Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 8

HOS-114245 · Präparat HOS-094063

Rifabutin Posaconazole increased the Cmax and AUC of rifabutin by 31 % and 72 %, respectively. Concomitant use of posaconazole and rifabutin should be avoided unless the benefit to the patient outweighs the risk (see also above regarding the effect of rifabutin on plasma levels of posaconazole). If these medicinal products are co-administered, careful monitoring of full blood counts and adverse reactions related to increased rifabutin levels (e.g. uveitis) is 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): rifabutin (HOS-086262)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 8

HOS-114246 · Präparat HOS-094063

Sirolimus Repeat dose administration of posaconazole oral suspension (400 mg twice daily for 16 days) increased the Cmax and AUC of sirolimus (2 mg single dose) an average of 6.7-fold and 8.9-fold (range 3.1 to 17.5-fold), respectively, in healthy subjects. The effect of posaconazole on sirolimus in patients is unknown, but is expected to be variable due to the variable posaconazole exposure in patients. Co- administration of posaconazole with sirolimus is not recommended and should be avoided whenever possible. If it is considered that co-administration is unavoidable, then it is recommended that the dose of sirolimus should be greatly reduced at the time of initiation of posaconazole therapy and that there should be very frequent monitoring of trough concentrations of sirolimus in whole blood. Sirolimus concentrations should be measured upon initiation, during co-administration, and at discontinuation of posaconazole treatment, with sirolimus doses adjusted accordingly. It should be noted that the relationship between sirolimus trough concentration and AUC is changed during co-administration with posaconazole. As a result, sirolimus trough concentrations that fall within the usual therapeutic range may result in sub-therapeutic levels. Therefore, trough concentrations that fall in the upper part of the usual therapeutic range should be targeted and careful attention should be paid to clinical signs and symptoms, laboratory parameters and tissue biopsies.

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): sirolimus (HOS-085172)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 8–9

HOS-114247 · Präparat HOS-094063

8 Ciclosporin In heart transplant patients on stable doses of ciclosporin, posaconazole oral suspension 200 mg once daily increased ciclosporin concentrations requiring dose reductions. Cases of elevated ciclosporin levels resulting in serious adverse reactions, including nephrotoxicity and one fatal case of leukoencephalopathy, were reported in clinical efficacy studies. When initiating treatment with posaconazole in patients already receiving ciclosporin, the dose of ciclosporin should be reduced (e.g. to about three quarters of the current dose). Thereafter blood levels of ciclosporin should be monitored carefully during co-administration, and upon discontinuation of posaconazole treatment, and the dose of ciclosporin should be adjusted as necessary.

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

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 9

HOS-114248 · Präparat HOS-094063

Tacrolimus Posaconazole increased Cmax and AUC of tacrolimus (0.05 mg/kg body weight single dose) by 121 % and 358 %, respectively. Clinically significant interactions resulting in hospitalisation and/or posaconazole discontinuation were reported in clinical efficacy studies. When initiating posaconazole treatment in patients already receiving tacrolimus, the dose of tacrolimus should be reduced (e.g. to about one third of the current dose). Thereafter blood levels of tacrolimus should be monitored carefully during co-administration, and upon discontinuation of posaconazole, and the dose of tacrolimus should be adjusted as necessary.

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): tacrolimus (HOS-085202)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 9

HOS-114249 · Präparat HOS-094063

HIV Protease inhibitors As HIV protease inhibitors are CYP3A4 substrates, it is expected that posaconazole will increase plasma levels of these antiretroviral agents. Following co-administration of posaconazole oral suspension (400 mg twice daily) with atazanavir (300 mg once daily) for 7 days in healthy subjects Cmax and AUC of atazanavir increased by an average of 2.6-fold and 3.7-fold (range 1.2 to 26-fold), respectively. Following co-administration of posaconazole oral suspension (400 mg twice daily) with atazanavir and ritonavir (300/100 mg once daily) for 7 days in healthy subjects Cmax and AUC of atazanavir increased by an average of 1.5-fold and 2.5-fold (range 0.9 to 4.1-fold), respectively. The addition of posaconazole to therapy with atazanavir or with atazanavir plus ritonavir was associated with increases in plasma bilirubin levels. Frequent monitoring for adverse reactions and toxicity related to antiretroviral agents that are substrates of CYP3A4 is recommended during co- administration with posaconazole.

