Israel - English - Ministry of Health
SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
SALCO 100 IU
, solution for injection
QUALITATIVE AND QUANTITATIVE COMPOSITION
SALCO 100 IU/ml solution for injection – 1 ampoule contains:
SALCO is essentially sodium-free, see section 4.4.
For a full list of excipients, see section 6.1.
Solution for intramuscular, intravenous and subcutaneous injection.
Salco is a clear, colourless aqueous solution.
Calcitonin is indicated for:
Prevention of acute bone loss due to sudden immobilisation such as in
patients with recent osteoporotic fractures.
For the treatment of Paget's disease, only in patients who do not respond to
alternative treatments or for whom such treatments are not suitable, for
example those with severe renal impairment.
Treatment of hypercalcemia of malignancy.
Posology and method of administration
Salmon calcitonin may be administered at bedtime to reduce the incidence of
nausea or vomiting which may occur, especially at the initiation of therapy.
calcitonin use (see section 4.4), the treatment duration in all indications
should be limited to the shortest period of time possible and using the
minimum effective dose.
Prevention of acute bone loss due to sudden immobilisation such as in patients
with recent osteoporotic fractures
The recommended dosage is 100 IU daily or 50 IU twice daily, administered
subcutaneously or intramuscularly. The dose may be reduced to 50 IU daily at
the start of remobilisation. The recommended treatment duration is 2 weeks
and should not exceed 4 weeks in any case due to the association of the
increased risk of malignancies and long term calcitonin use.
The recommended dosage is 100 IU per day administered subcutaneously or
intramuscularly, however, a minimum dosage regimen of 50 IU three times a
week has achieved 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. Under exceptional
circumstances, e.g. in patients with impending pathologic fracture, treatment
duration may be extended up to a recommended maximum of 6 months.
Periodic re-treatment may be considered in these patients, and should take into
account the potential benefits and evidence of an increased risk of malignancies
and long term calcitonin use (see section 4.4).
The effect of calcitonin may be monitored by measurement of suitable markers
of bone remodeling, such as serum alkaline phosphatase or urinary
hydroxyproline or deoxypyridinoline.
The dose may be reduced after the condition of the patient has improved.
Hypercalcemia of malignancy:
The recommended starting dose is 100 IU every 6 to 8 hours by
subcutaneous or intramuscular injection. In addition, salmon calcitonin
could be administered by intravenous injection after previous rehydration.
If the response is not satisfactory after one or two days, the dose may be
increased to a maximum of 400 IU every 6 to 8 hours. In severe or emergency
cases, intravenous infusion with up to 10 IU/kg body weight in 500 ml 0.9%
w/v sodium chloride solution may be administered over a period of at least 6
The treatment duration is limited to the shortest possible time using the
minimum effective dose.
As salmon calcitonin is a peptide, adsorption onto the plastic of the infusion set
may occur. This has the potential to reduce the total dose delivered to the
patient. Frequent monitoring of the clinical and laboratory response including
the measurement of serum calcium is recommended especially in the early
phases of treatment. The dosing of SALCO should be individualized to the
patient’s specific requirements.
Experience with the use of calcitonin in the elderly has shown no evidence of
reduced tolerability or altered dosage requirements.
Patients with hepatic impairment
Experience with the use of calcitonin in patients with altered hepatic function has
shown no evidence of reduced tolerability or altered dosage requirements.
Patients with renal impairment
The metabolic clearance is much lower in patients with end-stage renal failure
than in healthy subjects. However, the clinical relevance of this finding is not
known (see section 5.2).
There is insufficient evidence to support the use of salmon calcitonin in
conditions associated with paediatric osteoporosis. Use of salmon calcitonin in
children 0 to 18 years is therefore not recommended.
Hypersensitivity to the active substance or to any of the excipients listed in
Calcitonin is also contraindicated in patients with hypocalcaemia.
