Fertility warning
This medicine may affect fertility.
Leaflet ETCAMAH 75mg film-coated tablets
- Product code:
- W72144001
- Quantity:
- 28
- Indicated for:
- ER-positive, HER2-negative locally advanced or metastatic breast cancer with an ESR1 mutation detected without progressi
- Route of administration:
- oral
- Substance:
- camizestrant (selective estrogen receptor degrader (SERD))
- ATC
- L02BA05 — Antineoplastic and immunomodulating agents | Hormone antagonists and related agents | Anti-estrogens
Camizestrant is a hormonal treatment for adults with ER-positive, HER2-negative, locally advanced or metastatic breast cancer. It is combined with a CDK4/6 inhibitor when an ESR1 mutation is detected before disease progression on first-line endocrine therapy plus a CDK4/6 inhibitor. It blocks and promotes breakdown of oestrogen receptors, slowing tumour growth.
Take it by mouth once daily, with or without food. Swallow the tablet whole without crushing or chewing. An oncologist supervises treatment, and mutation testing is required to select eligible patients. ECGs and blood tests are performed before and during therapy. Do not change the accompanying medicines yourself.
It can cause a slow pulse and visual effects such as flashes of light or blurred vision. In combination with a CDK4/6 inhibitor, tiredness, nausea, diarrhoea, anaemia and low white blood cell counts with infection risk may occur. Possible heart rhythm problems require attention to other medicines and electrolyte levels.
Tell the doctor urgently about fainting, palpitations, severe dizziness, fever or persistent visual symptoms. Avoid pregnancy and use the recommended contraception, including after treatment. Do not breastfeed during therapy or for 4 weeks after the last dose. Report all medicines and supplements, as some interactions can be important.
Take it by mouth once daily, with or without food. Swallow the tablet whole without crushing or chewing. An oncologist supervises treatment, and mutation testing is required to select eligible patients. ECGs and blood tests are performed before and during therapy. Do not change the accompanying medicines yourself.
It can cause a slow pulse and visual effects such as flashes of light or blurred vision. In combination with a CDK4/6 inhibitor, tiredness, nausea, diarrhoea, anaemia and low white blood cell counts with infection risk may occur. Possible heart rhythm problems require attention to other medicines and electrolyte levels.
Tell the doctor urgently about fainting, palpitations, severe dizziness, fever or persistent visual symptoms. Avoid pregnancy and use the recommended contraception, including after treatment. Do not breastfeed during therapy or for 4 weeks after the last dose. Report all medicines and supplements, as some interactions can be important.
General data about ETCAMAH 75mg
- Substance:
- camizestrant
- Date of latest medicines list:
- 01-09-2026
- Product code:
- W72144001
- Strength:
- 75mg
- Pharmaceutical form:
- film-coated tablets
- Quantity:
- 28
- Product type:
- Original
- Prescription status:
- P-RF — Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.
Official documents
- Added to database:
- 21/07/2026
Warnings:
Driving impairment
This medicine may affect your ability to drive or use machines.
Contraception required
Effective contraception is required during treatment.
Contraindicated during breastfeeding
Do not use this medicine while breastfeeding.
Major drug interactions
This medicine may have important interactions with other medicines.
Additional monitoring
This medicine is subject to additional monitoring.
Requires periodic laboratory tests
Periodic laboratory tests may be required during treatment.
Do not split / crush / chew
Do not split, crush, or chew this medicine.
Pregnancy warning
Use during pregnancy only on medical advice.
Pediatric warning
Use in children only as recommended in the leaflet or by a doctor.
Cardiac risk / QT prolongation / arrhythmias
This medicine may increase the risk of heart rhythm disturbances.
Teratogenic / fetal risk
This medicine may affect fetal development.
Vision disturbances
This medicine may cause vision disturbances.
Summary of product characteristics for ETCAMAH 75mg film-coated tablets
Find in leaflet
Summary of product characteristics for ETCAMAH 75mg
1. NAME OF THE MEDICINAL PRODUCT
Etcamah 75 mg film-coated tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 75 mg of camizestrant.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Film-coated tablet (tablet).
Beige, round, bi-convex, film-coated tablet, debossed with ‘CM’ above ‘75’ on one side and plain onthe reverse. Approximate diameter: 9 mm.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Etcamah in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) is indicatedfor the treatment of adult patients with ER-positive, HER2-negative, locally advanced or metastaticbreast cancer upon detection of ESR1-mutation and without disease progression during first-lineendocrine therapy in combination with a CDK4/6 inhibitor (for biomarker based patient-selection, seesection 4.2 and 5.1).
In pre- or peri-menopausal women and in men, Etcamah plus a CDK4/6 inhibitor should be combinedwith a luteinizing hormone releasing hormone (LHRH) agonist or antagonist.
4.2 Posology and method of administration
Treatment should be initiated and supervised by a physician experienced in the use of anticancermedicinal products.
Patient selection
Patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer on first-lineendocrine treatment should be selected for treatment based on the presence of ESR1-mutations inplasma or tumour specimen collected every 3 months until an ESR1-mutation has been detected, andwhich should be assessed by a CE-marked in vitro diagnostic (IVD) medical device with thecorresponding intended purpose (see section 5.1). If a CE-marked IVD is not available, an alternativevalidated test should be used.
PosologyThe recommended dose of Etcamah in combination with a CDK4/6 inhibitor is 75 mg once daily. The
CDK4/6 inhibitor should be continued at the same dose at the time of initiation with Etcamah as whenthe ESR1m was detected.
Please also refer to the summary of product characteristics (SmPC) of the CDK4/6 inhibitor or LHRHagonist or antagonist for the recommended dosing information. If the CDK4/6 inhibitor is permanentlydiscontinued, Etcamah should also be discontinued.
