ABSTRACT
INTRODUCTION: MetforminHydrochloride is an antidiabetic used for many years, currently; it considered the first choice in treatment of type 2 diabetes (T2D). It decreases insulin resistance, does not induce hypoglycaemia, increases glucose utilization in the liver and skeletal muscle, and decreases hepatic glucose production. Its adverse effects (AE) are gastrointestinal, decrease in vitamin B12 absorption, abnormalities of hemogram and rarely skin reactions. The objective of this study was to report the type and frequency of AEs of Metformin Hydrochloride used in the therapeutic management of T2D patients admitted to the medical center and the diabetes home of Sidi Bel-Abbès in Algeria. MATERIALS AND METHODS: A cross-sectional descriptive study was carried out over a period of four months, from January 1st, 2017 to April 30th, 2017, involving 130 patients treated with Metformin Hydrochloride consulting at Mimoun City Diabetes Home and Gambetta Diabetes Center in the town of Sidi Bel-Abbès. The primary outcome measure was the determination of the type and frequency of AEs related to normal dosages or overdose use of Metformin Hydrochloride in T2D. Data were collected from patient records, using a questionnaire, and analyzed using Statistical Package for the Social Sciences, version 20 software. RESULTS: 130 patients were included, including 82 women, with a mean age of 51.08±8.85 years (30-66). One hundred and ninety-eight (198) AEs were reported, an average of 1.52 AEs per patient. Among them, 95 (47.98%) AEs are digestive disorders (30.77% of patients suffered from diarrhea, 10.77% had nausea and vomiting, 8.46% suffered from abdominal pain and bloating, 3.85% lost their taste, 7.69% complained of epigastric cramps and 11.54% of anorexia), 29 (14.65%) AEs are hypoglycaemia, 73 (36.87%) AEs are other symptoms and 1 (0.50%) EI is vitamin B12 deficiency and no cases of lactic acidosis or allergic reaction were reported. Five (3.85%) patients had a total and lasting intolerance to Metformin Hydrochloride leading to its discontinuation following persistent diarrhoea. CONCLUSION: AEs of Metformin Hydrochloride used in the management of T2D patients consulting at the medical center and the Diabetes home of Sidi Bel-Abbès are frequent. Digestive disorders were the most frequent, diarrhea was very frequent and led to discontinuation of treatment in 3.85% of T2D patients, followed by nausea and vomiting, then abdominal pain, bloating and epigastric cramps, and rarely taste metallic. Hypoglycaemia was frequent following its association with insulin, the onset of headaches and fatigue were frequent, but no case of lactic acidosis or allergic reaction was reported. Due to a lack of means, the dosage of homocysteine and methylmalonic acid had not been carried out to confirm the vitamin B12 deficiency in the patient whose level was less than 200ng/mL. A precise assessment of the imputability of reported AEs is necessary.
Subject(s)
Acidosis, Lactic , Diabetes Mellitus, Type 2 , Drug-Related Side Effects and Adverse Reactions , Hypersensitivity , Hypoglycemia , Metformin , Nuns , Vitamin B 12 Deficiency , Humans , Female , Adult , Middle Aged , Metformin/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Cross-Sectional Studies , Muscle Cramp/chemically induced , Muscle Cramp/complications , Muscle Cramp/drug therapy , Vitamin B 12/therapeutic use , Hypoglycemic Agents/adverse effects , Vitamin B 12 Deficiency/chemically induced , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/drug therapy , Hypoglycemia/chemically induced , Hypoglycemia/complications , Hypoglycemia/drug therapy , Hypersensitivity/complications , Hypersensitivity/drug therapySubject(s)
Antineoplastic Agents , Carcinoma, Basal Cell , Skin Neoplasms , Humans , Prospective Studies , Muscle Cramp/chemically induced , Muscle Cramp/drug therapy , Carcinoma, Basal Cell/drug therapy , Anilides/adverse effects , Skin Neoplasms/drug therapy , Spasm/chemically induced , Spasm/drug therapy , Antineoplastic Agents/therapeutic useABSTRACT
Here, we reported two cases with hyperthyroidism who complained of myalgia and muscle cramps during treatment with methimazole tablets (or Thyrozol, the brand name). One case experienced muscle cramps after taking Thyrozol for 6 months, and by this time the patient's thyroid function had returned to normal. In the other case, pain caused by muscular cramps began after the patient took Thyrozol for two weeks and the patient's thyroid function had not returned to normal yet at the time. In both cases, pain caused by muscle cramps appeared while the patients were taking Thyrozol. The myalgia persisted in spite of a reduction in the Thyrozol dose, but was significantly relieved with the discontinuation of Thyrozol. Myalgia and muscle cramps did not recur after the patients were switched to methimazole ointment. There was a strong temporal association between oral administration of Thyrozol and pain caused by muscle cramps, which may indicate that myalgia and muscle cramps are adverse reactions of Thyrozol. Looking into the relevant literature on the topic, we explored in this report the possible mechanisms of the onset of muscle cramps associated with Thyrozol, and compared the adverse reactions of two different formulations of methimazole, intending to provide more clinical experience for the treatment of hyperthyroidism and the management of rare adverse reactions related to antithyroid drugs.
