Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Norvir

Norvir 100 mg powder for oral suspension · Abschnitt 4.5 · PDF-Seite 19

HOS-086290 · Präparat HOS-083284

Endothelin antagonists Co-administration of bosentan and ritonavir may increase steady state Bosentan bosentan maximum concentrations (Cmax) and area under the curve (AUC)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosentan (HOS-086291)

Wechselwirkungen · Norvir

Norvir 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 51

HOS-086464 · Präparat HOS-083284

Endothelin antagonists Bosentan Co-administration of bosentan and ritonavir may increase steady state bosentan maximum concentrations (Cmax) and area under the curve (AUC).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosentan (HOS-086291)

Wechselwirkungen · Viagra

VIAGRA 25 mg film-coated tablets VIAGRA 50 mg film-coated tablets VIAGRA 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6–7

HOS-088790 · Präparat HOS-083727

Although specific interaction studies were not conducted for all medicinal products, population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and potassium sparing diuretics, angiotensin converting enzyme inhibitors, calcium channel blockers, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates). In a study of healthy male volunteers, co-administration of the endothelin antagonist, bosentan, (an inducer of CYP3A4 [moderate], CYP2C9 and possibly of CYP2C19) at steady state (125 mg twice a day) with sildenafil at steady state (80 mg three times a day) resulted in 62.6% and 55.4% decrease in sildenafil AUC and Cmax, respectively. Therefore, concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil. 6 Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate component it has the potential to result in a serious interaction with sildenafil.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): rifampin (HOS-088791) nicorandil (HOS-088792) calcium (HOS-085615) serotonin (HOS-085477) potassium (HOS-086929) bosentan (HOS-086291) phenytoin (HOS-084531) warfarin (HOS-085950) tolbutamide (HOS-086568)

Wechselwirkungen · Viagra

VIAGRA 25 mg film-coated tablets VIAGRA 50 mg film-coated tablets VIAGRA 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-088807 · Präparat HOS-083727

In healthy male volunteers, sildenafil at steady state (80 mg three times a day) resulted in a 49.8% increase in bosentan AUC and a 42% increase in bosentan Cmax (125 mg twice a day).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosentan (HOS-086291)

Wechselwirkungen · Viagra

VIAGRA 50 mg orodispersible tablets · Abschnitt 4.5 · PDF-Seite 20

HOS-088849 · Präparat HOS-083727

Although specific interaction studies were not conducted for all medicinal products, population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and potassium sparing diuretics, angiotensin converting enzyme inhibitors, calcium channel blockers, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates). In a study of healthy male volunteers, co-administration of the endothelin antagonist, bosentan, (an inducer of CYP3A4 [moderate], CYP2C9 and possibly of CYP2C19) at steady state (125 mg twice a day) with sildenafil at steady state (80 mg three times a day) resulted in 62.6% and 55.4% decrease in sildenafil AUC and Cmax, respectively. Therefore, concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): rifampin (HOS-088791) calcium (HOS-085615) serotonin (HOS-085477) potassium (HOS-086929) bosentan (HOS-086291) phenytoin (HOS-084531) warfarin (HOS-085950) tolbutamide (HOS-086568)

Wechselwirkungen · Viagra

VIAGRA 50 mg orodispersible tablets · Abschnitt 4.5 · PDF-Seite 21

HOS-088861 · Präparat HOS-083727

In healthy male volunteers, sildenafil at steady state (80 mg three times a day) resulted in a 49.8% increase in bosentan AUC and a 42% increase in bosentan Cmax (125 mg twice a day).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosentan (HOS-086291)

