Sonidegib

Name: Sonidegib

What should I do if I forget a dose?

Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Sonidegib Side Effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Sonidegib can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have:

  • severe or unexplained muscle pain or tenderness (even if this occurs after you have stopped taking sonidegib);
  • muscle weakness;
  • little or no urinating;
  • dark colored urine; or
  • fever, unusual tiredness.

Common side effects may include:

  • stomach pain, nausea, vomiting, diarrhea;
  • loss of appetite, weight loss;
  • muscle spasms;
  • headache;
  • missed menstrual periods;
  • itchy skin, hair loss; or
  • changes in your sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Uses of Sonidegib

Sonidegib is a prescription medication used to treat adults with basal cell carcinoma, a type of skin cancer, that has come back following surgery or radiation or that cannot be treated with surgery or radiation. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Sonidegib Usage

Take sonidegib exactly as your healthcare provider tells you.

  • Take sonidegib 1 time each day.
  • Take sonidegib at least 1 hour before or 2 hours after a meal.
  • If you miss a dose, skip the missed dose. Take your next dose as scheduled.
  • Do not donate blood or blood products while you are taking sonidegib and for 20 months after your final dose.
  • Do not donate semen while taking sonidegib and for at least 8 months after your final dose.

What is the most important information I should know about sonidegib?

Do not use this medicine if you are pregnant. Sonidegib can cause severe birth defects or stillbirth if the mother or the father is taking this medicine at the time of conception or during pregnancy.

Use birth control to prevent pregnancy, whether you are a man or a woman. For women: Use birth control while taking sonidegib and for at least 20 months after you take your last dose. For Men: Use condoms during sex while you are taking sonidegib and for at least 8 months after you take your last dose. Use condoms even if you had a vasectomy, or if your partner is already pregnant or able to become pregnant.

Sonidegib can cause a condition that results in the breakdown of skeletal muscle tissue. Call your doctor right away if you have unexplained muscle pain or weakness.

What should I avoid while taking sonidegib?

Do not donate blood while you are taking sonidegib and for at least 20 months after your final dose of sonidegib.

Do not donate semen (sperm) while taking sonidegib and for at least 8 months after your final dose.

Sonidegib dosing information

Usual Adult Dose for Basal Cell Carcinoma:

200 mg orally once a day

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:
-This drug should be taken on an empty stomach at least 1 hour before or 2 hours after a meal.
-Prior to treatment initiation, serum creatinine kinase (CK) levels and renal function tests should be obtained from all patients, and the pregnancy status of females of reproductive potential should be verified.

Use: Treatment of adult patients 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.

What other drugs will affect sonidegib?

Other drugs may interact with sonidegib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Introduction

Antineoplastic agent; a hedgehog signaling pathway inhibitor.1 2 3 4 5

Cautions for Sonidegib

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryofetal toxicity and teratogenicity demonstrated in animals.1 (See Boxed Warning.)

Avoid pregnancy during therapy.1 Women of childbearing potential should use effective contraception during treatment and for at least 20 months following drug discontinuance.1

Because it is not known whether drug distributes into semen, sexually mature males (including those who have undergone successful vasectomy) must use a condom each time during sexual contact with a pregnant woman or woman of childbearing potential during and for at least 8 months after therapy.1 Men must not donate semen during and for at least 8 months after therapy.1

Patients must not donate blood or blood products during and for at least 20 months after therapy, because of potential for any sonidegib present in blood to be transfused into a pregnant woman.1

Obtain a pregnancy test prior to initiating therapy in women of childbearing potential.1

If pregnancy occurs in a female patient or female partner of male patient receiving sonidegib, apprise of potential fetal hazard.1 Report any suspected fetal exposure to the manufacturer at 888-669-6682.1

Other Warnings and Precautions

Musculoskeletal Effects

Musculoskeletal effects, possibly accompanied by increased CK concentrations, occur frequently.1 Rhabdomyolysis (i.e., serum CK concentrations >10 times baseline value; Scr concentrations ≥1.5-fold baseline value) reported in 1 patient receiving sonidegib 800 mg.1

Most common musculoskeletal effects include muscle spasms, musculoskeletal pain, myalgia.1 Musculoskeletal pain and myalgia usually precede increased CK concentrations.1 Some patients experienced musculoskeletal effects requiring medical intervention with magnesium supplementation, muscle relaxants, analgesics, IV hydration, and/or hospitalization.1

Median time to onset of grade 2 or greater elevations in CK concentrations: 12.9 weeks.1 Median time to resolution of increased CK concentrations to grade 1 or less: 12 days.1

