Lanreotide Injection (Somatulin® Depot)
Pharmacology Update
Lanreotide Injection (Somatulin® Depot)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
A second somatostatin (growth hormone inhibiting hormone) analog is available for the long-term treatment of acromegaly in patients who have not responded to other treatment modalities. Lanreotide is a synthetic cyclical octapeptide, similar to octreotide (Sandostatin) with biological activity similar to naturally occurring somatostatin. The drug was approved with an Orphan designation for treating a rare disease. It is manufactured by Ipsen Biotech in France and marketed by Tercica, Inc as Somatulin Depot.
Indications
Lanreotide is indicated for the long-term treatment of acromegaly in patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy.1
Dosage
The recommended starting dose is 90 mg given by deep subcutaneous injection (superior external quadrant of the buttock) at 4-week intervals for 3 months. The dose is 60 mg for patients with moderate and severe renal or hepatic impairment. The dose is then adjusted based on growth hormone (GH) and insulin growth factor-1 (IGF-1) levels.1
Lanreotide in available as 60 mg, 90 mg, and 120 mg single-use, pre-filled syringes.
Potential Advantages
Lanreotide is premixed and supplied as single use syringes for deep subcutaneous injection while the other available long-acting somatostatin analog, octreotide (Sandostatin LAR Depot), must be administered intragluteally under the supervision of a physician.
Potential Disadvantages
Adverse events are generally related to the pharmacology of lanreotide. These include gall stone formation, and inhibits the release of insulin, glucagon, and thyroid releasing hormone. Most common adverse events include abdominal pain, diarrhea, nausea, bradycardia, hypertension, injection site effects, anemia, and weight decrease. Diabetics may require an adjustment of their diabetes medication. Lanreotide may decrease the bioavailability of cyclosporine.1
Comments
Somatostatin analogs (octreotide and lanreotide) act on the somatostatin receptor subtypes 2 and 5 resulting in the inhibition of the release of growth hormone. These analogs have plasma half-lives about 20 times that of native somatostatin. The efficacy of lanreotide was shown in two long-term, randomized studies.1 In the first study (n = 108), active acromegaly patients with GH > 5 ng/ml were randomized to a single dose 60 mg, 90, 120 mg, placebo. Each patient then entered a fixed-dose phase (16 weeks) followed by dose-titration phase (32 weeks). At 52-weeks or last observation carried forward, the median reduction in GH was 75.5% and median reduction in IGF-1 was 55.4%. Forty-four percent achieved age-adjusted normal IGF-1 and GH ≥ 2.5 ng/ml. Improvement achieved at 16-weeks was maintained for the duration of the study. In the second study (n = 63), patients with IGF-1 concentrations ≤ 1.3 times ULN were administered 90 mg for 4 months followed by dose titration phase up to 48 weeks. At the end of the study the median reduction in IGF-1 was 50.3% with 38% achieving age-adjusted ICF-1 and GH ≥ 2.5 ng/ml. The median GH reduction was 78.6%. In addition to biochemical changes somatostatin analogs shrink pituitary adenomas, improve sleep apnea, reduce left ventricular hypertrophy, improve diastolic function, shorten and normalize QT complex, improve lipid profiles, reduce fatigue and headaches, improve paresthesias, perspiration, osteoarthralgia, carpal tunnel syndrome, and reduce soft tissue enlargement.2 Studies of lanreotide in patients previously treated with octreotide LAR or crossover studies involving 10 to 23 patients suggest similar efficacy and adverse events between long acting forms of lanreotide and octreotide.3,4,5 Some patients may be dosed every 6-8 weeks instead of every 4 weeks with out loss of efficacy.4
Clinical Implications
Acromegaly is a rare endocrine disorder caused by a growth hormone producing pituitary tumor resulting in over production of GH and ICF-1. It is associated with significant morbidity and reduction in life expectancy of 5 to 10 years.6 The goal of therapy is to relieve symptoms, restore metabolic changes due to GH excess, and achieve normal physiologic GH levels. First line therapy is surgery or radiotherapy or a combination. Pharmacotherapy includes somatostatin analogs and dopamine agonist.7 Lanreotide offers another, potentially more patient-friendly somatostatin analog.
References
1. Somatulin Depot Product Information. Ipsen Pharma Biotech. August 2007.
2. Ben-Shlomo A, Melmed S. Mol Cell Endocrinol. 2008; doi:10.1016/j.mi\ce.2007.11.024.
3. Andries M et al. Clin Endocrinol. 2008;68(3):473-480.
4. Ronchi CL, et al. Clin Endocrinol. 2007;67(4):512-519.
5. Ashwell SG, et al. European Journal of Endocrinology. 2004;150:4773-4780.
6. FDA news. http://www.fda.gov/bbs/topics/NEWS/2007NEW01692.html.
7. Biermasz N, et al. Expert Opin Pharmacother. 2005;6(14):2393-2405.
A second somatostatin (growth hormone inhibiting hormone) analog is available for the long-term treatment of acromegaly in patients who have not responded to other treatment modalities.Subscribe Now for Access
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