BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment barriers.DAAs co-prescribed wi...BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment barriers.DAAs co-prescribed with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pibrentasvir due to potent cytochrome P450(CYP)3A4 induction.Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite time.Sofosbuvirvelpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment failure.This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible,impractical or unacceptable.However,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhibitory effect,may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction.CASE SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b,and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir,while co-prescribed carbamazepine for seizure disorders.Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants.DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration,and taken with meals to improve absorption.Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.CONCLUSION DAA therapies,including glecaprevir-pibrentasvir,warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine,particularly if AED substitution is not feasible.展开更多
BACKGROUND Apatinib is an orally bioavailable small-molecule receptor tyrosine kinase inhibitor.In December 2014,the China Food and Drug Administration made it the first anti-angiogenic therapy to be approved for trea...BACKGROUND Apatinib is an orally bioavailable small-molecule receptor tyrosine kinase inhibitor.In December 2014,the China Food and Drug Administration made it the first anti-angiogenic therapy to be approved for treating metastatic gastric cancer.It was specifically designated as a third-line or later treatment for metastatic gastric cancer.CASE SUMMARY Here,we present a case of advanced renal cell carcinoma(RCC)with multiple metastases(Stage IV)in a 48-year-old male with an extremely poor general status(Karnofsky 30%).He was initially given pazopanib as a targeted therapeutic.However,he experienced severe adverse reactions within two weeks,including grade IV oral mucositis.We,thus,tried switching his targeted treatment to an apatinib dose of 250 mg once daily since April 2018.The patient demonstrated striking benefits from this switch to the apatinib palliative treatment.Nearly one month later,his pain and other associated symptoms were alleviated.The patient was able to move freely and had an excellent general status(Karnofsky 90%).His progress has been followed up with regularly,allowing for a documented progression-free survival interval of approximately 32 mo.CONCLUSION This case suggests that,like other multi-target drugs,apatinib may be a useful first-line therapeutic drug for advanced RCC.It may be a particularly helpful curative option when patients are found to be intolerant of other targeted drugs.展开更多
文摘BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment barriers.DAAs co-prescribed with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pibrentasvir due to potent cytochrome P450(CYP)3A4 induction.Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite time.Sofosbuvirvelpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment failure.This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible,impractical or unacceptable.However,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhibitory effect,may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction.CASE SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b,and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir,while co-prescribed carbamazepine for seizure disorders.Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants.DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration,and taken with meals to improve absorption.Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.CONCLUSION DAA therapies,including glecaprevir-pibrentasvir,warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine,particularly if AED substitution is not feasible.
文摘BACKGROUND Apatinib is an orally bioavailable small-molecule receptor tyrosine kinase inhibitor.In December 2014,the China Food and Drug Administration made it the first anti-angiogenic therapy to be approved for treating metastatic gastric cancer.It was specifically designated as a third-line or later treatment for metastatic gastric cancer.CASE SUMMARY Here,we present a case of advanced renal cell carcinoma(RCC)with multiple metastases(Stage IV)in a 48-year-old male with an extremely poor general status(Karnofsky 30%).He was initially given pazopanib as a targeted therapeutic.However,he experienced severe adverse reactions within two weeks,including grade IV oral mucositis.We,thus,tried switching his targeted treatment to an apatinib dose of 250 mg once daily since April 2018.The patient demonstrated striking benefits from this switch to the apatinib palliative treatment.Nearly one month later,his pain and other associated symptoms were alleviated.The patient was able to move freely and had an excellent general status(Karnofsky 90%).His progress has been followed up with regularly,allowing for a documented progression-free survival interval of approximately 32 mo.CONCLUSION This case suggests that,like other multi-target drugs,apatinib may be a useful first-line therapeutic drug for advanced RCC.It may be a particularly helpful curative option when patients are found to be intolerant of other targeted drugs.
