Pasireotide/Somatomedins 1929
was reported to be healthy and normal at 6 months of been tried in an attempt to limit adverse effects such as age. Transplacental passage of pegvisomant was considered oedema, jaw pain, headache, Bells' palsy, and retinal to be either absent or minimal, based on samples of mater oedema.4 nal and cord blood. There was also no evidence of sub Mecasermin has also been reported to improve insulin stantial secretion into breast milk, and the authors sug sensitivity and to lower concentrations of insulin, glucose, gested that any that might be ingested would be likely to and C-peptide in patients with syndromes of severe insulin undergo rapid gastric hydrolysis. resistance or type 2 diabetes mellitus.' There is also a report of a woman who continued to 1. Thrailkill KM. Insulin�like growth factor-! in diabetes mellitus: its receive pegvisomant during a single cycle of NF and until a physiology, metabolic effects, and potential clinical utility. Diabetes positive pregnancy test, with no apparent adverse effect on Technol Ther 2000; 2: 69-80. the fetus. The child was reported to be normal at I year of 2. Acerini CL, et al. Randomised placebo�controlled trial of human recombinant insulin-like growth factor I plus intensive insulin therapy age.2 in adolescents with insulin-dependent diabetes mellitus. Lancet 1997; l. Brian SR, et al. Treatment of acromegaly with pegvisomant during 3SO: 1199-1204. pregnancy: maternal and fetal effects. J Clin Endocri.nolMetab 2007; 92.: 3. Thrailkill KM, et al. Cotherapy with recombinant human insulin-like 3374-7. growth factor I and insulin improves glycemic control in type 1 diabetes. 2. Qureshi A, et al. IVF/ICSI in a woman with active acromegaly: successful Diabetes Care 1999; 22: 585-92. outcome following treatment with pegvisomant. J Assist Reprod Genet 4. Clemmons DR, et al. The combination of insulin-like growth factor I and 23: 2006; 439-42. insulin·like growth factor�binding protein�3 reduces insulin require ments in insulin-dependent type l diabetes: evidence for in vivo Interactions biological activity. J Clin Endocrinol Metab 2000; 85: 1518-24. Pegvisomant may increase insulin sensitivity. In patients with diabetes, doses of insulin or oral hypoglycaemics may Growth retardation. Mecasennin is used in the treatment need to be decreased because of the increased risk of of growth retardation (p. I9I8.3) including Laron-type hypoglycaemia. Patients taking opioid analgesics may dwarfism (growth hormone resistance or insensitivity). It require higher serum concentrations of pegvisomant to Uses and Administration is given to children and adolescents with severe primary achieve appropriate IGF-I suppression. The somatomedins are a group of polypeptide hormones, IGF-I deficiency, which includes patients with mutations some of which are involved in mediating the effects of in the growth hormone receptor or post-growth hormone Pharmacokinetics growth hormone in the body. Insulin-like growth factor I receptor signalling pathway, and IGF-I gene defects. They (IGF-I) is believed to be responsible for many of the anabolic have low concentrations of IGF-I and normal or elevated Pegvisomant is absorbed slowly after subcutaneous effects of growth hormone. It is secreted primarily by the concentrations of growth hormone; they are not growth injection, and peak serum concentrations occur after liver, regulated principally by growth hormone and insulin hormone deficient and cannot be expected to respond to about 33 to 77 hours. It is slowly eliminated from serum, secretion; IGF-I may also be secreted in other tissues, where growth hormone therapy. It is also used in children with with a half-life estimated to range from 74 to 172 hours. it may exert local hormonal (paracrine) effects. In the growth hormone gene deletion who have developed neu Renal clearance of pegvisomant is negligible. circulation, IGF-I is almost completely protein bound; 6 tralising antibodies to growth hormone. Mecasermin has i binding proteins have been identified and production of stimulated linear growth and normalised biochemical �-��P.�.r�t �".