Drug: Complera

COMPLERA is a fixed-dose combination tablet containing emtricitabine, rilpivirine hydrochloride, and tenofovir DF. EMTRIVA is the brand name for emtricitabine, a synthetic nucleoside analog of cytidine. Edurant is the brand name for rilpivirine, a non-nucleoside reverse transcriptase inhibitor. VIREAD is the brand name for tenofovir DF, which is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. VIREAD and EMTRIVA are the components of TRUVADA. COMPLERA tablets are for oral administration. 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 tablets include the following inactive ingredients: pregelatinized starch, lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, povidone, polysorbate 20. The tablets are film-coated with a coating material containing polyethylene glycol, hypromellose, lactose monohydrate, triacetin, titanium dioxide, iron oxide red, FD&C Blue #2 aluminum lake, FD&C Yellow #6 aluminum lake. Emtricitabine The chemical name of emtricitabine is 5-fluoro-1-[(2R,5S)-2- (hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position. It has a molecular formula of C8H10FN3O3S and a molecular weight of 247.24. It has the following structural formula: Emtricitabine is a white to off-white crystalline powder with a solubility of approximately 112 mg per mL in water at 25 °C. Rilpivirine Rilpivirine is available as the hydrochloride salt. The chemical name for rilpivirine hydrochloride is 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile monohydrochloride. Its molecular formula is C22H18N6 • HCl and its molecular weight is 402.88. Rilpivirine hydrochloride has the following structural formula: Rilpivirine hydrochloride is a white to almost white powder. Rilpivirine hydrochloride is practically insoluble in water over a wide pH range. Tenofovir Disoproxil Fumarate Tenofovir DF is a fumaric acid salt of the bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir. The chemical name of tenofovir DF is 9-[(R)-2 [[bis[[(isopropoxycarbonyl)oxy]- methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of C19H30N5O10P • C4H4O4 and a molecular weight of 635.52. It has the following structural formula: Tenofovir DF is a white to off-white crystalline powder with a solubility of 13.4 mg per mL in water at 25 °C. All dosages are expressed in terms of tenofovir DF except where otherwise noted.

Source: http://www.rxlist.com

The following adverse drug reactions are discussed in other sections of the labeling:
  • Lactic Acidosis/Severe Hepatomegaly with Steatosis [See BOXED WARNING, WARNINGS AND PRECAUTIONS].
  • Severe Acute Exacerbations of Hepatitis B [See BOXED WARNING, WARNINGS AND PRECAUTIONS].
  • Skin and Hypersensitivity Reactions [See WARNINGS AND PRECAUTIONS].
  • New Onset or Worsening Renal Impairment [See WARNINGS AND PRECAUTIONS].
  • Depressive Disorders [See WARNINGS AND PRECAUTIONS].
  • Hepatotoxicity [See WARNINGS AND PRECAUTIONS].
  • Bone Effects of Tenofovir DF [See WARNINGS AND PRECAUTIONS].
  • Immune Reconstitution Syndrome [See WARNINGS AND PRECAUTIONS].
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-naïve 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, virologically-suppressed subjects switching to COMPLERA from a regimen containing a ritonavir-boosted 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-naïve 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-naïve 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 Who Received 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 -0.6 (95% CI: -13.3; 12.2) 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 postmarketing experience in patients receiving 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. COMPLERA Skin and Subcutaneous Tissue Disorders Severe skin and hypersensitivity reactions including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) 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 Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate tablets) Side Effects Center for a complete guide to possible side effectsLearn More »

Source: http://www.rxlist.com

Adults The recommended dose of COMPLERA is one tablet taken orally once daily with food [See CLINICAL PHARMACOLOGY]. Renal Impairment Because COMPLERA is a fixed-dose combination, it should not be prescribed for patients requiring dose reduction such as those with moderate or severe renal impairment (estimated creatinine clearance below 50 mL per minute). Rifabutin Coadministration If COMPLERA is coadministered with rifabutin, an additional 25 mg tablet of rilpivirine (Edurant®) once per day is recommended to be taken concomitantly with COMPLERA and with a meal for the duration of the rifabutin coadministration [See DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Source: http://www.rxlist.com

