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Complera

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Tivicay is an integrase strand transfer inhibitor that interferes with one of the enzymes necessary for HIV to multiply. "...

Complera

Complera

Complera Side Effects Center

Medical Editor: Charles Patrick Davis, MD, PhD

Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) tablets are composed of three antiviral compounds that are indicated for use as a complete regimen for the treatment of HIV-1 infection in adults that have had no prior antiviral treatments. There is no generic for Complera. Complera provides a complete treatment for HIV infection. Do not take other HIV medicines with Complera. Side effects of Complera can include new or worsening renal impairment, depressive disorders, and decreases in bone density. Common side effects are headache, insomnia, rash, and depression.

Complera is a combination drug and is available only in one strength as follows: each tablet contains 200 mg of emtricitabine, 27.5 mg of rilpivirine hydrochloride (equivalent to 25 mg of rilpivirine), and 300 mg of tenofovir DF (equivalent to 245 mg of tenofovir disoproxil) as active ingredients. The recommended dose of Complera is one tablet taken orally once daily with a meal. Serious side effects may include lactic acidosis and severe hepatomegaly with steatosis. Women should talk to their healthcare providers if they are pregnant or planning to become pregnant. It is not known if Complera will harm unborn children. Also, there is a pregnancy registry for women who take antiviral medicines during pregnancy. Its purpose is to collect information about the health of women and their babies. Women should speak with a healthcare provider about how to take part in this registry. The Centers for Disease Control and Prevention (CDC) recommends that mothers with HIV not breastfeed because they can pass the HIV through their milk to the baby. It is not known if Complera can pass through breast milk and harm babies. Nursing mothers should talk to their healthcare providers about the best way to feed their babies. Complera is not recommended for patients less than 18 years of age.

Our Complera 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.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Complera in Detail - Patient Information: Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

This medication may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as:

  • muscle pain or weakness;
  • numb or cold feeling in your arms and legs;
  • trouble breathing;
  • feeling dizzy, light-headed, tired, or very weak;
  • stomach pain, nausea with vomiting; or
  • fast or uneven heart rate.

Call your doctor at once if you have any of these other serious side effects:

  • signs of liver damage - nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • confusion, severe depression, unusual thoughts or behavior, suicidal thoughts or actions;
  • increased thirst and urination, weakness, constipation;
  • urinating less than usual or not at all;
  • swelling, rapid weight gain, feeling short of breath;
  • signs of infection such as fever, chills, skin lesions, or cough with yellow or green mucus.

Less serious side effects may include:

  • headache, mild tired feeling;
  • dizziness, depressed mood;
  • sleep problems (insomnia), strange dreams;
  • diarrhea, mild nausea; 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 Complera (Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Tablets) »

What is Prescribing information?

The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.

Complera FDA Prescribing Information: Side Effects
(Adverse Reactions)

SIDE EFFECTS

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

Adverse Reactions From Clinical Trials Experience

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.

In HIV-1-Infected Subjects With No Antiretroviral Treatment History

Studies C209 and C215 - Treatment-Emergent Adverse Drug Reactions: The safety assessment of rilpivirine, used in combination with other antiretroviral drugs, is based on the Week 96 pooled data from 1368 subjects in the Phase 3 trials TMC278-C209 (ECHO) and TMC278-C215 (THRIVE) in antiretroviral treatment-naive HIV-1-infected adult subjects. A total of 686 subjects received rilpivirine in combination with other antiretroviral drugs as background regimen; most (N=550) received emtricitabine/tenofovir DF as background regimen. The number of subjects randomized to the control arm efavirenz was 682, of which 546 received emtricitabine/tenofovir DF as background regimen [See Clinical Studies]. The median duration of exposure for subjects in either treatment arm was 104 weeks.

Adverse drug reactions (ADR) observed at Week 96 in subjects who received rilpivirine or efavirenz plus emtricitabine/tenofovir DF as background regimen are shown in Table 1. No new types of adverse reactions were identified between Week 48 and Week 96. The adverse drug reactions observed in this subset of subjects were generally consistent with those seen for the overall patient population participating in these studies (refer to the prescribing information for Edurant).

The proportion of subjects who discontinued treatment with rilpivirine or efavirenz + emtricitabine/tenofovir DF due to ADR, regardless of severity, was 2% and 5%, respectively. The most common ADRs leading to discontinuation were psychiatric disorders: 9 (1.6%) subjects in the rilpivirine + emtricitabine/tenofovir DF arm and 12 (2.2%) subjects in the efavirenz + emtricitabine/tenofovir DF arm. Rash led to discontinuation in 1 (0.2%) subject in the rilpivirine + emtricitabine/tenofovir DF arm and 10 (1.8%) subjects in the efavirenz + emtricitabine/tenofovir DF arm.

Common Adverse Drug Reactions

Clinical ADRs to rilpivirine or efavirenz of at least moderate intensity ( ≥ Grade 2) reported in at least 2% of adult subjects are shown in Table 1.