Treatment durationTreatment with Etcamah should continue as long as clinical benefit is observed or until unacceptabletoxicity occurs.
Missed doseIf a dose of Etcamah is missed, it can be taken immediately within 6 hours after the time it is usuallytaken. After more than 6 hours, the dose should be skipped for that day. The next dose of Etcamahshould be taken at the usual time.
VomitingIf the patient vomits, an additional dose should not be taken. The next dose of Etcamah should betaken at the usual time.
Monitoring for Etcamah in combination with CDK4/6 inhibitors
For the combination of Etcamah with a CDK4/6 inhibitor, ECG should be assessed before initiatingtreatment, at approximately day 8 and day 15 of the first cycle, and then as clinically indicated.
Thereafter, monitoring during combination treatment should be performed according to therecommendations in the SmPC of the co-administered CDK4/6 inhibitor. In case of QTc prolongationduring treatment, more frequent ECG monitoring is recommended.
In addition, for the combination of Etcamah with ribociclib, treatment should be initiated only inpatients with QTcF values less than 450 msec, and analysis of electrolytes should be performed beforeinitiating combination treatment, at day 15 and as clinically indicated. Refer to the ribociclib SmPCfor dose modification guidelines and other relevant safety information.
Dose adjustmentsTreatment with Etcamah may be temporarily interrupted and/or discontinued to manage adversereactions per dose modification guideline provided in Table 1.
Table 1 Recommended dose modification for Etcamah
NCI CTCAE (v5.0) Toxicity Action
Bradycardia a Symptomatic, Consider holding Etcamah dosing whilst evaluating concomitant
CTCAE Grade ≥ 2 medicinal products known to cause bradycardia. If no contributingconcomitant medicinal product is identified, withhold Etcamah untilbradycardia symptoms resolve. If a contributing concomitantmedicinal product is identified, consider discontinuing or modifyingthe dose of this agent until bradycardia symptoms resolve and thenrestart Etcamah dosing.
Consider reassessing the heart rate after restart of Etcamah dosing atnext clinical visit or as clinically indicated.
Permanently discontinue Etcamah for persistent symptomaticbradycardia.
Visual effects b CTCAE Consider referring to an eye care professional, if visual symptoms
Grade ≥ 2/limiting are progressive, persistent, or interfere with instrumental ADLs.
instrumental ADLs
Decision regarding treatment interruption should be based onclinical assessment.
NCI CTCAE (v5.0) Toxicity Action
Grade 3 or higher adverse Hold Etcamah dosing until resolution to CTCAE Grade 2 or below,event assessed as causally then restart Etcamah dosing.
related to Etcamah
Consider permanently discontinuing Etcamah for recurrent Grade 3or higher AEs.
ADL = Activities of daily living; AE = Adverse Event; CTCAE = Common Terminology Criteria for Adverse
Events; NCI = National Cancer Institute.
a. Bradycardia includes bradycardia and sinus bradycardia.
b. Visual effects include photopsia, vision blurred, visual impairment, diplopia, and photophobia of eye disorders
MedDRA SOC, and visual perseveration of nervous system disorders MedDRA SOC.
No clinically relevant pharmacokinetic interaction was observed when camizestrant was co-administered with abemaciclib or palbociclib. When camizestrant 75 mg was administered incombination with ribociclib, camizestrant exposure increased to levels comparable to those observedwith a 150 mg monotherapy dose (see section 4.9).
Special populationsElderly
No dose adjustment of camizestrant is required for elderly patients (see section 5.2).
Renal impairmentNo dose adjustment of camizestrant is required for patients with mild or moderate renal impairment.
Etcamah is not recommended for patients with severe renal impairment (see section 5.2).
Hepatic impairmentNo dose adjustment of camizestrant is required for patients with mild (NCI criteria) hepaticimpairment. As a precautionary measure, the use of camizestrant in patients with moderate and severehepatic impairment should be avoided. Patients with mild hepatic impairment are allowed to takecamizestrant (see sections 4.4 and 5.2).
Paediatric populationThe safety and efficacy of camizestrant in children aged 0-18 years has not been established. No dataare available.
Method of administrationOral use.
The tablet should be swallowed whole with water and may be taken with or without food, atapproximately the same time each day. Etcamah should not be ingested if it is broken, cracked, orotherwise not intact. The tablet should not be chewed, crushed, dissolved, or divided because thesemethods have not been studied in clinical studies.
4.3 Contraindications
Breast-feeding (see section 4.6).
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Bradycardia, when combined with medicinal products known to increase the risk of QTc prolongation
Bradycardia and QTc prolongation have been reported with camizestrant and CDK4/6 inhibitorcombination treatment (see section 4.8). A non-fatal Torsades de Pointes was observed in a patientwith bradycardia and QTc prolongation for camizestrant in combination with ribociclib. Consideringbradycardia in the context of potential QTc prolongation may increase the risk of arrhythmia, cautionshould be exercised when administering camizestrant in combination with agents known to cause QTcprolongation, e.g. ribociclib. Refer to monitoring recommendations (see section 4.2).
Hepatic impairmentCamizestrant is metabolised by the liver. Patients with impaired hepatic function are expected to haveincreased exposure to camizestrant. As a precautionary measure, the use of camizestrant in patientswith moderate and severe hepatic impairment should be avoided. Patients with mild hepaticimpairment are allowed to take camizestrant. No dose adjustment of camizestrant is required forpatients with mild (NCI criteria) hepatic impairment (see sections 4.2 and 5.2).
Sodium contentThis medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to sayessentially ‘sodium-free’.
