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Emtriva Side Effects

Generic Name: emtricitabine

Please note - some side effects for Emtriva may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Emtriva - for the Consumer

Emtriva

All medicines may cause side effects, but many people have no, or minor side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Emtriva:

Abnormal dreams; change in color of skin on palms or soles of feet; cough; diarrhea; dizziness; headache; indigestion or stomach upset; joint or muscle pain; mild stomach pain; nausea; runny nose; sleeplessness; tiredness; vomiting; weakness or lack of energy.

Seek medical attention right away if any of these SEVERE side effects occur when using Emtriva:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); burning, numbness, or tingling; depression; fast or difficult breathing; fast, slow, or irregular heartbeat; feeling unusually cold; fever, chills, or sore throat; general feeling of being unwell; muscle pain or tenderness; severe or persistent cough; severe or persistent nausea or vomiting; severe or persistent stomach discomfort, pain, or tenderness; sluggishness; symptoms of liver problems (eg, dark urine, pale stools, persistent loss of appetite, yellowing of the eyes or skin); unusual drowsiness, dizziness, or light-headedness; unusual muscle pain or tenderness; unusual tiredness or weakness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Emtriva Solution

All medicines may cause side effects, but many people have no, or minor side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Emtriva Solution:

Abnormal dreams; change in color of skin on palms or soles of feet; cough; diarrhea; dizziness; headache; indigestion or stomach upset; joint or muscle pain; mild stomach pain; nausea; runny nose; sleeplessness; tiredness; vomiting; weakness or lack of energy.

Seek medical attention right away if any of these SEVERE side effects occur when using Emtriva Solution:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); burning, numbness, or tingling; depression; fast or difficult breathing; fast, slow, or irregular heartbeat; feeling unusually cold; fever, chills, or sore throat; general feeling of being unwell; muscle pain or tenderness; severe or persistent cough; severe or persistent nausea or vomiting; severe or persistent stomach discomfort, pain, or tenderness; sluggishness; symptoms of liver problems (eg, dark urine, pale stools, persistent loss of appetite, yellowing of the eyes or skin); unusual drowsiness, dizziness, or light-headedness; unusual muscle pain or tenderness; unusual tiredness or weakness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Emtriva Side Effects - for the Professional

Emtriva

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

Adverse Reactions from Clinical Trials Experience

Adult Patients

More than 2,000 adult patients with HIV-1 infection have been treated with Emtriva alone or in combination with other antiretroviral agents for periods of 10 days to 200 weeks in clinical trials.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the 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.

The most common adverse reactions (incidence ≥10%, any severity) identified from any of the 3 large controlled clinical trials include headache, diarrhea nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis.

Studies 301A and 303 - Treatment Emergent Adverse Reactions: The most common adverse reactions that occurred in patients receiving Emtriva with other antiretroviral agents in clinical studies 301A and 303 were headache, diarrhea, nausea, and rash, which were generally of mild to moderate severity. Approximately 1% of patients discontinued participation in the clinical studies due to these events. All adverse reactions were reported with similar frequency in Emtriva and control treatment groups with the exception of skin discoloration which was reported with higher frequency in the Emtriva treated group.

Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

A summary of Emtriva treatment emergent clinical adverse reactions in studies 301A and 303 is provided in Table 2.

Table 2 Selected Treatment-Emergent Adverse Reactions (All Grades, Regardless of Causality) Reported in ≥3% of Emtriva-Treated Patients in Either Study 301A or 303 (0–48 Weeks)
303 301A
Emtriva
+ ZDV/d4T
+ NNRTI/PI
(N=294)
Lamivudine
+ ZDV/d4T
+ NNRTI/PI
(N=146)
Emtriva
+ didanosine + efavirenz
(N=286)
Stavudine
+ didanosine
+ efavirenz
(N=285)
*
Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, and allergic reaction.
Body as a Whole
  Abdominal pain 8% 11% 14% 17%
  Asthenia 16% 10% 12% 17%
  Headache 13% 6% 22% 25%
Digestive System
  Diarrhea 23% 18% 23% 32%
  Dyspepsia 4% 5% 8% 12%
  Nausea 18% 12% 13% 23%
  Vomiting 9% 7% 9% 12%
Musculoskeletal
  Arthralgia 3% 4% 5% 6%
  Myalgia 4% 4% 6% 3%
Nervous System
  Abnormal dreams 2% <1% 11% 19%
  Depressive disorders 6% 10% 9% 13%
  Dizziness 4% 5% 25% 26%
  Insomnia 7% 3% 16% 21%
  Neuropathy/peripheral neuritis 4% 3% 4% 13%
  Paresthesia 5% 7% 6% 12%
Respiratory
  Increased cough 14% 11% 14% 8%
  Rhinitis 18% 12% 12% 10%
Skin
  Rash event* 17% 14% 30% 33%

Studies 301A and 303 - Laboratory Abnormalities:

Laboratory abnormalities in these studies occurred with similar frequency in the Emtriva and comparator groups. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 3 below.

