TreatmentTreatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
- Brand name: Samogy
- Generic Name: Sotorasib
- Strength: 120mg
- Dosage Form: film-coated tablets
PHOSOTOR (sotorasib) is indicated as monotherapy for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), who have progressed on, or are intolerant to, platinum-based chemotherapy and/or anti PD-1/PD-L1 immunotherapy.
Posology and method of administration
Treatment with PHOSOTOR (sotorasib) must be initiated by a physician experienced in the use of anticancer medicinal products.
The presence of a KRAS G12C mutation must be confirmed using a validated test prior to initiation of Samogy therapy.
The recommended dose of PHOSOTOR (sotorasib) is 960 mg (eight 120 mg tablets) orally once daily, at the same time each day, with or without food.
Duration of treatment
Treatment with PHOSOTOR (sotorasib) is recommended until disease progression or unacceptable toxicity.
If less than 6 hours have passed since the scheduled time of dosing, the patient should take the dose as normal. If more than 6 hours have passed since the scheduled time of dosing, the patient must not take the dose. Treatment should be continued as prescribed the next day. Additional doses should not be taken in place of a missed dose.
If vomiting occurs after taking PHOSOTOR (sotorasib) and, the patient must not take an additional dose on the same day, and treatment must be continued as prescribed the next day.
Warnings and precautions for use:
PHOSOTOR (sotorasib) can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Sotorasib has been associated with transient elevations of serum transaminases (ALT and AST) (see section 4.8). These elevations improved or resolved with dose modification or permanent discontinuation of treatment and did not result in any cases of liver failure or fatal cases in clinical studies. Cases of liver enzyme increase can be asymptomatic. Liver function tests (ALT, AST, and total bilirubin) must be monitored prior to the start of PHOSOTOR (sotorasib), every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Based on the severity of the laboratory abnormalities, treatment with PHOSOTOR (sotorasib) must be stopped until recovered to ≤ grade 1 or to baseline grade, and the dose must either be modified or permanently discontinue treatment as recommended (see section 4.2).
Interstitial Lung Disease (ILD)/Pneumonitis
ILD/pneumonitis occurred in patients treated with PHOSOTOR (sotorasib) with prior exposure to immunotherapy or radiotherapy (see section 4.8). Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnoea, cough, fever). Immediately withhold PHOSOTOR (sotorasib) in patients with suspected ILD/pneumonitis and permanently discontinue PHOSOTOR (sotorasib)if no other potential causes of ILD/pneumonitis are identified (see section 4.2)
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.
Interaction with other medicinal products and other forms of interaction
Effects of other medicinal products on sotorasib
Co-administration of sotorasib with a PPI (omeprazole) or an H2 receptor antagonist (famotidine) led to a decrease in sotorasib concentrations.
Under fed conditions (standard-calorie moderate-fat meals), co-administration of multiple doses of omeprazole with a single dose of 960 mg sotorasib decreased sotorasib Cmax by 65% and AUC by 57%. Co-administration of a single dose of famotidine given 10 hours prior and 2 hours after a single dose of 960 mg sotorasib decreased sotorasib Cmax by 35% and AUC by 38%.
Under fasted conditions, co-administration of multiple doses of omeprazole with a single dose of 960 mg sotorasib decreased sotorasib Cmax by 57% and AUC by 42%.
Co-administration of PPIs and H2 receptor antagonists with PHOSOTOR (Sotorasib) is not recommended because the impact on sotorasib efficacy is unknown. If treatment with an acid-reducing agent is required, PHOSOTOR (Sotorasib) should be taken 4 hours before or 10 hours after administration of a local antacid (see section 4.2).
Strong CYP3A4 inducers
Co-administration of sotorasib with multiple doses of a strong CYP3A4 inducer (rifampicin) decreased sotorasib Cmax by 35% and AUC by 51%. Co-administration of strong CYP3A4 inducers with PHOSOTOR (Sotorasib) is not recommended because the impact on sotorasib efficacy is unknown.
Effect of sotorasib on other medicinal products
Sotorasib is a moderate CYP3A4 inducer. Co-administration of sotorasib with CYP3A4 substrates led to a decrease in their plasma concentrations, which may reduce the efficacy of these substrates.
Co-administration of sotorasib with midazolam (a sensitive CYP3A4 substrate) decreased midazolam Cmax by 48% and AUC by 53%.
Avoid co-administration of PHOSOTOR (Sotorasib) with CYP3A4 substrates with narrow therapeutic indices. If co-administration cannot be avoided, adjust the CYP3A4 substrate dosage in accordance with the current summary of product characteristics.
There is no clinical experience with overdose with sotorasib. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required.