First introduced into the market in the early 1990s, nevirapine is an FDA-approved medication and plays a role in treating human immunodeficiency virus (HIV) in patients. Classified as an NNRTI, or Non-nucleoside reverse transcriptase inhibitor, this medication is utilized in conjunction with other antiretroviral therapy (ART) medications. When prescribed, nevirapine is in combination with two nucleoside reverse transcriptase inhibitors (NRTI) such as zidovudine, lamivudine, abacavir, etc. The rationale behind administering more than one medication is to decrease the chances of the virus developing a resistance to the treatment and making it ineffective.
Outside of its primary use as a medication to treat HIV, recent studies have also found that nevirapine may be able to function as a medication for diseases other than those for which it was initially intended. One such example of this is in the case of thyroid cancer. In a recently conducted experimental study, thyroid cancer cells of a human differentiated cell line received treatment with nevirapine, and the results showed that post-treatment, there was significant repression of both cell migration and invasion.
The primary mechanism by which non-nucleoside reverse transcriptase inhibitors such as nevirapine function is through binding to the reverse transcriptases, which are unique to HIV. The binding of the nevirapine causes the formation of a hydrophobic pocket near the active site of the reverse transcriptase. This new pocket causes there to be an alteration in the three-dimensional configuration of the substrate-binding site, which then ultimately leads to hindering HIV DNA synthesis. An important point to note is that while nevirapine is effective against HIV-1, it is not against HIV-2 since it is non-competitive as an inhibitor.
Adult patients: this medication is administered orally and has a variable dosage depending on the length of time of the drug's administration. During the initial 14 days of the administration, the dosage given is 200 mg tablet once daily. For every day following the first 14 days, the dosage given is 200 mg tablet twice daily. This medication is given in combination with other antiretroviral drugs.
Pediatric patients: this medication is administered orally in liquid form, and has a variable dosage depending on how long the medication has been administered. During the initial 14 days of administration, the dosage given is 150 mg/m once daily. For every day following the first 14 days, the dosage given is 150 mg/m twice daily.
Routine examination of serum nevirapine levels in patients on this medication is crucial; this is because different levels of nevirapine present are indicative of the medication’s effectiveness, or lack thereof in suppressing the targeted viral infection. Previously conducted clinical research has found that a plasma trough concentration of nevirapine greater than 4000 ng/mL correlates highly with the medication’s ability to suppress the viral load of HIV such that it is undetectable. A plasma trough concentration of nevirapine less than 3000 ng/mL strongly correlates with the probability of virologic failure in patients receiving ART involving nevirapine.
It is also critical to conduct routine checks of liver function in patients being treated with nevirapine, as it is known to have potentially severe hepatotoxic side effects.
Beyond monitoring of nevirapine singularly, understanding its pharmacokinetic interaction with enzymes and other drugs is also of great importance. Patients seeking treatment for HIV may present with a prior list of medications that they already take, and being aware of those medications’ potential interactions with nevirapine and the side effects of nevirapine can prevent unpredictable interactions. For example, nevirapine is a known inducer of cytochrome P450 enzyme, which means that this effect will impact any medication metabolized by this enzyme, and its dosing and administration will have to be adjusted accordingly for any given patient. Another significant interaction is that of nevirapine and methadone. Both nevirapine and methadone are metabolized by CYP2B6, which is a member of the human cytochrome P450 superfamily, but nevirapine is also an inducer of this enzyme. Due to nevirapine’s ability to upregulate CYP2B6’s metabolic function, methadone becomes metabolized significantly more quickly when administered simultaneously with nevirapine. This situation can pose a danger to the patient if the dosing of methadone is not adjusted accordingly, as someone utilizing it may metabolize it too quickly and then begin to exhibit withdrawal symptoms.
When discussing the toxicity of this drug, it is often secondary to the hepatic damage caused by the drug. There is currently no known antidote for nevirapine overdose.
Another essential point to note regarding the toxicity of nevirapine is that of the currently known NNRTIs and protease inhibitors; it is the only one that has not shown any negative effect on lipids to date.
Managing patients who are taking nevirapine requires several factors, one of which is cohesive interprofessional teamwork. For treatment to be conducted smoothly and for the patient to receive the most significant benefit possible from it, every member of the healthcare team – from the pharmacist to nursing staff to physicians – must be well informed about the treatment regimen and must actively work to ensure all members of the team are on the same page.
Another critical component is the meticulous and regular follow-up with said patients. Because of this medication’s known potential for causing hepatotoxicity in those consuming it, patients’ liver functions must be monitored, especially in the beginning stages of treatment.
It is also important to note that the effectiveness of this medication relies heavily on patient compliance with taking the medication as prescribed. It is up to healthcare professionals to ensure patients are well informed about the responsibilities they have in ensuring they receive maximal improvement from the treatment. Healthcare professionals must further ensure that they view their patients as more than their illness and consider factors such as social support, finances, mental health when monitoring patient adherence. Below are some examples of recommendations for methods to increase the success of HIV treatment in patients on antiviral therapy:
|||Hirasawa M,Hagihara K,Abe K,Ando O,Hirayama N, Interaction of Nevirapine with the Peptide Binding Groove of HLA-DRB1*01:01 and Its Effect on the Conformation of HLA-Peptide Complex. International journal of molecular sciences. 2018 Jun 4; [PubMed PMID: 29867033]|
|||Hedrich WD,Hassan HE,Wang H, Insights into CYP2B6-mediated drug-drug interactions. Acta pharmaceutica Sinica. B. 2016 Sep; [PubMed PMID: 27709010]|
|||Shang H,Zhao J,Yao J,Wang H,Wang S,Dong J,Liao L, Nevirapine inhibits migration and invasion in dedifferentiated thyroid cancer cells. Thoracic cancer. 2019 Dec; [PubMed PMID: 31631580]|
|||Xu X,Long H,Xi B,Ji B,Li Z,Dang Y,Jiang C,Yao Y,Yang J, Molecular Network-Based Drug Prediction in Thyroid Cancer. International journal of molecular sciences. 2019 Jan 11; [PubMed PMID: 30641858]|
|||Arts EJ,Hazuda DJ, HIV-1 antiretroviral drug therapy. Cold Spring Harbor perspectives in medicine. 2012 Apr; [PubMed PMID: 22474613]|
|||Muret P,Piedoux S,Solas C,Quaranta S, [Evidence-based therapeutic drug monitoring for nevirapine]. Therapie. 2011 May-Jun; [PubMed PMID: 21819802]|
|||Notter J,Bregenzer A,Vernazza P,Kahlert CR, Nevirapine in HIV maintenance therapy - can [PubMed PMID: 31017649]|
|||Back D,Gibbons S,Khoo S, Pharmacokinetic drug interactions with nevirapine. Journal of acquired immune deficiency syndromes (1999). 2003 Sep; [PubMed PMID: 14562853]|
|||Kamara DA,Smith C,Ryom L,Reiss P,Rickenbach M,Phillips A,Mocroft A,De Wit S,Law M,Monforte AD,Dabis F,Pradier C,Lundgren JD,Sabin C, Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study. Antiviral therapy. 2016; [PubMed PMID: 27114439]|
|||Thompson MA,Mugavero MJ,Amico KR,Cargill VA,Chang LW,Gross R,Orrell C,Altice FL,Bangsberg DR,Bartlett JG,Beckwith CG,Dowshen N,Gordon CM,Horn T,Kumar P,Scott JD,Stirratt MJ,Remien RH,Simoni JM,Nachega JB, Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care panel. Annals of internal medicine. 2012 Jun 5; [PubMed PMID: 22393036]|