Table 1 : Selected Treatment-Emergent Adverse Drug Reactionsa(Grades 2-4) Reported in ≥ 2% of Subjects Receiving Rilpivirine or Efavirenz in Combination with Emtricitabine/Tenofovir DF in Studies C209 and C215(Week 96 analysis)

  Rilpivirine + FTC/TDF
N=550
Efavirenz + FTC/TDF
N=546
Gastrointestinal Disorder
  Nausea 1% 2%
Nervous System Disorders
  Headache 2% 2%
  Dizziness 1% 7%
Psychiatric Disorders
  Depressive disordersb 2% 2%
  Insomnia 2% 2%
  Abnormal dreams 1% 3%
Skin and Subcutaneous Tissue Disorders
  Rash 1% 5%
a Frequencies of adverse reactions are based on all Grades 2-4 treatment-emergent adverse events assessed to be related to study drug.
b Includes adverse drug reactions reported as depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicide ideation.

Rilpivirine

Treatment-emergent adverse drug reactions of at least moderate intensity ( ≥ Grade 2) that occurred in less than 2% of subjects treated with rilpivirine plus any of the allowed background regimens (N=686) in clinical studies C209 and C215 include (grouped by Body System): vomiting, diarrhea, abdominal discomfort, abdominal pain, fatigue, cholecystitis, cholelithiasis, decreased appetite, somnolence, sleep disorders, anxiety, glomerulonephritis membranous, glomerulonephritis mesangioproliferative, and nephrolithiasis.

In Virologically-Suppressed HIV-1-Infected Subjects

No new adverse reactions to COMPLERA were identified in stable, virologicallysuppressed subjects switching to COMPLERA from a regimen containing a ritonavirboosted protease inhibitor; however the frequency of adverse reactions increased by 20% (Study 106) after switching to COMPLERA.

Emtricitabine and Tenofovir Disoproxil Fumarate

The following adverse reactions were observed in clinical trials of emtricitabine or tenofovir DF in combination with other antiretroviral agents:

The most common adverse drug reactions occurring in at least 10% of HIV-1-infected treatment-naive adult subjects in a Phase 3 clinical trial of emtricitabine and tenofovir DF in combination with another antiretroviral agent are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. In addition, adverse drug reactions that occurred in at least 5% of treatment-experienced or treatment-naive subjects receiving emtricitabine or tenofovir DF with other antiretroviral agents in clinical trials include abdominal pain, dyspepsia, vomiting, fever, pain, nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, arthralgia, back pain, myalgia, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), anxiety, increased cough, and rhinitis.

Skin discoloration has been reported with higher frequency among emtricitabine-treated subjects; it was manifested by hyperpigmentation on the palms and/or soles and was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Laboratory Abnormalities

The percentage of subjects treated with rilpivirine + emtricitabine/tenofovir DF or efavirenz + emtricitabine/tenofovir DF in studies C209 and C215 with selected treatment-emergent laboratory abnormalities (Grades 1 to 4), representing worst grade toxicity, are presented in Table 2.

Table 2 : Selected Laboratory Abnormalities (Grades 1-4) Reported in Subjects WhoReceived Rilpivirine or Efavirenz in Combination with Emtricitabine/Tenofovir DF in Studies C209 and C215 (Week 96 Analysis)

Laboratory Parameter Abnormality, (%) DAIDS Toxicity Range Rilpivirine + FTC/TDF
N=550
Efavirenz + FTC/TDF
N=546
BIOCHEMISTRY
Increased Creatinine
  Grade 1 1.1-1.3 x ULNa 6% 1%
  Grade 2 > 1.3-1.8 x ULN 1% 1%
  Grade 3 > 1.8-3.4 x ULN < 1% 0
  Grade 4 > 3.4 x ULN 0 < 1%
Increased AST
  Grade 1 1.25-2.5 x ULN 16% 19%
  Grade 2 > 2.5-5.0 x ULN 4% 7%
  Grade 3 > 5.0-10.0 x ULN 2% 3%
  Grade 4 > 10.0 x ULN 1% 1%
Increased ALT
  Grade 1 1.25-2.5 x ULN 19% 22%
 Grade 2 > 2.5-5.0 x ULN 5% 7%
  Grade 3 > 5.0-10.0 x ULN 1% 2%
  Grade 4 > 10.0 x ULN 1% 1%
Increased Total Bilirubin
  Grade 1 1.1-1.5 x ULN 6% < 1%
  Grade 2 > 1.5-2.5 x ULN 3% 1%
  Grade 3 > 2.5-5.0 x ULN 1% < 1%
Increased Total Cholesterol (fasted)
  Grade 1 200-239 mg/dL 14% 31%
  Grade 2 240-300 mg/dL 6% 18%
  Grade 3 > 300 mg/dL < 1% 2%
Increased LDL Cholesterol (fasted)
  Grade 1 130-159 mg/dL 13% 28%
  Grade 2 160-190 mg/dL 5% 13%
  Grade 3 > 190 mg/dL 1% 4%
Increased Triglycerides (fasted)
  Grade 2 500-750 mg/dL 1% 2%
  Grade 3 751-1,200 mg/dL 1% 2%
  Grade 4 > 1,200 mg/dL 0 1%
N = number of subjects per treatment group
a ULN = Upper limit of normal value.
Note: Percentages were calculated versus the number of subjects in ITT population with emtricitabine + tenofovir DF as background regimen.

