Symfi Lo

Last updated on RxList: 7/19/2021
Symfi Lo Side Effects Center

Last reviewed on RxList 3/22/2018

Symfi Lo (efavirenz, lamivudine and tenofovir disoproxil fumarate) is a three-drug combination of a non-nucleoside reverse transcriptase inhibitor, and two nucleo(t)side reverse transcriptase inhibitors 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. Common side effects of Symfi Lo include:

The recommended dose of Symfi Lo is one tablet taken orally once daily on an empty stomach, preferably at bedtime. Symfi Lo may interact with other antiretroviral medications, drugs that prolong the QTc interval, antivirals, aminoglycosides, high-dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDs), antimycobacterials, anticoagulants, anticonvulsants, antidepressants, antifungals, some antibiotics, antimalarials, calcium channel blockers, HMG-CoA reductase inhibitors (“statins”), hepatitis B and C antiviral agents, hormonal contraceptives, immunosuppressants, sorbitol, and narcotics. Tell your doctor all medications and supplements you use. Tell your doctor if you are pregnant or plan to become pregnant before using Symfi Lo; women should avoid pregnancy during EFV therapy, a component of Symfi Lo, and for 12 weeks after discontinuation. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Symfi Lo during pregnancy. Breastfeeding is not recommended while using Symfi Lo due to the potential for HIV transmission.

Our Symfi Lo (efavirenz, lamivudine and tenofovir disoproxil fumarate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Symfi Lo Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Call your doctor at once if you have:

  • severe dizziness or drowsiness, trouble concentrating, strange dreams;
  • confusion, thinking problems, seeing or hearing things that are not real (may occur months to years after you start taking this medicine);
  • fast or pounding heartbeats, fluttering in your chest, and sudden dizziness (like you might pass out);
  • problems with balance or coordination;
  • new or worsening bone pain;
  • pain in your arms, legs, hands, or feet;
  • lactic acidosis--unusual muscle pain, trouble breathing, stomach pain, vomiting, irregular heart rate, dizziness, feeling cold, or feeling very weak or tired;
  • pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting;
  • unusual thoughts--fear, paranoia, feeling sad or hopeless, thoughts of hurting yourself or others; or
  • liver problems--swelling around your midsection, upper stomach pain, unusual tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Symfi affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:

  • signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss;
  • trouble speaking or swallowing, problems with balance or eye movement, weakness or prickly feeling; or
  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.

Common side effects may include:

  • headache, dizziness;
  • depression, thinking problems;
  • nausea, diarrhea;
  • sleep problems (insomnia);
  • pain;
  • weakness, tiredness;
  • cough, stuffy nose, sinus pain;
  • rash; or
  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Symfi Lo (Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate Tablets)

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Symfi Lo Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in other sections of the labeling:

  • Lactic Acidosis/Severe Hepatomegaly with Steatosis [see WARNINGS AND PRECAUTIONS].
  • Exacerbations of Hepatitis B [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
  • New Onset or Worsening Renal Impairment [see WARNINGS AND PRECAUTIONS].
  • Psychiatric Symptoms [see WARNINGS AND PRECAUTIONS].
  • Nervous System Symptoms [see WARNINGS AND PRECAUTIONS].
  • Skin and Systemic Hypersensitivity Reaction [see WARNINGS AND PRECAUTIONS].
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS].
  • Hepatic Decompensation in Patients Co-infected with HIV-1 and Hepatitis C [see WARNINGS AND PRECAUTIONS].
  • Pancreatitis [see WARNINGS AND PRECAUTIONS].
  • Decreases in Bone Mineral Density [see WARNINGS AND PRECAUTIONS].
  • Immune Reconstitution Syndrome [see WARNINGS AND PRECAUTIONS].
  • Fat Redistribution [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, the adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Efavirenz, Lamivudine And Tenofovir Disoproxil Fumarate

Treatment-Naive Patients

Study 903 -Adverse Reactions

The most common adverse reactions seen in a double-blind comparative controlled study in which 600 treatment-naive subjects received TDF (N = 299) or stavudine (d4T) (N = 301) in combination with 3TC and EFV for 144 weeks were mild to moderate gastrointestinal events and dizziness.

