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COMPLERA is a brand name for Emtricitabine, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE ........................................................................................................ 3 CONTRAINDICATIONS ............................................................................................................................. 4 WARNINGS AND PRECAUTIONS…
Verbatim from this product's HC label. Tap a section to expand.
Recommended Dose and Dosage Adjustment The recommended dose of COMPLERA is one tablet, once daily, which must be taken with food to obtain optimal absorption (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics). When dose modification is necessary, separate preparations of RPV, FTC, and TDF should be used (see DRUG INTERACTIONS, Drug-Drug Interactions).
Rifabutin Coadminstration:
If COMPLERA is coadministered with rifabutin, an additional 25 mg tablet of RPV (Edurant) per day is recommended to be taken concomitantly with COMPLERA, for the duration of the rifabutin coadministration (see DRUG INTERACTIONS, Drug-Drug Interactions).
Dose Adjustment for Renal Impairment Because COMPLERA is a fixed-dose combination, it should not be prescribed for patients requiring dosage reduction such as those with moderate or severe renal impairment (creatinine clearance <50 mL/min) (see WARNINGS AND PRECAUTIONS).
Missed Dose 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. OVERDOSAGE 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 FTC 1200 mg were administered to 11 patients. No severe adverse reactions were reported.
The effects of higher doses are not known. For management of a suspected drug overdose, please contact your regional Poison Control Centre. 5 hours of FTC dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min), however, a single treatment does not significantly affect FTC Cmax or AUC.
It is not known whether FTC can be removed by peritoneal dialysis.
Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs including TDF, a component of COMPLERA, in combination with other antiretrovirals (see WARNINGS AND PRECAUTIONS: Hepatic/Biliary/Pancreatic).
Post-treatment Exacerbation of Hepatitis B COMPLERA is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of COMPLERA have not been established in patients coinfected with HBV and HIV.
Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV after the discontinuation of FTC or TDF, two of the components of COMPLERA. Hepatic function should be closely monitored with both clinical and laboratory follow-up for at least several months in patients who discontinue COMPLERA and are coinfected with HIV and HBV.
If appropriate, initiation of anti-hepatitis B therapy may be warranted (see WARNINGS AND PRECAUTIONS: Special Populations). Nephrotoxicity Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia) has been reported with the use of TDF during clinical practice (see WARNINGS AND PRECAUTIONS: Renal).
General As a fixed-dose combination of FTC, RPV and TDF, COMPLERA should not be administered concurrently with other medicinal products containing any of the same active components (ATRIPLA®, EMTRIVA®, STRIBILD®, TRUVADA®, and VIREAD®) or with medicinal products containing tenofovir alafenamide (TAF) (BIKTARVY®, DESCOVY®, GENVOYA®, ODEFSEY®, Symtuza™, and VEMLIDY®).
g. with rifabutin) (see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS). Due to similarities between FTC and lamivudine, COMPLERA should not be administered with drugs containing lamivudine, including Combivir, 3TC, Heptovir, Kivexa, Triumeq and Trizivir.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Rilpivirine:
There is no specific antidote for overdose with RPV. Human experience of overdose with Edurant is limited. Since RPV is highly bound to plasma protein, dialysis is unlikely to result in significant removal of RPV.
Tenofovir disoproxil fumarate:
Limited clinical experience at doses higher than the therapeutic dose of VIREAD 300 mg is available. In one study, 600 mg TDF was administered to 8 patients orally for 28 days. 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.
ACTION AND CLINICAL PHARMACOLOGY Mechanism of Action COMPLERA is a fixed-dose combination of antiretroviral drugs FTC, RPV, and TDF.
Emtricitabine:
Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 RT by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination.
Emtricitabine 5′-triphosphate is a weak inhibitor of mammalian DNA polymerases , , , and mitochondrial DNA polymerase .
Rilpivirine:
Rilpivirine is a diarylpyrimidine NNRTI of HIV-1. Rilpivirine activity is mediated by non-competitive inhibition of HIV-1 RT. Rilpivirine does not inhibit the human cellular DNA polymerases , , and mitochondrial DNA polymerase .
Tenofovir disoproxil fumarate:
Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form COMPLERA® (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) tablets Product Monograph Page 33 tenofovir diphosphate.
