scholarly journals A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma

2021 ◽  
pp. 107815522110313
Author(s):  
Emre Demir ◽  
Osman Sütcüoğlu ◽  
Beril Demir ◽  
Oktay Ünsal ◽  
Ozan Yazıcı
Keyword(s):  
Drug Interactions ◽  
Toxic Hepatitis ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Aldehyde Oxidase ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Drug Induced ◽  
Metastatic Osteosarcoma ◽  
Grade 3

Introduction Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known. Case report The patient diagnosed with metastatic osteosarcoma was given high dose methotrexate treatment, and favipiravir was started on the third day of the treatment with suspicion of SARS-CoV2 infection. Grade 3 hepatotoxicity developed after favipiravir. Management & outcome: The acute viral hepatitis panel and autoimmune liver disease panel were negative. The ultrasound of the abdomen was unremarkable for any hepatobiliary pathology. The all viral and hepatobiliary possible etiological factors were ruled out. The patient’s liver enzymes increased just after (12 hours later) the initiation of favipiravir, and we diagnosed toxic hepatitis caused by favipiravir-methotrexate interaction. Therefore, methylprednisolone 1 mg/kg dose was started for a presumed diagnosis of toxic hepatitis. Hepatotoxicity completely regressed after favipiravir was discontinued. Discussion Favipiravir may inhibit methotrexate elimination by inhibiting aldehyde oxidase and its sequential use may cause hepatotoxicity in this case. The clinicians should keep in mind possible drug interactions while using new antiviral agents against SARS-CoV2 like favipiravir.

Effects of Carnosine on Cyclophosphamide-Induced Hematopoietic Suppression in Mice

2014 ◽  
Vol 42 (01) ◽  
pp. 131-142 ◽  
Author(s):  
Meng Xu ◽  
Rong-Rong He ◽  
Yu-Jia Zhai ◽  
Keiichi Abe ◽  
Hiroshi Kurihara
Keyword(s):  
Side Effects ◽  
Antioxidant Activities ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Drug Induced ◽  
Meat Extract ◽  
Beta Alanine ◽  
Spontaneous Proliferation ◽  
Leukocyte Counts ◽  
Cyclophosphamide Administration

Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.

Phase II trial of sequential temozolomide (TMZ) and high-dose bolus (HDB) IL-2 in patients with metastatic melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8037-8037
Author(s):  
S. S. Agarwala ◽  
A. A. Tarhini ◽  
J. M. Kirkwood ◽  
C. Cai ◽  
L. Stover ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Single Agent ◽  
Stage Iv ◽  
Median Number ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Female Age ◽  
Grade 3

8037 Background: Previous biochemotherapy (BCT) regimens for metastatic melanoma have utilized lower doses of IL-2 and multiple chemotherapeutic agents, adding to toxicity, but not to efficacy. Methods: We designed a 2-stage Simon phase II study testing a unique BCT approach of single agent chemotherapy with TMZ given in an extended schedule (75 mg/m² per day for 3 weeks PO) followed by HDB IL-2 (600,000 U/Kg/dose, maximum 14 doses administered over 5 days). Cycles were repeated every 28 days with a two-week interval between alternate cycles. The first stage accrued 20 patients with promising activity and safety permitting enrollment of additional patients. Results: Thirty-one patients (20 male, 11 female), age 27–74 (median 47) have been enrolled to date. All had AJCC stage IV melanoma (7 M1a, 5 M1b, 19 M1c) and had not previously received therapy for metastatic disease. Twelve had received prior adjuvant interferon. A total of 88 cycles of therapy have been administered (median of 2 cycles per patient; 5 patients continue on therapy). The median number of doses was 9 (range 7–12) during cycle 1, and 6 (range 4–11) during cycle 2. Three patients did not receive any IL-2 due to disease progression, and 6 patients received only one cycle of IL-2. Twenty two patients who received at least 2 cycles are evaluable for response. All 31 patients are evaluable for toxicity. Grade 3 toxicities included hepatic (8), hematologic (4 leukopenia, 2 thrombocytopenia), diarrhea (1). No grade 3–4 cardiovascular or renal toxicities were noted. Overall response rate is 22.7% (2 complete lasting 10.8 and 17+ months, 3 partial lasting 3.7 and 16+ months, 1+ month). Responses were seen in both M1a and M1c disease. Fourteen patients had stable disease after 2 cycles and 10 of these have progressed. As of 12/31/2005, the 4 month PFS rate is 74% [40%, 88%], median TTP is 24 weeks [11, 32] and median OS is 71 weeks (31.4, inf). Conclusions: HDB IL-2 can be safely administered in combination with single agent temozolomide in an extended schedule and appears to have promising efficacy and lower toxicity than previously used BCT regimens. Further follow-up will determine if durability of response exceeds that of single agent HDB IL-2. [Table: see text]

