Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Verzenios

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HOS-137588 · Präparat HOS-098067

The most commonly occurring adverse reactions are diarrhoea, infections, neutropenia, leukopenia, anaemia, fatigue, nausea, vomiting, alopecia and decreased appetite.

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

Nebenwirkungen · Verzenios

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HOS-137589 · Präparat HOS-098067

Of the most common adverse reactions, Grade ≥ 3 events were less than 5 % with the exception of neutropenia, leukopenia, and diarrhoea.

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

Nebenwirkungen · Verzenios

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HOS-137590 · Präparat HOS-098067

Tabulated list of adverse reactions

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

Nebenwirkungen · Verzenios

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HOS-137591 · Präparat HOS-098067

In the following table, adverse reactions are listed in order of MedDRA body system organ class and frequency. Frequency gradings are: 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), and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

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Nebenwirkungen · Verzenios

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HOS-137592 · Präparat HOS-098067

Table 8. Adverse reactions reported in the phase 3 studies of abemaciclib in combination with endocrine therapya (N = 3 559) and during post-marketing experience

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Nebenwirkungen · Verzenios

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HOS-137593 · Präparat HOS-098067

System organ class Very common Common Uncommon Rare Infections and Infections b infestations Blood and lymphatic Neutropenia Febrile system disorders Leukopenia neutropenia e Anaemia Thrombocytopenia Lymphopenia h Metabolism and Decreased appetite nutrition disorders Nervous system Headache f disorders Dysgeusia g Dizziness g Eye disorders Lacrimation Photopsia increased Keratitis Vascular disorders Venous thromboembolism c

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Nebenwirkungen · Verzenios

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HOS-137594 · Präparat HOS-098067

Respiratory, thoracic ILD/pneumonitis d and mediastinal disorders

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Nebenwirkungen · Verzenios

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HOS-137595 · Präparat HOS-098067

Gastrointestinal Diarrhoea Dyspepsia f disorders Vomiting Nausea Stomatitis f Skin and subcutaneous Alopecia g Nail disorder f Erythema tissue disorders Pruritus g Dry skin e multiforme Rash g Musculoskeletal and Muscular connective tissue weakness e disorders General disorders and Pyrexia e administration site Fatigue conditions

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Nebenwirkungen · Verzenios

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HOS-137596 · Präparat HOS-098067

10  Investigations Alanine aminotransferase increased g Aspartate aminotransferase increased g a Abemaciclib in combination with anastrozole, letrozole, exemestane, tamoxifen, or fulvestrant. b Infections include all reported preferred terms that are part of the system organ class infections and infestations. c Venous thromboembolic events include deep vein thrombosis (DVT), pulmonary embolism, cerebral venous sinus thrombosis, subclavian, axillary vein thrombosis, DVT inferior vena cava and pelvic venous thrombosis. d ILD/pneumonitis for early breast cancer (EBC) include all reported preferred terms that are part of the MedDRA SMQ interstitial lung disease. For metastatic breast cancer (mBC) preferred terms include interstitial lung disease, pneumonitis, organising pneumonia, pulmonary fibrosis and bronchiolitis obliterans. e Considered ADRs in the mBC setting only (MONARCH 2 and MONARCH 3). f Considered ADRs in the EBC setting only (monarchE). g Common frequency in the EBC setting (monarchE), very common in the mBC setting (MONARCH 2 and MONARCH 3). h Common frequency in mBC setting (MONARCH 2 and MONARCH 3), very common in the EBC setting (monarchE).

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Nebenwirkungen · Verzenios

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HOS-137597 · Präparat HOS-098067

Description of selected adverse reactions

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Nebenwirkungen · Verzenios

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HOS-137598 · Präparat HOS-098067

Neutropenia Neutropenia was reported frequently across studies. In the monarchE study, neutropenia was reported in 45.8 % of patients. Grade 3 or 4 decrease in neutrophil counts (based on laboratory findings) was reported in 19.1 % of patients receiving abemaciclib in combination with endocrine therapy with a median time to onset of 30 days, and median time to resolution of 16 days. Febrile neutropenia was reported in 0.3 % patients. In MONARCH 2 and MONARCH 3 studies, neutropenia was reported in 45.1 % of patients. Grade 3 or 4 decrease in neutrophil counts (based on laboratory findings) was reported in 28.2 % of patients receiving abemaciclib in combination with aromatase inhibitors or fulvestrant. The median time to onset of Grade 3 or 4 neutropenia was 29 to 33 days, and median time to resolution was 11 to 15 days. Febrile neutropenia was reported in 0.9 % patients. Dose modification is recommended for patients who develop Grade 3 or 4 neutropenia (see section 4.2).

