scholarly journals Importance of Therapeutic Drug Monitoring to Detect Drug Interaction between Pazopanib and Warfarin: A Case Report

2020 ◽  
Vol 23 ◽  
pp. 200-205
Author(s):  
Shinya Takasaki ◽  
Hisanobu Adachi ◽  
Yoshihide Kawasaki ◽  
Masafumi Kikuchi ◽  
Akihiro Ito ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Liver Dysfunction ◽  
Kinase Inhibitor ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Close Monitoring ◽  
Blood Concentrations ◽  
Patients At Risk

Pazopanib is an orally available multi-tyrosine kinase inhibitor and has been used to treat renal cell carcinoma (RCC). Here, we report the case of a patient with RCC with an increased prothrombin time-international normalized ratio (PT-INR) due to pazopanib therapy. In addition, we have reported the change in the blood levels of pazopanib. A 75-year-old man underwent a left nephrectomy for RCC. Four years later, his cancer recurred and pazopanib therapy was initiated. He was also taking warfarin for atrial fibrillation and his PT-INR was constant at approximately 2. His warfarin dose was reduced from 3.5 mg/day to 3.0 mg/day on day 10 because his PT-INR increased from 2.19 to 3.07 compared to that before starting pazopanib. On day 28, his PT-INR further increased to 4.34, and his aspartate aminotransferase, alanine transaminase, and alkaline phosphatase levels increased. The target concentration of pazopanib was 20.5 to 50.3 µg/mL, but his blood concentrations were 92.1 µg/mL on day 6 and 93.7 µg/mL on day 13. Therefore, both pazopanib and warfarin were discontinued. One week later, his laboratory tests recovered, and hence, warfarin treatment was resumed. However, pazopanib therapy was terminated due to concerns about liver dysfunction. His hepatic dysfunction and increased PT-INR were considered to be due to pazopanib treatment. Pazopanib has been reported to have no effect on the pharmacokinetics of warfarin in clinical patients. In this case, blood levels of pazopanib were abnormally high, possibly causing liver dysfunction and drug interactions, leading to his PT-INR prolongation. TDM monitoring, in addition to the recommended monitoring for pazopanib hepatotoxicity, may help identify patients at risk for drug interactions. For patients receiving concomitant pazopanib and warfarin, close monitoring of PT-INR is warranted.

scholarly journals International Normalized Ratio (INR) Increases amongst Two Patients Living with HIV on Warfarin after Being Switched from a Nevirapine to a Dolutegravir-Based Antiretroviral Regimen

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Natalie Sang ◽  
Sonak Pastakia ◽  
Samuel Nyanje
Keyword(s):  
Drug Interactions ◽  
International Normalized Ratio ◽  
Hiv Treatment ◽  
Treatment Programs ◽  
Cytochrome P450 Enzyme ◽  
Close Monitoring ◽  
Medication Regimen ◽  
Emergency Plan ◽  
First Case ◽  
Living With Hiv

The increased use of dolutegravir-based regimens in the treatment of HIV is unmasking drug interactions, particularly in patients who were previously on nevirapine. Nevirapine is an enzyme inducer and increases the dosing requirements for cytochrome P450 enzyme substrates including warfarin. Upon discontinuing nevirapine, close monitoring of drugs with narrow therapeutic indices is paramount since dosing requirements may significantly reduce, increasing the probability of toxicity development. We present two cases describing interactions experienced by patients living with HIV, while transitioning from nevirapine to dolutegravir-based HIV regimens. The first case describes a 70-year-old man living with HIV and diabetes, while the second case describes a 60-year-old woman living with HIV. They were diagnosed with unprovoked deep vein thrombi, and while receiving treatment with warfarin, their HIV medication regimen was changed from lamivudine, zidovudine, nevirapine, and septrin to lamivudine, tenofovir, dolutegravir, and septrin. During the weeks following this switch, warfarin requirements decreased resulting in supratherapeutic INRs. With the continued promotion of dolutegravir-based HIV regimens as the preferred option for the treatment of HIV in President’s Emergency Plan for AIDS Relief (PEPFAR) supported HIV treatment programs in Africa, clinicians must be aware of the potentially life-threatening consequences of switching antiretroviral regimens. It is hoped that a greater awareness of this potential side effect could lead to increased monitoring and prevention of the consequences of drug interactions.

