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Coformulations of Antiretroviral Therapy

Effectiveness, Tolerability, Adherence, Simplicity

The Leading Edge of HIV Treatment

 

Atripla
A combination of  emtricitabine + efavirenz + tenofovir
Approved 7/12/2006
Forms Available 300 mg tenofovir / 200 mg emtricitabine / 600 mg efavirenz in tablet form
Dosing 1 tablet once a day without food
Dosing at bedtime may improve tolerability to the efavirenz component.
Renal dosing Dosing interval
Ccr 30-49 cc/min
Dosing interval
Ccr < 30 cc/min
Not recommended Not recommended
Hepatic dosing: no data available
Food dependence Food increases efavirenz absorption and therefore may produce increased CNS side effects.

Take Atripla on an empty stomach.

Adverse Effects Same as tenofovir and emtricitabine and efavirenz (see above or click on the drug name)
Efavirenz may cause CNS stimulation, restlessness, nightmares, depression, exacerbation of underlying mental health problems, rash or chemical hepatitis.
Tenofovir may cause nephropathy, Fanconi-like syndrome, or loss of bone mineralization.
Emtricitabine rarely causes discoloration of palms or soles.
Interactions Same as tenofovir and emtricitabine and efavirenz (see above or click on the drug name)
If Atripla is used with didanosine, reduce the dose of didanosine EC to 250 mg daily maximum.
Atripla should be used cautiously if at all with atazanavir as the triple interaction of efavirenz, tenofovir, and atazanavir has not been well studied.
Laboratory

Monitoring

Monthly CBC for 3 months, then every 3 months if stable
Consider monthly creatinine measurements in lean individuals or those with renal insufficiency
Monthly liver profile for 3 months, then every 3 months and as indicated if stable

Monitor urine glucose and protein at baseline and periodically

Warning

Rare lactic acidosis and hepatic steatosis.
Do not used fixed dose combination in persons with renal insufficiency.
Severe acute exacerbations of chronic hepatitis B may be observed with sudden discontinuation of lamivudine, emtricitabine, Truvada, Trizivir, Epzicom, Atripla.
Avoid use of efavirenz-containing medications in persons who require high levels of mental acuity or concentration in their work or lives, and in those with poor-controlled mental health issues such as schizophrenia or manic-depressive disorders.

Fanconi syndrome (bone pain, glycosuria, hypophosphatemia, elevated serum creatinine) has been observed with tenofovir.  Monitor serum phosphorous, urine glucose and protein at baseline and periodically.

Contraindication None

Suggested Usage

In general Atripla should be used in persons who are naive to treatment as most persons who are treatment experienced may harbor resistance mutations to lamivudine/emtricitabine and/or NNRTIs.
Resistance testing should be done prior to using Atripla.
Do not use in combination with Sustiva, lamivudine, emtricitabine, Epzicom, Combivir, or Trizivir due to identical mechanism of action or duplication of efavirenz or emtricitabine dosing.
Encourage exercise and calcium intake to minimize bone loss.
Advise patient to avoid dehydration.
Do not discontinue abruptly in patients with chronic hepatitis B without consideration of continuation of lamivudine or some other agent active against hepatitis B.

Complete prescribing information

Atripla Prescribing Info
Also see http://www.atripla.com for further info as it becomes available.
Patient handout for this drug HERE.

 

 

 

Complera
A combination of  emtricitabine + rilpivirine + tenofovir
Approved 8/102011
Forms Available 300 mg tenofovir / 200 mg emtricitabine / 50 mg rilpivirine, in tablet form
Dosing 1 tablet once a day with food
This coformulation, Complera, should be taken with a least 400 calories of food, preferably a meal.
Renal dosing Dosing interval
Ccr 30-49 cc/min
Dosing interval
Ccr < 30 cc/min
Not recommended Not recommended
Hepatic dosing: no data available
Food dependence Food increases rilpivirine absorption and is essential for absorption.

Take Complera with a meal, at least 400 calories

Adverse Effects Same as tenofovir and emtricitabine and rilpivirine (see above or click on the drug name)
Rilpivirine does not usually produce any side effects but rash, liver dysfunction, and depression may occur.
Tenofovir may cause nephropathy, Fanconi-like syndrome, or loss of bone mineralization.
Emtricitabine rarely causes discoloration of palms or soles.
Interactions Same as tenofovir and emtricitabine and rilpivirine (see above or click on the drug name)
Complera should not be used with proton pump inhibitors (e.g., omeprazole) and histamine-2 (H2) blockers should be separated by at least 12 hours from Complera or rilpivirine dosing

Use concomitant agents with nephrotoxic potential cautiously
Complera should not be used in combination with other antiretroviral agents.

