Erivedge

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Erivedge 150 mg hard capsules  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains 150 mg of vismodegib. 
 
Excipient with known effect: 
Each hard capsule contains 71.5 mg lactose monohydrate per capsule. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule (capsule). 
 
Pink coloured opaque body marked “150 mg” and a grey opaque cap marked “VISMO” with black ink. 
The size of the capsule is ‘Size 1’ (dimensions 19.0 x 6.6 mm). 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indication 
 
Erivedge is indicated for the treatment of adult patients with: 
• symptomatic metastatic basal cell carcinoma 
• locally advanced basal cell carcinoma inappropriate for surgery or radiotherapy (see section 5.1). 
 
4.2 Posology and method of administration 
 
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 trials, 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. 
 



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Special populations 
 
Elderly 
No dose adjustment is required in patients ≥ 65years of age (see section 5.2). Of a total number of 
138 patients in 4 clinical trials of Erivedge in advanced basal cell carcinoma, approximately 40 % of 
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. 
 
Hepatic impairment 
No dose adjustment is required in patients with mild, moderate or severe hepatic impairment defined 
based on National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG)- criteria for 
hepatic impairment:  

• mild:total bilirubin (TB) ≤ upper limit of normal (ULN), aspartate aminotransferase 
(AST)>ULN or ULN<TB≤1.5xULN, AST any 

• moderate: 1.5 x ULN < TB < 3 x ULN, AST any 
• severe: 3 x ULN < TB < 10 x ULN, AST any  

(see section 5.2) 
 
Paediatric population 
The safety and efficacy of Erivedge in children and adolescents aged below 18 years have not been 
established. 
Due to safety concerns (see sections 4.4 and 5.3), this medicinal product should not be used in children 
and adolescents aged below 18 years. 
 
Method of administration  
Erivedge is for oral use.The capsules must be swallowed whole with water, with or without food 
(see section 5.2). The capsules must not be opened, to avoid unintended exposure to patients and 
health care providers. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
• Women who are pregnant or breast-feeding (see sections 4.4 and 4.6). 
• Women of childbearing potential who do not comply with the Erivedge Pregnancy Prevention 

Programme (see sections 4.4 and 4.6). 
• Coadministration of St John's wort (Hypericum perforatum) (see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
Embryo-foetal death or severe birth defects 
Erivedge may cause embryo-foetal death or severe birth defects when administered to a pregnant 
woman (see section 4.6). Hedgehog pathway inhibitors, (see section 5.1) such as vismodegib, have 
been demonstrated to be embryotoxic and/or teratogenic in multiple animal species and can cause 
severe malformations, including craniofacial anomalies, midline defects and limb defects 
(see section 5.3). Erivedge must not be used during pregnancy. 
 



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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, 
• 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.  
A WCBP must understand that: 
• Erivedge exposes a teratogenic risk to the unborn child, 
• She must not take Erivedge if she is pregnant or plans to become pregnant, 
• She must have a negative pregnancy test, conducted by a health care provider within 7 days 

before starting Erivedge treatment,  
• She must have a negative pregnancy test monthly during treatment, even if she has become 

amenorrhoeic, 
• She must not become pregnant while taking Erivedge and for 24 months after her final dose, 
• She must be able to comply with effective contraceptive measures, 
• She must use 2 methods of recommended contraception (see the ‘Contraception' section below 

and section 4.6) 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. To avoid potential foetal exposure during pregnancy, a male patient 
must understand that: 
• Erivedge exposes a teratogenic risk to the unborn child if he engages in unprotected sexual 

activity with a pregnant woman, 
• He must always use the recommended contraception (see the ‘Contraception' section below and 

section 4.6),  
• 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.  
 
Contraception 
WCBP 
Female patients must use two methods of recommended contraception including one highly effective 
method and a barrier method during Erivedge therapy and for 24 months after the final dose 
(see section 4.6).  
 



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Men 
Male patients must always use a condom (with spermicide, if available), even after a vasectomy, when 
having sex with a female partner while taking Erivedge and for 2 months after the final dose 
(see section 4.6). 
 
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). Prescriptions of Erivedge should be limited 
to 28 days of treatment and continuation of treatment requires a new prescription. 
 
Educational material 
In order to assist health care providers and patients to avoid embryonic and foetal exposure to 
Erivedge the Marketing Authorisation Holder will provide educational materials (Erivedge Pregnancy 
Prevention Programme) to reinforce the potential risks associated with the use of Erivedge.  
 
Effects on post-natal development 
Premature fusion of the epiphyses and precocious puberty have been reported in paediatric patients 
exposed to Erivedge. Due to the long drug elimination half-life, these events may occur or progress 
after drug discontinuation. In animal species, vismodegib has been shown to cause severe irreversible 
changes in growing teeth (degeneration/necrosis of odontoblasts, formation of fluid-filled cysts in the 
dental pulp, ossification of the root canal, and haemorrhage) and closure of the epiphyseal growth 
plate. The findings of premature fusion of the epiphyses indicate a potential risk for short stature and 
tooth deformities to infants and children (see section 5.3). 
 
Blood donation 
Patients should not donate blood while taking Erivedge and for 24 months after the final dose. 
 
Semen donation 
Male patients should not donate semen while taking Erivedge and for 2 months after the final dose. 
 
Interactions 
Concomitant treatment with strong CYP inducers (e.g. rifampicin, carbamazepine or phenytoin) 
should be avoided, as a risk for decreased plasma concentrations and decreased efficacy of vismodegib 
cannot be excluded (see also section 4.5).    
 
Severe cutaneous adverse reactions  

Severe cutaneous adverse reactions (SCARs) including cases of Stevens-Johnson syndrome/Toxic 
epidermal necrolysis (SJS/TEN), Drug reaction with eosinophilia and systemic symptoms (DRESS) 
and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening, have been 
reported during post-marketing use (see section 4.8). If the patient has developed any of these 
reactions with the use of vismodegib, treatment with vismodegib must not be restarted in this patient at 
any time.  
 
Cutaneous squamous cell carcinoma (cuSCC)  
Patients with advanced BCC have an increased risk of developing cuSCC. Cases of cuSCC have been 
reported in advanced BCC patients treated with Erivedge. It has not been determined whether cuSCC 
is related to Erivedge treatment. Therefore, all patients should be monitored routinely while taking 
Erivedge, and cuSCC should be treated according to the standard of care. 
 



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Additional precautions  
Patients should be instructed never to give this medicinal product to another person. Any unused 
capsules at the end of treatment should immediately be disposed of by the patient in accordance with 
local requirements (if applicable, e.g. by returning the capsules to their pharmacist or physician). 
 