COMPLERA is a complete regimen for the treatment of HIV-1 infection; therefore, COMPLERA should not be administered with other antiretroviral medications. Information regarding potential drug-drug interactions with other antiretroviral medications is not provided. Please refer to the Edurant, VIREAD and EMTRIVA prescribing information as needed. There were no drug-drug interaction trials conducted with the fixed-dose combination tablet. Drug interaction studies were conducted with emtricitabine, rilpivirine, or tenofovir DF, the components of COMPLERA. This section describes clinically relevant drug interactions with COMPLERA [See DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and CLINICAL PHARMACOLOGY]. Drugs Inducing Or Inhibiting CYP3A Enzymes Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of rilpivirine [See CLINICAL PHARMACOLOGY, CONTRAINDICATIONS]. Coadministration of rilpivirine and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. Coadministration of rilpivirine and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine. Rilpivirine at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of drugs metabolized by CYP enzymes. Drugs Increasing Gastric pH Coadministration of rilpivirine with drugs that increase gastric pH may decrease plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs [See Table 4]. Drugs Affecting Renal Function Because emtricitabine and tenofovir are primarily eliminated by the kidneys through a combination of glomerular filtration and active tubular secretion, coadministration of COMPLERA with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine, tenofovir, and/or other renally eliminated drugs. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [See WARNINGS AND PRECAUTIONS]. QT Prolonging Drugs There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval of the electrocardiogram. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram [See CLINICAL PHARMACOLOGY]. COMPLERA should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. Established And Other Potentially Significant Drug Interactions Important drug interaction information for COMPLERA is summarized in Table 4. The drug interactions described are based on studies conducted with emtricitabine, rilpivirine, or tenofovir DF as individual medications that may occur with COMPLERA or are potential drug interactions; no drug interaction studies have been conducted using COMPLERA [for pharmacokinetic data see CLINICAL PHARMACOLOGY, Tables 6-7]. The tables include potentially significant interactions, but are not all inclusive. Table 4 : Established and Other Potentially Significanta Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction
Concomitant Drug Class: Drug Name Effect on Concentrationb Clinical Comment Antacids: antacids (e.g., aluminium, magnesium hydroxide, or calcium carbonate) ↔ rilpivirine (antacids taken at least 2 hours before or at least 4 hours after rilpivirine)
↓ rilpivirine (concomitant intake) The combination of COMPLERA and antacids should be used with caution as coadministration may cause significant decreases in rilpivirine plasma concentrations (increase in gastric pH). Antacids should only be administered either at least 2 hours before or at least 4 hours after COMPLERA. Antimycobacterials: rifabutin ↓ rilpivirinec Concomitant use of COMPLERA with rifabutin may cause significant decreases in rilpivirine plasma concentrations (induction of CYP3A enzymes). If COMPLERA is coadministered with rifabutin, an additional 25 mg tablet of rilpivirine (Edurant) once per day is recommended to be taken concomitantly with COMPLERA and with a meal for the duration of rifabutin coadministration. Azole Antifungal Agents:
fluconazole
itraconazole
ketoconazole
posaconazole
voriconazole ↑ rilpivirinec,d
↓ ketoconazolec,d Concomitant use of COMPLERA with azole antifungal agents may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required when COMPLERA is coadministered with azole antifungal agents. Clinically monitor for breakthrough fungal infections when azole antifungals are coadministered with COMPLERA. H2-Receptor Antagonists:
cimetidine
famotidine
nizatidine
ranitidine ↔ rilpivirinec,d (famotidine taken 12 hours before rilpivirine or 4 hours after rilpivirine)
↓ rilpivirinec,d (famotidine taken 2 hours before rilpivirine) The combination of COMPLERA and H2-receptor antagonists should be used with caution as coadministration may cause significant decreases in rilpivirine plasma concentrations (increase in gastric pH). H2-receptor antagonists should only be administered at least 12 hours before or at least 4 hours after COMPLERA. Macrolide or Ketolide Antibiotics:
clarithromycin
erythromycin
telithromycin ↑ rilpivirine
↔ clarithromycin
↔ erythromycin
↔ telithromycin Concomitant use of COMPLERA with clarithromycin, erythromycin or telithromycin may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). Where possible, alternatives such as azithromycin should be considered. Narcotic Analgesics:
methadone ↓ R(-) methadonec
↓ S(+) methadonec
↔ rilpivirinec
↔ methadonec (when used with tenofovir) No dose adjustments are required when initiating coadministration of methadone with COMPLERA. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. a This table is not all inclusive.
b Increase = ↑; Decrease = ↓; No Effect = ↔;
c The interaction was evaluated in a clinical study. All other drug-drug interactions shown are predicted.
d This interaction study has been performed with a dose higher than the recommended dose for rilpivirine. The dosing recommendation is applicable to the recommended dose of rilpivirine 25 mg once daily. Drugs With No Observed Or Predicted Interactions With COMPLERA No clinically significant drug interactions have been observed between emtricitabine and the following medications: famciclovir or tenofovir DF. Similarly, no clinically significant drug interactions have been observed between tenofovir DF and the following medications: entecavir, methadone, oral contraceptives, ribavirin, or tacrolimus in studies conducted in healthy subjects. No clinically significant drug interactions have been observed between rilpivirine and the following medications: acetaminophen, atorvastatin, chlorzoxazone, ethinyl estradiol,norethindrone, sildenafil, telaprevir, or tenofovir DF. Rilpivirine did not have a clinically significant effect on the pharmacokinetics of digoxin or metformin. No clinically relevant drug-drug interaction is expected when rilpivirine is coadministered with ribavirin. Read the Complera Drug Interactions Center for a complete guide to possible interactions Learn More »

