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Development of palliative medicine in the United Kingdom and Ireland
Published in Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita, Textbook of Palliative Medicine and Supportive Care, 2015
There are many potential drug interactions in the palliative care of HIV-infected individuals. In this regard, the PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are the most problematic. For example, the PI ritonavir is a potent inhibitor of CYP3A4 enzyme of the hepatic cytochrome P450 enzyme system. As a result, ritonavir significantly slows the metabolism of several palliative medications. Ritonavir therapy increases plasma levels and prolongs the duration of activity of benzodiazepines (in particular, midazolam and triazolam), bupropion, and ergot derivatives. These medications should not be used in combination with ritonavir. Furthermore, ritonavir decreases plasma levels of methadone, fentanyl, codeine, and hydrocodone. Increased dosages of these medications may be needed when used concomitantly with ritonavir. Ritonavir is the PI most likely to interact with other medications. Among the remaining PIs, nelfinavir, fosamprenavir, and indinavir are less likely to interact with other drugs. Saquinavir is least likely. Â 80 Ritonavir is frequently used in a fixed dose combination capsule with another PI, lopinavir (Kaletra). The NNRTIs efavirenz and nevirapine reduce plasma levels of methadone by 35%-50%. An increase in methadone dosage of approximately 20% is required to prevent narcotic withdrawal symptoms when efavirenz is added to a stable methadone regimen. The NNRTI delavirdine increases plasma levels of methadone and amphetamines (see Tables 92.1 and 92.2).
Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Ritonavir is an antiviral used to treat HIV. A total of 3,155 women used it in the first trimester of pregnancy and the frequency of birth defects was not increased (Antiretroviral Registry, 2018). It appears to have minimal placental transfer at about 5 percent.
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
HIV-AIDS is one of the most serious healthcare problems associated with morbidity and mortality across the globe. HAART is considered the effective treatment regimen for the management of HIV-AIDS. Protease inhibitors are the key components of the HAART regimen for HIV-AIDS treatment. Ritonavir exhibits a potential antiviral activity against HIV in in vitro and in vivo studies. However, various adverse effects that include hepatotoxicity, hypertriglyceridemia, increase in serum cholesterol, and others limited its use as a protease inhibitor in HIV-AIDS treatment. The researchers are developing various types of nanoformulations to address the issues associated with Ritonavir. These nanoformulations include polymeric, solid lipid nanoparticles, and nanostructured lipid carriers. Few researchers targeted the lymphatic system to enhance bioavailability by avoiding first pass metabolism and improving exposure to the lymphoidal organs. HIV reservoirs are mainly situated in lymphoidal organs. Hence, lymphatic targeting helps eradicate the viral load from the body and avoids the risk of recurrent increase in the count of viral RNA copies. These studies mainly focus on improving bioavailability to reduce the dose as adverse effects are dose-dependent. However, alternative novel formulations that help enhance oral bioavailability and are also capable of reducing drug-induced side effects are much needed for the safe and efficacious treatment for HIV-AIDS management.
Safety and efficacy of anti-SARS-CoV-2 monoclonal antibodies in pregnancy
Published in Expert Opinion on Drug Safety, 2022
Antonio Riccardo Buonomo, Nunzia Esposito, Isabella Di Filippo, Gabriele Saccone, Biagio Pinchera, Riccardo Scotto, Giuseppe Bifulco, Ivan Gentile
Nirmatrelvir plus ritonavir could be offered to pregnant women with any additional risk factor for severe COVID-19 (obesity, third trimester of gestational age, any concomitant immunosuppressive therapy, unvaccinated patients). In fact, ritonavir has a documented safe risk profile in pregnancy as it is widely used in HIV-positive patients. Moreover, in animal studies, no nirmatrelvir-related maternal toxicity was demonstrated. In fact, no effects on fetal body weight, on fetal external, visceral, or skeletal morphological development either in rats or in rabbit models were shown. Nirmatrelvir/ritonavir should not be withheld from pregnant patients if the potential benefits outweigh the potential risks [20]. Early treatment with antivirals should be initiated within 5 days from symptoms onset. For all antiviral drug therapies, patients should be informed of the benefits and theoretical concerns with limited data and be involved in the decision.
Beyond one pill, once daily: current challenges of antiretroviral therapy management in the United States
Published in Expert Review of Clinical Pharmacology, 2019
Mary Clare Masters, Karen M. Krueger, Janna L. Williams, Lindsay Morrison, Susan E. Cohn
Cobicistat is not recommended during pregnancy. Cobicistat’s reliance on metabolic inhibition raised concern that metabolic changes in pregnancy might affect its efficacy. Initial case reports of pregnant women treated with elvitegravir/cobicistat containing ART revealed 44% lower cobicistat exposure during pregnancy than in the postpartum period [93]. Subsequently, a multicenter phase IV trial evaluating cobicistat and elvitegravir pharmacokinetics during the second trimester, third trimester, and postpartum period found that elvitegravir exposure was lower during pregnancy than during the postpartum period [94]. In this study, the lowest values were noted during the third trimester. In fact, only 47% of participants in the 2nd trimester and 38% in the 3rd trimester met the target area under the concentration curve (AUC) goal. Similarly, cobicistat exposure was found to be lower during pregnancy than during the postpartum period. Such unfavorable pharmacokinetics preclude the use of cobicistat-containing regimens during pregnancy. Presently ritonavir is the preferred boosting agent during pregnancy [90].