|St. john's wort|
QT time prolongation
Adverse drug events
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Explanations of the substances for patients
We have no additional warnings for the combination of dextropropoxyphene, alprazolam and st. john's wort. Please also consult the relevant specialist information.
|St. john's wort||1||1||1|
The changes in exposure mentioned relate to changes in the plasma concentration-time curve [AUC]. We did not detect any change in exposure to dextropropoxyphene, when combined with alprazolam (100%). We cannot currently estimate the influence of st. john's wort. We do not expect any change in exposure for st. john's wort, when combined with dextropropoxyphene (100%) and alprazolam (100%). Alprazolam exposure is reduced to 77%, when combined with dextropropoxyphene (155%) and st. john's wort (60%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
The bioavailability of dextropropoxyphene is unknown. Protein binding [Pb] is not known. The metabolism mainly takes place via CYP3A4.
Alprazolam has a high oral bioavailability [ F ] of 88%, which is why the maximum plasma levels [Cmax] tend to change little during an interaction. The terminal half-life [ t12 ] is 11.7 hours and constant plasma levels [ Css ] are reached after approximately 46.8 hours. The protein binding [ Pb ] is moderately strong at 70.2% and the volume of distribution [ Vd ] is 50 liters in the middle range, Since the substance has a low hepatic extraction rate of 0.04, displacement from protein binding [Pb] in the context of an interaction can increase exposure. The metabolism mainly takes place via CYP3A4.
The bioavailability, half-life, and volume of distribution of st. john's wort are unknown to us.
|Serotonergic Effects a||1||Ø||Ø||+|
Recommendation: As a precautionary measure, symptoms of serotonergic overstimulation should be taken into account, especially after increasing the dose and at doses in the upper therapeutic range.
Rating: St. john's wort has a mild effect on the serotonergic system. The risk of a serotonergic syndrome can be classified as low with this medication if the dosage is in the usual range. According to our knowledge, neither dextropropoxyphene nor alprazolam increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø||Ø|
Rating: According to our findings, neither dextropropoxyphene, alprazolam nor st. john's wort increase anticholinergic activity.
QT time prolongation
We do not know of any QT-prolonging potential for dextropropoxyphene, alprazolam and st. john's wort.
General adverse effects
|Side effects||∑ frequency||dex||alp||st.|
|Coordination problem||24.8 %||n.a.||24.8||n.a.|
|Memory impairment||24.3 %||n.a.||24.3||n.a.|
|Increased appetite||19.9 %||n.a.||19.9||n.a.|
|Weight gain||14.9 %||n.a.||14.9||n.a.|
Xerostomia (12.4%): alprazolam
Dyspepsis: st. john's wort
Depression (11.7%): alprazolam
Rebound effect: alprazolam
Restlessness: st. john's wort
Reduced libido (10.2%): alprazolam
Confusion (6%): alprazolam
Stevens johnson syndrome: alprazolam
Photosensitivity: st. john's wort
Liver failure: alprazolam
Based on your
Abstract: Alprazolam is a short-acting triazolobenzodiazepine with anxiolytic and antidepressant properties. It has a half-life of 10-15 hours after multiple oral doses. Approximately 20% of an oral dose is excreted unchanged in the urine. The major urinary metabolites are alpha-OH alprazolam glucuronide and 3-HMB benzophenone glucuronide. The objective of this study was to characterize the reactivity of alprazolam and three metabolites in the Abbott ADx and TDx urinary benzodiazepine assays compared with the EMIT d.a.u. benzodiazepine assay. Alprazolam (at 300 ng/mL) gave an equivalent response as the 300 ng/mL low control (nordiazepam). alpha-OH alprazolam gave an equivalent response to this control between 300-500 ng/mL and 4-OH alprazolam between 500-1000 ng/mL. The 3-HMB benzophenone was not positive even at 10,000 ng/mL. The ADx screening assay was positive in 26 of 31 urine specimens collected from alprazolam-treated patients. All 31 of these specimens were confirmed positive for alpha-OH alprazolam by GC/MS after enzymatic hydrolysis and formation of a TMS derivative. For the TDx, 27 of 31 specimens were positive for benzodiazepines and all 31 were confirmed by GC/MS. All 5 of the negative ADx specimens and 4 of 5 TDx specimens contained 150-400 ng/mL of alpha-OH alprazolam. In conclusion, both the ADx and TDx urine benzodiazepine assays are acceptable screening assays for alprazolam use when the alpha-OH alprazolam concentration is greater than 400 ng/mL.
