CALCITONIN SALMON

Central and peripheral nervous system disorders:

Paresthesia (tingling of the hands), dizziness, seizures, visual and hearing impairment, headache, tremor, tinnitus.

Endocrine disorders:

Secondary hyperparathyroidism did not develop in patients with Paget's disease as a result of the transient hypocalcemia following calcitonin administration.

Eye disorders:

Pain in the eyes.

Gastrointestinal disorders:

Nausea with or without vomiting has been noted in about 10% of patients treated with Calcitonin-Salmon. It is most evident when treatment is first initiated and tends to decrease or disappear with continued administration. Abdominal pain, diarrhea.

General and administration site disorders:

Local inflammatory reactions at the site of injection have been reported in about 10% of patients. Feverish sensation.

Immune system disorders:

Evidence of systemic allergic reactions was minimal. Administration of Calcitonin-Salmon has been reported in a few cases to cause serious allergic-type reactions (for example, bronchospasms, swelling of the tongue or throat and anaphylactic shock), and in one case, death due to anaphylaxis (see PRECAUTIONS, Potential allergenicity of Calcitonin Salmon Injection USP).

Skin rashes and pruritus of the ear lobes have also been reported. The usual laboratory parameters of liver and kidney function and of hematologic status remained within normal limits. In approximately one-half the patients tested after six months or more of treatment, indications of circulating antibodies to calcitonin were obtained.

In most of the patients the level of antibodies was not high enough to interfere with the effect of exogenous calcitonin. In a few patients resistance to calcitonin was attributed to high levels of antibodies.

Metabolism and nutrition disorders:

Decreased appetite, anorexia, and a metallic and/or salty taste. 4% for the nasal formulation).

Urinary disorders:

Nocturia, polyuria.

Vascular disorders:

Flushing of the face, ears, hands and feet occurred in about 2-5% of patients. Hypertension. _____________________________________________________________________________ Calcitonin Salmon Injection USP Product Monograph Page 6 of 20 SYMPTOMS AND TREATMENT OF OVERDOSAGE Symptoms: The pharmacologic actions of Calcitonin Salmon Injection USP suggest that hypocalcemic tetany could occur in overdose.

Therefore, provisions for the parenteral administration of calcium should be available for the treatment of overdose (see PRECAUTIONS). Dose-dependent adverse effects such as nausea, vomiting, flushing, and dizziness can occur when calcitonin is administered for parenteral use (see ADVERSE REACTIONS).

Treatment:

There is no specific antidote. In the event of a suspected overdose, discontinue treatment temporarily, maintain the patient under observation and implement supportive treatment as indicated. For management of a suspected drug overdose, contact your regional poison control centre.

DOSAGE AND ADMINISTRATION Due to evidence of an increased risk of malignancies with long term calcitonin use, the treatment duration should be limited to the shortest period of time possible and using the minimum effective dose. Adults: 1.

U. U. three times a week is sufficient to maintain clinical and biochemical improvement. Dosage is to be adjusted to the individual patient’s needs. Treatment should be discontinued once the patient has responded and symptoms have resolved.

Duration of treatment should not normally exceed 3 months due to evidence of an increased risk of malignancies with long term calcitonin use. g. in patients with impending pathologic fracture, treatment duration may be extended up to a recommended maximum of 6 months.

Drug effect should be monitored by periodic measurement of bone remodeling markers such as serum alkaline phosphatase and 24-hour urinary hydroxyproline or deoxypyridinoline and evaluation of symptoms. A decrease toward normal of the biochemical abnormalities is usually seen, if it is going to occur, within the first few months.

Bone pain may also decrease during that time. In any patient with a good initial response who later relapses, either clinically or biochemically, the possibility of antibody formation should be explored to detect titers that interfere with the action of calcitonin.

U. per day does not usually appear to elicit an improved response. U. of Calcitonin Salmon Injection USP are injected IM. The patient is then permitted to eat his usual breakfast. At 3 & 6 hours post-injection additional blood samples are drawn and the patient is released.

The serum calcium values are then compared. 5 mg/dL) or more from fasting level at 3 and 6 hours is usually seen in the responsive patient. 3 mg/dL) or less constitute an inadequate response to calcitonin in the patient with active Paget's disease.

If the hypocalcemic action of calcitonin is lost, further therapy with Calcitonin Salmon Injection USP will not be effective. 2. U. /kg body weight every 12 hours by subcutaneous or intramuscular injection. If the response to this dose is not satisfactory after one or two days, the dose may be […]

Patients who are hypersensitive to Calcitonin Salmon Injection USP or to any ingredient in the formulation or component of the container. For a complete listing, see DOSAGE FORMS and PHARMACEUTICAL INFORMATION, Composition sections of the Product Monograph.

