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Human Immunodeficiency Virus Infection
Published in Thomas T. Yoshikawa, Shobita Rajagopalan, Antibiotic Therapy for Geriatric Patients, 2005
Patient understanding, willingness to adhere to treatment, their current and future pill burden, severity of HIV infection, potential adverse drug reactions and interactions, and comorbidities are significant factors in deciding whether to initiate treatment. The patient's current drugs should be reviewed and the potential for drug-drug interactions assessed. Most antiretroviral drug interactions are mediated through inhibition or induction of hepatic enzymes. All Pis and NNRTIs are metabolized in the liver by the CYP system. Lipid-lowering statins, calcium channel blockers, sildenafil (Viagra), and St. John's Wort may have significant interactions. These drugs are frequently used in older patients with comorbidities and their interactions should be determined. St. John's Wort, an over-the-counter medication used for depression, may have significant interactions with all of the Pis and NNRTIs and should not be used. Bepridil, a type 4 calcium channel blocker indicated for chronic angina pectoris, should not be used with the Pis ritonavir, amprenavir, and atazanavir. Peak concentrations and half-life are markedly increased in the elderly (>74 years). The risk of cardiotoxicity, including arrhythmias, heart block, and prolonged QT interval on electrocardiogram, would be significant. Simvastatin and lovastatin should not be used with any of the Pis or with the NNRTI, delavirdine, which would result in large increases in statin levels and increased risk of myopathy and rhabdomyo-lysis. Sildenafil may significantly increase levels of the Pis. Use of sildenafil in patients aged >65 years is associated with increased serum levels of the drug and thus an even greater tendency for toxicity including myocardial ischemia when used with Pis.
One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study
Published in Journal of Asthma, 2023
Masaharu Shinkai, Motohiro Ebisawa, Yasushi Fukushima, Satomi Takeuchi, Hiroshi Okada, Tatsuro Tokiyo, Nobuya Hayashi, Mami Takikawa, Gene Colice, Gun Almqvist
AESIs reported during the on-treatment period are described in Supplementary Table 4. Severe infections were reported in nine (13.8%) patients during the on-treatment period and included herpes zoster and oral herpes (two [3.1%] patients each), and viral gastroenteritis, genital herpes simplex, influenza, lung abscess, and tonsillitis (one [1.5%] patient each). None of these events were assessed by the investigator as causally related to tezepelumab. Injection site reactions occurred in two patients (3.1%) and were classed as mild, non-serious AEs of injection site erythema on the abdominal wall, which were assessed by the investigator to be causally related to tezepelumab administration. During the study, no AESIs of opportunistic infection, helminth infection, anaphylactic reaction, hypersensitivity, malignancy, or Guillain–Barré syndrome were reported, and no patient had confirmed immune complex disease. The male patient had a mild, non-serious AE of drug-induced liver injury on Day 171, but this was attributed to bepridil hydrochloride monohydrate that was used to treat an AE of atrial fibrillation and was assessed by the investigator to be unrelated to tezepelumab.
Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup
Published in Clinical Toxicology, 2021
Anselm Wong, Robert S. Hoffman, Steven J. Walsh, Darren M. Roberts, Sophie Gosselin, Timothy E. Bunchman, Sofia Kebede, Valery Lavergne, Marc Ghannoum
The poor dialyzability of CCBs was confirmed in vivo, in both pharmacokinetic experiments of patients with ESKD given a therapeutic dose of a CCB (many of which were well conducted and enrolled several patients prospectively) and in toxicokinetic analyses of poisoned patients. A total of 210 patients had pharmacokinetic or toxicokinetic data related to ECTR (amlodipine = 32, benidipine = 10, bepridil = 6, diltiazem = 20, felodipine = 5, isradipine = 8, mibefradil = 5, nicardipine = 15, nifedipine = 32, nisoldipine = 15, nitrendipine = 10, verapamil = 52). To illustrate the proportionally insignificant impact of ECTR for removal of CCBs, Table 2 presents data of ECTR clearance of various CCBs compared to their endogenous clearance; at best, extracorporeal clearance (regardless of the modality) enhances total body clearance of any CCB by 10% (and usually much less). While most publications are dated, it is not expected that results would vary much if performed again today with higher efficiency ECTRs and more performant vascular access.
Emerging therapeutic targets in the short QT syndrome
Published in Expert Opinion on Therapeutic Targets, 2018
Jules C Hancox, Dominic G Whittaker, Chunyun Du, A. Graham Stuart, Henggui Zhang
One cautionary note in respect of IhERG/IKr block is that whilst in vitro data on T618I hERG have pointed toward effectiveness of a range of drugs with IKr inhibitory effects including both sotalol and quinidine [50,51], these in vitro predictions have not translated universally to patients. Thus, sotalol has been tried but found to be ineffective at prolonging QTc interval in T618I carriers [49,110]. Quinidine has been found to prolong QTc interval but not to prevent arrhythmias in all T618I patients receiving it [49]. Bepridil, which has not been tested in vitro against T618I hERG, has been found to be effective in a T618I patient with VF refractory to other treatment [49]. Further work is required to understand the deviation between experimental and in vivo pharmacology in respect of T618I hERG SQT1 carriers.