Epivir

Common Name: lamivudine or 3TC

Brand Name: Epivir

Class: nucleoside analogs (also called nucleoside reverse transcriptase inhibitors, NRTIs or nukes)

Standard dose: One 300 mg tablet once a day (or one 150 mg tablet twice daily), with or without food, and no food restrictions. Dose is lowered for people with kidney impairment. Dose for children 3 months to 16 years of age is 4 mg per 2.2 pounds twice daily to a maximum of 150 mg twice daily. A strawberry/banana-flavored liquid is available. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $432.16 / month for 300 mg tablets, $115.33/ month for 240 ml bottle

Manufacturer contact: ViiV Healthcare, 1 (877) 844-8872

Potential side effects and toxicity: This remains one of the most easily tolerated HIV medications. Side effects (rarely seen) may include headache, nausea, vomiting, diarrhea, fever, fatigue, hair loss, insomnia, malaise (general ill feeling), nasal symptoms, cough, peripheral neuropathy, low white blood cells, and anemia.

Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged, fatty liver.

Potential drug interactions: No significant drug interactions. Do not take Epzicom, Combivir, Trizivir, Truvada, Atripla, Emtriva, or Epivir-HBV while taking Epivir, since they contain Epivir or medication equivalent to Epivir.

Tips: Exciting benefit: drug resistance that the virus develops against Epivir -- the M184V mutation -- makes the virus less fit to replicate and has even been shown to keep T-cells from dropping during a treatment interruption as much as they would have otherwise. It is also approved for treatment of hepatitis B virus (HBV), under the brand name Epivir-HBV. Patients co-infected with HIV/HBV should use Epivir with Viread as their nucleoside backbone to increase activity and avoid HBV resistance. If you have hepatitis B and HIV, this drug works for both diseases, but make sure you are taking Epivir at HIV doses -- always ask your doctor or pharmacist. Worsening of hepatitis B (HBV) in people co-infected with HIV/HBV has occurred when Epivir was discontinued. These patients should be closely monitored by their physician. Epivir is also available combined with Retrovir (zidovudine, AZT), called Combivir (one tablet twice a day); in a once-daily formula with Ziagen (Epzicom, one tablet daily); and in a triple combination with both Retrovir and Ziagen (Trizivir, one tablet twice a day). Please see package insert for more complete potential side effects and interactions.

Doctor

Epivir (lamivudine, known also as 3TC) was among the first antivirals to be widely used in the regimens containing only two nucleosides that were common just before the current "HAART" or three-drug era started in the late 1990s. Lamivudine was approved by the FDA in 1995 for twice-daily dosing and again in 2002 for once-daily dosing as studies showed similar responses with once-daily use when given in combination with two other antivirals. It is a component of the fixed dose combinations Combivir, Trizivir, and Epzicom. Epivir is also approved for hepatitis B infection, but should not be used as a single drug for that virus either, as resistance will typically occur rendering this drug and others less active as a result. Lamivudine, or a closely related antiviral emtricitabine [Emtriva], forms the nucleoside backbone for nearly all HAART regimens since the HAART era began. While its use is often associated with long term successful virus suppression, it is one of the drugs in the regimen to which resistance is commonly observed if there is less than complete virus suppression. Resistance to 3TC leads to cross resistance to FTC as well. The expected 3TC resistance mutation, referred to as M184V, slightly improves the antiretroviral activity of AZT and tenofovir, which leads some clinicians to maintain the use of these combinations even after resistance occurs. Also of interest is that this mutation causes HIV to be less "fit" than wild type, meaning that despite resistance development, HIV is still partially suppressed by about one-half log due to the impact of this M184V mutation. It is very well tolerated by nearly all who take it with only rare reports of drug toxicity. It must be dose adjusted in individuals who have reduced kidney function. Overall, the generally favorable tolerability of 3TC has historically made it a commonly used drug, though its use is typically linked to the fixed dose combinations containing either abacavir or AZT. One other issue is that this drug will be "generic" sometime in 2010, but the impact of this change on insurance coverage for HIV treatment is not yet clear. -- Cal Cohen, M.D.

Activist

An easy to tolerate twice-daily drug, it quickly develops the M184V resistance mutation. Paradoxically, this makes HIV more susceptible to AZT which is why it's usually used in combo drugs like Combivir (AZT+3TC), Epzicom (abacavir+3TC), or Trizivir (AZT+abacavir+3TC). It also has activity against hepatitis B virus -- so those with hep B should check with their doctors before going on Epivir to avoid potential resistance to a drug for HBV. -- Jeff Taylor