"March 7, 2013 -- An FDA panel voted to stop recommending calcitonin salmon for the treatment of osteoporosis in women who are at least five years past menopause.
The committee voted 12-9 against continued marketing of the drug, citing"...
Mechanism Of Action
Calcitonin-salmon is a calcitonin receptor agonist. Calcitonin-salmon acts primarily on bone, but direct renal effects and actions on the gastrointestinal tract are also recognized. Calcitoninsalmon appears to have actions essentially identical to calcitonins of mammalian origin, but its potency per mg is greater and it has a longer duration of action.
The actions of calcitonin on bone and its role in normal human bone physiology are still not completely elucidated, although calcitonin receptors have been discovered in osteoclasts and osteoblasts.
The information below, describing the clinical pharmacology of calcitonin, has been derived from studies with injectable calcitonin-salmon. The mean bioavailability of calcitonin-salmon nasal spray is approximately 3% of the injectable calcitonin-salmon in healthy subjects and, therefore, the conclusions concerning the clinical pharmacology of this preparation may be different.
Single injections of calcitonin-salmon caused a marked transient inhibition of the ongoing bone resorptive process. With prolonged use, there is a persistent, smaller decrease in the rate of bone resorption. Histologically, this is associated with a decreased number of osteoclasts and an apparent decrease in their resorptive activity.
In healthy adults, who have a relatively low rate of bone resorption, the administration of exogenous calcitonin-salmon results in decreases in serum calcium within the limits of the normal range. In healthy children and in patients whose bone resorption is more rapid, decreases in serum calcium are more pronounced in response to calcitonin-salmon.
Studies with injectable calcitonin-salmon show increases in the excretion of filtered phosphate, calcium, and sodium by decreasing their tubular reabsorption. Comparable studies have not been conducted with Fortical nasal spray.
Some evidence from studies with injectable preparations suggests that calcitonin-salmon may have effects on the gastrointestinal tract. Short-term administration of injectable calcitoninsalmon results in marked transient decreases in the volume and acidity of gastric juice and in the volume and the trypsin and amylase content of pancreatic juice. Whether these effects continue to be elicited after each injection of calcitonin-salmon during chronic therapy has not been investigated. These studies have not been conducted with Fortical nasal spray.
In two clinical studies designed to evaluate the pharmacodynamic response to calcitonin-salmon nasal spray, administration of 100-1600 International Units to healthy volunteers resulted in rapid and sustained small decreases within the normal range for both total serum calcium and serum ionized calcium. Single doses of calcitonin-salmon greater than 400 International Units did not produce any further biological response to the drug.
The pharmacokinetic properties of Fortical nasal spray after multiple dose administration were shown to be similar to that of a commercially available calcitonin-salmon product in healthy volunteers. Fortical nasal spray is absorbed rapidly by the nasal mucosa. In healthy volunteers approximately 3% (range 0.3%-30.6%) of a nasally administered dose is bioavailable compared to the same dose administered by intramuscular injection. Peak plasma concentrations of drug appear approximately 10 minutes after nasal administration. The terminal half-life (t½) of calcitonin-salmon is calculated to be about 23 minutes. There is no accumulation of the drug on repeated nasal administration at 10 hour intervals for up to 15 days. Absorption of Fortical nasal spray has not been studied in postmenopausal women.
Two randomized, placebo-controlled, two-year trials were conducted in 266 postmenopausal women who were greater than 5 years postmenopause with spinal, forearm or femoral bone mineral density (BMD) at least one standard deviation below the normal value for healthy premenopausal women (T-score < -1). In both studies, a total of 144 patients received calcitonin-salmon nasal spray 200 International Units or placebo daily. The intent-to-treat population comprised 139 patients who had at least one follow-up BMD measurement. In study 1, patients also received 500 mg daily calcium supplements, while in study 2, patients received no calcium supplementation. The primary endpoint for both studies was percent change in lumbar spine BMD at 2 years. Calcitonin-salmon nasal spray increased lumbar vertebral BMD relative to placebo in women with low bone mass who were greater than 5 years post menopause (see Table 3 below).
Table 3: Calcitonin-salmon nasal spray: Lumbar Spine
Bone Mineral Density In Women Greater Than 5 years Postmenopause With Low Bone
|Lumbar Spine Bone Mineral Density, Mean Change From Baseline (in %) at Month 24|
|Study 1 (with calcium supplement)
n (ITT) = 100
|Study 2 (no calcium supplement)
n (ITT) = 39
|Calcitonin-salmon 200 IU NS daily||+1.56||+1.02|
|p-value†||< 0.05||< 0.005|
|ITT: Intent To Treat
IU: International Units
NS: nasal spray
†p-values by parametric testing (2-tailed 2-sample t-test)
No effects of calcitonin-salmon nasal spray on cortical bone of the forearm or hip were demonstrated.
In clinical studies of postmenopausal osteoporosis, bone biopsy and radial bone mass assessments at baseline and after 26 months of daily injectable calcitonin-salmon indicate that calcitonin therapy results in the formation of normal bone.
Last reviewed on RxList: 7/24/2014
This monograph has been modified to include the generic and brand name in many instances.
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