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Nucleoside (NRTI) & Nucleotide (NtRTI) Reverse Transcriptase Inhibitors

Detailed Prescribing Information

October 2005

 

Direct Links to NRTI Info
Principles of NRTI / NtRTI Use
Generic Brand
Zidovudine Retrovir
Zalcitabine Hivid
Didanosine Videx, Videx EC
Stavudine Zerit, Zerit-XR
Lamivudine Epivir
Abacavir Ziagen
Emtricitabine Emtriva
Tenofovir Viread
Combination NRTIs
ZDV/3TC Combivir
ZDV/3TC/ABC Trizivir
ABC/3TC Epzicom
TDF/FTC Truvada
Summary Information
NRTI & NtRTI Toxicity and Resistance Information Summary
Acceptable NRTI & NtRTI Combinations
NRTI Combinations to Avoid


 

 

Retrovir = zidovudine = AZT or ZDV
Also a component of
Combivir and Trizivir
Forms Available

100 mg caps & 300 mg tabs
Syrup 10 mg/cc in bottles of 240 cc

(300 mg ZDV + 3TC 150 mg = Combivir)

(300 mg ZDV + 150 mg 3TC + 300 mg abacavir = one Trizivir tablet)

Dosing 300 mg twice a day
Renal dosing: 100 mg every 6-8 hours
Hepatic dosing: a dosing reduction may be necessary in mild to moderate hepatic insufficiency - follow hematologic parameters closely
Food dependence Best taken on an empty stomach or will low-fat food (fatty food decreases absorption)
Adverse Effects

Actually relatively well tolerated in most patients

Bone marrow depression with leukopenia and anemia (not thrombocytopenia)

Macrocytic anemia (consider if zidovudine is essential rHuEPO) 

Leukopenia, granulocytopenia (consider GM-CSF or G-CSF if zidovudine is essential or important)

Mild GI upset is common (usually mild), nausea (sometimes severe)

Headache usually mild and improves with time.

Some liver toxicity, especially with heavy alcohol use.

Mitochondrial toxicity: zidovudine may contribute to fat redistribution / lipoatrophy; rare hepatic steatosis and lactic acidosis

Interactions

Zidovudine intensifies other marrow suppressive agents:

    Ganciclovir

    Sulfadiazine

    Sulfamethoxazole/trimethoprim (esp treatment dosing)

    Dapsone

    Antineoplastic chemotherapy

    Interferon

Suggested lab follow-up Monitor CBC at baseline and monthly x 3, then periodically and PRN
If the patient has pre-existing leukopenia or anemia, consider using another agent, follow labs closely, or use colony stimulating factors.
Warning Avoid use with stavudine (in vitro and in vivo antagonism)
Rare lactic acidosis especially in persons with underlying liver disease: nausea, malaise, anion gap acidosis, renal failure, hepatic steatosis
Complete prescribing information Retrovir http://www.gsk.com/products/retrovir_us.htm
Combivir http://www.gsk.com/products/prescriptionmedicines.shtml
Trizivir Prescribing Information

 

 

 

 

Videx  or Videx-EC = didanosine = ddI

Forms Available

125mg, 200 mg, 250 mg, 400 mg enteric-coated (Videx EC) capsules
100 mg, 125 mg, 150 mg and 200 mg chewable or dispersable wafers

Dosing

Wt. < 60 kg:       

one 250 mg EC capsule daily on an empty stomach*  or
one 125 mg wafer chewed or dispersed twice a day (consider two 125 mg wafers chewed once daily)


Wt. > 60 kg:    

one 400 mg enteric-coated capsule once a day on an empty stomach* or

two 100 mg wafers chewed or dispersed twice a day on an empty stomach*  or

two 200 mg wafers chewed or dispersed daily on an empty stomach*


*An empty stomach is defined as at least one hour before food or at least two hours after food

Renal dosing1 of EC form weight < 60 kg weight > 60 kg
Ccr
(cc/min)
Dose
(mg)
Ccr
(cc/min)
Dose
(mg)
>60 250 >60 400
30-59 125 30-59 250
10-29 125 10-29 125
<10 100
wafer-form
<10 125
Hepatic dosing: unknown - monitor patients carefully for toxicity
Food dependence Take on an empty stomach