Abstract: Alprazolam, a triazolobenzodiazepine, is the first of this new class of benzodiazepine drugs to be marketed in the United States and Canada. It achieves peak serum levels in 0.7 to 2.1 hours and has a serum half-life of 12 to 15 hours. When given in the recommended daily dosage of 0.5 to 4.0 mg, it is as effective as diazepam and chlordiazepoxide as an anxiolytic agent. Its currently approved indication is for the treatment of anxiety disorders and symptoms of anxiety, including anxiety associated with depression. Although currently not approved for the treatment of depressive disorders, studies published to date have demonstrated that alprazolam compares favorably with standard tricyclic antidepressants. Also undergoing investigation is the potential role of alprazolam in the treatment of panic disorders. Alprazolam has been used in elderly patients with beneficial results and a low frequency of adverse reactions. Its primary side effect, drowsiness, is less than that produced by diazepam at comparable doses. Data on toxicity, tolerance, and withdrawal profile are limited, but alprazolam seems to be at least comparable to other benzodiazepines. Drug interaction data are also limited, and care should be exercised when prescribing alprazolam for patients taking other psychotropic drugs because of potential additive depressant effects.
Abstract: Six fasting male subjects (20-32 years of age) received an oral tablet and an IV 1.0-mg dose of alprazolam in a crossover-design study. Alprazolam plasma concentration in multiple samples during 36 h after dosing was determined by electron-capture gas-liquid chromatography. Psychomotor performance tests, digit-symbol substitution (DSS), and perceptual speed (PS) were administered at 0, 1.25, 2.25, 5.0, and 12.5 h. Sedation was assessed by the subjects and by an observer using the Stanford Sleepiness Scale and a Nurse Rating Sedation Scale (NRSS), respectively. Mean kinetic parameters after IV and oral alprazolam were as follows: volume of distribution (Vd) 0.72 and 0.84 l/kg; elimination half-life (t1/2) 11.7 and 11.8 h; clearance (Cl) 0.74 and 0.89 ml/min/kg. There were no significant differences between IV and oral alprazolam in Vd, t1/2, or area under the curve. The mean fraction absorbed after oral administration was 0.92. Performance on PS and DSS tests was impaired at 1.25 and 2.5 h, but had returned to baseline at 5.0 h for both treatments. Onset of sedation was rapid after IV administration and the average time of peak sedation was 0.48 h. Sedation scores were significantly lower during hour 1 after oral administration than after IV, but were not significantly different at later times. Alprazolam is fully available after oral administration and kinetic parameters are not affected by route of administration. With the exception of rapidity of onset, the pharmacodynamic profiles of IV and oral alprazolam are very similar after a 1.0-mg dose.
Abstract: No Abstract available
Abstract: OBJECTIVE: Our objective was to evaluate the effect of the CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy volunteers. METHODS: Nineteen healthy male volunteers were divided into 3 groups on the basis of the genetic polymorphism of CYP3A5. The groups comprised subjects with CYP3A5*1/*1 (n=5), CYP3A5*1/*3 (n=7), or CYP3A5*3/*3 (n=7). After a single oral 1-mg dose of alprazolam, plasma concentrations of alprazolam were measured up to 72 hours, together with assessment of psychomotor function by use of the Digit Symbol Substitution Test, according to CYP3A5 genotype. RESULTS: The area under the plasma concentration-time curve for alprazolam was significantly greater in subjects with CYP3A5*3/*3 (830.5+/-160.4 ng . h/mL [mean+/-SD]) than in those with CYP3A5*1/*1 (599.9+/-141.0 ng . h/mL) (P=.030). The oral clearance of alprazolam was also significantly different between the CYP3A5*1/*1 group (3.5+/-0.8 L/h) and CYP3A5*3/*3 group (2.5+/-0.5 L/h) (P=.036). Although a trend was noted for the area under the Digit Symbol Substitution Test score change-time curve (area under the effect curve) to be greater in subjects with CYP3A5*3/*3 (177.2+/-84.6) than in those with CYP3A5*1/*1 (107.5+/-44), the difference did not reach statistical significance (P=.148). CONCLUSIONS: The CYP3A5*3 genotype affects the disposition of alprazolam and thus influences the plasma levels of alprazolam.