Consumer medicine information

Miacalcic

Calcitonin salmon (salcatonin)

BRAND INFORMATION

Brand name

Miacalcic Solution for injection

Active ingredient

Calcitonin salmon (salcatonin)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Miacalcic.

What is in this leaflet

This leaflet answers some common questions about Miacalcic.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page.

Some more recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine.

You can also download the most up to date leaflet from www.novartis.com.au.

Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Miacalcic against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Miacalcic is used for

Miacalcic contains salcatonin, which is similar to calcitonin, a hormone produced by the body.

  • Miacalcic is used to treat Paget's disease when other therapies cannot be used or have proven unsuccessful

Paget's disease is a chronic disorder of the bones of the skeleton. Bone is a living tissue and, just like other parts of the body, it is constantly being renewed. This process is called bone remodelling.

Remodelling involves two types of bone cells - osteoclasts, which break down old bone and osteoblasts, which make new bone. In people with Paget's disease the osteoclasts in some bones are overactive, causing the bone to break down more quickly than usual. The osteoblasts then try to work faster to replace the lost bone. The new bone that is formed may be thicker but weaker than normal, which can cause pain and may lead to fractures (broken bones).

Miacalcic works by slowing down the breakdown of bone by the osteoclasts. This allows bone remodelling to go back to normal and protects the bones from being weakened. Miacalcic may also relieve bone pain.

  • Miacalcic is also used to treat hypercalcaemia (high calcium levels in the blood)

It helps to reduce the level of calcium in the blood when it becomes too high.

Ask your doctor if you have any questions about why Miacalcic has been prescribed for you.

Your doctor may have prescribed this medicine for another reason.

Miacalcic is only available with a doctor's prescription. It is not addictive.

Miacalcic is not recommended for children except in special cases, since experience with using Miacalcic in this age group is limited.

Before you use Miacalcic

When you must not use it

Do not use Miacalcic if you have an allergy to:

  • salcatonin, the active ingredient in Miacalcic
  • any of the other ingredients listed at the end of this leaflet

You may get hives or an itchy skin rash, swelling of the face, lips, tongue or throat, wheezing or troubled breathing, fast heart beat, faintness or other symptoms if you use it.

Your doctor may have performed a skin test to check for an allergy before giving you this medicine. See the 'Side effects' section of this leaflet for more information about allergic reactions.

Do not use Miacalcic if you are pregnant or breast-feeding.

There is not enough experience with Miacalcic in pregnant women or nursing mothers to recommend its use. Your doctor can discuss with you the risks and benefits of using this medicine while you are pregnant or breast-feeding.

Do not use Miacalcic if the packaging is torn or shows signs of tampering.

In that case, return it to your pharmacist.

Do not use Miacalcic after the use by (expiry) date printed on the pack or ampoule.

If you use it after the expiry date has passed, it may not work as well as it should.

Before you start to use it

Tell your doctor if you have any problems with your kidneys.

Your doctor may want to prescribe a lower dose of Miacalcic than usual if you have a kidney problem.

Taking other medicines

Tell your doctor if you are taking lithium.

Your dosage may need to be adjusted.

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Other medicines may affect the way Miacalcic works. Your doctor or pharmacist can tell you what to do if you are taking any other medicines.

If you have not told your doctor about any of these things, tell him/her before you use Miacalcic.

How to use Miacalcic

Follow all directions given to you by your doctor and pharmacist carefully.

These directions may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How it is given

Miacalcic cannot be taken by mouth because it is rapidly broken down in the stomach. Instead it is given as an injection. It can be injected intravenously (into the vein) or intramuscularly (into the muscle of the thigh or buttock). It can also be injected subcutaneously. That means that it is injected into the layer of fat just under the skin.

If you will be giving the subcutaneous injections yourself, your doctor or nurse will teach you how to inject yourself properly.

If you are not sure about anything, ask your doctor or nurse before you start.

How much is given

The dose of Miacalcic depends on the condition being treated.

For Paget's disease: the usual dose is 80 to 100 I.U. (international units) of Miacalcic each day or every second day. The dose is given by intramuscular or subcutaneous injection. The dose of Miacalcic may be adjusted depending on the response to treatment. This medicine may be needed for anywhere from a few months to a few years.

