Calcitonin salmon

Included as part of the PRECAUTIONS section.

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.

Pharmacodynamics

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.

Pharmacokinetics

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.

Clinical Studies

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 Mass

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.

>10%

Rhinitis (12%)

1-10%

Arthralgia (4%)

Back pain (5%)

Expistaxis (4%)

Injection site reactions (10%)

Nausea (10%)

Headache (3%)

Flushing of face or hands (2-5%)

<1%

Abdominal pain

Possible allergic reactions

Appetite decreased

Edema of feet

Eye pain

Feverish sensation

Nausea

Nocturia

Possible local irritative effects in the respiratory tract

Salty taste

Frequency Not Defined

Tremors

IM/SC Administration

Patients should receive adequate calcium (at least 1000 mg/day elemental calcium) and vitamin D (at least 400 IU/day)

Intranasal Administration

Store unopened nasal spray in the refrigerator

Before using the first dose, wait until the bottle has reached room temperature and prime the pump before it is used for the first time

To administer, the nozzle should be carefully placed into the nostril with the patient’s head in the upright position, then the pump should be firmly depressed toward the bottle

The pump should not be primed before each daily use

Do not use this medication if you are allergic to salmon calcitonin.

Before using calcitonin injection, tell your doctor if you are allergic to any food or drugs. You may need a dose adjustment or special tests to safely use this medication.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether calcitonin passes into breast milk or if it could harm a nursing baby. Calcitonin may slow breast milk production. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Use the medication as soon as you remember the missed dose. If it is almost time for your next dose, skip the missed dose and use the medicine at your next regularly scheduled time. Do not use extra medicine to make up the missed dose.

To make sure you are not allergic to this medication, your doctor may perform an allergy skin test before your first dose of calcitonin nasal.

Before using calcitonin nasal, tell your doctor if you have any nasal or sinus problems such as nasal deformities, a chronic infection, or nasal pain.

Avoid using any other nasal sprays or medicines at the same time you use calcitonin nasal unless your doctor has told you to.

Call your doctor at once if you have any type of severe irritation of your nose, or if you feel light-headed or faint.

Less serious nasal irritation is more likely to occur, such as minor bleeding, redness, itching, tenderness, dryness, crusting, scabs, or nasal congestion.

To be sure this medication is not causing harmful side effects to the inside of your nose, your doctor may want to check your nasal passages on a regular basis. Do not miss any scheduled visits to your doctor.

Avoid using any other nasal sprays or nasal medications at the same time you use calcitonin nasal unless your doctor has told you to.

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