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How to Fine Tune Your Meds
When it comes to HIV, it's become clear that everything -- including the devil -- is in the details. While we're learning to fine tune our use of the current drug arsenal, side effects and viral resistance remain serious problems that prevent people from sticking to these regimens long-term. That's the view experts have taken in revising treatment guidelines for HIV drugs. They've tackled thorny problems like drug interactions and toxicity: how drugs are absorbed, how they interact with food and other drugs, and how they affect pregnancy. What's left out are such decisions as when and how to recycle drugs, how best to use new tests that measure drug resistance, and how to manage drug failures before they happen.
Eighteen antiretroviral drugs and one anticancer drug, hydroxurea, are being used to treat HIV infection, including two newcomers: Abbott's potent new protease inhibitor, ABT-378 (lopinavir), available through a nationwide expanded access program (888-711-7193); and Gilead's oral PMPA, a.k.a. tenofovir, a nucleotide reverse transcriptase inhibitor, available on a compassionate-use basis* (800-445-3235). Both offer hope for people needing new salvage therapies, but for now, few slots are available through these programs.
Insiders are also encouraged about new data on three-"nuke" cocktails, which would allow people to save other drugs for later use. The same holds for non-nukes like Sustiva, which, new reports suggest, may prove better than protease inhibitors for long-term control of HIV (viral suppression) and tolerability. Looking ahead, Gilead's promising nucleotide drug adefovir is speeding through the drug pipeline, but activists worry about its effect on the kidneys.
We've revised our own table, to make room for the expanding list of drug interactions (see below), with each chart designed to note the main features of each drug. For a more complete list and updates, check with your doctor or community organization. -ACD, EB
| Nucleoside analog reverse transcriptase inhibitors are potent in combination with other drugs; used alone, they lead to HIV resistance. AZT, d4T, 3TC, and abacavir penetrate the blood-brain barrier. Drug class side effect: Lactic acidosis, lipodystrophy (fat distribution). |
| Drug/Dosage | Side Effects | Recommendations |
Retrovir (AZT/ zidovudine)
Glaxo Wellcome
Dose: 300-600 mg/day
Approved for pediatric use. (more) | Nausea, vomiting, anemia, low white-blood-cell counts, bone-marrow damage, headaches, rash, itching, weakness, loss of appetite, muscle loss. | Best on empty stomach; take AZT with food if you have stomach irritation. Take vitamin E, erythropoieitin alpha (EPO), or G-CSF to prevent possible blood-cell damage; B vitamins and manganese. Warning: A structural flaw in AZT may lead to HIV resistance. |
| Combivir (3TC 150 mg/AZT 300 mg) | See 3TC and AZT. | Watch for anemia. |
Epivir (3TC, lamivudine)
Glaxo Wellcome
300 mg/day (Two 150 mg/day)
Liquid solution for pediatric use. (more) | Headache, nausea, fatigue, low white-blood-cell count, rare hair loss, neuropathy. | Watch for anemia and neutropenia. Monitor triglycerides for pancreatitis, especially in children. Take with or without food. |
Videx (ddI/didanosine)
Bristol-Myers Squibb 400 mg/day
Approved for pediatric use. (more) | Stomach pain, diarrhea, pancreatitis, hepatitis, seizures, headaches; neuropathy with high doses. | Avoid alcohol, which increases risk of pancreatitis. Take on empty stomach at least 30 minutes before meal. |
Hivid (ddC/zalcitabine)
Hoffmann-La Roche
Three 0.75 mg doses/day
Approved for pediatric use. (more) | Skin rashes, canker sores, inflammation of mouth, nausea, neuropathy, upset stomach, pancreatitis, liver damage. | Watch for neuropathy and pancreatitis. Avoid taking with food if possible. |
Zerit (d4T/stavudine)
Bristol-Myers Squibb
Two 40-mg doses/day
Liquid solution for pediatric use. (more) | Neuropathy, pancreatitis, insomnia, hyperactivity; elevated liver enzymes and anemia at high doses. | Watch for neuropathy and pancreatitis. Take with or without food. |
* Ziagen (abacavir, 1592U89)
Glaxo Wellcome
300 mg twice a day
Approved for pediatric use. (more) | Headache, fatigue; rare allergy (fever, rash, nausea,dizziness, vomiting); abdominal pain, GI and liver problems. Rare: Serious hypersensitivity. | Warning: Stop drug immediately and don't try again if any sign of allergy. Avoid during pregnancy. |
| Nucleotide analog reverse transcriptase inhibitors appear potent against HIV. Unknown penetration of blood-brain barrier.