Source: http://www.rxlist.com

COMPLERA, a combination of two nucleoside analog HIV 1 reverse transcriptase inhibitors (emtricitabine and tenofovir disoproxil fumarate) and one non-nucleoside reverse transcriptase inhibitor (rilpivirine), is indicated for use as a complete regimen for the treatment of HIV-1 infection in adult patients with no antiretroviral treatment history and with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy, and in certain virologically-suppressed (HIV-1 RNA < 50 copies/mL) adult patients on a stable antiretroviral regimen at start of therapy in order to replace their current antiretroviral treatment regimen (see below).
  • The following points should be considered when initiating therapy with COMPLERA in adult patients with no antiretroviral treatment history:
    • More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥ 50 copies/mL) compared to rilpivirine-treated subjects with HIV-1 RNA less than or equal to 100,000 copies/mL [See Clinical Studies].
    • Regardless of HIV-1 RNA level at the start of therapy, more rilpivirine-treated subjects with CD4+ cell count less than 200 cells/mm3 experienced virologic failure compared to rilpivirine-treated subjects with CD4+ cell count greater than or equal to 200 cells/mm3 [See Clinical Studies].
    • The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz [See Microbiology].
    • More subjects treated with rilpivirine developed tenofovir and lamivudine/emtricitabine associated resistance compared to efavirenz [See Microbiology].
  • The efficacy of COMPLERA was established in patients who were virologically-suppressed (HIV-1 RNA < 50 copies/mL) on stable ritonavir-boosted protease inhibitor-containing regimen. The following points should be met when considering replacing the current regimen with COMPLERA in virologically-suppressed adults [See Clinical Studies]:
    • Patients should have no history of virologic failure.
    • Patients should have been stably suppressed (HIV-1 RNA < 50 copies/mL) for at least 6 months prior to switching therapy.
    • Patients should currently be on their first or second antiretroviral regimen prior to switching therapy.
    • Patients should have no current or past history of resistance to any of the three components of COMPLERA.
Additional monitoring of HIV-1 RNA and regimen tolerability is recommended after replacing therapy to assess for potential virologic failure or rebound. COMPLERA is not recommended for patients less than 18 years of age [See Use in Specific Populations].

Source: http://www.rxlist.com

COMPLERA should not be coadministered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to COMPLERA or to the class of NNRTIs [See DRUG INTERACTIONS and CLINICAL PHARMACOLOGY]:
  • the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
  • the antimycobacterials rifampin, rifapentine
  • proton pump inhibitors, such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
  • the glucocorticoid systemic dexamethasone (more than a single dose)
  • St. John's wort (Hypericum perforatum)
Last reviewed on RxList: 5/19/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with COMPLERA consists of general supportive measures including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient. Emtricitabine: Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA. In one clinical pharmacology study, single doses of emtricitabine 1200 mg were administered to 11 subjects. No severe adverse reactions were reported. The effects of higher doses are not known. Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL per minute and a dialysate flow rate of 600 mL per minute). It is not known whether emtricitabine can be removed by peritoneal dialysis. Rilpivirine: There is no specific antidote for overdose with rilpivirine. Human experience of overdose with rilpivirine is limited. Since rilpivirine is highly bound to plasma protein, dialysis is unlikely to result in significant removal of rilpivirine. Administration of activated charcoal may be used to aid in removal of unabsorbed active substance. Tenofovir Disoproxil Fumarate: Limited clinical experience at doses higher than the therapeutic dose of VIREAD 300 mg is available. In one study, 600 mg tenofovir DF was administered to 8 subjects orally for 28 days, and no severe adverse reactions were reported. The effects of higher doses are not known. Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of VIREAD, a four-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.