Possible exception: when used with tenofovir, this medication (Videx-EC)  may be taken with or without food

Adverse Effects Well tolerated in most patients

Diarrhea and GI upset common with wafer form

5-10% incidence of subclinical to rare fatal pancreatitis

Peripheral neuropathy - less common than zalcitabine or stavudine

Bad taste in mouth from wafer form of didanosine

Rare lactic acidosis and hepatic steatosis especially in setting of hepatitis C, ribavirin therapy, and concomitant stavudine

Didanosine may contribute to fat redistribution

Interactions Ribavirin increased didanosine exposure increasing the risk for lactic acidosis and/or pancreatitis
Ganciclovir raises ddI blood levels significantly: may need ddI dose reduction

Wafer form of didanosine lowers absorption of indinavir (see indinavir dosing below)

Wafer form decreases absorption of delavirdine

Tenofovir increases ddI levels: observe for ddI-related toxicity & reduce ddI-EC to 250 mg daily

Tenofovir and didanosine may produce mitochondrial toxicity and increased nephrotoxicity

Suggested lab follow-up Monitor lipase at baseline and monthly x 3-6 months, then periodically and PRN
Warning Avoid use with ddC/zalcitabine (increased peripheral neuropathy)

Contraindicated with prior history of pancreatitis or elevated lipase / p-amylase

Contraindicated in moderate to heavy alcohol users.
Pancreatitis may be fatal.  Consider pancreatitis first in the differential diagnosis in patients on didanosine with compatible symptoms.

Avoid use with d4T/stavudine if possible
Rare lactic acidosis especially in persons with underlying liver disease: nausea, malaise, anion gap acidosis, renal failure, hepatic steatosis

Contraindications Pancreatitis - clinical or subclinical - in the past
Moderate to heavy alcohol ingestion
Concomitant use of ribavirin
Usage suggestions The extended-release form of didanosine (Videx-EC) has largely supplanted the wafer form (immediate-release) of didanosine due to decreased dose frequency and markedly improved side-effect profile.
Strongly discourage anything more than occasional alcohol use.
Complete prescribing information http://www.videxec.com/

 


 

 

Hivid  = zalcitabine = ddC
Forms Available 0.375 and 0.75 mg tablets
Dosing

Wt. < 60 kg: 0.375 mg po three times a day


Wt. > 60 kg: 0.75 mg po three times a day

Renal dosing1 Ccr
(cc/min)
Dose
(mg)
10-40 0.75 twice a day
<10 0.75 daily
hemodialysis not recommended
Hepatic dosing: unknown but zalcitabine does not undergo significant hepatic metabolism
Food dependence This medication may be taken with or without food.
Adverse Effects Well tolerated in most patients

25% incidence of peripheral neuropathy, oral ulcers, skin rash

<1% incidence of pancreatitis.

Rare lactic acidosis and hepatic steatosis

Peripheral neuropathy - initially involves soles of feet, spreads cephlad, and may initially present as foreign body sensation.
Monitor level of discomfort frequently and stop with any progression from "minimal" or “mild.”

“Coasting effect” =  peripheral neuropathy may continue to worsen for several weeks after discontinuation and then decrease in some cases.

Interactions Increased neurotoxicity of other neuropathic drugs
Suggested lab follow-up Serum lipase testing as indicated
Warning

Avoid use with d4T, ddI due to increased neurotoxicity.

Usage suggestions Zalcitabine has been largely abandoned due to the high incidence of peripheral neuropathy and its relative low potency.

