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LUMAKRAS ® (sotorasib) Brief Prescribing Information
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.Healthcare professionals are asked to report any suspected adverse reactions Please refer to the Summary of Product Characteristics before prescribing LUMAKRAS ® Pharmaceutical Form LUMAKRAS is Film-coated tablet. Yellow, oblong‑shaped, immediate release, film-coated, debossed with “AMG” on one side and “120” on the opposite side Indications: LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C‑mutated locally advanced or metastatic non‑small cell lung cancer (NSCLC), as determined by an approved test (please refer to SmPC), who have received at least one prior systemic therapy.This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). , Posology and method of administration Patient selection Select patients for treatment of locally advanced or metastatic NSCLC with LUMAKRAS based on the presence of KRAS G12C mutation in tumor or plasma specimens. If no mutation is detected in a plasma specimen, test tumor tissue. Posology The recommended dosage of LUMAKRAS is 960 mg (eight 120 mg tablets) orally once daily until disease progression or unacceptable toxicity.Take LUMAKRAS at the same time each day with or without food (please refer to SmPC). Swallow tablets whole. Do not chew, crush or split tablets. If a dose of LUMAKRAS is missed by more than 6 hours, take the next dose as prescribed the next day. Do not take 2 doses at the same time to make up for the missed dose.If vomiting occurs after taking LUMAKRAS, do not take an additional dose. Take the next dose as prescribed the next day.Dosage Modifications for Adverse Reactions
LUMAKRAS dose reduction levels are summarized in SmPC. Dosage modifications for adverse reactions are provided in SmPC. If adverse reactions occur, a maximum of two dose reductions are permitted. Discontinue LUMAKRAS if patients are unable to tolerate the minimum dose of 240 mg once daily. Coadministration of LUMAKRAS with Acid‑Reducing Agents Avoid coadministration of proton pump inhibitors (PPIs) and H2 receptor antagonists with LUMAKRAS. If treatment with an acid‑reducing agent cannot be avoided, take LUMAKRAS 4 hours before or 10 hours after administration of a local antacid (please refer to SmPC). Administration to Patients Who Have Difficulty Swallowing Solids Disperse tablets in 120 mL (4 ounces) of non‑carbonated, room‑temperature water without crushing. No other liquids should be used. Stir until tablets are dispersed into small pieces (the tablets will not completely dissolve) and drink immediately or within 2 hours. The appearance of the mixture may range from pale yellow to bright yellow. Swallow the tablet dispersion. Do not chew pieces of the tablet. Rinse the container with an additional 120 mL of water and drink. If the mixture is not consumed immediately, stir the mixture again to ensure that tablets are dispersed. Contraindications None. Special warnings and precautions for use Hepatotoxicity LUMAKRAS can cause hepatotoxicity, which may lead to drug‑induced liver injury and hepatitis. Among 357 patients who received LUMAKRAS in CodeBreaK 100 (please refer to SmPC), hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. The median time to first onset of increased ALT/AST was 9 weeks (range: 0.3 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 7% of patients. LUMAKRAS was discontinued due to increased ALT/AST in 2.0% of patients. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity. Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of LUMAKRAS, 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. Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction (please refer to SmPC) Interstitial Lung Disease (ILD)/Pneumonitis LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100 (see section 4.8 in SmPC), ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 2 weeks (range: 2 to 18 weeks). LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified (please refer to SmPC). Lactose intolerance LUMAKRAS contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose‑galactose malabsorption should not take this medicinal product. Sodium This medicinal product 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 Drugs on LUMAKRAS Acid‑Reducing Agents Coadministration of LUMAKRAS with gastric acid‑reducing agents decreased sotorasib concentrations (please refer to SmPC), which may reduce the efficacy of sotorasib. Avoid coadministration of LUMAKRAS with proton pump inhibitors (PPIs), H2 receptor antagonists, and locally acting antacids. If coadministration with an acid‑reducing agent cannot be avoided, administer LUMAKRAS 4 hours before or 10 hours after administration of a locally acting antacid (please refer to SmPC) Strong CYP3A4 Inducers Coadministration of LUMAKRAS with a strong CYP3A4 inducer decreased sotorasib concentrations (see section 5.2 in SmPC), which may reduce the efficacy of sotorasib. Avoid coadministration of LUMAKRAS with strong CYP3A4 inducers. Effects of LUMAKRAS on Other Drugs CYP3A4 Substrates Coadministration of LUMAKRAS with a CYP3A4 substrate decreased its plasma concentrations (please refer to SmPC), which may reduce the efficacy of the substrate. Avoid coadministration of LUMAKRAS with CYP3A4 sensitive substrates, for which minimal concentration changes may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. P‑glycoprotein (P‑gp) Substrates Coadministration of LUMAKRAS with a P‑gp substrate (digoxin) increased digoxin plasma concentrations (see section 5.2 in SmPC), which may increase the adverse reactions of digoxin. Avoid coadministration of LUMAKRAS with P‑gp substrates, for which minimal concentration changes may lead to serious toxicities. If coadministration cannot be avoided, decrease the P‑gp substrate dosage in accordance with its Prescribing Information.Fertility, pregnancy and lactation Pregnancy Risk Summary There are no available data on LUMAKRAS use in pregnant women. In rat and rabbit embryo‑fetal development studies, oral sotorasib did not cause adverse developmental effects or embryo‑lethality at exposures up to 4.6 times the human exposure at the 960 mg clinical dose (see Data) Lactation Risk Summary There are no data on the presence of sotorasib or its metabolites in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LUMAKRAS and for 1 week after the final dose. Pediatric Use The safety and effectiveness of LUMAKRAS have not been established in pediatric patients.Geriatric Use Of the 357 patients with any tumor type who received LUMAKRAS 960 mg orally once daily in CodeBreaK 100, 46% were 65 and over, and 10% were 75 and over. No overall differences in safety or effectiveness were observed between older patients and younger patients. Effects on ability to drive and use machines LUMAKRAS has no or negligible influence on the ability to drive and use machines. Undesirable effects The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity (see section 4.4 in SmPC) Interstitial Lung Disease (ILD)/Pneumonitis (please refer to SmPC) Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to LUMAKRAS as a single agent at 960 mg orally once daily in 357 patients with NSCLC and other solid tumors with KRAS G12C mutation enrolled in CodeBreaK 100, 28% were exposed for 6 months or longer and 3% were exposed for greater than one year. Non‑Small Cell Lung Cancer The safety of LUMAKRAS was evaluated in a subset of patients with KRAS G12C‑mutated locally advanced or metastatic NSCLC in CodeBreaK 100. Patients received LUMAKRAS 960 mg orally once daily until disease progression or unacceptable toxicity (n = 204). Among patients who received LUMAKRAS, 39% were exposed for 6 months or longer and 3% were exposed for greater than one year. The median age of patients who received LUMAKRAS was 66 years (range: 37 to 86); 55% female; 80% White, 15% Asian, and 3% Black. Serious adverse reactions occurred in 50% of patients treated with LUMAKRAS. Serious adverse reactions in ≥ 2% of patients were pneumonia (8%), hepatotoxicity (3.4%), and diarrhea (2%). Fatal adverse reactions occurred in 3.4% of patients who received LUMAKRAS due to respiratory failure (0.8%), pneumonitis (0.4%), cardiac arrest (0.4%), cardiac failure (0.4%), gastric ulcer (0.4%), and pneumonia (0.4%). Permanent discontinuation of LUMAKRAS due to an adverse reaction occurred in 9% of patients. Adverse reactions resulting in permanent discontinuation of LUMAKRAS in ≥ 2% of patients included hepatotoxicity (4.9%). Dosage interruptions of LUMAKRAS due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dosage interruption in ≥ 2% of patients were hepatotoxicity (11%), diarrhea (8%), musculoskeletal pain (3.9%), nausea (2.9%), and pneumonia (2.5%). Dose reductions of LUMAKRAS due to an adverse reaction occurred in 5% of patients. Adverse reactions which required dose reductions in ≥ 2% of patients included increased ALT (2.9%) and increased AST (2.5%). The most common adverse reactions (≥ 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium. . Overdose In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. There is no specific antidote for overdose with LUMAKRAS . Special precautions for storage Store at 20°C to 25°C. Excursions permitted from 15°C to 30°C
.Special precautions for disposal This medicinal product may pose a risk to the environment (see section 5.3 in Smpc). Any unused medicinal product or waste material should be disposed of in accordance with local requirements. .Legal category:POM Administrative information: Marketing Authorisation Holder: Amgen Inc, United States . product license Number:Lumakras2707233934 date of revision of text: May 2021 Local representive in Saudi Arabia: Salehiya Trading Est. Address: P.O.Box 991, Riyadh 11421, Kingdom of Saudi Arabia. Tel: 00966 1 464 6955 Ext. 127
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Any suspected adverse reactions should be reported immediately to Amgen in accordance with local spontaneous reporting requirements. Amgen Fax: +966-11-2799301 or send to mailbox: Safety-MEA@amgen.com and/or National Pharmacovigilance Centre (NPC), Email: npc.drug@sfda.gov.sa SFDA Call Center: 19999, website: http://ade.sfda.gov.sa For any questions or require additional information, please contact Amgen Medical Information medinfo-mea@amgen.com. |