An Examination of Student Pharmacists' Perceptions Toward Immunization.

Introduction: Pharmacists are considered the most accessible health care professionals, especially when it comes to preventative services such as immunizations. Studies have assessed student knowledge and comfort in administering vaccinations immediately after receiving formal training or completing a vaccination clinic experience; however, few have examined students after applying the knowledge to a pharmacy work experience. A survey of student pharmacists regarding these experiences may identify areas that students are less confident in and thus where immunization training could be improved. Methods: A non-validated survey was created in Google Forms and distributed via email from November through December of 2019. The survey was sent to student pharmacists enrolled in one doctor of pharmacy program at a US institution in Western New York who had completed immunization training almost one year prior to the survey. Results: The survey was distributed to 365 student pharmacists. A total of 189 students (51.8%) completed the survey. Student perceptions of providing immunizations were positive overall, with 173 students (91.5%) responding that they agreed or strongly agreed to feeling confident administering intramuscular injections. In contrast, only 110 students (58.2%) agreed or strongly agreed to feeling confident administering subcutaneous injections. Also, 111 students (58.7%) indicated they had not administered an immunization in the 9 months after they had completed their immunization training. Conclusions: Based on this cohort, perceptions are positive overall; however, there is room for continued improvement in training pharmacy students for immunization proficiency as well as increasing the cooperation of pharmacies to allow students to immunize.

Pharmacokinetic drug interactions of integrase strand transfer inhibitors.

The integrase strand transfer inhibitor (INSTI)-containing regimens are currently considered as the first-line treatment of human immunodeficiency virus (HIV) infection. Although possessing a common mechanism of action to inhibit HIV integrase irreversibly to stop HIV replication cycle, the INSTIs, including raltegravir, elvitegravir, dolutegravir, and bictegravir, differ in pharmacokinetic characteristics. While raltegravir undergoes biotransformation by the UDP-glucuronosyltransferases (UGTs), elvitegravir is primarily metabolized by cytochrome P450 (CYP) 3A4 and co-formulated with cobicistat to increase its plasma exposure. The metabolism pathways of dolutegravir and bictegravir are similar, both including CYP3A and UGT1A1, and both agents are substrates to different drug transporters. Because of their differences in metabolism, INSTIs interact with other medications differently through CYP enzymes and transporters as inducers or inhibitors. These drug interactions may become an important consideration in the long-term clinical use because the life expectancy of people with HIV (PWH) approaches to that of the general population. Also, common geriatric challenges such as multimorbidity and polypharmacy have been increasingly recognized in PWH. This review provides a summary of pharmacokinetic interactions with INSTIs and future perspectives in implications of INSTI drug interactions.

Macitentan for the treatment of pulmonary arterial hypertension.

OBJECTIVE: To review the pharmacology, safety, and efficacy of macitentan. DATA SOURCES: PubMed, EMBASE, and ClinicalTrials.gov were searched using the terms macitentan and ACT-064992. STUDY SELECTION AND DATA EXTRACTION: Phase II and III trials were reviewed in our primary analysis; data from phase I trials and other studies were reported as applicable. DATA SYNTHESIS: Macitentan is a dual endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). Current treatment options for PAH include 2 other ERAs, phosphodiesterase type 5 inhibitors, prostanoids, and calcium channel blockers. Recently published guidelines do not assert a preference for individual agents. Two trials evaluated the safety and efficacy of macitentan. The phase II study was a 12-month placebo-controlled trial involving patients with idiopathic pulmonary fibrosis; the primary end point was change in forced vital capacity. No significant treatment effect was observed. The phase III study was a placebo-controlled trial involving patients with PAH. The primary end point was time to first occurrence of a composite of outcomes, including all-cause death and PAH worsening. Over a median period of 115 weeks, macitentan 10 mg and 3 mg daily significantly reduced morbidity and mortality. Commonly reported adverse effects included worsening of PAH, peripheral edema, upper-respiratory-tract infection, and anemia. CONCLUSIONS: Macitentan represents the latest addition to the PAH armamentarium. Compared with other ERAs, clinical advantages may include fewer contraindications, use in hepatic impairment, and once-daily administration. However, further comparative studies are necessary to ascertain its place in therapy.

Antiretroviral therapy : pharmacokinetic considerations in patients with renal or hepatic impairment.

