Valcyte^®

(valganciclovir hydrochloride)
Indications and Important Safety Information

INDICATIONS

Adult Patients: Valcyte^® (valganciclovir hydrochloride) tablets are indicated for the prevention of cytomegalovirus (CMV) disease in kidney, heart, or kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

Pediatric Patients: Valcyte (valganciclovir hydrochloride) for oral solution and tablets are indicated for the prevention of CMV disease in kidney or heart transplant patients (4 months to 16 years of age) at high risk.

Limitations of Use:

• Valcyte is not indicated for use in either adult or pediatric liver transplant patients
• The safety and efficacy of Valcyte have not been established for:
  • Prevention of CMV disease in solid organ transplants other than those indicated
  • Prevention of CMV disease in pediatric solid organ transplant patients <4 months of age
  • Treatment of congenital CMV disease

IMPORTANT DOSING INFORMATION

• Adult patients should use Valcyte tablets, not Valcyte for oral solution
• Valcyte should be taken with food
• The bioavailability of ganciclovir for Valcyte is significantly higher than from ganciclovir capsules. Therefore, Valcyte tablets cannot be substituted for ganciclovir capsules on a one-to-one basis
• Valcyte tablets should not be broken or crushed
• Valcyte for oral solution must be prepared by the pharmacist prior to dispensing to patient
• Mycophenolate mofetil (MMF): May increase ganciclovir concentrations and levels of MMF metabolites in patients with renal impairment. Monitor for ganciclovir and MMF toxicity

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

Valcyte is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction to valganciclovir, ganciclovir, or any component of the formulation.

WARNINGS AND PRECAUTIONS

• Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been observed
• Do not administer if the absolute neutrophil count is <500 cells/µL, the platelet count is <25,000/µL, or the hemoglobin is <8 g/dL
• Use with caution in patients with pre-existing cytopenias, or who have received or who are receiving myelosuppressive drugs or irradiation
• Advise women of childbearing potential to use effective contraception during treatment and for at least 30 days following treatment with Valcyte. Advise men to practice barrier contraception during and for at least 90 days following treatment
• Acute renal failure may occur in:
  • Elderly patients with or without reduced renal function
  • Patients receiving potential nephrotoxic drugs
  • Patients without adequate hydration

ADVERSE REACTIONS

Adult Patients: The most common adverse events and laboratory abnormalities reported in at least one indication by >20% of patients treated with Valcyte tablets are diarrhea, pyrexia, nausea, tremor, neutropenia, anemia, graft rejection, thrombocytopenia, and vomiting.

Pediatric Patients: The most common adverse events and laboratory abnormalities reported in >10% of solid organ transplant recipients treated with Valcyte for oral solution or tablets are diarrhea, pyrexia, hypertension, upper respiratory tract infection, vomiting, anemia, neutropenia, constipation, nausea, and cough.

Please click here for Valcyte full Prescribing Information, including Boxed WARNING, and for additional Important Safety Information.

CellCept^®

(mycophenolate mofetil)
Indication and Important Safety Information

INDICATION

CellCept^® (mycophenolate mofetil) is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. CellCept should be used concomitantly with cyclosporine and corticosteroids.

CellCept Intravenous is an alternative dosage form to CellCept capsules, tablets and oral suspension. CellCept Intravenous should be administered within 24 hours following transplantation. CellCept Intravenous can be administered for up to 14 days; patients should be switched to oral CellCept as soon as they can tolerate oral medication.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

CellCept is contraindicated in patients with a hypersensitivity to mycophenolate mofetil, mycophenolic acid or any component of the drug product. CellCept Intravenous is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN).

WARNINGS

• Pregnancy category D: Mycophenolate mofetil (MMF) can cause fetal harm when administered to a pregnant female. Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, and kidney. Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.
• Patients receiving immunosuppressive regimens involving combinations of drugs, including CellCept, as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin.
• CellCept has been administered in combination with the following agents in clinical trials: antithymocyte globulin, OKT3, cyclosporine and corticosteroids. The efficacy and safety of the use of CellCept in combination with other immunosuppressive agents have not been determined.
• Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections, fatal infections and sepsis.
• Immunosuppressed patients are at increased risk of opportunistic infections, including activation of latent viral infections. These include sometimes fatal cases of progressive multifocal leukoencephalopathy (PML) and BK virus-associated nephropathy (BKVAN).

  
  In immunosuppressed patients with neurological symptoms, consider PML in the differential diagnosis and consult with a neurologist as clinically indicated. Consider reducing the amount of immunosuppression and be cognizant of the risk that reduced immunosuppression represents to the graft.

  Consider reducing immunosuppression for patients who develop evidence of BKVAN.

• Monitor patients for neutropenia. If neutropenia develops [absolute neutrophil count (ANC) <1.3 x 10³/µL], dosing with CellCept should be interrupted or the dose reduced, appropriate diagnostic tests performed and the patient managed appropriately.
• Cases of pure red cell aplasia (PRCA) have been reported in patients treated with CellCept in combination with other immunosuppressive agents.
• CAUTION: NEVER ADMINISTER CELLCEPT INTRAVENOUS SOLUTION BY RAPID OR BOLUS INTRAVENOUS INJECTION.

Precautions

• Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.
  • Pregnancy Testing: a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL must be administered immediately before starting CellCept. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. In the event of a positive pregnancy test, females should be counseled with regard to whether the maternal benefits of mycophenolate treatment may outweigh the risks to the fetus in certain situations, please report the pregnancy to Mycophenolate Pregnancy Registry
    (1-800-617-8191).
  • Contraception: Patients taking CellCept must receive contraceptive counseling and use acceptable contraception (see Table 8 of the full Prescribing Information for acceptable contraception methods). Patients must use acceptable birth control during entire CellCept therapy, and for 6 weeks after stopping CellCept, unless the patient chooses abstinence.
• CellCept may be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.
• A higher incidence of opportunistic infections was observed in cardiac transplant patients treated with CellCept than in those receiving azathioprine therapy.
• CellCept should not be administered concomitantly with azathioprine and used with caution when used in the concomitant administration with drugs that interfere with enterohepatic recirculation.
• CellCept should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT), such as Lesch-Nyhan or Kelley-Seegmiller syndrome.
• Gastrointestinal bleeding (requiring hospitalization) has been observed.
• During treatment with CellCept, avoid the use of live attenuated vaccines and advise patients that vaccinations may be less effective.
• Care should be taken if CellCept Oral Suspension is administered to patients with phenylketonuria.

Adverse Reactions

• The principal adverse reactions associated with the administration of CellCept include diarrhea, leukopenia, sepsis, vomiting, and there is evidence of a higher frequency of certain types of infections, eg, opportunistic infections (see WARNINGS in full Prescribing Information). Phlebitis and thrombosis have been reported with intravenous administration. Please refer to the full Prescribing Information for additional ADVERSE REACTIONS.

 

Please click here for CellCept full Prescribing Information, including Boxed WARNING and Medication Guide, for additional Important Safety Information.