For hypercalcaemia: the usual dose is 5 to 10 I.U. of Miacalcic per kg of body weight per day. It can be given intravenously or by intramuscular or subcutaneous injection.

If you forget to use it

If it is more than 4 hours until your next dose is due, inject the dose as soon as you remember and then go back to injecting it as you would normally.

If it is less than 4 hours until your next dose is due, wait and inject your dose at the usual time.

Do not use a double dose to make up for the one that you missed.

It won't do any harm if you miss a dose but some of your symptoms may come back temporarily until you get back on schedule.

If you have trouble remembering when to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that an overdose has happened. Do this even if there are no signs of discomfort or poisoning.

While you are using Miacalcic

Things you must do

Keep all of your doctor's appointments so that your progress can be checked.

If you have to take Miacalcic for a long time (for example, to treat Paget's disease), your doctor may want you to have X-rays or blood and urine tests from time to time to make sure Miacalcic is working and to prevent unwanted side effects from happening. If you are receiving Miacalcic solution for injection or infusion for a long time, tell your doctor and your doctor would evaluate the benefit against possible risks and advise you. Using Miacalcic for a long time might increase the risk of cancer.

See your doctor if your symptoms reappear.

Sometimes after using Miacalcic for a while, your symptoms may reappear (this is called a "rebound" effect). If this happens, your doctor may stop Miacalcic for a short time and then start it again. This helps to restore the good effects of the medicine.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are having treatment with Miacalcic.

Tell any other doctor, dentist or pharmacist who treats you that you are having treatment with Miacalcic.

Things you must not do

Do not give this medicine to anyone else, even if their symptoms seem to be the same as yours.

Do not use Miacalcic to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how Miacalcic affects you.

This medicine may cause dizziness in some people. Make sure you know how you react to Miacalcic before you drive a car, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Miacalcic.

All medicines can have side effects. Sometimes they are serious, but most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following side effects and they worry you:

  • redness, swelling or pain at the site of injection
  • nausea or vomiting
  • abdominal pain
  • a hot flushed face
  • dizziness
  • frequent passing of urine or passing large amounts of urine
  • diarrhoea
  • headache
  • fever and chills
  • pain in the joints
  • numbness, tingling or cramps in arms or legs
  • itching of the palms of the hands
  • unusual taste
  • fatigue
  • visual disturbances
  • trembling

Stop using Miacalcic and tell your doctor immediately or go to Accident and Emergency at your nearest hospital if any of the following happen:

  • a severe reaction at the site of injection
  • swelling of the face, lips, tongue or throat
  • swelling of other parts of the body such as legs or ankles
  • tightness in the chest, wheezing or troubled breathing
  • hives or an itchy skin rash (can affect entire body)
  • fast heartbeat
  • fainting

You may be having a serious allergic reaction to Miacalcic and may need urgent medical attention or hospitalisation. Allergic reactions are rare.

Tell your doctor if you notice anything else that is making you feel unwell.

Other side effects not listed above may happen in some people.

After using Miacalcic

Storage

  • Keep the ampoules in the carton until it is time to use them.
  • Keep your ampoules in the refrigerator (about 2°C to 8°C). Do not freeze.

Keep the medicine where children cannot reach it.

Disposal

Throw out any Miacalcic left in the ampoule once the dose has been injected.

Miacalcic does not contain any preservatives.

Dispose of the used ampoules safely.

If your doctor tells you to stop using Miacalcic or you find that it has passed the expiry date or has been left out of the fridge, ask your pharmacist what to do with any medicine you have left over.

Product description

What it looks like

Each Miacalcic pack contains 5 ampoules of salcatonin.

Ingredients

Each 1 mL ampoule of Miacalcic contains either 50 I.U. or 100 I.U. salcatonin (also known as salmon calcitonin). The ampoule also contains glacial acetic acid, sodium acetate, sodium chloride and water for injections.

Sponsor

Miacalcic is supplied in Australia by:

NOVARTIS Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone 1 800 671 203

® = Registered Trademark

This leaflet was prepared in September 2015.

Australian Registration Number:
50 I.U./1 mL ampoule: AUST R 13364
100 I.U./1 mL ampoule: AUST R 13363

For Internal Use Only:

(CMI mia080915c.doc) based on PI (mia080915i.doc)

BRAND INFORMATION

Brand name

Miacalcic Solution for injection

Active ingredient

Calcitonin salmon (salcatonin)

Schedule

S4

 

Name of the medicine

Salcatonin (as polyacetate polyhydrate).

