Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 6

HOS-151025 · Präparat HOS-100442

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-151026 · Präparat HOS-100442

Effect of other medicinal products on Balversa

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

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-151027 · Präparat HOS-100442

Moderate CYP2C9 or strong CYP3A4 inhibitors Co-administration with a moderate CYP2C9 or strong CYP3A4 inhibitor increased erdafitinib exposure and may lead to increased drug-related toxicity. Erdafitinib mean ratios (90% CI) for Cmax and AUC∞ were 121% (99.9, 147) and 148% (120, 182), respectively, when co-administered with fluconazole, a moderate CYP2C9 and CYP3A4 inhibitor, relative to erdafitinib alone. Cmax of erdafitinib was 105% (90% CI: 86.7, 127) and AUC∞ was 134% (90% CI: 109, 164) when co- administered with itraconazole, a strong CYP3A4 inhibitor and P-gp inhibitor, relative to erdafitinib alone. Consider alternative agents with no or minimal enzyme inhibition potential. If Balversa is co-administered with a moderate CYP2C9 or strong CYP3A4 inhibitor (such as itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole, miconazole, ceritinib, clarithromycin, telithromycin, elvitegravir, ritonavir, paritaprevir, saquinavir, nefazodone, nelfinavir, tipranavir, lopinavir, amiodarone, piperine), reduce the Balversa dose to the next lower dose based on tolerability (see section 4.2). If the moderate CYP2C9 or strong CYP3A4 inhibitor is discontinued, the Balversa dose may be adjusted as tolerated (see section 4.4).

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): ceritinib (HOS-086215) nefazodone (HOS-084519) lopinavir (HOS-086269) nelfinavir (HOS-084520) ketoconazole (HOS-084513) voriconazole (HOS-084524) piperine (HOS-143945) lead (HOS-085592) telithromycin (HOS-084523) itraconazole (HOS-084516) saquinavir (HOS-084522) fluconazole (HOS-087945) clarithromycin (HOS-084517) ritonavir (HOS-084521) amiodarone (HOS-085596) paritaprevir (HOS-110301) posaconazole (HOS-085622) elvitegravir (HOS-088110) miconazole (HOS-115630) tipranavir (HOS-086184)

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-151046 · Präparat HOS-100442

Grapefruit or Seville oranges should be avoided while taking Balversa due to strong CYP3A4 inhibition (see section 4.2).

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

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-151047 · Präparat HOS-100442

Strong or moderate CYP3A4 inducers Co-administration with carbamazepine, a strong CYP3A4 and weak CYP2C9 inducer leads to decreased erdafitinib exposure. Mean ratios of Cmax and AUC∞ for erdafitinib was 65.4% (90% CI: 60.8, 70.5) and 37.7% (90% CI: 35.4, 40.2), respectively, when co-administered with carbamazepine relative to erdafitinib alone. Avoid co-administration of Balversa with strong CYP3A4 inducers (such as apalutamide, enzalutamide, lumacaftor, ivosidenib, mitotane, rifapentine, rifampicin, carbamazepine, phenytoin, and St. John’s wort). If Balversa is co-administered with a moderate CYP3A4 inducer (such as dabrafenib, bosentan, cenobamate, elagolix, efavirenz, etravirine, lorlatinib, mitapivat, modafinil, pexidartinib, phenobarbital, primidone, repotrectinib, rifabutin, sotorasib, telotristat ethyl), the dose should be cautiously increased by 1 to 2 mg and adjusted gradually every two to three weeks based on clinical monitoring for adverse reactions, not to exceed 9 mg. If the moderate CYP3A4 inducer is discontinued, the Balversa dose may be adjusted as tolerated (see sections 4.2 and 4.4).

