Efavirenz, Lamivudine and Tenofovir disoproxil

SYMFI ® (efavirenz, lamivudine and tenofovir disoproxil fumarate) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients weighing at least 40 kg. SYMFI is a three-drug combination of efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), both nucleo(t)side reverse transcriptase inhibitors and is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric patients weighing at least 40 kg.

SYMFI is a fixed-dose combination of antiviral drugs EFV, 3TC, and TDF with antiviral activity against HIV-1. Mechanism of Action Efavirenz EFV is an NNRTI of HIV-1. EFV activity is mediated predominantly by noncompetitive inhibition of HIV-1 reverse transcriptase (RT). HIV-2 RT and human cellular DNA polymerases α, β, γ, and δ are not inhibited by EFV. 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.

• Testing: Prior to initiation and during treatment with SYMFI, 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 on an empty stomach, preferably at bedtime. • Renal Impairment: Not recommended in patients with CrCL less than 50 mL/min or patients with end-stage renal disease requiring hemodialysis. • Hepatic Impairment: Not recommended for patients with moderate or severe hepatic impairment. Use caution in patients with mild hepatic impairment.

SYMFI is contraindicated: • in patients with a previous hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components contained in the formulation. • when coadministered with elbasvir and grazoprevir. • SYMFI is contraindicated in patients with previous hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product. • Coadministration with elbasvir/grazoprevir.

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, two components of SYMFI. 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. Avoid administering SYMFI with concurrent or recent use of nephrotoxic drugs.

The following adverse reactions are discussed in other sections of the labeling: • Exacerbations of Hepatitis B. • Lactic Acidosis/Severe Hepatomegaly with Steatosis. • New Onset or Worsening Renal Impairment. • Psychiatric Symptoms. • Nervous System Symptoms. • Skin and Systemic Hypersensitivity Reaction. • Hepatotoxicity. • Pancreatitis. • Bone Loss and Mineralization Effects. • Immune Reconstitution Syndrome. • Fat Redistribution. • Most common adverse reactions are impaired concentration, abnormal dreams, headache, nausea, malaise and fatigue, nasal signs and symptoms, diarrhea, rash, dizziness, insomnia, pain, depression, asthenia, and cough.

• SYMFI should not be administered with other antiretroviral medications for the treatment of HIV-1 infection. • Coadministration of SYMFI can alter the concentrations of other drugs and other drugs may alter the concentration of SYMFI. The potential for drug-drug interactions should be considered before and during therapy.

Store below 30°C (86°F).