Mild adverse reactions (Grade 1) were common with a similar incidence in both arms, and included dizziness, diarrhea, and nausea. Selected moderate to severe adverse reactions are summarized in Table 1.

Table 1: Selected Adverse Reactionsa (Grades 2-4) Reported in ≥ 5% in Any Treatment Group in Study 903 (0-144 Weeks)

  TDF+ 3TC + EFV
N = 299
d4T + 3TC + EFV
N = 301
Body as a Whole
Headache 14% 17%
Pain 13% 12%
Fever 8% 7%
Abdominal pain 7% 12%
Back pain 9% 8%
Asthenia 6% 7%
Digestive System
Diarrhea 11% 13%
Nausea 8% 9%
Dyspepsia 4% 5%
Vomiting 5% 9%
Metabolic Disorders
Lipodystrophyb 1% 8%
Musculoskeletal
Arthralgia 5% 7%
Myalgia 3% 5%
Nervous System
Depression 11% 10%
Insomnia 5% 8%
Dizziness 3% 6%
Peripheral neuropathyc 1% 5%
Anxiety 6% 6%
Respiratory
Pneumonia 5% 5%
Skin and Appendages
Rash eventd 18% 12%
a Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug.
b Lipodystrophy represents a variety of investigator-described adverse events not a protocol-defined syndrome.
c Peripheral neuropathy includes peripheral neuritis and neuropathy.
d Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash.

ENCORE1 Study -Adverse Reactions

The most common adverse reactions seen in a double-blind comparative controlled study in which 630 treatment-naive subjects received EFV 400 mg (N = 321) or EFV 600 mg (N = 309) in combination with fixed-dose emtricitabine (FTC)/TDF for 48 weeks were mild to moderate gastrointestinal events, dizziness, abnormal dreams, and rash. Selected clinical adverse reactions of moderate or severe intensity reported in ≥ 2% of treatment-naive patients receiving combination therapy including EFV 400 mg and EFV 600 mg are presented in Table 2.

Table 2: Selected Adverse Reactionsa (Grades 2-4) Reported in ≥ 2% in Either Treatment Group in the ENCORE1 Study through Week 48

  EFV 400 mg + FTC/TDF
N = 321
EFV 600 mg + FTC/TDF
N = 309
Rash eventb 9% 13%
Dizziness 6% 9%
Insomnia 3% 4%
Abnormal dreams 2% 2%
Headache 1% 3%
Diarrhea 2% 3%
Vomiting 1% 2%
Pyrexia 2% 1%
Upper respiratory tract infection 3% 1%
Nasopharyngitis 3% 2%
Herpes zoster 3% 1%
Gastroenteritis 2% 2%
a Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug.
b Rash events include dermatitis allergic, drug hypersensitivity, pruritus generalized, eosinophilic pustular folliculitis, rash, rash erythematous, rash generalized, rash macular, rash maculopapular, rash morbilliform, rash papular, rash pruritic, rash vesicular, and urticaria.

Laboratory Abnormalities: With the exception of fasting cholesterol and fasting triglyceride elevations that were more common in the stavudine group (40% and 9%) compared with TDF (19% and 1%) respectively, laboratory abnormalities observed in this study occurred with similar frequency in the tenofovir disoproxil fumarate and stavudine treatment arms. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 3.

Table 3: Grade 3/4 Laboratory Abnormalities Reported in ≥ 1% of Patients Randomized to Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate in Study 903 (0-144 Weeks)

  TDF + 3TC + EFV
N = 299
d4T + 3TC + EFV
N = 301
Any ≥ Grade 3 Laboratory Abnormality 36% 42%
Fasting Cholesterol (> 240 mg/dL) 19% 40%
Creatine Kinase (M: > 990 U/L; F: > 845 U/L) 12% 12%
Serum Amylase (> 175 U/L) 9% 8%
AST (M: > 180 U/L; F: > 170 U/L) 5% 7%
ALT (M: > 215 U/L; F: > 170 U/L) 4% 5%
Hematuria (> 100 RBC/HPF) 7% 7%
Neutrophils (< 750/mm³) 3% 1%
Fasting Triglycerides (> 750 mg/dL) 1% 9%

In ENCORE1 study, a summary of Grade 3 and 4 laboratory abnormalities is provided in Table 4.