Thalidomide-Induced Peropheral Neuropathy in Newly Diagnosed and Pre-Treated Multiple Myeloma Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4898-4898
Author(s):  
Patrizia Tosi ◽  
Elena Zamagni ◽  
Claudia Cellini ◽  
Delia Cangini ◽  
Paola Tacchetti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Term Therapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Drug Induced ◽  
Patients At Risk ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Long Term Therapy

Abstract Thalidomide is remarkably active in advanced relapsed and refractory multiple myeloma (MM), so that its use has been recently proposed either in newly diagnosed patients or as maintenance treatment after conventional or high-dose therapy. This latter therapeutic approach has risen the concern of side effects occurring after long-term therapy with this drug. In order to investigate this issue we analyzed the outcome of 74 patients who have been treated with thalidomide + dexamethasone for longer than 8 months at our Institution. Thirty-four patients (18M, 16F, median age = 55 years) had newly diagnosed symptomatic MM and were treated with four monthly courses of thalidomide 200mg/day + dexamethasone 40 mg on days 1 to 4 (even cycles), or on days 1 to 4, 9 to 12 and 17 to 20 (odd cycles), followed by cyclophosphamide 7g/m2 + G-CSF, peripheral blood stem cell (PBSC) collection, and double autologous PBSC transplant. Thalidomide + dexamethasone was administered throughout the whole treatment program. Forty patients (27M, 13F, median age = 61 years) were treated with thalidomide 200mg/day +dexamehasone 40mg on days 1–4 every four weeks as salvage therapy for relapsed (n = 14) or progressive (n=26) MM. Neurotoxicity was the most troublesome and frequent toxic effect that was observed after > 8 months treatment, the incidence averaging 74% in newly diagnosed patients and 75% in pretreated ones. Symptoms included paresthesias, tremor and dizziness; serial electromyographic studies revealed a symmetrical, mainly sensory peripheral neuropathy, with minor motor involvement. The severity of neuropathy, graded according the NCI-CTC 2.0 scoring system, varied greatly in the two groups of patients, as pretreated patients showed grade 2 and 3 toxicity in 32.5% and 27.5% of the cases, respectively, while the majority of newly diagnosed patients complained about grade 1 toxicity (57%), and none of them experienced grade 3 toxicity. In both groups thalidomide neurotoxicity was not related to sex, M protein isotype, and thalidomide daily dose. In pretreated patients, a significant correlation between grade 2 + 3 neurotoxicty and longer disease duration was found, thus suggesting that subclinical MM-related neurotoxicity could favour drug-induced toxic effects. These results suggest that long-term thalidomide therapy in MM may be hampered by the remarkable neurotoxicity of the drug, and that a neurological evaluation should be mandatory prior to thalidomide treatment, in order to identify patients at risk of developing a periperal neuropathy.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

High-dose methotrexate-induced reversible grade 4 hyperbilirubinaemia and transaminitis in an adolescent with Burkitt Leukaemia

2021 ◽  
Vol 14 (1) ◽  
pp. e237512
Author(s):  
Sanjeev Khera ◽  
Randhir Ranjan ◽  
Sateesh Ramachandran ◽  
Ajay Beriwal
Keyword(s):  
Liver Injury ◽  
Clinical Significance ◽  
Short Latency ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Dose Methotrexate

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.

scholarly journals Protease Inhibitors as Antiviral Agents

1998 ◽  
Vol 11 (4) ◽  
pp. 614-627 ◽  
Author(s):  
A. K. Patick ◽  
K. E. Potts
Keyword(s):  
Protease Inhibitors ◽  
Viral Infections ◽  
Critical Role ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Structural Proteins ◽  
Viral Protease ◽  
Virus Particles ◽  
Viral Proteases ◽  
Viral Polyprotein

SUMMARY Currently, there are a number of approved antiviral agents for use in the treatment of viral infections. However, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach. Accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. Molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses by effecting the cleavage of high-molecular-weight viral polyprotein precursors to yield functional products or by catalyzing the processing of the structural proteins necessary for assembly and morphogenesis of virus particles. This review summarizes some of the important general features of virus-encoded proteases and highlights new advances and/or specific challenges that are associated with the research and development of viral protease inhibitors. Specifically, the viral proteases encoded by the herpesvirus, retrovirus, hepatitis C virus, and human rhinovirus families are discussed.

scholarly journals Use of a Consultation Service Following Pharmacogenomic Testing in Psychiatry

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 179-180
Author(s):  
Daniel Dowd ◽  
David S. Krause
Keyword(s):  
Mental Illness ◽  
Drug Interactions ◽  
Metabolic Pathways ◽  
Patient Characteristics ◽  
Healthcare Resource Utilization ◽  
Machine Learning Algorithms ◽  
Mental Illnesses ◽  
Variable Response ◽  
Drug Induced ◽  
Commercial Laboratory

