Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Muscle-related adverse reactions
In the phase II pivotal study, muscle spasms, myalgia, myopathy and cases of CK elevations were observed. The majority of patients treated with Odomzo 200 mg daily who had grade 2 or higher CK elevations developed muscle symptoms prior to the CK elevations. For most patients, muscle symptoms and CK elevations resolved with appropriate management.

All patients starting therapy with Odomzo must be informed of the risk of muscle-related adverse reactions, including the possibility of rhabdomyolysis. They must be instructed to report promptly any unexplained muscle pain, tenderness or weakness occurring during treatment with Odomzo or if symptoms persist after discontinuing treatment.

CK levels should be checked prior to starting treatment and as clinically indicated thereafter, e.g. if muscle-related symptoms are reported. If clinically notable elevation of CK is detected, renal function should be assessed (see section 4.2).

Dose modification or interruption guidelines should be followed (see section 4.2).
Management of high-grade CK elevation using supportive therapy, including proper hydration, should be considered according to local standards of medical practice and treatment guidelines.

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity (e.g. CYP3A4 inhibitors, chloroquine, hydroxychloroquine, fibric acid derivatives, penicillamine, zidovudine, niacin and HMG-CoA reductase inhibitors) (see section 4.5).

Patients with neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) must be closely monitored due to an increased risk of muscle toxicity.

Embryofoetal death or severe birth defects

Odomzo may cause embryo-foetal death or severe birth defects when administered to pregnant women. Based on the mechanism of action, in animal studies, sonidegib has been shown to be teratogenic and foetotoxic. Women taking Odomzo must not be pregnant or become pregnant during treatment and for 20 months after ending treatment.

Criteria defining a woman of childbearing potential

A woman of childbearing potential is defined in the Odomzo 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 Odomzo.

Counselling

For women of childbearing potential
Odomzo is contraindicated in women of childbearing potential who do not comply with the Odomzo Pregnancy Prevention Programme. A woman of childbearing potential must understand that:
•    Odomzo exposes a teratogenic risk to the unborn child.
•    She must not take Odomzo if she is pregnant or plans to become pregnant.
•    She must have a negative pregnancy test, conducted by a healthcare professional within 7 days before starting Odomzo treatment.
•    She must have a negative pregnancy test monthly during treatment, even if she has become amenorrhoeic.
•    She must not become pregnant while taking Odomzo and for 20 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 Odomzo, unless she commits to not having sexual intercourse (abstinence).
•    She must tell her healthcare provider if any of the following occur during treatment and during the 20 months after her final dose: o     she becomes pregnant or thinks for any reason that she may be pregnant, o     she misses her expected menstrual period,
o     she stops using contraception unless she commits to not having sexual intercourse (abstinence),
o     she needs to change contraception.
•    She must not breast-feed while taking Odomzo and for 20 months after the final dose.

For men
Sonidegib may pass into the semen. To avoid potential foetal exposure during pregnancy, a male patient must understand that:
•    Odomzo 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 Odomzo or during the 6 months after his final dose.

For healthcare professionals
Healthcare professionals must educate patients so they understand and acknowledge all the conditions of the Odomzo Pregnancy Prevention Programme.

Contraception

Women of child-bearing potential
Women of child-bearing potential must use two methods of recommended contraception, including one highly effective method and a barrier method, while taking Odomzo and for 20 months after ending treatment (see section 4.6).


Men
Male patients, even those who have had a vasectomy, must always use a condom (with spermicide, if available) when having sex with a female partner while taking Odomzo and for 6 months after ending treatment (see sections 4.6 and 5.3).

Pregnancy testing

The pregnancy status of women of child-bearing potential must be established within 7 days prior to the initiation of Odomzo treatment and monthly during treatment by means of a test performed by a healthcare professional. Pregnancy tests should have a minimum sensitivity of 25 mIU/ml as per local availability. In the event of pregnancy, treatment must not be initiated.
In case of pregnancy occurring during treatment, Odomzo must be stopped immediately (see section 5.3). Patients who present with amenorrhoea during treatment with Odomzo should continue monthly pregnancy testing while on treatment.

Prescribing and dispensing restrictions for women of childbearing potential 
The initial prescription and dispensing of Odomzo should occur within 7 days of a negative pregnancy test. Prescriptions of Odomzo should be limited to 30 days of treatment, with continuation of treatment requiring a new prescription.

Educational material

In order to help healthcare providers and patients avoid embryonic and foetal exposure to Odomzo, the Marketing Authorisation Holder will provide educational materials (Odomzo Pregnancy Prevention Programme) to reinforce the potential risks associated with use of the medicinal product.

Blood donation

Patients should be instructed not to donate blood while taking Odomzo and for at least 20 months after ending treatment.

Semen donation

Male patients should not donate semen while taking Odomzo and for at least 6 months after ending treatment.

Premature fusion of the epiphyses
Premature fusion of the epiphyses has been reported in paediatric patients exposed to Hedgehog (Hh) pathway inhibitors. In some cases, fusion progressed after drug discontinuation (see section 4.8).

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 sonidegib cannot be excluded (see also section 4.5).


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 Odomzo. It has not been determined whether cuSCC is related to Odomzo treatment. Therefore, all patients should be monitored routinely while taking Odomzo, and cuSCC should be treated according to the standard of care.


Additional precautions
Patients should be instructed never to give this medicinal product to another person. Any capsules that remain unused at the end of treatment should immediately be disposed of by the patient in accordance with local requirements (e.g. by returning the capsules to their pharmacist or physician).

Excipients

Odomzo capsules contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Effects on Driving

4.7    Effects on ability to drive and use machines

Odomzo has no or negligible influence on the ability to drive and use machines.