Excipients 
Erivedge capsules contain lactose monohydrate. Patients with a rare hereditary problem of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium 
free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of concomitant medicinal products on vismodegib 
 
Clinically significant PK interactions between vismodegib and pH elevating agents are not expected. 
Results from a clinical study demonstrated a 33% decrease in vismodegib unbound drug 
concentrations after 7 days co-treatment with 20 mg rabeprazole (a proton pump inhibitor) given 2 h 
before each vismodegib administration. This interaction is not expected to be clinically significant.  
 
Clinically significant PK interactions between vismodegib and CYP450 inhibitors are not expected. 
Results from a clinical study demonstrated a 57% increase in vismodegib unbound drug 
concentrations on day 7 after co-treatment with 400 mg fluconazole (a moderate CYP2C9 inhibitor) 
daily, but this interaction is not expected to be clinically significant. Itraconazole (a strong CYP3A4 
inhibitor) 200 mg daily did not influence vismodegib AUC0-24h after 7 days co-treament in healthy 
volunteers. 
  
Clinically significant PK interactions between vismodegib and P-gp inhibitors are not expected. 
Results from a clinical study demonstrated no clinically significant PK interaction between 
vismodegib and itraconazole (a strong P-glycoprotein inhibitor) in healthy volunteers. 
 
When vismodegib is administered with CYP inducers (rifampicin, carbamazepine, phenytoin, 
St. John´s wort), exposure to vismodegib may be decreased (see sections 4.3 and 4.4). 
 
Effects of vismodegib on concomitant medicinal products 
 
Contraceptive steroids 
Results of a drug-drug interaction study conducted in cancer patients demonstrated that the systemic 
exposure of ethinyl estradiol and norethindrone is not altered when co-administered with vismodegib. 
However, the interaction study was of only 7 days duration and it cannot be excluded that vismodegib 
upon longer treatment is an inducer of enzymes which metabolise contraceptive steroids. Induction 
could lead to decreases in systemic exposure of the contraceptive steroids and thereby reduced 
contraceptive efficacy. 
 
Effects on specific enzymes and transporters 
In vitro studies indicate that vismodegib has the potential to act as an inhibitor of breast cancer 
resistance protein (BCRP). In vivo interaction data is not available. It may not be excluded that 
vismodegib may give rise to increased exposure of medicinal products transported by this protein, 
such as rosuvastatin, topotecan, and sulfasalazin. Concomitant administration should be performed 
with caution and a dose adjustment may be necessary. 
 
Clinically significant PK interactions between vismodegib and CYP450 substrates are not expected. In 
vitro, CYP2C8 was the most sensitive CYP isoform for vismodegib inhibition. However, results of a 
drug-drug interaction study conducted in cancer patients demonstrated that the systemic exposure of 
rosiglitazone (a CYP2C8 substrate) is not altered when co-administered with vismodegib. Thus 
inhibition of CYP enzymes by vismodegib in vivo may be excluded. 



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In vitro, vismodegib is an inhibitor of OATP1B1. It cannot be excluded that vismodegib may increase 
the exposure to substrates of OATP1B1, e.g. bosentan, ezetimibe, glibenclamide, repaglinide, 
valsartan and statins. In particular, caution should be exercised if vismodegib is administered in 
combination with any statin.  
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential (WCBP) 
Due to the risk of embryo-foetal death or severe birth defects caused by vismodegib, women taking 
Erivedge must not be pregnant or become pregnant during treatment and for 24 months after the final 
dose (see sections 4.3 and 4.4). 
Erivedge is contraindicated in WCBP who do not comply with the Erivedge Pregnancy Prevention 
Programme. 
 
In case of pregnancy or missed menstrual periods 
If the patient does become pregnant, misses a menstrual period, or suspects for any reason that she 
may be pregnant, she must notify her treating physician immediately. 
Persistent lack of menses during treatment with Erivedge should be assumed to indicate pregnancy 
until medical evaluation and confirmation. 
 
Contraception in males and females 
Women of childbearing potential (WCBP) 
WCBP must be able to comply with effective contraceptive measures. She must use two methods of 
recommended contraception including one highly effective method and a barrier method during 
Erivedge therapy and for 24 months after the final dose. WCBP, whose periods are irregular or 
stopped, must follow all the advice on effective contraception. 
 
Men 
Vismodegib is present in semen. To avoid potential foetal exposure during pregnancy, male patients 
must always use a condom (with spermicide, if available), even after a vasectomy, when having sex 
with a female partner while taking Erivedge and for 2 months after the final dose. 
 
The following are recommended forms of highly effective methods:  
• Hormonal depot injection,  
• Tubal sterilisation,  
• Vasectomy,  
• Intrauterine device (IUD).  

 
The following are recommended forms of barrier methods:  
• Any male condom (with spermicide, if available), 
• Diaphragm (with spermicide, if available). 
 
Pregnancy 
Erivedge may cause embryo-foetal death or severe birth defects when administered to a pregnant 
woman (see section 4.4). Hedgehog pathway inhibitors (see section 5.1) such as vismodegib, have 
been demonstrated to be embryotoxic and/or teratogenic in multiple animal species and can cause 
severe malformations, including craniofacial anomalies, midline defects and limb defects 
(see section 5.3). In case of pregnancy in a woman treated with Erivedge, treatment must be stopped 
immediately. 
 
Breast-feeding  
The extent to which vismodegib is excreted in breast milk is not known. Due to its potential to cause 
serious developmental defects women must not breast-feed while taking Erivedge and for 24 months 
after the final dose (see sections 4.3 and 5.3). 
 



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Fertility 
Human female fertility may be compromised by treatment with Erivedge (see section 5.3). 
Reversibility of fertility impairment is unknown. Additionally, amenorrhoea has been observed in 
clinical trials in WCBP (see section 4.8). Fertility preservation strategies should be discussed with 
WCBP prior to starting treatment with Erivedge.  
 
Fertility impairment in human males is not expected (see Section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Erivedge has no or negligible influence on the ability to drive and use machines. 
 
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 trials 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 trials 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 trials 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. 
 