Wechselwirkungen · Viagra

VIAGRA 50 mg orodispersible films · Abschnitt 4.5 · PDF-Seite 34

HOS-088899 · Präparat HOS-083727

Although specific interaction studies were not conducted for all medicinal products, population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and potassium sparing diuretics, angiotensin converting enzyme inhibitors, calcium channel blockers, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates). In a study of healthy male volunteers, co-administration of the endothelin antagonist, bosentan, (an inducer of CYP3A4 [moderate], CYP2C9 and possibly of CYP2C19) at steady state (125 mg twice a day) with sildenafil at steady state (80 mg three times a day) resulted in 62.6% and 55.4% decrease in sildenafil AUC and Cmax, respectively. Therefore, concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): rifampin (HOS-088791) calcium (HOS-085615) serotonin (HOS-085477) potassium (HOS-086929) bosentan (HOS-086291) phenytoin (HOS-084531) warfarin (HOS-085950) tolbutamide (HOS-086568)

Wechselwirkungen · Viagra

VIAGRA 50 mg orodispersible films · Abschnitt 4.5 · PDF-Seite 35

HOS-088912 · Präparat HOS-083727

In healthy male volunteers, sildenafil at steady state (80 mg three times a day) resulted in a 49.8% increase in bosentan AUC and a 42% increase in bosentan Cmax (125 mg twice a day).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosentan (HOS-086291)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 25–26

HOS-108940 · Präparat HOS-093083

Methadone Methadone: ↓ Monitoring plasma concentrations of methadone is recommended. Oral contraceptives Ethinyl Oestradiol Ethinyl Oestradiol: ↓ In case of co-administration of Kaletra with contraceptives containing ethinyl oestradiol (whatever the contraceptive formulation e.g. oral or patch), additional methods of contraception must be used. Smoking cessation aids Bupropion Buproprion and its active If the co-administration of Kaletra metabolite, hydroxybupropion: with bupropion is judged AUC and Cmax ↓ ~50% unavoidable, this should be done under close clinical monitoring for This effect may be due to bupropion efficacy, without induction of bupropion exceeding the recommended metabolism. dosage, despite the observed induction. Thyroid hormone replacement therapy Levothyroxine Post-marketing cases have been Thyroid-stimulating hormone reported indicating a potential (TSH) should be monitored in interaction between ritonavir patients treated with levothyroxine containing products and at least the first month after levothyroxine. starting and/or ending lopinavir/ritonavir treatment. Vasodilating agents 25  Bosentan Lopinavir - ritonavir: Caution should be exercised in Lopinavir/ritonavir plasma administering Kaletra with concentrations may decrease due bosentan. to CYP3A4 induction by When Kaletra is administered bosentan. concomitantly with bosentan, the efficacy of the HIV therapy should Bosentan: be monitored and patients should AUC: ↑ 5-fold be closely observed for bosentan Cmax: ↑ 6-fold toxicity, especially during the first Initially, bosentan Cmin: ↑ by week of co-administration. approximately 48-fold. Due to CYP3A4 inhibition by lopinavir/ritonavir. Riociguat Serum concentrations may be The co-administration of riociguat increased due to CYP3A and with Kaletra is not recommended P-gp inhibition by (see section 4.4 and refer to lopinavir/ritonavir. riociguat SmPC). Other medicinal products Based on known metabolic profiles, clinically significant interactions are not expected between Kaletra and dapsone, trimethoprim/sulfamethoxazole, azithromycin or fluconazole.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): sulfamethoxazole (HOS-084533) bupropion (HOS-086329) riociguat (HOS-086293) methadone (HOS-086198) trimethoprim (HOS-085184) azithromycin (HOS-088112) fluconazole (HOS-087945) bosentan (HOS-086291) dapsone (HOS-088141) levothyroxine (HOS-086339)

