Pregabalin-induced sexual disinhibition

2017 ◽  
Vol 37 (1) ◽  
pp. 55-58
Author(s):  
R. Murphy ◽  
D. McGuinness ◽  
B. Hallahan
Keyword(s):  
Adverse Effects ◽  
Dose Reduction ◽  
Anxiety Symptoms ◽  
Published Data ◽  
Inhibitory Neurotransmitter ◽  
Sexual Side Effects ◽  
Significant Amelioration ◽  
Sexual Disinhibition ◽  
Require Dose ◽  
Require Dose Reduction

IntroductionSexual side effects have rarely been reported secondary to treatment with Pregabalin, a structural analogue of the inhibitory neurotransmitter gamma amino butyric acid (GABA).MethodWe present the case of AB, a 27-year-old single man with a diagnosis of recurrent depressive disorder who was prescribed pregabalin to alleviate the significant anxiety symptoms he was experiencing.ResultsA significant amelioration in anxiety symptoms was attained; however, he developed the adverse effects of acute sexual disinhibition and increased libido. These adverse effects were temporally related to treatment with pregabalin and reduced with dose reduction of this agent.ConclusionsTo date, limited published data are available relating such a reaction to pregabalin. A greater clinical recognition of this association between pregabalin and sexual disinhibition, would allow clinicians to intervene at an earlier stage of this adverse effect and potentially as in this case, management may only require dose reduction rather than treatment discontinuation.

scholarly journals Neoral conversion from Sandimmune in maintenance renal transplant patients: an individualized approach.

1998 ◽  
Vol 9 (7) ◽  
pp. 1293-1300
Author(s):  
J J Curtis ◽  
M Lynn ◽  
P A Jones
Keyword(s):  
Renal Transplant ◽  
Dose Reduction ◽  
Close Monitoring ◽  
Dose Ratio ◽  
Transplant Patients ◽  
Individualized Approach ◽  
Renal Transplant Patients ◽  
Require Dose ◽  
Trough Levels ◽  
Require Dose Reduction

When converting maintenance renal allograft recipients from Sandimmune (cyclosporin A [CsA]) to Neoral (CsA-microemulsion [CsA-ME]), a dose conversion ratio of 1:1 may not be optimal, in part because of the variability in absorption of the CsA formulation of cyclosporine. After conversion using a 1:1 dose ratio, an individualized approach to the management of dosing was applied. In this article, close monitoring, which began at the time of conversion, and rapid response to potentially meaningful changes in cyclosporine trough levels early in the postconversion course were used to maintain patients' cyclosporine troughs at preconversion levels. The results of cyclosporine dose changes after converting stable, maintenance renal transplant patients from CsA (once daily and twice daily) to CsA-ME (twice daily) during 52 wk of follow-up are reported. Most patients (87.2%) required CsA-ME dose reduction to maintain preconversion trough levels, and 64% of the patients attained their CsA-ME maintenance dose by study week 4. Logistic regression analysis identified one significant predictor concerning the week 52 CsA-ME dose: patients converted from CsA doses > or = 4.0 mg/kg per d were more likely to require dose reduction (P < 0.0001). Although firm guidelines for dose modification after conversion from CsA to CsA-ME cannot be provided because of the individual nature of cyclosporine absorption, an individualized approach to patient management is recommended. Patients with higher CsA doses before conversion are particularly likely to require dose reduction early in the postconversion course. With CsA-ME, good absorbers of cyclosporine remain good absorbers, or become better absorbers, whereas poor absorbers become good absorbers.

Mild to moderate liver dysfunction does not require dose reduction of oral or intravenous vinorelbine: Results of a pharmacokinetic study

2010 ◽  
Vol 46 (2) ◽  
pp. 266-269 ◽  
Author(s):  
Jos J. Kitzen ◽  
Christian Puozzo ◽  
Maja J. de Jonge ◽  
Maud Brandely ◽  
Jaap Verweij
Keyword(s):  
Dose Reduction ◽  
Pharmacokinetic Study ◽  
Liver Dysfunction ◽  
Require Dose ◽  
Require Dose Reduction

