Sonidegib (trade name Odomzo) is an oral small molecule drug that inhibits the Hedgehog signaling pathway, which is involved in cellular growth, differentiation, and repair. This drug specifically targets the Smoothened (SMO) protein, a molecule that plays a crucial role in the Hedgehog pathway.

Sonidegib has been approved for the treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred after surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. Basal cell carcinoma is the most common type of skin cancer.

Sonidegib (Odomzo - Novartis) is a Hedgehog signaling pathway inhibitor that has been approved for the treatment of basal cell carcinoma.

Sonidegib (Odomzo) Uses:

• Locally advanced basal cell carcinoma:
  • With locally advanced basal cell carcinoma (BCC), treatment of adult patients, that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

Vismodegib is another hedgehog pathway inhibitor used to treat skin cancer.

Sonidegib Dose in Adults

Note:

• Before starting the medicine, make sure women who could become pregnant are not pregnant.
• Also, do blood tests to check muscle health and kidney function for everyone.

Sonidegib Dose in the treatment of locally advanced Basal cell carcinoma:

• Take 200 mg of Sonidegib by mouth once a day. Continue until the disease gets worse or the side effects become too much to handle.

If you forget a dose:

• Don't take the missed dose. Just take the next one when it's time.

Sonidegib Use in Children:

The safety and efficacy of the drug in children have not been established.

Sonidegib Pregnancy Risk  Category: D

Warning: Taking Sonidegib while pregnant can cause serious harm or death to the baby. It can also cause severe birth defects.

• If a woman can become pregnant, make sure she isn't pregnant before she starts taking this medicine.
• Women who can get pregnant should use birth control while taking Sonidegib and for 20 months after the last dose.
• Men might have the drug in their semen. They should use condoms while taking the medicine and for 8 months after stopping, even if they've had a vasectomy. This is to protect any partners who might get pregnant.
• Men shouldn't donate sperm while on the drug and for 8 months after stopping.

Sonidegib use during breastfeeding:

• We don't know if Sonidegib is passed into breast milk.
• Because it might harm a breastfeeding baby, the maker of the medicine says not to breastfeed while taking it and for 20 months after stopping.

Sonidegib Dose in Kidney Disease:

• If your kidneys clear 30 to 89 mL/minute: The maker of the medicine doesn't give special dose instructions. People with mild or moderate kidney problems had similar experiences with the drug as those with normal kidney function.
• If your kidneys clear less than 30 mL/minute: The maker of the medicine doesn't give special dose instructions.

Sonidegib Dose in Liver disease:

For people with mild, moderate, or severe liver problems (known as Child-Pugh classes A, B, and C): The maker of the medicine doesn't give special dose instructions. People with liver problems had similar experiences with the drug as those with normal liver function.

Common Side Effects of Sonidegib (Odomzo):

• Central Nervous System:
  • Fatigue
  • Headache
  • Pain
• Dermatologic:
  • Alopecia
• Endocrine & Metabolic:
  • Hyperglycemia
  • Weight Loss
  • Increased Serum ALT
  • Increased Serum AST
  • Increased Amylase
• Gastrointestinal:
  • Dysgeusia
  • Increased Serum Lipase
  • Nausea
  • Diarrhea
  • Decreased Appetite
  • Abdominal Pain
  • Vomiting
• Hematologic & Oncologic:
  • Anemia
  • Lymphocytopenia
• Neuromuscular & Skeletal:
  • Increased Creatine Phosphokinase
  • Muscle Spasm
  • Musculoskeletal Pain
  • Myalgia
• Renal:
  • Increased Serum Creatinine

Less Common Side Effects of Sonidegib (Odomzo):

• Dermatologic:
  • Pruritus

Contraindications to Sonidegib (Odomzo):

• The instructions from the manufacturer don't mention any reasons not to use it.

Warnings and Precautions

Amenorrhea:

• Amenorrhea means not having a menstrual period.
• In this case, it's saying that women who could potentially get pregnant didn't have their period for at least 18 months.

