxicity risk.(1)

CLINICAL EFFECTS: Concurrent use of tenofovir and other nephrotoxic agents may result in renal toxicity and acute renal failure.(1) Reports of acute renal failure and Fanconi syndrome have been reported with tenofovir use.(2,3) However, this has been reported in 3 case reports and the renal failure may have been complicated by other pre-existing conditions.(2)

PREDISPOSING FACTORS: Pre-existing renal dysfunction, long duration of use, low body weight, concomitant use of drugs that may increase tenofovir levels may increase the risk of nephrotoxicity.(1)

PATIENT MANAGEMENT: The US prescribing information for tenofovir recommends avoiding concurrent or recent use of a nephrotoxic agent.(3) Evaluate renal function prior to initiation of concurrent therapy and continue renal function monitoring during therapy. Dose adjustments may be required for impaired renal function. Tenofovir should be avoided with high-dose or multiple NSAIDs. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction.(3) Patients receiving concurrent NSAIDs with tenofovir should be monitored for possible renal toxicity.(1,2) The dosing interval should be adjusted in patients with a baseline creatinine clearance of less than 50 ml/min.(1-3)

DISCUSSION: From March 18, 2003 to December 1, 2005, Health Canada received 10 reports of nephrotoxic reactions with tenofovir. Three of these occurred following the addition of a NSAID to tenofovir therapy. In the first report, a patient maintained on tenofovir for 29 months developed acute renal failure and acute tubular necrosis requiring dialysis 5 days after beginning indomethacin (100 mg rectally twice daily). In the second report, a patient maintained on tenofovir for 7 months developed acute renal failure and acute tubular necrosis after taking 90 tablets of naproxen (375 mg) over 2 months. The patient died. In the third report, a patient maintained on tenofovir for over a year developed acute renal failure and nephrotic syndrome after 2 months of valdecoxib (20 mg daily) therapy. Symptoms subsided following discontinuation of valdecoxib.(1)

Valganciclovir is contraindicated in patients who have had a clinically important hypersensitivity reaction (e.g., anaphylaxis) to valganciclovir, ganciclovir, or any ingredient in the formulation.

• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Severe bone marrow depression

• Acute renal failure
• Anemia
• Aplastic anemia
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Dehydration
• Granulocytopenic disorder
• Neutropenic disorder
• Pregnancy
• Thrombocytopenic disorder

• Kidney disease with likely reduction in glomerular filtration rate (GFr)

Adverse effects occurring in 20% or more of adults receiving valganciclovir include diarrhea, pyrexia, fatigue, nausea, tremor, neutropenia, anemia, leukopenia, thrombocytopenia, headache, insomnia, urinary tract infection, and vomiting.

Adverse effects occurring in 20% or more of pediatric patients receiving valganciclovir include diarrhea, pyrexia, upper respiratory tract infection, urinary tract infection, vomiting, neutropenia, leukopenia, and headache.

More Frequent

• Anemia
• Fever
• Neutropenic disorder
• Retinal detachment
• Thrombocytopenic disorder

Less Frequent

• Hallucinations
• Hemorrhage
• Hyperkalemia
• Hypersensitivity drug reaction
• Hypophosphatemia
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Pancytopenia
• Seizure disorder

Rare or Very Rare

• Abnormal hepatic function tests
• Acute renal failure
• Agranulocytosis
• Anaphylaxis
• Aplastic anemia
• Ascites
• Drug-induced psychosis
• Dyspnea
• Granulocytopenic disorder
• Hypertension
• Leukopenia
• Pleural effusions

More Frequent

• Acute abdominal pain
• Diarrhea
• Headache disorder
• Insomnia
• Nausea
• Paresthesia
• Peripheral neuropathy
• Tremor
• Urinary tract infection
• Vomiting

Less Frequent

• Acute cognitive impairment
• Agitation
• Candidiasis
• Hematuria
• Night sweats
• Ocular pain
• Peripheral edema
• Symptoms of anxiety
• Weight loss

Rare or Very Rare

• Abdominal distension
• Acne vulgaris
• Anorexia
• Arthralgia
• Back pain
• Constipation
• Cough
• Cramps
• Depression
• Dizziness
• Dyspepsia
• Dysuria
• Edema
• Fatigue
• Female infertility
• General weakness
• Oligospermia
• Pain
• Pharyngitis
• Pruritus of skin
• Skin inflammation
• Upper respiratory infection

No enhanced messaging available.

