SYMFI LO

SYMFI LO- efavirenz, lamivudine and tenofovir disoproxil fumarate tablet, film coated
Mylan Specialty L.P.

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 (5.1) ].

1 INDICATIONS AND USAGE

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.

2 DOSAGE AND ADMINISTRATION

2.1 Testing Prior to Initiation and During Treatment with SYMFI LO

Prior to initiation of SYMFI LO, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1)].

It is recommended that serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose, and urine protein be assessed before initiating SYMFI LO and during therapy in all patients as clinically appropriate [see Warnings and Precautions (5.4)].

Monitor hepatic function prior to and during treatment with SYMFI LO [see Warnings and Precautions (5.9)].

2.2 Recommended Dosage for Adult and Pediatric Patients Weighing at Least 35 kg

SYMFI LO is a three-drug fixed-dose combination product containing 400 mg of efavirenz (EFV), 300 mg of lamivudine (3TC), and 300 mg of tenofovir disoproxil fumarate (TDF). The recommended dosage of SYMFI LO in HIV-1-infected adults and pediatric patients weighing at least 35 kg is one tablet taken orally once daily. SYMFI LO tablets should be taken on an empty stomach, preferably at bedtime. Dosing at bedtime may improve the tolerability of nervous system symptoms [see Warnings and Precautions (5.6) and Adverse Reactions (6.1)].

2.3 Not Recommended in Renal Impairment

Because SYMFI LO is a fixed-dose combination tablet 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 [see Use in Specific Populations (8.6)].

2.4 Not Recommended in Moderate to Severe Hepatic Impairment

SYMFI LO is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) [see Warnings and Precautions (5.9) and Use in Specific Populations (8.7)].

3 DOSAGE FORMS AND STRENGTHS

Tablets: 400 mg of efavirenz, 300 mg of lamivudine, and 300 mg of tenofovir disoproxil fumarate (equivalent to 245 mg of tenofovir disoproxil).

The 400 mg/300 mg/300 mg tablets are white to off-white, film-coated, oval, unscored tablets debossed with “M ” on one side and “TLE ” on the other side.

4 CONTRAINDICATIONS

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 [see Warnings and Precautions (5.8)].
when coadministered with elbasvir and grazoprevir [see Warnings and Precautions (5.3) and Drug Interactions (7.5)].

5 WARNINGS AND PRECAUTIONS

5.1 Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV

Posttreatment Exacerbations of Hepatitis

All patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy [see Dosage and Administration (2.1) ]. Discontinuation of anti-HBV therapy, including 3TC and TDF, may be associated with severe acute exacerbations of hepatitis B. Patients infected with HBV who discontinue SYMFI LO should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

Important Differences Among Lamivudine-Containing Products

SYMFI LO tablets contain a higher dose of the same active ingredient, 3TC, than EPIVIR-HBV® tablets. EPIVIR-HBV was developed for patients with chronic hepatitis B. The formulation and dosage of 3TC in EPIVIR-HBV are not appropriate for patients co-infected with HIV-1 and HBV. Safety and efficacy of 3TC have not been established for treatment of chronic hepatitis B in patients co-infected with HIV-1 and HBV.

If treatment with EPIVIR-HBV, TDF, or a tenofovir alafenamide (TAF)-containing product is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV-1 infection, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV-1 treatment.

5.2 Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. Female sex and obesity may be risk factors for the development of lactic acidosis and severe hepatomegaly with steatosis in patients treated with antiretroviral nucleoside analogues. 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.

5.3 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

The concomitant use of SYMFI LO and other drugs may result in known or potentially significant drug interactions, some of which may lead to [see Contraindications (4) and Drug Interactions (7.5)]:

Loss of therapeutic effect of SYMFI LO and possible development of resistance.
Possible clinically significant adverse reactions from greater exposures of concomitant drugs.

See Table 5 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during therapy with SYMFI LO; review concomitant medications during therapy with SYMFI LO; and monitor for the adverse reactions associated with the concomitant drugs.

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