cholecalciferol and Drug-Related-Side-Effects-and-Adverse-Reactions

Interactions between drugs and vitamin D have received only little or no attention in the medical and pharmaceutical world in the past. Since more and more drugs are used for the treatment of patients, this topic is increasingly relevant. As such interactions impact the health of the patient and the action and side effects of the drug, physicians and pharmacists should pay more attention to such interactions in the future. A number of drugs can interfere with the vitamin D and bone metabolism. The drug-induced activation of the pregnane X receptor (PXR) is likely to enhance CYP24 expression and the catabolism of 25(OH)D, leading to vitamin D deficiency. PXR-ligands include a wide variety of pharmaceutical agents, such as antiepileptic drugs, taxol, rifampicin, and human immunodeficiency virus protease inhibitors such as ritonavir and saquinavir. Beside this, the medication oriented supplementation of vitamin D can also ameliorate the pharmacologic action of many drugs, such as bisphosphonates, statins and cytostatic drugs.

Topics: Bone and Bones; Cholecalciferol; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Pregnane X Receptor; Receptors, Steroid; Vitamin D Deficiency

Rodenticides are second only to insecticides in the prevalence of pesticide exposure. Hundreds of rodenticide products currently exist, yet only a handful of them are involved in most toxicoses of companion animals. The most commonly reported toxicoses in the United States are those caused by anticoagulant rodenticides, bromethalin, cholecalciferol, strychnine, and zinc phosphide. The pathophysiologic findings, diagnosis, and treatment of each of these five rodenticides are discussed.

Topics: Aniline Compounds; Animals; Cat Diseases; Cats; Cholecalciferol; Dog Diseases; Dogs; Drug-Related Side Effects and Adverse Reactions; Phosphines; Rodenticides; Strychnine; Zinc Compounds

The use of high-dose vitamin D supplementation has increased in recent years. However, relatively little is known about the safety of long-term high doses.. To investigate the safety of a monthly high-dose of vitamin D. Data were collected in a randomized, double blind, placebo-controlled trial of 5108 adults aged 50-84 years old from Auckland, New Zealand. Participants were given monthly doses of 100,000 IU vitamin D. In total, 419 (16.5%) participants taking vitamin D and 399 (15.8%) taking placebo reported ≥1 adverse event. Compared to placebo, the hazard ratio (HR) of reporting first adverse event in the vitamin D group was 1.03 (95% CI: 0.90, 1.18; p = 0.63). Despite a slightly higher incidence of recurrent adverse events in vitamin D arm, the incidence rate ratio (1.17) was not significantly higher in vitamin D (95% CI: 0.97, 1.41; p = 0.10). All regression results were adjusted for age, sex, and ethnicity. There was no difference between study arms in terms of participants' allocation perception (p = 0.52).. Monthly supplementation of 100,000 IU vitamin D3 for a median of 3.3 years did not affect participant-reported adverse events.. clinicaltrials.gov Identifier: ACTRN12611000402943; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12611000402943.

Topics: Aged; Aged, 80 and over; Cholecalciferol; Dietary Supplements; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Incidence; Male; Middle Aged; Self Report

The purpose of the study was to evaluate the efficacy and safety of vitamin D3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I-IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n = 56) or 4000 IU D3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL).

Topics: Adult; Aged; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Arthralgia; Bone Density; Breast Neoplasms; Cholecalciferol; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Letrozole; Middle Aged; Musculoskeletal Diseases; Nitriles; Triazoles; Vitamin D

Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines' levels.. In a randomized, double blind study of 45 IFNβ-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented.. 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed.. Vitamin D supplementation to IFN-β treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN-β related FLS.. ClinicalTrials.gov ID: NCT01005095.

Topics: Adult; Aged; Cholecalciferol; Cytokines; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Interferon-beta; Interleukin-17; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Treatment Outcome