Wechselwirkungen · Kaletra

Kaletra 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 61

HOS-109024 · Präparat HOS-093083

Thyroid hormone replacement therapy Levothyroxine Post-marketing cases have been Thyroid-stimulating hormone (TSH) reported indicating a potential should be monitored in patients interaction between ritonavir treated with levothyroxine at least the containing products and first month after starting and/or levothyroxine. ending lopinavir/ritonavir treatment. Vasodilating agents Bosentan Lopinavir - ritonavir: Caution should be exercised in Lopinavir/ritonavir plasma administering Kaletra with bosentan. concentrations may decrease due When Kaletra is administered to CYP3A4 induction by concomitantly with bosentan, the bosentan. efficacy of the HIV therapy should be monitored and patients should be Bosentan: closely observed for bosentan AUC: ↑ 5-fold toxicity, especially during the first Cmax: ↑ 6-fold week of co-administration. Initially, bosentan Cmin: ↑ by approximately 48-fold. Due to CYP3A4 inhibition by lopinavir/ritonavir. Riociguat Serum concentrations may be The co-administration of riociguat increased due to CYP3A and P-gp with Kaletra is not recommended inhibition by lopinavir/ritonavir. (see section 4.4 and refer to riociguat SmPC). Other medicinal products Based on known metabolic profiles, clinically significant interactions are not expected between Kaletra and dapsone, trimethoprim/sulfamethoxazole, azithromycin or fluconazole.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): sulfamethoxazole (HOS-084533) riociguat (HOS-086293) trimethoprim (HOS-085184) azithromycin (HOS-088112) fluconazole (HOS-087945) bosentan (HOS-086291) dapsone (HOS-088141) levothyroxine (HOS-086339)

Wechselwirkungen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 96–97

HOS-109102 · Präparat HOS-093083

96  Oral contraceptives Ethinyl Oestradiol Ethinyl Oestradiol: ↓ In case of co-administration of Kaletra with contraceptives containing ethinyl oestradiol (whatever the contraceptive formulation e.g. oral or patch), additional methods of contraception must be used. Smoking cessation aids Bupropion Buproprion and its active If the co-administration of Kaletra metabolite, hydroxybupropion: with bupropion is judged AUC and Cmax ↓ ~50% unavoidable, this should be done under close clinical monitoring for This effect may be due to bupropion efficacy, without induction of bupropion exceeding the recommended metabolism. dosage, despite the observed induction. Thyroid hormone replacement therapy Levothyroxine Post-marketing cases have been Thyroid-stimulating hormone reported indicating a potential (TSH) should be monitored in interaction between ritonavir patients treated with levothyroxine containing products and at least the first month after starting levothyroxine. and/or ending lopinavir/ritonavir treatment. Vasodilating agents Bosentan Lopinavir - ritonavir: Caution should be exercised in Lopinavir/ritonavir plasma administering Kaletra with concentrations may decrease due bosentan. to CYP3A4 induction by When Kaletra is administered bosentan. concomitantly with bosentan, the efficacy of the HIV therapy should Bosentan: be monitored and patients should be AUC: ↑ 5-fold closely observed for bosentan Cmax: ↑ 6-fold toxicity, especially during the first Initially, bosentan Cmin: ↑ by week of coadministration. approximately 48-fold. Due to CYP3A4 inhibition by lopinavir/ritonavir. Riociguat Serum concentrations may be The co-administration of riociguat increased due to CYP3A and with Kaletra is not recommended P-gp inhibition by (see section 4.4 and refer to lopinavir/ritonavir. riociguat SmPC). Other medicinal products Based on known metabolic profiles, clinically significant interactions are not expected between Kaletra and dapsone, trimethoprim/sulfamethoxazole, azithromycin or fluconazole.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): sulfamethoxazole (HOS-084533) bupropion (HOS-086329) riociguat (HOS-086293) trimethoprim (HOS-085184) azithromycin (HOS-088112) fluconazole (HOS-087945) bosentan (HOS-086291) dapsone (HOS-088141) levothyroxine (HOS-086339)

Gegenanzeigen · Tracleer

Tracleer 62.5 mg film-coated tablets Tracleer 125 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-109915 · Präparat HOS-093279

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1  Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C (see section 5.2)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Gegenanzeigen · Tracleer

Tracleer 62.5 mg film-coated tablets Tracleer 125 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 4–5

HOS-109916 · Präparat HOS-093279

4  Baseline values of liver aminotransferases, i.e., aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), greater than 3  the upper limit of normal (ULN; see section 4.4)  Concomitant use of cyclosporine A (see section 4.5)  Pregnancy (see sections 4.4 and 4.6)  Women of childbearing potential who are not using reliable methods of contraception (see sections 4.4, 4.5 and 4.6)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): aspartate (HOS-088948) cyclosporine (HOS-084512) alanine (HOS-088949)

