sonidegib

Absorption: <10% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: >97%.

Metabolism/Excretion: Mostly metabolized in the liver by the CYP3A isoenzyme. 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 ⬆ ⬇

(plasma concentrations)

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;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

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

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia, pruritus

Endo: hyperglycemia, amenorrhea

GI: abdominal pain, diarrhea, nausea, vomiting, ↑liver enzymes

GU: ↑serum creatinine

Hemat: anemia, lymphopenia

Metab: ↓appetite, ↓weight

MS: muscle spasms, musculoskeletal pain, myalgia, RHABDOMYOLYSIS

Neuro: fatigue, headache, dysgeusia

Misc: generalized pain

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inhibitors, including itraconazole, ketoconazole, nefazodone, posaconazole, or voriconazole, may ↑ levels and risk of toxicity; concurrent use should be avoided.
Moderate CYP3A inhibitors, including atazanavir, diltiazem, or fluconazole, may ↑ levels and risk of toxicity; concurrent use should be avoided.
Strong or moderate CYP3A inducers, including carbamazepine, efavirenz, modafinil, phenobarbital, rifabutine, or rifampin, may ↓ levels and effectiveness; concurrent use should be avoided.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; concurrent use 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:

Verify negative pregnancy status before starting therapy.
Obtain serum 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 times upper limit of normal (ULN) until resolution of clinical signs and symptoms. If 1st occurrence of or recurrent serum CK between 2.5 and 5 times ULN, interrupt therapy; resume sonidegib at 200 mg once daily on resolution of clinical signs and symptoms. If serum CK >2.5 times ULN with worsening renal function, serum CK >10 times ULN, or recurrent serum CK >5 times ULN, permanently discontinue sonidegib.
- May cause hyperglycemia and ↑ 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 hr after meals.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. 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 notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patients to notify health care professional promptly if any new unexplained muscle pain, tenderness or weakness, dark urine, or ↓ 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.
Rep: May cause fetal harm. Caution females with reproductive potential to use effective contraception and avoid breastfeeding during therapy and for 20 mo after last dose. Advise males with female partners of reproductive potential of potential risk of exposure through semen, use condoms, and avoid donating semen during therapy and for 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 ⬆ ⬇