Adverse reactions : תופעות לוואי

4.8     Undesirable effects

Summary of the safety profile
The most common adverse drug reactions (ADR) occurring in ≥ 30 % of patients, were muscle spasms (74.6 %), alopecia (65.9%), dysgeusia (58.7%), weight decreased (50.0%), fatigue (47.1%), nausea (34.8 %) and diarrhea (33.3%).

Tabulated list of adverse reactions
ADRs are presented in table 1 below by system organ class (SOC) and absolute frequency.
Frequencies 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)
Not known (cannot be estimated from the available data).
Within each frequency grouping, ADRs are presented in the order of decreasing seriousness.

The safety of Erivedge has been evaluated in clinical studies with 138 patients treated for advanced basal cell carcinoma (aBCC), which includes both metastatic BCC (mBCC) and locally advanced BCC (laBCC). In four open label phase 1 and 2 clinical studies patients were treated with at least one dose of Erivedge monotherapy at doses  150 mg. Doses > 150 mg did not result in higher plasma concentrations in clinical studies and patients on doses > 150 mg have been included in the analysis.
Additionally, safety was assessed in a post approval study that included 1215 aBCC patients evaluable for safety and treated with 150 mg. In general the safety profile observed was consistent in both mBCC and laBCC patients and across studies as described below.


Table 1         ADRs occurring in patients treated with Erivedge

MedDRA SOC                Very common                  Common                     Frequency not known Endocrine disorders                                                               precocious puberty**** 
Metabolism and            decreased appetite           dehydration nutrition disorders
Nervous system            dysgeusia                    hypogeusia disorder                  ageusia
Gastrointestinal          nausea                       abdominal pain upper disorders                 diarrhoea                    abdominal pain constipation vomiting dyspepsia
Hepatobiliary                                          hepatic enzymes            drug induced liver disorders                                              increased**                injury***** 
Skin and                  alopecia                     madarosis                  Stevens-Johnson syndrome subcutaneous tissue       pruritus                     abnormal hair growth       (SJS)/toxic epidermal disorders                 rash                                                    necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms
(DRESS) and acute generalised exanthematous pustulosis (AGEP)******
Musculoskeletal and       muscle spasms                back pain                  epiphyses premature connective tissue         arthralgia                   musculoskeletal chest      fusion**** disorders                 pain in extremity            pain myalgia flank pain musculoskeletal pain blood creatine phosphokinase increased***
Reproductive system       amenorrhoea* and breast disorders
General disorders         weight decreased             asthenia and administration        fatigue site conditions           pain
All reporting is based on ADRs of all grades using National Cancer Institute - Common Terminology Criteria for Adverse Events v 3.0 except where noted.
*Of the 138 patients with advanced BCC, 10 were WCBP. Amongst these women, amenorrhoea was observed in 3 patients (30 %).
MedDRA  Medical Dictionary for Regulatory Activities.
**Includes preferred terms: liver function test abnormal, blood bilirubin increased, gamma-glutamyl transferase increased, aspartate aminotransferase increased, alkaline phosphatase increased, liver hepatic enzyme increased.
*** Observed in patients during a post-approval study with 1215 safety evaluable patients.
****Individual cases have been reported in patients with medulloblastoma during post-marketing use (see section   4.4)
***** Cases of drug induced liver injury have been reported in patients during post-marketing use.
******Cases of SCAR (including SJS/TEN, DRESS and AGEP) have been reported in patients during post- marketing use.


Reporting of suspected adverse reactions
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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il