559 Benzocaine-Lidocaine-Tetracaine (BLT) Cream Adverse Effects in Burn Patients: A Case Report and Literature Review

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S129-S129
Author(s):  
Todd A Walroth ◽  
Michelle E Brown ◽  
Katelyn Gordon ◽  
Moises Martinez ◽  
Cortni Grooms ◽  
...  
Keyword(s):  
Literature Review ◽  
Adverse Effects ◽  
Surface Area ◽  
Total Body Surface Area ◽  
Neurological Deficits ◽  
Published Data ◽  
Burn Patients ◽  
Burn Wound ◽  
Lidocaine Concentration ◽  
Topical Lidocaine

Abstract Introduction Historically, BLT cream has been used at our burn center in laser procedures and tattoo removal with 6–8% lidocaine to improve tolerance of outpatient procedures. Recently, the laser BLT formulation (8%) has been trialed as an opioid-sparing alternative for managing pain during inpatient microneedling procedures. When utilizing this formulation for microneedling, the high percentage of lidocaine absorption may correlate with adverse central nervous system (CNS) effects. Methods A literature evaluation and retrospective chart review of burn patients receiving BLT cream for inpatient microneedling was performed. Results From January to June 2020, two elderly females (77 and 78 years old) received several doses of BLT cream during inpatient microneedling procedures with no documented adverse events attributed to the medication. A 68 year old male with a total body surface area (TBSA) of 8% reported dizziness shortly after he received BLT cream. Vitals were normal, but the patient was unable to focus his eyes or communicate clearly. Neurological exam revealed sluggish, pinpoint pupils. Patient remained disoriented with gargling and tongue thrusting though vitals remained stable. At this time, the remainder of the BLT cream was removed from the wound and his mentation returned to baseline within 90 minutes. No residual neurologic deficits occurred. No other potential causes were identified. Literature review revealed topical lidocaine can be absorbed systemically and cause CNS depression, confusion, and disorientation. Based on limited published data in healthy patients, it is recommended to use no more than 5% of topical lidocaine in large quantities, especially over raw surfaces or blistered areas. The amount of lidocaine systemically absorbed is linked to both the duration of application and the surface area over which it is applied. Using study data from lidocaine/prilocaine 2.5% cream and lidocaine patches, we explored a safer BLT formulation for burn patients as published data do not exist for this group. Conclusions Based on our review, we determined 2% to be the maximum lidocaine concentration to apply to a burn wound, 5% TBSA as the maximum surface area involved, and total exposure time limited to 30 minutes or less to reduce incidence of adverse effects. Specifically, formulations with a higher lidocaine concentration applied to a burn wound have the potential to result in untoward neurological deficits.

scholarly journals Safety and Tolerability of Lidocaine Infusions as a Component of Multimodal Postoperative Analgesia in Children

2019 ◽  
Vol 24 (1) ◽  
pp. 34-38 ◽  
Author(s):  
Katherine Lemming ◽  
Gary Fang ◽  
Marcia L. Buck
Keyword(s):  
Pain Management ◽  
Postoperative Pain ◽  
Adverse Effects ◽  
Dose Reduction ◽  
Postoperative Analgesia ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Postoperative Pain Management ◽  
Nuss Procedure ◽  
The Mean

OBJECTIVES Use of lidocaine as part of a multimodal approach to postoperative pain management has increased in adults; however, limited information is available regarding safety and tolerability in pediatrics. This study's primary objective was to evaluate the incidence of adverse effects related to lidocaine infusions in a sample of pediatric patients. METHODS A retrospective analysis was conducted in pediatric patients receiving lidocaine infusion for the management of postoperative analgesia at the University of Virginia Health System. RESULTS A total of 50 patients with 51 infusions were included in the final analysis. The median patient age was 14 years (range, 2–17 years). The most frequent surgeries were spinal fusion (30%), Nuss procedure for pectus excavatum (16%), and nephrectomy (6%). The mean ± SD starting rate was 13.6 ± 6.5 mcg/kg/min. The mean infusion rate during administration was 15.2 ± 6.3 mcg/kg/min, with 14.4 ± 6.2 mcg/kg/min at discontinuation. The mean length of therapy was 30.6 ± 22 hours. A total of 12 infusions (24%) were associated with adverse effects, primarily neurologic ones, including paresthesias in the upper extremities (10%) and visual disturbances (4%). The average time to onset was 16.2 ± 15.2 hours. Seven infusions were discontinued, whereas the remaining infusions resulted in either dose reduction or continuation without further incident. No patients experienced toxicity requiring treatment with lipid emulsion. CONCLUSIONS In this sample, lidocaine was a well-tolerated addition to multimodal postoperative pain management in the pediatric population. Although adverse effects were common, they were mild and resolved with either dose reduction or discontinuation.

