Temixys (lamivudine and tenofovir disoproxil fumarate)

Temixys may cause serious side effects, including:

• New or worse kidney problems, including kidney failure. Your healthcare provider may do blood and urine tests to check your kidneys before and during treatment with Temixys. Tell your healthcare provider if you get signs and symptoms of kidney problems, including bone pain that does not go away or worsening bone pain, pain in your arms, hands, legs or feet, broken (fractured) bones, muscle pain or weakness.
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when an HIV-1 infected person start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after starting your HIV-1 medicine.
• Bone problems can happen in some children or adults who take Temixys. Bone problems include bone pain, softening or thinning of bones, which may lead to fractures. Your healthcare provider may need to do tests to check your bones or your child's bones. Tell your healthcare provider if you have any bone pain, pain in your hands or feet, or muscle pain or weakness during treatment with Temixys.
• Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat.
• Severe liver problems. In rare cases, severe liver problems can happen that can lead to death. Tell your healthcare provider right away if you get these symptoms: skin or the white part of your eyes turns yellow, dark “tea-colored” urine, light-colored stools, loss of appetite for several days or longer, nausea, or stomach-area pain.
• Use with interferon and ribavirin-based regimens. Worsening of liver disease that has caused death has happened in people infected with HIV-1 and hepatitis C virus who were taking antiretroviral medicines for HIV-1 and were also being treated for hepatitis C with interferon alfa with or without ribavirin. If you are taking Temixys and interferon with or without ribavirin, tell your healthcare provider if you have any new symptoms.
• Risk of inflammation of the pancreas (pancreatitis). Children may be at risk for developing pancreatitis during treatment with Temixys if they:
  • have taken nucleoside analogue medicines in the past
  • have a history of pancreatitis
  • have other risk factors for pancreatitis

Call your healthcare provider right away if your child develops signs and symptoms of pancreatitis includingsevere upper stomach-area pain, with or without nausea and vomiting. Your healthcare provider may tell you to stop giving Temixys to your child if their symptoms and blood test results show that your child may have pancreatitis. The most common side effects of Temixys include:

• • rash
  • headache
  • pain
  • diarrhea
  • depression

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Temixys.

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

Testing Prior To Initiation And During Treatment With Temixys

• Prior to initiation treatment with Temixys, test patients for hepatitis B virus infection.
• Prior to initiation and during use of Temixys, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.

Recommended Dose For Adult And Pediatric Patients Weighing At Least 35 kg

• Temixys is a two-drug fixed-dose combination product containing 300 mg of lamivudine (3TC) and 300 mg of tenofovir disoproxil fumarate (TDF). The recommended dosage of Temixys in HIV-1 infected adult and pediatric patients weighing at least 35 kg is one tablet taken orally once daily with or without food.

Not Recommended In Renal Impairment

• Because Temixys is a fixed-dose combination formulation and cannot be dose adjusted, it is not recommended for patients with impaired renal function (creatinine clearance less than 50 mL/min) or patients with end-stage renal disease (ESRD) requiring hemodialysis.

Drugs Affecting Renal Function

Tenofovir, a component of Temixys, is primarily eliminated by the kidneys. Coadministration of Temixys with drugs that are eliminated by active tubular secretion may increase serum concentrations of tenofovir and/or coadministered drug. Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs. Drugs that decrease renal function may increase concentrations of tenofovir.

Do not administer Temixys with Hepsera (adefovir dipivoxil).

Established And Significant Interactions

Table 3 provides a listing of established or clinically significant drug interactions. The drug interactions described are based on studies conducted with TDF.

Table 3: Established and Significant^a Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Trials

Drugs Inhibiting Organic Cation Transporters

• 3TC, a component of Temixys, is predominantly eliminated in the urine by active organic cationic secretion.
• The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim).
• No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of 3TC.

Sorbitol

• Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine.

• Available data from the APR show no difference in the risk of overall major birth defects for 3TC compared to the background rate for major birth defects of 2.7% in U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
• Available data from the APR show no increase in the overall risk of major birth defects with first trimester exposure for tenofovir disoproxil fumarate (TDF) (2.1%) compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Temixys during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
• Women with HIV-1 infection should not breastfeed because HIV-1 can be passed to the baby in the breast milk