starting place Signifor Generic Name: Pasireotide Class: Somatostatin Agonists Chemical Name: Cyclo[(2S)-2-phenylglycyl-d-tryptophyl-l-lysyl-O-(phenylmethyl)-l-tyrosyl-l-phenylalanyl-(4R)-4-[[[(2-aminoethyl)amino]carbonyl]oxy]-l-prolyl] Molecular Formula: C 58 H 66 N 10 O 9 CAS Number: 396091-73-9 Overview Side Effects Dosage Professional Interactions More Pregnancy Warnings User Reviews Support Group Q & A Pricing & Coupons Introduction Synthetic polypeptide pharmacologically related to somatostatin (growth hormone [GH, somatropin] release-inhibiting factor). 1 12 Slideshow Always Hungry? You Just Might Have One Of These Conditions Uses for Signifor Cushing's Disease Treatment of Cushing's disease in adults who are not candidates for pituitary surgery or in whom surgery was not curative. 1 3 Designated an orphan drug by FDA for use in this condition. 4 Treatment of choice for patients with Cushing's disease is pituitary (transsphenoidal) surgery; pasireotide considered a second-line treatment option. 7 8 9 10 12 Signifor Dosage and Administration General Prior to initiating therapy, measure fasting plasma glucose and HbA 1c , and perform liver function tests, ECG, and gallbladder ultrasound to establish baseline values. 1 Generally repeat these tests at periodic intervals during therapy to monitor for potentially serious adverse effects. 1 (See Warnings/Precautions under Cautions.) Prior to therapy, initiate intensive and optimal antidiabetic therapy in patients with poorly controlled diabetes mellitus at baseline. 1 (See Hyperglycemia and Diabetes Mellitus under Cautions.) Administration Sub-Q Administration Administer by sub-Q injection. 1 Patients may self-administer drug after appropriate training. 1 Recommended sites of injection include upper thigh or abdomen; avoid areas that are red, inflamed, or irritated. 1 Gently pinch skin at injection site and quickly insert needle at an approximately 45 angle. 1 Rotate injection site with each dose. 1 Dosage Available as pasireotide diaspartate; dosage expressed in terms of pasireotide. 1 Adults Cushing's Disease Sub-Q Initially, 0.6 or 0.9 mg twice daily. 1 Adjust subsequent dosage based on response (e.g., urinary free cortisol concentrations, symptoms) and tolerance. 1 Recommended dosage range is 0.3 0.9 mg twice daily. 1 For patients initially receiving 0.6 mg twice daily, may consider dosage increase to 0.9 mg twice daily to improve treatment response depending on patient tolerance. 1 May temporarily reduce dosage to manage adverse effects; dosage reduction by 0.3-mg decrements per dose is suggested. 1 Continuation of treatment as long as patient is deriving benefit (i.e., as assessed by clinically meaningful reductions in 24-hour urinary free cortisol concentrations and/or improvements in clinical manifestations) is recommended. 1 Response usually evident by 2 months of therapy. 1 12 13 Special Populations Hepatic Impairment Sub-Q Patients with moderate hepatic impairment (Child-Pugh class B): Initially, 0.3 mg twice daily; recommended maximum dosage is 0.6 mg twice daily. 1 Patients with severe hepatic impairment (Child-Pugh class C): Avoid use. 1 Renal Impairment Dosage adjustments not required. 1 Geriatric Patients Select dosage with caution because of greater frequency of decreased hepatic, renal, and/or cardiac function, and of concomitant disease or other drug therapy in geriatric patients. 1 Cautions for Signifor Contraindications Manufacturer states none known. 1 Warnings/Precautions Warnings Hypocortisolism Risk of hypocortisolism since pasireotide suppresses corticotropin (ACTH) secretion. 1 Monitor for manifestations of hypocortisolism. 1 (See Advice to Patients.) If hypocortisolism occurs, consider temporary dosage reduction, interruption in therapy, or temporary use of glucocorticoid replacement therapy. 1 Hyperglycemia and Diabetes Mellitus Risk of hyperglycemia and diabetes mellitus. 1 3 5 8 12 15 16 17 18 Cushing's disease may contribute to this risk. 1 3 10 15 Hyperglycemia-related adverse effects reported frequently in clinical studies. 1 3 12 13 Usually occurs shortly after drug initiation, and persists throughout duration of therapy; glucose concentrations may be stabilized with use of antidiabetic agents. 1 3 12 13 Closely monitor glycemic status, particularly in patients with preexisting diabetes mellitus or impaired glucose tolerance. 