Complete prescribing information

http://www.rocheusa.com/products/hivid/pi.html

 

 

 

Zerit  and Zerit-XR*  = stavudine = d4T
*XR formulation not available as of May 2005
Forms Available immediate release form 15, 20, 30, 40 mg caps
*extended-release form
37.5 mg, 50 mg, 75 mg, and 100 mg [not available June 2004]

Powder for oral solution (1 mg/ml after reconstitution)

Dosing

Immediate-release form:

Wt. > 60 kg: 40 mg twice a day

Wt. < 60 kg, OR if restarting after mild peripheral neuropathy resolves: 30 mg twice a day


Extended-release form:

Wt>60 kg: 100 mg daily

Wt<60 kg: 75 mg daily

Renal dosing1 Creatinine
Clearance
(cc/min)
Weight
(kg)
< 60 > 60
> 50 30 mg twice a day 40 mg twice a day
26-50 15 mg twice a day 20 mg twice a day
10-25 15 mg daily 20 mg daily
hemodialysis 15 mg daily 20 mg daily
Hepatic dosing: limited data - stavudine pharmacokinetics were not altered in 5 non-HIV-infected volunteers with cirrhosis - however, see Warnings below
Food dependence This medication may be taken with or without food.
Adverse Effects Fairly well tolerated in most patients

Peripheral neuropathy (10-20%) [consider baseline neuropathy exam]

Rare pancreatitis, lactic acidosis and hepatic steatosis

Increasingly associated with fat redistribution, hyperlipidemia, metabolic syndrome

Interactions LIkely increased neurotoxicity of other neuropathic drugs including stavudine, didanosine, zalcitabine
Suggested lab follow-up Lipase testing as desired or indicated for symptomatology compatible with pancreatitis
Warning Avoid use with zalcitabine due to increased neurotoxicity and zidovudine (in vitro/in vivo antagonism).
Concomitant use with ddI/didanosine and hydroxyurea may increase the risk of fat redistribution, peripheral neuropathy, pancreatitis, and/or lactic acidosis.
Use with extreme caution in the setting of liver disease especially hepatitis C
Usage suggestions The extended release form of stavudine has not been widely available at the time of this writing (July 2005), but it certainly may be the preferred form in many cases.

In general (in the author's opinion) stavudine should not be used especially in older, more ill or more immunodeficient patients without compelling reasons due to the issues of lipoatrophy, dyslipidemia, and peripheral neuropathy that are associated increasingly with this drug.
Do not use with other mitochondrial toxins (ddC, ddI)
Do not use with zidovudine, Combivir, or Trizivir due to antagonism (with zidovudine.)

Complete prescribing information

http://www.zerit.com/

 

 

 

Epivir  = lamivudine = 3TC
Also a component of
Combivir, Trizivir, & Epzicom
Forms Available 150 mg or 300 mg tablets; liquid 50 mg/5 cc
3TC 150 mg combined with ZDV 300 mg as Combivir
3TC 150 mg combined with ZDV 300 mg and abacavir 300 mg as Trizivir
3TC 300 mg combined with abacavir 600 mg as Epzicom
Dosing 150 mg twice a day or 300 mg once a day
Reduce dosing for renal failure
Renal dosing1 Ccr
(cc/min)
Dose
(mg)
> 50 150 twice a day or 300 daily
30-49 150 daily
15-29 150 first dose, then 100 daily
5-14 150 first dose, then 50 daily
< 5 insufficient data
consider 150 first dose, then 25 daily
Hepatic dosing: no dose adjustment is required
Food dependence This medication may be taken with or without food.
Adverse Effects Few if any (hair loss?)
Rare lactic acidosis and hepatic steatosis

Rarely associated with pancreatitis.

Interactions None significant
Suggested lab follow-up  Lipase testing as indicated
Warning Flare of hepatitis B if lamivudine is discontinued suddenly.
Low barrier to one-step mutation.  Use only with other potent agents.

Suggested Usage

Do not use in combination with emtricitabine, Truvada, Epzicom, Combivir, or Trizivir due to identical mechanism of action or duplication of lamivudine dosing.

