Non-nucleoside reverse transcriptase inhibitors

background

Non-nucleoside reverse transcriptase inhibitors (NNRTIs), also called non-nucleoside analogues, are a type of medication called antiretrovirals. They are used to treat patients with HIV (human immunodeficiency virus). These drugs interfere with the virus' ability to multiply. Although they are not curative, these drugs have been shown to effectively slow the replication of the virus in the body when taken in combination with other antiretrovirals. As a result, the patient's immune system is strengthened and the patient has an increased life expectancy.
Currently, the U.S. Food and Drug Administration (FDA) has approved three NNRTIs, including delavirdine (Rescriptor®), efavirenz (Sustiva®), and nevirapine (Viramune®)
HIV primarily targets the body's CD4 T-cells, which are white blood cells that help coordinate the immune system's response to infection and disease. Therefore, HIV patients are vulnerable to opportunistic infections. These infections occur in patients who have weakened immune systems. Some opportunistic infections may lead to the development of AIDS (acquired immune deficiency syndrome).
Antiretrovirals are able to suppress HIV, which boosts the patient's immune system. These drugs have also been shown to dramatically slow the progression of opportunistic infections.
HIV patients typically receive a combination of antiretroviral drugs because a single patient may have several different strains (types) of the virus circulating in the blood. The different strains of the virus may respond differently to specific types of drugs. Therefore, highly active antiretroviral therapy (HAART), which is a combination of drugs from at least two different classes, is recommended. There are four major classes of antiretrovirals: fusion inhibitors, protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Each drug class disrupts different stages of HIV's life cycle.

Related Terms

Achlorhydria, acquired immune deficiency syndrome, acquired immunodeficiency syndrome, AIDS, antiretrovirals, antiretroviral therapy, ART, CD4 cells, delavirdine, efavirenz, fusion inhibitors, immune, immune defense system, immunocompromised, immunodeficiency, HAART, highly active antiretroviral therapy, HIV, human immunodeficiency virus, nevirapine, nucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors, OI, opportunistic infections, protease inhibitors, reverse transcriptase, reverse transcriptase inhibitors, suppressed virus, viral infection, viral suppression, virus, weakened immune system, white blood cells.

function

Normally, the HIV enzyme called reverse transcriptase uses the nucleic acids (building blocks) inside the patient's cell to multiply. When patients take non-nucleoside reverse transcriptase inhibitors (NNRTIs), the drug attaches to HIV's enzyme before it can use the patient's nucleic acid to multiply. As a result, the virus' ability to replicate and infect new cells is significantly reduced.
NNRTIs have been shown to decrease the amount of viral particles in the patient's blood (viral load), boost the immune system, and increase life expectancy.

general precautions

Patients should always take their medications exactly as prescribed by their healthcare providers.
Patients should tell their healthcare providers if they are taking any other drugs (prescription or over-the-counter), herbs, or supplements because they may interact with treatment.
Patients should tell their healthcare providers if they have any other medical conditions, especially liver disease or kidney disease, because alternative doses or medications may be needed.
Patients should tell their healthcare providers if they are pregnant, think they may be pregnant, or are trying to become pregnant because some antiretrovirals are unsafe during pregnancy and may cause birth defects in the baby.
Antiretrovirals do not reduce the risk of transmitting HIV to others. Even if antiretrovirals are able to suppress the virus to undetectable levels, it can still be transmitted to others.
Antiretrovirals do not cure HIV/AIDS. However, they have been shown to significantly reduce the amount of HIV in the blood.

delavirdine (rescriptor®)

The U.S. Food and Drug Administration (FDA) approved delavirdine (Rescriptor®) on April 4, 1997 for the treatment of HIV in adults in combination with other antiretrovirals. It is usually combined with two other nucleoside reverse transcriptase inhibitors.
Delavirdine is available in tablet form in 100 milligram and 200 milligram strengths. The tablet is usually swallowed. However, the 100-milligram tablet can be dissolved in water if the patient is unable to swallow pills.
Adults typically take 400 milligrams three times daily. Some patients may require different doses. Patients should take medications exactly as prescribed by their healthcare providers. If patients are also taking the antiretroviral didanosine (Videx®) or antacids (such as Pepcid®), patients should wait at least one hour before taking delavirdine. This is because delavirdine needs stomach acids in order to be absorbed properly. If patients have a condition called achlorhydria, in which the body does not produce enough stomach acids, patients should take delavirdine with acidic liquids, such as orange juice or cranberry juice. Avoid with liver disease.
Patients should tell their healthcare providers if they are taking any other drugs (prescription or over-the-counter), herbs, or supplements. Delavirdine has been shown to interact with antibiotics, such as rifapentine (Priftin®), rifabutin (Mycobutin®), and rifampin (Rifadin®); antihistamines, such as astemizole (Hismanal®); acid reflux/heartburn drugs, such as cisapride (Propulsid®), cimetidine (Tagamet®), famotidine (Pepcid®), ranitidine (Zantac®), lansoprazole (Prevacid®), esomeprazole (Nexium®), omeprazole (Prilosec®), and pantoprazole (Protonix®); sedatives, such as midazolam (Versed®) and triazolam (Halcion®); ergot medications for migraines (such as Wigraine® and Cafergot®), and cholesterol lowering drugs, such as simvastatin (Zocor®) and lovastatin (Mevacor®).
Although other non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been shown to decrease the effectiveness of birth control pills, it remains unknown whether delavirdine has similar effects.
Delavirdine has been shown to increase levels of all protease inhibitors. Therefore, doses of protease inhibitors may need to be decreased in patients who are also taking delavirdine.
Serious side effects may include severe skin rash that causes blisters and is accompanied by muscle or joint pain, fever, redness, swelling of the eyes, and sores in the mouth. Other severe symptoms may include kidney damage, anemia (low levels of iron in the blood), and liver or muscle damage. Patients should tell their healthcare providers if any of these side effects develop.
Delavirdine has been shown to increase blood levels of erectile dysfunction drugs, such as sildenafil (Viagra®) and vardenafil (Levitra®). Therefore, doses of these drugs may need to be decreased in patients taking delavirdine.
Many HIV patients develop a less serious skin rash on the upper body and arms one to three weeks after starting the medication. This rash usually clears up in about two weeks. Other less serious side effects may include headache, fatigue, vomiting, nausea, and diarrhea. These side effects generally lessen over time.

