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Phototoxic reaction to oral terbinafine due to Tinea capitis in a child.

We report the case of an 18-month-old boy who developed a phototoxic skin reaction to terbinafine on his scalp, ears, and face in the form o … cation of antifungal cream (miconazole), 10% Ichthyol cream in the evening, and antifungal shampoo (ketoconazole) twice a week. After two weeks of therapy, we observed initial regression of scalp lesions. Oral terbinafine was well-tolerated, and the patient did not experience any side-effects. Laboratory findings included liver function tests and were within n …

Randomized clinical trial to compare the efficacy of ivermectin versus placebo to negativize nasopharyngeal PCR in patients with early COVID-19 in Peru (SAINT-Peru): a structured summary of a study protocol for randomized controlled trial.

OBJECTIVES: The primary objective is to determine the effect of a daily dose of ivermectin administered in three consecutive days to non-sev … dine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir, cobicistat or critical CYP3A4 substrate drugs such as warfarin. Exclusion criteria 1. COVID-19 pneumonia diagnosed by the attending physician (oxygen saturation < 95% or lung examination) 2. Positive …

A Comprehensive Review of the Diagnosis and Management of Acute Liver Failure.

Acute liver failure (ALF) is a rare and specific form of severe hepatic dysfunction characterized by coagulopathy and hepatic encephalopathy in a patient with no known liver disease. ALF carries a high morbidity and mortality. Careful attention should be given to hemodynamics and metabolic parameters along with the active surveillance of infections. Timely transfer and supportive management are important in an intensive care unit in a liver transplant center. Identifying patients who will and will not improve with medical management and may need emergent liver transplantation is critical. In t

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… The most common causes of non-acetaminophen toxicity are antituberculosis drugs (mainly isoniazid), antimicrobials (nitrofurantoin and ketoconazole), antiepileptics (valproic acid, phenytoin), and non-steroidal anti-inflammatory drugs (NSAIDs) [ 3 ]. … Cytomegalovirus Epstein–Barr virus Herpes simplex virus 1 and 2 Varicella-zoster virus Adenovirus Dengue virus Medications | Acetaminophen Anti-tuberculosis (Isoniazid, Rifampin, Pyrazinamide) Statins Non-steroidal anti-inflammatory drugs Sulfa drugs Phenytoin Carbamazepine MDMA (ecstasy) Flucloxacillin Ketoconazole …

Case Report: Erythema gyratum repens associated with adenomyosis and endometriosis: an immunological twist?

A 37-year-old non-Caucasian woman presented with a 2-year history of pruritic, concentric erythematous plaques refractory to multiple topical and systemic therapies. The clinical findings were highly suggestive of erythema gyratum repens (EGR), a rare figurate dermatosis classically associated with paraneoplastic syndromes. Routine laboratory investigations and an autoantibody panel were unremarkable, except for a significantly elevated CA-125 level. A targeted gynecological assessment, prompted by a chronic history of pelvic pain and menorrhagia, identified severe adenomyosis with concomitant

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… Prior empiric treatments included topical clobetasol propionate 0.05% ointment twice daily for 6 weeks, oral prednisone (0.5 mg/kg/day) for 2 weeks, topical ketoconazole 2% cream for 4 weeks, and oral fluconazole 150 mg weekly for 4 weeks, all without clinical improvement. …

Oxidized Lipids in Persistent Pain States.

Chemotherapy, nerve injuries, or diseases like multiple sclerosis can cause pathophysiological processes of persistent and neuropathic pain. Thereby, the activation threshold of ion channels is reduced in peripheral sensory neurons to normally noxious stimuli like heat, cold, acid, or mechanical due to sensitization processes. This leads to enhanced neuronal activity, which can result in mechanical allodynia, cold allodynia, thermal hyperalgesia, spontaneous pain, and may initiate persistent and neuropathic pain. The treatment options for persistent and neuropathic pain patients are limited; f

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… . | MIA model for osteoarthritis and osteotomy model; partial sciatic nerve injury- induced neuropathic pain | ( Inoue et al., 2008 ; Thirunavukkarasu et al., 2017 ) CYP2J2 | Oxidizes fatty acids (LA, AA) | Increased in the PNS during inflammatory and paclitaxel-induced neuropathic pain | Ketoconazole … In this context, treatment of rodents with the unspecific CYP-epoxygenase inhibitor ketoconazole caused a reduction of pain hypersensitivity during CFA-induced inflammation ( Ruparel et al., 2012a ). CYP-epoxygenases are essential proteins for the biotransformation of xenobiotic substances. …

Do payers value rarity? An analysis of the relationship between disease rarity and orphan drug prices in Europe.