Laboratory

Monitoring

When initiating therapy with Complera, check HIV RNA measurements at frequent intervals to assess effectiveness and adherence [e.g., week 2-3, week 4-6, and monthly until HIV RNA is undetectable]

Monthly CBC for 3 months, then every 3 months if stable
Consider monthly creatinine measurements in lean individuals, those with renal insufficiency, and patients taking other nephrotoxic drugs
Monthly liver profile for 3 months, then every 3 months and as indicated if stable

Monitor urine glucose and protein at baseline and periodically

Warning Rare lactic acidosis and hepatic steatosis.
Do not used fixed dose combination in persons with renal insufficiency.
Severe acute exacerbations of chronic hepatitis B may be observed with sudden discontinuation of lamivudine, emtricitabine, Truvada, Trizivir, Epzicom, Atripla, Complera, Stribild.
Use Complera and rilpivirine cautiously in patients with moderate to severe depression.

Fanconi syndrome (bone pain, glycosuria, hypophosphatemia, elevated serum creatinine) has been observed with tenofovir.  Monitor serum phosphorous, urine glucose and protein at baseline and periodically.

Contraindication See prescribing info below

Suggested Usage

In general Complera should be used in persons who are naive to treatment as most persons who are treatment experienced may harbor resistance mutations to lamivudine/emtricitabine and/or NNRTIs.
Resistance testing should be done prior to using Complera, even in persons naive to antiretroviral therapy.
Do not use with other antiretroviral agents.
Encourage exercise and calcium intake to minimize bone loss.
Advise patient to avoid dehydration.
Do not discontinue abruptly in patients with chronic hepatitis B without consideration of continuation of lamivudine or some other agent active against hepatitis B.

Complete prescribing information

Complera prescribing info
Also see http://www.complera.com for further info as it becomes available.
Patient handout for this drug HERE.

 

 

 

 

Stribild
A combination of  emtricitabine + elvitegravir + cobicistat + tenofovir
Approved 8/27/2012
Forms Available 300 mg tenofovir / 200 mg emtricitabine / 150 mg elvitegravir / 150 mg cobicistat, in tablet form
Dosing 1 tablet once a day with food
Renal dosing at initiation

(see below for adjustments during treatment)

Dosing interval
Ccr 30-69 cc/min
Dosing interval
Ccr < 30 cc/min
Not recommended Not recommended
Hepatic dosing: no data available
Food dependence Take Stribild with food
Adverse Effects Same as tenofovir and emtricitabine and elvitegravir and cobicistat (see above or click on the drug name)
Elvitegravir does not usually produce any side effects but some nausea or diarrhea may occur.  Rash is also possible.

Cobicistat usually does not produce side effects but nausea or diarrhea may occur.  Rash is also possible.
Tenofovir may cause nephropathy, Fanconi-like syndrome, or loss of bone mineralization.
Emtricitabine rarely causes discoloration of palms or soles.

Interactions Same as tenofovir and emtricitabine and elitegravir/cobicistat.

Use concomitant agents with nephrotoxic potential cautiously.
Stribild should not be used in combination with other antiretroviral agents.

Laboratory
Monitoring
When initiating therapy with Stribild, check HIV RNA measurements at frequent intervals to assess effectiveness and adherence [e.g., week 2-3, week 4-6, and monthly until HIV RNA is undetectable]

Check baseline urine glucose and protein and monitor periodically thereafter.

Monthly CBC, metabolic profile for 3 months, then every 3 months if stable
Consider monthly creatinine measurements in lean individuals, those with renal insufficiency, and patients taking other nephrotoxic drugs
Monthly liver profile for 3 months, then every 3 months and as indicated if stable

Warning Rare lactic acidosis and hepatic steatosis (obesity and prolonged exposure to NRTI medications may be risk factors)
Do not used fixed dose combination in persons with renal insufficiency.
Severe acute exacerbations of chronic hepatitis B may be observed with sudden discontinuation of lamivudine, emtricitabine, Truvada, Trizivir, Epzicom, Atripla, Complera, Stribild.
Use Stribild cautiously in patients who are taking other nephrotoxic agents or who are at risk of dehydration (e.g., diarrhea diseases, esophagitis, nausea and vomiting).