Special warnings and precautions for use
Because calcitonin is a peptide, the possibility of systemic allergic reactions
exists and allergic-type reactions including isolated cases of anaphylactic shock
have been reported in patients receiving calcitonin. Such reactions should be
differentiated from generalised or local flushing, which are common non-allergic
effects of calcitonin (see section 4.8). Skin testing should be conducted in
patients with suspected sensitivity to calcitonin prior to their treatment with
Analyses of randomised controlled trials conducted in patients with
osteoarthritis and osteoporosis have shown that calcitonin is associated with a
statistically significant increase in the risk of cancer compared to patients treated
with placebo. These trials demonstrated an increase in the absolute risk of cancer
occurrence for patients treated with calcitonin compared to placebo which varied
between 0.7% and 2.4% with long term therapy. Patients in these trials were
treated with oral or 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
SALCO contains less than 23 mg sodium per 1 ml and can be considered
Interaction with other medicinal products and other forms of interaction
Serum calcium levels may be transiently decreased to below normal levels
following administration of calcitonin, notably upon initiation of therapy in
patients with abnormally high rates of bone turnover. This effect is diminished as
osteoclastic activity is reduced. However, care should be exercised in patients
receiving concurrent treatment with cardiac glycosides or calcium channel
blocking agents. Dosages of these drugs may require adjustment in view of
the fact that their effects may be modified by changes in cellular electrolyte
The use of calcitonin in combination with bisphosphonates may result in an
additive calcium-lowering effect.
Concomitant use of calcitonin and lithium may lead to a reduction in plasma
lithium concentrations. The dose of lithium may need to be adjusted.
Fertility, pregnancy and lactation
Calcitonin has not been studied in pregnant women. Calcitonin should be used
during pregnancy only if treatment is considered absolutely essential by the
It is not known if the substance is excreted in human milk. In animals, salmon
calcitonin has been shown to decrease lactation and to be excreted in milk (see
section 5.3). Therefore, breast-feeding is not recommended during treatment.
There are no data regarding a potential influence of SALCO on human fertility.
Effects on ability to drive and use machines
No studies exist on the effects of SALCO on the ability to drive and use
machines. SALCO may cause fatigue, dizziness and visual disturbances (see
section 4.8) which may impair the patient’s reactions. Patients must therefore
be warned that these effects may occur, in which case they should not drive or
The most frequently observed undesirable effects are nausea, vomiting and
flushing. They are dose dependent and more frequent after i.v. than after i.m.
or s.c. administration.
Adverse drug reactions from multiple sources including clinical trials and
post- marketing experience are listed by MedDRA system organ class. Within
each system organ class, the adverse drug reactions are ranked by frequency,
with the most frequent reactions first. Within each frequency grouping,
adverse drug reactions are presented in order of decreasing seriousness.
Adverse reactions have been ranked under headings of frequency using the
following convention: Very common (≥1/10); common (≥1/100 to <1/10);
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare
(<1/10,000), not known (cannot be estimated from the available data).
Neoplasms benign, malignant and unspecified (including cysts and polyps)
Malignancy (with long term use)
Immune system disorders
Serious allergic-type reactions such as
bronchospasm, swelling of the tongue and
throat, anaphylactic shock.
Metabolism and nutrition disorders
Transient decrease of calcemia
Nervous system disorders
Dizziness, headache, dysgeusia.
Flushing (facial or upper body)
Nausea with or without vomiting
Diarrhoea, abdominal pain.
Skin and subcutaneous tissue disorders
Rash generalised, pruritus.
Musculoskeletal and connective tissue disorders
Musculoskeletal pain including arthralgia.
Renal and urinary disorders
General disorders and administration site conditions
Influenza-like illness, oedema (facial, peripheral
and generalised), injection site reaction
generalised), injection site reaction
The frequencies of the above listed undesirable effects are partly based on
results from clinical trials with Miacalcic (calcitonin salmon) Nasal Spray.
Development of neutralising antibodies to calcitonin. The development of
these antibodies is not usually related to loss of clinical efficacy, although their
presence in a small percentage of patients following long-term therapy with
calcitonin may result in a reduced response to the product. The presence of
antibodies appears to bear no relationship to allergic reactions, which are rare.
Calcitonin receptor down-regulation may also result in a reduced clinical
response in a small percentage of patients following long-term therapy.
Nausea with or without vomiting is noted in approximately 10% of patients
treated with calcitonin. The effect is more evident on initiation of therapy and
tends to decrease or disappear with continued administration or a reduction in
dose. An antiemetic may be administered, if required. Nausea/vomiting are
less frequent when the injection is done in the evening and after meals.
In case of patients with high bone remodelling (Paget’s disease and young
patients) a transient decrease of calcemia may occur between the 4
hour after administration, usually asymptomatic.