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): lumacaftor (HOS-139029) phenobarbital (HOS-085617) modafinil (HOS-090546) carbamazepine (HOS-085618) rifabutin (HOS-086262) apalutamide (HOS-086212) sotorasib (HOS-147831) etravirine (HOS-088088) dabrafenib (HOS-109452) telotristat ethyl (HOS-141158) mitapivat (HOS-147878) mitotane (HOS-112479) elagolix (HOS-112109) lorlatinib (HOS-140195) rifapentine (HOS-116386) ivosidenib (HOS-112046) efavirenz (HOS-087947) bosentan (HOS-086291) phenytoin (HOS-084531) repotrectinib (HOS-151068) enzalutamide (HOS-116829) pexidartinib (HOS-150766) cenobamate (HOS-146930) primidone (HOS-090551)

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-151072 · Präparat HOS-100442

Effect of Balversa on other medicinal products

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

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-151073 · Präparat HOS-100442

Major CYP isoform substrates (including hormonal contraceptives) Mean ratios of Cmax and AUC∞ for midazolam (a sensitive CYP3A4 substrate) were 86.3% (90% CI: 73.5, 101) and 82.1% (90% CI: 70.8, 95.2), respectively, when co-administered with erdafitinib relative to midazolam alone. Erdafitinib does not have a clinically meaningful effect on midazolam PK. However, it cannot be excluded that CYP3A4 induction after administration of Balversa alone or concomitant administration of other CYP3A4 inducers together with Balversa may reduce the efficacy of hormonal contraceptives.

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): midazolam (HOS-086167)

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-151075 · Präparat HOS-100442

9 Patients using hormonal contraceptives should be advised to use an alternative contraceptive not affected by enzyme inducers (e.g., non-hormonal intrauterine device) or an additional nonhormonal contraception (e.g., condom) during treatment with and until 1 month after the last dose of Balversa (see section 4.4).

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

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-151076 · Präparat HOS-100442

P-Glycoprotein (P-gp) substrates Erdafitinib is an inhibitor of P-gp. Concomitant administration of Balversa with P-gp substrates may increase their systemic exposure. Oral narrow therapeutic index P gp substrates (such as colchicine, digoxin, dabigatran, and apixaban) should be taken at least 6 hours before or after erdafitinib to minimise the potential for interactions.

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) dabigatran (HOS-112096) apixaban (HOS-112091) colchicine (HOS-086147)

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-151080 · Präparat HOS-100442

Organic cation transporter 2 (OCT2) substrates Mean ratios of Cmax and AUC∞ for metformin (a sensitive OCT2 substrate) were 109% (90% CI: 90.3, 131) and 114% (90% CI: 93.2, 139), respectively, when co-administered with erdafitinib relative to metformin alone. Erdafitinib does not have a clinically meaningful effect on metformin PK.

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): metformin (HOS-091032)

Wechselwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10

HOS-151082 · Präparat HOS-100442

Medicinal products that can alter serum phosphate levels In patients receiving Balversa, medicinal products that can alter serum phosphate levels should be avoided until assessment of serum phosphate level between 14 and 21 days after initiating treatment due to potential impact on up-titration decision.

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-151083 · Präparat HOS-100442

Summary of the safety profile The most common adverse reactions were hyperphosphataemia (78.5%), diarrhoea (55.5%), stomatitis (52.8%), dry mouth (39.9%), decreased appetite (31.7%), anaemia (28.2%), dry skin (28.0%), central serous retinopathy (28.0%), constipation (27.3%), dysgeusia (26.3%), palmar-plantar erythrodysaesthesia syndrome (PPES) (25.5%), alopecia (23.2%), asthenia (23.0%), alanine aminotransferase increased (21.7%), onycholysis (21.7%), fatigue (20.3%), nausea (18.6%), weight decreased (18.4%), aspartate aminotransferase increased (18.0%), dry eye (16.7%), nail discolouration (15.9%), vomiting (13.8%), blood creatinine increased (13.8%), hyponatraemia (13.4%), paronychia (12.5%), nail dystrophy (11.9%), onychomadesis (11.5%), epistaxis (10.6%), nail disorder (10.2%) and abdominal pain (10.0%). Most common Grade 3 or higher ADRs were stomatitis (10.6%), hyponatraemia (8.8%), palmar-plantar erythrodysaesthesia syndrome (7.9%), onycholysis (4.8%), diarrhoea (4.0%), hyperphosphataemia (2.9%), decreased appetite (2.5%), and nail dystrophy (2.5%). Grade 3 or 4 related TEAEs (47.6% vs 43.5%) and related serious adverse events (14.6% vs 10.5%) were reported more frequently for patients 65 years and older versus patients <65 years.