Source: http://www.rxlist.com

Dosage Forms And Strengths COMPLERA is available as tablets. Each tablet contains 200 mg of emtricitabine (FTC), 27.5 mg of rilpivirine hydrochloride (equivalent to 25 mg of rilpivirine) and 300 mg of tenofovir disoproxil fumarate (tenofovir DF or TDF, equivalent to 245 mg of tenofovir disoproxil). The tablets are purplish-pink, capsule-shaped, film-coated, debossed with “GSI” on one side and plain-faced on the other side. Storage And Handling COMPLERA tablets are purplish-pink, capsule-shaped, film-coated, debossed with “GSI” on one side and plain-faced on the other side. Each bottle contains 30 tablets (NDC 61958-1101-1), a silica gel desiccant, polyester fiber coil, and is closed with a child-resistant closure. Store at 25 °C (77 °F), excursions permitted to 15 °C–30 °C (59 °F–86 °F) (see USP Controlled Room Temperature).
  • Keep container tightly closed
  • Dispense only in original container
  • Do not use if seal over bottle opening is broken or missing.
Manufactured and distributed by: Gilead Sciences, Inc., Foster City, CA 94404. Revised: May 2015 Last reviewed on RxList: 5/19/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Lactic Acidosis/Severe Hepatomegaly With Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir DF, a component of COMPLERA, in combination with other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with COMPLERA 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). Patients Coinfected With HIV-1 And HBV It is recommended that all patients with HIV-1 be tested for the presence of chronic hepatitis B virus before initiating antiretroviral therapy. COMPLERA is not approved for the treatment of chronic HBV infection and the safety and efficacy of COMPLERA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir DF, two of the components of COMPLERA. In some patients infected with HBV and treated with EMTRIVA®, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Patients who are coinfected with HIV-1 and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with COMPLERA. If appropriate, initiation of anti-hepatitis B therapy may be warranted. Skin And Hypersensitivity Reactions Severe skin and hypersensitivity reactions have been reported during the postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries. During the Phase 3 clinical trials, treatment-related rashes with at least Grade 2 severity were reported in 1% of subjects receiving rilpivirine plus emtricitabine/tenofovir DF. Overall, most rashes were Grade 1 or 2 and occurred in the first four to six weeks of therapy [see ADVERSE REACTIONS]. Discontinue COMPLERA immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia. Clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated. New Onset Or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir DF [See ADVERSE REACTIONS]. It is recommended that estimated creatinine clearance be assessed in all patients prior to initiating therapy and as clinically appropriate during therapy with COMPLERA. In patients at risk of renal dysfunction, including patients who have previously experienced renal events while receiving HEPSERA®, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein be assessed prior to initiation of COMPLERA, and periodically during COMPLERA therapy. COMPLERA should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs)) [See DRUG INTERACTIONS]. Cases of acute renal failure after initiation of high dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir DF. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients. Emtricitabine and tenofovir are principally eliminated by the kidney; however, rilpivirine is not. Since COMPLERA is a combination product and the dose of the individual components cannot be altered, patients with estimated creatinine clearance below 50 mL per minute should not receive COMPLERA. Drug Interactions Caution should be given to prescribing COMPLERA with drugs that may reduce the exposure of rilpivirine [See CONTRAINDICATIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY]. In healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram [See DRUG INTERACTIONSand CLINICAL PHARMACOLOGY]. COMPLERA should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. Depressive Disorders The adverse reaction depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) has been reported with rilpivirine. During the Phase 3 trials (N=1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among rilpivirine (N=686) or efavirenz (N=682) was 9% and 8%, respectively. Most events were mild or moderate in severity. The incidence of Grades 3 and 4 depressive disorders (regardless of causality) was 1% for both rilpivirine and efavirenz. The incidence of discontinuation due to depressive disorders among rilpivirine or efavirenz was 1% in each arm. Suicidal ideation was reported in 4 subjects in each arm while suicide attempt was reported in 2 subjects in the rilpivirine arm. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to COMPLERA, and if so, to determine whether the risks of continued therapy outweigh the benefits. Hepatotoxicity Hepatic adverse events have been reported in patients receiving a rilpivirine containing regimen. Patients with underlying hepatitis B or C, or marked elevations in liver-associated tests prior to treatment may be at increased risk for worsening or development of liver-associated test elevations with use of COMPLERA. A few cases of hepatic toxicity have been reported in patients receiving a rilpivirine containing regimen who had no pre-existing hepatic disease or other identifiable risk factors. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with COMPLERA is recommended in patients with underlying hepatic disease such as hepatitis B or C, or in patients with marked elevations in liver-associated tests prior to treatment initiation. Liver-associated test monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. Bone Effects Of Tenofovir DF Bone Mineral Density In clinical trials in HIV-1-infected adults, tenofovir DF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving tenofovir DF. For more information, please consult the VIREAD® prescribing information. The effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Assessment of BMD should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and Vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected then appropriate consultation should be obtained. Mineralization Defects 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 tenofovir DF [See ADVERSE REACTIONS]. Arthralgias and muscle pain or weakness have also been reported in cases of proximal renal tubulopathy. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving products containing tenofovir DF [See New Onset or Worsening Renal Impairment above]. Coadministration With Other Products COMPLERA should not be administered concurrently with other medicinal products containing the active components emtricitabine or tenofovir DF (ATRIPLA®, EMTRIVA, STRIBILD®, TRUVADA®, VIREAD), with medicinal products containing lamivudine (Epivir®, Epivir-HBV®, Epzicom®, Combivir®, Trizivir®), or with adefovir dipivoxil (HEPSERA). COMPLERA should not be administered with rilpivirine (Edurant) unless needed for dose adjustment (e.g., with rifabutin) [See DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS]. Fat Redistribution 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 antiretroviral therapy. The mechanism and long-term consequences of these events are unknown. A causal relationship has not been established. Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of COMPLERA. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment. Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment. Patient Counseling Information Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION). A statement to patients and healthcare providers is included on the product's bottle label: ALERT: Find out about medicines that should NOT be taken with COMPLERA. A Patient Package Insert for COMPLERA is available for patient information. Information For Patients
  • Patients should be advised that:
  • Patients should remain under the care of a healthcare provider when using COMPLERA.
  • Patients should be informed that COMPLERA is not a cure for HIV infection. Patients should stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses. Patients should be told that sustained decreases in plasma HIV RNA have been associated with a reduced risk of progression to AIDS and death.
  • Patients should be advised to continue to practice safer sex and to use latex or polyurethane condoms to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions or blood. Patients should be advised never to re-use or share needles.
  • Patients should be advised not to breastfeed because at least two of the drugs contained in COMPLERA can be passed to the baby in breast milk. It is not known whether this could harm the baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in breast milk.
  • It is important to take COMPLERA on a regular dosing schedule with food and to avoid missing doses. A protein drink is not a substitute for food. If the healthcare provider decides to stop COMPLERA and the patient is switched to new medicines to treat HIV that includes rilpivirine tablets, the rilpivirine tablets should be taken only with a meal.
  • If the patient misses a dose of COMPLERA within 12 hours of the time it is usually taken, the patient should take COMPLERA with food as soon as possible and then take the next dose of COMPLERA at the regularly scheduled time. If a patient misses a dose of COMPLERA by more than 12 hours, the patient should not take the missed dose, but resume the usual dosing schedule. Inform the patient that he or she should not take more or less than the prescribed dose of COMPLERA at any one time.
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Treatment with COMPLERA should be suspended in any patients who develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity (including nausea, vomiting, unusual or unexpected stomach discomfort, and weakness) [See WARNINGS AND PRECAUTIONS].
  • Patients with HIV-1 should be tested for hepatitis B virus (HBV) before initiating antiretroviral therapy. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued EMTRIVA or VIREAD [See WARNINGS AND PRECAUTIONS]. COMPLERA should not be discontinued without first informing their healthcare provider.