Flushing (facial or upper body) is not an allergic reaction but is due to a
pharmacological effect and is usually observed 10 to 20 minutes after
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Any suspected adverse events should be reported to the Ministry of Health
according to the National Regulation by using an online form
and e-mailed to the Registration Holder’s Patient Safety Unit at:
Nausea, vomiting, flushing and dizziness are known to be dose dependent when
calcitonin is administered parenterally. Single doses (up to 10,000 IU) of
injectable salmon calcitonin have been administered without adverse reactions,
other than nausea and vomiting, and exacerbation of pharmacological effects.
Should symptoms of overdose appear, treatment should be symptomatic.
The pharmacological properties of the synthetic and recombinant peptides have
been demonstrated to be qualitatively and quantitatively equivalent.
Calcitonin is a calciotropic hormone, which inhibits bone resorption by a direct
action on osteoclasts. By inhibiting osteoclast activity via its specific receptors,
calcitonin has been shown to have analgesic activity in animal models.
Calcitonin markedly reduces bone turnover in conditions with an increased rate
of bone resorption such as Paget’s disease and acute bone loss due to sudden
The absence of mineralisation defect with calcitonin has been demonstrated by
bone histomorphometric studies both in man and in animals.
Decreases in bone resorption as judged by a reduction in urinary
treatment in both normal volunteers and patients with bone-related disorders,
including Paget’s disease and osteoporosis.
The calcium-lowering effect of calcitonin is caused both by a decrease in the
efflux of calcium from the bone to the ECF and inhibition of renal tubular
reabsorption of calcium.
General characteristics of the active substance
Salmon calcitonin is rapidly absorbed and eliminated.
Peak plasma concentrations are attained within the first hour of administration.
After subcutaneous administration, peak plasma levels are reached in about
proteolysis in the kidney following parenteral administration. The metabolites
lack the specific biological activity of calcitonin.
Bioavailability following subcutaneous and intramuscular injection in humans is
Calcitonin has a short absorption half-life of 10-15 minutes. The elimination
half-life is about 1 hour for intramuscular administration and 1 to 1.5 hours for
fragments of the molecule. Therefore, the metabolic clearance is much lower
in patients with end-stage renal failure than in healthy subjects. However, the
clinical relevance of this finding is not known.
Plasma protein binding is 30 to 40%.
Characteristics in patients
There is a relationship between the subcutaneous dose of calcitonin and peak
concentrations. Following parenteral administration of 100 IU
calcitonin, peak plasma concentration lies between about 200 and 400 pg/ml.
Higher blood levels may be associated with increased incidence of nausea and
Preclinical safety data
Conventional long term toxicity, reproduction, mutagenicity and
carcinogenicity studies have been performed in laboratory animals.
Salmon calcitonin is devoid of embryotoxic, teratogenic and mutagenic
An increased incidence of pituitary adenomas has been reported in rats
given synthetic salmon calcitonin for 1 year. This is considered a species-
specific effect and of no clinical relevance. It is not known whether salmon
calcitonin crosses the placental barrier.
In lactating animals given calcitonin, suppression of milk production has
been observed. Calcitonin is secreted into the milk.
List of excipients
Glacial acetic acid
Sodium acetate trihydrate
Water for injection
Glass or hard plastic i.v. containers should not be used.
The expiry date is indicated on the packaging materials.
Special precautions for storage
Store in a refrigerator (between 2°C and 8°C). Store product in its original
package to protect it from light.
Use immediately after opening.
Nature and contents of container
Type I, transparent glass ampoules containing 1 ml of solution. SALCO
ampoules 100 IU/ml are supplied as packs containing 1,2,3,4 and 5 ampoules.
Not all pack sizes may be marketed.
Special precautions for disposal
SALCO ampoule 100 IU/ml should be inspected visually. If the liquid is not
clear and colourless, or contains any particles, or the ampoule is damaged, do
not use the medicine.
Solutions for infusion should be prepared immediately before use in soft plastic
PVC infusion bags. Glass or hard plastic i.v. containers should not be used.
The ampoules are for single use only. Remaining contents should be discarded.
Allow to reach room temperature before intramuscular or subcutaneous use.
Laboratorio Italiano Biochimico Farmaceutico LISAPHARMA S.p.A.
Via Licinio, 11 – 22036 ERBA (CO)
12 Beit Harishonim St., Emek Heffer
The format of this leaflet was determined by the Ministry of Health and its content was checked
and approved in August 2017.