4.5 Interaction with other medicinal products and other forms of interaction
Camizestrant is a reversible inhibitor of CYP3A4/5 and CYP2B6 and cause inhibition of drugtransporters P-gp, BCRP and OATP1B1. Camizestrant is a potent, time-dependent, irreversibleinhibitor of CYP2C9 and CYP2C19. Camizestrant is a substrate for CYP3A4/5 and P-gp.
Effects of other medicinal products on camizestrant
CYP3A4/5 inducers
The exposure to camizestrant is expected to decrease if co-administered with moderate and strong
CYP3A4/5 inducers. Clinically, a single 75 mg camizestrant dose co-administered orally with repeatdoses of carbamazepine, a strong CYP3A4/5 inducer, resulted in camizestrant geometric mean ratiosfor Cmax and AUC of 0.41 [90% CI: 0.37,0.46] and 0.29 [90% CI: 0.28,0.32], respectively. The co-administration of camizestrant and a strong CYP3A4/5 inducer (including but not limited to:
carbamazepine, phenytoin, rifampicin and St John’s Wort) should be avoided. An alternativemedicinal product with no or weak potential to induce CYP3A4/5 should be considered.
When co-administering camizestrant in combination with ribociclib, plus a moderate CYP3A4/5inducer (including but not limited to: e.g. bosentan, nafcillin, modafinil and phenobarbital), no doseadjustment of camizestrant is necessary. When co-administering camizestrant in combination withabemaciclib or palbociclib, the use of such moderate CYP3A4/5 inducers should be avoided byswitching to an alternate concomitant drug product (see section 5.2).
CYP3A4/5 inhibitors
In a clinical study, concomitant use of itraconazole, a strong CYP3A4/5 inhibitor, increasedcamizestrant geometric mean Cmax and AUCinf by 1.37-fold and 1.90-fold, respectively. Camizestrantin combination with ribociclib should be avoided in patients taking strong CYP3A4/5 inhibitors. Inaddition, caution should be exercised when combining camizestrant and ribociclib in combination withweak (e.g., chlorzoxazone and fosaprepitant) and moderate (e.g., aprepitant and diltiazem) CYP3A4/5inhibitors.
Effects of camizestrant on other medicinal products
CYP2C9 and CYP2C19 substrates
In vitro data in conjunction with mechanistic static modelling show that camizestrant is a potentirreversible, time-dependent inhibitor of both CYP2C9 and CYP2C19. This means that the inhibitionis irreversible and in order to reinstate functionality, the enzymes need to be synthesised again.
Therefore, camizestrant is expected to increase the exposure levels of medicinal products that aresubstrates of CYP2C9 and/or CYP2C19. No in vivo clinical data is available. Medicinal products thatare sensitive substrates (including but not limited to: clobazam, omeprazole, pantoprazole andproguanil) or substrates with narrow therapeutic index of CYP2C9 and/or CYP2C19 (including butnot limited to: phenytoin and warfarin) should be stopped at least 2 weeks before the first dose of
Etcamah and not used for at least 2 weeks after the last dose of Etcamah.
The co-administration of camizestrant and moderately sensitive substrates of CYP2C9 (including butnot limited to: flurbiprofen, siponimod and glyburide) and/or CYP2C19 (including but not limited to:
esomeprazole, voriconazole and lansoprazole) may be allowed with caution; however, alternativemedicinal products should be considered if possible.
CYP3A4/5 substrates
In a clinical study, concomitant use of camizestrant increased midazolam, a sensitive CYP3A4/5substrate, geometric mean Cmax by 1.50-fold and AUC by 1.99-fold respectively, therefore,camizestrant is a weak inhibitor of CYP3A4/5. Camizestrant should be used with caution when co-administered with sensitive CYP3A4/5 substrates (including but not limited to: budesonide, buspirone,dronedarone, ivabradine, lurasidone, midazolam, quetiapine, sildenafil and simvastatin). Narrowtherapeutic index CYP3A4/5 substrates (e.g. alfentanil and fentanyl) may require dose adjustment andshould be monitored closely.
OATP1B1 sensitive substrates
In vitro data show that camizestrant is an inhibitor of OATP1B1. Therefore, camizestrant may increasethe exposure levels of medicinal products that are substrates of OATP1B1 including but not limited toglyburide, and lovastatin. No in vivo clinical data is available. Medicinal products which have anarrow therapeutic index and are sensitive substrates of OATP1B1 should be avoided. Thosemedicinal products which are sensitive substrates of OATP1B1 are permitted but caution should beexercised and patients monitored closely for possible drug interactions.
BCRP sensitive substrates
In vitro data show that camizestrant is an inhibitor of Breast Cancer Resistance Protein (BCRP).
Therefore, camizestrant may increase the exposure levels of medicinal products that are substrates of
BCRP. No in vivo clinical data is available. Those medicinal products that are sensitive substrates of
BCRP e.g. rosuvastatin, sulfasalazine and sofosbuvir, are permitted but caution should be exercisedand patients monitored closely for possible drug interactions. Medicinal products that have a narrowtherapeutic index and are sensitive substrates of BCRP should be avoided.
P-gp sensitive substrates
In vitro data show that camizestrant is an inhibitor of P-glycoprotein (P-gp). Therefore, camizestrantmay increase the exposure levels of medicinal products that are substrates of P-gp including but notlimited to: edoxaban, digoxin, fexofenadine and dabigatran etexilate. No in vivo clinical data isavailable. Medicinal products which have a narrow therapeutic index and are sensitive substrates of P-gp should be avoided. Those medicinal products which are sensitive substrates of P-gp are permittedbut caution should be exercised and patients monitored closely for possible drug interactions.
CYP2B6 sensitive substrates
In vitro data show that camizestrant is an inhibitor of Cytochrome P450 2B6 (CYP2B6). Therefore,camizestrant may increase the exposure levels of medicinal products that are substrates of CYP2B6.