Inductive Effect of a Ritonavir-Containing Hepatitis C Treatment Regimen on Warfarin in a Patient—A Case Report

2018 ◽  
Vol 32 (4) ◽  
pp. 470-473 ◽  
Author(s):  
Audrey C. Rosene ◽  
Jaymee L. Gaspar
Keyword(s):  
Hepatitis C ◽  
Treatment Regimen ◽  
Case Reports ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Close Monitoring ◽  
Anticoagulation Management ◽  
Hepatitis C Treatment ◽  
History Of ◽  
Repeated Use

The warfarin management strategy for a mechanical mitral valve patient initiated on a ritonavir-based hepatitis C treatment regimen is described. A 62-year-old male with a past medical history of hepatitis C genotype 1a and stable warfarin dose history was initiated on a concomitant Viekira Pak® (VP) regimen containing ritonavir. Prior to initiation of the VP for hepatitis C treatment, the patient was stable on a warfarin dose of 40 mg/wk for 5 months. During treatment with VP, the patient experienced a markedly decreased international normalized ratio (INR) and warfarin requirements ultimately increased 125% from baseline (90 mg/wk). Effective anticoagulation management throughout and surrounding the treatment period for hepatitis C involved frequent warfarin dose adjustments, including preemptive changes, close monitoring, and repeated use of enoxaparin to ensure adequate thrombotic prophylaxis. This is believed to be the first reported case describing the management of warfarin in a patient with hepatitis C who received VP and required a drastically increased weekly warfarin dose. The possible mechanisms suggestive of this interaction and similar case reports in the literature are discussed.

scholarly journals 2112. Voriconazole for Primary Prophylaxis: A Decade of Trends and Outcomes

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S715-S715
Author(s):  
Ahmad Mourad ◽  
Melissa D Johnson ◽  
John R Perfect
Keyword(s):  
Drug Interactions ◽  
Fungal Infections ◽  
Primary Prophylaxis ◽  
Antifungal Prophylaxis ◽  
University Hospital ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Blood Concentrations ◽  
The Mean ◽  
Microbiological Data

Abstract Background Invasive fungal infections (IFI) continue to affect the immunocompromised patient population. Many of these patients require antifungal prophylaxis. Voriconazole is an azole antifungal that has been utilized for preventing IFIs but does not have an approved indication for prophylaxis. Methods Adult patients admitted to Duke University Hospital from January 1, 2005 to December 31, 2015 who had received at least 2 days of systemic voriconazole as primary prophylaxis were included in this retrospective medical records review. Demographics, underlying comorbidities, adverse events, drug interactions, voriconazole blood concentrations, and microbiological data were assessed. Results Our review identified 403 patients receiving voriconazole for primary prophylaxis. 220 (55.6%) were male, 303 (75.2%) were Caucasian, and the mean age was 46.0 ± 15.7 years. 233 (57.8%) had leukemia, and 63 (15.6%) had lymphoma. 301 (74.7%) underwent hematopoietic transplant (BMT), and 45 (11.2%) had a solid-organ transplant. 176 (43.7%) patients received chemotherapy and 261 (64.8%) received immunosuppressive drugs. The mean voriconazole total daily maintenance dose was 416.1 ± 65.9 mg (5.5 ± 1.6 mg/kg/day). Patients received inpatient voriconazole for a mean of 19.5 ± 16.5 days. 371 (92.1%) patients received a concomitant interacting drug. Only 140 (43.7%) patients had therapeutic drug monitoring. The mean first voriconazole serum concentration was 1.8 ± 1.7 mg/L. 87 (21.6%) patients discontinued voriconazole prematurely; 41 (10.2% overall) of these patients had an adverse event requiring discontinuation. 5 had breakthrough fungal infections with microbiological data identifying a fungal species, which included Rhizopus spp. among others. Conclusion Voriconazole is frequently used for primary prophylaxis of IFIs and most commonly in BMT. It appears to be relatively well tolerated with some adverse side-effects (~10%) despite many potential drug–drug interactions and provides appropriate fungal coverage for many immunosuppressed patients. However, few patients had breakthrough fungal infections while receiving voriconazole. In a real-world setting, voriconazole can provide antifungal prevention in certain high-risk patients. Disclosures All authors: No reported disclosures.

Possible Amiodarone−Warfarin Interaction: A Reemphasis on a Potentially Dangerous Drug−Drug Interaction

2007 ◽  
Vol 20 (6) ◽  
pp. 469-473
Author(s):  
Roda Plakogiannis ◽  
Regina Ginzburg
Keyword(s):  
Potent Inhibitor ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Warfarin Interaction ◽  
Bleeding Complications ◽  
Cytochrome P450 Enzyme ◽  
Close Monitoring ◽  
Probability Scale ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System

This article reports two patients with delayed amiodarone— warfarin interaction resulting in a significant elevation in the international normalized ratio. One patient developed episodes of nosebleeds. Amiodarone is a potent inhibitor of the cytochrome P450 enzyme system. Warfarin undergoes metabolism via the same isoenzyme, potentially leading to prolongation of elevated international normalized ratio levels. A decrease in the warfarin dose is thus warranted when coadministered with amiodarone to circumvent the potential danger of this interaction, which can go unnoticed because several weeks of therapy may be necessary to discern an elevated international normalized ratio. The Naranjo probability scale indicated a possible relationship between the elevated international normalized ratio levels and the coadministration of amiodarone and warfarin. With the coadministration of warfarin and amiodarone, frequent and close monitoring of warfarin is paramount, especially in the initial weeks of therapy, in an effort to prevent supratherapeutic international normalized ratios and bleeding complications.

Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy

2019 ◽  
Vol 74 (8) ◽  
pp. 2341-2346 ◽  
Author(s):  
E Furfaro ◽  
A Signori ◽  
C Di Grazia ◽  
A Dominietto ◽  
A M Raiola ◽  
...  
Keyword(s):  
Roc Curve ◽  
Liver Function Tests ◽  
Fixed Time ◽  
High Serum ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Roc Curve Analysis ◽  
Blood Concentrations ◽  
Length Of Treatment ◽  
Days Of Therapy

Abstract Background Isavuconazole is the newest triazole antifungal approved for the treatment of invasive aspergillosis (IA) and invasive mucormycosis in adult patients. Objectives To characterize the assessment of the blood levels of isavuconazole and their association with efficacy and toxicity. Methods From January 2017 to May 2018, blood samples obtained from patients receiving isavuconazole were analysed for therapeutic drug monitoring. Factors influencing the blood concentrations of isavuconazole, such as weight, length of treatment, route of administration and results of selected liver function tests, were analysed in univariate and multivariate models. The receiver operating characteristic (ROC) curve was analysed to detect the best cut-off for isavuconazole toxicity. Results A total of 264 isavuconazole blood concentrations in 19 patients were analysed. The median value of isavuconazole concentration in all patients during the first 30 days of therapy was 3.69 mg/L (range 0.64–8.13 mg/L). A linear increase of 0.032 mg/L (range 0.023–0.041 mg/L) for each day of treatment (P = 0.002) was observed. In multivariate analysis the association between the length of treatment and higher levels of isavuconazole (P < 0.001) and higher serum GGT and lower isavuconazole levels (P = 0.001) was confirmed. Adverse events, mainly gastrointestinal, were reported in six patients (31.6%). Based on time-dependent and fixed-time ROC curve analysis, 4.87 mg/L and 5.13 mg/L, respectively, were the identified thresholds for toxicity. Conclusions Isavuconazole was efficacious and well tolerated. Side effects, mainly gastrointestinal, were associated with prolonged administration and high serum levels.

scholarly journals Buprenorphine–cannabis interaction in patients undergoing opioid maintenance therapy

2020 ◽  
Author(s):  
Christopher Vierke ◽  
Brigitte Marxen ◽  
Michael Boettcher ◽  
Christoph Hiemke ◽  
Ursula Havemann-Reinecke
Keyword(s):  
Maintenance Therapy ◽  
Illicit Drugs ◽  
Cannabis Use ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Opioid Agonist ◽  
Blood Concentrations ◽  
Opioid Maintenance Therapy ◽  
Regular Control ◽  
Pharmacologically Active

AbstractBuprenorphine is a partial μ-opioid agonist widely used for opioid maintenance therapy (OMT). It is mainly metabolized to pharmacologically active norbuprenorphine by the cytochrome P450 (CYP) isozyme 3A4. This may give rise to drug–drug interactions under combinations with inhibitors or inducers of CYP3A4. Cannabis is a potential inhibitor of CYP3A4, and there is a large degree of concomitant cannabis use among OMT patients. We performed a retrospective analysis on liver healthy OMT patients substituted with buprenorphine, either with (n = 15) or without (n = 17) concomitant use of cannabis. Patients with additional illicit drugs or medications affecting CYP3A were excluded. Measured blood concentrations of buprenorphine and norbuprenorphine were compared between the two groups. Cannabis users and non-users received similar doses, but users had 2.7-fold higher concentrations of buprenorphine (p < 0.01) and 1.4-fold for norbuprenorphine (1.4-fold, p = 0.07). Moreover, the metabolite-to-parent drug ratio was 0.98 in non-users and 0.38 in users (p = 0.02). Female gender did not produce significant effects. These findings indicate that cannabis use decreases the formation of norbuprenorphine and elevates buprenorphine and norbuprenorphine concentrations in blood most probably by inhibition of CYP3A4. The pharmacokinetic interaction may give rise to enhanced or altered opioid activity and risk of intoxications. Physicians should inform patients about this risk and supervise cannabis users by regular control of buprenorphine blood levels, i.e., by therapeutic drug monitoring.

scholarly journals Clinical Use and Monitoring of Antiepileptic Drugs

2018 ◽  
Vol 3 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Claire E Knezevic ◽  
Mark A Marzinke
Keyword(s):  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Neurological Disorders ◽  
Genetic Factors ◽  
Patient Specific ◽  
Therapeutic Drug ◽  
Clinical Tests ◽  
Blood Concentrations ◽  
Specific Factors