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Table 1  ADRs occurring in patients treated with Erivedge 
 
MedDRA SOC Very common Common Frequency not known 
Metabolism and 
nutrition disorders 

Decreased appetite 
 

Dehydration 
 

 

Nervous system 
disorder 

Dysgeusia  
Ageusia 

Hypogeusia  

Gastrointestinal 
disorders 

Nausea 
Diarrhoea 
Constipation 
Vomiting 
Dyspepsia 

Abdominal pain upper 
Abdominal pain 
 

 

Hepatobiliary 
disorders 
 

 Hepatic enzymes 
increased** 
 

Drug induced liver 
injury***** 

Skin and 
subcutaneous tissue 
disorders 

Alopecia 
Pruritus 
Rash 

Madarosis 
Abnormal hair growth 
 

Stevens-Johnson Syndrome 
(SJS)/Toxic Epidermal 
Necrolysis (TEN), Drug 
Reaction with Eosinophilia 
and Systemic Symptoms 
(DRESS) and Acute 
Generalised Exanthematous 
Pustulosis (AGEP)****** 

Musculoskeletal and 
connective tissue 
disorders 

Muscle spasms 
Arthralgia 
Pain in extremity 
 

Back pain 
Musculoskeletal chest 
pain 
Myalgia 
Flank pain 
Musculoskeletal pain 
Blood creatine 
phosphokinase 
increased*** 

Epiphyses premature 
fusion**** 
 

Endocrine disorders   Precocious puberty**** 

Reproductive system 
and breast disorders 

Amenorrhoea*   

General disorders 
and administration 
site conditions 

Weight decreased 
Fatigue 
Pain 

Asthenia 
 

 

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. Healthcare 



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professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Erivedge has been administered at doses 3.6 times higher than the recommended 150 mg daily dose. 
No increases in plasma vismodegib levels or toxicity were observed during these clinical trials. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, ATC code: L01XX43. 
 
Mechanism of action 
Vismodegib is an orally available small-molecule inhibitor of the Hedgehog pathway. Hedgehog 
pathway signalling through the Smoothened transmembrane protein (SMO) leads to the activation and 
nuclear localisation of Glioma-Associated Oncogene (GLI) transcription factors and induction of 
Hedgehog target genes. Many of these genes are involved in proliferation, survival, and differentiation. 
Vismodegib binds to and inhibits the SMO protein thereby blocking Hedgehog signal transduction. 
 
Clinical efficacy and safety 
The pivotal trial, ERIVANCE BCC (SHH4476g), was an international, single-arm, multi-centre, 
2-cohort study. Metastatic BCC was defined as BCC that had spread beyond the skin to other parts of 
the body, including the lymph nodes, lung, bones and/or internal organs. LaBCC patients had 
cutaneous lesions that were inappropriate for surgery (inoperable, multiply recurrent where curative 
resection deemed to be unlikely or for whom surgery would result in substantial deformity or 
morbidity) and for which radiotherapy was unsuccessful or contraindicated or inappropriate. Prior to 
study enrolment, diagnosis of BCC was confirmed by histology. Patients with Gorlin syndrome who 
had at least one aBCC lesion and met inclusion criteria were eligible to participate in the study. 
Patients were treated with oral daily dosing of Erivedge at 150 mg.  
 
The median age of the efficacy evaluable population was 62 years (46 % were at least 65 years old), 
61 % male and 100 % White. For the mBCC cohort, 97 % of patients had prior therapy including 
surgery (97 %), radiotherapy (58 %), and systemic therapies (30 %). For the laBCC cohort (n = 63), 
94 % of patients had prior therapies including surgery (89 %), radiotherapy (27 %), and 
systemic/topical therapies (11 %). The median duration of treatment was 12.9 months (range 0.7 to 
47.8 months).  
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


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The primary endpoint was objective response rate (ORR) as assessed by an independent review 
facility (IRF) as summarised in Table 2. Objective response was defined as a complete or partial 
response determined on two consecutive assessments separated by at least 4 weeks. In the mBCC 
cohort, tumour response was assessed according to the Response Evaluation Criteria in Solid Tumours 
(RECIST) version 1.0. In the laBCC cohort, tumour response was assessed based on visual assessment 
of external tumour and ulceration, tumour imaging (where appropriate), and tumour biopsy. A patient 
was considered a responder in the laBCC cohort if at least one of the following criteria was met and 
the patient did not experience progression: (1) ≥ 30 % reduction in lesion size [sum of the longest 
diameter (SLD)], from baseline in target lesions by radiography; (2) ≥ 30 % reduction in SLD from 
baseline in externally visible dimension of target lesions; (3) Complete resolution of ulceration in all 
target lesions. Key data are summarised in Table 2: 
 
Table 2  SHH4476g Erivedge Efficacy Results (IRF 21 months and Investigator assessed 

39 months follow-up after last patient enrolled): efficacy-evaluable patients*,† 
 

 
 

 
IRF-Assessed 

 
Investigator-Assessed 

 
mBCC 
(n = 33) 

laBCC** 
(n = 63) 

mBCC 
(n = 33) 

laBCC** 
(n = 63) 

Responders  11 (33.3 %) 30 (47.6 %) 16 (48.5 %) 38 (60.3 %) 
95 % CI for overall 
response 

(19.2 %, 51.8 %) (35.5 %, 60.6 %) (30.8%, 66.2 %) (47.2 %, 71.7 %) 

Complete Response 0  14 (22.2 %)  0  20 (31.7 %) 
Partial Response 11 (33.3 %) 16 (25.4 %)  16 (48.5 %) 18 (28.6 %) 
Stable disease  20 22 14 15 
Progressive disease ‡ 1 8 2 6 
Median Duration of 
Response (months) 

7.6 9.5 14.8  26.2 

(95 % CI) (5.5, 9.4) (7.4, 21.4) (5.6, 17.0) (9.0, 37.6) 
Median Progression 
Free survival (months) 

9.5 9.5 9.3  12.9 

(95 % CI) (7.4,11.1) (7.4, 14.8) (7.4, 16.6) (10.2, 28.0) 
Median OS, 
(months) 
(95 % CI) 

  33.4 
(18.1, NE)  

NE 
(NE, NE) 

1-year survival 
rate 
(95 % CI) 

  78.7 % 
(64.7, 92.7) 

93.2 % 
(86.8, 99.6) 

NE = not estimable 
* Efficacy-evaluable patient population is defined as all enrolled patients who received any amount of Erivedge and 
for whom the independent pathologist’s interpretation of archival tissue or baseline biopsy was consistent with BCC.  
† Unevaluable/missing data included 1 mBCC and 4 laBCC patients. 
‡ Progression in laBCC cohort is defined as meeting any of the following criteria: (1) ≥ 20 % increase in the sum of 
the longest dimensions (SLD) from nadir in target lesions (either by radiography or by externally visible dimension), 
(2) New ulceration of target lesions persisting without evidence of healing for at least 2 weeks, (3) New lesions by 
radiography or physical examination, (4) Progression of non-target lesions by RECIST. 
**54 % of laBCC patients had no histopathologic evidence of BCC at 24 weeks. 

 
As shown in the waterfall plots in figures 1 and 2, which chart maximum reduction in target lesion(s) 
size for each patient, the majority of patients in both cohorts experienced tumour shrinkage as assessed 
by the IRF. 
 



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Figure 1 SHH4476g Metastatic BCC Cohort 
 

 
 
Note: Tumour size is based on sum of longest dimensions of target lesions. PD = progressive disease, SD = stable disease, 
PR = partial response. 3 patients had a best percent change in tumour size of 0; these are represented by minimal positive bars 
in the figure. Four patients were excluded from the figure: 3 patients with stable disease were assessed by non-target lesions 
only and 1 patient was unevaluable.  
 