No in vivo clinical data are available. Those medicinal products that are sensitive substrates of
CYP2B6 including but not limited to: bupropion, nevirapine, ketamine, and cyclophosphamide shouldbe avoided. All other CYP2B6 substrates are permitted but caution should be exercised and patientsmonitored closely for possible drug interactions.
Medicinal products known to prolong the QT interval
Camizestrant in combination with ribociclib has been studied clinically, a non-fatal Torsades de
Pointes was observed in a patient with bradycardia and QTc prolongation for camizestrant incombination with ribociclib. It is recommended to monitor patients clinically and adjust doses asspecified in the approved ribociclib SmPC. Co-administration of other medicinal products known toprolong the QT interval and/or have a known risk of Torsades de Pointes (e.g. ciprofloxacin,levofloxacin, ondansetron, escitalopram, venlafaxine, fluconazole, chloroquine, halofantrine,clarithromycin, azithromycin, haloperidol, methadone, moxifloxacin, bepridil, and pimozide) shouldbe avoided. If concomitant use cannot be avoided, monitor ECGs as clinically indicated (see section4.2).
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
Based on its mechanism of action and preclinical data, camizestrant may cause foetal harm whenadministered to a pregnant woman. Women of childbearing potential should be advised to avoidbecoming pregnant while receiving camizestrant. A pregnancy test should be performed and verifiedas negative on women of childbearing potential prior to initiating treatment and re-testing should beconsidered throughout treatment.
Contraception in males and femalesWomen of childbearing potential and men with women partners of childbearing potential have to useeffective contraception during treatment with camizestrant and for the following periods aftercompletion of treatment with camizestrant: at least 4 weeks for females and 1 week for males.
PregnancyThere are no data from the use of camizestrant in pregnant women. Studies in animals have shownreproductive toxicity, including embryo lethality and dystocia (see section 5.3). Based on animal dataand its mechanism of action, camizestrant should not be used during pregnancy unless the clinicalcondition of the women requires treatment with camizestrant.
Breast-feedingIt is not known whether camizestrant and its metabolites are excreted in human milk. Based on animaldata (see section 5.3), a risk to the breast-fed child cannot be excluded. Breast-feeding must bediscontinued prior to treatment with camizestrant and must not be resumed until 4 weeks following thelast dose (see section 4.3).
FertilityThere are no data on the effect of camizestrant on human fertility. Results from animal studies haveshown that camizestrant has marked effects on male and female reproductive organs in mice, rats anddogs and functional effects on female and male fertility in rats (see section 5.3).
4.7 Effects on ability to drive and use machines
Etcamah in combination with a CDK4/6 inhibitor, has a minor influence on the ability to drive and usemachines as the combination may cause fatigue and dizziness (see section 4.8). Etcamah, may causetransient visual effects in the peripheral vision consisting mainly of photopsia, which has no ornegligible influence on the ability to drive. However, patients who experience these symptoms shouldbe advised to observe caution when driving or operating machinery.
4.8 Undesirable effects
Summary of the safety profile
The summary of the safety profile of Etcamah is based on pooled data from 263 patients who received
Etcamah in combination with a CDK4/6 inhibitor in phase III (SERENA-6) and phase I (SERENA-1)studies.
The most common adverse reactions (≥ 15%) for Etcamah in combination with a CDK4/6 inhibitorwere neutropenia (59.7%), visual effects (40.7%), infections (38.4%), diarrhoea (21.3%), nausea(21.3%), anaemia (21.3%), fatigue (20.5%) bradycardia (19.8%) and leukopenia (15.6%). Amongthese, ADRs identified for Etcamah were visual effects (40.7%) and bradycardia (19.8%).
The common Grade 3 or 4 adverse reactions (≥ 2%) for Etcamah in combination with a CDK4/6inhibitor were neutropenia (46.4%), leukopenia (9.1%), anaemia (3.4%), infections (3.4%) and alanineaminotransferase increase (2.3%).
The common serious adverse reactions (≥ 1%) reported in patients receiving Etcamah in combinationwith a CDK4/6 inhibitor included infections (3.4%) and pyrexia (1.1%).
Adverse reactions leading to treatment discontinuation of Etcamah in patients receiving Etcamah incombination with a CDK4/6 inhibitor were neutropenia (0.4%) and electrocardiogram QT prolonged(0.4%).
The most common adverse reactions (≥ 2%) leading to dose modification of Etcamah in patientsreceiving Etcamah in combination with a CDK4/6 inhibitor were infections (6.8%), neutropenia(6.5%), bradycardia (4.2%), electrocardiogram QT prolonged (3.4%), diarrhoea (2.3%), vomiting(2.3%) and visual effects (2.3%).
Tabulated list of adverse reactionsAdverse drug reactions identified for Etcamah in the Etcamah and CDK4/6 inhibitors combination arevisual effects and bradycardia. Also included in Table 2 are adverse reactions, and their respectiveincidence, identified for the Etcamah and CDK4/6 inhibitors combination in the Etcamah incombination with a CDK4/6 inhibitor pool (n = 263).
In SERENA-6, the median duration of exposure to Etcamah in combination with a CDK4/6 inhibitorwas 15.54 months and to AI in combination with a CDK4/6 inhibitor was 7.36 months.
The adverse reaction frequencies from clinical studies are based on all-cause adverse eventfrequencies, where a proportion of the events for an adverse reaction may have causes other than thedrug, such as the disease, other medication or unrelated causes.
Adverse reactions are listed by MedDRA System Organ Class (SOC) and by descending frequency ofthe MedDRA grouped term. 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) andnot known (cannot be estimated from available data). Within each frequency grouping, adversereactions are presented in the order of decreasing seriousness.