Complete prescribing information

Epivir prescribing information

 

 

 

Ziagen = abacavir
Also a component of
Trizivir & Epzicom
Forms Available 300 mg tabs

Solution 20 mg/cc

300 mg AZT + 150 mg 3TC + 300 mg abacavir as Trizivir
300 mg 3TC + 600 mg abacavir as Epzicom

Dosing 300 mg twice a day
Renal dosing1: no adjustment necessary
Hepatic dosing: in mild liver disease, reduce dose to 200 mg twice a day; in severe disease, abacavir is contraindicated
Food dependence This medication may be taken with or without food.
Adverse Effects Nausea which usually improves, headache.

Rare lactic acidosis and hepatic steatosis

5-8% incidence of Abacavir Hypersensitivity Syndrome (usually occurs in first 6 weeks of therapy) which is characterized by the following:

          Worsens with each dose

          Fever

          Rash

          Progressive nausea, malaise

          Pulmonary symptoms
          Diarrhea

Treatment of hypersensitivity syndrome: Discontinue abacavir and supportive care.

DO NOT RECHALLENGE.

DO NOT attempt desensitization

See Ziagen administration protocol below.
There is a slightly higher incidence of abacavir hypersensitivity with single daily dosing (Epzicom).

Interactions Unclear interaction with tenofovir: do not use without a PI or NNRTI until further information available.
Suggested lab follow-up CBC, comprehensive metabolic profile monthly x 3 months and then as indicated.
Warning Rechallenge of patient with abacavir hypersensitivity reaction is usually fatal.
Contraindications Previous abacavir hypersensitivity

Suggested

Administration

Protocol
including
Evaluation & Management
of
Suspected or Proven
Hypersensitivity Syndrome

Do not start patients on nevirapine or sulfamethoxazole/trimethoprim simultaneously if possible to avoid confusion over etiology of any hypersensitivity that develops.

 

1.  Educate patient about the abacavir hypersensitivity syndrome and provide a written summary of the syndrome as well as contact information for the provider [patient handout HERE]

2.  Patient should be instructed to avoid travel for the first 6 weeks of therapy with abacavir if possible

3.  Patient should be instructed to notify provider of any symptoms compatible with the syndrome promptly

4.  Patient should be instructed to NOT discontinue the abacavir until seen by the provider unless the syndrome is already severe

5.  Patient should be physically seen by the provider as soon as possible if symptoms compatible with abacavir hypersensitivity develop

a.  If a detailed evaluation reveals a high likelihood of the syndrome, the abacavir should be discontinued promptly and permanently.  The supply of the drug should be disposed of with a witness present preferably or returned to the healthcare provider

b.  If the detailed evaluation is equivocal, the patient should be monitored very frequently or at least daily.  If the symptomatology increases with each subsequent dose of abacavir, the diagnosis is then certain, and the drug should be stopped permanently.  Drug should be returned to the provider or disposed of with a witness present.

If the patient discontinues the abacavir prior to being seen by a provider experienced in abacavir hypersensitivity evaluation, it is important to regard the patient as having had definite abacavir hypersensitivity, and the drug should be permanently discontinued.  

 

Rechallenge with abacavir for diagnostic or therapeutic purposes is CONTRAINDICATED.

Suggested Usage

Do not use in combination with Epzicom or Trizivir due to identical mechanism of action or duplication of abacavir dosing.

Complete prescribing information

http://www.gsk.com/products/ziagen_us.htm

 


 

Viread  = tenofovir = TDF
Also a component of Truvada
Forms Available 300 mg tabs
Dosing 300 mg daily
Renal dosing1 Ccr
(cc/min)
Dose
(mg)
> 50 300 daily
30-49 300  every 48h
10-29 300  every 3-4 days
hemodialysis 300  once a week
Hepatic dosing: no dose adjustment necessary based on pharmacokinetics in non-HIV-infected volunteers with liver disease
Food dependence This medication is best taken with food.
When taken with didanosine, this medication may be taken with or without food.
Adverse Effects Accentuation of nephrotoxicity of other drugs or conditions?
Rare nephrotoxicity has been noted in individuals with low body mass index.
Bone mineral density (BMD) decreases particularly of the lumbar spine are seen more frequently with tenofovir than with stavudine. (for more info, click HERE)
Interactions Increased didanosine levels: reduce dose of Videx-EC to 250 mg daily
Unclear reaction with
abacavir
: do not use this combo without a PI or NNRTI until further information is available.
Lopinavir/ritonavir increases tenofovir levels significantly: consider monitoring renal function closely
Suggested lab follow-up Monitor serum creatinine in selected patients (preexisting renal dysfunction, low body mass index, other nephrotoxic drugs, etc.)
Warning Rare lactic acidosis (least likely to produce this effect of NRTIs?)