Background and Objective: Orphan drugs have been a highlight of discussions due to their higher prices than non-orphan drugs. There is currently no European consensus on the method of value assessment for orphan drugs. This study assessed the relationship between the prevalence of rare diseases and the annual treatment cost of orphan drugs in France, Germany, Italy, Norway, Spain, Sweden, and UK. Methods: Approved orphan drugs and prevalence data were extracted from the European Medicines Agency website. Annual treatment costs were calculated using ex-factory price. Simple regression was used

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… Haemophilia B 0.10 Ilaris* Cryopirin associated syndromes 0.05 Imbruvica Mantle cell lymphoma 0.17 Imnovid Multiple myeloma 2.20 Increlex Laron syndrome 2.00 Inovelon Epilepsy 1.50 Jakavi* Chronic idiopathic myelofibrosis 0.50 Kalydeco Cystic fibrosis 1.20 Kanuma Lysosomal acid lipase deficiency 0.20 Ketoconazole … Cryopirin associated syndromes | 0.05 Imbruvica | Mantle cell lymphoma | 0.17 Imnovid | Multiple myeloma | 2.20 Increlex | Laron syndrome | 2.00 Inovelon | Epilepsy | 1.50 Jakavi* | Chronic idiopathic myelofibrosis | 0.50 Kalydeco | Cystic fibrosis | 1.20 Kanuma | Lysosomal acid lipase deficiency | 0.20 Ketoconazole …

Case Report: Acute Kidney Injury Due to Chronic Milk-Alkali Syndrome in a Patient With Colon Cancer.

BACKGROUND: Common causes of hypercalcemia include primary hyperparathyroidism and paraneoplastic syndrome of malignancy. Because of this, physicians can easily miss extrinsic causes of hypercalcemia such as milk-alkali syndrome in patients with cancer. We successfully treated a case of acute kidney injury due to severe hypercalcemia caused by milk-alkali syndrome due to long-term milk drinking in a patient with colon cancer. CASE DESCRIPTION: A 62-year-old man was referred to nephrology for hypercalcemia and azotemia that was found during preoperative evaluation for colon cancer surgery. The

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… Ketoconazole and hydroxychloroquine are used for hypercalcemia related to sarcoidosis. And hemodialysis with low or zero calcium dialysate and continuous renal replacement therapy are useful in patients with severe hypercalcemia and azotemia like this patient ( 1 ). …

Fungal, Viral, and Other Oddball Infections and the Immunosuppressed Patient

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… Effective treatment involves nystatin suspensions, oral ketoconazole, fluconazole, or itraconazole. Oropharyngeal candidiasis should be treated with fluconazole for 7 days and perhaps beyond for immunocompromised patients. …

Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor.

Model-informed drug development (MIDD) was central to the development of the oral proteasome inhibitor ixazomib, facilitating internal decisions (switch from body surface area (BSA)-based to fixed dosing, inclusive phase III trials, portfolio prioritization of ixazomib-based combinations, phase III dose for maintenance treatment), regulatory review (model-informed QT analysis, benefit-risk of 4 mg dose), and product labeling (absolute bioavailability and intrinsic/extrinsic factors). This review discusses the impact of MIDD in enabling patient-centric therapeutic optimization during the develo

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… ixazomib was metabolized by multiple CYP isoforms, with 42% relative contribution of CYP3A4 estimated based on the results of in vitro studies using human cDNA‐expressed CYP isozymes. 1 In clinical DDI studies, ixazomib AUC was not meaningfully altered upon coadministration of strong CYP3A inhibitors (ketoconazole … The effects of coadministration of the strong CYP3A inhibitors ritonavir and itraconazole on the PK of ixazomib were investigated, and findings showed similar geometric least‐squares mean AUC ratios to those simulated for ketoconazole and clarithromycin ( Figure 3 b ). …

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience.

Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts' immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The

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… In castration-resistant prostate cancer, with the invention of new class antitestosterone drugs (enzalutamide and abiraterone), the role for CYP, etoposide, estramustine, and ketoconazole diminished. … On the other hand, in a limited number of patients who were progressed on standard approaches and still in need for treatment, oral etoposide and ketoconazole may have a role. …

Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome.