Table 4: Grades 3-4 Laboratory Abnormalities in ≥ 2% in Either Treatment Group Through Week 48

Laboratory Parameter EFV 400 mg + FTC + TDF
N = 321
EFV 600 mg + FTC + TDF
N = 309
ALT 5% 3%
AST 2% 2%
Total bilirubin 0.3% 3%
Cholesterol 2% 5%
Neutrophils 2% 3%
Phosphorus 2% 3%

Pancreatitis

Pancreatitis, which has been fatal in some cases, has been observed in antiretroviral nucleoside-experienced pediatric subjects receiving 3TC alone or in combination with other antiretroviral agents [see WARNINGS AND PRECAUTIONS].

Changes In Bone Mineral Density

In HIV-1-infected adult subjects in Study 903, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in subjects receiving TDF + 3TC + EFV (-2.2% ± 3.9) compared with subjects receiving d4T + 3TC + EFV (-1.0% ± 4.6) through 144 weeks. Changes in BMD at the hip were similar between the two treatment groups (-2.8% ± 3.5 in the TDF group vs. -2.4% ± 4.5 in the d4T group). In both groups, the majority of the reduction in BMD occurred in the first 24-48 weeks of the trial and this reduction was sustained through Week 144. Twenty-eight percent of TDF-treated subjects vs. 21% of the d4T-treated subjects lost at least 5% of BMD at the spine or 7% of BMD at the hip. Clinically relevant fractures (excluding fingers and toes) were reported in 4 subjects in the TDF group and 6 subjects in the d4T group. In addition, there were significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C telopeptide, and urinary N telopeptide) and higher serum parathyroid hormone levels and 1,25 Vitamin D levels in the TDF group relative to the d4T group; however, except for bone-specific alkaline phosphatase, these changes resulted in values that remained within the normal range [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions have been identified during post-approval use for each of the individual components of SYMFI LO (EFV, 3TC, and TDF). Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to EFV, 3TC, and TDF.

Efavirenz

Body as a Whole: allergic reactions, asthenia, redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].

Central and Peripheral Nervous System: abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, vertigo.

Endocrine: gynecomastia.

Gastrointestinal: constipation, malabsorption.

Cardiovascular: flushing, palpitations.

Liver and Biliary System: hepatic enzyme increase, hepatic failure, hepatitis.

Metabolic and Nutritional: hypercholesterolemia, hypertriglyceridemia.

Musculoskeletal: arthralgia, myalgia, myopathy.

Psychiatric: aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide, catatonia.

Respiratory: dyspnea.

Skin and Appendages: erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome.

Special Senses: abnormal vision, tinnitus.

Lamivudine

Body as a Whole: redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].

Endocrine and Metabolic: hyperglycemia.

General: weakness. Hemic and Lymphatic: anemia (including pure red cell aplasia and severe anemias progressing on therapy).

Hepatic and Pancreatic: lactic acidosis and hepatic steatosis, posttreatment exacerbation of hepatitis B [see BOXED WARNING, WARNINGS AND PRECAUTIONS].

Hypersensitivity: anaphylaxis, urticaria.

Musculoskeletal: muscle weakness, CPK elevation, rhabdomyolysis.

Skin: Alopecia, pruritus.

Tenofovir Disoproxil Fumarate

Immune System Disorders: allergic reaction, including angioedema.

Metabolism and Nutrition Disorders: lactic acidosis, hypokalemia, hypophosphatemia.

Respiratory, Thoracic, and Mediastinal Disorders: dyspnea.

Gastrointestinal Disorders: pancreatitis, increased amylase, abdominal pain.

Renal and Urinary Disorders: renal insufficiency, acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria [see WARNINGS AND PRECAUTIONS].

Hepatobiliary Disorders: hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT).

Skin and Subcutaneous Tissue Disorders: rash. Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy.

General Disorders and Administration Site Conditions: asthenia.

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

Read the entire FDA prescribing information for Symfi Lo (Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate Tablets)

© Symfi Lo Patient Information is supplied by Cerner Multum, Inc. and Symfi Lo Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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