Possible flare of hepatitis B if tenofovir is discontinued suddenly.

Suggested Usage

Do not use in combination with Truvada due to identical mechanism of action or duplication of tenofovir dosing.

Complete prescribing information

http://www.viread.com



 

Emtriva  = emtricitabine = FTC
Also a component of Truvada
Forms Available 200 mg caps: 10 mg/ml oral solution
Dosing 200 mg daily
Renal dosing1 Ccr
(cc/min)
Dose
(mg)
> 50 200 dailyay
30-49 200 q48h
15-29 200 q72h
<15 200 q96h
hemodialysis 200 q96h
give dose after dialysis
Hepatic dosing: insufficient data, but there appears to be no hepatic metabolism
Food dependence This medication may be taken with or without food.
Adverse Effects Very well tolerated

Diarrhea, nausea, rash at incidence similar to other agents
Skin discoloration, usually mild and asymptomatic: palms and/or soles 3%

Flare of hepatitis B if stopped suddenly.

Interactions None significant
Suggested lab follow-up None
Warning Rare lactic acidosis

Low barrier to one-step mutational resistance
Possible flare of hepatitis B if emtricitabine is discontinued suddenly.

Suggested Usage Do not use in combination with lamivudine, Truvada, Epzicom, Combivir, or Trizivir due to identical mechanism of action (with lamivudine) or duplication of emtricitabine dosing.

Complete prescribing information

http://www.emtriva.com/fpi.pdf

 

 

 

Fixed Dose Combination NRTI Formulations

 

 

 

Combivir
A combination of zidovudine + lamivudine
Forms Available 300 mg zidovudine / 150 mg lamivudine in tablets
Dosing 1 tablet twice a day
Renal dosing: not recommended
Hepatic dosing: not recommended
Food dependence This medication is best taken on an empty stomach.
Adverse Effects Same as zidovudine plus lamivudine
Interactions Same as zidovudine plus lamivudine
Suggested lab follow-up Monthly CBC x 3 months, then q3months if stable
Warning Rare lactic acidosis and hepatic steatosis.
Use cautiously in patients with anemia
Possible flare of hepatitis B if Combivir is discontinued suddenly.

Suggested Usage

Do not use in combination with lamivudine, emtricitabine, Truvada, Epzicom, or Trizivir due to identical mechanism of action or duplication of lamivudine dosing.
Do not use Combivir with stavudine due to antagonism with the zidovudine component.

Complete prescribing information

http://www.combivir.com

 

 

 

Trizivir
A combination of zidovudine + lamivudine + abacavir
Forms Available 300 mg zidovudine / 150 mg lamivudine in tablets / 300 mg abacavir in tablets
Dosing 1 tablet twice a day
Renal dosing: not recommended
Hepatic dosing: not recommended
Food dependence This medication is best taken on an empty stomach.
Adverse Effects Same as zidovudine plus lamivudine plus abacavir
Interactions Same as zidovudine plus lamivudine plus abacavir
Suggested lab follow-up Monthly CBC x 3 months, then q3months if stable
Warning 5% incidence of abacavir hypersensitivity (see abacavir above)

Rare lactic acidosis and hepatic steatosis.
Possible flare of hepatitis B if Trizivir is discontinued suddenly.

Contraindication Previous abacavir hypersensitivity

Suggested administration protocol

Click HERE to review abacavir administration protocol

Suggested Usage

Do not use in combination with lamivudine, emtricitabine, Truvada, Epzicom, or Combivir due to identical mechanism of action or duplication of lamivudine dosing.
Do not use Trizivir with stavudine due to antagonism with the zidovudine component.