Table 3 Treatment-Emergent Grade 3/4 Laboratory Abnormalities Reported in ≥1% of Emtriva-Treated Patients in Either Study 301A or 303
303 301A
Emtriva
+ ZDV/d4T
+ NNRTI/PI
(N=294)
Lamivudine
+ ZDV/d4T
+ NNRTI/PI
(N=146)
Emtriva
+ Didanosine
+ Efavirenz
(N=286)
Stavudine
+ Didanosine
+ Efavirenz
(N=285)
*
ULN = Upper limit of normal
Percentage with grade 3 or grade 4 laboratory abnormality 31% 28% 34% 38%
ALT (>5.0 × ULN*) 2% 1% 5% 6%
AST (>5.0 × ULN) 3% <1% 6% 9%
Bilirubin (>2.5 × ULN) 1% 2% <1% <1%
Creatine kinase
(>4.0 × ULN)
11% 14% 12% 11%
Neutrophils (<750 mm3) 5% 3% 5% 7%
Pancreatic amylase
(>2.0 × ULN)
2% 2% <1% 1%
Serum amylase
(>2.0 × ULN)
2% 2% 5% 10%
Serum glucose
<40 or >250 mg/dL)
3% 3% 2% 3%
Serum lipase
(>2.0 × ULN)
<1% <1% 1% 2%
Triglycerides
(>750 mg/dL)
10% 8% 9% 6%

Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naïve patients received either VIREAD + Emtriva administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this study were generally consistent with those seen in previous studies in treatment-experienced or treatment-naïve patients (Table 4).

Table 4 Selected Treatment-Emergent Adverse Reactions* (Grades 2–4) Reported in ≥5% in Any Treatment Group in Study 934 (0–144 Weeks)
TDF + Emtriva + EFV AZT/3TC + EFV
N=257 N=254
*
Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug.
From Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + Emtriva with efavirenz.
Rash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular.
Gastrointestinal Disorder
  Diarrhea 9% 5%
  Nausea 9% 7%
  Vomiting 2% 5%
General Disorders and Administration Site Condition
  Fatigue 9% 8%
Infections and Infestations
  Sinusitis 8% 4%
  Upper respiratory tract infections 8% 5%
  Nasopharyngitis 5% 3%
Nervous System Disorders
  Headache 6% 5%
  Dizziness 8% 7%
Psychiatric Disorders
  Depression 9% 7%
  Insomnia 5% 7%
Skin and Subcutaneous Tissue Disorders
  Rash event 7% 9%

Study 934 – Laboratory Abnormalities: Significant laboratory abnormalities observed in this study are shown in Table 5.

Table 5 Significant Laboratory Abnormalities Reported in ≥1% of Patients in Any Treatment Group in Study 934 (0–144 Weeks)
TDF* + Emtriva + EFV AZT/3TC + EFV
N=257 N=254
*
From Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + Emtriva with efavirenz.
Any ≥ Grade 3 Laboratory Abnormality 30% 26%
Fasting Cholesterol (>240 mg/dL) 22% 24%
Creatine Kinase
(M: >990 U/L)
(F: >845 U/L)
9% 7%
Serum Amylase (>175 U/L) 8% 4%
Alkaline Phosphatase (>550 U/L) 1% 0%
AST
(M: >180 U/L)
(F: >170 U/L)
3% 3%
ALT
(M: >215 U/L)
(F: >170 U/L)
2% 3%
Hemoglobin (<8.0 mg/dL) 0% 4%
Hyperglycemia (>250 mg/dL) 2% 1%
Hematuria (>75 RBC/HPF) 3% 2%
Glycosuria (3+) <1% 1%
Neutrophils (<750/mm3) 3% 5%
Fasting Triglycerides (>750 mg/dL) 4% 2%

Pediatric Patients

Assessment of adverse reactions is based on data from Study 203, an open label, uncontrolled study of 116 HIV-1-infected pediatric patients who received emtricitabine through 48 weeks. The adverse reaction profile in pediatric patients was generally comparable to that observed in clinical studies of Emtriva in adult patients [See Adverse Reactions (6.1)]. Hyperpigmentation was more frequent in children. Additional adverse reactions identified from this study include anemia.

