Erismodegib
Erismodegib Uses, Dosage, Side Effects, Food Interaction and all others data.
Erismodegib is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was FDA approved in 2015 for the treatment of basal cell carcinoma.
Erismodegib has been shown to inhibit a transmembrane protein called SMO which plays a role in Hh signal transduction. This has resulted in inhibition of Hh signaling as well as antitumour activity in various animal models. In a transgenic mouse model of islet cell neoplasms, tumour volume was reduce by 95% in mice treated with sonidegib when compared with untreated mice. (2)
| Trade Name | Erismodegib |
| Availability | Prescription only |
| Generic | Sonidegib |
| Sonidegib Other Names | Erismodegib, Sonidegib |
| Related Drugs | fluorouracil topical, imiquimod topical, Efudex, Aldara, Libtayo, Erivedge |
| Type | |
| Formula | C26H26F3N3O3 |
| Weight | Average: 485.507 Monoisotopic: 485.192626198 |
| Protein binding | Sonidegib is over 97% bound to plasma proteins, and binding is independent of concentration. (2) |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Erismodegib is an antineoplastic agent used for the treatment of locally advanced recurrent basal cell carcinoma (BCC) following surgery and radiation therapy, or in cases where surgery or radiation therapy are not appropriate.
Erismodegib is approved for use in the US and EU for treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred post surgery or radiation therapy. It is also approved for adult patients with BCC who are not eligible for surgery or radiation therapy. (2)
Erismodegib is also used to associated treatment for these conditions: Refractory, locally advanced Basal cell carcinoma
How Erismodegib works
The hedgehog pathway is involved in many human cancers. Erismodegib effectively inhibits the regulator called smoothened (Smo), preventing the hedgehog pathway from functioning. As a result, tumours that depend on the hedgehog pathway are unable to grow. (1)
Toxicity
Adverse events occurred more frequently with higher doses, 800 mg once daily when compared to a lower dose of 200 mg once daily. In the 200 mg group, frequent adverse events (occurring in ≥2% of patients) included: elevated creatine phosphokinase (6%), increased lipase (5%), muscle spasms (3%), asthenia (3%), and hypertension (3%). In the 800 mg group, frequent adverse events included: elevated creatine phosphokinase (13%), increased lipase (5%), weight loss (5%), muscle spasms (5%), decreased appetite (4%), rhabdomyolysis (3%), nausea (3%), hypertension (3%), increased alanine aminotransferase (3%), increased aspartate aminotransferase (3%), fatigue (2%), syncope (2%), anaemia (2%), dehydration (2%), hyperkalaemia (2%) and myalgia (2%). Rhabdomyolysis cases reported by investigators were not confirmed by the adjudication committee on muscle toxicity or the independent safety review. (2)
Food Interaction
- Exercise caution with grapefruit products. Grapefruit inhibits the CYP3A metabolism of sonidegib, which may increase its serum concentration.
- Exercise caution with St. John's Wort. This herb induces the CYP3A metabolism of sonidegib, which may reduce its serum concentration.
- Take on an empty stomach. Take sonidegib at least 1 hour before or 2 hours after eating.
[Moderate] ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of sonidegib.
According to the product labeling, administration of sonidegib with a high-fat meal (approximately 1000 calories; 50% from fat) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 7.4- to 7.8-fold.
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of sonidegib.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.
In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.
Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Increased exposure to sonidegib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, nausea, vomiting, diarrhea, anorexia, weight loss, alopecia, pruritus, and dysgeusia.
MANAGEMENT: Erismodegib should be administered on an empty stomach, at least 1 hour before or 2 hours after a meal.
Patients should avoid consumption of grapefruit or grapefruit juice during treatment with sonidegib.
Erismodegib Drug Interaction
Unknown: charcoal, sulfamethoxazole / trimethoprim, ubiquinone, copper gluconate, ethanol, glycerin, heparin, sodium iodide, arginine, levocarnitine, cysteine, lithium, acetaminophen, bioflavonoids, vitamin a topical, bioflavonoids, sotalol, tramadol, valproic acid, thiamine
Erismodegib Disease Interaction
Volume of Distribution
Estimated volume of distribution = 9166 L (2)
Elimination Route
Erismodegib is rapidly absorbed in the fasted state with peak concentrations occurring 2-4 hours after administration. (2) However, the total absorption of Erismodegib is low (roughly 6-7%). (1)
Half Life
Half-life ~ 28 days (2)
Elimination Route
Around 70% of Erismodegib is eliminated in the feces, while 30% is eliminated in the urine. (2)
Innovators Monograph
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