Abstract Background Antiepileptic drugs (AEDs) have been used for the treatment of epilepsy and other neurological disorders since the late 19th century. There are currently several classes of AEDs available for epilepsy management, many of which are also used to treat migraines, bipolar disorder, schizophrenia, depression, and neuropathic pain. Because of their molecular and mechanistic diversity, as well as the potential for drug–drug interactions, AEDs are prescribed and monitored in a highly personalized manner. Content This review provides a general overview of the use of AEDs with a focus on the role of therapeutic drug monitoring. Discussed topics include mechanisms of action, guidelines on the clinical applications of AEDs, clinical tests available for AED monitoring, and genetic factors known to affect AED efficacy. Summary Implementation of AED therapies is highly individualized, with many patient-specific factors considered for drug and dosage selection. Both therapeutic efficacy and target blood concentrations must be established for each patient to achieve seizure mitigation or cessation. The use of an AED with any additional drug, including other AEDs, requires an evaluation of potential drug–drug interactions. Furthermore, AEDs are commonly used for nonepilepsy indications, often in off-label administration to treat neurological or psychiatric disorders.

scholarly journals Blood Micronutrient and Thyroid Hormone Concentrations in the Oldest-Old

2000 ◽  
Vol 85 (6) ◽  
pp. 2260-2265 ◽  
Author(s):  
Giovanni Ravaglia ◽  
Paola Forti ◽  
Fabiola Maioli ◽  
Barbara Nesi ◽  
Loredana Pratelli ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Oldest Old ◽  
Serum Zinc ◽  
Blood Levels ◽  
Elderly Age ◽  
Blood Concentrations ◽  
Significant Difference ◽  
Plasma Retinol ◽  
Age Range

Several micronutrients are involved in thyroid hormone metabolism, but it is unclear whether their marginal deficits may contribute to the alterations in thyroid function observed in extreme aging. The relationships among blood concentrations of thyroid hormones and selenium, zinc, retinol, and α-tocopherol were studied in 44 healthy Northern Italian oldest-old subjects (age range, 90–107 yr), selected by the criteria of the SENIEUR protocol. Control groups included 44 healthy adult (age range, 20–65 yr) and 44 SENIEUR elderly (age range, 65–89 yr) subjects. Oldest-old subjects had higher TSH (P &lt; 0.01) and lower free T3 (FT3)/freeT4 (FT4) ratio, zinc, and selenium serum values (P &lt; 0.001) than adult and elderly control subjects. No significant difference was found for plasma retinol and α-tocopherol values. The associations between micronutrients and thyroid hormones were evaluated by multivariate analysis. In oldest-old subjects, plasma retinol was negatively associated with FT4 (P = 0.019) and TSH serum levels (P = 0.040), whereas serum zinc was positively associated with serum FT3 (P = 0.010) and FT3/FT4 ratio (P = 0.011). In younger subjects, no significant association was found among thyroid variables and micronutrients. In conclusion, blood levels of specific micronutrients are associated with serum iodothyronine levels in extreme aging.

scholarly journals Prognostic value of cardio-hepatic-skeletal muscle syndrome in patients with heart failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takumi Noda ◽  
Kentaro Kamiya ◽  
Nobuaki Hamazaki ◽  
Kohei Nozaki ◽  
Takafumi Ichikawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Physical Function ◽  
Grip Strength ◽  
Liver Dysfunction ◽  
Gait Speed ◽  
International Normalized Ratio ◽  
Walking Distance ◽  
Leg Strength ◽  
Function Test ◽  
End Stage

AbstractAlthough heart failure (HF) and liver dysfunction often coexist because of complex cardiohepatic interactions, the association between liver dysfunction and physical dysfunction, and between coexistence of both and prognosis in HF patients remains unclear. We reviewed 895 patients with HF (mean age, 69.4 ± 14.2 years) who underwent liver function test using model for end-stage liver disease excluding international normalized ratio (MELD-XI) score and physical function test (grip strength, leg strength, gait speed, and 6-min walking distance [6MWD]). In the multiple regression analysis, MELD-XI score was independently associated with lower grip strength, leg strength, gait speed, and 6MWD (all P < 0.001). One hundred thirty deaths occurred over a median follow-up period of 1.67 years (interquartile range: 0.62–3.04). For all-cause mortality, patients with high MELD-XI scores and reduced physical functions were found to have a significantly higher mortality risk even after adjusting for several covariates (grip strength, hazard ratio [HR]: 3.80, P < 0.001; leg strength, HR: 4.65, P < 0.001; gait speed, HR: 2.49, P = 0.001, and 6MWD, HR: 5.48, P < 0.001). Liver dysfunction was correlated with reduced physical function. Moreover, the coexistence of lower physical function and liver dysfunction considerably affected prognosis in patients with HF.

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