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): atazanavir (HOS-086180) protease (HOS-085623) ritonavir (HOS-084521)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 9

HOS-114250 · Präparat HOS-094063

Calcium channel blockers metabolised through CYP3A4 (e.g. diltiazem, verapamil, nifedipine, nisoldipine) Frequent monitoring for adverse reactions and toxicity related to calcium channel blockers is recommended during co-administration with posaconazole. Dose adjustment of calcium channel blockers may be required.

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): diltiazem (HOS-086288) nifedipine (HOS-086289) calcium (HOS-085615) nisoldipine (HOS-114251) verapamil (HOS-090602)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 9

HOS-114252 · Präparat HOS-094063

Digoxin Administration of other azoles has been associated with increases in digoxin levels. Therefore, posaconazole may increase plasma concentration of digoxin and digoxin levels need to be monitored when initiating or discontinuing posaconazole treatment.

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): digoxin (HOS-086172)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 9

HOS-114253 · Präparat HOS-094063

Sulfonylureas Glucose concentrations decreased in some healthy volunteers when glipizide was co-administered with posaconazole. Monitoring of glucose concentrations is recommended in diabetic patients.

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): glipizide (HOS-109460) glucose (HOS-088412)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 9

HOS-114254 · Präparat HOS-094063

All-trans retinoic acid (ATRA) or tretinoin As ATRA is metabolised by the hepatic CYP450 enzymes, notably CYP3A4, concomitant administration with posaconazole, which is a strong inhibitor of CYP3A4, may lead to increased exposure to tretinoin resulting in an increased toxicity (especially hypercalcaemia). Serum calcium levels should be monitored and, if needed, appropriate dose adjustments of tretinoin should be considered during the treatment with posaconazole, and during the following days after treatment.

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): calcium (HOS-085615) tretinoin (HOS-109447) lead (HOS-085592)

Wechselwirkungen · Noxafil

Noxafil 40 mg/mL oral suspension · Abschnitt 4.5 · PDF-Seite 9

HOS-114255 · Präparat HOS-094063

Paediatric population Interaction studies have only been performed in adults.

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

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114280 · Präparat HOS-094063

Effects of other medicinal products on posaconazole Posaconazole is metabolised via UDP glucuronidation (phase 2 enzymes) and is a substrate for p-glycoprotein (P-gp) efflux in vitro. Therefore, inhibitors (e.g. verapamil, ciclosporin, quinidine, clarithromycin, erythromycin, etc.) or inducers (e.g. rifampicin, rifabutin, certain anticonvulsants, etc.) of these clearance pathways may increase or decrease posaconazole plasma concentrations, respectively.

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): rifabutin (HOS-086262) quinidine (HOS-085593) clarithromycin (HOS-084517) erythromycin (HOS-084514) verapamil (HOS-090602)

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114281 · Präparat HOS-094063

Flucloxacillin Flucloxacillin (a CYP450 inducer) may decrease plasma posaconazole concentrations. Concomitant use of posaconazole and flucloxacillin should be avoided unless the benefit to the patient outweighs the risk (see section 4.4).

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

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114282 · Präparat HOS-094063

Rifabutin Rifabutin (300 mg once a day) decreased the Cmax (maximum plasma concentration) and AUC (area under the plasma concentration time curve) of posaconazole to 57 % and 51 %, respectively. Concomitant use of posaconazole and rifabutin and similar inducers (e.g. rifampicin) should be avoided unless the benefit to the patient outweighs the risk. See also below regarding the effect of posaconazole on rifabutin plasma levels.

