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Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) |
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Detailed Prescribing Information |
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April 2005 |
| Direct Links to NNRTI Info | |
| Key Points | |
| Generic | Brand |
| Delavirdine | Rescriptor |
| Nevirapine | Viramune |
| Efavirenz | Sustiva |
| NNRTI Summary Information | |
| Delavirdine = Rescriptor | |
| Forms Available | 100 mg tabs |
| Dosing | 4x100 mg three times a day |
| Contraindication |
Concomitant rifampin, alprazolam,
midazolam, triazolam, pimozide, or ergot derivative therapy St John's Wort is expected to decrease delavirdine levels and therefore should not be used Simvastatin, lovastatin |
| Adverse Effects |
33% incidence of rash, usually mild and NONPROGRESSIVE with continued treatment 5% of persons with rash will develop, mucosal involvement, and/or Stevens-Johnson syndrome (aka erythema multiforme major) Hepatitis which may be severe |
| Interactions |
Increases PI levels Antacids and proton pump inhibitors inhibit absorption of delavirdine |
| Suggested lab follow-up | Liver profile at 14 days, 30 days, and monthly x 3 months, then q3months |
| Warning | Low barrier to one-step mutation. Use only with other potent agents. |
| Complete prescribing information | http://www.rescriptor.com |
| Nevirapine = Viramune | |
| Forms Available | 200 mg tabs |
| Dosing | 200 mg daily x 14 days, then increase to 200 mg twice a day or 2x200 mg once a day |
| Contraindication |
Concomitant rifampin therapy Previous progressive hypersensitivity or moderate or greater hypersensitivity to nevirapine |
| Avoid nevirapine use in antiretroviral-naive women with CD4-lymphocyte counts > 250 or men with CD4-lymphocyte counts > 400 | |
| Adverse Effects |
33% incidence of rash, usually mild and NONPROGRESSIVE with continued treatment 5% of persons with rash will develop, mucosal involvement, and/or Stevens-Johnson syndrome (aka erythema multiforme major) Hepatitis which may be severe and more likely in the setting of higher CD4-lymphocyte counts, female gender, pre-existing hepatitis, single daily dosing. |
| Interactions |
Nevirapine decreases protease inhibitor levels (compensate by increasing PI dosage 25-33%). Compensate for this interaction by the following dose modifications:
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Nevirapine effects levels of
other drugs: Decreases oral contraceptive pill (OCP) efficacy Decreases methadone, fentanyl, imidazole antifungal drug levels Decreases warfarin efficacy |
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| Unknown interactions with atazanavir, fosamprenavir: avoid nevirapine use with these protease inhibitors until further information is available | |
| Suggested lab follow-up | Liver profile at 14 days, 30 days, and monthly x 3 months, then every 3 months |
| Warning |
Low barrier to one-step mutation. Use only with
other potent agents. Nevirapine should not be used in postexposure prophylaxis due to reports of fatal hepatotoxicity. |
| Women who start nevirapine therapy with CD4 cells counts greater than 250 (and possibly men with CD4 counts > 400) have a 12x greater risk of hepatitis due to nevirapine. The risk is greatest for the first 6 weeks of therapy but patients should be monitored carefully for at least the first 18 weeks of therapy. | |
| Sudden discontinuation of nevirapine-containing antiretrovirals may result in prolonged subtherapeutic serum levels of nevirapine in the setting of viral replication. Subtherapeutic drug levels may be associated with the development of mutational resistance and loss of activity for nevirapine and the NNRTI class as it exists currently (May 2004). See Administration Protocol below for further information on discontinuation strategies. | |
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Administration Protocol |
Initiation of antiretroviral
regimens containing nevirapine
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Discontinuation of antiretrovirals including nevirapine: (select one option
below)
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| Complete prescribing information | http://www.viramune.com |
| Efavirenz = Sustiva | |
| Forms Available | 50 mg, 100mg, 200 mg capsules; 600 mg tablets |
| Dosing |