Patterns Of Non-Hematological Adverse Effects In Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP) Treated With Ponatinib – Experience At a Single Institution

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4019-4019 ◽  
Author(s):  
Preetesh Jain ◽  
Hagop M. Kantarjian ◽  
Carlos Guillermo Romo ◽  
Alfonso Quintas-Cardama ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Effects ◽  
Dose Reduction ◽  
Research Funding ◽  
Skin Toxicity ◽  
Qtc Prolongation ◽  
Single Institution ◽  
Dry Skin ◽  
Starting Dose ◽  
Grade 3

Abstract Introduction Ponatinib is a multi-targeted tyrosine kinase inhibitor (TKI) efficacious in pts with refractory CML. Ponatinib inhibits other tyrosine kinases (e.g. RET, FGFR, FLT3) that may lead to off target adverse effects (AE). We report a single-institution experience of frequencies of non-hematological AE among pts on therapy with ponatinib. Methods A total of 90 pts with CML-CP[49 relapsed refractory (RR), 41 frontline] treated at our institution on clinical trials with ponatinib were analyzed. AE were recorded on each pt visit and charts were reviewed for AE and risk factors. Results For RR pts (n=49)the starting dose of ponatinib was 45 mg in 42 (86%) pts. 39 (80%) had dose interruptions, due in 17 (44%) to grade 3 thrombocytopenia and in 22 (56%) to non-hematological AE (elevated pancreatic enzymes 7 pts of whom 5 had pancreatitis; body aches and headache 7; hypertension 7; skin toxicity 5; fatigue 5). 35 pts (71%) had dose reduction to 30 or 15 mg. Hypertension (H.T.) stage 2 (≥160/100 mm Hg) occurred in 15 (31%) pts; only 2 of new onset. Blood pressure was controlled in all with antihypertensives. Other cardiovascular AE included QTc prolongation in 1 pt, atrial fibrillation in 1 pt, acute myocardial infarction in 3, venous thrombosis in 3, arterial thrombosis in 4, transient ischemic attack (TIA) in 1 and Raynaud’s in 1. No pt discontinued ponatinib due to cardiovascular AE’s. Symptomatic pancreatitis developed in 8 pts (16%). Grade 3/4 elevations in serum lipase and amylase occurred in 12 (24%) pts and 2 (4%) pts respectively. Median days to onset of pancreatitis was 24 (range 7-456). 27 pts (55%) developed cutaneous toxicity including xerosis/dry skin in 10 (37%) and grade 3 erythroderma and exfoliation of the skin in 5. Four pts died, none related to ponatinib. 13 pts went off the study: 5 went to SCT, 3 progressed, 1 pt died in CCyR of multiple co-morbidities, 1 pt had progressive melanoma, 1 pt was transferred to another hospital, and 2 for ponatinib-related AE (headache in 1 and headache, fatigue, depression, and abdominal pain in 1). For pts in frontline setting (n=41) the starting dose was 45 mg in all. 29 pts (71%) had dose interruptions due to one or more of the following: grade 3/4 pancreatic enzyme elevation in 16, myelosuppression in 4, and various non-hematological AE in 15 (skin toxicity in 4, fatigue in 2, headache in 1, chest pain in 2, elevated liver enzymes in 2, suspected seizure vs. TIA in 1, grade 3 diarrhea in 1, memory disturbances in 1, and grade 3 hypertension in 1, erectile dysfunction in 1). 24 pts (59%) had dose reduction, from 45 mg to 30 mg in 20 pts and then to 15 mg in 4 pts. H.T. stage 2 occurred in 3 (7%) pts usually among patients with pre-existing H.T. Other cardiovascular AE included grade 2 QTc prolongation in 1 pt, possible TIA vs. possible seizure in 1, and Raynaud’s in 2. Pancreatitis was seen in 12 pts (29%) with grade 1-2 and 6 pts (15%) with grade 3/4. Grade 3/4 lipase/amylase elevations occurred in 16 (39%) and 3 (7%) pts. Median days to the onset of pancreatitis were 6 (4-22). 34 pts (83%) developed skin toxicity with rash (any grade) in 25 pts (61%), xerosis/dry skin in 18 pts (44%) and grade 3 erythroderma and skin exfoliation in 2 (pts may have had ≥1 type of skin AE). 2 pts discontinued therapy, due to severe xerosis in 1 and recurrent gra 4 neutropenia in another. 1 pt developed grade 2 pericarditis possibly related to ponatinib. For all the 90 pts, risk factors for cardiovascular and pancreatic toxicities included 20 (22%) smokers, 2 heavy alcohol consumers, 27 (30%) obese (BMI ≥30 Kg/m2), 30 (33%) with hypertriglyceridemia, 17 (19%) had hypercholesterolemia and 10 pts were receiving lipid lowering therapies. Conclusions Ponatinib is generally well tolerated and AEs can usually be properly managed. AE are more common in RR pts with greater frequency of hypertension, cardiovascular complications, headache, dry mouth and dose interruptions. Most pts are able to continue therapy after dose adjustments. Disclosures: Kantarjian: ARIAD: Research Funding. Cortes:Ariad, Pfizer, Teva: Consultancy; Ariad, BMS, Novartis, Pfizer, Teva: Research Funding.