Safety and efficacy of valganciclovir have not been established in pediatric patients younger than 1 month of age.

Use of valganciclovir for the prevention of CMV disease in pediatric heart transplant recipients 1 month to 16 years of age is based on safety and pharmacokinetic data from 2 studies in pediatric solid organ transplant recipients and is supported by efficacy data from studies in adult solid organ transplant recipients.

Use of valganciclovir for the prevention of CMV disease in pediatric kidney transplant recipients 4 months to 16 years of age is based on safety, tolerability, and pharmacokinetic data from 2 open-label studies in solid organ transplant recipients in this age group and is supported by efficacy data from studies in adult solid organ transplant recipients.

Safety and efficacy of valganciclovir have not been established for prevention of CMV disease in pediatric heart transplant recipients younger than 1 month of age, pediatric kidney transplant recipients younger than 4 months of age, or pediatric liver transplant recipients of any age.

The safety profile of valganciclovir in pediatric patients generally is similar to that observed in adults. However, upper respiratory tract infection, pyrexia, nasopharyngitis, anemia, abdominal pain, and neutropenia have been reported more frequently in pediatric patients than in adults.

In animal studies, ganciclovir caused maternal and fetal toxicity, embryofetal mortality, and teratogenicity. Valganciclovir is expected to have reproductive toxicity similar to ganciclovir. (See Teratogenesis under Warnings/Precautions: Warnings, in Cautions.)

Data are not available regarding use of valganciclovir in pregnant women to establish the presence or absence of drug-associated risk. An ex vivo placental model indicates that ganciclovir crosses the human placenta by passive diffusion and is not saturable over a concentration range of 1-10 mg/mL.

Although most maternal CMV infections are asymptomatic or may be associated with a self-limited mononucleosis-like syndrome, CMV infections in pregnant immunocompromised patients (e.g., those with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), transplant recipients) may be symptomatic and result in substantial maternal morbidity and mortality. Perinatal transmission of CMV from infected mothers to their neonates can occur resulting in congenital CMV infection and disease. (See Congenital Cytomegalovirus Disease under Uses: Treatment of Cytomegalovirus Infection and Disease.)

Females of childbearing potential should undergo pregnancy testing before initiation of valganciclovir. In addition, pregnancy should be avoided in female patients receiving valganciclovir and in females with male partners receiving valganciclovir.

Females of childbearing potential should be advised to use an effective method of contraception during and for at least 30 days after valganciclovir therapy and male patients should be advised to use a reliable method of barrier contraception during and for at least 90 days after valganciclovir therapy.

It is not known whether valganciclovir or ganciclovir is distributed into human milk, affects the breast-fed infant, or affects milk production. Animal data from studies using ganciclovir indicate that the drug is distributed into milk of lactating rats.

Because of the potential for serious adverse effects in nursing infants, valganciclovir is not recommended in breast-feeding women. HIV-infected mothers should be instructed not to breast-feed their infants because of the risk of transmission of HIV.

Dosage of valganciclovir for geriatric patients should be selected with caution, usually starting at the low end of the dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function. Renal function should be assessed before and during valganciclovir therapy and appropriate dosage adjustments made as necessary. (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Safety and efficacy of valganciclovir have not been specifically evaluated in geriatric patients 65 years of age or older and there were insufficient numbers of individuals in this age group in clinical studies to determine whether they respond differently than younger adults. Pharmacokinetics of the drug have been not studied in geriatric patients.

Because geriatric individuals frequently have decreased renal function and because valganciclovir is substantially excreted by the kidneys, particular attention should be paid to assessing renal function before and during valganciclovir therapy in this age group. If evidence of renal impairment exists or develops, appropriate dosage adjustments should be made. In general, dosage should be selected carefully, usually starting at the low end of the dosage range, taking into account the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.