Subject(s)
Hyperthyroidism , Methimazole , Humans , Methimazole/adverse effects , Muscle Cramp/chemically induced , Myalgia , Hyperthyroidism/drug therapy , TabletsABSTRACT
BACKGROUND: Muscle cramp is possibly related to peripheral nerve hyperexcitability (PNH), and one of the most debilitating symptoms frequently encountered in patients with liver cirrhosis. We investigated whether pregabalin, a gamma-aminobutyric acid analogue, can suppress neuronal excitability and reduce muscle cramps in cirrhotic patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in which study participants with cirrhosis from a single tertiary center were enrolled. Primary endpoint was the relative change in cramp frequency from the run-in to standard dose treatment phase (4 weeks per each). Secondary endpoints included the responder rate, and the changes in cramp frequency during sleep, pain intensity, health-related quality of life (Liver Disease Quality of Life Instrument, Short Form-36) and electrophysiological measures of PNH. RESULTS: This study was terminated early because of insufficient accrual. 80% (n = 56) of the target number of participants (n = 70) were randomized to pregabalin (n = 29) or placebo (n = 27). Median baseline frequency of muscle cramps (interquartile range) was 5.8 (3.5-10) per week in the pregabalin group and 6.5 (4.0-10) in the placebo group (P = 0.970). The primary analysis showed a significant reduction in cramp frequency with pregabalin compared to placebo (-36% vs. 4.5% for the percentage change, P = 0.010). Secondary outcomes did not differ significantly between the two groups. Adverse effects with pregabalin were mainly dizziness and lethargy. CONCLUSION: With multiple problems emerging from premature termination in mind, the results suggested an acceptable safety profile and favorable effect of pregabalin in reducing muscle cramps compared to placebo in cirrhotic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01271660.
Subject(s)
Muscle Cramp , Quality of Life , Analgesics/adverse effects , Double-Blind Method , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Muscle Cramp/chemically induced , Muscle Cramp/etiology , Pregabalin/adverse effects , Treatment Outcome , gamma-Aminobutyric Acid/adverse effectsABSTRACT
Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine 'loading-phase' required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.
Subject(s)
Creatine/adverse effects , Dietary Supplements/adverse effects , Adiposity/drug effects , Adolescent , Adult , Alopecia/chemically induced , Body Water/drug effects , Child , Creatine/administration & dosage , Creatine/chemistry , Creatine/metabolism , Dehydration/chemically induced , Female , Humans , Kidney/drug effects , Kidney Diseases/chemically induced , Male , Muscle Cramp/chemically induced , Muscle, Skeletal/drug effects , Sex Factors , Sports Nutritional Physiological Phenomena , Testosterone/metabolism , Testosterone Congeners/pharmacologyABSTRACT
Despite the popularity of theraphosids, detailed reports on bite symptoms are still limited to few geographic regions and subfamilies. We therefore examined 363 published bite reports and noticed muscles cramps caused by theraphosids from nearly all continents and subfamilies. Symptoms are mostly locally restricted and mild, but 12.7% of victims experience pronounced cramps with highest incidence rates by Poecilotheriinae, Harpactirinae and Stromatopelminae subfamilies. We discuss how variations in venom quantity correlate with muscle cramp prevalence.
