Truqap · 4.6 Fertility, pregnancy, and lactation · 1

HOS-100387 · has-adverse-reaction-information · PDF-Seite 12

Summary of safety profile The summary of safety profile of TRUQAP is based on data from 355 patients who received TRUQAP plus fulvestrant in the phase III (CAPItello-291) study. The median duration of exposure to capivasertib in CAPItello-291 was 5.4 months, with 28.2% patients exposed ≥ 12 months. The most common adverse reactions were diarrhoea (72.4%), rash (40.6%), nausea (34.6%), fatigue (32.1%), vomiting (21.4%), hyperglycaemia (19.2%), stomatitis (18.6%), , headache (17.2%),decreased appetite (16.9%), and urinary tract infection (16.6%). The most common grade 3 or 4 adverse reactions were rash (12.4%), diarrhoea (10.4%), anaemia (3.4%) hypokalaemia (2.8%), hyperglycaemia (2.5%), and stomatitis (2.3%). Serious adverse reactions were seen in 9% of patients receiving TRUQAP plus fulvestrant. Most common serious adverse reactions reported in patients receiving TRUQAP plus fulvestrant included rash (2.3%), diarrhoea (2.5%) and vomiting (1.1%). Dose reductions due to adverse reactions were reported in 18.9% of patients. The most common adverse reactions leading to dose reduction of TRUQAP were diarrhoea (8.7%) and rash (4.5%). Treatment discontinuation due to adverse reactions occurred in 10.4% of patients. The most common adverse reactions leading to treatment discontinuation were rash (4.5%), diarrhoea (2.3%) and vomiting (2%). Tabulated list of adverse reactions Table 8 lists the adverse reactions based on pooled data from patients treated with TRUQAP plus fulvestrant in clinical studies at the recommended dose. Adverse drug reactions (ADRs) are organised by MedDRA System Organ Class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness. Frequencies of occurrence of adverse reactions are defined as: 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 available data). 12 Table 8 Adverse drug reactions observed in patients treated with TRUQAP MedDRA SOC MedDRA term Any grade (%) Infections and Urinary tract infection1 Very common infestations Blood and lymphatic Anaemia Very common system disorders Immune system Hypersensitivity2 Common disorders Metabolism a

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100383 · has-contraindication-information · PDF-Seite 7

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

HOS-100382 · has-indication-information · PDF-Seite 2

TRUQAP is indicated in combination with fulvestrant for the treatment of adult patients with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following recurrence or progression on or after an endocrine-based regimen (see section 5.1). In pre- or perimenopausal women, TRUQAP plus fulvestrant should be combined with a luteinising hormone releasing hormone (LHRH) agonist. For men, administration of LHRH agonist according to current clinical practice standards should be considered.

HOS-100385 · has-interaction-information · PDF-Seite 10

Capivasertib is primarily metabolised by CYP3A4 and UGT2B7 enzymes. In vivo, capivasertib is a weak, time-dependent inhibitor of CYP3A. Medicinal products that may increase capivasertib plasma concentrations Strong CYP3A4 inhibitors Co-administration of TRUQAP with strong CYP3A4 inhibitors increases capivasertib concentration, which may increase the risk of TRUQAP toxicity. Co-administration with strong CYP3A4 inhibitors should be avoided (e.g. boceprevir, ceritinib, clarithromycin, cobicistat, conivaptan, ensitrelvir, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, mibefradil, mifepristone, nefazodone, nelfinavir, posaconazole, ribociclib, ritonavir, saquinavir, telaprevir, telithromycin, troleandomycin, tucatinib, voriconazole, grapefruit or grapefruit juice). If co-administration cannot be avoided, TRUQAP dose should be reduced (see section 4.2). Co-administration of multiple 200 mg doses of the strong CYP3A4 inhibitor itraconazole increased capivasertib total exposure (AUCinf) and the peak concentration (Cmax) by 95% and 70%, respectively, relative to capivasertib given alone. Moderate CYP3A4 inhibitors Co-administration of TRUQAP with moderate CYP3A4 inhibitors increases capivasertib concentration, which may increase the risk of TRUQAP toxicity. TRUQAP dose should be reduced when co-administered with moderate CYP3A4 inhibitor (e.g aprepitant, ciprofloxacin, cyclosporine, diltiazem, erythromycin, fluconazole, fluvoxamine, tofisopam, verapamil) (see section 4.2). Medicinal products that may decrease capivasertib plasma concentrations Strong CYP3A4 inducers Co-administration of TRUQAP with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John’s wort) should be avoided. Co-administration of capivasertib with strong CYP3A4 inducer enzalutamide decreased the capivasertib AUC by approximately 40% to 50%. Moderate CYP3A4 inducers Co-administration of capivasertib with moderate CYP3A4 inducer has the potential to decrease the concentration of capivasertib. This may reduce the efficacy of TRUQAP. Co-administration of moderate CYP3A4 inducers should be avoided (e.g. bosentan, cenobamate, dabrafenib, elagolix, etravirine, lersivirine, lesinurad, lopinavir, lorlatinib, metamizole, mitapivat, modafinil, nafcillin, pexidartinib, phenobarbital, rifabutin, semagacestat, sotorasib, talviraline, telotristat ethyl, thioridazine). Medicinal products whose plasma concentrations may be altered by capivasertib Substrate