Table 2 Adverse drug reactions reported in the Etcamah and CDK4/6 inhibitor combination(n = 263) a
MedDRA SOC MedDRA Term All Grades Grade 3 or 4category category
Infections and Infectionsd,e,f,g Very common Commoninfestations
Blood and lymphatic Neutropenia e,f,g,h Very common Very commonsystem disorders
Anaemiae,f,g,i Very common Common
Leukopeniae,f,g,j Very common Common
Thrombocytopeniae,f,g,k Very common Common
Lymphopeniaf,g Common Uncommon
Febrile neutropeniae,f,g Uncommon Uncommon
Metabolism and Decreased appetitee,f,g Common Uncommonnutrition disorders
Hypokalaemiag Common Common
Hypophosphatemiag Common Uncommon
Hypocalcaemiag Common Uncommon
Nervous system Dizzinessf,g Very common Uncommondisorders
Headachef,g Very common Uncommon
Dysgeusiae,f Common Uncommon
Syncopeg Common Uncommon
Eye disorders Visual effectsb Very common Uncommon
Dry eyee,g Very common -
Cardiac disorders Bradycardiac Very common -
Torsades de Pointesg Uncommon Uncommon
Vascular disorders Deep vein thrombosise,f Common Uncommon
Embolisme Uncommon Uncommon
Respiratory, thoracic Coughg Very common -and mediastinalgdisorders Dyspnoea Common Uncommon
Pulmonary embolisme,f Uncommon Uncommon
Gastrointestinal Diarrhoeae,f,g Very common Commondisorders
Nauseae,f,g Very common Uncommon
Vomitinge,f,g Very common Uncommon
Constipationg Common -
Abdominal paing Common Common
Stomatitise,f,g Common -
Skin and subcutaneous Pruritusf,g Common -tissue disorders
Alopeciae,f,g Common -
Musculoskeletal and Back paing Very common Commonconnective tissuedisorders
General disorders and Fatiguee,f,g Very common Commonadministration siteconditions Astheniae,g Very common Uncommon
Pyrexiae,f,g Common Uncommon
Investigations Aspartate Common Uncommonaminotransferaseincreased e,f,g
Alanine Common Commonaminotransferaseincreasede,f,g
Blood creatinine Common -increasede,g
Electrocardiogram QT Common Commonprolongedl
a. Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE), version 5.0.
b. Visual effects include photopsia, vision blurred, visual impairment, diplopia, and photophobia of eyedisorders MedDRA SOC, and visual perseveration of nervous system disorders MedDRA SOC. In additionto camizestrant, vision blurred is an ADR for palbociclib and photopsia is an ADR for abemaciclib.
c. Bradycardia includes bradycardia and sinus bradycardia.
d. All PTs under the Infections and Infestation SOC.
e. ADR for camizestrant and palbociclib combination.
f. ADR for camizestrant and abemaciclib combination.g. ADR for camizestrant and ribociclib combination.h. Neutropenia includes neutropenia and neutrophil count decreased.i. Anaemia includes anaemia, anaemia macrocytic and iron deficiency anaemia.j. Leukopenia includes leukopenia and white blood cell count decreased.k. Thrombocytopenia includes thrombocytopenia and platelet count decreased.
Description of selected adverse reaction
Bradycardia
Among the 19.8% patients with bradycardia reported, 85% patients had bradycardia reported asasymptomatic CTCAE Grade 1, while the remaining 15% had Grade 2 adverse reactions reported.
Bradycardia exhibited a time-dependent onset where a gradual decrease in heart rate can reach a stablenadir at approximately 14 days and generally recovered following treatment cessation in a similar timecourse.
Bradycardia in the presence of drug-induced QTc prolongation has the potential to increase the risk ofarrhythmia. QTc prolongation has been reported as an adverse reaction in 18 patients (6.8%) withinthe Etcamah and CDK4/6 inhibitor combination (see Table 2). Of those, 14 were reported as Grade 1or Grade 2; 3 were reported as Grade 3 and a Torsades de Pointes (Grade 4) was observed in a patientwith bradycardia and QTc prolongation for camizestrant in combination with ribociclib in a phase 1study. The Grade 3 and 4 events were in combination with ribociclib. Additional monitoring isrecommended (see sections 4.2 and 4.4).
Visual effects
Of the 40.7% patients who reported visual effects, the majority (92.5%) experienced CTCAE Grade 1adverse reactions, while 6.5% patients experienced CTCAE Grade 2 adverse reactions and 0.9%
CTCAE Grade 3 adverse reaction (photopsia) occurred. The most common visual effect was photopsia(24.0%). The median time to the onset of the first visual effect was 9 days. Visual effects ADRs weretypically intermittent, of brief duration, and not continuous throughout the day. Visual effects werereported not to worsen over time in patients. Ophthalmological review of patients reporting visualeffects showed no evidence of structural effects on the eye or clinically meaningful changes in visualacuity attributed to Etcamah (see section 5.1).
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.
4.9 Overdose
There is no specific treatment in the event of Etcamah overdose. No Maximum Tolerated Dose (MTD)was reached in the phase I studies in which patients received a daily monotherapy dose up to 450 mg.
The safety profile of patients treated with once daily doses of 150 mg Etcamah was consistent with theestablished safety profile of Etcamah at the recommended 75 mg once daily dose (see section 4.8). Incase of suspected overdose, patients should be closely monitored and treated symptomatically, ifnecessary.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Endocrine therapy, Anti-estrogens, ATC code: L02BA05
Mechanism of actionCamizestrant is an oral selective oestrogen receptor degrader (SERD) and oestrogen receptor (ER)antagonist.
Camizestrant binds to the ligand binding domain of ERα, antagonising the activity of ERα encoded byboth wild-type ESR1 and mutated ESR1, and inducing proteasome-dependent degradation of ERα,without agonising ERα.