Renal dysfunction:  monitor renal function closely if serum creatinine increases by greater than 0.4 mg per dL and stop Stribild if the creatinine clearance drops below 50 mL/minute.

Fanconi syndrome (bone pain, glycosuria, hypophosphatemia, elevated serum creatinine) has been observed with tenofovir.  Monitor serum phosphorous, urine glucose and protein at baseline and periodically.

Contraindication alfuzosin: potential for increased level of alfuzosin levels and hypotension

rifampin: levels of elvitegravir and cobicistat may be decreased, resulting in subtherapeutic concentrations

dihydroergotamine, ergotamin, methylergonovine: potential for serious and/or life-threatening events such as acute ergot toxicity (vasospasm and ischemia of tissues or extremities)

cisapride: potential for serious and/or life-threatening events such as cardiac arrhythmias

St. John's wort (hypericum perforatum): levels of elvitegravir and cobicistat may be decreased, resulting in subtherapeutic concentrations

lovastatin, simvastatin: increased levels of statin drug which might result in myopathy, including rhabdomyolysis

pimozide: potential to cause life-threatening events such as cardiac arrhythmias

sildenafil: when dosed as Revatio (20 mg three times a day) as there is an increased risk for visual disturbances, hypotension, syncope

triazolam, oral-administered midazolam: there may be large increases in the concentrations of these benzodiazapines which may results in sedation or respiratory depression

Suggested Usage

In general Stribild should be used in persons who are naive to treatment as most persons who are treatment experienced may harbor resistance mutations to lamivudine/emtricitabine and/or integrase inhibitors.

Stribild should not be used in persons with creatinine clearance of less than 70 cc/min.
Resistance testing should be done prior to using Stribild, even in persons naive to antiretroviral therapy.
Do not use with other antiretroviral agents.
Encourage exercise and calcium intake to minimize bone loss.
Advise patients to avoid dehydration.
Do not discontinue abruptly in patients with chronic hepatitis B without consideration of continuation of lamivudine or some other agent active against hepatitis B.

Complete prescribing information

Stribild Prescribing Info
Also see http://www.stribild.com for further info as it becomes available.
Patient handout for this drug HERE.

 

 

 

Next Page Click HERE for Antiretroviral Summary Information


 

Links to Antiretroviral Sections
Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI)
AZT  |  ddI  |  d4T  |  3TC  |  ABC  |  FTC  |  TDF  ||| Coformulation NRTI:  Combivir  |  Trizivir  |  Epzicom  |  Truvada
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI)
efavirenz  |  nevirapine  |  delavirdine  |  etravirine  |  rilpivirine
Protease Inhibitors (PI)  |  Boosted Protease Inhibitors
saquinavir  indinavir  |  ritonavir  |  nelfinavir  |  lopinavir + ritonavir  |  atazanavir  |  fosamprenavir  | tipranavir
Co-receptor Inhibitors
maraviroc
Fusion Inhibitors
enfuvirtide
Integrase Inhibitors
raltegravir  |  elvitegravir  |  dolutegravir
Antiretroviral Metabolic Inhibitors
cobicistat  |  ritonavir
Coformulations
Atripla (efavirenz/tenofovir/emtricitabine)  |  Complera (rilpivirine/tenofovir/emtricitabine)  | Stribild (elvitegravir/cobicistat/tenofovir/emtricitabine)


 

Quick Menu / Table of Contents
Introduction Principles Management NRTI Info NNRTI Info
PI Info Fusion Inhibitors Coreceptor Inhibitors Integrase Inhibitors Drug Summary
Coformulation Antiretroviral Therapy
Investigational Adherence Lab Evaluation Resistance Tests PEP
Antiretroviral Tables OI Prevention Vaccinations TB Therapy Hepatitis Therapy
OI Diagnosis OI Therapy Bibliography Links Palliative Therapy

 

Updated 3/5/2013

 


 

1. Renal dosing information from: Ian R. McNicholl & Rudolph A. Rodriguez, MD, Dosing of Antiretroviral Drugs in Renal Insufficiency and Hemodialysis, May 2004
http://hivinsite.ucsf.edu/InSite?page=md-rr-18