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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Efavirenz is a non-nucleoside reverse transcriptase inhibitor used to treat HIV. Among 1040 infant born after first trimester exposure to Efavirenz there was no increased frequency of birth defects (Antiretroviral Registry, 2018). However, the drug carries a warning that neural tube effects have been observed in human infants and offspring of animals; treat with Efavirenz during organogenesis. Importantly, non-human primates who were given the drug at concentrations similar to the human therapeutic dose had a 15-percent rate of neural tube defects.
Human immunodeficiency virus (HIV)
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Richard Basilan, William Salzer
For ARV-naive, nonpregnant patients who meet criteria for initiation of ARV therapy, present guidelines recommend the use of an NNRTI-based, a PI-based, or an integrase inhibitor–based regimen. All regimens would also include two NRTIs. Purely NRTI-based regimens, such as Trizivir (a combination of zidovudine, lamivudine, and abacavir), are no longer recommended as they have been found to have higher rates of virologic failure. For an NNRTI-based regimen, the preferred agents include efavirenz with emtricitabine and tenofovir (available as combination pill Atripla™). Use of efavirenz should be avoided during the first trimester of pregnancy, as well as in women who are of reproductive age and are not taking sufficient steps to avoid pregnancy, given its known teratogenicity in animal and human studies. An alternative NNRTI-based regimen would include nevirapine with zidovudine and lamivudine (Combivir™). It should be noted that nevirapine should be avoided in patients with moderate-to-severe hepatic impairment (Child Pugh B or C), as well as females with a CD4 count >250 cells/mL as both groups have an increased risk for potentially fatal hepatitis.
Investigational Nanomedicines in 2016: A Review of Nanotherapeutics Currently Undergoing Clinical Trials *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Joseph M. Caster, Artish N. Patel, Tian Zhang, Andrew Wang
Saint Stephens Aids Trust and the University of Liverpool are investigating polymeric nanoformulations of two antiretroviral agents used for HIV treatment. Efavirenz is a non-nucleoside reverse transcriptase inhibitor clinically used as the preferred first line treatment for HIV infection [70]. Lopinavir is a protease inhibitor commonly utilized in combination therapy. Nano-formulations of these antiretroviral agents aim to reduce total dosage and cost in order to improve patient tolerability while maintaining clinical efficacy. Preclinical studies have demonstrated bioequivalent efficacy in suppressing HIV-1 replication and slower emergence of drug resistance with HIV-IIIB and subtype A virus. Development of NANOEfavirenz and NANOLopinavir has reached phase I trials examining safety and tolerability in HIV negative, healthy patients as well as the bioequivalence of these nanoformulations to the free drugs Sustiva (Efavirenz) and Kaletra (Lopinavir/Ritonavir). Results have yet to be published.
Effect of PEGylation on drug uptake, biodistribution, and tissue toxicity of efavirenz–ritonavir loaded PAMAM G4 dendrimers
Published in Pharmaceutical Development and Technology, 2023
Rohini Kharwade, Nilesh Mahajan, Sachin More, Amol Warokar, Sachin Mendhi, Akshay Dhobley, Devendra Palve
According to the current drug regimen, efavirenz (EFV) is a first-preferred non-nucleoside reverse transcriptase inhibitor used in anti-HIV therapy. Unfortunately, its low bioavailability and higher metabolism rate require very high doses for therapeutic effects. However, its high dose is associated with a G-T polymorphism at position 516 (516GrT) of CYP2B6 and causes persistent central nervous system (CNS)-associated side effects (Adkins and Noble 1998; Vrouenraets et al. 2007). Therefore, ritonavir (RTV) is recommended with EFV as a booster dose to enhance the bioavailability of both drugs. RTV also has an inhibitory action on CY450 3A4 and increased the AUC of RTV and EFV by 18% and 21%, respectively (Barry et al. 1999). However, limited bioavailability, lymphatic absorption, and distribution mechanisms restrict its entry into the viral reservoirs. Hence, to overcome the above-mentioned problems and deliver an optimum and sustained release of EFV into viral reservoir tissue by reducing the dose and side effects could be the rational approach (Parienti et al. 2010; Hull and Montaner 2011).
Characterization, in vitro dissolution, and pharmacokinetics of different batches of efavirenz raw materials
Published in Drug Development and Industrial Pharmacy, 2021
Danilo César Galindo Bedor, Noely Camila Tavares Cavalcanti Bedor, João Gomes Pontes Neto, Lucas José de Alencar Danda, Flávio Martins de Oliveira, Guilherme Henrique Onório de Oliveira, José Lamartine Soares Sobrinho, Eric Beyssac, Whocely Victor de Castro, Davi Pereira de Santana
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used against the Human Immunodeficiency Virus (HIV) [1]. It was first licensed in the US in 1998 and marketed as immediate-release capsules (200 mg) and tablets (600 mg) for once-daily dose treatment [1]. The inactive ingredients of the capsules are lactose monohydrate, magnesium stearate, sodium lauryl sulfate, and sodium starch glycolate, whereas the excipients in the tablet formulation consisted of croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate [2]. The presence of the surfactant SLS in both formulations suggests that the solubility of EFV is a major concern to achieve adequate oral bioavailability. In fact, EFV is a crystalline but lipophilic solid with low aqueous solubility (0.9 µg/mL) and intrinsic dissolution rate of 0.037 mg/cm2/min (Figure 1) [3].
Efavirenz-Associated Retinal Toxicity Presenting with Night Vision Defects in Patients with Human Immunodeficiency Virus
Published in Ocular Immunology and Inflammation, 2020
Sridharan Sudharshan, Kolli Dileep Kumar, Muna Bhende, Jyotirmay Biswas, Poongulali Selvamuthu
All our patients presented with retinitis-pigmentosa-like symptoms, presenting with poor night vision and a recent history of initiation of HAART or a change in drug regime. Efavirenz was the common anti-retroviral drug that was added recently into their HAART regime in all patients. Literature reporting retinal toxicity with Efavirenz is very limited,12,13 with few studies on large cohort of patients even showing it to be safe even after prolonged use.14 Not all patients on efavirenz seem to experience visual function abnormalities. This wide inter-patient variability in efavirenz toxicity could possibly be due to variability in pharmacokinetics as a result of polymorphisms in the major metabolizing enzyme i.e. cytochrome P450 CYP2B6.15 Studies have reported histological changes in the lateral geniculate body in Wistar rats due to efavirenz which could possibly affect visual sensibilities.16