efavirenz (sustiva®)

The U.S. Food and Drug Administration (FDA) approved efavirenz (Sustiva®), also called EFV, September 17, 1998 for the treatment of HIV with other antiretrovirals (usually two nucleoside reverse transcriptase inhibitors) in patients ages three and older. Efavirenz has also been used in combination with other antiretrovirals to prevent the transmission of HIV in patients who were accidentally exposed to the virus at work.
Efavirenz is taken by mouth as a capsule or tablet. A liquid formulation is currently under development. This drug can be taken with or without food. However, it should not be taken with a high-fat meal because this reduces the amount of drug that is able to be absorbed into the blood.
According to the U.S. Department of Health and Human Services (DHHS) treatment guidelines, efavirenz is the recommended non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV patients who are just starting treatment.
Adults and children who weigh more than 88 pounds typically take 600 milligrams once daily. Pediatric doses for children who way less than 88 pounds is dependent on weight. Some patients may require different doses. Patients should always take medications exactly as prescribed.
Patients should tell their healthcare providers if they are taking any other drugs (prescription or over-the-counter), herbs, or supplements. Efavirenz has been shown to interact with other drugs, including cisapride (Propulsid®), midazolam (Versed®), triazolam (Halcion), and ergot medicines (like Cafergot®). Also, efavirenz may reduce the effectiveness of birth control pills. A second method of birth control is recommended. Avoid if pregnant or thinking of becoming pregnant because efavirenz may cause birth defects.
Serious side effects may include confusion, hallucinations (seeing or hearing things that are not there), and memory loss. There have been a few reports of depression, paranoia, and suicidal thoughts, which is more common among patients with a history of mental illnesses. Some patients may develop a severe rash that causes blisters. Patients should tell their healthcare providers if they experience any of these side effects.
Other less serious side effects may include diarrhea, nausea, difficulty sleeping, abnormal dreams, dizziness, headache, and difficulty concentrating. These side effects generally lessen over time. Because efavirenz may cause dizziness, some healthcare providers recommend taking it before bed.
Efavirenz may cause patients to test positive for marijuana during a test for illicit drug use. Patients should tell the person collecting a urine sample that they are taking efavirenz. That way, the laboratory technician can consider a more sensitive drug test to prevent a false-positive result.

nevirapine (viramune®)

The U.S. Food and Drug Administration (FDA) approved nevirapine (Viramune®) on June 21, 1996 for the treatment of HIV with other antiretrovirals (usually two nucleoside reverse transcriptase inhibitors) in adults and children.
Nevirapine is available as an oral tablet and a powder that is mixed with liquid (oral suspension).
Adults typically take 200 milligrams once daily for the first 14 days, followed by 200 milligrams twice daily. Pediatric doses are dependent on age and weight. No patient should receive doses greater than 400 milligrams a day. Patients with kidney problems who are on dialysis generally take a 200-milligram tablet after each treatment. Patients should always take medications exactly as prescribed.
Recent research shows that nevirapine can pass into the brain, which may help suppress HIV that is infecting brain cells. When HIV infects brain cells, conditions, such as AIDS-related dementia, may develop. Studies suggest that nevirapine may help treat and prevent the risk of developing such conditions.
Patients should tell their healthcare providers if they are taking any other drugs (prescription or over-the-counter), herbs, or supplements. Nevirapine has been shown to interact with other drugs including antibiotics such as rifampin (Rifadin®) and rifapentine (Priftin®) and antifungals such as ketoconazole (Nizoral®). Also, nevirapine may reduce the effectiveness of birth control pills. A second method of birth control is recommended. Nevirapine has been shown to decrease the amount of ethinyl estradiol in the blood, which can increase the risk of pregnancy.
Nevirapine has been shown to reduce the amount of several protease inhibitors in the blood, including atazanavir (Reyataz®), saquinavir (Invirase®), indinavir (Crizivan®), lopinavir/ritonavir (Kaletra®), fosamprenavir (Lexiva®), and amprenavir (Agenerase®). Therefore, doses of these protease inhibitors may need to be increased if taken with nevirapine.
Nevirapine has been shown to increase the amount of some protease inhibitors, including nelfinavir (Viracept®) and ritonavir (Norvir®), in the blood. Therefore, doses of these protease inhibitors may need to be decreased if taken with nevirapine.
If patients develop severe skin rashes, sore throat, chills, fever, or other flu-like symptoms, they should consult their healthcare providers immediately because they may be signs of liver damage.
Other less serious side effects may include diarrhea, stomach pain, nausea, and headache. These symptoms generally lessen over time.