you finance Sebelipase Alfa Class: Enzymes Chemical Name: Cholesterol (human gene LIPA) esterase, Molecular Formula: C 1968 H 2945 N 507 O 551 S 15 CAS Number: 1276027-63-4 Brands: Kanuma Overview Side Effects Dosage Professional Pregnancy More User Reviews Support Group Q & A Introduction Biosynthetic (recombinant DNA origin) form of human lysosomal acid lipase. 1 5 Slideshow Insomnia and Sleep Deprivation: The Case For A Good Night's Sleep Uses for Sebelipase Alfa Lysosomal Acid Lipase Deficiency Treatment of lysosomal acid lipase deficiency 1 7 (designated an orphan drug by FDA for this use). 2 Survival benefit demonstrated in patients with rapidly progressive infantile-onset disease (i.e., Wolman disease). 1 8 9 In pediatric patients and adults with late-onset disease (i.e., cholesterol ester storage disease), improvements in disease-related lipid and hepatic abnormalities demonstrated. 1 7 Effects on cardiovascular morbidity and mortality and progression of liver disease not established. 1 7 Sebelipase Alfa Dosage and Administration Administration IV Administration For solution compatibility information, see Compatibility under Stability. Administer by IV infusion. 1 Administer using an inline, low-protein-binding 0.2-mcm filter. 1 Contains no preservatives; use immediately following preparation. 1 (See Storage under Stability.) Discard any unused portions. 1 Dilution Prior to administration, must dilute commercially available sebelipase alfa injection concentrate. 1 Determine number of vials to be diluted based on patient s weight and recommended dose of 1 or 3 mg/kg. 1 Remove required number of vials from refrigerator and allow to reach room temperature; do not shake. 1 Withdraw appropriate dose from vials and dilute with 0.9% sodium chloride injection to prepare a final concentration of 0.1 1.5 mg/mL. 1 See Table 1 for recommended total infusion volumes based on patient's weight and prescribed dose. 1 For patients presenting within the first 6 months of life who do not achieve optimal clinical response with a dose of 1 mg/kg. 1 Table 1: Total Infusion Volumes Patient Weight (kg) Total Infusion Volume (mL) for 1-mg/kg Dose Total Infusion Volume (mL) for 3-mg/kg Dose 1 10.9 10 25 11 24.9 25 50 25 49.9 50 100 50 99.9 100 250 100 120.9 250 500 Mix diluted solution gently; do not shake. 1 The solution should appear clear to slightly opalescent and colorless to slightly colored; thin translucent fibers or particles may be present. 1 Do not administer if solution appears cloudy or if other particulate matter observed. 1 Rate of Administration Infuse over at least 2 hours. 1 Consider longer infusion times in patients receiving a dose of 3 mg/kg or in patients who experience hypersensitivity reactions. 1 Consider shorter infusion time of 1 hour, if tolerated, in patients receiving a dose of 1 mg/kg. 1 Dosage Pediatric Patients Lysosomal Acid Lipase Deficiency Infants with Rapidly Progressive Lysosomal Acid Lipase Deficiency Presenting Within the First 6 Months of Life IV 1 mg/kg once weekly. 1 In patients not achieving optimal clinical response, may increase to 3 mg/kg once weekly. 1 Pediatric Patients with Lysosomal Acid Lipase Deficiency IV 1 mg/kg once every 2 weeks. 1 Adults Lysosomal Acid Lipase Deficiency IV 1 mg/kg once every 2 weeks. 1 Special Populations No special population dosage recommendations at this time. 1 Cautions for Sebelipase Alfa Contraindications No known contraindications. 1 Warnings/Precautions Sensitivity Reactions Hypersensitivity Hypersensitivity reactions, including anaphylaxis, reported. 1 Generally during or within 4 hours of the infusion. 1 Anaphylaxis reported as early as the sixth infusion to as late as 1 year after treatment initiation. 1 Ensure that appropriate medical support is readily available during administration. 1 Closely observe patients during and after administration. 1 Manage hypersensitivity reactions based on severity. 1 If anaphylaxis or other severe hypersensitivity reaction occurs, discontinue sebelipase alfa immediately and initiate appropriate medical treatment. 1 For hypersensitivity reactions of lesser severity, may temporarily interrupt infusion, lower infusion rate, and/or administer antihistamines, antipyretics, and/or corticosteroids. 1 If infusion is interrupted, resume at a slower rate; subsequently increase rate as tolerated. 1 To prevent subsequent reactions in patients experiencing hypersensitivity, may consider premedication with antipyretics and/or antihistamines. 1 Consider risks and benefits of retreatment following a severe hypersensitivity reaction. 1 If drug is readministered, monitor patient with appropriate resuscitation measures available. 1 Egg Allergy Consider risks and benefits of treatment in patients with known systemic hypersensitivity reactions to eggs or egg products. 1 Antibody Formation Development of antibodies, including neutralizing antibodies, to sebelipase alfa reported. 1 7 Hypersensitivity reactions and possible reduced efficacy (decreased growth) observed in antibody-positive infants. 1 No clear association between development of antibodies and efficacy in adults and pediatric patients. 1 7 Specific Populations Pregnancy No available data in pregnant women; animal studies have not suggested any evidence of adverse embryofetal effects. 1 Lactation Not known whether sebelipase alfa is distributed into milk. 1 Consider known benefits of breast-feeding along with mother's need for sebelipase alfa and any potential adverse effects of the drug or disease on the infant. 1 Pediatric Use Safety and efficacy established in pediatric patients 1 month of age. 1 Geriatric Use Not studied in patients 65 years of age. 1 Not known whether geriatric patients respond differently than younger patients. 