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Odomzo is a brand name for Sonidegib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Odomzo is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) who are not amenable to curative surgery or radiation therapy.
Verbatim from this product's EMA label. Tap a section to expand.
Odomzo 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 200 mg sonidegib taken orally once daily. Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity develops.
Dose modifications for creatine phosphokinase (CK) elevations and muscle-related adverse reactions Temporary dose interruption and/or dose reduction of Odomzo therapy may be required for CK elevations and muscle-related adverse reactions.
3 Table 1 summarises recommendations for dose interruption and/or dose reduction of Odomzo therapy in the management of symptomatic CK elevations and muscle-related adverse reactions (such as myalgia, myopathy, and/or spasm). 5 x ULN] • Continue treatment at the same dose and monitor CK levels weekly until resolution to baseline level and then monthly thereafter.
Monitor muscle symptoms for changes until resolution to baseline. • Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated. 5 x ULN - 5 x ULN] • Interrupt treatment and monitor CK levels weekly until resolution to baseline level.
• Monitor muscle symptoms for changes until resolution to baseline. Upon resolution, resume treatment at the same dose level and measure CK monthly thereafter. • Check renal function (serum creatinine) regularly and ensure that the patient is adequately hydrated.
• If symptoms re-occur, interrupt treatment until resolution to baseline. Re-introduce sonidegib at 200 mg every other day and follow the same monitoring recommendations. If symptoms persist despite alternate-day dosing, consider discontinuing treatment.
Grade 3 or 4 without renal impairment (serum Cr ≤ ULN) [Grade 3 (CK elevation >5 x ULN - 10 x ULN)] [Grade 4 (CK elevation >10 x ULN)] • Interrupt treatment and monitor CK levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline.
• Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated. • If renal function is not impaired and CK resolves to baseline, consider resuming treatment at 200 mg every other day. CK levels should be measured weekly for 2 months after re-administration of sonidegib and monthly thereafter.
Summary of the safety profile The phase II pivotal study evaluated the safety of Odomzo in a total of 229 adult patients with locally advanced or metastatic BCC. Patients were treated with Odomzo 200 mg daily (n=79) or with Odomzo 800 mg daily (n=150).
3 months). One death occurred while on treatment or within 30 days of the last dose taken in either metastatic BCC or locally advanced BCC patients taking Odomzo 200 mg. The most common adverse drug reactions occurring in ≥10% of patients treated with Odomzo 200 mg were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhoea, weight decreased, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting and pruritus.
The most common grade 3/4 adverse drug reactions occurring in ≥2% of patients treated with Odomzo 200 mg were fatigue, weight decreased and muscle spasms. Among adverse drug reactions reported (Table 2), the frequency was greater in patients taking Odomzo 800 mg than in patients taking Odomzo 200 mg except for musculoskeletal pain, diarrhoea, abdominal pain, headache and pruritus.
This was also true for grade 3/4 adverse reactions, except fatigue. 11 Tabulated list of adverse drug reactions Adverse drug reactions for the recommended dose from the phase II pivotal clinical study (Table 2) are listed by Medical Dictionary for Regulatory Activities (MedDRA) version 18 system organ class.
Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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).
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. g. if muscle-related symptoms are reported. 2).
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. g. 5). g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) must be closely monitored due to an increased risk of muscle toxicity.
6 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.
1. 6). 6).
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4 Grade 2, 3 or 4 with renal impairment (serum Cr > ULN) • If renal function is impaired, interrupt treatment and ensure that the patient is adequately hydrated and evaluate other secondary causes of renal impairment. • Monitor CK and serum creatinine levels weekly until resolution to baseline.
Monitor muscle symptoms for changes until resolution to baseline. • If CK and serum creatinine levels return to baseline consider resuming treatment at 200 mg every other day and measure CK levels weekly for 2 months and monthly thereafter; otherwise discontinue treatment permanently.
03, developed by the National Cancer Institute (USA). The CTCAE is a standardised classification of adverse events used in assessing medicinal products for cancer therapy. Cr: creatinine; ULN: upper limit of normal Other dose modifications Management of severe or intolerable adverse reactions may require temporary dose interruption (with or without a subsequent dose reduction) or discontinuation.