3x200 mg or 600 mg daily Usually taken at bedtime but if too much stimulation or dreaming, dosing can be done in the AM |
| Meal dependence |
High fat meals elevate Cmax of capsule by 40%
and tablets by 80% which may result in increased CNS stimulation and adverse
events. Consider initiating therapy on an empty stomach and if tolerated administer with low fat and then regular feeds. |
| Contraindication |
Pregnancy or desire to become pregnant or
inadequate birth control precautions Do not use with saquinavir as the sole protease inhibitor Midazolam, triazolam, and ergot derivatives are not to be used with Sustiva. St. John's Wort may decrease Sustiva levels and is therefore not to be used. Voriconazole should not be used with efavirenz. |
| Adverse Effects |
50% CNS stimulation including sleeplessness, confusion, nightmares: this may be debilitating over short-term or long-term 5% incidence of rash, usually mild and NONPROGRESSIVE with continued treatment Hepatitis which may be severe |
| Interactions |
Efavirenz decreases PI levels (compensate by increasing PI dosage 25-33%)
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Decreases oral contraceptive pill efficacy Decreases methadone, fentanyl, imidazole antifungal drug levels Decreases warfarin efficacy Decreases voriconazole levels to subtherapeutic |
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| Suggested lab follow-up | Liver profile at 30 days and every 2-3 months and as indicated |
| Warning | Low barrier to one-step mutation. Use only with other potent agents. |
| Sudden discontinuation of efavirenz-containing antiretroviral regimens without substitution of other potent antiretroviral or antiretroviral combination may result in prolonged subtherapeutic serum levels of nevirapine. These subtherapeutic drug levels may result in the development of mutational resistance and loss of activity for efavirenz and the NNRTI class as it exists currently (May 2004) See Usage Suggestions below for further information. | |
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Administration Protocol |
Initiation of efavirenz: Initiate therapy during a period that is noncritical for CNS function in the patient's life (eg on a work weekend). Dosing may be suggested either immediately before bedtime or in the AM, whichever is better tolerated by the patient. Tolerance to these CNS effects (sleeplessness, nightmares, alteration of mentation, stimulation) may improve over the first two weeks of therapy. Observe dosing interactions with protease inhibitors carefully (see above) |
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Discontinuation of efavirenz: It is recommended that when antiretrovirals are discontinued that include nevirapine and efavirenz, a potent and active protease inhibitor should be substituted first for the NNRTI. This PI substitution therapy should then be continued for 2 weeks. At that point when NNRTI serum and/or intracellular levels are essentially zero, the PI-based substitute antiretroviral therapy may be stopped. Alternatively stop the efavirenz for 5 days prior to stopping the NRTI backbone. |
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| Complete prescribing information | http://www.sustiva.com |
| NNRTI Summary Information | ||||||
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Generic Brand |
Pill Burden per day |
Dosing Frequency per day |
Rash |
PI Drug Levels |
Other |
High Level Resistance Mutations |
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nevirapine Viramune |
2 | 1-2 | 33% | ↓ 25-33% |
hepatitis risk 12x higher for women CD4>250 |
K103N, Y181C/I, Y188C/L/H, G190A/S, M230L |
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delavirdine Rescriptor |
12 | 3 | 33% | ↑↑ | hepatitis | K103N, Y181C/I, Y188C/L/H, G190A/S, M230L, P236L |
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efavirenz Sustiva |
1 | 1 | 5% | ↓ 25-33% |
%50 CNS stimulation pregnancy contraindication |
K103N, Y181C/I, Y188C/L/H, M230L |
For detailed NNRTI Mutation information, please consult with HIVResistanceWeb.com or check the HIV Resistance Test section of this site.
| Next Page | Click HERE for Key Protease Inhibitor Information or HERE for Detailed PI Info |
| Links to Antiretroviral Sections |
| Nucleoside & Nucleothree times a daye 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 |
8.5.2005
