Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Aug 2019
ReviewFremanezumab for the preventive treatment of migraine in adults.
Introduction: The Calcitonin Gene-Related Peptide (CGRP) has been implicated in migraine pathophysiology due to its role in neurogenic inflammation and transmission of trigeminovascular nociceptive signal. New molecules targeting CGRP and its receptor have been developed as migraine-specific preventative treatments. Fremanezumab (or TEV-48,125, LBR-101), a human monoclonal antibody against CGRP, has been recently approved for clinical use by FDA and EMA. ⋯ Long-term effects of CGRP block in cardiovascular, grastrointestinal and bone functions should be evaluated in ongoing trials, since CGRP is involved in multiple biological activities in the human body. Nevertheless, targeting CGRP itself allows the receptor binding with other ligands involved in several physiological functions. Thus, the long-term treatment with Fremanezumab is expected to be associated with a lower risk of severe adverse effects.
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Expert Rev Clin Pharmacol · Aug 2019
ReviewSolriamfetol for the treatment of excessive daytime sleepiness associated with narcolepsy.
Introduction: Narcolepsy is a chronic disabling condition, excessive daytime somnolence is the main symptoms of it. There is currently no cure for narcolepsy, and hence there is a great need for new treatment options. Solriamfetol is a new selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects. ⋯ Clinical trials showed that solriamfetol could significantly improve the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy. Solriamfetol was well tolerated. Very common adverse reactions were headache, nausea, decreased appetite, insomnia, and anxiety.
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Expert Rev Clin Pharmacol · Jul 2019
ReviewLiterature review of the evidence regarding intravenous lipid administration in drug-induced cardiotoxicity.
Introduction: Intravenous lipid emulsion (ILE) administration is capable of reversing the acute cardiac and neurological toxicity caused by local anesthetic agents. In recent years, ILE has also been explored as a potential antidote for cardiotoxicity caused by non-anesthetic agents too. Areas covered: The potential mechanisms, safety, and efficacy of this approach are considered. ⋯ Clinical improvement was observed in 57 of 59 patients with local anesthetic toxicity (96.6%); there were 239 patients where toxicity was due to non-anesthetic agents, and ILE apparently improved clinical outcome in 215 (72.1%). Expert opinion: Response rates were similar between ILE treated toxicity caused by lipid soluble and non-lipid soluble drugs. Potential adverse effects of ILE include interference with laboratory assays, acute pancreatitis, and adult respiratory distress syndrome, although the rate of occurrence is difficult to ascertain.
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Expert Rev Clin Pharmacol · Jul 2019
ReviewAlternatives to antibiotics in an era of difficult-to-treat resistance: new insights.
Introduction: The rise of antibiotic resistance, the limited efficacy and the adverse events associated with antibiotics have urged the development of alternative measures to treat bacterial infections. Novel therapies which are pathogen specific and are safer to the healthy microbiome are being developed. Areas covered: This manuscript provides a compact overview of the feasibility and clinical impact of the latest novel therapies, with a focus on monoclonal antibodies (mAbs), vaccines, stem cells, bacteriophages, and liposomes. ⋯ Stem cells and bacteriophages still have a long way to go. Vaccines are always desirable to prevent infections but again there is a lack of confirmatory results. Broad spectrum liposomes have shown promising results in treating severely infected patients and could be game changers in patient management.
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Expert Rev Clin Pharmacol · Jun 2019
ReviewClinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura.
Introduction: Caplacizumab is a humanized anti-von Willebrand Factor (vWF) Nanobody® for the treatment of acquired Thrombotic Thrombocytopenic Purpura (aTTP). Caplacizumab targets the A1-domain of vWF, inhibiting the interaction between vWF and platelets. Clinical studies conducted in aTTP patients confirmed the rapid and sustained complete suppression of the vWF activity using an initial intravenous dose of 10 mg, and a maintenance subcutaneous 10 mg daily dosing regimen, with corresponding favorable efficacy and safety profiles. ⋯ Renal and hepatic impairment are not expected to influence the exposure to the drug, and no direct or indirect drug-drug pharmacokinetic interactions are anticipated based on the mechanism of action and the specificity of the pharmacodynamic effect of caplacizumab. Expert opinion: Caplacizumab prevents the interaction between vWF and platelets, offering a direct and rapid therapeutic intervention to stop microthrombosis. The combination of caplacizumab with plasma exchange and immunosuppression represents an important, potentially life-saving advance in the treatment of aTTP patients.