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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Nelfinavir is an antiretroviral drug used to treat HIV infections. 1212 women used it during the first trimester of pregnancy, and the frequency of birth defects was not increased in offspring (Antiretroviral Registry, 2018). It is an FDA pregnancy risk category B drug.
Nelfinavir
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Suzanne M. Crowe, Lars Ostergaard, John Mills
The drug is marketed by Pfizer in the USA, Canada, and Japan and by Roche in the rest of the world, including the European market and Australia. Nelfinavir received FDA approval in 1997. Nelfinavir is indicated for the treatment of HIV infection in combination with other antiretroviral drugs. In June 2007, nelfinavir was recalled from the European Union (EU) markets because of a process-related impurity in nelfinavir mesylate (EMEA, 2007). Excess levels of ethyl methanesulfonate (EMS) were found in the Roche-manufactured active pharmaceutical ingredient in nelfinavir licensed for use in EU countries. EMS is a potential human carcinogen, found to be carcinogenic in animal studies but with no data from humans. Pfizer-manufactured nelfinavir products marketed in the USA were found to have substantially lower concentrations of EMS and are still on the market, but with restrictions in recommendations (Pfizer, information for prescribers, 2013). Recent data indicate that individuals exposed to the contaminated nelfinavir during 2006–2007 thus far do not demonstrate an increase in risk of developing cancer (Boettiger et al., 2016).
Optimising Antiretroviral Therapy Via Pharmacokinetics
Published in Anne George, K. S. Joshy, Mathew Sebastian, Oluwatobi Samuel Oluwafemi, Sabu Thomas, Holistic Approaches to Infectious Diseases, 2017
Nelfinavir inhibits HIV-1 protease and is always used in combination with any other two-antiretroviral drugs. It has a few benefits over other protease inhibitors in a way that it is well tolerated in pregnancy, can be used in patients completely intolerant to ritonavir, has a low grade interaction with methadone and may be well tolerated in hepatitis-C virus co-infected patients. Adult oral dosage is 750 mg thrice a day (Carr et al., 2005).
Recent advances in nanoformulation development of Ritonavir, a key protease inhibitor used in the treatment of HIV-AIDS
Published in Expert Opinion on Drug Delivery, 2022
Srinivas Reddy Jitta, Navya Ajitkumar Bhaskaran, Shirleen Miriam Marques, Lalit Kumar
Saquinavir is the first-ever protease inhibitor for the treatment of HIV, approved by the US Food and Drug Administration (US FDA). Saquinavir has very poor solubility in the aqueous phase, and its solubility is highly pH-dependent. Along with poor solubility, metabolism by hepatic and small intestinal enzymes are the main reasons for the poor bioavailability [40–42]. Second-generation protease inhibitors used in the treatment of HIV, such as Darunavir, are associated with low oral bioavailability, adverse effects such as liver toxicity and skin rashes. High lipophilic nature, low water solubility, and first-pass metabolism are the major factors for low oral bioavailability [43,44]. Indinavir, a specific protease inhibitor used to treat HIV infection, belongs to BCS class IV with low permeability and low solubility. Clinical application of this drug is limited by low gastrointestinal absorption, short half-life, and extensive hepatic first-pass metabolism [1,45]. Nelfinavir mesylate is an HIV protease inhibitor and an important integral component of highly active antiretroviral therapy (HAART) used in the treatment of AIDS [46]. Lopinavir, a protease inhibitor used in the treatment of HIV, and this drug block the ability of HIV protease to cleave polyprotein resulting in the formation of noninfectious immature virions [38]. Lopinavir exhibits poor oral bioavailability as it is a substrate for the P-gp system and CYP 3A4 present in both intestine and liver [38,47].
Population pharmacokinetics and model-informed precision dosing of lamivudine in Chinese HIV-infected patients with mild and moderate impaired renal function
Published in Expert Review of Clinical Pharmacology, 2022
Haini Wen, Lin Yin, Jiangrong Wang, Lin Zhang, Tao Sun, Feng Xu, Minxin Zhang, Li Liu, Renfang Zhang, Xiaoqian Liu, Xianmin Meng, Yaru Xing, Hongzhou Lu, Zheng Jiao, Lijun Zhang
The major concern for lamivudine dosing based on renal function is the increase in the pill burden, since availability of lamivudine as a single agent in multiple dosing and multiple fixed-dose combination formulations is not universal across countries [28]. In the current study, two different dosing strategies (200 mg q24h and 300 mg q36h) for patients with mildly impaired renal function (CCR 50–70 ml/min) were proposed to accommodate different formulations and product strengths of lamivudine. A previous study identified the co-administration of nelfinavir as a significant covariate of lamivudine PK [9]. However, the present study showed that the co-administration of nelfinavir had no effect on lamivudine PK. A possible explanation for this is that the current study included only 7% of patients who were co-administered nelfinavir with lamivudine.
Clinical profile of acute pancreatitis following treatment with protease inhibitors: a real-world analysis of post-marketing surveillance data
Published in Expert Opinion on Drug Safety, 2021
Wangjun Qin, Bin Zhao, Yongguang Shang, Lei Zhang
We also assessed and compared the fatality rates of AP associated with PIs to investigate differences in the severity of AP associated with various PIs. It was observed that AP was generally associated with poor outcomes, exhibiting a fatality rate of 14.02%, which was more than two times that of a cohort study following 5,970 HIV-infected patients [39]. In that study, five patients died of pancreatitis during their hospitalization, yielding an in-hospital mortality rate of 5.9% for AP. As there is no consensus definition of acute pancreatitis, the different inclusion criteria used in the two studies may have resulted in different specificities and sensitivities of case inclusion. This may have caused the difference between the fatality rates in the two studies. Furthermore, we found that among all 271 reported PI-induced AP cases, compared with the other PIs, ritonavir (18.87%) and lopinavir/ritonavir (22.73%) appeared to be associated with a higher risk of death. However, based on the collected data, there was no significant difference in fatality rates across different PI regimens (Pearson’s chi-square test for overall comparison, p= 0.730). Fatal events occurred in 1 (25.00%) of 4 patients treated with saquinavir and 1 (20.00%) of 5 patients treated with nelfinavir; however, there were not enough cases reported to draw a conclusion, and continued surveillance is needed.