BACKGROUND: Subfertility due to anovulation is a common problem in women. First-line oral treatment is with antioestrogens such as clomiphen … ing of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were ve …

Keyword Index for Volume 98

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… intra-arterial chemotherapy 1039 intracranial invasion 363 intrauterine factors 664 invasion 113, 356, 1274 invasive breast cancer 277 invasive ductal carcinoma 1993 invasiveness 1348 ionising radiation 1226 Iran 1857 irinotecan 693, 1210, 1312, 1619 iron 580 job satisfaction 1046 job stress 1046 ketoconazole …

Effect of eszopiclone on sleep, fatigue, and pain in patients with mucositis associated with hematologic malignancies.

PurposePatients with malignancy sometimes develop painful mucositis and require patient-controlled analgesia (PCA) to treat their pain. Pain disrupts sleep and there is some evidence that analgesic medications also disrupt sleep. This study examined whether treatment with the sedative hypnotic eszopiclone could improve self-reports of sleep, fatigue, and pain as well as decrease opioid self-administered via PCA.MethodsInpatients who developed mucositis severe enough to require PCA treatment were randomized double-blind to a 2-day trial on eszopiclone or placebo-administered at bedtime. Patient

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… Patients who were >64 years or individuals receiving potent 3A4 inhibitors such as ketoconazole received 2 mg eszopiclone. These doses are commonly employed and the dose adjustment for older patients and for patients receiving 3A4 inhibitors is suggested in the prescribing information. …

Vincristine-Induced Seizure from Drug Interactions: A Case Report and Review of Literature.

Vincristine (VCR) as a key drug for the treatment of acute lymphoblastic leukemia (ALL) is associated with neurotoxicity. We present a young man with a history of controlled childhood seizures who was diagnosed with pre-B-cell ALL and developed generalized tonic-clonic seizures following the Cancer and Leukemia Group B (CALGB) 8811 regimen. The patient also received oral itraconazole to prevent fungal infection initiated by chemotherapy. Possible causes of seizure, including electrolyte abnormalities, hypoglycemia, central nervous system infection or inflammation, were ruled out. According to

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… CYP2C9 (moderate), CYP3A4 (moderate) Itraconazole | 28.3–47.4 h | CYP3A4 (strong), P-gp/ABCB1 Voriconazole | Variable, dose dependent | CYP3A4 (strong), CYP2C19 (moderate), CYP2C9 (weak) Posaconazole | Oral suspension: 35 h (range: 20–66 h), tablet: 26–31 h, injection: 27 h | CYP3A4 (strong), P-gp/ABCB1 Ketoconazole …

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed b

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… Ketoconazole is being used for treating patients with recurrent glioma or BC brain metastasis [ 83 ]. The antifungal drug ketoconazole blocks the effect of tGLI1, a protein involved in upregulation of the cancer stem-cell subpopulation and in the activation of astrocytes in glioblastomas [ 91 ]. … An FDA-Approved Antifungal, Ketoconazole, and Its Novel Derivative Suppress TGLI1-Mediated Breast Cancer Brain Metastasis by Inhibiting the DNA-Binding Activity of Brain Metastasis-Promoting Transcription Factor TGLI1 Cancers 2022 14 4256 10.3390/cancers14174256 36077791 PMC9454738 92. Brandl M. …

Development Trends of Janus Kinase Inhibitors (JAKi) Over Three Decades: From Common to Rare Diseases.

Janus kinase inhibitors (JAKi) have undergone three decades of research and development, demonstrating substantial therapeutic efficacy and broad clinical applicability in autoimmune diseases, inflammatory disorders, hematopoietic malignancies, and a spectrum of rare diseases. However, their research and development are constrained by three key challenges: the difficulty in target selection and safety concerns arising from their effects on cellular signaling pathways, as well as the challenges in formulating optimal dosing regimens due to interindividual variability in pharmacokinetics. In thi

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… Gupta et al reported that the area under the curve (AUC) and maximal plasma concentration (C max ) increased by 79% and 27%, respectively, with fluconazole co-administration and by 103% and 16%, respectively, with ketoconazole respectively. 98 Patients with impaired hepatic function require longer dosing … Evaluation of the effect of fluconazole and ketoconazole on the pharmacokinetics of tofacitinib in healthy adult subjects . Clin Pharmacol Drug Dev . 2014 ; 3 ( 1 ): 72 – 77 . doi: 10.1002/cpdd.71 27128233 99. Zheng J , Xin Y , Zhang J , et al. …

Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma.