Pomalidomide Plus Dexamethasone (Pd) in the Treatment of Asian Patients with Relapsed/Refractory Myeloma (RRMM) Who Are Previously Treated with Bortezomib and Refractory to Lenalidomide - Interim Analysis of a Trial By the Asian Myeloma Network (AMN)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2130-2130
Author(s):  
Wee J Chng ◽  
Kihyun Kim ◽  
Jeffrey Huang ◽  
Chor Sang Chim ◽  
Hiroshi Kosugi ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Median Duration ◽  
Prospective Trial ◽  
Safety Data ◽  
Published Data ◽  
Base Line ◽  
Asian Patients ◽  
Duration Of Response ◽  
Previously Treated ◽  
Grade 3

Abstract Background Pomalidomide is a 3rdgeneration immunomodulatory drug that has been approved for the treatment of Patients who progress after prior treatment with bortezomib and lenalidomide. Experience with pomalidomide in Asian patients is very limited till date. In addition, it is unclear if pomalidomide will work in patients who have been exposed to a newer generation of treatments for myeloma including carfilzomib, ixazomib, panobinostat and daratumumab. Method We conducted a prospective trial of pomalidomide (4mg daily for 21 days every 4 weeks) plus dexamethasone (40mg once weekly) in myeloma patients who have relapsed after prior bortezomib and are refractory to lenalidomide from Singapore, Korea, Japan, Hong Kong and Taiwan (NCT02158702). Patients were allowed up to 6 prior lines of treatment. If there is less than a minimal response after 3 cycles of pomalidomide and dexamethasone, including progression within 3 cycles, cyclophosphamide 300mg/m2can be added. The trial was started in December 2014 and is still ongoing. To date, 121 patients have been recruited. This interim report presents data available up till the data cut-off date of 30 April 2016. Results Eighty-six patients have available base line information and safety data. 55% of patients are male and median age of the cohort is 65 years old. 37% and 27% of patients are International Stage System (ISS) stage 2 and 3 respectively. 35% of patients have abnormal creatinine clearance. Median prior line of treatment is 4. 24% of patients required dose reduction of pomalidomide, 8% require dose reduction of dexamethasone. 70% of patients experience adverse events (AEs) of any grade (31% of episodes grade 3 or higher), with 35% of these episodes related to the study drugs. 47% of patients experienced serious AEs (SAEs) of any grade (91% of episodes grade 3 or higher), with 42% of these episodes related to the study drugs. Almost all of these events are related to cytopenias and infections. Only 1 patient experienced each of these AEs: grade 3 peripheral neuropathy, VTE or grade 3 renal impairment. Five patients withdrew due to toxicity. Fifteen patients died while on the study, 5 from disease progression, 2 from late stage disease, and 8 from sepsis or pneumonia. The median overall length of follow-up is 5 months. The overall median PFS (N=65) was 6.5 months. Those treated with only Pd (n=53) have a median PFS of 6.5 months. Patients with cyclophosphamide added (Pcd) had a median PFS of 5.8 months. Achievement of a partial response (PR) or better was significantly associated with improved PFS. There was no observed difference in PFS by age, number of prior lines of treatment, ISS stage or the presence of high-risk genetics. Overall median OS was 14 months. For those treated with only Pd, the median OS was 14 months whereas it is 10 months for those on Pcd. Forty-four patients have data for response assessment. 22 (50%) achieved a PR or deeper response with 1 achieving CR and 1 stringent CR. The median duration of response was 8.4 months for those who had achieved a PR or more. Eight out of those 44 patients required the addition of cyclophosphamide due to suboptimal response, 2 of whom subsequently achieved a PR. In these patients the median duration of response was 4.7 months. Eleven patients were previously treated with carfilzomib, ixazomib, panobinostat, elotuzumab or daratumumab in clinical trials. Amongst these, 6 (55%) obtained a PR or better and were able to maintain the response for 10 months. In this group, the PFS was 5.5 months and the median OS was 10.3 months. Conclusion This is the first prospective report of the efficacy and safety of Pd in Asian patients with RRMM. The combination is highly active in patients who are heavily pre-treated. Our results compare favorably with previously published data from the US and Europe. The regimen appears to be active across age groups, risk categories and prior lines of treatment. In particular, it is very active even in patients who have progressed following treatment with the latest generations of approved drugs including monoclonal antibodies. In patients who have a suboptimal response, the addition of cyclophosphamide can salvage meaningful response. The regimen is well tolerated and toxicity manageable. A randomized study comparing Pcd to Pd will commence soon. Disclosures Chng: Celgene: Honoraria, Research Funding. Sakamoto:Takeda Pharmaceutical: Consultancy; Yakult: Other: Remuneration. Durie:Amgen: Consultancy; Takeda: Consultancy; Janssen: Consultancy.

