Case report: delirium due to a diltiazem-fentanyl CYP3A4 drug interaction

Levin, Tomer T.; Bakr, Mohamed Hussien; Nikolova, Tanya

doi:10.1016/j.genhosppsych.2010.08.003

Cited by 23 publications

(17 citation statements)

References 6 publications

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“…These precursors are hydroxylated in the liver into 25(OH)D by 25-hydroxylases of cytochrome P450 isoenzymes, like CYP27A1, CYP2R1, CYP3A4 and CYPJ3. As calciumchannel blockers act as an inhibitor of CYP3A4, the formation of 25(OH)D may decrease, resulting in lower serum 25(OH)D (26,27,28).…”

Section: Discussionmentioning

confidence: 99%

The impact of medication on vitamin D status in older individuals

Sohl

Schoor

Jongh

et al. 2012

European Journal of Endocrinology

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Objective: Vitamin D deficiency and polypharmacy are common in the elderly. However, knowledge on the associations between the use of specific medicines and serum 25-hydroxyvitamin D (25(OH)D) is limited. The aim of this study was to (better) define the associations between the use of specific medicines and serum 25(OH)D. Methods: Two different cohorts (1995/1996 and 2002/2003) from the Longitudinal Aging Study Amsterdam (LASA) were used for cross-sectional analyses. LASA is based on an age and sex-stratified random sample of the Dutch older population. Study participants were aged 65-88 years in the first cohort (nZ1301) and 55-65 years in the second cohort (nZ736). Serum 25(OH)D of users of several groups of medicines were compared with levels of non-users using multiple linear regression analysis. Results: Of all participants, 75.4% (first cohort) and 61.1% (second cohort) were using at least one medicine. In both cohorts, the number of medicines was associated with lower serum 25(OH)D. In the first cohort, after adjustment for confounding, users of any kind of medicine, loop diuretics and inhaled corticosteroids (only men) had respectively 4.4 nmol/l (P!0.01), 4.7 nmol/l (PZ0.04) and 7.3 nmol/l (PZ0.02) lower serum 25(OH)D than non-users. In the second cohort, the use of oral antidiabetics, calcium-channel blockers and angiotensin-converting enzyme inhibitors was associated with respectively 7.4 nmol/l (PZ0.04), 7.7 nmol/l (PZ0.01) and 7.6 nmol/l (P!0.01) lower serum 25(OH)D. Conclusions: These data show that users of several medicines have lower serum 25(OH)D than nonusers. Vitamin D supplementation may be considered in patients with chronic use of medicines.

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Section: Discussionmentioning

confidence: 99%

The impact of medication on vitamin D status in older individuals

Sohl

Schoor

Jongh

et al. 2012

European Journal of Endocrinology

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“…Fatal drug interactions between fentanyl and CYP3A inhibitors, eg, fluconazole, clarithromycin, diltiazem, and itraconazole have been reported in chronic pain patients treated with transdermal fentanyl resulting in opioid intoxications of these patients …”

mentioning

confidence: 99%

“…7,9 Fatal drug interactions between fentanyl and CYP3A inhibitors, eg, fluconazole, clarithromycin, diltiazem, and itraconazole have been reported in chronic pain patients treated with transdermal fentanyl resulting in opioid intoxications of these patients. [10][11][12][13] In contrast, drug interaction studies with potent CYP3A inhibitors (ie, ritonavir, troleandomycin, itraconazole, voriconazole, and fluconazole) demonstrated only a moderate increase in systemic fentanyl exposure. [14][15][16][17] One of the most potent inhibitors of…”

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confidence: 99%

Pharmacokinetic interaction of intravenous fentanyl with ketoconazole

Ziesenitz

König

Mahlke

et al. 2015

The Journal of Clinical Pharmacology

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Fentanyl is primarily metabolized by CYP3A, but has also been suggested to act as a weak inhibitor of CYP3A. We investigated the influence of CYP3A inhibition by ketoconazole on the pharmacokinetics of intravenously administered fentanyl and the effect of fentanyl on CYP3A activity. A prospective, open-label, randomized, monocentre, crossover study was conducted in 16 healthy volunteers. They received fentanyl alone (5 microgram per kilogram) or fentanyl plus ketoconazole (200 milligram orally B.I.D. over 2 days). Naloxone (2 × 0.2 milligram i.v.) was given simultaneously with fentanyl to mitigate any opioid effect. Midazolam was administered as a CYP3A probe drug. Fentanyl and its metabolites were quantified by LC/MS/MS in blood and urine samples obtained over 24 hour. Exposure of fentanyl (AUC0- ∞ ) was significantly increased to 133% and systemic clearance was reduced to 78% by ketoconazole, norfentanyl formation was significantly delayed and partial metabolic clearance decreased to 18%. Fentanyl had no influence on midazolam exposure and CYP3A activity whereas ketoconazole decreased CYP3A activity to 13%. Although fentanyl N-dealkylation is substantially inhibited by ketoconazole, exposure of fentanyl itself increased by one third only. Clinically fentanyl dosage adjustments may become necessary when ketoconazole or other strong CYP3A inhibitors are given simultaneously. Fentanyl itself does not influence CYP3A activity.

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“…Commonly used cardiac medications that inhibit CYP3A4 or are metabolized through CYP3A4 include non-DHP CCBs and statin medications. In particular, non-DHP CCBs have multiple reports of pharmacokinetic interactions or clinically significant DDI when administered with fentanyl (70,72). A careful approach is warranted, like with benzodiazepines, when using CYP3A4-altering or metabolized medications in patients receiving opiates for interventional procedures.…”

Section: Antiplateletsmentioning

confidence: 99%

Drug–Drug Interactions in Cardiovascular Catheterizations and Interventions

Dunn

Holmes

Moliterno

2012

JACC: Cardiovascular Interventions

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Patients presenting for invasive cardiovascular procedures are frequently taking a variety of medications aimed to treat risk factors related to heart and vascular disease. During the procedure, antithrombotic, sedative, and analgesic medications are commonly needed, and after interventional procedures, new medications are often added for primary and secondary prevention of ischemic events. In addition to these prescribed medications, the use of over-the-counter drugs and supplements continues to rise. Most elderly patients, for example, are taking 5 or more prescribed medications and 1 or more supplements, and they often have some degree of renal insufficiency. This polypharmacy might result in drug-drug interactions that affect the balance of thrombotic and bleeding events during the procedure and during long-term treatment. Mixing of anticoagulants, for instance, might lead to periprocedural bleeding, and this is associated with an increase in long-term adverse events. Furthermore, the range of possible interactions with thienopyridine antiplatelets is of concern, because these drugs are essential to immediate and extended interventional success. The practical challenges in the field are great-some drug-drug interactions are likely present yet not well understood due to limited assays, whereas other interactions have well-described biological effects but seem to be more theoretical, because there is little to no clinical impact. Interventional providers need to be attentive to the potential for drug-drug interaction, the associated harm, and the appropriate action, if any, to minimize the potential for medication-related adverse events. This review will focus on drug-drug interactions that have the potential to affect procedural success, either through increases in immediate complications or compromising longer-term outcome.

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Case report: delirium due to a diltiazem-fentanyl CYP3A4 drug interaction

Cited by 23 publications

References 6 publications

The impact of medication on vitamin D status in older individuals

The impact of medication on vitamin D status in older individuals

Pharmacokinetic interaction of intravenous fentanyl with ketoconazole

Drug–Drug Interactions in Cardiovascular Catheterizations and Interventions

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