Excipients.

Sodium acetate 0.2%, glacial acetic acid 0.2% and sodium chloride 0.75%.

Description

Salcatonin is a synthesised polypeptide hormone structurally identical to salmon calcitonin. It contains 32 amino acids in linear sequence with a disulphide bridge at positions 1 and 7. MW: 3,431.9 (free peptide). CAS: 47931-85-1. Salcatonin is a white or grey tinged white amorphous powder, very soluble in water and very slightly soluble in alcohol.
Naturally occurring calcitonin is synthesised by parafollicular cells in the thyroid gland of mammals and the ultimobranchial gland of birds and fish. The potency of salmon calcitonin is standardised according to its ability to lower plasma calcium levels of rats as compared to the international reference standard.
Each mL Miacalcic injection contains 50 or 100 IU salcatonin (present as polyacetate polyhydrate), sodium acetate 0.2%, glacial acetic acid 0.2% and sodium chloride 0.75%.

Pharmacology

Pharmacotherapeutic group, ATC code.

Regulator of calcium homeostasis, H05BA01.
The secretion and biosynthesis of calcitonin in both animals and man are regulated by the concentration of calcium in plasma. When the calcium concentration is high the amount of the hormone increases.
The pharmacological activity of salmon calcitonin is the same as that of mammalian calcitonin. In man, data on relative potency are sparse, but salcatonin is thought to be at least 10-40 times as potent by weight as porcine or human calcitonin in producing hypocalcaemia depending on methodology. Presumably due to its greater affinity for receptor binding sites in bone and kidney, and slower rate of metabolism, salcatonin has a longer duration of action.
Calcitonin inhibits osteoclastic bone resorption, altering both the number and/or resorptive activity of osteoclasts. There is suggestive evidence in animals and man that calcitonin may promote bone and collagen formation via an increase in osteoblastic activity. However, the exact role of calcitonin on osteoblastic activity has not been fully established.
Calcitonin decreases the rate of bone turnover in conditions with an increased rate of bone resorption and formation, such as active Paget's disease, malignant osteolysis and some forms of osteoporosis characterised by a high bone turnover. This can be measured biochemically as a decrease in urine hydroxyproline excretion and a decrease in serum alkaline phosphatase levels.
Calcitonin treatment of Paget's disease may relieve bone pain, lower skin temperature over involved bone, decrease excessive cardiac output, stabilise hearing and allow radiographic and histological regression of bone lesions. Clinical experience demonstrates that salcatonin possesses analgesic activity. Investigations have shown binding sites specific to salcatonin in some areas of the central nervous system.
Calcitonin increases the excretion of phosphate, calcium and sodium by decreasing their tubular reabsorption.
Calcitonin is effective in diminishing hypercalcaemia in patients with hyperparathyroidism, vitamin D intoxication and osteolytic bone metastases.
The gastrointestinal effects attributed to calcitonin include the inhibition of gastric acid secretion, stimulation of the intestinal secretion of water and electrolytes, inhibition of pancreatic enzyme secretion and modifications of glucose insulin relationships. Calcitonin probably has no major effects on the intestinal absorption of calcium and does not affect gastrointestinal motility.

Mechanism of action.

It has been postulated that cyclic AMP is involved in the secretion of calcitonin, which binds specifically to the membrane receptors of the target tissue and stimulates cyclic AMP accumulation.

Pharmacokinetics.

Absorption.

Due to its polypeptide nature, salcatonin is not administered by the oral route as intestinal proteases inactivate the drug. It is administered by s.c., i.m., or i.v. routes. The onset of action is immediate after intravenous administration and occurs in about 15 minutes following intramuscular or subcutaneous administration, with peak plasma levels being attained within one hour. After subcutaneous administration, peak plasma levels are reached in about 23 minutes. The bioavailability of salcatonin is about 70% following both i.m. and s.c. administration.
Protein binding: 30-40%.
Volume of distribution: 0.15-0.30 litres/kg.

Metabolism.