Care of elderly patients after hip fracture is not well established.. We enrolled 173 patients with acute hip fracture who were 65 years or older (79.2% women; mean age, 84 years; 77.4% living at home). Using a factorial design, we randomly allocated patients to extended physiotherapy (PT) (supervised 60 min/d during acute care plus an unsupervised home program) vs standard PT (supervised 30 min/d during acute care plus no home program; single-blinded), and to cholecalciferol therapy, 2000 vs 800 IU/d (double-blinded). Primary outcome was rate of falls; secondary outcome was rate of hospital readmissions during the 12-month follow-up. All analyses included 173 individuals and used multivariate Poisson regression analyses.. At baseline, 50.9% of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7% of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions. Because this was a factorial design trial, all analyses tested the main effect of each treatment while controlling for the other in 173 participants. Extended vs standard PT reduced the rate of falls by 25% (95% confidence interval [CI], -44% to -1%). Cholecalciferol treatment, 2000 vs 800 IU/d, did not reduce falls (28%; 95% CI, -4% to 68%), but reduced the rate of hospital readmissions by 39% (95% CI, -62% to -1%).. Extended PT was successful in reducing falls but not hospital readmissions, whereas cholecalciferol treatment, 2000 IU/d, was successful in reducing hospital readmission but not falls. Thus, the 2 strategies may be useful together because they address 2 different and important complications after hip fracture.

Topics: Accidental Falls; Aged; Aged, 80 and over; Bone Density Conservation Agents; Cholecalciferol; Combined Modality Therapy; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Hip Fractures; Humans; Male; Multivariate Analysis; Patient Readmission; Physical Therapy Modalities; Poisson Distribution; Recurrence; Regression Analysis; Switzerland

Recent evidence has demonstrated that both acute and chronic exposure to particulate air pollution are risk factors for respiratory tract infections and increased mortality from sepsis. There is therefore an urgent need to establish the impact of ambient particulate matter (PM) on innate immune cells and to establish potential strategies to mitigate against adverse effects. PM has previously been reported to have potential adverse effects on neutrophil function. In the present study, we investigated the impact of standard urban PM (SRM1648a, NIST) and PM

Topics: Cholecalciferol; Drug-Related Side Effects and Adverse Reactions; Escherichia coli; Humans; Interleukin-8; Lipopolysaccharides; Neutrophils; Vitamin D; Vitamins

Knowledge about complications of chronic ultra-high dose vitamin D supplementation is limited. We report a patient with primary progressive multiple sclerosis (MS) who presented with generalized weakness caused by hypercalcemia after uncontrolled intake of more than 50,000 IU of cholecalciferol per day over several months. Various treatment strategies were required to achieve normocalcemia. However, renal function improved only partly and further progression of MS was observed. We conclude that patients need to be informed about the risks of uncontrolled vitamin D intake and neurologists need to be alert of biochemical alterations and symptoms of vitamin D toxicity.

Topics: Cholecalciferol; Drug-Related Side Effects and Adverse Reactions; Humans; Hypercalcemia; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Renal Insufficiency; Vitamins

To determine the effects of caffeine ingestion on the development of femur and role of vitamin D3 in preventing these effects in BALB/c mice.. Experimental study.. Department of Anatomy, Army Medical College, Rawalpindi, in cooperation with NIH (National Institute of Health), Islamabad, from October 2014 to October 2015.. Thirty (100%) BALB/c mice, 50% male and female each, three weeks old, weighing 12-14 grams were taken and divided equally and randomly into three groups, each having 10 (33.3%) mice; 5 (16.6%) male and female. G1 (control group) was given normal diet with water ad libitum. G2and G3(experimental groups) were given 10 mg of caffeine per 100g body weight, three days a week, through oral gavage for 60 days on alternate days. However, experimental group G3was additionally provided 0.1µg vitamin D3daily, through oral gavage for 60 days. Experimental groups were compared with control group and data was analyzed statistically.. The mean weight of mice femur of G1(control group) was 0.387 ±0.019 g; while mean weights of right femur of G2and G3(experimental groups) were 0.316 ±0.020 g and 0.345 ±0.020 g, respectively. Similarly, mean right femur length of group G1 was 20.70 ±0.609 mm; while for groups G2 and G3, it was 24.382 ±1.087 mm and 22.966 ±0.822 mm, respectively. In comparison with group G1for groups G2and G3, femur weight decreased, however femur length increased.. Caffeine intake caused femur length to increase and weight to decrease, but treatment with vitamin D3.

Topics: Animals; Caffeine; Cholecalciferol; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Femur; Mice; Mice, Inbred BALB C; Protective Agents

Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60-70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the "Rule of Three" was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Models, Biological; Predictive Value of Tests

Topics: Adrenal Cortex Hormones; Cholecalciferol; Drug-Related Side Effects and Adverse Reactions; Metabolism; Rats; Research; Toxicology