Complete prescribing information

Trizivir Prescribing Info

 

 

 

Epzicom
A combination of lamivudine + abacavir
Approved 8-2-2004
Forms Available 300 mg lamivudine / 600 mg abacavir in tablets
Dosing 1 tablet once a day
Renal dosing: not recommended for Ccr < 50 cc/min
Hepatic dosing: not recommended for hepatic failure
Food dependence Epzicom may be taken with or without food.
Adverse Effects Same as lamivudine plus abacavir (see above or click on the drug name)
Interactions Same as lamivudine plus abacavir (see above or click on the drug name)
Suggested lab follow-up Monthly CBC x 3 months, then every 3months if stable
Warning 5-8% incidence of abacavir hypersensitivity (see abacavir above)
The incidence of abacavir hypersensitivity is slightly higher (8%) with single daily dosing of abacavir in this formulation.

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 Epzicom.

Contraindication Previous abacavir hypersensitivity

Suggested administration protocol

Click HERE to review abacavir administration protocol

Suggested Usage

Do not use in combination with lamivudine, emtricitabine, Truvada, Combivir, or Trizivir due to identical mechanism of action or duplication of lamivudine dosing.

Complete prescribing information

Epzicom Prescribing Info

 

 

 

Truvada
A combination of tenofovir + emtricitabine
Approved 8-2-2004
Forms Available 300 mg tenofovir / 200 mg emtricitabine in tablet form
Dosing 1 tablet once a day with or without food
Renal dosing Dosing interval
Ccr 30-49 cc/min
Dosing interval
Ccr < 30 cc/min
48 hours Not recommended
Hepatic dosing: very little data, but preliminary information suggests little effect on dosing.
Food dependence None significant.
Adverse Effects Same as tenofovir and emtricitabine (see above or click on the drug name)
Interactions Same as tenofovir and emtricitabine (see above or click on the drug name)
Suggested lab follow-up Monthly CBC x 3 months, then every 3 months if stable
Consider monthly creatinine measurements in lean individuals or those with renal insufficiency
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 Truvada.

Contraindication None

Suggested Usage

Do not use in combination with lamivudine, emtricitabine, Epzicom, Combivir, or Trizivir due to identical mechanism of action or duplication of emtricitabine dosing.

Complete prescribing information

Truvada Prescribing Info
Also see http://www.truvada.com for further info as it becomes available.

 

 

NRTI Summary Information

 

 

NRTI & NtRTI Toxicity and Resistance Information Summary

Generic
Brand
Nomenclature

Pill Burden
per day
Bone
Marrow
Peripheral
Neuropathy
Pancreatitis Lipo Mitochondrial
Toxicity
Other Active
Against
Hep
B
Hypersensitivity
Associated
With M184V
High Level
Resistance Mutations
zidovudine
Retrovir

AZT, ZDV

2 +++ Rare   + ++ Nausea,
headache
  Yes Q151M, T215Y/F
lamivudine
Epivir
3TC
1-2     Rare   + Rare hair loss Yes   M184V
zalcitabine
Hivid
ddC
3   ++++ + ++ +++ Poor potency?
Rare rash
    K65R, T69D/N/S/A/ins
didanosine
Videx-EC
ddI
1   ++ ++ ++ ++ Active in the setting of multi-NRTI resistance?     K65R, Q151M,
L74V
abacavir
Ziagen
ABC
2       + + Hypersensitivity 5%,
nausea, headache
    M184V, Q151M
tenofovir
Viread
TDF
1       ? + Rare nephrotoxicity Yes Yes K65R
emtricitabine
Emtriva
FTC
1         + 3% skin hyperpigmentation Yes   M184V
stavudine
Zerit
d4T
1-2 + ++++ + +++ ++++     Yes Q151M

 

Lipo = potential for fat cell mitochondrial toxicity and clinical syndrome of fat redistribution, hyperlipidemia, Type 2 diabetes

 

For detailed NRTI & NtRTI Mutation information, please consult with the Antiretroviral Resistance section of this site, HIVResistanceWeb.com or check the links section.