1 3 5 9 13 15 16 Assess baseline glycemic status prior to initiating therapy; ensure that optimal glycemic control is achieved. 1 16 (See General under Dosage and Administration.) Monitor blood glucose concentrations weekly for the first 2 3 months of therapy, then periodically thereafter as clinically indicated. 1 Initiate or adjust antidiabetic therapy if hyperglycemia develops. 1 3 15 16 If uncontrolled hyperglycemia persists despite appropriate medical management, reduce pasireotide or discontinue treatment. 1 16 After discontinuance of therapy, monitor glycemic status according to current standards of care. 1 Cardiovascular Effects Risk of bradycardia. 1 Closely monitor patients with cardiac disease and/or other risk factors for bradycardia. 1 (See Drugs that Cause Bradycardia under Interactions.) Risk of QT-interval prolongation. 1 3 Observed following administration of therapeutic and supratherapeutic dosages of pasireotide. 1 Use with caution in patients with a substantial risk for QT-interval prolongation. 1 (See Drugs that Prolong the QT Interval under Interactions.) Obtain baseline ECG; consider periodic monitoring of QT interval during therapy. 1 Correct hypokalemia and hypomagnesemia (if present) prior to initiating therapy; monitor potassium and magnesium concentrations periodically during therapy. 1 Hepatic Effects Elevations in ALT or AST concentrations reported; generally transient and not associated with clinically important effects. 1 Perform liver function tests at baseline and at periodic intervals during therapy (i.e., after 1 2 weeks of treatment, then monthly for 3 months, every 6 months thereafter). 1 If ALT is elevated, repeat test as follows: in patients with normal ALT concentrations at baseline, perform repeat test within 1 week if ALT is 3 5 times ULN or within 48 hours if ALT >5 times ULN; in patients with abnormal ALT concentrations at baseline, perform repeat test within 1 week if ALT is 3 5 times ULN or sooner if ALT >5 times ULN. 1 If ALT concentrations remain elevated or continue to rise upon a repeat test, temporarily interrupt therapy and investigate probable cause. 1 May reinitiate pasireotide therapy cautiously and with close observation once abnormalities resolve to normal or near-normal values and if some other likely cause found. 1 If results of any liver function tests (e.g., ALT, AST, alkaline phosphatase, total bilirubin) are >5 times the baseline value or ULN, perform serial measurements of these tests at least weekly. 1 Biliary Effects Cholelithiasis reported; in some cases, hospitalization or intervention (e.g., cholecystectomy) required. 1 3 12 Perform gallbladder ultrasound prior to therapy and periodically thereafter (i.e., every 6 12 months during therapy). 1 Pituitary Hormone Deficiency Deficiencies of pituitary hormones other than ACTH (e.g., thyrotropin [thyroid-stimulation hormone; TSH], GH, insulin-like growth factor I [IGF-I]) may occur. 1 8 17 Risk is particularly high in patients following transsphenoidal surgery and/or pituitary irradiation. 1 Evaluate pituitary function prior to initiation of therapy; consider periodic monitoring during therapy if clinically indicated. 1 Specific Populations Pregnancy Category C. 1 Lactation Distributed into milk in rats; not known whether distributed into human milk. 1 Avoid use in nursing women; if use is necessary, exercise caution. 1 Pediatric Use Safety and efficacy not established. 1 Geriatric Use Insufficient experience in patients 65 years of age to determine whether geriatric patients respond differently than younger adults. 1 (See Geriatric Populations under Dosage and Administration.) Hepatic Impairment Systemic exposure to pasireotide substantially increased in patients with moderate or severe hepatic impairment. 1 14 (See Special Populations under Pharmacokinetics.) Dosage adjustment required for patients with moderate hepatic impairment. 1 14 (See Hepatic Impairment under Dosage and Administration.) Avoid use in patients with severe hepatic impairment. 1 Renal Impairment Renal impairment not expected to substantially affect systemic exposure of pasireotide because drug only minimally eliminated in urine. 1 (See Renal Impairment under Dosage and Administration.) Common Adverse Effects Diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, diabetes mellitus. 1 3 Interactions for Signifor Not a substrate, inhibitor, or inducer of any major CYP isoenzymes. 