Dosing and uses of Odomzo (sonidegib)
Adult dosage forms and strengths
capsule
- 200mg
Basal Cell Carcinoma
Indicated for adults with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy
200 mg PO qDay on empty stomach 1 hr before or 2 hr after meals
Continue treatment until disease progression or unacceptable toxicity
Dosage modifications
Renal impairment: No dose adjustment required
Hepatic impairment
- Hepatic impairment: Mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment: No dose adjustment required
Interrupt sonidegib for
- Severe or intolerable musculoskeletal adverse reactions
- First occurrence of serum CK elevation between 2.5 and 10 x ULN
- Recurrent serum CK elevation between 2.5 and 5 x ULN
- Resume dose at 200 mg daily upon resolution of clinical signs and symptoms
Permanently discontinue sonidegib for
- Serum CK elevation >2.5 x ULN with worsening renal function
- Serum CK elevation >10 x ULN
- Recurrent serum CK elevation >5 x ULN
- Recurrent severe or intolerable musculoskeletal adverse reactions
Dosing Considerations
Verify the pregnancy status of females of reproductive potential prior to initiating
Obtain serum CK levels and renal function tests in all patients prior to initiating
Pediatric dosage forms and strengths
Safety and efficacy not established
Odomzo (sonidegib) adverse (side) effects
>10%
Muscle spasms (54%)
Alopecia (53%)
Dysgeusia (46%)
Fatigue (41%)
Nausea (39%)
Diarrhea (32%)
Musculoskeletal pain (32%)
Decreased weight (30%)
Decreased appetite (23%)
Myalgia (19%)
Abdominal pain (18%)
Headache (15%)
Pain (14%)
Vomiting (11%)
Chemistry and hematology laboratory tests
- Increased serum creatinine (92%)
- Increased serum creatine kinase (61%)
- Hyperglycemia (51%)
- Increased lipase (43%)
- Anemia (32%)
- Lymphopenia (28%)
- Increased ALT or AST (19%)
- Increased amylase (16%)
1-10%
Pruritus (10%)
Warnings
Black box warnings
Based on sonidegib’s mechanism of action, can cause embryo-fetal death or severe birth defects when administered to a pregnant woman
Sonidegib is embryotoxic, fetotoxic, and teratogenic in animals
Verify pregnancy status of females of reproductive potential prior to initiating; advise females of reproductive potential to use effective contraception during treatment and for at least 20 months after the last dose
Advise male patients to use condoms, even after a vasectomy, to avoid potential drug exposure to pregnant partners and female partners of reproductive potential during treatment and for at least 8 months after the last dose
Contraindications
None
Cautions
Can cause embryo-fetal death or severe birth defects when administered to a pregnant woman (see Black box warnings and Pregnancy sections)
Advise patients not to donate blood or blood products while taking sonidegib and for at least 20 months after the last dose because their blood or blood products might be given to a female of reproductive potentiaL
Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase elevations, occur with Hedgehog pathway inhibitors
Avoid coadministration with moderate/strong CYP3A inhibitors or inducers
Pregnancy and lactation
Pregnancy
Based on sonidegib’s mechanism of action, can cause fetal harm when administered to a pregnant woman
There are no available data on the use in pregnant women
In animal reproduction studies, oral administration of sonidegib during organogenesis at doses below the recommended human dose of 200 mg resulted in embryotoxicity, fetotoxicity, and teratogenicity in rabbits (teratogenic effects observed included severe midline defects, missing digits, and other irreversible malformations)
Verify pregnancy status of females of reproductive potential prior to initiating
Advise females of reproductive potential to use effective contraception during treatment and for at least 20 months after the last dose
Do not donate blood for at least 20 months after the last dose
Males
- Unknown if sonidegib is present in semen
- Advise male patients to use condoms, even after a vasectomy, to avoid potential drug exposure to pregnant partners and female partners of reproductive potential during treatment and for at least 8 months after the last dose
- Do not donate semen for at least 8 month or blood for at least 20 months
Lactation
Unknown if distributed in human breast milk
Because of the potential for serious adverse reactions in breastfed infants from sonidegib, advise a nursing woman not to breastfeed during treatment and for 20 months after the last dose
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Odomzo (sonidegib)
Mechanism of action
Hedgehog (Hh) pathway inhibitor; the Hh signaling pathway is important in embryogenesis, but in adults, it is mostly inactive; signaling is relayed by key proteins, including smoothened (SMO)
Hh ligand-expressing cancerous epithelial cells that are activated by the Hh signaling pathway may cause growth promotion; sonidegib binds to and inhibits SMO, a transmembrane protein involved in Hedgehog signal transduction
Absorption
<10% of oral dose is absorbed
Peak plasma time: 2-4 hr (fasting)
Peak plasma concentration: 1030 ng/mL
Minimum plasma concentration: 890 ng/mL
AUC: 22 mcg·h/mL
Distribution
Protein bound: >97%
Vd (Vss/F): 9,166 L
Metabolism
Primarily metabolized by CYP3A
The main circulating compound was unchanged sonidegib (36% of circulating radioactivity)
Elimination
Half-life: 28 days
Excretion: 70% feces; 30% urine
Administration
Instructions
Swallow capsule on an empty stomach, at least 1 hr before or 2 hr after a meaL
If a dose is missed, resume dosing with the next scheduled dose
Storage
Store at controlled room temperature (25°C [77°F]); excursions permitted to 15-30°C (59-86°F)