Subject(s)
Spider Bites , Spider Venoms , Spiders , Animals , Muscle Cramp/chemically induced , Spasm/chemically inducedSubject(s)
Anilides/adverse effects , Biphenyl Compounds/therapeutic use , Carcinoma, Basal Cell/drug therapy , Pyridines/adverse effects , Pyridines/therapeutic use , Skin Neoplasms/drug therapy , Aged , Carcinoma, Basal Cell/secondary , Dysgeusia/chemically induced , Female , Humans , Male , Middle Aged , Muscle Cramp/chemically induced , Nausea/chemically induced , Skin Neoplasms/pathologyABSTRACT
Introduction Muscle cramps constitute one of the leading adverse events of imatinib, the standard first-line treatment for advanced gastrointestinal stromal tumor (GIST). This study aims to assess the impact of L-carnitine on relieving cramps in patients with GIST taking imatinib. Materials and methods We reviewed our prospective database for patients with GIST who took L-carnitine (500-mg tablet, 2-3 times daily) for muscle cramps in Asan Medical Center. The assessment tool included severity by the numeric rating scale (NRS), frequency, duration of cramps, and questionnaire for the disturbance in basic activities of daily living (ADL), instrumental ADL (iADL), outdoor activity, or sleeping before and after L-carnitine treatment. Results We examined 42 patients [median age: 60 (range: 17-81) years; males, 52.4%] who received L-carnitine for cramps on NRS ≥ 4 intensity during 2016-2017. In 83.3% of patients (n = 35), the NRS score declined to <4 points, with 8 patients (19.0%) experiencing complete disappearance of symptoms [median response time: 10 (range: 2-30) days]. Moreover, the median duration of each episode and frequency decreased from 5 to 2 min and from 30 to 3 times per month (P < 0.001), respectively. We observed substantial improvement in all quality-of-life aspects after L-carnitine (ADL, 73.2%-14.6%; iADL, 73.2%-17.1%; sleeping, 78.0%-22.0%; outdoor activity, 68.3%-17.1%; P < 0.001). ConclusionL-carnitine could effectively relieve imatinib-related muscle cramps in patients with GIST. Accordingly, a randomized phase 3 study is currently ongoing (NCT03426722).
Subject(s)
Antineoplastic Agents/adverse effects , Carnitine/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Stromal Tumors/drug therapy , Imatinib Mesylate/adverse effects , Muscle Cramp/chemically induced , Protein Kinase Inhibitors/adverse effects , Activities of Daily Living , Adolescent , Adult , Aged , Aged, 80 and over , Carnitine/blood , Female , Gastrointestinal Neoplasms/blood , Gastrointestinal Stromal Tumors/blood , Humans , Male , Middle Aged , Quality of Life , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Severe hypokalemia with severe neurological impairment and electrocardiogram (ECG) abnormalities due to the misuse of triamterene/hydrochlorothiazide (HCTZ) in a bodybuilder has not yet been reported. CASE REPORT: A 22-year-old bodybuilder developed acute generalized muscle cramps, sensory disturbance of the distal lower and upper limbs, quadriparesis, and urinary retention. These abnormalities were attributed to severe hypokalemia of 1.8 mmol/L (normal range 3.4-4.5 mmol/L) due to misuse of triamterene/HCTZ together with fluid restriction. He was cardiologically asymptomatic, but ECG revealed a corrected QT (QTc) interval of 625 ms. On intravenous application of fluids along with intravenous and oral substitution of potassium, his condition rapidly improved, such that the sensory disturbances, quadriparesis, and bladder dysfunction completely resolved within 2 days after admission. CONCLUSIONS: Self-medication with diuretics along with fluid restriction may result in severe hypokalemia, paralysis, and ECG abnormalities. Those responsible for the management of bodybuilding studios and competitions must be aware of the potential severe health threats caused by self-medication with diuretics and anabolic steroids. Although triamterene is potassium-sparing, it may enhance the potassium-lowering effect of HCTZ.