Pulmonary toxicity of cytotoxic agents: A meta-analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19573-19573
Author(s):  
Y. Takiguchi ◽  
Y. Tada ◽  
K. Kurosu ◽  
S. Sakao ◽  
K. Tatsumi ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Comparative Studies ◽  
Pulmonary Toxicity ◽  
Literature Search ◽  
Meta Analysis ◽  
Best Supportive Care ◽  
Cytotoxic Agents ◽  
Published Data ◽  
Toxicity Data ◽  
Anti Cancer

19573 Background: Pulmonary toxicity is one of the most serious adverse effects of cytotoxic agents, and affected patients require discontinuation of the anti-cancer therapy, and it even proves fatal in many cases. Its incidence, however, may be considerably biased, as it may be influenced by many factors such as intercurrent medications or co-morbidities. The purpose of our study was to evaluate the incidences of pulmonary toxicity by cytotoxic agents in published data relating to prospective randomized comparative studies. Methods: A Medline literature search was conducted to extract prospective randomized comparative studies (either phase II or III) that included docetaxel, paclitaxel, irinotecan, vinorelbine and gemcitabine. Comparisons had to be performed between regimens with and without one of these agents, in addition to best supportive care with or without other common agent(s), so as to be able to clearly attribute the toxicity to the agent. Reports lacking detailed toxicity data were excluded. Results: The table below summarizes the results of the finally evaluated 47 studies (5 to 12 per agent) fulfilling the criteria. As many studies showed no pulmonary toxicity, standard statistical methods for meta-analysis were not applicable. Conclusions: The present study analyzing data in prospective randomized comparative studies might minimize bias of the relative incidence of pulmonary toxicity. Pulmonary toxicity was rarely encountered in randomized comparative studies. No increase in frequency was shown by the inclusion of any of the five cytotoxic agents. [Table: see text] No significant financial relationships to disclose.

Effect of PSK on FOLFOX4-induced peripheral neuropathy and bone marrow suppression in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 596-596
Author(s):  
M. Shibata ◽  
T. Shimura ◽  
K. Gonda ◽  
I. Nakamura ◽  
S. Ohki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bone Marrow ◽  
Adverse Effects ◽  
Metastatic Colorectal Cancer ◽  
Progressive Disease ◽  
Complete Response ◽  
Bone Marrow Suppression ◽  
Published Data ◽  
Pulmonary Cancer ◽  
Cold Sensitive

