Drug interaction can occur whenever a patient is administered two or more drugs simultaneously. In this issue drug interaction occurs when drug is withdrawn from the patients. The outcome of drug interaction can be beneficial or harmful. A vigilance is needed while prescribing the drugs. In some circumstances the drug interactions are complicated and problematic. No single Anti-Retroviral Drug (ARV) is appropriate in all clinical situations. Pharmacokinetics has an important role to play in the clinical practice of Anti-Retroviral Drug therapy, as it is important in estimating individualized drug dosage regimens necessary to achieve concentration without causing unacceptable toxicity. In this paper 25 patients on Etravirine and Rilpivirine were taking concomitantly with equal doses in equal intervals of time. This was a retrospective study shows that Etravirine level increases significantly after withdrawing the Rilpivirine. Therapeutic window of Etravirine is narrow, one has to be vigilant in maintain the concentration of Etravirine within therapeutic range. So dosage regimen is important and TDM is a vital programme which helps to keep the level within therapeutic objective.

 
Keywords: Etravirine; Rilpivirine 

Etravirine and Rilpivirine are the two vital drugs to control the HIV epidemic. Both these drugs are measured easily in the laboratory as a therapeutic drug monitoring programme. A physician knows their drug-drug interaction but the extent of variability of these drugs makes their concentration to be measured necessarily after every three months. Once the Rilpivirine is switched off from the drug regimen, the concentration of Etravirine increases slowly with the passage of time as it takes one or two weeks. Data from extensive literature, case study, research report and library National AIDS Research Institute [1]. A single ARV drug is appropriate in all clinical situations and HIVists agrees that proper diagnosis and classification is important in individualizing pharmacotherapy [2]. Therapeutic decisions should be made on a variety of specific factors such as onset of drug effect, presences of renal or hepatic diseases, possibility of drug disease interaction, possibility of pregnancy, the age of the patients, and adherence to therapy issues and prior history of ARV use. Many of the new drugs are approved only for adjunctive and drug interactions should also be considered [3]. Although monotherapy remains the mainstay for the treatment of HIV, combination of Anti-Retroviral Drugs [ARVs] are used frequently in patients not responding to a single medication. ARVs may also be combined with drugs used to treat comorbid or associated conditions. When multiple drug therapy is used, there is possibility of clinically relevant drug interaction, which in patients with HIV is particularly common for a variety of reasons [4-5]. Pharmacokinetics is the quantitative description of what happens to a drug when it enters the body, and includes the process of drug absorption, distribution, metabolism and elimination [ADME] and how these processes effects the concentration obtained. Drug-drug interactions between Etravirine and Rilpivirine are well established but the withdrawal of Rilpivirine as inducers produces the Etravirine toxicity, so the Etravirine level increases after 2 weeks of time. So the optimization of dose regimen of Etravirine is an important step in the therapeutically monitored tools in the successful outcome of the therapy in the HIV control. Retrospective study of 25 HIVist patients who were on the Etravirine and Rilpivirine taking equal doses for 2-3 years time. After the withdrawal of Rilpivirine the level of Etravirine went up significantly, it needs vigilance in such situation. Instead of benefits for the patients harmful effects are stopped. TDM program is required to determine drug concentration and in turn the technique is vital to be optimized [6]. There is the need to find out the steady state or breakthrough level to appreciate the relevance of the parameters in ARV drug therapy [7]. An awareness of ARV clinical pharmacokinetics will thus aid the choice of an optimal dosage schedule for each patient [8]. The concentrations in multiple doses have to be maintained at steady state when the absorption and elimination remains constant. All patients with chronic HIV can be expected to develop during their life time concomitant non-HIV related diseases that require additional drug therapy, increasing the potential for drug interactions and toxicity. Thus, it is desirable that the drugs do not cause interactions that can precipitate toxicity [9]. It is important to recognize that interactions are not with only one drug but it occurs when two drugs are given together they influence each other. In addition, another important concept is that drug interactions may occur not only when an inducer or inhibitor is added to a patient’s medication regimen, but also when the inducing [i.e Etravirine] or inhibiting [i.e Rilpivirine] agents is removed.   ​

Clinically important ARV interactions are frequently observed in clinical practice, and often they can be anticipated by knowledge of the underlying mechanism. Whenever possible, these interactions should be prevented by avoiding the unnecessary use of poly-ART, and by selecting co medications which are less likely to interact. If the use of potentially interacting drugs cannot be avoided, adverse clinical consequences may be minimized, as appropriate, by individualized dose adjustments guided by careful monitoring of clinical response and measurement of drug concentrations. There is a need to estimate the Etravirine and Rilpivirine levels through HPLC method. That can resolve the metabolite status of the patients. 

Eminent scientist Dr. R.S.Paranjape for data collection and guidance received for manuscript preparation. This study was supported by scientist interactions National AIDS Research Institute Pune. ​

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