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100386 · has-pregnancy-information · PDF-Seite 11

Women of childbearing potential/Contraception in males and females Women of childbearing potential should be advised to avoid becoming pregnant while receiving TRUQAP. A pregnancy test should be performed on women of childbearing potential prior to initiating treatment and verified as negative. Re-testing should be considered throughout treatment. Patients should be advised to use effective contraception during the use of TRUQAP and for the following periods after completion of treatment with TRUQAP: at least 4 weeks for females and 16 weeks for males. Pregnancy There are no data from the use of TRUQAP in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Therefore, TRUQAP is not recommended during pregnancy and in women of childbearing potential not using contraception. 11 Breast-feeding It is not known whether capivasertib or its metabolites are excreted in human milk. Exposure to capivasertib was confirmed in suckling rat pups which may indicate the excretion of capivasertib in milk. A risk to the breast-fed child cannot be excluded (see section 5.3). Breast-feeding should be discontinued during treatment with TRUQAP. Fertility There are no clinical data on fertility. In animal studies, no adverse effect on female reproductive organs was observed, but the effect on female fertility in rats was not studied. Capivasertib has resulted in testicular toxicity and may impair fertility in males of reproductive potential (see section 5.3). Please refer to section 4.6 of the prescribing information for fulvestrant.

HOS-100384 · has-warning-information · PDF-Seite 7

Hyperglycaemia The safety and efficacy of TRUQAP in patients with preexisting Type 1 diabetes or Type 2 diabetes requiring insulin and/or in patients with HbA1C ˃ 8.0% (63.9 mmol/mol) has not been studied as these patients were excluded from the phase III clinical study. This study included 21 (5.9%) patients in the TRUQAP plus fulvestrant arm with HbA1C ≥ 6.5%. Hyperglycaemia was more frequently reported in patients with a baseline HbA1C ≥ 6.5% (38.1% of patients) than those with a baseline HbA1C < 6.5% (17.8%). Severe hyperglycaemia, associated with diabetic ketoacidosis (DKA) and with fatal outcomes occurred in patients treated with TRUQAP (see section 4.8). DKA can occur at any time during TRUQAP treatment. In some reported cases, DKA developed in less than 10 days. Patients with history of diabetes mellitus may require intensified anti-diabetic treatment and should be closely monitored. Consultation with a diabetologist or a healthcare professional experienced in the treatment of hyperglycaemia is recommended for patients with diabetes. Before initiating treatment with TRUQAP, patients should be informed about TRUQAP’s potential to cause hyperglycaemia (see section 4.8) and requested to immediately contact their healthcare professional if hyperglycaemia symptoms (e.g. excessive thirst, urinating more often than usual or greater amount of urine than usual, or increased appetite with weight loss) occur. In a setting of additional co-morbidities and treatments (e.g. dehydration, malnourishment, concurrent chemotherapy/steroids, sepsis), the risk of hyperglycaemia progressing to diabetic ketoacidosis may be higher. DKA should be considered as one of the differential diagnoses in the event of additional nonspecific symptoms such as nausea, vomiting, abdominal pain, difficulty breathing, fruity odour on 7 breath, confusion, unusual fatigue, or sleepiness. In patients where DKA is suspected, TRUQAP treatment should be interrupted immediately. If DKA is confirmed, then TRUQAP should be permanently discontinued. Patients must be tested for fasting blood glucose (FG) levels and HbA1C prior to start of treatment with TRUQAP and in accordance with the intervals stated in Table 7. Based on the severity of hyperglycaemia, TRUQAP dosing may be interrupted, reduced, or permanently discontinued (see section 4.2, Table 3). More frequent blood glucose monitoring is recommended in patients that develop hyperglycae

Auszug; vollständigen Abschnitt im Original lesen.