4% (intranasal route)) in patients treated with calcitonin therapy compared to patients treated with placebo. Patients in these trials were treated with long-term oral and intra-nasal formulations however it is likely that an increased risk also applies when calcitonin is administered subcutaneously, intramuscularly or intravenously especially for long-term use, as systemic exposure to calcitonin in such patients is expected to be higher than for other formulations.

Pregnancy:

Reproduction studies in two species (rats and rabbits) have revealed decreases in fetal birth weight, and data in humans are not available to exclude a possible adverse effect on the fetus. Use of this drug in women who are or may become pregnant requires a determination that the potential benefit to the patient outweighs the possibility of risk to the fetus.

Nursing Mothers:

Calcitonin-Salmon has been shown to inhibit lactation in animals and should not be administered to nursing mothers.

Children (< 18 years of age):

The safe use of Calcitonin-Salmon in children has not been established.

PRECAUTIONS Potential allergenicity of Calcitonin Salmon Injection USP:

Skin testing should be considered prior to treatment of patients with suspected sensitivity to calcitonin. U. P. ). ) on the inner aspect of the forearm. Observe the injection site 15 minutes after injection. The appearance of more than mild erythema or wheal constitutes a positive response.

Because calcitonin is protein in nature, the possibility of a systemic allergic reaction cannot be overlooked. Administration of Calcitonin-Salmon has been reported in a few cases to cause serious allergic-type reactions (for example, bronchospasms, swelling of the tongue or throat and anaphylactic shock), and in one case, death due to anaphylaxis.

The usual provisions should be made for the emergency treatment of such a reaction should it occur. _____________________________________________________________________________ Calcitonin Salmon Injection USP Product Monograph Page 4 of 20 Allergic reactions should be differentiated from generalized flushing and hypotension.

e. muscle cramps, twitching). Provisions for parenteral calcium administration should be available during the first several administrations of calcitonin. In patient’s with active Paget’s disease, a decrease in serum calcium was observed after the injection of up to 100 units of subcutaneous calcitonin, which can be asymptomatic, was evident by the end of the first hour and maximal from 4 to 6 hours.

Antibody development:

Calcitonin administration can and does lead to antibody development. This is minimal when the hormone is injected in the absence of an adjuvant or when it is not complexed with a larger protein. Gelatin and acetate buffer solutions have been shown to have little or no adjuvant-like action in comparison to Freund's adjuvant.

The antibodies which develop when calcitonin is administered repeatedly with Freund's adjuvant are measurable in the circulation by radio-immunoassay techniques. In no instance has any systemic allergic or anaphylactic effect been reported in animal studies with calcitonin, in spite of the known development of circulating antibodies.

Laboratory Tests:

Periodic examinations of serum calcium and urine sediment of patients on chronic therapy are recommended. Coarse granular casts and casts containing renal tubular epithelial cells were reported in young adult volunteers at bed rest who were given salmon calcitonin to study its effect on immobilization osteoporosis.

There was no other evidence of renal abnormality and the urine sediment became normal after calcitonin was stopped.

Instructions for the patient:

Careful instruction in sterile injection technique should be given to the patient and to other persons who may administer Calcitonin Salmon Injection USP. INTERACTIONS Concomitant use of Calcitonin Salmon Injection USP and lithium may lead to a reduction in plasma lithium concentrations.

The dose of lithium may need to be adjusted; blood monitoring of lithium is recommended. _____________________________________________________________________________ Calcitonin Salmon Injection USP Product Monograph Page 5 of 20 ADVERSE REACTIONS Central and peripheral nervous system disorders: Paresthesia (tingling of the hands), dizziness, seizures, visual and hearing impairment, headache, tremor, tinnitus.

Endocrine disorders:

Secondary hyperparathyroidism did not develop in patients with Paget's disease as a result of the transient hypocalcemia following calcitonin administration.

Eye disorders:

Pain in the eyes.

Gastrointestinal disorders:

Nausea with or without vomiting has been noted in about 10% of patients treated with Calcitonin-Salmon. It is most evident when treatment is first initiated and tends to decrease or disappear with continued administration. Abdominal pain, diarrhea.

General and administration site disorders:

Local inflammatory reactions at the site of injection have been reported in about 10% of patients. Feverish sensation. Immune system […]