sonidegib

Absorption: <10% absorbed following oral administration.

Distribution: Crosses the placenta.

Protein Binding: >97%.

Metabolism/Excretion: Mostly metabolized in the liver by the CYP3A enzyme system. Mostly eliminated by the hepatic route; 70% excreted in feces (unchanged drug and metabolites); 30% in urine (as unchanged drug).

Half-Life: 28 days.

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Blood donation should be avoided during and for 20 mo following treatment;
Concurrent use of strong CYP3A inhibitors or prolonged (>14 days) use of moderate CYP3A inhibitors;
Concurrent use of strong or moderate CYP3A inducers;
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential and men with female partners of reproductive potential;
Geri: risk of adverse reactions.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia, pruritus

Endo: hyperglycemia, amenorrhea

GI: ↓appetite, , abdominal pain, diarrhea, nausea, vomiting, ↑liver enzymes, , dysgeusia

GU: ↑serum creatinine

Hemat: anemia, lymphopenia

Metab: ↓weight

MS: muscle spasms, musculoskeletal pain, myalgia, ↑CK, RHABDOMYOLYSIS

Neuro: fatigue, headache

Misc: generalized pain

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of strong CYP3A inhibitors including itraconazole, ketoconazole, nefazodone, posaconazole, or voriconazole↑ levels/toxicity and should be avoided.
Concurrent prolonged (> 14 days) use of moderate CYP3A inhibitors including atazanavir, diltiazem or fluconazole↑ levels/toxicity and should be avoided.
Concurrent use of strong or moderate CYP3A inducersincluding carbamazepine, efavirenz, modafinil, phenobarbital, rifabutineor rifampin↓ levels/effectiveness and should be avoided.

Drug-Natural Products:

Concurrent use of St. John's wort↓ blood levels and may ↓ effectiveness and should be avoided.

Route/Dosage ⬆ ⬇

PO (Adults ): 200 mg once daily.

Availability ⬆ ⬇

Capsules: 200 mg

Assessment ⬆ ⬇

Assess lesions prior to and periodically during therapy.
Monitor for musculoskeletal adverse reactions (muscle spasms, musculoskeletal pain, myalgia) during therapy. If severe or intolerable, interrupt therapy. If severe or intolerable musculoskeletal adverse reactions recurrent, permanently discontinue sonidegib. May require magnesium supplementation, muscle relaxants, and nonopioid or opioid analgesics.

Lab Test Considerations:

Obtain serum creatine kinase (CK) and creatinine level prior to starting and periodically during therapy and as clinically indicated. Obtain serum CK and serum creatinine levels at least weekly in patients with musculoskeletal adverse reactions with concurrent serum CK ↑ >2.5 X upper limit of normal until resolution of clinical signs and symptoms. If 1st occurrence of or recurrent serum CK ↑ between 2.5 and 5 X upper limit of normal, interrupt therapy. Resume sonidegib at 200 mg daily upon resolution of clinical signs and symptoms. If serum CK ↑ >2.5 X upper limit of normal with worsening renal function, serum CK ↑ >10 X upper limit of normal, recurrent serum CK ↑ >5 X upper limit of normal, permanently discontinue sonidegib.
- May cause hyperglycemia, ↑ serum lipase, ALT, AST, and amylase.
- May cause anemia and lymphopenia.

Implementation ⬆ ⬇

PO: Administer once daily on an empty stomach ≥1 hr before or 2 hrs after meals.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take sonidegib as directed on an empty stomach. If a dose is missed, omit and take next dose at scheduled time. Advise patient to read Patient Information prior to starting therapy and with each Rx refill in case of changes.
Advise patients to notify health care professional promptly if any new unexplained muscle pain, tenderness or weakness, dark urine, or decreased amount of urine occurs during therapy or persists after discontinuing sonidegib.
Discuss with patient the possibility of hair loss. Explore methods of coping.
Rep: Advise patient not to donate blood or blood products while taking and for at least 20 mo after the last dose of sonidegib because blood or blood products might be given to a female of reproductive potential. Advise male patient to avoid donating semen during and for at least 8 mo after final dose.
Rep: Sonidegib is teratogenic. Caution females with reproductive potential to use effective contraception and avoid breastfeeding during and for at least20 mo after last dose. Advise males with female partners of reproductive potential of potential risk of exposure through semen and to use condoms during and for at least 8 mo after last dose. Advise females who may have been exposed to sonidegib during pregnancy, either directly or through seminal fluid, to contact Sun Pharmaceutical Industries Inc. at 1-800-406-7984.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