Lamivudine and Tenofovir disoproxil

CIMDUO ® (lamivudine and tenofovir disoproxil fumarate) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients weighing at least 35 kg. CIMDUO is a two-drug combination of lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), both nucleo(t)side reverse transcriptase inhibitors and is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients weighing at least 35 kg.

CIMDUO is a fixed-dose combination of antiviral drugs 3TC and TDF with antiviral activity against HIV-1. Mechanism of Action Lamivudine 3TC is a synthetic nucleoside analogue with activity against HIV-1 and HBV. Intracellularly, 3TC is phosphorylated to its active 5’‑triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC‑TP is inhibition of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. Tenofovir Disoproxil Fumarate TDF is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. TDF requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate.

• Testing: Prior to initiation and during treatment with CIMDUO, patients should be tested for hepatitis B virus infection, and estimated creatinine clearance, urine glucose, and urine protein should be obtained. • Recommended dose: One tablet taken orally once daily with or without food. • Renal Impairment: Not recommended in patients with CrCL less than 50 mL/min or patients with end-stage renal disease requiring hemodialysis.

CIMDUO is contraindicated in patients with a previous hypersensitivity reaction to any of the components contained in the formulation. • CIMDUO is contraindicated in patients with previous hypersensitivity to any of the components of this product.

Boxed warning (post treatment acute exacerbations of hepatitis b): Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine or tenofovir disoproxil fumarate, components of CIMDUO. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. • Lactic Acidosis/Severe Hepatomegaly with Steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. • New Onset or Worsening Renal Impairment: Can include acute renal failure and Fanconi syndrome. Assess estimated creatinine clearance before initiating treatment with tenofovir disoproxil fumarate, a component of CIMDUO.

The following adverse reactions are discussed in other sections of the labeling: • Lactic Acidosis/Severe Hepatomegaly with Steatosis. • Exacerbations of Hepatitis B. • New Onset or Worsening Renal Impairment. • Hepatic Decompensation in Patients Co-infected with HIV-1 and Hepatitis C. • Pancreatitis. • Decreases in Bone Mineral Density. • Immune Reconstitution Syndrome. • Fat Redistribution. • Most common adverse reactions (> 10% with CIMDUO) are headache, pain, depression, diarrhea, and rash.

• Atazanavir: Atazanavir should be coadministered with ritonavir when coadministered with CIMDUO. • HIV-1 Protease Inhibitors: Monitor for evidence of tenofovir toxicity when CIMDUO is coadministrated with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. • Sorbitol: Avoid chronic administration of sorbitol with CIMDUO.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).