Selected treatment-emergent adverse events, regardless of causality, reported in patients during 48 weeks of treatment were the following: infection (44%), hyperpigmentation (32%), increased cough (28%), vomiting (23%), otitis media (23%), rash (21%), rhinitis (20%), diarrhea (20%), fever (18%), pneumonia (15%), gastroenteritis (11%), abdominal pain (10%), and anemia (7%). Treatment-emergent grade 3/4 laboratory abnormalities were experienced by 9% of pediatric patients, including amylase >2.0 × ULN (n=4), neutrophils <750/mm3 (n=3), ALT >5 × ULN (n=2), elevated CPK (>4 × ULN) (n=2) and one patient each with elevated bilirubin (>3.0 × ULN), elevated GGT (>10 × ULN), elevated lipase (>2.5 × ULN), decreased hemoglobin (<7 g/dL), and decreased glucose (<40 mg/dL).

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Side Effects by Body System - for Healthcare Professionals

General

The most common side effects reported during any of 3 large controlled clinical trials were headache, diarrhea, nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis.

During 2 clinical trials, the most common side effects associated with emtricitabine in combination with other antiretrovirals were headache, diarrhea, nausea, and rash. Most were of mild to moderate severity. Treatment was discontinued due to these adverse effects in approximately 1% of patients.

Side effects have been reported for emtricitabine when taken in combination with other antiretroviral agents.

Dermatologic

Dermatological side effects have included rash event (any Grade: up to 30%; Grades 2 to 4: 7%). "Rash event" included rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, exfoliative rash, generalized rash, macular rash, pruritic rash, vesicular rash, and allergic reaction. Skin discoloration (palmar-plantar hyperpigmentation) has been reported.

Nervous system

Nervous system side effects have included dizziness (any Grade: up to 25%; Grades 2 to 4: 8%), headache (any Grade: up to 22%; Grades 2 to 4: 6%), insomnia (any Grade: up to 16%; Grades 2 to 4: 5%), paresthesia (any Grade: up to 6%), neuropathy/peripheral neuritis (any Grade: 4%), and somnolence.

Gastrointestinal

Gastrointestinal side effects have included diarrhea (any Grade: 23%; Grades 2 to 4: 9%), nausea (any Grade: up to 18%; Grades 2 to 4: 9%), vomiting (any Grade: 9%; Grades 2 to 4: 2%), and dyspepsia (any Grade: up to 8%).

Metabolic

Metabolic side effects have included blood glucose changes (less than 40 or greater than 250 mg/dL; up to 3%), hyperglycemia (greater than 250 mg/dL; 2%), and increased fasting cholesterol (greater than 240 mg/dL; 22%), triglycerides (greater than 750 mg/dL; up to 10%), serum amylase (greater than 2 times ULN: up to 5%; greater than 175 units/L: 8%), fasting triglycerides (greater than 750 mg/dL; 4%), pancreatic amylase (greater than 2 times ULN; up to 2%), serum lipase (greater than 2 times ULN; up to 1%), and alkaline phosphatase (greater than 550 units/L; 1%). Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy.

Respiratory

Respiratory side effects have included rhinitis (any Grade: up to 18%), increased cough (any Grade: 14%), sinusitis (Grades 2 to 4: 8%), upper respiratory tract infections (Grades 2 to 4: 8%), and nasopharyngitis (Grades 2 to 4: 5%).

Other

Other side effects have included asthenia (any Grade: up to 16%), abdominal pain (any Grade: up to 14%), and fatigue (Grades 2 to 4: 9%).

Musculoskeletal

Increased creatine kinase (greater than 990 units/L in males and 845 units/L in females) has been reported in 9% of patients.

Musculoskeletal side effects have included elevated creatine kinase (greater than 4 times ULN; up to 12%), myalgia (any Grade: up to 6%), and arthralgia (any Grade: up to 5%).

Psychiatric

Psychiatric side effects have included abnormal dreams (any Grade: up to 11%), depressive disorders (any Grade: up to 9%), and depression (Grades 2 to 4: 9%).

Hepatic

Increased AST (greater than 180 units/L in males and 170 units/L in females) has been reported in 3% of patients. Increased ALT (greater than 215 units/L in males and 170 units/L in females) has been reported in 2% of patients.

Hepatic side effects have included elevated AST (greater than 5 times ULN; up to 6%), ALT (greater than 5 times ULN; up to 5%), and bilirubin (greater than 2.5 times ULN; up to 1%). Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of emtricitabine and other nucleoside analogs alone or in combination with other antiretroviral agents. Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and hepatitis B after discontinuation of emtricitabine and were associated with liver failure and liver decompensation in some patients.

Immunologic

Immunologic side effects have included immune reconstitution syndrome. Autoimmune disorders (e.g., Graves' disease, polymyositis, and Guillain-Barre syndrome) have been reported in the setting of immune reconstitution.

Hematologic

Hematologic side effects have included decreased neutrophils (less than 750/mm3; up to 5%).

Genitourinary

Genitourinary side effects have included hematuria (greater than 75 RBC/HPF; 3%) and glycosuria (3 plus; less than 1%).

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