Sonidegib (Oral)

Often marketed as Odomzo, Sonidegib is an anticancer agent developed by Novartis.

Overview

Sonidegib is a relatively new medicine which is primarily used to treat certain types of cancer. It is known as a Hedgehog signalling pathway inhibitor. The Hedgehog signalling pathway transmits information to new cells which require proper cell differentiation. Different parts of embryonic cells have differing concentrations of hedgehog signalling proteins. It is one of the key regulators in human development, and numerous cancers are associated with the malfunctioning of this pathway.

In July 2015, Sonidegib was approved for the treatment of basal-cell carcinoma caused by malfunctions in the hedgehog signalling pathway. It functions by binding and inhibiting activation of the hedgehog pathway in order to interfere with the spread and growth of cancer cells within the body, and has been effective in the treatment of breast cancer, skin cancer, pancreatic cancer and more. It has also been shown to be significantly effective against in vitro and in vivo melanoma. When invasive surgery or radiation cannot be used, Sonidegib is often a first-line choice of treatment.

This medicine is administered orally and excreted hepatically. It does not currently have approval for medical use within the EU although it is expected to be greenlit as a suitable anti-cancer agent within the next two years, as US studies have already proven its safety and efficacy. In some instances, a doctor may prescribe Sonidegib for "off-label"use, for purposes other than those stated by the manufacturer.

Conditions treated

Type of medicine

  • Anti-cancer agent

Side effects

Along with its desired effects, Sonidegib may also cause some unwanted side effects. The most common side effects reported by patients using this medicine include joint pain, difficulty moving, muscle pains, stiffness, swollen joints, general aches, abdominal pain, decreased appetite, diarrhea, changes in taste, hair loss or thinning hair, itchy skin, vomiting and/or nausea. Other side effects experienced rarely by patients, although often enough to warrant mentioning, include fever, dark-colored urine and/or unusual weakness or tiredness.

As the patient continues treatment with the medicine as prescribed by a doctor, most (if not all) of these side effects should lessen. If any side effects persist over time or appear to get worse, the patient should follow this up with his or her doctor. For symptoms which cause minor discomfort, a physician or healthcare professional may be able to advise the patient on how they can alleviate symptoms using natural or over the counter remedies.

The majority of patients will typically only encounter minimal side effects while being treated with Sonidegib, if they experience any at all. The drug is used to treat serious illness and as such, many practitioners agree that the benefit of Sonidegib use greatly outweighs the risk of minor discomfort experienced due to the side effects.

Approximately 92% of patients undergoing treatment with Sonidegib experienced an increase in serum creatinine. 61% experienced an increase in creatinine kinase, and 54% reported musculoskeletal pain. Around half of patients being treated with the drug experienced alopecia or at least some form of hair loss.

Dosage

As with all medicines, it is imperative that the patient only takes Sonidegib exactly as prescribed by their doctor. This means that patients should refrain from taking more of this medication than advised, in terms of dose size and frequency. It is important for patients to pay attention to the instructions of their physician when the medication is prescribed, as well as following instructions printed on the medication packaging.

When determining the most suitable dose size, a doctor will take a number of factors into account. The strength of the dose, the number of doses to be taken on a daily or weekly basis and the period the patient should spend undergoing treatment with Sonidegib will all inform the doctor's decision when coming to a conclusion as to the most effective dose. External factors, such as the height, weight and age of the patient will also have some bearing on this outcome. The reason why the patient has been prescribed the drug will also affect dosage.

The manufacturers of this medicine provide general dosage instructions on the literature provided with it. However, it must be reiterated that these guidelines may be altered by the patient's doctor. Factors mentioned above, as well as factors which arise during patient-doctor discussion will help a doctor to establish the best possible course of treatment.

For the treatment of cancers such as basal cell carcinoma, Sonidegib oral capsules are generally taken in doses of 200mg, once a day. It is recommended that Sonidegib is taken on an empty stomach, at least one hour before a meal or two hours afterwards. This is to ensure the maximum efficacy of the medicine and to prevent certain side effects.

Before treatment, renal function tests and serum creatinine kinase levels should be monitored. In females, pregnancy status and reproductive potential should be verified before beginning a course of treatment with this medicine.

Therapy with Sonidegib should continue until satisfactory progression or unacceptable levels of toxicity occur. Sonidegib can be a long-term treatment and patients should be prepared to take the medicine regularly for months or even years.

In some instances, dosage adjustments may be required. If any of the following conditions are reported, treatment should be interrupted until clinical signs and symptoms have been resolved, at which point treatment at 200mg per day can be resumed:

  • First instance of serum CK elevation between 2.5 - 10x ULN
  • Recurring instances of serum CK elevation between 2.5 - 5x ULN
  • Intolerable or severe musculoskeletal reactions

Treatment with Sonidegib should be permanently discontinued in patients who experience the following conditions:

  • Serum CK elevation greater than 10x ULN
  • Recurrent serum CK elevation greater than 5x ULN
  • Reccurring instances of severe or unbearable musculoskeletal reactions
  • Serum CK elevation above 2.5x ULN when renal functioning is worsening

Patients are advised against taking double doses. In the event that a patient accidentally misses a dose, they are advised to skip the dose and resume treatment the following day with the next dose in the schedule. Double doses can lead to overdose, and this can cause heightened side effects or even death.