Subject(s)
Diuretics/adverse effects , Hydrochlorothiazide/adverse effects , Hypokalemia/chemically induced , Paralysis/chemically induced , Self Medication/adverse effects , Triamterene/adverse effects , Weight Lifting , Diuretics/administration & dosage , Electrocardiography , Fluid Therapy , Humans , Hydrochlorothiazide/administration & dosage , Hypokalemia/therapy , Male , Muscle Cramp/chemically induced , Paralysis/therapy , Potassium/administration & dosage , Quadriplegia/chemically induced , Quadriplegia/therapy , Somatosensory Disorders/chemically induced , Somatosensory Disorders/therapy , Triamterene/administration & dosage , Urinary Retention/chemically induced , Urinary Retention/therapy , Young AdultABSTRACT
OBJECTIVE: To review evidence-based data with respect to safety and efficacy of alternate-day statin therapy in dyslipidaemia compared to the standard daily dose. METHODS: The literature review was conducted at Aga Khan University Hospital, Karachi from July, 2016 to August, 2017. Electronic database search was carried out to compile available literature using PubMed, Excerpta Medica database and Google Scholar. The most relevant evidence-based research articles published over 10 years were selected. The latest search was dated August 03, 2017. RESULTS: A total of 2,074 articles were initially located. Alternate day statin regimen was reported in 53% of articles. Adverse effects on muscle and tendon were reported in 69% of articles. After scrutiny, 19(0.9%) studies covering alternate-day statin-mediated muscle and tendon disorders and 9(0.4%) studies encompassing the potential pathophysiological mechanisms of statin-associated muscle and tendon injury were selected. Except pravastatin and lovastatin, alternate-day statin therapy was almost as effective in lowering total cholesterol, low-density lipoprotein cholesterol and triglycerides as the daily dosing with low incidence of muscle toxicity and tends in opathy. CONCLUSIONS: Alternate-day statin regimen was found to be very well tolerated and might be an effective and safe remedy in clinical practice.
Subject(s)
Dyslipidemias/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Muscle Cramp/chemically induced , Myalgia/chemically induced , Tendinopathy/chemically induced , Humans , Muscular Diseases/chemically inducedABSTRACT
Until recently, advanced BCC were only accessible to a highly morbid surgery not necessarily proving to be carcinologic, and leaving terrible dysmorphic sequelae hard to accept by the patient. Another possibility, the only one in case of metastatic BCC, was chemotherapy which efficacy has never been proven in a clinical trial. Radiotherapy is most often not accessible because of previous radiotherapy or because of the localization or the extension of the lesion. The discovery of the importance of the sonic hedgehog pathway in the physiopathology of BCC has opened a new strategy with the development of targeted anti SMO drugs inactivating the pathway. Two molecules have become available following Phase I and II studies: vismodegib (Erivedge®) the first in class indicated for locally advanced and metastatic BCC and sonidegib (Odomzo®) indicated only for locally advanced BCC. The pharmacokinetic profiles of sonidegib and vismodegib showed several differences. No head to head comparative studies are available between these two drugs. Their pivotal phase II studies had similar study designs and endpoints. The objective response rate (ORR) by central review for vismodegib was 47.6% (95% CI 35.5-60.6) at 21 months follow-up. The ORR for sonidegib according to central review at 18 months follow-up is 56.1% (95% CI 43.3-68.3). Although both treatments share a similar adverse event profile with possible numerically differences in incidence, most patients will discontinue hedgehog inhibitors treatment in the long term because of side effects. Some resistant cases to these drugs have been described but are rather rare. In case of resistance or bad tolerability to the drug future hopes rely on immunotherapy currently under investigation. © 2018. Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma.