Monitor CK and Scr concentrations at baseline, periodically during therapy, and as clinically indicated.1 If musculoskeletal symptoms and elevations in CK concentrations of >2.5 times ULN occur, monitor CK and Scr concentrations at least weekly until resolution.1 Temporary interruption, dosage reduction, or discontinuance of drug may be necessary depending on severity of musculoskeletal symptoms.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Impairment of Female Fertility

May impair female fertility based on animal findings.1

Specific Populations

Pregnancy

May cause fetal harm.1 (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether distributed into milk.1 Discontinue nursing during therapy and for at least 20 months after drug discontinuance.1 10

Effects of sonidegib on nursing infants or human milk production unknown.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No overall differences in efficacy in geriatric patients (≥65 years of age) compared with younger adults.1 Increased incidence of grade 3 or 4 adverse effects, serious adverse effects, or adverse effects requiring interruption or discontinuance of therapy in geriatric patients compared with younger adults.1

Hepatic Impairment

In a population pharmacokinetic analysis, systemic exposure not altered by mild hepatic impairment; no dosage adjustment necessary in such patients.1 9 (See Special Populations under Pharmacokinetics.)

Not studied in patients with moderate or severe hepatic impairment.1 9

Renal Impairment

In a population pharmacokinetic analysis, systemic exposure not altered by mild (Clcr 60–89 mL/minute) or moderate (Clcr of 30–59 mL/minute) renal impairment; dosage adjustment not necessary in such patients.1 9 (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Muscle spasms,1 2 alopecia,1 2 dysgeusia,1 2 fatigue,1 2 nausea,1 2 diarrhea,1 2 musculoskeletal pain,1 weight loss,1 2 decreased appetite,1 2 myalgia,1 2 abdominal pain,1 headache,1 2 pain,1 vomiting,1 pruritus,1 arthralgia.2

Laboratory abnormalities: Increased Scr,1 increased CK,1 hyperglycemia,1 increased lipase,1 anemia,1 lymphopenia,1 elevated AST and ALT concentrations,1 increased amylase.1

Amenorrhea lasting at least 18 months reported in 2 of 14 premenopausal women receiving sonidegib (200 or 800 mg once daily).1

Sonidegib Pharmacokinetics

Absorption

Bioavailability

<10% absorbed.1 4 5

Systemic exposure and peak plasma concentrations increase in a dose-proportional manner following administration of sonidegib 100–400 mg.1 3

Peak plasma sonidegib concentrations are attained about 2–4 hours after oral administration under fasting conditions.1

Steady-state concentrations are achieved within approximately 4 months.1

Estimated systemic accumulation is 19-fold.1

Food

Administration with a high-fat meal increased AUC and peak plasma concentrations by 7.4- to 7.8-fold.1 Fivefold increase in bioavailability reported after administration with a high-fat meal in a population pharmacokinetic analysis.9

Special Populations

Mild hepatic impairment: Systemic exposure was similar to that in patients with normal hepatic function.1 9 (See Hepatic Impairment under Dosage and Administration.) Moderate or severe hepatic impairment: Pharmacokinetics not studied.1 9

Mild (Clcr 60–89 mL/minute) or moderate (Clcr 30–59 mL/minute) renal impairment: Systemic exposure was similar to that in patients with normal renal function.1 9 (See Renal Impairment under Dosage and Administration.)

Age, gender, body weight, or ethnicity: No clinically important effects on sonidegib pharmacokinetics.1 9 Systemic exposure following administration of sonidegib (single 200-mg dose) increased by 1.7-fold in healthy Japanese individuals versus those from Western countries.1

Distribution

Extent

Not known whether distributed into human milk or semen.1 (See Lactation and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Not known whether distributed into semen.1

Plasma Protein Binding

>97%.1

Elimination

Metabolism

Metabolized mainly by CYP3A.1

Elimination Route

Eliminated mainly in feces (70%) and to a lesser extent in urine (30%).1

Half-life

Estimated terminal half-life: 28–29.6 days.1 9

Commonly used brand name(s)

In the U.S.

  • Odomzo

Available Dosage Forms:

  • Capsule

Therapeutic Class: Antineoplastic Agent

How do I store and/or throw out Sonidegib?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Pronunciation

(soe ni DEG ib)

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

In Summary

Commonly reported side effects of sonidegib include: muscle spasm, musculoskeletal pain, and myalgia. See below for a comprehensive list of adverse effects.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

-Mild Hepatic Impairment (total bilirubin at the upper limit of normal or less and AST greater than ULN OR total bilirubin greater than 1 to 1.5 x ULN): No adjustment recommended
-Moderate and Severe Hepatic Impairment: Data not available

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