atazanavir and cobicistat
Regulatory sources consulted
Approved indications
- Combination treatment of HIV-1 in adults and adolescents aged at least 12 years and weighing at least 35 kg without relevant atazanavir resistance.
Contraindications
Absolute
- Clinically significant hypersensitivity to atazanavir, cobicistat, or excipients.
- Moderate or severe hepatic impairment.
- Use of narrow-therapeutic-index CYP3A substrates or contraindicated strong inducers.
Clinical warnings
- It may cause PR prolongation, hyperbilirubinemia, cholelithiasis, and nephrolithiasis. — CIMA/AEMPS, ficha técnica 1151025001
- Major warning · Cobicistat raises creatinine and may worsen renal toxicity with certain antiretrovirals. — CIMA/AEMPS, ficha técnica 1151025001
- It may cause severe cutaneous reactions, including SJS/TEN, and interstitial nephritis or chronic kidney disease; stop and assess if compatible signs occur. — CIMA/AEMPS, ficha técnica 1151025001
Drug interactions
- HighProton-pump inhibitors, H2 antagonists, and antacids
Mechanism: Reduced acidity decreases atazanavir absorption.
Recommendation: Separate antacids by at least 2 hours before or after. Give H2 antagonists simultaneously with EVOTAZ or at least 10 hours before, within dose limits based on treatment history. In treatment-naive people, limit omeprazole to 20 mg and give EVOTAZ at least 12 hours after the PPI; avoid PPIs in treatment-experienced people.
CIMA/AEMPS, ficha técnica 1151025001
Adverse events
Common (≥1%)
Jaundice, nausea, and diarrhea
Rare but serious
Heart block, nephrolithiasis, cholelithiasis, and hepatotoxicity
Pregnancy and lactation
It is not recommended during pregnancy because of lower exposure; use an alternative regimen. Do not breastfeed during HIV treatment.
Recent literature (PubMed)
HIV reverse transcriptase (RT) inhibitors are the important components of highly active antiretroviral therapies (HAARTs) for anti-HIV treatment and pre-exposure prophylaxis in clinical practice. Many RT inhibitors and their combination regimens have been approved in the past ten years, but a review on their drug discovery, pharmacology, and clinical efficacy is lacking. Here, we provide a comprehensive review of RT inhibitors (tenofovir alafenamide, rilpivirine, doravirine, dapivirine, azvudine and elsulfavirine) approved in the past decade, regarding their drug discovery, pharmacology, and clinical efficacy in randomized controlled trials. Novel RT inhibitors such as islatravir, MK-8504, MK-8507, MK8583, IQP-0528, and MIV-150 will be also highlighted. Future development may focus on the new generation of novel antiretroviral inhibitors with higher bioavailability, longer elimination half-life, more favorable side-effect profiles, fewer drug-drug interactions, and higher activities against circulating drug-resistant strains.
Viruses cause a variety of diseases in the human body. Antiviral agents are used to prevent the production of disease-causing viruses. These agents obstruct and kill the virus's translation and replication. Because viruses share the metabolic processes of the majority of host cells, finding targeted medicines for the virus is difficult. In the ongoing search for better antiviral agents, the USFDA approved EVOTAZ, a new drug discovered for the treatment of Human Immunodeficiency Virus (HIV). It is a once-daily (OD) fixed-dose combination of Cobicistat, a cytochrome P450 (CYP) enzyme inhibitor, and Atazanavir, a protease inhibitor. The combination drug was created in such a way that it can inhibit both CYP enzymes and proteases at the same time, resulting in the virus's death. The drug is not effective in children under the age of 18; however, it is still being studied for various parameters. This review article focuses on EVOTAZ's preclinical and clinical aspects, as well as its efficacy and safety profiles.
In addition to antiretroviral therapy (ART), people with HIV often take medications to treat comorbidities. It is therefore important to assess these medications for potential drug-drug interactions, which may affect the safety and efficacy of ART. Three phase I studies were conducted in adult participants without HIV. The pharmacokinetics (PK) and safety of bictegravir (administered alone or as bictegravir/emtricitabine/tenofovir alafenamide fumarate [TAF]) were assessed when co-administered with inducers (rifampin, rifabutin, and rifapentine) or inhibitors (atazanavir ± cobicistat, darunavir + cobicistat, and voriconazole) of cytochrome P450 3A4 (CYP3A4), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), and/or P-glycoprotein (P-gp). PK parameters were compared using analysis of variance to calculate geometric least-square mean ratios and 90% confidence intervals. Overall, 172 participants were enrolled. CYP3A4 inhibition (voriconazole) moderately increased bictegravir exposure (61% increase in area under the concentration-time curve extrapolated to infinity [AUCinf]), whereas dual CYP3A4 and UGT1A1 inhibition (atazanavir) led to a 315% increase in AUCinf. P-gp inhibition had a minimal effect on bictegravir exposure. Induction of CYP3A4, UGT1A1, and/or P-gp by rifampin, rifabutin, and rifapentine led to decreases in bictegravir exposure and/or trough concentration (Ctrough). Bictegravir and bictegravir/emtricitabine/TAF were well tolerated alone and in combination with other drugs. Inhibition of CYP3A4 or UGT1A1 alone is unlikely to cause clinically meaningful changes in bictegravir exposure; only potent inhibitors of both pathways are expected to significantly affect bictegravir PK. Induction of CYP3A4 with/without UGT1A1 significantly influenced bictegravir PK, although Ctrough remained above the protein-adjusted 95% effective concentration. These findings should be considered when co-administering medications with bictegravir.
Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.