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 LO. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment [see Warnings and Precautions (5.2)].
SYMFI LO 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.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
All patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy.
The concomitant use of SYMFI LO and other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of SYMFI LO and possible development of resistance or possible clinically significant adverse reactions from greater exposures of concomitant drugs. TDF, a component of SYMFI LO is principally eliminated by the kidney.
Renal impairment, including cases of acute renal failure and Fanconi syndrome. It is recommended that estimated creatinine clearance be assessed in all patients prior to initiating therapy. In patients at risk of renal dysfunction, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein be assessed prior to initiation and periodically during therapy. SYMFI LO should be avoided with concurrent or recent use of a nephrotoxic agent.
Serious psychiatric adverse experiences have been reported in patients treated with efavirenz (EFV), a component of SYMFI LO. In controlled trials in patients treated with regimens containing EFV the following serious psychiatric events occurred: severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions.
Patients receiving EFV, a component of SYMFI LO, in controlled trials reported central nervous system symptoms. These symptoms included, but were not limited to, dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, and hallucinations and usually began 1 to 2 days after initiating therapy and resolve in 2 to 4 weeks. Dosing at bedtime may improve tolerability. These symptoms were not predictive of subsequent onset of the less frequent psychiatric symptoms.
EFV, a component of SYMFI LO, may cause fetal harm when administered during the first trimester to a pregnant woman. Females of reproductive potential who are receiving EFV should avoid pregnancy.
In controlled clinical trials, patients treated with 600 mg EFV experienced new-onset skin rash associated with blistering, moist desquamation, or ulceration. EFV should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. EFV can generally be reinitiated in patients interrupting therapy because of rash.
EFV, a component of SYMFI LO, is not recommended for patients with moderate or severe hepatic impairment. Careful monitoring is recommended for patients with mild hepatic impairment Monitoring of liver enzymes before and during treatment is recommended for all patients. Consider discontinuing SYMFI LO in patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range. Discontinue SYMFI LO if elevation of serum transaminases is accompanied by clinical signs or symptoms of hepatitis or hepatic decompensation.
Hepatic decompensation, some fatal, has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy and interferon and ribavirin-based regimens. Monitor for treatment-associated toxicities.
Use in caution in pediatric patients with a history of pancreatitis or other significant risk factors for pancreatitis.
Convulsions have been observed in patients receiving EFV, generally in the presence of known medical history of seizures. Caution should be taken in any patient with a history of seizures.
Treatment with EFV has resulted in increases in the concentration of total cholesterol and triglycerides. Cholesterol and triglyceride testing should be performed before initiating EFV therapy and at periodic intervals during therapy.
Decreases in Bone Mineral Density have been observed in HIV-1 infected patients. Consider assessment of bone mineral density in patients with a history of pathologic fracture or other risk factors for osteoporosis or bone loss.
Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of TDF.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barre syndrome) have also been reported to occur in the setting of immune reconstitution inpatients treated with combination antiretroviral therapy, including EFV, 3TC, and TDF.
In HIV-1 infected patients, redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving combination antiretroviral therapy.
QTc prolongation has been observed with the use of EFV.
Most common adverse reactions (> 5% with SYMFI LO components) are rash and dizziness.
SYMFI LO® (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 35 kg.
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