AbstractBackgroundThere is a plethora of drugs available to psychiatrists for treatment of mental illness, which can vary in efficacy, tolerability, metabolic pathways and drug-drug interactions. Psychotropics are the second most commonly listed therapeutic class mentioned in the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling. Pharmacogenomic (PGx) assays are increasingly used in psychiatry to help select safe and appropriate medication for a variety of mental illnesses. Our commercial laboratory offers PGx expert consultations by PharmDs and PhDs to clinician-users. Our database contains valuable information regarding the treatment of a diverse and challenging population.MethodsGenomind offers a PGx assay currently measuring variants of 24 genes relevant for selection of drugs with a mental illness indication. Since 2012 we have analyzed > 250,000 DNA samples. Between 10/18 - 8/20 6,401 reports received a consult. The data contained herein are derived from those consults. Consultants record information on prior meds, reason for failure or intolerability, potential risk-associated or useful drugs based on the genetic variants. Consultants only recommend specific drugs and doses consistent with a published PGx guideline.ResultsThe 5 most commonly discussed genes were SLC6A4, MTHFR, CACNA1C, COMT and BDNF. The 3 most commonly discussed drugs were fluoxetine, lithium and duloxetine. The most common reasons for drug failure were inefficacy and drug induced “agitation, irritability and/or anxiety”. SSRIs were the most common class of discontinued drug; sertraline, escitalopram and fluoxetine were the three most commonly reported discontinuations and were also the 3 most likely to be associated with “no improvement”. Aripiprazole was the most commonly reported discontinued atypical antipsychotic. The providers rated 94% of consultations as extremely or very helpful at the time of consult. An independent validation survey of 128 providers confirmed these ratings, with 96% reporting a rating of “very helpful” or “extremely helpful”. In addition, 94% reported that these consults were superior to PGx consults provided through other laboratories. Patient characteristics captured during consults via a Clinical Global Impressions-Severity (CGI-S) scale revealed that the majority of patients were moderately (54%) or markedly ill (23%). The most frequent symptoms reported were depression, anxiety, insomnia and inattentiveness.DiscussionThe large variety of psychotropic drugs available to providers, and their highly variable response rates, tolerability, capacity for drug-drug interactions and metabolic pathways present a challenge for even expert psychopharmacologists. Consultation with experts in PGx provides additional useful information that may improve outcomes and decrease healthcare resource utilization. This database may provide future opportunities for machine learning algorithms to further inform implications of included gene variants.FundingGenomind, Inc.

Myoclonus Due to Chlorambucil in Two Adults with Lymphoma

1997 ◽  
Vol 31 (2) ◽  
pp. 171-174 ◽  
Author(s):  
Andrew Rj Wyllie ◽  
Charles D Bayliff ◽  
Michael J Kovacs
Keyword(s):  
Nephrotic Syndrome ◽  
Science Citation Index ◽  
Low Dose ◽  
Citation Index ◽  
Science Citation ◽  
Data Sources ◽  
High Dose ◽  
Drug Induced ◽  
Neurologic Status ◽  
Subsequent Decrease

Objective To report myoclonus due to chlorambucil therapy in two adults with lymphoma, and to review the literature of chlorambucil neurotoxicity in adults. Case Summaries Case 1: An 81-year-old man with lymphoma being treated with chlorambucil developed jerking movements and stiffness that persisted for 3 days and intensified at night. The dosage of chlorambucil was decreased with a subsequent decrease in symptomatology. Resolution of the myoclonus occurred with discontinuation of the chlorambucil. Rechallenge evoked a return of tremors the next day that later became constant and again resolved on discontinuation of chlorambucil. Case 2: A 75-year-old woman with lymphoma being treated with chlorambucil developed jerking movements in her limbs, particularly in her arms and right hip. The symptoms were so severe they prevented the patient from leaving her house. All symptoms resolved within 2–3 days after the cycle was completed and did not return. She was diagnosed as having had chlorambucil-induced myoclonus. Data Sources Searches were performed on MEDLINE, CancerLit, and Science Citation Index Review to identify reports and articles discussing chlorambucil-induced neurotoxicity, particularly myoclonus. Discussion Chlorambucil-induced myoclonus has been described in overdose situations and in the treatment of nephrotic syndrome in children. Three cases of reversible myoclonic activity associated with high-dose chlorambucil in adults have also been described. In each case, the myoclonus resolved following discontinuation of the drug. Only one other conclusive case of low-dose chlorambucil-induced myoclonus in an adult has been described. The two cases presented here are unique in that the myoclonus occurred in adults receiving low-dose chlorambucil who had no myoclonus before or after treatment with the drug. Conclusions From the cases reviewed, it appears that chlorambucil may induce myoclonus in adults receiving therapeutic dosages of chlorambucil. The neurologic status of patients receiving chlorambucil should be followed closely during treatment. If myoclonus develops, drug-induced myoclonus should be considered, as well as discontinuation of the drug.

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