Erivedge

Erivedge should only be prescribed by or under the supervision of a specialist physician experienced in the management of the approved indication. Posology The recommended dose is one 150 mg capsule taken once daily. Missed doses If a dose is missed, patients should be instructed not to take the missed dose but to resume with the next scheduled dose.

Duration of treatment In clinical studies, treatment with Erivedge was continued until disease progression or until unacceptable toxicity. Treatment interruptions of up to 4 weeks were allowed based on individual tolerability. Benefit of continued treatment should be regularly assessed, with the optimal duration of therapy varying for each individual patient.

2). Of a total number of 138 patients in 4 clinical studies of Erivedge in advanced basal cell carcinoma, approximately 40 % of 3 patients were ≥ 65 years old and no overall differences in safety and efficacy were observed between these patients and younger patients.

Renal impairment Mild and moderate renal impairment is not expected to impact the elimination of vismodegib and no dose adjustment is needed. Very limited data is available in patients with severe renal impairment. Patients with severe renal impairment should be carefully monitored for adverse reactions.

5 x ULN < TB < 3 x ULN, AST any severe: 3 x ULN < TB < 10 x ULN, AST any Paediatric population The safety and efficacy of Erivedge in children and adolescents aged below 18 years have not been established. 3), this medicinal product should not be used in children and adolescents aged below 18 years.

Method of administration Erivedge is for oral use. 2). The capsules must not be opened, to avoid unintended exposure to patients and health care providers.

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. 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. 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.

6). 3). 3). Criteria for a woman of childbearing potential (WCBP) A WCBP is defined in the Erivedge Pregnancy Prevention Programme as:  a sexually mature female who  has menstruated at any time during the previous 12 consecutive months,  has not undergone a hysterectomy or a bilateral oophorectomy, or who does not have medically-confirmed permanent premature ovarian failure,  does not have a XY genotype, Turner’s syndrome, or uterine agenesis, 4  becomes amenorrhoeic following cancer therapy, including treatment with Erivedge.

Counselling For a WCBP Erivedge is contraindicated in a WCBP who does not comply with the Erivedge Pregnancy Prevention Programme. 6) while she is taking Erivedge, unless she commits to not having sexual intercourse (abstinence),  She must tell her healthcare provider if any of the following occur during treatment and for 24 months after her final dose:  If she becomes pregnant or think for any reason that she may be pregnant,  If she misses her expected menstrual period,  If she stops using contraception unless she commits to not having sexual intercourse (abstinence),  If she needs to change contraception during treatment,  She must not breast-feed while taking Erivedge and for 24 months after the final dose.

For men Vismodegib is present in semen. 6),  He will tell his healthcare provider if his female partner becomes pregnant while he is taking Erivedge or during the 2 months after his final dose. For health care providers (HCP) HCPs must educate the patients so they understand and acknowledge all the conditions of the Erivedge Pregnancy Prevention Programme.

6). 6). 5 Pregnancy testing In a WCBP, a medically supervised pregnancy test, conducted by a heath care provider, should be performed within 7 days prior to initiating treatment and monthly during treatment. Pregnancy tests should have a minimum sensitivity of 25 mIU/mL as per local availability.

Patients who present with amenorrhoea during treatment with Erivedge should continue monthly pregnancy testing while on treatment. Prescribing and dispensing restrictions for WCBP The initial prescription and dispensing of Erivedge should occur within a maximum of 7 days of a negative pregnancy test (day of pregnancy test = day 1).

1. 6). 6). 5).