Subject(s)
Anilides/therapeutic use , Antineoplastic Agents/therapeutic use , Biphenyl Compounds/therapeutic use , Carcinoma, Basal Cell/drug therapy , Molecular Targeted Therapy , Pyridines/therapeutic use , Skin Neoplasms/drug therapy , Smoothened Receptor/antagonists & inhibitors , Alopecia/chemically induced , Anilides/adverse effects , Anilides/pharmacokinetics , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Basal Cell Nevus Syndrome/drug therapy , Basal Cell Nevus Syndrome/genetics , Biphenyl Compounds/adverse effects , Biphenyl Compounds/pharmacokinetics , Carcinoma, Basal Cell/metabolism , Cisplatin/administration & dosage , Clinical Trials as Topic , Drug Resistance, Neoplasm , Dysgeusia/chemically induced , Fluorouracil/administration & dosage , Hedgehog Proteins/physiology , Humans , Multicenter Studies as Topic , Muscle Cramp/chemically induced , Mutation , Neoplasm Proteins/physiology , Patched-1 Receptor/genetics , Patched-1 Receptor/physiology , Patched-2 Receptor/genetics , Patched-2 Receptor/physiology , Pyridines/adverse effects , Pyridines/pharmacokinetics , Signal Transduction/drug effects , Skin Neoplasms/metabolism , Smoothened Receptor/geneticsABSTRACT
OBJECTIVES: The objective of this study was to investigate the influence of treatment with cholinesterase inhibitors (ChEIs) and calcineurin inhibitors (CNIs) on the occurrence of cramps in myasthenia gravis (MG) patients. METHODS: The frequency and duration of cramp and serum electrolytes were evaluated in 81 patients with MG. The patients were classified using Myasthenia Gravis Foundation of America postintervention status scores based on the treatment and the responsiveness to the treatment. Quantitative MG score, MG activities of daily living score, MG composite score, or MG quality of life 15 score was used to assess the health-related quality of life (QOL). RESULTS: Muscle cramps developed in 44 (54.3%) of 81 MG patients. The scores of MG activities of daily living, MG composite, or MG-QOL 15-item questionnaire in patients with cramp were significantly higher than those in patients without cramps (P = 0.002, P = 0.01, or P = 0.0022, respectively). The serum magnesium concentrations were lower in patients treated with CNI (n = 16) than in those not treated with CNI (n = 65) (P = 0.002). The probability of cramps was significantly higher in patients treated with ChEIs (≥180 mg/d) in addition to CNI than in patients who were treated with a low dose of ChEIs (≤60 mg/d) without concomitant CNI treatment (P = 0.017). CONCLUSIONS: Our data suggested that treatment with a high dose of ChEI and CNI accelerated the probability of cramps and reduced the QOL in MG patients.
Subject(s)
Calcineurin Inhibitors/administration & dosage , Calcineurin Inhibitors/adverse effects , Cholinesterase Inhibitors/administration & dosage , Cholinesterase Inhibitors/adverse effects , Muscle Cramp/chemically induced , Myasthenia Gravis/drug therapy , Activities of Daily Living , Aged , Calcium/blood , Cohort Studies , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Magnesium/blood , Male , Middle Aged , Muscle Cramp/blood , Myasthenia Gravis/blood , Quality of Life , Retrospective Studies , Surveys and QuestionnairesABSTRACT
Cabozantinib is a multikinase inhibitor approved for the treatment of metastatic medullary thyroid cancer and advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. While associations between serum creatine kinase (CK) elevations and other tyrosine kinase inhibitors used for the treatment of solid malignancies have been previously reported, we report a case of cabozantinib-associated CK elevation that was associated with musculoskeletal complaints by an RCC patient. Nine days following initiation of cabozantinib, the patient reported muscle cramps and serum CK had increased from levels 12 months earlier that were within normal limits to a grade 1 elevation of 244 units/L. Despite a dose reduction, her CK continued to rise over the next 2 months, leading to a peak CK of 914 units/L. Due to this grade 3 elevation, cabozantinib was permanently discontinued, and her CK subsequently returned to a grade 1 elevation within one week and then to baseline within 3 weeks. The temporal relationship between drug exposure and CK increase strongly suggests causality. To the authors' knowledge, this is the first reported case of CK elevation attributed to cabozantinib, but cabozantinib-induced CK elevations could be under-reported, and providers should monitor for musculoskeletal complaints during cabozantinib therapy.