Emtricitabine or Tenofovir Disoproxil Fumarate

The following laboratory abnormalities have been previously reported in subjects treated with emtricitabine or tenofovir DF with other antiretroviral agents in other clinical trials: Grade 3 or 4 laboratory abnormalities of increased pancreatic amylase ( > 2.0 x ULN), increased serum amylase ( > 175 U/L), increased lipase ( > 3.0 x ULN), increased alkaline phosphatase ( > 550 U/L), increased or decreased serum glucose ( < 40 or > 250 mg/dL), increased glycosuria ( ≥ 3+), increased creatine kinase (M: > 990 U/L; F: > 845 U/L), decreased neutrophils ( < 750/mm³) and increased hematuria ( > 75 RBC/HPF) occurred.

Adrenal Function

In the pooled Phase 3 trials of C209 and C215, in subjects treated with rilpivirine plus any of the allowed background regimen (N=686), at Week 96, there was an overall mean change from baseline in basal cortisol of -19.1 (95% CI: -30.9; -7.4) nmol/L in the rilpivirine group, and of +0.1 (95% CI: -12.6; 12.8) nmol/L in the efavirenz group. At Week 96, the mean change from baseline in ACTH-stimulated cortisol levels was lower in the rilpivirine group (+18.4 ± 8.36 nmol/L) than in the efavirenz group (+54.1 ± 7.24 nmol/L). Mean values for both basal and ACTH-stimulated cortisol values at Week 96 were within the normal range. Overall, there were no serious adverse events, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency. Effects on adrenal function were comparable by background N(t)RTIs.

Serum Creatinine

In the pooled Phase 3 trials of C209 and C215 trials in subjects treated with rilpivirine plus any of the allowed background regimen (N=686), there was a small increase in serum creatinine over 96 weeks of treatment with rilpivirine. Most of this increase occurred within the first four weeks of treatment with a mean change of 0.1 mg/dL (range: -0.3 mg/dL to 0.6 mg/dL) observed through Week 96. In subjects who entered the trial with mild or moderate renal impairment, the serum creatinine increase observed was similar to that seen in subjects with normal renal function. These changes are not considered to be clinically relevant and no subject discontinued treatment due to increases in serum creatinine. Creatinine increases were comparable by background N(t)RTIs.

Serum Lipids

Changes from baseline in total cholesterol, LDL-cholesterol and triglycerides are presented in Table 3.

Table 3 : Lipid Values Reported in Subjects Receiving Rilpivirine or Efavirenz in Combination with Emtricitabine/Tenofovir DF in Studies C209 and C215a

Mean Pooled Data from the Week 96 Analysis of C209 and C215 Trials
Rilpivirine + FTC/TDF N=550 Efavirenz + FTC/TDF N=546
N Baseline Week 96 N Baseline Week 96
Mean (mg/dL) Mean (mg/dL) Mean Changeb (mg/dL) Mean (mg/dL) Mean (mg/dL) Mean Changeb (mg/dL)
Total Cholesterol (fasted) 430 162 164 2 401 160 186 26
HDL-cholesterol (fasted) 429 42 45 4 399 40 50 11
LDL-cholesterol (fasted) 427 97 97 -1 397 96 110 14
Triglycerides (fasted) 430 123 109 -14 401 127 133 6
N = number of subjects per treatment group
a Excludes subjects who received lipid lowering agents during the treatment period.
b The change from baseline is the mean of within-patient changes from baseline for patients with both baseline and Week 96 values.

Subjects Coinfected with Hepatitis B and/or Hepatitis C Virus

In patients coinfected with hepatitis B or C virus receiving rilpivirine in studies C209 and C215, the incidence of hepatic enzyme elevation was higher than in subjects receiving rilpivirine who were not coinfected. The same increase was also observed in the efavirenz arm. The pharmacokinetic exposure of rilpivirine in coinfected subjects was comparable to that in subjects without coinfection.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of rilpivirine-or tenofovir DF-containing regimens . Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Rilpivirine

Renal and Urinary Disorders

nephrotic syndrome

Emtricitabine

No postmarketing adverse reactions have been identified for inclusion in this section.

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

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

Renal and Urinary Disorders

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

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 Complera (Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate Tablets) »

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Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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