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| Drug/Dosage | Side Effects | Recommendations |
| *Preveon (adefovir dipivoxil, bis-POM PMEA) Gilead. 120 mg/day. Dose reduction to 60 mg/day recommended after 16-20 weeks.(more) | Kidney toxicity, nausea, diarrhea, elevated liver enzymes. Preveon depletes the body of a natural substance called L-carnitine. | Expanded access for those failing standard regimens. Monitor serum creatinine levels; check liver function; take with L-carnitine supplement. Good against herpes viruses. Take with or without food. |
| Non-nucleoside analog reverse transcriptase inhibitors (NNRTIs, or non-nukes) may interact with other cytochrome p450-processed drugs. NNRTIs have a mixed ability to penetrate the blood-brain barrier. Common side effect: mild rash. Some doctors build up drug doses slowly to avoid rash; others worry that dose building increases risk of drug resistance. (more) |
| Drug/Dosage | Side Effects | Recommendations |
Viramune (nevirapine)
Roxane Laboratories.
One 200-mg/day dose for 14 days then two 200-mg doses/day.
Approved for pediatric use. (more) | Fever, muscle soreness, elevated liver function, rash (possibly indicating life-threatening Stevens-Johnson syndrome in rare cases). | If rash develops, call your doctor; Benadryl or topical corticosteroids may relieve rash symptoms. Drug crosses the placenta. Take with or without food. |
Rescriptor (delavirdine)
Pharmacia & Upjohn.
400 mg three times a day.
Under study for pediatric use. (more) | Rash (possibly indicating life-threatening Stevens-Johnson syndrome in rare cases). | Take with or without food. Take with cranberry or orange juice if you have low stomach acid. If rash develops, call your doctor; Benadryl or topical corticosteroids may relieve rash symptoms. One study shows women may have higher blood levels of Rescriptor. |
Sustiva (efavirenz, DMP-266)
DuPont Merck. 600 mg once a day.
Approved for pediatric use. (more) | Light-headedness, dizziness, body ache, rash, diarrhea, nausea, flu-like symptoms. | Take before bedtime to avoid light-headedness; split dosage between a.m. and p.m. if sleeplessness is a problem. Warning: Not for use in early pregnancy (caused birth defects in some newborn monkeys). Take with or without food. |
| Drug/Dosage | Side Effects | Recommendations |
Fortovase (saquinavir)
Hoffmann-La Roche
1,200 mg three times a day. 400-800 mg twice a day with Norvir)
Invirase: old formula.
Under study for pediatric use. (more) | Diarrhea, gas, nausea, stomach cramps, heartburn, fatigue, numbness, rash; elevated liver enzymes. | Take with food or within two hours of eating. Fortovase is more potent than Invirase. Invirase not recommended as first-line therapy due to poor absorption and resistance issues. |
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Norvir (ritonavir)
Abbott Laboratories.
Six 100 mg. twice a day (400-mg doses twice a day with Fortovase). Available in pill and liquid form. Approved for pediatric use. (more) | Nausea, vomiting, weakness, diarrhea, rash, fatigue, numbness around mouth, changed taste in mouth, elevated liver enzymes. | Build up to optimal dose over a few days. Take with a full, high-protein meal. Yogurt may reduce side effects. See "Norvir Alert" for tips on taking liquid formulation. |
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Crixivan (indinavir)
Merck & Company.
Three 800-mg doses/day.
Under study for pediatric use. (more) | Kidney stones, anemia, rarely elevates liver enzymes. | Take on empty stomach with water one hour before or two hours after eating. Drink at least six glasses of water daily to avoid kidney stones. Alternative liquids: juice, skim milk, coffee, tea. Eat with fat free snacks. |
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Viracept (nelfinavir)
Agouron Pharmaceuticals
Three 750 mg doses/day.