Cardiac electrophysiologyExposure response analysis of potential QTcI prolongation of daily 75 mg to 300 mg of camizestrantmonotherapy was assessed in 30 patients. The predicted drug related mean QTcI prolongation was2.99 msec (95% CI: (-0.75, 6.73)) at the mean steady state Cmax with an upper bound of 6.09 msec(90% CI) following 75 mg camizestrant daily. At the recommended 75 mg dose of camizestrant, amean increase in QTcI > 10 msec was not observed.
Clinical efficacyER-positive, HER2-negative locally advanced or metastatic breast cancer
SERENA-6
SERENA-6 was a randomised, double-blind, circulating tumour DNA (ctDNA)-guided study to assessthe efficacy and safety of switching to Etcamah plus a CDK4/6 inhibitor (palbociclib, ribociclib orabemaciclib) versus continuing AI (letrozole or anastrozole) plus a CDK4/6 inhibitor in adultpre/peri/post-menopausal females and males with ER-positive/HER2-negative, locally advanced ormetastatic breast cancer with detectable ESR1-mutation assessed by ctDNA testing without diseaseprogression during first-line treatment with AI plus a CDK4/6 inhibitor. All patients were required tobe currently on treatment and have received ≥ 6 months of AI plus a CDK4/6 inhibitor treatment as theinitial endocrine based treatment with no evidence of disease progression as per investigatorassessment. Patients could have received one prior line of chemotherapy before the start of AI plus a
CDK4/6 inhibitor treatment. Patients with ECOG > 1, presence of widespread symptomatic metastaticvisceral disease, early progressors on CDK4/6 inhibitor; severe and uncontrolled cardiac comorbidity,severe hepatic impairment and/or QTc prolongation (defined as > 480 msec for combination withpalbociclib or abemaciclib; or ≥ 450 msec for combination with ribociclib were excluded. ESR1-mutation status was prospectively determined through testing of plasma-derived circulating tumour
DNA (ctDNA) using Guardant 360 CDx assay. Mutations in ESR1 that cause the indicated aminoacids changes were eligible for inclusion E380Q, V422del, S463P, L536H, L536P, L563R, Y537C,
Y537D, Y537N, Y537S, D538G. Based on results from the Guardant 360 assay, the most common
ESR1 alterations were variants at amino acids D538G, Y537S, and Y537N detected in 44.6%, 38.9%and 18.5% of patients with an eligible ESR1-mutation, respectively.
A total of 315 patients were randomised 1:1 to receive either Etcamah (n = 157, 75 mg once daily)plus a CDK4/6 inhibitor and a placebo of AI or continue AI plus a CDK4/6 inhibitor and placebo of
Etcamah (n = 158). The total percentage of randomised patients on palbociclib were 75.6%, ribociclibwere 14.9%, and abemaciclib were 9.5%. The choice of CDK4/6 inhibitor and its dose remained thesame at the time of randomisation for both arms. Randomisation was stratified by disease site (visceraldisease versus non-visceral disease), ESR1m detection (first test versus subsequent ctDNA tests), timefrom initiation of AI plus CDK4/6 inhibitor to randomisation (< 18 months versus ≥ 18 months), andtype of CDK4/6 inhibitor (palbociclib versus ribociclib versus abemaciclib). Pre/perimenopausalfemale patients and male patients taking concomitant LHRH agonist continued to receive it afterrandomisation. Treatment with Etcamah continued until disease progression or unacceptable toxicityoccurred.
The primary endpoint was progression free survival (PFS) as assessed by investigator per Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1. The key secondary endpoints were time fromrandomisation to second progression or death (PFS2) and overall survival (OS).
Demographic and baseline characteristics were well balanced between arms. Of the 315 patients, themedian age was 61.0 years (range 29.0 to 89.0 years and 36.8% were over 65 years of age); female(99.0%); male (1.0%); White (63.2%), Asian (23.2%), Black (1.9%), and other races (1.0%). Eastern
Cooperative Oncology Group (ECOG) performance status 0 (65.1%) or 1 (33.0%); 79.4% werepost-menopausal female and 20.6% were pre-/peri-menopausal female or male.
Efficacy results are summarized in Table 3 and Figure 1.
Table 3 Efficacy Results in SERENA-6 (DCO3: 02 Jan 2026)
Etcamah plus a CDK4/6
AI plus a CDK4/6 inhibitorinhibitor(n = 158)(n = 157)
Progression free survival (PFS) by Investigator assessment
Number of events a (%) 99 (63.1) 124 (78.5)
Median months b (95% CI) 16.76 (14.72, 19.35) 9.23 (7.23, 9.66)
Hazard ratio c (95% CI) 0.45 (0.34, 0.59)p-value d < 0.00001
Overall survival (OS) (30% maturity)
Number of events (%) 46 (29.3) 49 (31.0)
Median months b (95% CI) 41.20 (35.48, NC) 40.21 (36.50, 43.27)
Hazard ratio c 0.87 (0.57, 1.30)
a. Includes progression events that occur within 2 visits of last evaluable assessment.
b. The calculation is based on the Kaplan-Meier method.
c. A hazard ratio < 1 favours Etcamah plus CDK4/6 inhibitor treatment arm.
d. p value < 0.00001 achieved at DCO1 (28 Nov 2024).
Figure 1 Kaplan-Meier plot of progression-free survival by investigator assessment in SERENA-6
Etcamah + CDK 4/6 inhibitor
AI + CDK 4/6 inhibitor
Number of Time from randomisation (months) Number ofpatients at randomisedrisk patients/number
Months of events
Etcamah + CDK 4/6 inhibitor
AI + CDK 4/6 inhibitor
Paediatric populationThe European Medicines Agency has waived the obligation to submit the results of studies with
Etcamah in all subsets of the paediatric population in breast cancer (see section 4.2 for information onpaediatric use).
