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 dihydrocodeine and dibenzepin. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We do not expect any change in exposure for dihydrocodeine, when combined with dibenzepin (100%). We do not expect any change in exposure for dibenzepin, when combined with dihydrocodeine (100%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
Dihydrocodeine has a low oral bioavailability [ F ] of 20%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is rather short at 4 hours and constant plasma levels [ Css ] are reached quickly. Protein binding [ Pb ] is not known. The metabolism takes place via CYP2D6 and CYP3A4, among others.
Dibenzepin has a low oral bioavailability [ F ] of 25%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is rather short at 5 hours and constant plasma levels [ Css ] are reached quickly. The protein binding [ Pb ] is moderately strong at 80%. The metabolism does not take place via the common cytochromes.
|Serotonergic Effects a||1||+||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: Dihydrocodeine 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, dibenzepin does not increase serotonergic activity.
|Kiesel & Durán b||2||+||+|
Recommendation: As a precaution, attention should be paid to anticholinergic symptoms, especially after increasing the dose and at doses in the upper therapeutic range.
Rating: Dihydrocodeine and dibenzepin only have a mild effect on the anticholinergic system. The risk of anticholinergic syndrome with this medication is rather low if the dosage is in the usual range.
QT time prolongation
We do not know of any QT-prolonging potential for dihydrocodeine and dibenzepin.
General adverse effects
|Side effects||∑ frequency||dih||dib|
|Allergic skin reactions like pruritus and rash||0.0 %||0.1||n.a.|
Respiratory depression: dihydrocodeine
Based on your answers and scientific information, we assess the individual risk of undesirable side effects. These recommendations are intended to advise professionals and are not a substitute for consultation with a doctor. In the restricted test version (alpha), the risk of all substances has not yet been conclusively assessed.
Abstract: The antimuscarinic potency of dibenzepin (Noveril) was estimated by measuring (a) central in vivo effects in mice (antihypothermia and antitremor, both induced by oxotremorine), (b) peripheral in vivo activity (mydriasis caused by systemic administration of the drug), (c) the effects of dibenzepin on isolated smooth muscle from guinea pig ileum, and (d) in vitro determination of the affinity constant of dibezepine toward the muscarinic binding sites in whole mouse-brain homogenate. The data allowed the construction of a normalized antimuscarinic potency scale for some of the common tricyclic antidepressants. With a value of 1 for scopolamine, the following relative anticholinergic potencies were calculated: dibenzepin--1/600, nortriptylne--1/300, imipramine - 1/200, and amitriptyline - 1/75. These values suggest an explanation for the absence of clinically detectable anticholinergic side effects during treatment of depression with high doses of dibenzepin. Structural and spatial interrelations among various tricyclic antidepressants and scopolamine are discussed.
Abstract: Serum concentrations of dihydrocodeine and its acid metabolites have been determined in seven human volunteers (6 male) who received the drug orally (30 mg and 60 mg) and intravenously (30 mg) on separate occasions, and in twenty-four patients (12 male) receiving 25 mg or 50 mg of the drug intravenously. The concentrations were estimated by radioimmunoassay on reconstituted extracts from serum after an extraction process which effectively separates dihydrocodeine from its polar acidic metabolites. The intravenous data show that dihydrocodeine kinetics followed a two-compartment distribution model. The concentration curves after oral administration indicated relatively rapid absorption with mean peak concentrations at 1.6 h-1.8 h. The mean half-lives varied between 3.3 h-4.5 h. From the AUC, the mean bioavailability of orally administered drug was 21% (range 12-34%). The peak levels of the acidic metabolites occurred between 1.8 h-2.0 h after oral administration and 2.2 h-2.5 h after i.v. administration, and they were significantly greater after oral administration. The low bioavailability of dihydrocodeine, together with the earlier and higher plasma levels of the acid metabolites after oral administration is suggestive of substantial first-pass metabolism.