When dose interruption is required, consider resuming Odomzo at the same dose after resolution of the adverse reaction to ≤ grade 1. If dose reduction is required, then the dose should be reduced to 200 mg every other day. If the same adverse drug reaction occurs following the switch to alternate daily dosing and does not improve, consider discontinuing treatment with Odomzo.
2). Duration of treatment In clinical studies, treatment with Odomzo was continued until disease progression or until unacceptable toxicity. Treatment interruptions of up to 3 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.
Special populations Patients with renal impairment Sonidegib has not been studied in a dedicated pharmacokinetic study in patients with renal impairment. Based on the available data, sonidegib elimination via the kidney is negligible.
2). No efficacy and safety data are available in patients with severe renal impairment. 2). 2). 5 Paediatric population The safety and efficacy of Odomzo in children and adolescents aged below 18 years with basal cell carcinoma have not been established.
No data are available. Method of administration Odomzo is for oral use. The capsules must be swallowed whole. They must not be chewed or crushed. 3). Odomzo must be taken at least two hours after a meal […]
Table 2 Adverse drug reactions observed in the phase II pivotal study Primary system organ class Preferred term Frequency all grades 200 mg Metabolism and nutrition disorders Decreased appetite Very common Dehydration Common Nervous system disorders Dysgeusia Very common Headache Very common Gastrointestinal disorders Nausea Very common Diarrhoea Very common Abdominal pain Very common Vomiting Very common Dyspepsia Common Constipation Common Gastro-oesophageal reflux disorder Common Skin and subcutaneous tissue disorders Alopecia Very common Pruritus Very common Rash Common Abnormal hair growth Common Musculoskeletal and connective tissue disorders Muscle spasms Very common Musculoskeletal pain Very common Myalgia Very common Myopathy [muscular fatigue and muscular weakness] Common Reproductive system and breast disorders Amenorrhoea* Very common General disorders and administration site conditions Fatigue Very common Pain Very common Investigations Weight decreased Very common * Of the 79 patients receiving Odomzo 200 mg, 5 were women of childbearing age.
Among these women, amenorrhoea was observed in 1 patient (20%). 12 Clinically relevant laboratory abnormalities The most commonly reported grade 3/4 laboratory abnormalities with an incidence of ≥ 5% occurring in patients treated with Odomzo 200 mg were lipase increase and blood CK increase (Table 3).
03 Description of selected adverse drug reactions Muscle-related adverse reactions including CK elevation Muscle toxicity is the most clinically relevant side effect reported in patients receiving sonidegib therapy and is believed to be a class effect of inhibitors of the Hedgehog (Hh) signalling pathway.
In the phase II pivotal study muscle spasms were the most common “muscle-related” adverse reactions, and were reported in fewer patients in the Odomzo 200 mg group (54%) than in the Odomzo 800 mg group (69%). Grade 3/4 increase in blood CK was reported in 8% of patients taking Odomzo 200 mg.
The majority of patients who had grade 2 or higher CK elevations developed muscle symptoms prior to the CK elevations. 9 weeks (range 2 to 39 weeks) after initiating Odomzo therapy and a median time to resolution (to normalisation or grade 1) of 12 days (95% CI 8 to 14 days).
One patient receiving Odomzo 200 mg experienced muscle symptoms and CK elevations above 10x ULN and required intravenous fluids, compared to 6 patients receiving Odomzo 800 mg. 5-fold increase in serum creatinine from the pre-treatment or baseline level).
However, one reported case in a patient treated with Odomzo 800 mg in a non-pivotal study was confirmed. 3%) out of 14 women of either child-bearing potential or of child-bearing age sterilised by tubal ligation developed amenorrhoea while on treatment with Odomzo 200 mg or 800 mg once daily.
Paediatric population The evaluation of safety in the paediatric population is based on data from 16 adult and 60 paediatric […]
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. 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.
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.
6). 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. 3). Patients who present with amenorrhoea during treatment with Odomzo should continue monthly pregnancy testing while on treatment.
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