�...... some of these is also under the control of growth horinone. abnormalities in these patients.1 One study2 found the ProprietaryPreparations (details are given in Volume B) In addition to its anabolic effects IGF-I, which is structurally effect on growth velocity in the first year to be dose related to insulin, also has potent hypoglycaemic properties. dependent. The beneficial effect persisted during up to 8 Arg.: Somavert; Austria: Soma Single-ingredient Preparations. IGF-I is available as mecasermin, a product of years of treatment, but growth velocity gradually declined vert; Belg.: Somavert; Braz. : Somavert; Canad. : Somavert; Cz.: recombinant DNA technology. It is used in the treatment Somavert; Denm.: Somavert; Fin.: Somavert; Fr. : Somavert; over this time. During long-term use, growth hormone Ger.: Somavert; Gr.: Somavert; Hung.: Somavert; Irl. : Soma� of growth failure in children and adolescents with severe and insulin are persistently suppressed, preventing hypo vert; Israel: Somavert; Ital. : Somavert; Mex. : Somavert; Neth.: primary IGF-I deficiency or with growth hormone gene glycaemia and stabilising blood-glucose concentrations.' Somavert; Norw. : Somavert; Pol. : Somavert; Port. : Somavert; deletion who have developed neutralising antibodies to There is also an increase in the production of the insulin Singapore: Somavert; Spain: Somavert; Swed. : Somavert; growth hormone (see Growth Retardation, below). like growth factor binding protein-3, which prolongs the Switz. : Somavert; Turk.: Somavert; UK: Somavert; Ukr. : Soma However, it is not recommended for children less than 2 half-life of mecasermin so that a progressive dose reduc vert (CoM3BepT)t; USA: Somavert. years of age because of a lack of data. The starting dose of tion is needed to avoid overdosage and adverse effects.' mecasermin is 40 to 80 micrograms/kg twice daily by Some children with idiopathic short stature have a low subcutaneous injection. After 1 week, if this dose is concentration of IGF-1 of no apparent cause, which is less Pralmorelin Dihydrochloride (USAN, r!NNMJ ® tolerated, it may be increased by 40 micrograms/kg per dose severe than IGF-I deficiency from genetic causes. It has been to a maximum of I20micrograms/kg twice daily. suggested that these patients, who have normal concentra Mecasennin should be given within 20 minutes before or tions of growth hormone, might have a degree of growth after food, to minimise hypoglycaemia. The dose should be hormone insensitivity, and a study4 of IGF-I treatment reduced if hypoglycaemia occurs with recommended doses reported improvements in height velocity, dependent on despite adequate food intake. If the patient is unable to eat dose and age. However, this premise for IGF-I therapy has for any reason, the dose of mecasermin should be withheld. been criticised and a role for IGF-I treatment in idiopathic Mecasermin rinfabate is a recombinant protein complex short stature requires further study.' of IGF-I and its most abundant binding protein, insulin-like 1. Laron Z. The essential role of iGP-1: lessons from the long-term study and growth factor binding protein-3 (IGFBP-3). It has been treatment of children and adults with Laron syndrome. J Clin Endocrinol investigated for the management of amyotrophic lateral Metab 1999; 84: 4397-4404. sclerosis and myotonic muscular dystrophy. It is also under 2. Chemausek SD, et al. GH Insensitivity Syndrome Collaborative Group. investigation in the prevention of complications in preterm Long�term treatment with recombinant insulin·like growth factor (IGF)-1 in children with severe IGF-1 deficiency due to growth hormone neonates that may be associated with low endogenous insensitivity. J Clin Bndocrinol Metab 2007; 92: 902-10. concentrations of IGF-I. such as retinopathy of prematurity. 3. Laron Z. Laron syndrome (primary growth hormone resistance or Profile IGF-II (IGF-2) is thought to play an important role in insensitivity): the personal experience 1958-2003. J Clin Endocrinol Metab 2004; 89: 1031-44. Pralmorelin is a small synthetic peptide that stimulates the fetal growth, although its function in adults is uncertain. It is closely related in structure to IGF-I, but is not under the 4. Midyett LK, et al. Recombinant insulin-like growth factor (IGFH release of growth hormone. It is used in the diagnosis of treatment in short children with low IGF�I levels: �rst�year results from growth hormone deficiency; it has also been tried in the control of growth hormone. a randomized clinical trial. J Clin Endocrinol Metab 2010; 95: 611-19. treatment of growth retardation (p. I9I8.3). General reviews. 