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

Nebenwirkungen · Verzenios

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HOS-137599 · Präparat HOS-098067

Diarrhoea Diarrhoea was the most commonly reported adverse reaction (see Table 8). Incidence was greatest during the first month of abemaciclib treatment and was lower subsequently. In the monarchE study, the median time to onset of the first diarrhoea event of any grade was 8 days. The median duration of diarrhoea was 7 days for Grade 2 and 5 days for Grade 3. In MONARCH 2 and MONARCH 3 studies, the median time to onset of the first diarrhoea event of any grade was approximately 6 to 8 days. The median duration of diarrhoea was 9 to 12 days for Grade 2 and 6 to 8 days for Grade 3. Diarrhoea returned to baseline or lesser grade with supportive treatment such as loperamide and/or dose adjustment (see section 4.2).

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Nebenwirkungen · Verzenios

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HOS-137600 · Präparat HOS-098067

Increased aminotransferases In the monarchE study, ALT and AST elevations were reported frequently (12.3 % and 11.8 %, respectively) in patients receiving abemaciclib in combination with endocrine therapy. Grade 3 or 4 ALT or AST elevations (based on laboratory findings) were reported in 2.6 % and 1.6 % patients. The median time to onset of Grade 3 or 4 ALT elevation was 118 days, and median time to resolution was 14.5 days. The median time to onset of Grade 3 or 4 AST elevation was 90.5 days, and median time to resolution was 11 days. In MONARCH 2 and MONARCH 3 studies, ALT and AST elevations were reported frequently (15.1 % and 14.2 %, respectively) in patients receiving abemaciclib in combination with aromatase inhibitors or fulvestrant. Grade 3 or 4 ALT or AST elevations (based on laboratory findings) were reported in 6.1 % and 4.2 % patients. The median time to onset of Grade 3 11 or 4 ALT elevation was 57 to 61 days, and median time to resolution was 14 days. The median time to onset of Grade 3 or 4 AST elevation was 71 to 185 days, and median time to resolution was 13 to 15 days. Dose modification is recommended for patients who develop Grade 3 or 4 ALT or AST increase (see section 4.2).

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

Nebenwirkungen · Verzenios

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HOS-137601 · Präparat HOS-098067

Creatinine Although not an adverse reaction, abemaciclib has been shown to increase serum creatinine. In the monarchE study, 99.3 % of patients had serum creatinine elevations (based on laboratory findings), and of these, 0.5 % of patients had Grade 3 or 4 elevations. In patients receiving endocrine therapy alone, 91.0 % reported an increase in serum creatinine (all laboratory grades). In MONARCH 2 and MONARCH 3 studies, 98.3 % of patients had serum creatinine elevations (based on laboratory findings), and of these, 1.9 % of patients had Grade 3 or 4 elevations. In patients receiving an aromatase inhibitor or fulvestrant alone, 78.4 % reported an increase in serum creatinine (all laboratory grades). Abemaciclib has been shown to increase serum creatinine due to inhibition of renal tubular secretion transporters without affecting glomerular function (as measured by iohexol clearance) (see section 4.5). In clinical studies, increases in serum creatinine occurred within the first month of abemaciclib dosing, remained elevated but stable through the treatment period, were reversible upon treatment discontinuation, and were not accompanied by changes in markers of renal function, such as blood urea nitrogen (BUN), cystatin C, or calculated glomerular filtration rate based on cystatin C.

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Nebenwirkungen · Verzenios

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HOS-137602 · Präparat HOS-098067

Reporting of suspected adverse reactions

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Nebenwirkungen · Verzenios

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HOS-137603 · Präparat HOS-098067

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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

Wechselwirkungen · Etcamah

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HOS-153193 · Präparat HOS-100955

When co-administering camizestrant in combination with ribociclib, plus a moderate CYP3A4/5 inducer (including but not limited to: e.g. bosentan, nafcillin, modafinil and phenobarbital), no dose adjustment of camizestrant is necessary. When co-administering camizestrant in combination with abemaciclib or palbociclib, the use of such moderate CYP3A4/5 inducers should be avoided by switching to an alternate concomitant drug product (see section 5.2).

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) abemaciclib (HOS-086209) palbociclib (HOS-126972) modafinil (HOS-090546) nafcillin (HOS-125452) ribociclib (HOS-109454) camizestrant (HOS-153187) bosentan (HOS-086291)