Hepatic and renal insufficiency due to co-infection, alcoholism, diabetes mellitus, family history, adverse effects of antiretrovirals and other factors are commonly seen in HIV-infected patients. Therefore, the use of antiretrovirals in this patient setting requires attention to the pharmacokinetic issues that clinicians must consider when prescribing highly active antiretroviral therapy for these patients. This review summarizes the current knowledge of the use of antiretrovirals in patients with hepatic or renal impairment, and makes dosing recommendations for this subpopulation of HIV-infected patients.

Factors associated with altered pharmacokinetics in substance users and non-substance users receiving lopinavir and atazanavir.

Substance use is highly prevalent in HIV-infected individuals in the United States, and clinical management is complicated by the need for antiretroviral treatment, addiction therapy, variable medication adherence, and co-morbidities. The interrelation between HIV and substance use prompted our investigation to examine substance use and self-reported medication adherence in patients receiving the HIV-1 protease inhibitors, atazanavir (ATV) or lopinavir (LPV). ATV and LPV pharmacokinetics were determined by measuring plasma concentrations in subjects with active substance use (SU group) or with no active substance use (NSU group). No difference in adherence was observed between groups (p > 0.05). The mean SU ATV trough was 0.550+/-0.45 microg/mL; the mean NSU ATV trough was 0.780+/-0.590 microg/mL (p > 0.05). The mean SU LPV trough was 4.02+/-2.39 microg/mL; the mean NSU LPV trough was 6.67+/-0.910 microg/mL (p = 0.01). Co-factors found to be associated with variation in ATV and LPV concentrations included concurrent methadone use, cigarette smoking, and substance use status. These data indicate that chronic HIV treatment may be assisted with plasma concentration monitoring to identify those patients who may require dosage modification and/or regimen adjustment in order to optimize antiretroviral effects.

Clinical pharmacodynamics of HIV-1 protease inhibitors: use of inhibitory quotients to optimise pharmacotherapy.

The introduction of HIV-1 protease inhibitors and non-nucleoside reverse transcriptase inhibitors in 1996 began an era described as that of highly active antiretroviral therapy. In addition, the more recent development and availability of HIV-1 genotypic and phenotypic resistance tests and advances in pharmacological assays that support therapeutic drug monitoring (TDM) have created tools that may help clinicians to provide more individualised treatment with HIV-1 protease inhibitors. All current treatment guidelines provide fixed doses of protease inhibitors with vague recommendations for the use of TDM in selected clinical situations. In patients with resistance to protease inhibitors, the combined use of resistance tests with TDM provide a mechanism for individualising the clinical pharmacodynamics of protease inhibitors. Current therapeutic approaches seek to include the monitoring of protease-inhibitor concentrations as part of a TDM programme with phenotypic assays to calculate an inhibitory quotient, virtual inhibitory quotient, or normalised inhibitory quotient, whereas genotypic tests are used with TDM to calculate a genotypic inhibitory quotient. Current investigation is focused on examining the predictive value of this approach for clinical monitoring.

Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a diverse group of compounds that inhibit HIV Type 1 reverse transcriptase. Although possessing a common mechanism of action, the approved NNRTIs, delavirdine, efavirenz and nevirapine, differ in structural and pharmacokinetic characteristics. Each of the NNRTIs undergoes biotransformation by the cytochrome P450 (CYP) enzyme system, thus making them prone to clinically significant drug interactions when combined with other antiretrovirals. In addition, they interact with other concurrent medications and complementary/alternative medicines, acting as either inducers or inhibitors of drug-metabolising CYP enzymes. These drug interactions become an important consideration in the clinical use of these agents when designing combination regimens, as recommended by current guidelines. This review provides an updated summary of pharmacokinetic interactions with NNRTIs.

Drug interactions with antiretrovirals.

The recent development of new antiretroviral drugs, along with the evolution in clinical practice guidelines that include the recommendation of the use of three- to four-drug combination regimens for achieving optimal suppression of viral replication, has focused clinicians on the relevance of drug-drug interactions in the chronic care of HIV-infected individuals. However, the routine clinical management of drug interactions is complicated by our expanding knowledge of the physiologic mechanisms underlying pharmacokinetic interactions, particularly as they relate to drug transport and tissue distribution (eg, P-glycoprotein) and biotransformation (hepatic cytochrome p450 mono-oxygenase induction and inhibition). This review provides an updated summary of key drug interactions that have been reported since its initial publication.