5. Collett�Solberg PP, Misra M. Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. The role of recombinant References. L Laron Z. Somatomedin-1 (insulin-like growth factor-!) in clinical use: facts and potential. Drugs 1993; 45: 1-8. human insulin�like growth factor·! in treating children with short Mericq V, et al. Effects of eight months treatment with graded doses of a 93: L 2. Bondy CA, et al. Clinical uses of insulin-like growth factor I. Ann Intern stature. J Clin Endocrinol Metab 2008; 10-18. growth hormone (GH)�releasing peptide in GH�deficient children. J Clin Med 1994; 124: 593-60 1. Endocrlnol Metab 1998; 83: 2355-60. 3. Le Raith D. Insulin-like growth factors. N Engl J Med 1997; 336: 633-40. 2. Mahajan T, Lightman SL. A simple test for growth hormone deficiency 4. Laron Z. Insulin�like growth factor 1 (IGP� 1): a growth hormone. Mol in adults. J Clin Endocrinol Metab 2000; 85: 1473-6. Motor neurone disease. Mecasermin has been investi Patho/ 2001; 54: 311-16. 3. Gondo RG, et a!. Growth hormone-releasing peptide-2 stimulates GH gated for the management of amyotrophic lateral sclerosis, 5. Kemp SF, et al. Efficacy and safety of mecasennin rinfabate. Expert Opin secretion in GH-deficient patients with mutated GH-releasing ho:nnone Bioi Ther2006; 6: 533-8. a form of motor neurone disease (p. 2605.2). A review of receptor. J Clin Endocrinol Metab 2001; 86: 3279-83. 6. Keating GM. Mecaserrnin. BioDrugs 2008; 22: 177-88. 2 studies concluded that there was not enough evidence � to assess the clinical efficacy of mecasermin.1 A later study ���P.�.�� ��-"-�·-·········································································· Administration in children. For details of mecasermin found no benefit from mecasermin.2 ProprietaryPreparations (details are given in Volume B) doses in children see Uses and Administration, above and 1. Mitchell JD, et al. Recombinant human insulin-like growth factor I Growth Retardation, below. (rhiGF·I) for amyotrophic lateral sclerosis/motor neuron disease. Single-ingredient Preparations. Jp n: GHRP. Available in The Cochrane Database of Systematic Reviews; Issue 4. Diabetes mellitus. Patients with type I diabetes mellitus Chichester: John Wiley; 2007 (accessed 21108/08). 2. Sorenson EJ, et al. Subcutaneous IGF-1 is not beneficial in 2-year ALS (p. 459.I) have low circulating levels of insulin-like trial. Neurology 2008; 71: 1770-5. Somatomedins ® growth factor I (IGF-I), and there has been considerable interest in the therapeutic potential of mecasermin in these patients.' Randomised studies2•3 have found that Osteoporosis. Mecasermin1 and mecasermin rinfabate2 mecasermin 40 micrograms/kg once or twice daily by sub have been investigated as stimulants of bone formation in cutaneous injection improves metabolic control in the osteoporosis (p. 1168.I). Some beneficial effects on bone short term when added to insulin therapy. Insulin doses density have been reported. can also be reduced in some patients ' However, the role I. Grinspoon S, et al. Effects of recombinant human IGF-1 and oral Description. Somatomedins are a group of polypeptide of IGF-I in the development of diabetic complications is contraceptive administration on bone density in anorexia nervosa. J Clin hormones related to insulin and usually known individually unclear and there has been some concern about its prolif Endocrinol Metab 2002; 87: 2883-91. 2. Boonen S, et al. Musculoskeletal effects of the recombinant human IGF· as insulin-like growth factors (IGFs), with molecular erative effect in diabetic retinopathy.' Optic disc swelling 1/IGP binding protein-3 complex in osteoporotic patients with proximal weights of about 7000 to 8000. They are synthesised in the and worsening of retinopathy have been reported with femoral fracture: a double-blind, placebo-controlled pilot study. J Clin liver, kidney, muscle, and other tissues. higher doses of mecasermin. 3 Mecasermin rinfabate has Bndocrinol Metab 2002; 87: 1593-9.
The symbol t denotes a preparation no longer actively marketed The symbol 0 denotes a substance whose use may be restricted in certain sports (see p. viii)