5.2 Pharmacokinetic properties
Camizestrant pharmacokinetic parameters have been characterized in healthy patients and breastcancer patients. Based on population pharmacokinetic (popPK) analysis, the pharmacokinetics ofcamizestrant at the 75 mg dose are characterized by an apparent plasma clearance of 69.1 L/h,
Probability of Progression-Free Survivalapparent volume of distribution (Vss/F) at steady state of 26.97 L/kg and a terminal half-life ofapproximately 23 hours. The camizestrant 75 mg dose oral bioavailability is 43% and steady state isreached by Day 5 following once daily dosing.
AbsorptionFollowing oral administration, camizestrant is absorbed with median peak plasma concentrationsachieved between approximately 2 to 4 hours after dosing.
Effect of foodSimilar exposures were observed following administration with a high fat meal or fasted overnightsupporting camizestrant being taken with or without food. Following a high fat meal, the fed to fasted
Cmax and AUC geometric mean ratios (90% CI) were 106.2% (90% CI: 94.3%, 119.7%) and 109.8%(90% CI: 104.4%, 115.5%), respectively.
DistributionBased on popPK analysis, camizestrant is distributed in the tissues with an apparent peripheral volumeof distribution of 8.69 L/kg. The apparent volume of distribution of camizestrant at steady state is26.97 L/kg.
Plasma protein binding of camizestrant is 75.3% (24.7% free). There is no evidence of concentrationdependent plasma protein binding. The blood to plasma ratio was 0.99.
BiotransformationMetabolism results from in vitro hepatocytes studies suggest that camizestrant undergoes multipleoxidation reactions in addition to direct N-glucuronidation and is primarily metabolised by CYP3A4/5and UGT1A4. Human metabolites of camizestrant were detected and quantified in pharmacokineticsamples from healthy female volunteers receiving a single oral dose of 75 mg [14C]-camizestrant(0.67 MBq). The major drug-related circulating materials were the N-glucuronide conjugate ofcamizestrant, the N-glucuronide of the acid metabolite and camizestrant which accounted for 20.1%,11.2%, and 13.6% of the circulating radioactivity in plasma. The other eight minor metabolites inplasma, each of which had a relative abundance lower than 10% of the total drug-related materials inplasma, were either oxidative metabolites or glucuronides of oxidative metabolites. No activemetabolites have been identified.
In vitro: Camizestrant does not inhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19 or CYP2E1and is a weak (IC50 > 100 µM) inhibitor of UGT1A1 and UGT2B7. Camizestrant does not causetime-dependent inhibition of CYP1A2, CYP2D6 and CYP3A4/5. Camizestrant has low potential tocause induction of CYP1A2, CYP2B6, and CYP3A4/5. For the drug transporters, camizestrant doesnot inhibit OATP1B3, OCT2, OAT1, OAT3, MATE1, and MATE2K and is not a substrate of BCRP,
OATP1B1 or OATP1B3.
EliminationFollowing single oral administration of 75 mg [14C]-camizestrant, mean of 82% of the radioactivityadministered was recovered in urine and faeces. Mean total radioactivity (65.1%) was recovered infaeces indicating faecal excretion was the main route of elimination following oral dosing; with 16.8%of the total radioactivity being recovered from the urine.
Linearity/non-linearityCamizestrant AUC and Cmax showed greater than dose-proportional increase over the dose range of 25to 450 mg.
Special populationsEffect of age, gender, race and weight
Based on popPK analyses (n = 756), no clinically significant relationships were identified betweenmodel predicted steady-state exposure, area under the curve at steady state (AUCss) and the followingcovariates: baseline median age 61 years (29 to 89 years) and racial groups. PopPK analysis showedbaseline median body weight was 69.9 kg (34.2 to 150 kg) and it affected apparent volume ofdistribution (V2/F), but this was not clinically relevant; it did not significantly impact apparent totalbody clearance (CL/F) or AUCss. No dose adjustments for camizestrant are required based on age,gender, race, or body weight.
Renal impairmentThe popPK analysis used continuous creatinine clearance. Baseline creatinine clearance (CrCL) wascalculated using the Cockcroft-Gault equation to evaluate the effect of renal function on camizestrant
PK; the median CrCL was 86.2 mL/min (range 22.8-303 mL/min). The analysis showed no clinicallymeaningful impact of mild and moderate renal impairment at baseline on camizestrant PK, indicatingthat no dose adjustment is necessary for patients with mild to moderate renal impairment.
There were limited patients with severe renal impairment and no patients on dialysis or with
CrCL < 15 mL/min were included in the clinical studies of camizestrant. Therefore, an appropriatedose of camizestrant has not been established for severe renal impairment patients and patients ondialysis (see section 4.2).
Hepatic impairmentBased on a pharmacokinetic study in patients following a single 75 mg dose, camizestrant exposuregeometric mean Cmax and AUC0-INF in patients with moderate (Child-Pugh B) hepatic impairment was2.4-fold and 2.7-fold, respectively, compared to patients with normal hepatic function. Camizestrantexposure geometric mean Cmax and AUC0-INF in patients with severe (Child-Pugh C) hepaticimpairment was 3.1-fold and 3.8-fold, respectively, compared to patients with normal hepaticfunction.
The exposure to camizestrant is higher than dose-proportional and increases with time until steadystate. The increase in exposure to camizestrant from single dose to steady state is not known insubjects with hepatic impairment (Child-Pugh). PopPK modelling did not indicate mild hepaticimpairment (NCI) as a significant covariate for camizestrant exposure. As precautionary measures,camizestrant should be avoided in subjects with moderate and severe hepatic impairment. Patientswith mild hepatic impairment are allowed to take camizestrant.