Approved for pediatric use: dose 20-30 mg/kg. (more) | Fatigue, rash, nausea, stomach cramps, diarrhea, elevated liver enzymes. | Take with food. Use Imodium, Lomotil to control diarrhea. Women should consult with their doctors prior to use. Dose desensitization can work for patients experiencing rash. |
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Angenerase (amprenavir/141W94)
Glaxo Wellcome
Two 1,200 mg/day.
Under study for pediatric use. (more) | Nausea, heacache, neuropathy, rash, diarrhea, fatigue. Rare: Stevens-Johnson syndrome. | Can be taken with or without food. Agenerase capsules contain high levels of vitamin E. Consult with your doctor about possible interactions with Vitamin E supplements or blood-thinning drugs. |
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| Drug/Dosage | Side Effects | Recommendations |
Hydrea (Hydroxyurea/HO)
Bristol-Myers Squibb.
Two 500-mg doses/day.
A chemotherapy drug;
probably penetrates blood-brain barrier.
Available for
pediatric use. (more) | Mild nausea, bone-marrow suppression, hair loss, rare dry mouth. Reduces CD8+ cell activation. Possible: neuropathy. | Animal studies suggest possible toxicity for pregnant women. Monitor bone-marrow suppression, liver and kidney function. Drug attacks a cell enzyme (ribonucleotide reductase); may work against proviral HIV in resting T-cells and macrophages (latent infection). |
Many HIV and other drugs are broken down in the body by the same p450 liver pathways: If two drugs arrive at the liver at the same time, only one can enter, the other may be delayed. This type of interaction can cause an increase or decrease of drug levels in the blood and affect how quickly the drugs arrive at their
target. The following table lists potentially significant drug-drug interactions. This selective, basic guide has been culled from several sources. For fuller updates, check these web sites: www.healthcg.com/hiv/treatment/interactions; www.projinf.org. Read the package insert for each drug you take carefully and ask your doctor about potential interactions with other types of medications, nutritional supplements, vitamins, and food. Bring all pills or meds you take with you to your doctor to ask about interactions.
KEY: X = don't use: contraindicated ! = serious interaction  = interacts  = increases blood levels of bolded drug  = decreases blood levels of bolded drug  = bolded drug increases levels of  = bolded drug decreases levels of |
AZT
! bone-marrow drugs (eg., ganciclovir, chemotherapies, antineoplastics), ribavirin.
Ziagen, Agenerase, Crixivan, atovaquone, MKC-442, fluconazole, methadone, probenecid, Bactrim, Septra, valproic acid.
clarithromycin, Viracept, rifabutin, rifampin, Norvir.
Ongoing use of Tylenol; Dapsone, pentamidine, flucytosine, Biaxin.
3TC
! ddC
Viracept, Bactrim/Septra.
Ziagen, Crixivan.
ranitidine, amantadine.
Combivir (see AZT, 3TC).
ddI
X ddC, tetracyclines.
! pentamidine, ethambutol, ganciclovir.
Methadone, Norvir, food.
antineoplastics, alcohol. Separate from doses of: cimetidine, ciprofloxacin, dapsone, Rescriptor, Crixivan, Nizoral, quinolones, ranitidine.
ddC
X ddI.
! pentamidine, 3TC. Avoid other neuropathy-causing drugs (ie., dapsone, isoniazid, cloramphenicol, ampho-B, antineoplastics, Antabuse).
probenecid, cimetidine.
aminoglycosides, antacids (Maalox), metoclopramide.
radiation therapy, pyrimethamne, sulfadiazine, IV Bactrim, ganciclovir, acyclovir, foscarnet.
d4T
Crixivan.
Methadone.
ganciclovir, IV pentamidine, neuropathy-causing drugs.
Ziagen
Agenerase, alcohol, AZT.
3TC.
Many other drugs may interact with Ziagen. See package insert.
Viramune
X cimetidine, clavulanic acid, dicumarol, erythromycin, warfarin, tolbutamide.