596 Background: FOLFOX4 has been confirmed as an effective treatment for metastatic colorectal cancer and is used as a postoperative adjuvant therapy. However adverse effects such as cold-sensitive paresthesia and bone marrow suppression are common and may necessitate changes in chemotherapy regimen despite FOLFOX effectiveness. PSK, a polysaccharide derived from a species of mushroom, has been developed in Japan as an immune-enhancing agent and is widely used in patients with gastric, colorectal and pulmonary cancer. PSK has also been reported to decrease some adverse effects of chemotherapy. Methods: FOLFOX4 combined with PSK was administered to patients with metastatic colorectal cancer and the results were evaluated. Eight cycles of FOLFOX4 and PSK (3.0 g/day, p.o.) were given to 25 patients with metastatic colorectal cancer (19 hepatic, 3 pulmonary and 3 peritoneal). Results: No patients showed CR (complete response, 0%) while PR (partial response), SD (stable disease) and PD (progressive disease) were seen in 48%, 36% and 16% of patients, respectively. Response rate was 48% and disease control rate was 84%. Frequency of adverse effects was significantly lower than described in the published data. Grades 1 and 3 neutropenia occurred in 48% and 24% of patients, respectively; grades 1 and 3 nausea in 48% and 4%, respectively; and grades 1, 2 and 3 sensory neurotoxicity in 52%, 4% and 0%, respectively. No patient dropped out due to adverse effects in this study. Conclusions: PSK plus FOLFOX4 seems as effective as FOLFOX4 monotherapy, and significantly less toxic. These results suggest that this combination therapy may be more effective when given for a longer period, with lower incidence of adverse effects. No significant financial relationships to disclose.

scholarly journals Assessing Steroid Toxicity in the Elderly with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5557-5557
Author(s):  
Vidhya Nair ◽  
Hadi Mohammed ◽  
Sharmeen Mahmood ◽  
Pushpinderdeep Singh Kahlon ◽  
Philip Kuriakose
Keyword(s):  
Central Nervous System ◽  
Multiple Myeloma ◽  
Nervous System ◽  
Adverse Effects ◽  
Elderly Patients ◽  
Dose Reduction ◽  
The Elderly ◽  
High Dose ◽  
Full Dose ◽  
Starting Dose

Background The mainstay of treatment for Multiple Myeloma (MM) includes various combinations of chemotherapy, which generally includes high dose steroids. The median age at diagnosis for MM is above 60 years. Patients above the age of 70 may not be considered for an auto peripheral blood transplant, resulting in being treated with chemotherapy alone. This often leads to a relatively long period of steroid exposure. Increasing age is a risk factor for decreased tolerance to steroids, and increased drug toxicity. As such, the steroid dose (usually Dexamethasone) is often considered for reduction in patients above a certain age. However, there are no clear guidelines regarding a standard dose to use in the elderly, nor is there uniformity among clinicians in the way doses are chosen. Purpose To assess a) the starting dose of Dexamethasone (dex) in the elderly, b) frequency of dose reduction of dexamethasone, c) adverse effects of dex treatment in the elderly with MM, and d) average time after dose reduction. Methods We performed a 10 year retrospective chart review on patients, age 70 or greater treated at Henry Ford Health System with a diagnosis of MM from 2000-2015. Patients were grouped by age 70-75 years, 76-80 years, and greater than 80 years based on when treatment was initiated. We investigated the starting treatment dose of dex, ranging from 1-20 mg weekly and 21-40 mg weekly. Secondly, we assessed for the occurrence of dose reduction; and, if present, the length of time to reducing the dose. Lastly, the types of adverse effects to dex leading to dose reduction were grouped by system, such as, central nervous system, musculoskeletal, endocrine, gastrointestinal and psychiatric. Data collected was categorical, thus, no statistical tests were performed as this was a descriptive study. Results A total of 150 patients were reviewed and 91 patients met the inclusion criteria. Of these patients, 8 (8.8%) were started at doses between 1-20 mg and majority (62.5%) were ages 70-75, thus, there was no relation between lower starting dose and age. Of the 91 patients, 24 (26.4%) had a dose reduction and 11 (12.1%) had both chemotherapy and dex discontinued prior to therapy completion. Majority (87.5%) of patients that had a dose reduction were initially started at 40 mg. The reasons for dose reduction included adverse effects grouped by musculoskeletal (29.17%), psychiatric (16.67%), endocrine (12.3%), central nervous system (4.17%), and gastrointestinal (4.17%). Of note, 8 patients (33.3%) had dose reductions as result of their clinical trial requirement. The average length of dex therapy before dose reduction was 17.2 months. Conclusion The majority of elderly patients (age 70 or above) with MM tolerated full doses of dex without adverse effects. Secondly, there was no relation between lower starting dose for dex and advanced age. However, since there were limited patients (n=8) who started at a low dose, other than those on clinical trials, we were not able to do a comparison of starting doses. But we were able to show that the majority of patients tolerated full dose, despite their age. The most frequent cause of steroid toxicity was musculoskeletal, such as leg swelling. On average, elderly patients were able to tolerate full dose of dex for over 1 year prior to requiring a dose reduction. Summary Our data demonstrates no correlation between advanced age in MM and lack of tolerability of high dose steroids. In conclusion, current findings do not justify reduced doses solely based on age alone. Future studies could include investigating statistical analysis on steroid exposure and survivorship. Disclosures Kuriakose: Alexion: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy.