Figure 2 SHH4476g Locally Advanced BCC Cohort   
 

 
 
Note: Tumour size is based on sum of longest dimensions of target lesions. PD = progressive disease, SD = stable disease, 
R = response, * = complete resolution of ulceration(s). Response assessment was based on a composite endpoint defined as 
above. Four patients did not have lesion measurements and were not included in the plot.  
 



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Time to maximum tumour reduction 
Among patients who achieved tumour reduction, the median time to maximum tumour reduction 
occurred in 5.6 and 5.5 months for laBCC and mBCC patients respectively, based on the IRF 
assessment. According to investigator assessment, the median time to maximum tumour reduction 
occurred in 6.7 and 5.5 months for laBCC and mBCC patients respectively.  
 
Cardiac electrophysiology 
In a thorough QTc study in 60 healthy subjects, there was no effect of therapeutic doses of Erivedge 
on the QTc interval. 
 
Post approval study results 
A post-approval, open-label, non-comparative, multicenter, phase II clinical trial (MO25616) was 
conducted in 1232 patients with advanced BCC, of whom 1215 patients were evaluable for efficacy 
and safety with laBCC (n = 1119) or mBCC (n = 96). LaBCC was defined as cutaneous lesions that 
were inappropriate for surgery (inoperable, or for whom surgery would result in substantial deformity) 
and for which radiotherapy was unsuccessful or contraindicated. Metastatic BCC was defined as 
histologically confirmed distant metastasis. Prior to study enrollment, diagnosis of BCC was 
confirmed by histology. Patients were treated with oral daily dosing of Erivedge at 150mg.  
The median age for all patients was 72 years. The majority of patients were male (57%); 8% had 
mBCC whereas 92% had laBCC. For the metastatic cohort, the majority of patients had prior therapies, 
including surgery (91%), radiotherapy (62%) and systemic therapy (16%). For the locally advanced 
cohort, the majority of patients had prior therapies, including surgery (85%), radiotherapy (28%) and 
systemic therapy (7%). The median duration of treatment for all patients was 8.6 months (range 0 to 
44.1).  
Among patients in the efficacy-evaluable population with measurable and histologically confirmed 
disease, 68.5% and 36.9% responded to treatment in the laBCC and mBCC cohorts, respectively, by 
RECIST v1.1. Of patients who had a confirmed response (partial or complete), the median Duration of 
Response was 23.0 months (95% CI:  20.4, 26.7) in the laBCC cohort and 13.9 months (95% CI:  9.2, 
NE) in the mBCC cohort. Complete response was achieved in 4.8% patients in the mBCC cohort and 
33.4% in the laBCC cohort. Partial response was achieved in 32.1% patients in the mBCC cohort and 
35.1% in the laBCC cohort. 
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Erivedge in all subsets of the paediatric population with basal cell carcinoma (see section 4.2 for 
information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Erivedge is a highly permeable compound with low aqueous solubility (BCS Class 2). The single dose 
mean (CV %) absolute bioavailability of Erivedge is 31.8 (14.5) %. Absorption is saturable as 
evidenced by the lack of dose proportional increase in exposure after a single dose of 270 mg and 
540 mg Erivedge. Under clinically relevant conditions (steady state), the PK of vismodegib is not 
affected by food. Therefore, Erivedge may be taken without regard to meals. 
 
Distribution 
The volume of distribution for vismodegib is low, ranging from 16.4 to 26.6 L. In vitro binding of 
vismodegib to human plasma proteins is high (97 %) at clinically relevant concentrations. Vismodegib 
binds to both human serum albumin and alpha-1-acid glycoprotein (AAG). In vitro binding to AAG is 
saturable at clinically relevant concentrations. Ex vivo plasma protein binding in human patients is 
> 99 %. Vismodegib concentrations are strongly correlated with AAG levels, showing parallel 
fluctuations of AAG and total vismodegib over time and consistently low unbound vismodegib levels. 
 
Biotransformation 
Vismodegib is slowly eliminated by a combination of metabolism and excretion of parent drug 
substance. Vismodegib is predominant in plasma, with concentrations representing greater than 98 % 



14 

of the total circulating concentrations (including associated metabolites). Metabolic pathways of 
vismodegib in humans include oxidation, glucuronidation, and an uncommon pyridine ring cleavage. 
CYP2C9 appears to contribute in part to vismodegib metabolism in vivo. 
 
Elimination 
After oral administration of a radiolabelled dose, vismodegib is absorbed and slowly eliminated by a 
combination of metabolism and excretion of parent drug substance, the majority of which is recovered 
in the faeces (82 % of the administered dose), with 4.4 % of the administered dose recovered in urine. 
Vismodegib and associated metabolic products are eliminated primarily by the hepatic route. 
After continuous once-daily dosing, the pharmacokinetics of vismodegib appears to be nonlinear due 
to saturable absorption and saturable protein binding. After a single oral dose, vismodegib has a 
terminal half-life of ca. 12 days.  
The apparent half-life of vismodegib at steady-state is estimated to be 4 days with continuous daily 
dosing. Upon continuous daily dosing, there is a 3 fold accumulation of vismodegib total plasma 
concentrations. 
 
Vismodegib inhibits UGT2B7 in vitro and it may not be excluded that inhibition can take place in vivo 
in the intestine. 
 
Special populations 
Elderly 
There are limited data in older people. In clinical trials with aBCC, approximately 40 % of patients 
were of geriatric age (≥ 65 years). Population pharmacokinetic analyses suggest that age did not have a 
clinically significant impact on steady-state concentration of vismodegib. 
 
Gender 
Based on population pharmacokinetic analysis of combined data from 121 males and 104 females, 
gender did not appear to affect the pharmacokinetics of vismodegib. 
 
Race 
There are limited data in non-Caucasian patients. Since the number of subjects who were not 
Caucasian comprised only < 3% of the total population (6 Black, 219 Caucasian), race was not 
evaluated as a covariate in the population pharmacokinetic analysis. 
 
Renal impairment 
Renal excretion of orally administered vismodegib is low. Therefore, mild and moderate renal 
impairment is unlikely to have a clinically significant effect on the pharmacokinetics of vismodegib. 
Based on a population PK analysis in patients with mild (BSA-indexed CrCl 50 to 80 mL/min, n=58) 
and  moderate (BSA-indexed CrCl 30 to 50 mL/min, n=16) renal impairment, mild and moderate 
impaired renal function had no clinically significant effect on the pharmacokinetics of vismodegib 
(see section 4.2). Very limited data is available in patients with severe renal impairments. 
 
