Adult: For patients who have progressed on, or are intolerant to platinum-based chemotherapy and/or anti-programmed death 1 (PD-1)/anti-programmed death ligand 1 (PD-L1) immunotherapy: 960 mg once daily. Continue until disease progression or unacceptable toxicity occurs. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guidelines).
Administration
film-coated tab: May be taken with or without food. Take at the same time each day. Swallow whole, do not chew/crush/split. For patients w/ difficulty swallowing, disperse tab in 120 mL of non-carbonated, room temp water w/o crushing. No other liqd should be used. Stir until tab disperses into small pieces (the tab will not completely dissolve) & drink immediately or w/in 2 hr. The appearance of the mixt may range from pale yellow to bright yellow. Do not chew pieces of tab. Rinse glass w/ another 120 mL of water & drink.
Contraindications
Lactation.
Special Precautions
Patient with lung diseases. Hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Hepatotoxicity, which may progress to hepatitis and drug-induced liver injury. Blood and lymphatic system disorders: Anaemia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, constipation. General disorders and administration site conditions: Fatigue, pyrexia, oedema. Investigations: Increased serum ALT, serum AST, serum alkaline phosphatase, serum bilirubin, and GGT; decreased Hb, lymphocyte and albumin levels; increased urinary protein and aPTT. Metabolism and nutrition disorders: Decreased appetite, hypokalaemia, hypocalcaemia, hyponatraemia. Musculoskeletal and connective tissue disorders: Back pain, musculoskeletal pain, arthralgia. Nervous system disorders: Headache. Renal and urinary disorders: UTI. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, pneumonia. Skin and subcutaneous tissue disorders: Rash. Potentially Fatal: ILD/pneumonitis.
PO: Z (Avoid in pregnancy unless benefits outweigh risks.)
Patient Counseling Information
Women of childbearing potential must use proven birth control methods during therapy and for at least 7 days after stopping the treatment. Consider using other reliable contraceptive methods recommended by the doctor as hormonal contraceptives may be ineffective. Discontinue breastfeeding during therapy and for 7 days after the last dose.
Monitoring Parameters
Prior to initiation of therapy, confirm the presence of Kirsten rat sarcoma viral oncogene homolog (KRAS G12C) mutation in the tumour or plasma specimen; if a mutation is not detected in the plasma specimen, the tumour tissue may be tested. Monitor LFTs (AST, ALT, total bilirubin) before starting therapy, every 3 weeks for the 1st 3 months, then once monthly or as clinically required (test more frequently in patients who develop increased transaminase and/or bilirubin levels). Assess for new or worsening pulmonary symptoms that may indicate ILD or pneumonitis (e.g. fever, cough, dyspnoea).
Drug Interactions
Decreased serum concentration with strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, mitotane, enzalutamide), PPIs (e.g. omeprazole), and histamine 2 (H2)-receptor antagonists (e.g. famotidine); sotorasib must be taken 4 hours before or 10 hours following administration of acid-reducing agents. May reduce the plasma concentrations and efficacy of CYP3A4 substrates (e.g. midazolam, alfentanil, ciclosporin, sirolimus, tacrolimus, quinidine, hormonal contraceptives). May increase the plasma concentrations of BCRP substrates (e.g. rosuvastatin, topotecan) and digoxin (P-gp substrate).
Food Interaction
Decreased serum concentration with St. John's wort.
Action
Description: Mechanism of Action: Sotorasib is an irreversible and selective inhibitor of Kirsten rat sarcoma viral oncogene homolog (KRAS G12C), a mutated rat sarcoma (RAS) GTPase involved in the signalling and cell growth of tumour cells. It forms covalent and irreversible binding to the unique cysteine of KRAS G12C, thereby blocking tumour cell signalling and survival, inhibiting cell growth, and promoting apoptosis selectively in KRAS G12C cell lines only. Wild-type KRAS is not affected. Pharmacokinetics: Absorption: Time to peak plasma concentration: 1 hour (median). Distribution: Plasma protein binding: 89%. Metabolism: Undergoes non-enzymatic conjugation and oxidative metabolism by CYP3A isoenzymes. Excretion: Mainly via faeces (approx 74%; 53% as unchanged drug); urine (6%; 1% as unchanged drug). Terminal elimination half-life: 5 hours.
Chemical Structure
Sotorasib Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 137278711, Sotorasib. https://pubchem.ncbi.nlm.nih.gov/compound/Sotorasib. Accessed Mar. 29, 2023.
L01XX73 - sotorasib ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Sotorasib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/02/2023.Anon. Sotorasib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/02/2023.Buckingham R (ed). Sotorasib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/02/2023.Joint Formulary Committee. Sotorasib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/02/2023.Lumakras (Amgen). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 02/02/2023.Lumakras Tablet, Coated (Amgen Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/02/2023.Lumykras 120 mg Film-coated Tablets (Amgen Europe B.V.). European Medicines Agency [online]. Accessed 02/02/2023.
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