scholarly journals Dose Reductions Related to Adverse Effects in Patients with Waldenström Macroglobulinemia Treated with the BTK-Inhibitor Ibrutinib

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3529-3529
Author(s):  
Shayna Sarosiek ◽  
Joshua Gustine ◽  
Catherine A Flynn ◽  
Carly Leventoff ◽  
Timothy P White ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Dose Reduction ◽  
Research Funding ◽  
Medication Side Effects ◽  
Hematologic Response ◽  
Medication Side ◽  
Treatment Naïve ◽  
Btk Inhibitor ◽  
Dose Reductions

Abstract The BTK-inhibitor ibrutinib is the first FDA approved therapy for Waldenström macroglobulinemia (WM) and produces overall response rates &gt;90% and long-term disease control in both treatment naïve and previously treated patients. Despite the remarkable efficacy of ibrutinib, dose reduction is often required for intolerance. In this study, we analyzed those patients requiring a dose reduction and evaluated the time to dose reduction, the symptoms leading to dose reduction, the rate of improvement in symptoms after dose reduction, and the hematologic response at 12 months after dose reduction. 385 patients received treatment with ibrutinib in our clinic from May 2012 through October 2020. Their baseline characteristics are shown in Table 1. Starting dose for these patients was 560 mg (n=11); 420 mg (n=358); 280 (n=15); 140 mg (n=1). Approximately 1/3 of all patients were treatment naïve at the time ibrutinib was initiated. Anemia, constitutional symptoms, and symptomatic hyperviscosity (or risk of hyperviscosity) were the most common reasons for treatment initiation. Reasons for dose reduction are shown in Table 2. Ninety-five patients (25%) required at least one dose reduction of ibrutinib. Twenty-three patients (6%) required a second dose reduction. Of the patients requiring dose reductions, 1 patient started at 280 mg and reduced to 140 mg, 91 patients started ibrutinib at 420 mg (1 patient ultimately had dose reduction to 70 mg, 22 patients to 140 mg, and 68 patients to 280 mg), and three patients started ibrutinib at 560 mg in the setting of Bing-Neel syndrome (2 patients had dose reduction to 420 mg and 1 patient to 280 mg). Patients requiring a dose reduction had a median age of 71 years (range, 46-96) at the time of ibrutinib initiation versus 66 years (range, 40-93) for those not requiring a dose reduction (p&lt;0.001). Forty-five patients (47%) of patients requiring dose reduction were female versus 98 (34%) not requiring dose reduction (p=0.017). Median time to first dose reduction was 7.3 months (range, 0.5-75) and median time to second dose reduction from initiation of ibrutinib was 23 months (range, 3-75). Of the 95 patients requiring a dose reduction, 40 patients (42% of all patients with dose reductions) had improvement in at least 1 of the medication side effects after the initial dose reduction. Twenty-two patients (23%) had complete resolution of adverse effects. Twenty-six patients (27%) had no change in symptoms and 10 of these patients required an additional dose reduction. After the second dose reduction, 5 patients had improvement or resolution in symptoms. Two patients had no adverse effects prior to dose reduction and medication was reduced simply due to drug interaction. Of the 48 patients with 1-year hematologic follow-up data available, 10 patients (21%) had improvement in hematologic response and 35 patients (73%) maintained their hematologic response despite dose reduction. Three patients (6%) had worsening of hematologic response after dose reduction. In conclusion, one quarter of WM patients in this series on ibrutinib required a dose reduction due to development of intolerable medication side effects. In the majority of these patients, adverse effects improved or resolved with dose reduction. Importantly, hematologic response remained stable or improved in most patients despite dose reduction. Figure 1 Figure 1. Disclosures Treon: BeiGene: Consultancy, Research Funding; Eli Lily: Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

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