Subject(s)
Anilides/adverse effects , Creatine Kinase/blood , Musculoskeletal Diseases/blood , Musculoskeletal Diseases/chemically induced , Pyridines/adverse effects , Female , Humans , Middle Aged , Muscle Cramp/chemically induced , Musculoskeletal Diseases/enzymologyABSTRACT
Statins are widely prescribed, yet statin muscle pain limits their use, leading to increased cardiovascular risk. No validated therapy for statin muscle pain exists. The goal of the study was to assess whether metformin was associated with reduced muscle pain. A secondary analysis of data from the ACCORD trial was performed. An ACCORD sub-study assessed patients for muscle cramps and leg/calve pain while walking, typical non-severe statin muscle pain symptoms. We compared muscle pain between patients using a statin (n = 445) or both a statin and metformin (n = 869) at baseline. Overall patient characteristics were balanced between groups. Unadjusted analysis showed fewer reports of muscle cramps (35%) and leg/calve pain while walking (40%) with statins and metformin compared to statin only (muscle cramps, 42%; leg/calve pain while walking, 47%). Multivariable regression demonstrated a 22% odds reduction for muscle cramps (P = 0.049) and a 29% odds reduction for leg/calve pain while walking (P = 0.01). Metformin appears to reduce the risk of non-severe statin muscle pain and additional research is needed to confirm the findings and assess metformin's impact on statin adherence and related cardiovascular outcomes.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Muscle Cramp/prevention & control , Muscle, Skeletal/drug effects , Myalgia/prevention & control , Aged , Biological Specimen Banks , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Electronic Health Records , Female , Follow-Up Studies , Humans , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Incidence , Male , Middle Aged , Muscle Cramp/chemically induced , Muscle Cramp/epidemiology , Muscle Cramp/physiopathology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiopathology , Myalgia/chemically induced , Myalgia/epidemiology , Myalgia/physiopathology , National Heart, Lung, and Blood Institute (U.S.) , Randomized Controlled Trials as Topic , Risk , Severity of Illness Index , United States/epidemiology , WalkingSubject(s)
Amitriptyline/analogs & derivatives , Anilides/adverse effects , Muscle Cramp/chemically induced , Muscle Cramp/drug therapy , Muscle Relaxants, Central/therapeutic use , Pyridines/adverse effects , Aged , Amitriptyline/therapeutic use , Female , Humans , Male , Middle Aged , Retrospective StudiesSubject(s)
Amines/therapeutic use , Anilides/adverse effects , Cyclohexanecarboxylic Acids/therapeutic use , Disease Management , Muscle Cramp/chemically induced , Muscle Cramp/drug therapy , Pyridines/adverse effects , gamma-Aminobutyric Acid/therapeutic use , Aged, 80 and over , Analgesics/therapeutic use , Gabapentin , Humans , Male , Muscle Cramp/diagnosisABSTRACT
PURPOSE: The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia. METHODS: Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients' characteristics or not. RESULTS: We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender. CONCLUSIONS: The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib.
Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Imatinib Mesylate/adverse effects , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Octamer Transcription Factor-1/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Aged , Aged, 80 and over , Edema/chemically induced , Edema/genetics , Factor Analysis, Statistical , Female , Genotype , Humans , Male , Middle Aged , Muscle Cramp/chemically induced , Muscle Cramp/genetics , Pharmacogenetics , Polymorphism, Genetic , Prognosis , Sex CharacteristicsSubject(s)
Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/drug therapy , Lower Extremity/blood supply , Muscle Cramp/chemically induced , Tamoxifen/adverse effects , Female , Humans , Muscle Cramp/diagnosis , Muscle Cramp/metabolism , Muscle Cramp/physiopathology , Nitric Oxide/metabolism , Posture , Regional Blood Flow , VasodilationABSTRACT
Muscle cramps are side effects commonly associated with tyrosine kinase inhibitor (TKI) treatment. Patients suffering from muscle cramps are treated with various medications such as calcium, magnesium and vitamin supplements, but these therapies are often ineffective. We report two patients with chronic myelogenous leukemia who developed muscle cramps caused by TKI. These patients were treated successfully with levocarnitine. Both of our cases revealed the beneficial effects of levocarnitine treatment on TKI-induced muscle cramps.