Musculoskeletal toxicity:

• Musculoskeletal problems were common in more than two-thirds of patients who took sonidegib.
• These problems included muscle spasms, muscle pain, and muscle aches, and some were quite severe (grade 3 or 4).
• Many patients also had high levels of a substance called creatine kinase in their blood, which often happened along with muscle pain and aches.
• When these levels were moderately high or worse (grade 2 or higher), it usually took about 13 weeks for symptoms to show up, and it took around 12 days for them to get better.
• Some patients needed medical treatment for these muscle problems, like magnesium supplements, muscle relaxants, or pain medications.
• In rare cases, a severe muscle condition called rhabdomyolysis was seen in one patient who took a higher dose than approved by the FDA.
• Doctors should check patients' creatine kinase levels and creatinine levels in their blood before starting the treatment and regularly during it, especially if there are muscle symptoms.
• Patients should let their doctors know if they experience new, unexplained muscle pain, tenderness, or weakness either while taking the medication or after stopping it.
• In some cases, treatment may need to be paused or stopped.

Renal impairment:

• Many patients who took sonidegib showed higher levels of a substance called creatinine in their blood, but for most of them, these levels were still in the normal range (more than 75% of patients).
• Even though people with kidney problems don't need a change in their dose, it's important for doctors to check their creatinine levels before they start taking the medication and from time to time, especially if there are muscle problems.

Sonidegib: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Serum Creatine Kinase (CK) and Serum Creatinine:

• Doctors will regularly check your blood for creatine kinase (CK) levels.
• They will also measure your creatinine levels before you start the treatment and during the treatment.
• If you have muscle problems or high CK levels (more than 2.5 times the upper limit of normal), they will check your creatinine levels at least once a week until the issue is resolved.

Liver Function:

• Your liver function will be monitored to ensure the medication is not harming your liver.

Pregnancy Status:

• Your doctor will check whether you are pregnant or not, as this medication can be harmful to a developing baby.

Signs/Symptoms of Musculoskeletal Toxicity:

• Be sure to tell your doctor if you experience any muscle-related problems or pain, as these could be side effects of the medication.

How to administer Sonidegib (Odomzo)?

• Take this medication by mouth, but make sure your stomach is empty.
• That means you should take it at least 1 hour before eating or wait for 2 hours after a meal before taking it.

Mechanism of action of Sonidegib (Odomzo):

• Basal cell cancer is linked to changes in a pathway called Hedgehog.
• Hedgehog is responsible for controlling how cells grow and develop in the early stages of life.
• Normally, Hedgehog is not very active in adult tissues. However, when there are mutations related to basal cell cancer, it can become too active. This causes skin basal cells to grow uncontrollably.
• Sonidegib is a medication that specifically targets the Hedgehog pathway.
• It works by attaching to a protein called Smoothened homologue (SMO), which is involved in transmitting signals in the Hedgehog pathway. When Sonidegib binds to SMO, it blocks the pathway's activity. This helps stop the uncontrolled growth of basal cells in basal cell cancer.

Absorption:

• Less than 10% of the medication is absorbed into the bloodstream.

Effect of Food:

• When taken with a high-fat meal (about 1,000 calories with 50% fat), the amount of the medication in the blood (AUC and C) increases by about 7.4 to 7.8 times.

Distribution:

• The medication is distributed throughout the body, and the total volume it spreads to is approximately 9,166 liters.

Protein Binding:

• Over 97% of the medication in the bloodstream is bound to proteins.

Metabolism:

• The medication is primarily broken down by the liver through a process involving an enzyme called CYP3A.

Bioavailability:

• Less than 10% of the medication from an oral dose actually gets absorbed into the bloodstream.

Half-life elimination:

• It takes about 28 days for half of the medication to be removed from the body.

Time to Peak:

• The time it takes for the medication to reach its highest concentration in the blood is typically 2 to 4 hours after taking it.

Excretion:

• The medication is mainly eliminated from the body through the feces (about 70%) and a smaller portion through urine (about 30%).

International Brands of Sonidegib:

• Odomzo
• Odomo

Sonidegib Brand Names in Pakistan:

Not available.