In this report, a panel of European myeloma experts discuss the role of pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Based on the available evidence, the combination of pomalidomide and low-dose dexamethasone is a well-tolerated and effective treatment option for patients with RRMM who have exhausted treatment with lenalidomide and bortezomib. The optimal starting dose of pomalidomide is 4 mg given on days 1-21 of each 28-day cycle, whereas dexamethasone is administered at a dose of 40 mg weekly (reduced to 20 mg for patients aged >75 years). The treatment

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… Table 1 Pharmacokinetic properties of lenalidomide and pomalidomide 17 , 88 Abbreviations: CYP, cytochrome P 450; P-gp, P-glycoprotein. a Common P-gp inhibitors include cyclosporine, clarithromycin, itraconazole, ketoconazole, quinidine and verapamil. b Common strong inhibitors of CYP1A2 include ciprofloxacin … ∼9.5 Myeloma patients | ∼3–5 | ∼7.5 | | Excretion (% excreted unchanged in urine) | 82 | 2 | | Key drug–drug interactions P-gp substrate | Yes; monitor closely if co-administered with P-gp inhibitors a | Yes; but no clinically relevant effect seen when co-administered with the P-gp inhibitor ketoconazole …

The SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT) to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission in low risk, non-severe COVID-19 patients in the first 48 hours after symptoms onset: A structured summary of a study protocol for a randomized control pilot trial.

OBJECTIVES: The primary objective is to determine the efficacy of a single dose of ivermectin, administered to low risk, non-severe COVID-19 … dine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat. Use of critical CYP3A4 substrate drugs such as warfarin. *Women of child bearing age may participate if they use a safe contraceptive method for the entire period of the study and at lea …

Нейрофармакология каннабиноидов: всеобъемлющий обзор доклинических и клинических данных о экстрактах гемп-деривных веществ и активных соединениях.

Каннабис сатива содержит более 120 фитоканнабиноидов, причем наиболее характерными из них являются Δ9-тетрагидроканнабинол (THC) и каннабидиол (CBD). В настоящем обзоре обобщаются доклинические и клинические данные об экстрактах гематома, каннабиноидах и активных соединениях. THC действует главным образом как частичный агонист каннабиноидного рецептора типа 1 (CB1) и типа 2 (CB2), приводящий к психоактивным, аппетитным, антиэметическим и анальгетическим эффектам. КБР не является опьяняющим и имеет мультимодальный профиль, включающий негативную аллостерическую модуляцию CB1, обратное агонизм CB

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… CBD inhibits CYP2C19, CYP3A4, and several UGT isoforms, while both CBD and THC are substrates of CYP3A4 and CYP2C subfamily enzymes, so inhibitors (e.g., ketoconazole) raise and inducers (e.g., rifampin) lower cannabinoid exposure. … Mechanism/Enzyme | Affected Drugs | Clinical Consequence and Management CBD inhibits CYP2C19 | Clobazam (→N-desmethylclobazam), diazepam, omeprazole | ↑Active metabolite > 200%; increased sedation—monitor and reduce clobazam dose CBD/THC via CYP3A4 | Ketoconazole, clarithromycin (inhibitors); rifampin …

Evaluation of Proteasome Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, and it has a worse prognosis than non-small cell lung cancer. The pathomechanism of IPF is not fully understood, but it has been suggested that repeated microinjuries of epithelial cells induce a wound healing response, during which fibroblasts differentiate into myofibroblasts. These activated myofibroblasts express α smooth muscle actin and release extracellular matrix to promote matrix deposition and tissue remodeling. Under physiological conditions, the remodeling process stops once wound heal

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… Since nintedanib is a substrate of P-glycoprotein (P-gp) and CYP3A4, the co-administration with oral doses of P-gp and CYP3A4 inhibitors (e.g., ketoconazole and erythromycin) should be avoided, so as not to increase exposure to nintedanib [ 97 ]. … Effects of Ketoconazole and Rifampicin on the Pharmacokinetics of Nintedanib in Healthy Subjects. Eur. J. Drug Metab. Pharmacokinet. 2018;43:533–541. doi: 10.1007/s13318-018-0467-9. 98. …