1 Common Adverse Effects Infants with rapidly progressive lysosomal acid lipase deficiency presenting within the first 6 months of life: Diarrhea, 1 vomiting, 1 fever, 1 rhinitis, 1 anemia, 1 cough, 1 nasopharyngitis, 1 urticaria. 1 Pediatric and adult patients with lysosomal acid lipase deficiency: Headache, 1 7 fever, 1 oropharyngeal pain, 1 7 nasopharyngitis, 1 7 abdominal pain, 7 asthenia, 1 7 constipation, 1 7 nausea. 1 7 Interactions for Sebelipase Alfa Formal drug interaction studies not performed to date. 8 Sebelipase Alfa Pharmacokinetics Pharmacokinetic profile of sebelipase alfa is based on data from adults and pediatric patients; pharmacokinetics not characterized in infants. 10 Absorption Bioavailability Nonlinear pharmacokinetics; greater than dose-proportional increase in exposure observed at doses of 1 3 mg/kg. 1 No substantial accumulation following repeated dosing. 1 Peak plasma concentrations occur approximately 1.1 1.3 hours after a dose in pediatric patients and adults. 1 Onset Increased LDL-cholesterol and triglyceride concentrations initially observed within the first 2 4 weeks; such parameters subsequently decreased to below pretreatment levels within 8 weeks of treatment. 1 7 Decreased ALT concentrations typically observed within 2 weeks of treatment. 1 7 Special Populations Pharmacokinetic profile similar between adolescents and adults. 1 Distribution Extent Not known whether sebelipase alfa distributes into milk. 1 Elimination Half-life Approximately 6 minutes. 1 9 Half-life similar across pediatric and adult patients of all age groups receiving 1 mg/kg once every other week. 1 Stability Storage Parenteral Injection for IV Infusion 2 8 C. 1 Protect from light. 1 Do not freeze; do not shake. 1 Following dilution, 2 8 C for 24 hours if protected from light. 1 Do not freeze. 1 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility 1 Compatible Sodium chloride 0.9% Actions Biosynthetic (recombinant DNA origin) form of human lysosomal acid lipase. 1 5 Binds to cell surface receptors and subsequently internalized into lysosomes; 1 catalyzes lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol, and free fatty acids. 1 Lysosomal acid lipase deficiency causes accumulation of cholesteryl esters and triglycerides in various cells and organs throughout the body leading to clinical manifestations including hepatomegaly, liver disease (e.g., jaundice, steatosis, fibrosis, cirrhosis), increased aminotransferase concentrations, malabsorption, growth failure, dyslipidemia (e.g., elevated LDL-cholesterol and triglyceride concentrations, decreased HDL-cholesterol concentrations), and atherosclerosis. 1 3 4 5 6 9 Treatment in patients with rapidly progressive infantile-onset lysosomal acid lipase deficiency (i.e., Wolman disease) increased survival rate beyond 12 months of age; treatment in pediatric and adult patients with later-onset disease (i.e., cholesterol ester storage disease) improved lipid parameters and decreased ALT concentrations. 1 7 Advice to Patients Risk of severe hypersensitivity reactions, including anaphylaxis. 1 Advise patients of the possible signs and symptoms of hypersensitivity reactions, and to seek immediate medical care if such manifestations occur. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Sebelipase Alfa Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral Injection concentrate, for IV infusion 2 mg/mL (20 mg) Kanuma Alexion AHFS DI Essentials. Copyright 2017, Selected Revisions March 22, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Alexion Pharmaceuticals. Kanuma (sebelipase alfa) injection, for intravenous use prescribing information. Cheshire, CT; 2015 Dec. 2. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2016 Jul 11. 3. Hoffman EP, Barr ML, Giovanni MA, et al. Lysosomal acid lipase deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993 2016. 4. Burton BK, Deegan PB, Enns GM et al. Clinical features of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr . 2015; 61:619-25. [PubMed 26252914] 5. Reiner Z, Guardamagna O, Nair D et al. Lysosomal acid lipase deficiency--an under-recognized cause of dyslipidaemia and liver dysfunction. Atherosclerosis . 2014; 235:21-30. [PubMed 24792990] 6. Jones SA, Valayannopoulos V, Schneider E et al. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med . 2016; 18:452-8. [PubMed 26312827] 7. Burton BK, Balwani M, Feillet F et al. A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med . 2015; 373:1010-20. [PubMed 26352813] 8. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 125561Orig1s000: Medical review. From FDA website. 9. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 125561Orig1s000: Summary Review. From FDA website. 10. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 125561Orig1s000: Clinical Pharmacology and Biopharmaceutics Review. From FDA website. Next Pregnancy Warnings Print this page Add to My Med List More about sebelipase alfa Side Effects During Pregnancy Dosage Information Support Group En Español 0 Reviews Add your own review/rating Drug class: lysosomal enzymes Consumer resources Sebelipase alfa Sebelipase alfa Intravenous (Advanced Reading) Professional resources Sebelipase Alfa (Wolters Kluwer) Other brands: Kanuma Related treatment guides Lysosomal Acid Lipase Deficiency} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class Lysosomal enzymes Related Drugs Lysosomal Acid Lipase Deficiency Kanuma , More... Sebelipase alfa Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } the sort of
Viscount St. Albans Sebelipase Alfa most of the people
EmoticonEmoticon