! ticarcillin, Nizoral. Avoid Bactrim/Septra for first 4-6 weeks of Viramune; monitor amoxicillin.
clarithromycin.
Crixivan, Norvir, Fortovase, may decrease Methadone, Viagra, birth control pills (estradiol).
rifampin, rifabutin, triazolam, midazolam. Fluconazole increases risk of rash. Many other drugs may interact with Viramune. See package insert.
Rescriptor
X alprazolam, cisapride, midazolam, terfenadine, triazolam, astemizole, rifabutin, rifampin, ergot derivatives, simvastatin, lovastatin, proton pump inhibitors, H-2 blockers.
! amphetamines, clarithromycin.
Fluconazole, fluoxetine, Nizoral.
Viracept, Preveon, carbamazepine, MKC-442, phenobarbitol, phenytoin.
Crixivan, Norvir, Fortovase; may increase estradiol, Viagra, dapsone, warfarin, quinidine.
Many other drugs may interact with Rescriptor. Monitor anticonvulsants. See package insert.
Sustiva
X astemizole, terfenidine, cisapride, midazolam, triazolam, ergot derivatives.
! clarithromycyn.
Norvir, fluconazole.
Agenerase, Fortovase, rifampin.
Viracept, birth control pills.
Crixivan, may decrease Viagra.
Sustiva may cause an initial false-positive reading on the CediaDau urine test, monitor warfarin.
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Preveon
X Drugs toxic to kidney. Use 7 days apart from amakacin, ampho-B, foscarnet, gentamycin, nonsteroidal antiinflammatory drugs, pentamidine, tobramycin.
! rifampin, isoniazid increases risk of side effects with Preveon.
Food.
Rescriptor.
Positive interaction with 3TC.
Hydrea
Positive interaction with ddI; in vitro synergy with AZT, but risk of bone marrow suppression. Monitor neuropathy-causing drugs.
PROTEASE DRUGS: Avoid the following: simvastatin, lovastatin, rifampin, rifabutin, Nizoral, astemizole, terfenadine, cisapride, midazolam, trazolam and ergot drugs. |
Fortovase
X amiodarone, quinidine.
clarithromycin, Rescriptor, Crixivan, Nizoral, Viracept, Norvir.
Sustiva, Viramune.
Viagra, trimethoprim; may significantly increase tamoxifen.
Agenerase, Bactrim, Septra, theophylline.
Many other drugs may interact with Fortovase. Check package insert.
Norvir
X amiodarone, astemizole, bepridil, buproprion, clozapine, diazapine, flecainide, pimozide.
! Birth control pills (use barrier methods), Viagra. A long list of drugs. Check package insert.
Rescriptor, fluconazole.
Viramune, rifampin.
erythromycin, clarithromycin, Sustiva, Norvir, Agenerase, Crixivan, Viracept, Fortovase; many other drugs. See package insert.
AZT, ddI; Methadone, Bactrim/ Septra, birth control, and many others.
Poor interactions with common antihistimines and antidepressants such as Prozac.
Crixivan
Rescriptor, Nizoral, Viracept, quinidine.
Agenerase, Sustiva, Viramune, MKC-442, food, fluconazole, grapefruit juice.
AZT, clarithromycin, birth control pills (estradiol), isoniazid, Viracept, Fortovase, Bactrim/Septra; may increase Viagra, agenerase.
3TC (slightly).
alcohol, fatty foods.
Viracept
! rifabutin.
Norvir, Agenerase, Fortovase, Crixivan, food, Nizoral. Rescriptor increases blood levels of Viracept, but decreases active metabolites.
MKC-442, rifampin.
AZT, Fortovase, Crixivan, Rescriptor, norethindrone.
Viagra, birth control pills.
Agenerase
X bepridil, high fat foods.
Ziagen, Crixivan, Nizoral, Norvir, clarithromycin.
Sustiva, Fortovase.
Sustiva, Nizoral, Viracept, AZT.
3TC (slightly); may decrease birth control pills (estradiol), Crixivan.
Monitor vitamin E supplements, blood-thinning drugs, lidocaine, warfarin, quinidine, amiodarone. |
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