Enzyme Inhibitors - Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

The next group of enzyme inhibitors that treat HIV includes the non-nucleoside reverse transcriptase inhibitors, known as the NNRTIs. Therapeutic uses for the NNRTIs include treating symptoms of HIV-1 infection. As with all medications for HIV, they must be combined with a regimen of several HIV medications to prevent resistance from occurring. HIV-1 infection is the genetic form of HIV seen in most clients worldwide, except for clients from West Africa, who have a slightly different form called HIV-2. Not all medications that treat HIV-1 can treat HIV-2. 

Prototype and Other Medications

Efavirenz—Classification: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)  

The prototype among the NNRTI medications is efavirenz. Other NNRTI medications include nevirapine, doravirine, etravirine, and rilpivirine.​​​​​​​

Expected Pharmacologic Action

Unlike nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs) are ready to work as soon as they are absorbed into the client’s body. In other words, they are already in an active form when the client ingests them. These medications become directly incorporated into the HIV DNA chain’s reverse transcriptase, which is necessary to take the HIV virus’ RNA and insert it into the host cell’s DNA. The NNRTI medications directly interfere with the replication of the HIV virus by stopping the growth of the DNA strand. This class of medications only works on the HIV-1 form of the virus. 

Adverse Drug Reactions

Adverse effects of the NNRTIs include rash, which occurs fairly frequently. However, if the rash becomes severe, the medication should be stopped because it may develop into Stevens-Johnson syndrome or erythema multiforme. Common gastrointestinal manifestations include abdominal pain, nausea, vomiting, and diarrhea. Elevated liver enzymes, in particular transaminase levels, may also occur.

Safety Alert

Stevens-Johnson syndrome is a rare type of reaction that occurs secondary to certain medications. It manifests as a painful red to purple skin rash that spreads rapidly and includes the development of blisters on the skin and in the mouth. A fever and sore throat may occur prior to the development of the rash. The blisters actually cause sloughing of the skin that can become infected and leave scars and irregular pigmentation upon healing. The most important thing to do when this type of reaction is observed is to immediately stop the offending medication. Cool moist compresses, antihistamines for itching, and analgesics for pain will be needed to promote comfort during the acute phase. If the area of lesions is large, ensure that the client is getting adequate fluid replacement for that which is being lost through the lesions either orally, intravenously, or both. Early identification of this syndrome can increase clients’ chances of stopping the reaction in its early stages before it gets to the point where recovery will take months and even involve the use of skin grafts to repair the damage. 

Interventions

When a client is taking one of the NNRTI medications, monitor for and report a rash. Rash that occurs along with fever, lesions in the mouth or eye, blisters, or muscle pain requires discontinuation of the medication. Also, monitor the client’s weight and watch for persistent gastrointestinal effects. Report symptoms that are persistent and/or any significant loss of weight. Finally, monitor periodic liver function tests, including transaminase levels, and report elevations. 

Administration

The NNRTIs are available in tablets for oral administration. Efavirenz should be administered once daily on an empty stomach. Taking the medication with food increases its concentration and results in increased adverse reactions. Do not take this medication with antacids.

Client Instructions

Clients taking NNRTIs should be instructed to immediately report rash and pruritus of the skin, as well as persistent nausea, vomiting, and diarrhea. Advise the client to comply with periodic liver function testing to prevent liver damage. Instruct the client to notify the provider before taking any new over-the-counter or prescribed medications due to multiple interactions. 

Contraindications and Precautions

The prototype NNRTI, efavirenz, is contraindicated in clients who have an allergy to the medication. It is also contraindicated during lactation and with concurrent administration of multiple medications. See the interaction section for medications contraindicated with efavirenz. Use caution when giving efavirenz to clients who have liver dysfunction or achlorhydria and to an older client.  

Interactions

Efavirenz interacts adversely with many medications. Inducers of P 450, including rifampin, rifabutin, phenytoin, and the herb St. John’s wort, affect efavirenz levels. In addition, efavirenz alters the common anti-cholesterol medications simvastatin and lovastatin. All these medications are contraindicated when clients take efavirenz. Also, use efavirenz with caution with the HIV protease inhibitors, saquinavir, warfarin, and dihydropyridine-type calcium channel blockers, such as nifedipine, because levels of these medications may also be increased. For an overview of the non-nucleoside reverse transcriptase inhibitor prototype, click the button to access a medication information table.