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-151084 · Präparat HOS-100442

Adverse reactions leading to dose reduction occurred in 59.7% of patients. Stomatitis (15.4%), palmar-plantar erythrodysaesthesia syndrome (9.6%), onycholysis (7.3%) and hyperphosphataemia (5.2%) were the most common adverse events leading to dose reduction.

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-151085 · Präparat HOS-100442

Adverse reactions leading to treatment discontinuation occurred in 19.4% of patients. Detachment of retinal pigment epithelium (1.7%) and stomatitis (1.5%) were the most common adverse events leading to treatment discontinuations.

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-151086 · Präparat HOS-100442

Tabulated list of adverse reactions The safety profile is based on pooled data from 479 locally advanced unresectable or metastatic urothelial carcinoma patients who were treated with Balversa in clinical studies. Patients were treated with Balversa at 8/9 mg starting dose orally once daily. Median duration of treatment was 4.8 months (range 0.1 to 43.4 months).

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-151087 · Präparat HOS-100442

Adverse reactions observed during clinical studies are listed below in Table 6 by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000).

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-151088 · Präparat HOS-100442

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11

HOS-151089 · Präparat HOS-100442

Table 6: Adverse reactions identified in clinical studies System organ class Frequency Adverse reaction Endocrine disorders common hyperparathyroidism Metabolism and nutrition very common hyperphosphataemia, hyponatraemia, disorders decreased appetite common hypercalcaemia, hypophosphataemia

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11–12

HOS-151090 · Präparat HOS-100442

11  Nervous system disorders very common dysgeusia Eye disorders very common central serous retinopathya, dry eye common ulcerative keratitis, keratitis, conjunctivitis, xerophthalmia, cataract, blepharitis, lacrimation increased Vascular disorders uncommon vascular calcification Respiratory, thoracic and very common epistaxis mediastinal disorders common nasal dryness Gastrointestinal disorders very common diarrhoea, stomatitisb, dry mouth, constipation, nausea, vomiting, abdominal pain common dyspepsia Skin and subcutaneous tissue very common paronychia, onycholysis, onychomadesis, disorders nail dystrophy, nail disorder, nail discolouration, palmar-plantar erythrodysaesthesia syndrome, alopecia, dry skin common onychalgia, onychoclasis, nail ridging, skin fissures, pruritus, skin exfoliation, xeroderma, hyperkeratosis, skin lesion, eczema, rash uncommon nail bed bleeding, nail discomfort, skin atrophy, palmar erythema, skin toxicity Renal and urinary disorders common acute kidney injury, renal impairment, renal failure Hepatobiliary disorders common hepatic cytolysis, hepatic function abnormal, hyperbilirubinaemia General disorders and very common asthenia, fatigue administration site conditions uncommon mucosal dryness Blood and lymphatic system very common anaemia disorders Investigations very common weight decreased, blood creatinine increased, alanine aminotransferase increased, aspartate aminotransferase increased a Central serous retinopathy includes Retinal detachment, Vitreous detachment, Retinal oedema, Retinopathy, Chorioretinopathy, Detachment of retinal pigment epithelium, Detachment of macular retinal pigment epithelium, Macular detachment, Serous retinal detachment, Subretinal fluid, Retinal thickening, Chorioretinitis, Serous retinopathy, Maculopathy, Choroidal effusion, vision blurred, visual impairment, visual acuity reduced. b Stomatitis includes mouth ulceration.

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

Nebenwirkungen · Balversa

Balversa 3 mg film-coated tablets Balversa 4 mg film-coated tablets Balversa 5 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12

HOS-151091 · Präparat HOS-100442

Description of selected adverse reactions

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