Tenofovir diphosphate inhibits the activity of HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases , , and mitochondrial DNA polymerase .
Pharmacodynamics Effects on Electrocardiogram The effect of RPV on the QTc interval of the ECG was evaluated in two Phase I studies in healthy adult volunteers. d. was examined in a double-blind, double-dummy, randomized, placebo- and active-controlled three-way crossover study in healthy adult volunteers (N=60, 35M/25F), with 13 ECG recordings over 24 hours on day 11 of treatment (steady-state).
d. was not associated with a statistically significant or clinically relevant effect on the QTc interval. d. d. was studied in a double-blind, double-dummy, randomized, placebo and active controlled, three-way crossover study in healthy adult volunteers (N=40, 22F/19M), with 13 ECG recordings over 24 hours on day 1 and day 11 of treatment.
d. d. arm. For QTc interval effects with long-term treatment in the target patient population, […]
Caution should be given to prescribing COMPLERA with drugs that may reduce the exposure of RPV (see CONTRAINDICATIONS and DRUG INTERACTIONS). COMPLERA should not be administered with HEPSERA (adefovir dipivoxil). COMPLERA® (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) tablets Product Monograph Page 6 Carcinogenesis and Mutagenesis Rilpivirine induced benign and malignant tumors in the liver of mice and rats.
These tumors are caused by the enzyme induction that RPV caused in these species which may be rodent- specific. In rats, RPV caused benign and malignant tumors of the thyroid follicular cells. These tumors are the result of continuous stimulation of the follicular cells due to the increased clearance of thyroxine caused by RPV in this species.
This effect is considered rat- specific. Cardiovascular COMPLERA should be administered with caution to patients who are suspected to be at an increased risk of experiencing proarrhythmic conditions such as clinically significant bradycardia, congenital prolongation of QTc interval, acute myocardial ischemia, hypokalemia or congestive heart failure (see ADVERSE REACTIONS, DRUG INTERACTIONS and ACTION AND CLINICAL PHARMACOLOGY).
In healthy subjects, RPV has been associated with prolongation of the QT interval of the electrocardiogram at doses of 75 mg and 300 mg once daily. In antiretroviral naïve, HIV-1 infected patients receiving RPV 25 mg once daily in Phase III clinical trials, which excluded subjects with high risk factors for proarrhythmia, the mean QTc interval increased gradually over 48 weeks and remained stable through Week 96.
An increase of >60 ms in QTcF interval resulting in abnormal values of >480 ms was reported in one patient. Prolongation of QT interval may increase the risk of cardiac arrhythmias. There is limited information available on the potential for a pharmacodynamic interaction between RPV and drugs that prolong the QTc interval of the electrocardiogram.
COMPLERA should be used with caution when coadministered with drugs with a known risk of Torsade de Pointes. Depressive Disorders During the Phase III trials of RPV in adult patients (N=686) through 96 weeks, the incidence of depressive disorder adverse drug reactions (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) of at least moderate intensity (Grades 2 to 4) was 5%.
The incidence of discontinuation due to depressive disorders was 1%. Suicide attempt was reported in 2 subjects while suicide ideation was reported in 4 subjects taking in RPV. The incidence of these events was similar in the control group.
Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to RPV, and if so, to determine whether the risks of continued therapy with COMPLERA outweigh the benefits.
COMPLERA® (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) tablets Product Monograph Page 7 Drug Interactions Use with Certain HCV Regimens: Tenofovir exposure is increased when COMPLERA is coadministered with HARVONI (ledipasvir/sofosbuvir), EPCLUSA® (sofosbuvir/velpatasvir), or VOSEVI® (sofosbuvir/velpatasvir/voxilaprevir).
Patients receiving COMPLERA concomitantly with HARVONI, EPCLUSA or VOSEVI, particularly those at increased risk for renal dysfunction, should be monitored for tenofovir-associated adverse reactions (see DRUG INTERACTIONS).
Endocrine and Metabolism Fat Redistribution:
Redistribution/accumulation of body fat (lipodystrophy) 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 currently unknown. A causal relationship has not been established. Hepatic/Biliary/Pancreatic […]