label: has adverse event

source_label: Hypertrophic cardiomyopathy and a decrease in left ventricular stroke volume from 10.5 to 5.9 mL

have_adverse_events: Yes

initial_unit_of_measurement: milligram per kilogram (mg/kg)

initial_frequency: Daily / Once per day (QD)

current_unit_of_measurement: milligram per kilogram (mg/kg)

current_frequency: Daily / Once per day (QD)

current_dose_change: Yes

unit_of_measurement_duration: Day(s)

additional_drug_info: The hypertrophic cardiomyopathy had decreased by 7 days after ACTH treatment was discontinued. Left ventricular stroke volume decreased from 10.5 to 5.9 mL.

sex: Female

age_group: < 1 month

country_treated: Japan


name: Left ventricular ejection fraction decreased (finding)


outcomes: Non-serious Medical Event Not Requiring Intervention

source_label: Mouth sore only once

initial_frequency: 2 times a day (BID)

initial_route: Oral (PO)

current_frequency: 2 times a day (BID)

current_route: Oral (PO)

treatment_begin_month: February

treatment_end_month: April

treatment_on_going: No

severity:
Outpatient
Inpatient
ICU/Critical Care

additional_drug_info: Patient born with severe hypertrophic cardiomyopathy with obstruction. Patient had open heart surgery (myectomy) at two months old 12/2019.  Everolimus started in February 2020. Continued medication with titrations until April 2022. No significant changes in hypertrophic cardiomyopathy. Decided to discontinue Everolimus to see impact on patient’s condition. Patient currently 4 yrs old and hypertrophic cardiomyopathy consider considered mild to moderate. No scientific evidence Everolimus contributed to HCM stabilization, but hopeful!

sex: Male

age_group: 1 - 5 years

ethnicity: Not Hispanic/Latino

country_treated: United States


source_label: Diarrhea

initial_unit_of_measurement: milligram (mg)

current_unit_of_measurement: milligram (mg)

current_dose_change: No

unit_of_measurement_duration: Week(s)

treatment_on_going: Yes

age_group: 6 - 10 years


outcomes: Treatment was Discontinued due to the Adverse Event

unit_of_measurement_duration: Month(s)

additional_drug_info: At day of life 3, she developed frequent atrial ectopy with rapid atrial rate and numerous P wave morphologies. Echocardiogram was performed and demonstrated early hypertrophic cardiomyopathy with concentric left ventricular hypertrophy, pulmonary valve stenosis, and atrial septal defect. Based on the cardiac manifestations, macrocephaly, and widely spaced nipples, a RASopathy sequencing panel was performed, revealing a RAF1 c.770C>T pathogenic variant. She was started onpropranolol and discharged on home oxygen at 4 weeks. At 6 weeks, she presented with respiratory failure because of coronavirus HKU1 requiring intubation. Her arrhythmias and hypertrophic cardiomyopathy progressed, and she was diagnosed with MAT. The MAT frequently degenerated to atrial flutter/fibrillation with rapid ventricular response requiring multiple cardioversions. Progressive escalation of antiarrhythmic therapies included esmolol infusion, nadolol, amiodarone, and flecainide without successful rhythm or rate control. She developed chylothoraces requiring pleural tubes with inability to extubate because of congestive heart failure and severe left mainstem bronchomalacia. At 17 weeks, she had 2 cardiac arrests caused by degeneration of her MAT in the setting of high antiarrhythmic doses, resulting in polymorphic ventricular tachycardia requiring defibrillation. Her flecainide was transitioned to diltiazem infusion while continuing on amiodarone and nadolol. Because of her recalcitrant MAT and progressive biventricular hypertrophy, management options were discussed including cardiac transplantation, and the decision was made to pursue compassionate use of pharmacological MEK inhibition.While on trametinib, she developed severe diarrhea for which her trametinib was held for 3 days and dose was reduced to 0.01875 mg/kg per day, during which atrial ectopy briefly returned. Amiodarone and diltiazem were slowly weaned and discontinued. She remained on trametinib and nadolol with trivial residual atrial ectopy <1% of beats. This case was reported in the published literature. The article reference information is: Meisner JK, Bradley DJ, Russell MW. Molecular Management of Multifocal Atrial Tachycardia in Noonan's Syndrome With MEK1/2 Inhibitor Trametinib. Circ Genom Precis Med. 2021;14(5):e003327. doi:10.1161/CIRCGEN.121.003327. PMID: 34463117. The free full text link to the article is: https://www.ahajournals.org/doi/10.1161/CIRCGEN.121.003327?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

ethnicity: Unknown


source_label: Dry Skin

additional_drug_info: This case report was extracted from a published article. The reference information for the article is: Leegaard A, Gregersen PA, Nielsen TØ, Bjerre JV, Handrup MM. Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome. Eur J Med Genet. 2022 Nov;65(11):104630. doi: 10.1016/j.ejmg.2022.104630. Epub 2022 Sep 30. PMID: 36184070.The free full-text of the article is available at: https://www.sciencedirect.com/science/article/pii/S1769721222002117?via%3Dihub

age_group: 4 - 6 months

country_treated: Denmark


source_label: Rhabdomyolysis

initial_route: Nasogastric (NG)

current_route: Gtube

treatment_begin_month: January

severity:
Outpatient
ICU/Critical Care

additional_drug_info: At dose of 0.025 mg/kg patient had clinically significant rhabdomyolysis with myoglobinuria. She had an elevated troponin which lead to temporary discontinuation of medication. While off trametinib patient continued to have intermittent elevated troponins, though to be due to her congenital heart disease and not trametinib. Did not have rhabdomyolysis at 0.0125 mg/kg dose. Checked patient's pharmacogenomics as well as trametinib level at the time of rhabdomyolysis which was normal.

age_group: 7 - 11 months

ethnicity: Hispanic/Latino


source_label: Rash