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): rifabutin (HOS-086262)

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114283 · Präparat HOS-094063

Efavirenz Efavirenz (400 mg once a day) decreased the Cmax and AUC of posaconazole by 45 % and 50 %, respectively. Concomitant use of posaconazole and efavirenz should be avoided unless the benefit to the patient outweighs the risk.

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): efavirenz (HOS-087947)

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114284 · Präparat HOS-094063

Fosamprenavir Combining fosamprenavir with posaconazole may lead to decreased posaconazole plasma concentrations. If concomitant administration is required, close monitoring for breakthrough fungal infections is recommended. Repeat dose administration of fosamprenavir (700 mg twice daily x 10 days) decreased the Cmax and AUC of posaconazole oral suspension (200 mg once daily on the 1st day, 200 mg twice daily on the 2nd day, then 400 mg twice daily x 8 Days) by 21 % and 23 %, respectively. The effect of posaconazole on fosamprenavir levels when fosamprenavir is given with ritonavir is unknown.

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): lead (HOS-085592) fosamprenavir (HOS-086182) ritonavir (HOS-084521)

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114285 · Präparat HOS-094063

Phenytoin Phenytoin (200 mg once a day) decreased the Cmax and AUC of posaconazole by 41 % and 50 %, respectively. Concomitant use of posaconazole and phenytoin and similar inducers (e.g. carbamazepine, phenobarbital, primidone) should be avoided unless the benefit to the patient outweighs the risk.

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): phenobarbital (HOS-085617) carbamazepine (HOS-085618) phenytoin (HOS-084531) primidone (HOS-090551)

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114286 · Präparat HOS-094063

H2 receptor antagonists and proton pump inhibitors No clinically relevant effects were observed when posaconazole tablets are concomitantly used with antacids, H2-receptor antagonists and proton pump inhibitors. No dose adjustment of posaconazole tablets is required when posaconazole tablets are concomitantly used with antacids, H2-receptor antagonists and proton pump inhibitors.

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

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-114287 · Präparat HOS-094063

Effects of posaconazole on other medicinal products Posaconazole is a potent inhibitor of CYP3A4. Co-administration of posaconazole with CYP3A4 substrates may result in large increases in exposure to CYP3A4 substrates as exemplified by the effects on tacrolimus, sirolimus, atazanavir and midazolam below. Caution is advised during co- administration of posaconazole with CYP3A4 substrates administered intravenously and the dose of

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): atazanavir (HOS-086180) tacrolimus (HOS-085202) sirolimus (HOS-085172) midazolam (HOS-086167)

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 24–25

HOS-114288 · Präparat HOS-094063

24 the CYP3A4 substrate may need to be reduced. If posaconazole is used concomitantly with CYP3A4 substrates that are administered orally, and for which an increase in plasma concentrations may be associated with unacceptable adverse reactions, plasma concentrations of the CYP3A4 substrate and/or adverse reactions should be closely monitored and the dose adjusted as needed. Several of the interaction studies were conducted in healthy volunteers in whom a higher exposure to posaconazole occurs compared to patients administered the same dose. The effect of posaconazole on CYP3A4 substrates in patients might be somewhat lower than that observed in healthy volunteers, and is expected to be variable between patients due to the variable posaconazole exposure in patients. The effect of co-administration with posaconazole on plasma levels of CYP3A4 substrates may also be variable within a patient.

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

Wechselwirkungen · Noxafil

Noxafil 100 mg gastro-resistant tablets · Abschnitt 4.5 · PDF-Seite 25

HOS-114289 · Präparat HOS-094063

Terfenadine, astemizole, cisapride, pimozide, halofantrine and quinidine (CYP3A4 substrates) Co-administration of posaconazole and terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine is contraindicated. Co-administration may result in increased plasma concentrations of these medicinal products, leading to QTc prolongation and rare occurrences of torsade de pointes (see section 4.3).

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): cisapride (HOS-085610) halofantrine (HOS-085606) quinidine (HOS-085593) pimozide (HOS-085600) astemizole (HOS-085608) terfenadine (HOS-085607)