If a patient experiences signs of an overdose, such as an extremely slow or fast heartbeat, or difficulty breathing, they may require immediate medical attention. Patients in this situation are therefore advised to contact their local poison control center on 1800-222-1222, the emergency services on 911, or to make their way to the nearest ER.

Interactions

The effects of a medicine can be changed if it interacts with other drugs or chemicals in the human body. All drugs can potentially interact, and in some cases it can lead to a medication becoming ineffective. In other instances, interactions can cause dangerous or even fatal side effects. Because of these risks, it is incredibly important for patients to keep a full, detailed list of all medicines they are currently taking, include dosage sizes, frequencies and history of use. This extends to complementary medicines, herbal supplements, vitamins and over the counter remedies as well as prescription medications.

Below is a partial list of medicines known to interact negatively with Sonidegib. Patients who are currently undergoing treatment with any of these medications should notify their doctor or healthcare provider prior to taking the first dose of Sonidegib:

  • Aprepitant
  • Atazanavir
  • Amprenavir
  • Boceprivir
  • Bosentan
  • Carbamazepine
  • Ciprofloxacin
  • Cobicistat
  • Clarithromycin
  • Conivaptan
  • Crizotinib
  • Clotrimazole
  • Dabrafenib
  • Dexamethasone
  • Dalopristin
  • Diltiazem
  • Darunavir
  • Dronedarone
  • Delavirdine
  • Efavirenz
  • Ephedrine
  • Etravirine
  • Enzalutamide
  • Erythromycin
  • Fluconazole
  • Fosaprepitant
  • Fosamprenavir
  • Fosphenytoin
  • Hyoscamine
  • Phenobarbital
  • Idelalisib
  • Imatinib
  • Isoniazid
  • Rifampin
  • Itraconazole
  • Indinavir
  • Isavuconazonium
  • Ketoconazole
  • Lopinavir
  • Modafinil
  • Mibefradil
  • Mitotane
  • Nafcillin
  • Nevirapine
  • Nefazodone
  • Nelfinavir
  • Ombitasvir
  • Posaconazole
  • Primidone
  • Phenytoin
  • Ribociclib
  • Rifapentine
  • Ritonavir
  • Rifampin
  • Saquinavir
  • Telaprevir
  • Trandolapril
  • Telithromycin
  • Troleandomycin
  • Verapamil
  • Viroconazole

Warnings

The absorption of Sonidegib into the bloodstream is significantly increased when there is food in the stomach. This can potentially increase side effects such as muscle weakness, muscle spasms, muscular pain, nausea, vomiting, appetite loss, weight loss, hair loss, itching, fatigue and taste abnormalities. Patients who continue to take this medication with food may also put themselves at risk of developing a rare albeit serious condition known as rhabdomyolysis which involves the rapid breakdown of skeletal muscle tissue. In certain cases, this condition can cause irreversible kidney damage leading to death. Therefore, patients with unexplained muscle pain, weakness or tenderness during the course of treatment with Sonidegib are advised to consult with their doctor as soon as possible, particularly if these symptoms are also accompanied by the passing of dark colored urine and a fever.

Patients undergoing treatment with Sonidegib should avoid grapefruit juice for the entirety of their treatment with this medicine. Certain compounds in grapefruit juice are known to increase the blood levels of this medication days after it has been consumed.

Pregnant women should not be treated with Sonidegib. This is because the drug is known to cause fetal harm based on its mechanism of action. Females of reproductive potential should conduct a pregnancy test prior to treatment with Sonidegib, and are advised to use effective contraception during treatment and for approximately 20 months after the last dose of the drug. Males of reproductive age should not donate semen and should use condoms during sexual intercourse for the duration of treatment with Sonidegib, and for at least 8 months after treatment has been completed also.

Patients who have previously been treated or are currently being treated with Sonidegib are advised not to give blood for at least twenty months after their last dose of the drug, in order to protect female recipients of reproductive age who require a blood transfusion.

Storage

Sonidegib should be stored out of the reach of children or pets, at room temperature. In addition to this, the manufacturer recommends that it is stored away from moisture and direct sunlight. It is therefore unsuitable for storage in a bathroom cabinet, and should ideally be kept in a dedicated medicine cupboard or drawer.

If the patient ceases treatment with this medicine and has a supply of the drug remaining, they should take care to dispose of it in a hygenic and safe manner.

Summary

Sonidegib is an effective treatment for numerous types of cancer, particularly for patients who are unable or unwilling to undergo surgery or radiotherapy. While it is incredibly beneficial as an anti-cancer agent, it also poses a risk to patients who do not abide by the directions of their doctor or otherwise fail to communicate effectively with them in regard to the medicines they are currently taking.

When used correctly, Sonidegib can help patients to completely recover from cancer and enable them to live a healthy, fulfilled life. To achieve this, doctor and patient must work together to eliminate the propensity for harmful interactions and to find the optimal dosage dependent on the type of cancer the patient is suffering from.

Resources
Last Reviewed:
December 25, 2017
Last Updated:
April 05, 2018
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