Hepatic impairment 
The major elimination pathways of vismodegib involve hepatic metabolism and biliary/intestinal 
secretion. In a clinical study in patients with hepatic impairment (degree of impairment based on 
subject’s AST and total bilirubin levels) following multiple doses of vismodegib, it was shown that in 
patients with mild (NCI-ODWG criteria, n=8), moderate (NCI-ODWG criteria, n=6), and severe 
(NCI-ODWG criteria, n=3) hepatic impairment, the pharmacokinetic profile of vismodegib was 
comparable to that of subjects with normal hepatic function (n=9) (see section 4.2). 
 
Paediatric population 
There are insufficient pharmacokinetic data in paediatric patients.  
 



15 

5.3 Preclinical safety data 
 
The preclinical safety profile of Erivedge was assessed in mice, rats, and dogs. 
 
Repeat-dose toxicity 
In general, the tolerability of Erivedge in repeat-dose toxicity studies in rats and dogs was limited by 
nonspecific manifestations of toxicity including decreased body weight gain and food consumption. 
Additional findings at clinically relevant exposures included faecal changes; skeletal muscle twitching 
or tremors; alopecia; swelling, follicular hyperkeratosis, and inflammation in paw pads; and increased 
LDL and HDL cholesterol. Decreased haematocrit or platelet count were observed in some dogs at 
clinically relevant exposures; however, there was no evidence of a primary effect on bone marrow in 
affected animals. 
 
Carcinogenicity 
Carcinogenicity studies were performed in mice and rats.  Carcinogenic potential was identified in rats 
only and was limited to benign hair follicle tumors, including pilomatricomas and keratoacanthomas 
respectively at ≥ 0.1-fold and ≥0.6-fold of the steady-state AUC(0-24h) of the recommended human 
dose. No malignant tumors were identified in either species tested. Benign hair follicle tumors have 
not been reported in clinical trials with Erivedge, and the relevance of this finding to humans is 
uncertain. 
 
Mutagenicity 
There was no evidence of genotoxicity in in vitro assays (reverse bacterial mutagenesis [Ames] and 
human lymphocyte chromosome aberration assays) or in the in vivo rat bone marrow micronucleus 
assay. 
 
Fertility 
In the dedicated 26-week vismodegib rat fertility study, significantly increased absolute weights of 
seminal vesicles and reduced absolute weights of prostate were observed. In addition, the ratio of 
organ weight to terminal body weight was significantly increased for epididymis, cauda epididymis, 
testes and seminal vesicles.  In the same study there were no histopathological findings in male 
reproductive organs and no effects on male fertility endpoints, including percent motile sperm, 
observed at 100 mg/kg/day at the end of dosing or recovery phase (corresponding to 1.3-fold of the 
steady-state AUC0-24h at the recommended human dose).  In addition, in the vismodegib general 
toxicity studies up to 26-week in sexually mature rats and dogs, no effects on male reproductive 
organs were observed. Increased number of degenerating germ cells and hypospermia in sexually 
immature dogs observed at ≥ 50 mg/kg/day in the 4-week general toxicity study was of undetermined 
relationship to vismodegib.   
 
In the dedicated 26-week vismodegib rat fertility study, vismodegib-related effects on female 
reproductive organs were observed at 100 mg/kg/day immediately after treatment discontinuation, 
including decreased implantations, increased percent preimplantation loss, and decreased number of 
dams with viable embryos. Similar findings were not observed after a 16 week recovery period.  No 
correlative histopathologic changes were observed.  The exposure in female rats at 100 mg/kg 
corresponds to 1.2-fold of the steady-state AUC0-24h at the recommended human dose.  In addition, 
in the vismodegib general 26-week toxicity study, decreased number of corpora lutea was observed at 
100 mg/kg/day; the effect was not reversed by the end of an 8 week recovery period. 
 
Teratogenicity 
In an embryo-foetal development study in which pregnant rats were administered vismodegib daily 
during organogenesis, vismodegib crossed the placenta and was severely toxic to the conceptus. 
Malformations, including craniofacial anomalies, open perineum, and absent and/or fused digits, were 
observed in foetuses of dams at a dose which corresponded to 20 % of the typical steady-state 
exposure in patients, and a 100 % incidence of embryolethality was observed at higher doses.  
 



16 

Post-natal development 
Dedicated studies to assess the potential of vismodegib to affect post-natal development have not been 
performed. However, irreversible defects in growing teeth and premature closure of the femoral 
epiphyseal plate, observed in rat toxicity studies at clinically relevant exposures, represent risks to 
post-natal development. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule contents 
Microcrystalline cellulose 
Lactose monohydrate 
Sodium lauril sulfate 
Povidone (K29/32) 
Sodium starch glycolate (Type A) 
Talc 
Magnesium stearate 
 
Capsule shell 
Iron oxide black (E172) 
Iron oxide red (E172) 
Titanium dioxide (E171) 
Gelatine 
 
Printing ink  
Shellac glaze 
Iron oxide black (E172) 
 
6.2 Incompatibilities 
 
Not applicable.  
 
6.3 Shelf life 
 
4 years 
 
6.4 Special precautions for storage 
 
Do not store above 30 °C. 
Keep the bottle tightly closed in order to protect from moisture. 
 
6.5 Nature and contents of container  
 
HDPE bottle with a child-resistant closure containing 28 hard capsules. Each pack contains one bottle. 
The bottle cap material is Polypropylene. The cap liner is aluminum foil-lined waxed pulp board. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product at the end of treatment must immediately be disposed of by the patient 
in accordance with local requirements (if applicable, e.g. by returning the capsules to the pharmacist or 
physician).  
 
 



17 

7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/848/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 12 July 2013 
Date of latest renewal: 26 May 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



19 

 
A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 Grenzach-Wyhlen 
Germany 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are 
set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines 
web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 
• Additional risk minimisation measures 
 

Prior to launch in each Member State, the Marketing Authorisation Holder (MAH) shall agree the 
following with the National Competent Authority: 

• The national part of the DHPC 



20 

• Methodology to collect information on the use of Erivedge and the compliance with the 
pregnancy pharmacovigilance programme and its effectiveness 

• The format and content of the Healthcare professional and patient material 

 

The MAH shall distribute a Direct Healthcare Professional Communication letter at launch of the 
product, which should contain the following: 

• A core text as agreed by the Rapporteur 

• National specific requirements as agreed with the National Competent Authority regarding: 

• Distribution of the product 

• Measures to ensure that all appropriate actions have been performed prior to Erivedge 
being prescribed and dispensed 

 
The MAH shall continuously ensure that all physicians who are expected to prescribe Erivedge are 
provided with the following: 
Product information 
Healthcare professional educational material 
Healthcare professional reminder card 
Patient educational material 
Patient reminder card 
 

The healthcare professional educational material for Erivedge should contain the following key 
elements: 

• Brief background on Erivedge, its licensed indication and posology 

• A requirement to inform patients of the teratogenic risks associated with Erivedge and the 
need to avoid foetal exposure  