 

 

Acceptable NRTI Combinations
[should be combined with PI or NNRTI in almost all instances]

Order
of
Preference
Regimen Rationale
1 abacavir + zidovudine + lamivudine (Trizivir) Pro: 3 drugs combined in one pill with twice a day dosing and good tolerance
Con: 3 drugs may be unnecessary
2 zidovudine + lamivudine (Combivir) Pro: 2 drugs combined in one pill with twice a day dosing and excellent tolerance
Con: slow onset of mitochondrial toxicity (lipoatrophy) and rapid onset of myelopsuppression and anemia possible
  tenofovir + emtricitabine (Truvada) 1 pill per day with excellent potency and tolerance
  abacavir + lamivudine (Epzicom) Pro: 1 pill per day with excellent potency and very good tolerance
Con: abacavir hypersensitivity possible
3 abacavir + tenofovir Pro: low mitochondrial toxicity and high potency; probably can be taken as 3 pills once a day
Con: abacavir hypersensitivity possible
4 tenofovir + didanosine-EC Pro: 2 pills with excellent potency, tolerance, and once-a-day dosing (adjust didanosine for interaction with tenofovir)
Con:  tenofovir and didanosine combination may limit CD4-lymphocyte response to virologic suppression; pancreatitis possible with didanosine
5 didanosine-EC + (emtricitabine or lamivudine-daily) Pro: 2 drug in 2-3 pills with excellent potency, tolerability once-a-day
Con: pancreatitis possible with didanosine
6 tenofovir + Combivir Pro: 3 drugs in 3 pills per day with excellent potency, good tolerance and twice a day dosing
Con: 3 NRTI drugs may be unnecessary, toxic, and expensive
7 abacavir + emtricitabine Pro: 2 drugs in 3 pills per day with excellent potency, excellent tolerance, and twice a day dosing
Con: abacavir hypersensitivity possible; abacavir and lamivudine co-formulated and therefore will reduce pill burden

 

lamivudine-daily = 300 mg lamivudine as a single daily dose of one or two pills

stavudine-daily = once-a-day stavudine extended-release form [not yet available May 2005]

 

 

NRTI Combinations To Avoid

AZT + d4T In vitro and in vivo antagonism
3TC + ddC In vitro antagonism
ddI + ddC Increased mitochondrial toxicity especially peripheral neuropathy
ddC + d4T Increased mitochondrial toxicity especially peripheral neuropathy
ddC + 3TC Poor potency?
ddC + ddI Increased mitochondrial toxicity especially peripheral neuropathy
ABC + TDF + 3TC Unclear interaction, but probably decreased ABC at cellular level; especially avoid single daily dosing of ABC in this combination without a PI or NNRTI; high failure rate and high rate of development of K65R and M184V mutations.  Although the high rate of failure has been seen in the setting of non-PI and non-NNRTI based regimens, it is probably prudent to avoid this combination even when used with other classes of antiretroviral therapy.
FTC + 3TC Identical mechanism of action and resistance; unlikely to increase the activity of each other; equivalent to monotherapy with FTC or 3TC
ddI + d4T Increased mitochondrial toxicity which may be severe

 

 

 

Next Page Click HERE for Key NNRTI Information or detailed NNRTI information


 

 

Links to Antiretroviral Sections (click on anything)
Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI)
AZT  |  ddC  |  ddI  |  d4T  |  3TC  |  ABC  |  FTC  |  TDF  |  Combivir  |  Trizivir  |  Epzicom  |  Truvada
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI)
efavirenz  |  nevirapine  |  delavirdine
Protease Inhibitors (PI)  |  Boosted Protease Inhibitors
saquinavir  indinavir  |  ritonavir  |  nelfinavir  |  amprenavir  |  lopinavir + ritonavir  |  atazanavir  |  fosamprenavir  | tipranavir
Fusion Inhibitors
enfuvirtide

 

 

Quick Menu / Table of Contents
Introduction Principles Management NRTI Key NRTI Info
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Drug Summary Investigational Adherence Lab Evaluation Resistance Tests
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Updated 10.2.2005

 


 

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