  • Patients should be informed that skin reactions ranging from mild to severe, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported with COMPLERA. Instruct patients to immediately stop taking COMPLERA and seek medical attention if they develop a rash associated with any of the following symptoms: fever, blisters, mucosal involvement, eye inflammation (conjunctivitis), severe allergic reaction causing swelling of the face, eyes, lips, mouth, tongue or throat which may lead to difficulty swallowing or breathing, and any signs and symptoms of liver problems, as they may be a sign of a more serious reaction. Patients should understand that if severe rash occurs, they will be closely monitored, laboratory tests will be performed and appropriate therapy will be initiated [See WARNINGS AND PRECAUTIONS].
  • Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported in association with the use of VIREAD. COMPLERA should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple NSAIDs) [See WARNINGS AND PRECAUTIONS].
  • COMPLERA may interact with many drugs; therefore, patients should be advised to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including St. John's wort [See WARNINGS AND PRECAUTIONS].
  • COMPLERA should not be coadministered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to COMPLERA or to the class of NNRTIs: the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin; the antimycobacterials rifampin, rifapentine; proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole; the glucocorticoid systemic dexamethasone (more than a single dose); or St. John's wort (Hypericum perforatum) [See CONTRAINDICATIONS].
  • For patients receiving rifabutin, an additional 25 mg tablet of rilpivirine (Edurant) once per day is recommended to be taken concomitantly with COMPLERA and with a meal for the duration of rifabutin coadministration.
  • Patients should be informed that depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) have been reported with COMPLERA. If they experience depressive symptoms, they should seek immediate medical evaluation [See WARNINGS AND PRECAUTIONS].
  • Patients should be informed that hepatotoxicity has been reported with COMPLERA [See WARNINGS AND PRECAUTIONS].
  • Decreases in bone mineral density have been observed with the use of VIREAD. Bone mineral density (BMD) monitoring should be considered in patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss [See WARNINGS AND PRECAUTIONS].
  • COMPLERA should not be coadministered with ATRIPLA, EMTRIVA, STRIBILD, TRUVADA, or VIREAD; or with drugs containing lamivudine, including Combivir, Epivir or Epivir-HBV, Epzicom, or Trizivir; or with HEPSERA. COMPLERA should not be coadministered with rilpivirine (Edurant) unless needed for dose adjustment (e.g., with rifabutin) [See WARNINGS AND PRECAUTIONS].
  • Redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known [See WARNINGS AND PRECAUTIONS].
  • In some patients with advanced HIV infection (AIDS), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body's immune response, enabling the body to fight infections that may have been present with no obvious symptoms. Patients should be advised to inform their healthcare provider immediately of any symptoms of infection [See WARNINGS AND PRECAUTIONS].
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Emtricitabine: In long-term carcinogenicity studies of emtricitabine, no drug-related increases in tumor incidence were found in mice at doses up to 750 mg per kg per day (26 times the human systemic exposure at the therapeutic dose of 200 mg per day) or in rats at doses up to 600 mg per kg per day (31 times the human systemic exposure at the therapeutic dose). Emtricitabine was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or mouse micronucleus assays. Emtricitabine did not affect fertility in male rats at approximately 140-fold or in male and female mice at approximately 60-fold higher exposures (AUC) than in humans given the recommended 200 mg daily dose. Fertility was normal in the offspring of mice exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60-fold higher than human exposures at the recommended 200 mg daily dose. Rilpivirine: Rilpivirine was evaluated for carcinogenic potential by oral gavage administration to mice and rats up to 104 weeks. Daily doses of 20, 60 and 160 mg per kg per day were administered to mice and doses of 40, 200, 500 and 1500 mg per kg per day were administered to rats. In rats, there were no drug related neoplasms. In mice, rilpivirine was positive for hepatocellular neoplasms in both males and females. The observed hepatocellular findings in mice may be rodent-specific. At the lowest tested doses in the carcinogenicity studies, the systemic exposures (based on AUC) to rilpivirine were 21 fold (mice) and 3 fold (rats), relative to those observed in humans at the recommended dose (25 mg once daily). Rilpivirine has tested negative in the absence and presence of a metabolic activation system, in the in vitro Ames reverse mutation assay and in vitro clastogenicity mouse lymphoma assay. Rilpivirine did not induce chromosomal damage in the in vivo micronucleus test in mice. In a study conducted in