• Description of the pregnancy prevention programme and categorisation of patients based on 
sex and childbearing potential 

• Information on the recommended forms of contraception both for women and men 

• Obligations of the health care professional in relation to the prescribing of Erivedge 

• The need to provide comprehensive advice and counselling to patients 

• To ensure that patients are capable of complying with the requirements for the safe 
use of Erivedge 

• The need to provide patients with the patient educational material and patient 
reminder cards 

• Safety advice for women of childbearing potential 

• The need for adequate contraceptive measures (even if the woman has amenorrhoea) 
during treatment and for 24 months after Erivedge treatment  

• Pregnancy test within a maximum of 7 days prior to treatment initiation, and monthly 
medically supervised pregnancy tests during treatment 

• The need to stop Erivedge immediately upon suspicion of pregnancy 

• The need for the patient to report a suspected pregnancy immediately to the treating 
healthcare professional 



21 

• Safety advice for men 

• The need to use condoms if his sexual partner is pregnant or a women of childbearing 
potential (even if the man has had a vasectomy) during treatment and for 2 months 
after Erivedge treatment 

• The need for the patient to report immediately to the treating healthcare professional if 
his partner becomes pregnant whilst he is taking Erivedge or shortly after he has 
stopped taking Erivedge 

• Not to donate semen during treatment and for 2 months after the final dose 
 

• Requirements in the event of pregnancy  

• Instructions to stop Erivedge upon suspicion of pregnancy 

• The need to refer the patient to a specialist physician  

• Local contact details for reporting of any suspected pregnancy 

• Pregnancy reporting form 

• Inform patients that they should not donate blood during treatment with Erivedge and for 
24 months after their final dose 

• Check list for healthcare professional ensuring that patients receive the appropriate 
counselling 

• The need to ensure all patients complete and sign the Erivedge Verification of Counselling 
Form which is to be present in the healthcare professional educational material 

• Adverse event reporting forms 

• Information on the methodology, agreed with the National Competent Authority, to collect 
information on the use of Erivedge and the compliance with the pregnancy pharmacovigilance 
programme and its effectiveness.  

 
The patient educational material for Erivedge should contain the following key elements: 

• Information for patients on the teratogenic risks associated with Erivedge and the need to 
avoid foetal exposure 

• Description of the patient reminder card 

• The need for adequate contraception and definition of adequate contraception 

• National or other applicable specific arrangements for a prescription for Erivedge to be 
dispensed 

• Not to give Erivedge to any other person 

• Information on the disposal of unwanted medication 

• The need to keep Erivedge capsules out of sight and reach of children 

• That the patient should not donate blood during treatment and for 24 months after their final 
dose 

• That the patient should not breastfeed during treatment and for 24 months after their final dose 

• That the patient should tell the healthcare professional about any adverse event 

• Information for women of childbearing potential 

• Description of the pregnancy prevention programme 



22 

• The need for adequate contraceptive measures during treatment and for 24 months 
after Erivedge treatment 

• Pregnancy test within a maximum of 7 days prior to treatment initiation, and monthly 
medically supervised pregnancy tests during treatment 

• The need to stop Erivedge immediately upon suspicion of pregnancy 

• The need for the patient to report a suspected pregnancy immediately to the treating 
healthcare professional 

• Information for men 

• The need to use condoms (even if the man has had a vasectomy) if his sexual partner 
is pregnant or a women of childbearing potential during treatment and for 2 months 
after Erivedge treatment 

• That if his partner becomes pregnant he should inform the treating healthcare 
professional immediately  

• Not to donate semen during treatment and for 2 months after the final dose 

 
The healthcare professional’s reminder card should contain the following key elements 

• Information for women of childbearing potential 

• The need for monthly pregnancy tests even if the patient has amenorrhoea   

• The need for adequate contraceptive measures during treatment and for 24 months 
after Erivedge treatment 

• Not to breastfeed during treatment and for 24 months after Erivedge treatment 

• Information for men 

• The need to use condoms when having sex with a female partner during treatment and 
for 2 months after Erivedge treatment 

• Not to donate semen during treatment and for 2 months after the final dose 

• The need to tell patients to report immediately to the treating healthcare professional if  
pregnancy is suspected in a female patient, or in a female partner of a male patient 

• The healthcare professional should assess the pregnancy status, counsel the patient on 
teratogenicity risk and refer the patient to a specialised physician for counselling  

• The healthcare professional should report confirmed pregnancies to the MAH 

• Remind patients to  return unused capsules at the end of the treatment (disposal will depend on 
local requirements) 

• Remind patients not to donate blood during treatment and for 24 months after the final dose 

 
The patient reminder card should contain the following key elements: 

• Information for patients of the teratogenic risks associated with Erivedge and the need to 
avoid foetal exposure 

• Not to donate blood during treatment and for 24 months after the final dose  

• Information for women of childbearing potential 

• The need for monthly pregnancy tests  

• The need for adequate contraceptive measures 



23 

• The need to contact the healthcare professional immediately if a pregnancy is 
suspected during treatment or in the 24 months following treatment  

• Information for men 

• The need to use condoms when having sex with a female partner  

• Not to donate semen during treatment and for 2 months after the final dose 

• The need to contact the healthcare professional if the female partner suspects that she 
is pregnant while the patient is treated with Erivedge or in the 2 months following 
treatment 

• To return unused capsules at the end of the treatment (disposal will depend on local 
requirements) 

• Emergency contact phone numbers 

 



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



26 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erivedge 150 mg hard capsules  
vismodegib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 150 mg of vismodegib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Do not crush, open or chew the capsule 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
Risk of severe birth defects  
Do not use while pregnant or breast-feeding 
You must follow the Erivedge Pregnancy Prevention Programme 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



27 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30 °C 
Keep the bottle tightly closed in order to protect from moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Unused capsules should be returned at the end of treatment 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/848/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
erivedge 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
<2D barcode carrying the unique identifier included> 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



28 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erivedge 150 mg hard capsules  
vismodegib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each capsule contains 150 mg of vismodegib. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Do not crush, open or chew the capsule 
Read the package leaflet before use 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
Risk of severe birth defects  
Do not use while pregnant or breast-feeding 
You must follow the Erivedge Pregnancy Prevention Programme 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



29 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30 °C 
Keep the bottle tightly closed in order to protect from moisture 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Unused capsules should be returned at the end of treatment 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/848/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 



31 

Package leaflet: Information for the patient 
 

Erivedge 150 mg hard capsules  
vismodegib 

 
Erivedge may cause severe birth defects. It may lead to the death of a baby before it is born or shortly 
after being born. You must not become pregnant while taking this medicine. You must follow the 
contraception advice described in this leaflet. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet  
 
1. What Erivedge is and what it is used for 
2. What you need to know before you take Erivedge 
3. How to take Erivedge 
4. Possible side effects 
5. How to store Erivedge 
6. Contents of the pack and other information 
 
 
1. What Erivedge is and what it is used for 
 
What Erivedge is 
Erivedge is an anti-cancer medicine and contains the active substance vismodegib.  
 