Gegenanzeigen · Tracleer

Tracleer 32 mg dispersible tablets · Abschnitt 4.3 · PDF-Seite 27

HOS-109971 · Präparat HOS-093279

 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1  Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C (see section 5.2)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Gegenanzeigen · Tracleer

Tracleer 32 mg dispersible tablets · Abschnitt 4.3 · PDF-Seite 27–28

HOS-109972 · Präparat HOS-093279

27  Baseline values of liver aminotransferases, i.e., aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), greater than 3  the upper limit of normal (ULN; see section 4.4)  Concomitant use of cyclosporine A (see section 4.5)  Pregnancy (see sections 4.4 and 4.6)  Women of childbearing potential who are not using reliable methods of contraception (see sections 4.4, 4.5 and 4.6)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): aspartate (HOS-088948) cyclosporine (HOS-084512) alanine (HOS-088949)

Wechselwirkungen · Tracleer

Tracleer 62.5 mg film-coated tablets Tracleer 125 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-109919 · Präparat HOS-093279

Bosentan is an inducer of the cytochrome P450 (CYP) isoenzymes CYP2C9 and CYP3A4. In vitro data also suggest an induction of CYP2C19. Consequently, plasma concentrations of substances metabolised by these isoenzymes will be decreased when Tracleer is co-administered. The possibility

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosentan (HOS-086291)

Wechselwirkungen · Tracleer

Tracleer 62.5 mg film-coated tablets Tracleer 125 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 7–8

HOS-109920 · Präparat HOS-093279

7 of altered efficacy of medicinal products metabolised by these isoenzymes should be considered. The dosage of these products may need to be adjusted after initiation, dose change or discontinuation of concomitant Tracleer treatment.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Tracleer

Tracleer 62.5 mg film-coated tablets Tracleer 125 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-109921 · Präparat HOS-093279

Bosentan is metabolised by CYP2C9 and CYP3A4. Inhibition of these isoenzymes may increase the plasma concentration of bosentan (see ketoconazole). The influence of CYP2C9 inhibitors on bosentan concentration has not been studied. The combination should be used with caution.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): ketoconazole (HOS-084513) bosentan (HOS-086291)

Wechselwirkungen · Tracleer

Tracleer 62.5 mg film-coated tablets Tracleer 125 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-109922 · Präparat HOS-093279

Fluconazole and other inhibitors of both CYP2C9 and CYP3A4: Co-administration with fluconazole, which inhibits mainly CYP2C9, but to some extent also CYP3A4, could lead to large increases in plasma concentrations of bosentan. The combination is not recommended. For the same reason, concomitant administration of both a potent CYP3A4 inhibitor (such as ketoconazole, itraconazole or ritonavir) and a CYP2C9 inhibitor (such as voriconazole) with Tracleer is not recommended.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): ketoconazole (HOS-084513) voriconazole (HOS-084524) lead (HOS-085592) itraconazole (HOS-084516) fluconazole (HOS-087945) ritonavir (HOS-084521) bosentan (HOS-086291)

Wechselwirkungen · Tracleer

Tracleer 62.5 mg film-coated tablets Tracleer 125 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-109923 · Präparat HOS-093279

Cyclosporine A: Co-administration of Tracleer and cyclosporine A (a calcineurin inhibitor) is contraindicated (see section 4.3). When co-administered, initial trough concentrations of bosentan were approximately 30-fold higher than those measured after bosentan alone. At steady state, bosentan plasma concentrations were 3- to 4-fold higher than with bosentan alone. The mechanism of this interaction is most likely inhibition of transport protein-mediated uptake of bosentan into hepatocytes by cyclosporine. The blood concentrations of cyclosporine A (a CYP3A4 substrate) decreased by approximately 50%. This is most likely due to induction of CYP3A4 by bosentan.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bosentan (HOS-086291) cyclosporine (HOS-084512)