Rilpivirine: Difference between revisions
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|indication=[[human immunodeficiency virus type 1]] ([[HIV-1]]) infection in antiretroviral treatment-naïve adult patients with [[HIV-1]] [[RNA]] less than or equal to 100,000 copies/mL at the start of therapy | |indication=[[human immunodeficiency virus type 1]] ([[HIV-1]]) infection in antiretroviral treatment-naïve adult patients with [[HIV-1]] [[RNA]] less than or equal to 100,000 copies/mL at the start of therapy | ||
|adverseReactions=[[depressive disorders]], [[headache]], [[insomnia]] and [[rash]] | |||
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b> | |blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b> | ||
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content) | |blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content) | ||
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*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]]. EDURANT should be used with caution when co-administered with a drug with a known risk of [[Torsade de Pointes]]. | *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]]. EDURANT should be used with caution when co-administered 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 EDURANT. During the Phase 3 trials (N = 1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among EDURANT (n = 686) or efavirenz (n = 682) was 9% and 8%, respectively. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 1% for both EDURANT and efavirenz. The incidence of discontinuation due to depressive disorders among EDURANT 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 EDURANT arm. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to EDURANT, and if so, to determine whether the risks of continued therapy outweigh the benefits. | *The adverse reaction [[depressive disorders]] ([[depressed mood]], [[depression]], [[dysphoria]], [[major depression]], [[mood altered]], [[negative thoughts]], [[suicide attempt]], [[suicidal ideation]]) has been reported with EDURANT. During the Phase 3 trials (N = 1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among EDURANT (n = 686) or [[efavirenz]] (n = 682) was 9% and 8%, respectively. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 [[depressive disorders]] (regardless of causality) was 1% for both EDURANT and [[efavirenz]]. The incidence of discontinuation due to depressive disorders among EDURANT 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 EDURANT arm. Patients with severe [[depressive symptoms]] should seek immediate medical evaluation to assess the possibility that the symptoms are related to EDURANT, 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 transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of EDURANT. 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 EDURANT is recommended in patients with underlying hepatic disease such as hepatitis B or C, or in patients with marked elevations in transaminases prior to treatment initiation. Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. | *Hepatic adverse events have been reported in patients receiving a rilpivirine containing regimen. Patients with underlying [[hepatitis B]] or [[hepatitis C]], or marked elevations in [[transaminases]] prior to treatment may be at increased risk for worsening or development of [[transaminase]] elevations with use of EDURANT. 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 EDURANT is recommended in patients with underlying hepatic disease such as [[hepatitis B]] or [[hepatitis C]], or in patients with marked elevations in [[transaminases]] prior to treatment initiation. *Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. | ||
====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 currently unknown. A causal relationship has not been established. | *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 currently 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 EDURANT. 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 jiroveci pneumonia or tuberculosis), which may necessitate further evaluation and treatment. | *[[Immune reconstitution syndrome]] has been reported in patients treated with combination antiretroviral therapy, including EDURANT. 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 jiroveci pneumonia]] 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 syndrome]]; however, the time to onset is more variable, and can occur many months after initiation of 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. | |||
|alcohol=Alcohol-Rilpivirine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. | |alcohol=Alcohol-Rilpivirine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. | ||
}} | }} | ||
Revision as of 15:28, 10 February 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]
Disclaimer
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Overview
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is FDA approved for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve adult patients with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy. Common adverse reactions include depressive disorders, headache, insomnia and rash.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
There is limited information regarding Rilpivirine FDA-Labeled Indications and Dosage (Adult) in the drug label.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Rilpivirine in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Rilpivirine in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Rilpivirine FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Rilpivirine in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Rilpivirine in pediatric patients.
Contraindications
EDURANT should not be co-administered 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 EDURANT 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)
- St John's wort (Hypericum perforatum)
Warnings
Drug Interactions
- Caution should be given to prescribing EDURANT with drugs that may reduce the exposure of rilpivirine.
- 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. EDURANT should be used with caution when co-administered 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 EDURANT. During the Phase 3 trials (N = 1368) through 96 weeks, the incidence of depressive disorders (regardless of causality, severity) reported among EDURANT (n = 686) or efavirenz (n = 682) was 9% and 8%, respectively. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 1% for both EDURANT and efavirenz. The incidence of discontinuation due to depressive disorders among EDURANT 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 EDURANT arm. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to EDURANT, 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 hepatitis C, or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of EDURANT. 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 EDURANT is recommended in patients with underlying hepatic disease such as hepatitis B or hepatitis C, or in patients with marked elevations in transaminases prior to treatment initiation. *Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors.
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 currently 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 EDURANT. 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 jiroveci pneumonia 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 syndrome; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Rilpivirine Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Rilpivirine Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Rilpivirine Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Rilpivirine in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Rilpivirine in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Rilpivirine during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Rilpivirine in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Rilpivirine in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Rilpivirine in geriatric settings.
Gender
There is no FDA guidance on the use of Rilpivirine with respect to specific gender populations.
Race
There is no FDA guidance on the use of Rilpivirine with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Rilpivirine in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Rilpivirine in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Rilpivirine in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Rilpivirine in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Rilpivirine Administration in the drug label.
Monitoring
There is limited information regarding Rilpivirine Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Rilpivirine and IV administrations.
Overdosage
There is limited information regarding Rilpivirine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Rilpivirine Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Rilpivirine Mechanism of Action in the drug label.
Structure
There is limited information regarding Rilpivirine Structure in the drug label.
Pharmacodynamics
There is limited information regarding Rilpivirine Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Rilpivirine Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Rilpivirine Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Rilpivirine Clinical Studies in the drug label.
How Supplied
There is limited information regarding Rilpivirine How Supplied in the drug label.
Storage
There is limited information regarding Rilpivirine Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Rilpivirine |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Rilpivirine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Rilpivirine Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Rilpivirine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Rilpivirine Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Rilpivirine Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [4]
Overview
Rilpivirine (TMC278) is a diarylpyrimidine under under investigation as a treatment for HIV infection. It is a non-nucleoside reverse transcriptase inhibitor with many times the potency of current available agents in that class, such as efavirenz.[1][2]It is expected to be FDA approved as soon as 2009.[3]
Category
Antiretroviral
US Brand Names
Edurant®
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Overdosage | Clinical Studies | Dosage and Administration | How Supplied | Labels and Packages
Mechanism of Action
A HIV-1 replication inhibitor acting by non-competitive inhibition of HIV-1 reverse transcriptase . It is a diarylpyrimidine non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1)
References
- ↑ Goebel F, Yakovlev A, Pozniak AL, Vinogradova E, Boogaerts G, Hoetelmans R, de Béthune MP, Peeters M, Woodfall B (2006). "Short-term antiviral activity of TMC278--a novel NNRTI--in treatment-naive HIV-1-infected subjects". AIDS. 20 (13): 1721–6. doi:10.1097/01.aids.0000242818.65215.bd. PMID 16931936.
- ↑ Pozniak A, Morales-Ramirez J, Mohap L et al. 48-Week Primary Analysis of Trial TMC278-C204: TMC278 Demonstrates Potent and Sustained Efficacy in ART-naïve Patients. Oral abstract 144LB.
- ↑ Steve Mitchell. HIV Market To Top 10 Billion Dollars. United Press International. April 11, 2007.