What Erivedge is used for 
Erivedge is used to treat adults with a type of skin cancer called advanced basal cell carcinoma. It is 
used when the cancer: 
• has spread to other parts of the body (called “metastatic” basal cell carcinoma)  
• has spread to areas nearby (called “locally advanced” basal cell carcinoma) and your doctor 

decides that treatment with surgery or radiation is inappropriate. 
 
How Erivedge works 
Basal cell carcinoma develops when DNA in normal skin cells becomes damaged and the body cannot 
repair the damage. This damage can change how certain proteins in these cells work and the damaged 
cells become cancerous and begin to grow and divide. Erivedge is an anti-cancer medicine that works 
by controlling one of the key proteins involved in basal cell carcinoma. This may slow down or stop 
the growth of the cancer cells, or may kill them. As a result, your skin cancer may shrink. 
 
 



32 

2. What you need to know before you take Erivedge 
 
Read the specific instructions given to you by your doctor, particularly on the effects of Erivedge on 
unborn babies. 
 
Read carefully and follow the instructions of the patient brochure and reminder card given to you by 
your doctor. 
 
Do not take Erivedge 
• if you are allergic to vismodegib or any of the other ingredients of this medicine (listed in 

section 6). 
• if you are pregnant, think you may be pregnant, or are planning to become pregnant during the 

course of treatment or during the 24 months after your final dose of this medicine. This is 
because Erivedge may harm or cause the death of your unborn baby. 

• if you are breast-feeding or plan to breast-feed during the course of treatment or during 
the 24 months after your final dose of this medicine. This is because it is unknown whether 
Erivedge can pass into your milk and cause harm to your baby. 

• if you are able to become pregnant but are unable or unwilling to follow the necessary 
pregnancy prevention measures that are listed in the Erivedge Pregnancy Prevention 
Programme,  

• if you are also taking St John’s wort (Hypericum perforatum) – a herbal medicine used for 
depression (see “Other medicines and Erivedge”). 

 
More information on the issues above is found in the sections “Pregnancy, breast-feeding and fertility” 
and “Contraception – for men and women”. 
 
Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or 
pharmacist before taking Erivedge. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Erivedge if you have questions on the information in 
this section: 
 
• You should not donate blood at any time during treatment and for 24 months after your final 

dose of this medicine. 
• If you are male, you should not donate semen at any time during treatment and for 2 months 

after the final dose.  
• Serious skin reactions have been reported in association with Erivedge treatment. Stop using 

Erivedge and seek medical attention immediately if you notice any of the symptoms described 
in section 4. 

• Your doctor should check your skin regularly for a type of cancer called “cutaneous squamous 
cell carcinoma’ (SCC). It is not known if SCC is related to treatment with Erivedge. Usually 
this type of lesion appears on sun-damaged skin, remains local and can be cured. Tell your 
doctor in case you notice any changes in your skin.• Never give this medicine to anyone 
else. You should return unused capsules at the end of your treatment. Talk to your doctor or 
pharmacist regarding where to return the capsules. 

 
Children and adolescents 
The use of Erivedge in children and adolescents under the age of 18 years is not recommended. This is 
because it is not known if it is safe or effective in this age group. Erivedge can cause bones to stop 
growing and lead to premature onset of puberty (before age 8 years in girls or age 9 years in boys). 
This can happen even after stopping Erivedge. Problems with growing teeth and bones were seen in 
animal studies with this medicine. 
 



33 

Other medicines and Erivedge 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
This also includes non-prescription medicines, vitamins and herbal medicines. 
 
Some medicines may affect how Erivedge works, or make it more likely that you will have side effects. 
Erivedge can also affect how some other medicines work.  
In particular, tell your doctor if you take any of the following medicines: 
• rifampicin – used for bacterial infections, 
• carbamazepine, phenytoin – used for epilepsy, 
• ezetimibe and statins , such as atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin – 

used for high cholesterol, 
• bosentan, glibenclamide, repaglinide, valsartan,   
• topotecan – used for certain types of cancer, 
• sulfasalazine – used for certain inflammatory disorders, and especially, 
• St. John’s wort (Hypericum perforatum) – a herbal medicine used for depression, since you 

must not use it at the same time as Erivedge. 
 

Pregnancy, breast-feeding and fertility 
Pregnancy 
Do not take Erivedge if you are pregnant, think you may be pregnant, or are planning to become 
pregnant during the course of treatment or during the 24 months after your final dose of this medicine. 
You must stop treatment and inform your doctor straight away if: you miss or think you have missed a 
period, or you have unusual menstrual bleeding, or suspect you are pregnant. If you do become 
pregnant during the treatment with Erivedge, you must stop the treatment and inform your doctor 
immediately. 

Erivedge may cause severe birth defects. It may also lead to the death of the unborn baby. Specific 
instructions (the Erivedge Pregnancy Prevention Programme), given to you by your doctor contain 
information particularly on the effects of Erivedge on unborn babies. 
 
Breast-feeding 
Do not breast-feed during your treatment and for 24 months after your final dose of this medicine. It is 
not known if Erivedge can pass into your breast milk and harm your baby. 
 
Fertility 
Erivedge may affect a woman’s ability to have children. Some women taking Erivedge have stopped 
having periods. If this happens to you, it is not known if your periods will come back. Talk to your 
doctor if you wish to have children in the future.  
 
Contraception – for men and women  
For women taking Erivedge 
Before starting the treatment, ask your doctor if you are able to become pregnant. Even if your periods 
have stopped, it is essential to ask your doctor if there is any risk that you could become pregnant. 

If you are able to become pregnant: 
• you must take precautions so that you do not become pregnant while taking Erivedge 
• use 2 methods of contraception, one highly effective method and one barrier method (please see 

the examples below) 
• you need to continue contraception for 24 months after your final dose of this medicine – 

because Erivedge may remain in your body for up to 24 months after your final dose. 
 
Method of recommended contraception: Talk to your doctor about the best two contraception methods 
for you.   
 



34 

Use one highly effective method, such as: 
• a contraceptive depot injection  
• an intra-uterine device (“the coil” or IUD) 
• surgical sterilisation. 
 
You must also use one barrier method, such as: 
• a condom (with spermicide, if available) 
• a diaphragm (with spermicide, if available). 
 
Your doctor will make sure to test you for pregnancy: 
• within a maximum of 7 days before starting treatment – to make sure that you are not already 

pregnant 
• every month during treatment.  
 
You must tell your doctor immediately during the course of treatment or during the 24 months after 
your final dose of this medicine if: 
• you think your contraception has failed for any reason, 
• your periods stop,  
• you stop using contraception,  
• you need to change contraception.  
 