rats, there were no effects on mating or fertility with rilpivirine up to 400 mg per kg per day, a dose of rilpivirine that showed maternal toxicity. This dose is associated with an exposure that is approximately 40 times higher than the exposure in humans at the recommended dose of 25 mg once daily. Tenofovir Disoproxil Fumarate: Long-term oral carcinogenicity studies of tenofovir DF in mice and rats were carried out at exposures up to approximately 16 times (mice) and 5 times (rats) those observed in humans at the therapeutic dose for HIV-1 infection. At the high dose in female mice, liver adenomas were increased at exposures 16 times that in humans. In rats, the study was negative for carcinogenic findings at exposures up to 5 times that observed in humans at the therapeutic dose. Tenofovir DF was mutagenic in the in vitro mouse lymphoma assay and negative in an in vitro bacterial mutagenicity test (Ames test). In an in vivo mouse micronucleus assay, tenofovir DF was negative when administered to male mice. There were no effects on fertility, mating performance or early embryonic development when tenofovir DF was administered to male rats at a dose equivalent to 10 times the human dose based on body surface area comparisons for 28 days prior to mating and to female rats for 15 days prior to mating through day seven of gestation. There was, however, an alteration of the estrous cycle in female rats. Use In Specific Populations Pregnancy Pregnancy Category B Emtricitabine: The incidence of fetal variations and malformations was not increased in embryofetal toxicity studies performed with emtricitabine in mice at exposures (AUC) approximately 60 times higher and in rabbits at approximately 120 times higher than human exposures at the recommended daily dose. Rilpivirine: Studies in animals have shown no evidence of embryonic or fetal toxicity or an effect on reproductive function. In offspring from rat and rabbit dams treated with rilpivirine during pregnancy and lactation, there were no toxicologically significant effects on developmental endpoints. The exposures at the embryo-fetal No Observed Adverse Effects Levels in rats and rabbits were respectively 15 and 70 times higher than the exposure in humans at the recommended dose of 25 mg once daily. Tenofovir Disoproxil Fumarate: Reproduction studies have been performed in rats and rabbits at doses up to 14 and 19 times the human dose based on body surface area comparisons and revealed no evidence of impaired fertility or harm to the fetus due to tenofovir. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, COMPLERA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Antiretroviral Pregnancy Registry: To monitor fetal outcomes of pregnant women exposed to COMPLERA, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients by calling 1-800-258-4263. Nursing Mothers The Centers for Disease Control and Prevention recommend that HIV infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Emtricitabine: Samples of breast milk obtained from five HIV-1-infected mothers show that emtricitabine is secreted in human milk. Breastfeeding infants whose mothers are being treated with emtricitabine may be at risk for developing viral resistance to emtricitabine. Other emtricitabine-associated risks in infants breastfed by mothers being treated with emtricitabine are unknown. Rilpivirine: Studies in lactating rats and their offspring indicate that rilpivirine was present in rat milk. It is not known whether rilpivirine is secreted in human milk. Tenofovir Disoproxil Fumarate: Samples of breast milk obtained from five HIV-1-infected mothers in the first post-partum week show that tenofovir is excreted in human milk. The impact of this exposure in breastfed infants is unknown. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving COMPLERA. Pediatric Use COMPLERA is not recommended for patients less than 18 years of age because not all the individual components of COMPLERA have safety, efficacy and dosing recommendations available for all pediatric age groups [See CLINICAL PHARMACOLOGY]. Geriatric Use Clinical studies of emtricitabine, rilpivirine, or tenofovir DF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for the elderly patients should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [See CLINICAL PHARMACOLOGY]. Renal Impairment Because COMPLERA is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment such as those with moderate, severe or end stage renal impairment (estimated creatinine clearance below 50 mL per minute) or that require dialysis [See WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY]. Hepatic Impairment No dose adjustment of COMPLERA is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. COMPLERA has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) [See CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 5/19/2015
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Health Services in

Drug Database Online

Welcome to Senior Healthcare Matters an online drug guide and dictionary, here you can get drug information and definitaions for most popular pharmaceutical and medicinal drugs, and specifically Complera. Find what medications you are taking today.