5.3 Preclinical safety data
Non-clinical/repeat-dose toxicity
In repeat-dose toxicity studies in mice, rats and dogs, the reproductive tract was identified as a targetorgan with histopathological findings occurring at exposures significantly below (female) or at 2-fold(male) human exposure at Maximum Recommended Human Dose (MRHD). There were relatedfindings in the adrenals (rats and mice) and pituitary (mice) glands. Findings were hormone-driven,based on the pharmacological action of camizestrant and therefore not relevant for post-menopausalwomen or pre- or peri menopausal women or men administered an LHRH agonist. Findings in themale reproductive tract of clinical relevance are described in the fertility section.
Macrophage aggregation (lung, spleen, thymus and mesenteric lymph nodes) and vacuolation (biliaryepithelium of the liver) were noted in the rat and/or mouse. This was confirmed as phospholipidosis inthe lung of rat, was reversible following 1-month dosing but was considered adverse in female rats inthe 6-month study at a total plasma exposure (AUC) of approximately 60-fold human exposure at
MRHD.
In mechanistic studies, camizestrant caused rod bipolar cell dysfunction in the retina of rats atclinically relevant exposures (approximately 5-fold human exposure at MRHD). The retina effects inrats were reversible and are consistent with the transient visual effects observed in humans.
Cardiovascular effects were observed across species (i.e. dogs and rats) and supported by mechanisticstudies. Heart rate reduction, related to decreased sinoatrial node pacemaker current activity via HCN4ion channels, was observed in animals and confirmed clinically (see section 4.4). In dogs and rats,additional delayed-onset cardiovascular functional effects included dose- and time-dependentdecreases in diastolic blood pressure, QA interval and PR interval, with increases in pulse pressure,
QT/QTc intervals and left ventricular parameters (dP/dt+ and dP/dt-). When assessed in dogs, QTcprolongation persisted for at least 3 days up to 4 weeks. The QTc prolongation was of unknownmechanism, independent of heart rate and unrelated to hERG inhibition and observed at maximumunbound plasma concentrations ≥ 4-fold those at human MRHD. Additional atrial prematurecomplexes (APCs) were observed in one telemetry and one toxicology dog at maximum free plasmalevels 12-fold and 33-fold human MRHD, respectively. Cardiomyopathy was observed in female ratsfollowing dosing for 6 months at total plasma exposures ≥ 11-fold the human AUC exposure at human
MRHD.
In dogs, combination dosing of camizestrant with atropine resulted in a significant increase in plasmaand brain exposure of atropine considered to be due to inhibition of atropine metabolism and,therefore, likely dog specific.
Mutagenicity and carcinogenicityCamizestrant was negative in the in vitro Ames and micronucleus assays, and the in vivo micronucleusstudy. Findings in the ovaries in chronic repeat-dose studies included hyperplasia at total plasmaexposures (AUC) ≥ 2-fold (rat granulosa cell) and 52-fold (dog sex cord stromal) relative to humanexposure at MRHD and benign granulosa cell tumours at total plasma exposures (AUC) ofapproximately 60-fold (rats) and 3.5-fold (dogs) relative to human exposure at MRHD. An interstitial(Leydig) cell adenoma was observed in the testis of a single dog at 13-fold human exposure at MRHD.
Findings are considered hormone-driven, based on the pharmacological action of camizestrant andtherefore not relevant for post-menopausal women or in pre- or peri menopausal women or menadministered an LHRH agonist.
Reproductive toxicityEmbryofoetal/developmental toxicity
Administration of camizestrant in a modified embryofoetal development study in rats resulted in acomplete lack of implantation in females when dosing at 0.1 mg/kg/day commenced prior toimplantation. When administration was restricted to the phase of organogenesis, camizestrant had noeffect on embryofoetal survival or development, but when dosed from implantation through parturitionand into lactation, camizestrant resulted in increased length of gestation, dystocia, impaired offspringsurvival and growth. Maternal exposures in this study were far below human exposure at MRHD.
FertilityIn a fertility study in female rats, camizestrant negatively affected oestrous cycles, mating behaviour,fertility and early embryonic survival which fully reversed following 1 month off dose. Effects wereobserved at maternal exposures below human exposure at MRHD.
In male rats and dogs, atrophy of the prostate gland, seminal vesicle and seminiferous tubules, tubulardilation of testis and changes in the epididymis (decreased sperm in rats and cell debris in dog) wereevident from the lowest dose in chronic studies at exposures ≥ 2-fold (rat) or ≥ 3.5-fold (dog) humanexposure at MRHD and were considered of clinical relevance. In male rats following 9 weeks ofdosing there were lower spermatid/sperm counts, a higher percentage of sperm abnormalities, lowersperm motility, and lower mating and pregnancy rates indicating an effect on male fertility. Effectswere observed at a total plasma exposure (AUC) ≥ 2-fold that observed at a clinical dose of 75 mg, buta no-effect level was not established. In that study, implantation loss and a decrease in number of livefoetuses was observed in non-dosed females paired with dosed males suggesting male-mediatedreproductive toxicity at a total plasma exposure (AUC) 27-fold the human exposure at MRHD.
Reversibility of male fertility findings was not assessed.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core
Cellulose, microcrystalline (type 102)
Calcium hydrogen phosphate
Sodium starch glycolate (Type A)
Magnesium stearate
Tablet coatingPolyvinyl alcohol
Titanium dioxide (E171)
Macrogol 3350
Talc
Iron oxide red (E172)
Iron oxide yellow (E172)
Iron oxide black (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
28x1 film-coated tablets in aluminium/aluminium perforated unit dose blisters. 2 blisters with 14 film-coated tablets each.
6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency https://www.ema.europa.eu.