For men taking Erivedge 
Erivedge can pass into semen. Always use a condom (with spermicide, if available) even after a 
vasectomy, when you have sex with a female partner. Do this during treatment and for 2 months after 
your final dose of this medicine.  
 
You should not donate semen at any time during treatment and for 2 months after your final dose of 
this medicine. 
 
Driving and using machines 
Erivedge is unlikely to affect your ability to drive, use any tools or machines. Talk to your doctor if 
you are not sure. 
 
Erivedge contains lactose and sodium 
Erivedge contains a type of sugar called lactose. If you have been told by your doctor that you have an 
intolerance to some sugars, contact your doctor before taking this medicine. 
This medicine contains less than 1 mmol sodium (23 mg) per capsule, i.e. essentially ‘sodium free’.  
 
 
3. How to take Erivedge 
 
Always take Erivedge exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure.  
 
Taking this medicine 
The recommended dose is one capsule each day. 
• Swallow the capsule whole with a drink of water. 
• Do not crush, open or chew the capsule, to avoid unintended exposure to the capsule contents. 
• Erivedge can be taken with or without food. 
 
If you take more Erivedge than you should 
If you take more Erivedge than you should, talk to your doctor. 
 
If you forget to take Erivedge 
Do not take a double dose to make up for a forgotten dose, but resume with the next scheduled dose. 



35 

 
If you stop taking Erivedge 
Do not stop taking this medicine without talking to your doctor first as this could make your treatment 
less effective. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, Erivedge can cause side effects, although not everybody gets them. 
 
Erivedge may cause severe birth defects. It may also lead to the death of a baby before it is born or 
shortly after being born. You must not become pregnant while taking this medicine (see section 2, “Do 
not take Erivedge” and “Pregnancy, breast-feeding and fertility”). 

 
Other side effects are presented in order of severity and frequency: 
 
Very common (may affect more than 1 in 10 people): 
• loss of monthly periods in women of childbearing age,  
• loss of appetite and weight loss,  
• feeling tired, 
• muscle spasm, 
• diarrhoea, 
• hair loss (alopecia), 
• rash, 
• a change in the way things taste or the complete loss of taste, 
• constipation, 
• vomiting or feeling like you want to vomit (nausea), 
• upset stomach or indigestion, 
• joint pain, 
• pain (in general) or pain in your arms, legs,  
• itchiness. 
 
Common (may affect up to 1 in 10 people): 
• pain in your chest, back or side, 
• lack of energy or weakness (asthenia), 
• loss of water from the body (dehydration), 
• muscle, tendon, ligament, bone pain,  
• stomach pain,  
• loss of taste, 
• abnormal hair growth, 
• eyelashes falling out (madarosis) 
•  changes in blood tests, which include increased values in liver tests or increased values in 

creatine phosphokinase (a protein mainly from muscle). 
 

Frequency not known  
• Bones stop growing (epiphyses premature fusion) 
• Premature puberty (precocious puberty) 
• Liver injury Serious skin reactions: 
• Reddish target-like macules or circular patches often with central blisters on the trunk, skin 

peeling, ulcers of mouth, throat, nose, genitals and eyes. The skin reactions are often preceded 
by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis). 



36 

• Widespread rash, fever, and enlarged lymph nodes (DRESS-syndrome or drug hypersensitivity 
syndrome). 

• Red, scaly widespread rash with bumps under the skin and blisters accompanied by fever at the 
initiation of treatment (acute generalised exanthematous pustulosis).                    

  
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Erivedge 
 
• Keep this medicine out of the sight and reach of children. 
• Do not use this medicine after the expiry date, which is stated on the bottle and carton after EXP. 

The expiry date refers to the last day of that month. 
• Do not store above 30 °C. 
• Keep the bottle tightly closed in order to protect from moisture. 
• Do not throw away any medicines via wastewater or household waste. 
• At the end of your treatment you should return all unused capsules. This will prevent misuse 

and help to protect the environment. Talk to your pharmacist or doctor regarding where to return 
the medicine. 

 
 
6. Contents of the pack and other information 
 
What Erivedge contains 
• The active substance is vismodegib. Each hard capsule contains 150 mg of vismodegib. 
• The other ingredients are: 
• Capsule contents: microcrystalline cellulose, lactose monohydrate, sodium lauril sulfate, 

povidone (K29/32), sodium starch glycolate (Type A), talc and magnesium stearate. 
• Capsule shell: iron oxide red (E172), iron oxide black (E172), titanium dioxide, gelatine, 
• Printing ink: shellac glaze and iron oxide black (E172). 

 
What Erivedge looks like and contents of the pack 
The capsules have a pink opaque coloured body marked “150 mg” and a grey cap 
marked "VISMO” in black edible ink. They are available in bottles with a child-resistant closure 
containing 28 capsules. Each pack contains one bottle. 
 
Marketing Authorisation Holder 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
Manufacturer 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 Grenzach-Wyhlen 
Germany 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


37 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. o. 
Tel: +420 - 2 20382111 
 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 
 

Danmark 
Roche a/s 
Tlf: +45 - 36 39 99 99 
 

Malta 
(See Ireland) 

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140 
 

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 177 380 
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Ελλάδα 
Roche (Hellas) A.E.  
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00 
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 

France 
Roche 
Tél: +33 (0) 1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 
 

Hrvatska 
Roche d.o.o 
Tel: +385 1 4722 333 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 

Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland  
Roche a/s 
c/o Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika  
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 
 

Suomi/Finland 
Roche Oy  
Puh/Tel: +358 (0) 10 554 500 
 



38 

Kύπρος  
Γ.Α.Σταμάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 6 7 039831 
 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

  
 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 
 
As part of the Erivedge Pregnancy Prevention Programme, all patients will receive a: 
• Patient Brochure  
• Patient Reminder Card 
Please refer to these documents for further information. 

 
 

 

 
 

http://www.ema.europa.eu/


39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

 



40 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for vismodegib, the scientific 
conclusions of the CHMP are as follows:  
Seven cases of severe cutaneous adverse reactions (SCARs) have been reported in association with 
vismodegib cumulatively. At least one case of Stevens-Johnson syndrome/Toxic epidermal 
necrolysis (SJS/TEN), 2 cases of Drug reaction with eosinophilia and systemic symptoms (DRESS) 
and one case of acute generalised exanthematous pustulosis (AGEP) are causally related to the 
treatment, based on clinical and pathological features, and the compatible temporal relationship. 
Although the number of identified cases is limited, the reactions are serious and the association with 
vismodegib is plausible. The PRAC therefore recommends that the Product Information should be 
updated accordingly.  
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds for the variation to the terms of the marketing authorisation(s) 

On the basis of the scientific conclusions for vismodegib the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing vismodegib is unchanged subject to the 
proposed changes to the product information. 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)