November 2001
2001-2002 Medical Management of HIV Infection. Johns Hopkins University, Baltimore, MD. 2001. Additional information from http://www.gilead.com/pdf/viread_pi.pdf.
| Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | |||||||
| Zidovudine (AZT, ZDV, Retrovir) |
Didanosine (ddl, Videx, Videx EC) |
Zalcitabine (ddC, Hivid) |
Stavudine (d4T, Zerit) |
Lamivudine (3TC, Epivir) |
Abacavir (ABC, Ziagen) |
Tenofovir (Viread) |
|
| Recommended Dose | 300 mg bid (or with 3TC as Combivir 1 tab bid) | Tablets or oral solution >60kg: 400 mg qd (EC) or 200 mg bid (tabs) or 250 mg bid (powder) <60kg: 250 mg qd or 125 mg bid (tabs) or 167 mg bid (powder) | 0.75 mg tid | >60kg: 40 mg bid <60kg: 30 mg bid |
150 mg bid or with AZT as Combivir (1 tab bid) <50kg: 2 mg/kg bid) | 300 mg bid | (Nucleotide analog) 300 mg once daily |
| Food Effect | None | Levels  55% Take 1 hr before or 1 hr after meal
|
None | None | None | None Alcohol |
Should be taken with a meal |
| Major Toxicity Class Toxicity |
Bone marrow suppression: anemia and/or neutropenia Subjective complaints: GI intolerance, headache, insomnia, asthenia |
Pancreatitis Peripheral neuropathy GI intolerance, nausea, diarrhea |
Peripheral neuropathy Stomatitis |
Peripheral neuropathy | (Minimal toxicity) | Hypersensitivity (2-5%), fever, nausea, vomiting, anorexia, cough, dyspena, malaise, morbilliform rash. May be life-threatening with rechallenge. | Bone (in animals) Renal (in animals) Mild to moderate gastrointestinal: nausea, vomiting, diarrhea, flatulence |
| Drug Interaction | Ribavirin may reduce AZT activity | Methadone ddI levels 41%, consider ddI dose increase
|
Methadone ddI levels 27%. No dose adjustment
|
None | None | None | Take two hours before or one hour after didanosine (if applicable) |
| Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) | |||
| Nevirapine (Viramune) |
Delavirdine (Rescriptor) |
Efavirenz (Sustiva) |
|
| Recommended Dose | 200 mg po qd x 14 days, then 200 mg po bid | 400 mg po tid | 600 mg po qd at hs |
| Food Effect | None | None | -50% with high fat meal; avoid after high fat meal |
| Drug Interaction | Induces cytochrome P450 enzymes PI interactions see Table 4-16 in Bartlett Guide* |
Methadone AUC decreased 60% titrate methadone dose Not recommended: Ketoconazole and rifampin Caution: anticonvulsant |
Inhibits and induces cytochrome P450 3A4 enzymes Contraindicated drugs: astemizole, midazolam, triazolam, cisapride, ergot alkaloids, tergenadine PI interactions: generally Possibly important drug interactions: see Chapter 4 in Bartlett Guide* Methadone AUC decreased 60% titrate methadone dose |
| Major Toxicity Class Toxicity |
Rash (15-30%) may require hospitalization; rare cases of Stevens-Johnson syndrome; hepatitis | Rash; headaches Increased transaminase levels |
Dizziness, "disconnectedness," somnolence, insomnia, bad dreams, confusion, amnesia, agitation, hallucinations, poor concentration 40% usually resolves after 2 weeks Take hs. Rash -- severe in 5%; rare reports of Stevens-Johnson syndrome. Teratogenic in cynomalgus monkeys Avoid in pregnancy, and women and men should use adequate contraception methods. False positive drug screening test for cannabinoids (marijuana) |
| Protease Inhibitors (PIs) | |||||||
| Indinavir** (Crixivan) |
Ritonavir (Norvir) |
Saquinavir** | Amprenavir (Agenerase) |
Nelfinavir (Viracept) |
Lopinavir + Ritonavir (Kaletra) |
||
| (Invirase) | (Fortovase) | ||||||
| Recommended Dose | 800 mg q 8h Separated ddI dose by 1 hr |
600 mg bid Separate ddI dose by 2 hr |
Not recommended as single PI 400 mg bid with RTV | 1,200 mg tid | 1,200 mg bid (caps) 1400 mg bid (oral solution) |
1,250 mg bid or 750 mg tid | 3 caps or 0.5mL twice daily 4 caps bid when used with efavirenz or nevirapine |
| Food Effect |
77%; take 1 hr before or 2 hours after meals; may take with low fat snack or skim milk |
 15%; take with food if possible to improve tolerability |
No food effect when taken with RTV |
6x; take with large meal unless taken with RTV |
High fat meal decreases AUC 20%; can be taken with or without food, but high fat meal should be avoided |
2-3x; take with meal or snack |
Fat increases AUC 50% to 80%; should be taken with food |
| Side Effects* | GI intolerance (10-15%); nephrolithiasis or nephrotoxicity (10-15%); headache; asthenia; dizziness; rash; metallic taste; ITP; alopecia; lab: increase indirect bilirubinemia (inconsequential) Class side effects* | GI intolerance (20-40%); paresthesias-circum-oral and extremities (10%); taste perversion (10%); lab: triglycerides increase in 60% and transaminase increase in 10-15%, CPK and uric acid increase Class side effects* | GI intolerance (10-20%); increase Class side effects* | GI intolerance (20-30%); headache; hypoglycemia; transaminase increase Class side effects* | GI intolerance (10-30%); rash (20-25% -- usually at 1-10 wks), Stevens-Johnson syndrome (1%); paresthesias (10-30% -- perioral or peripheral) Increase in liver function tests. Class side effects* | Diarrhea (10-30%) Class side effects* | GI intolerance: nausea, vomiting, diarrhea Elevated Lipids Asthenia Class side effects* |
* For full information on toxicity and drug interactions for PIs and class side effects, see Chapter 4 of Bartlett J.G. and Gallant J.E. 2001-2002 Medical Management of HIV Infection. Johns Hopkins University, Baltimore, MD. 2001. For information on tenofovir, see www.gilead.com/pdf/viread_pi.pdf.
** These two drugs usually used in combination with ritonavir (see HEPP News, February 2001).
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