1 12 May indirectly decrease activity of CYP isoenzymes via GH suppression (which is known to increase CYP enzyme activity). 1 Also not a substrate of breast cancer resistance protein (BCRP), organic cation transporter 1 (OCT1), or organic anion-transporting polypeptide (OATP) 1B1, 1B3, or 2B1. 1 Likely to be a substrate of P-glycoprotein (P-gp), but effect of P-gp on pharmacokinetics expected to be limited. 1 Drugs Metabolized by Hepatic Microsomal Enzymes CYP substrates: Potential pharmacokinetic interaction (decreased substrate clearance). 1 Drugs that Cause Bradycardia Potential for additive bradycardia; closely monitor patients receiving concomitant therapy. 1 Dosage adjustment of concomitant drug may be necessary. 1 Drugs that Prolong the QT Interval Potential additive effects on QT-interval prolongation. 1 Use concomitantly with caution. 1 Specific Drugs Drug Interaction Comments Antidiabetic agents (e.g., liraglutide, metformin, nateglinide) No evidence of substantial drug interaction 1 Antiarrhythmic agents Possible additive effects on QT-interval prolongation 1 Use concomitantly with caution 1 β-Adrenergic blocking agents Possible additive bradycardia 1 Monitor closely; dosage adjustment of β-blocker may be necessary 1 Bromocriptine Possible increased concentrations of bromocriptine 1 Bromocriptine dosage reduction may be necessary 1 Calcium-channel blocking agents Possible additive bradycardia 1 Monitor closely; dosage adjustment of calcium-channel blocker may be necessary 1 Cyclosporine Possible decreased bioavailability of cyclosporine 1 Cyclosporine dosage adjustment may be required to maintain therapeutic concentrations; consider increased monitoring 1 Signifor Pharmacokinetics Absorption Bioavailability Rapidly absorbed; peak plasma concentrations achieved within 0.25 0.5 hours. 1 17 18 19 Special Populations Moderate or severe hepatic impairment (Child-Pugh class B or C) increases AUC by 56 or 42%, respectively. 1 14 Mild hepatic impairment does not substantially affect AUC. 1 14 Distribution Extent Not known whether distributed into milk. 1 Plasma Protein Binding Approximately 88%. 1 Elimination Metabolism Not appreciably metabolized; detected mostly as unchanged drug in plasma, urine, and feces. 1 Elimination Route Elimination occurs principally via hepatic clearance, with minor renal contribution. 1 Half-life Effective half-life: approximately 12 hours in healthy individuals. 1 17 19 Stability Storage Parenteral Injection, for Sub-Q Use 25 C (may be exposed to 15 30 C); protect from light. 1 Actions Synthetic polypeptide pharmacologically related to natural endocrine hormone somatostatin. 1 12 Binds to and activates somatostatin receptors in the anterior pituitary, or resulting in inhibition of ACTH secretion and decreased cortisol secretion from adrenal glands. 1 12 Binds preferentially to somatostatin receptors 1, 2, 3, and 5 with greatest affinity for receptor subtype 5 (frequently overexpressed in corticotroph tumor cells from patients with Cushing's disease). 1 12 Differs from other currently available somatostatin analogs (lanreotide, octreotide) in its distinct somatostatin receptor-binding profile. 12 17 Advice to Patients Risk of hypocortisolism; importance of patients contacting clinician immediately if weakness, fatigue, loss of appetite, nausea, vomiting, hypotension, hyponatremia, or hypoglycemia occurs. 1 Risk of hyperglycemia and diabetes mellitus; importance of monitoring for excessive thirst, increased appetite with weight loss, high urine output, or fatigue. 1 Importance of close monitoring of blood glucose concentrations prior to and during therapy. 1 Risk of bradycardia and QT-interval prolongation; importance of patients contacting clinician immediately if abnormal heart beats, dizziness, or fainting occurs. 1 Risk of liver enzyme elevations; importance of monitoring liver function tests prior to and during therapy. 1 Risk of cholelithiasis; importance of gallbladder ultrasound prior to and periodically during therapy. 1 Risk of pituitary hormone deficiency; importance of monitoring pituitary function prior to and periodically during therapy. 1 Importance of patients reviewing the manufacturer's medication guide; importance of clinicians instructing patients on proper injection technique and disposal of unused medication. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, 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. Pasireotide Diaspartate Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral Injection, for subcutaneous use 0.3 mg (of pasireotide) Signifor Novartis 0.6 mg (of pasireotide) Signifor Novartis 0.9 mg (of pasireotide) Signifor Novartis AHFS DI Essentials. Copyright 2017, Selected Revisions December 2, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Novartis Pharmaceuticals. Signifor (pasireotide) injection, for subcutaneous use prescribing information. East Hanover, NJ; 2012 Dec. 3. Colao A, Petersenn S, Newell-Price J et al. A 12-month phase 3 study of pasireotide in Cushing's disease. N Engl J Med . 2012; 366:914-24. [PubMed 22397653] 4. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; [May 20, 2013]. From FDA web site . 5. Boscaro M, Ludlam WH, Atkinson B et al. Treatment of pituitary-dependent Cushing's disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab . 2009; 94:115-22. [PubMed 18957506] 7. Biller BM, Grossman AB, Stewart PM et al. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab . 2008; 93:2454-62. [PubMed 18413427] 8. Feelders RA, Hofland LJ. Medical treatment of Cushing's disease. J Clin Endocrinol Metab . 2013; 98:425-38. [PubMed 23345100] 9. Fleseriu M, Petersenn S. Medical management of Cushing's disease: what is the future?. Pituitary . 2012; 15:330-41. [PubMed 22674211] 10. Feelders RA, Yasothan U, Kirkpatrick P. Pasireotide. Nat Rev Drug Discov . 2012; 11:597-8. [PubMed 22850776] 11. Feelders RA, de Bruin C, Pereira AM et al. Pasireotide alone or with cabergoline and ketoconazole in Cushing's disease. N Engl J Med . 2010; 362:1846-8. [PubMed 20463350] 12. McKeage K. Pasireotide: A Review of Its Use in Cushing's Disease. Drugs . 2013; 73:563-74. [PubMed 23605695] 13. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 200677Orig1s000: Summary Review. From FDA website. 14. Horsmans Y, Hu K, Ruffin M et al. Effect of hepatic impairment on the pharmacokinetics of pasireotide (SOM230): results from a multicenter phase I study. J Clin Pharmacol . 2012; 52:552-8. [PubMed 22282526] 15. Colao A, De Block C, Gaztambide MS et al. Managing hyperglycemia in patients with Cushing's disease treated with pasireotide: medical expert recommendations. Pituitary . 2013; :. 16. Reznik Y, Bertherat J, Borson-Chazot F et al. Management of hyperglycaemia in Cushing's disease: experts' proposals on the use of pasireotide. Diabetes Metab . 2013; 39:34-41. [PubMed 23228667] 17. Golor G, Hu K, Ruffin M et al. A first-in-man study to evaluate the safety, tolerability, and pharmacokinetics of pasireotide (SOM230), a multireceptor-targeted somatostatin analog, in healthy volunteers. Drug Des Devel Ther . 2012; 6:71-9. [PubMed 22573933] 18. Petersenn S, Hu K, Maldonado M et al. Tolerability and dose proportional pharmacokinetics of pasireotide administered as a single dose or two divided doses in healthy male volunteers: a single-center, open-label, ascending-dose study. Clin Ther . 2012; 34:677-88. [PubMed 22364824] 19. Beglinger C, Hu K, Wang Y et al. Multiple once-daily subcutaneous doses of pasireotide were well tolerated in healthy male volunteers: a randomized, double-blind, placebo-controlled, cross-over, Phase I study. Endocrine . 2012; 42:366-74. [PubMed 22527887] Next Interactions Print this page Add to My Med List More about Signifor (pasireotide) Side Effects During Pregnancy Dosage Information Drug Interactions Support Group Pricing & Coupons En Español 0 Reviews Add your own review/rating Drug class: somatostatin and somatostatin analogs Consumer resources Signifor ... +3 more Professional resources Signifor Injection (FDA) Pasireotide (AHFS Monograph) Other brands: Signifor LAR Related treatment guides Cushing's Syndrome} 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 C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Manufacturer Novartis Pharmaceuticals Corporation Drug Class Somatostatin and somatostatin analogs Related Drugs Cushing's Syndrome dexamethasone , Decadron , cyproheptadine , mifepristone , Dexasone , Korlym , Dexpak Taperpak , aminoglutethimide , Baycadron , LoCort , Acthrel , Dexacen-4 , Solurex , Cytadren , pasireotide , More... Signifor Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } unique
the one you love Signifor which on reflection
EmoticonEmoticon