Studies suggest that salcatonin is rapidly metabolised to unidentified and inactive metabolites primarily in the kidneys, but also in the blood and peripheral tissues. The metabolic clearance rate of salcatonin appears to be lower than either porcine or synthetic human calcitonin.

Excretion.

Up to 95% of salcatonin and its metabolites are excreted by the kidney, of which less than 2% is unchanged drug.

Half-life.

The absorption half-life is reported to be 8-22 minutes. The elimination half-life is about 60 minutes following i.m. administration and 60-90 minutes following s.c. or i.v. administration. The apparent biological half-life is several hours.

Indications

Active Paget's disease in patients who do not respond to alternative treatments or for whom such treatments are not suitable.
Hypercalcaemia.

Contraindications

Pregnancy and lactation (see Precautions, Use in pregnancy and Use in lactation).
Hypersensitivity to salcatonin or to any of the excipients in the formulation.

Precautions

Hypersensitivity reactions.

Being a polypeptide, calcitonin may give rise in rare cases to localised or generalised hypersensitivity reactions. Allergic type reactions, including single cases of anaphylactic shock, have been reported. If such symptoms are observed and can definitely be ascribed to the effect of the drug, treatment should be discontinued. (See Escape phenomena.)

Malignancies.

Meta-analyses of randomised controlled trials conducted in patients with osteoarthritis and osteoporosis have shown that long-term calcitonin use is associated with a small but statistically significant increase in the incidence of malignancies compared to placebo (see Adverse Effects). These meta-analyses demonstrated an increase in the absolute rate of occurrence of malignancies for patients treated with calcitonin compared to placebo which varied between 0.7% and 2.36%. Numerical imbalances between calcitonin and placebo were observed after 6 to 12 months of therapy. The increased malignancy risk with the meta-analysis was heavily influenced by a single large 5 year trial, which had an observed risk difference of 3.4%. Imbalances in risk were still observed when analyses excluded basal cell carcinoma. There were several limitations with the meta-analysis data and it is not clear how these limitations affect the results. A mechanism for this observation has not been identified. Patients in these trials were treated with oral or intranasal formulations however it cannot be excluded that an increased risk also applies when calcitonin is administered subcutaneously, intramuscularly or intravenously. The benefits for the individual patient should be carefully evaluated against possible risks (see Adverse Effects).

Sensitivity testing.

It is advisable to perform a scratch or intradermal skin test to determine sensitivity before administration, as calcitonin is a protein. A 1 in 100 dilution should be used.

Escape phenomena.

Escape phenomena seen sometimes in long-term therapy are usually due to a saturation of the binding sites rather than to the development of antibodies. After an interruption of treatment, the therapeutic response to Miacalcic is restored. (See Adverse Effects, Immunological.)

Use in children.

Long-term safety and efficacy have not been established in children, and therefore calcitonin is not recommended for paediatric use except in exceptional circumstances. Calcitonin has been used in familial hyperphosphatasaemia. Unless the physician considers that prolonged treatment is indicated on compelling medical grounds, prolonged treatment should be avoided as calcitonin may interfere with bone growth. In the absence of specific dosage experience in children, the doses relating to bodyweight should be used cautiously. Dosage should be adjusted to desired effect.

Use in pregnancy.

(Category B2)
There is no information on the drug's use in pregnancy and therefore the drug should not be used in pregnant women or those likely to become pregnant unless the expected benefits outweigh any potential risk.

Use in lactation.

Animal studies suggest that calcitonin might suppress lactation in nursing mothers. Treatment during lactation is not recommended.

Effects on ability to drive and use machines.

Miacalcic may cause fatigue, dizziness and visual disturbances (see Adverse Effects) which may impair the reactions of the patient. Patients should be warned that these effects may occur, in which case they should not drive or use machines.

Interactions

Concomitant use of calcitonin and lithium may lead to a reduction in plasma concentrations. The dose of lithium may need to be adjusted.

Adverse Effects

For Miacalcic ampoules no recent frequency estimations based on clinical trials are available. Estimations based on the number of postmarketing reports received lead to frequencies lower than those reported in controlled clinical trials with Miacalcic nasal spray. For events attributed to the systemic administration of salcatonin therefore the same (higher) frequency categories as used for the nasal spray were also used for Miacalcic ampoules.
Adverse reactions below 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. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): 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).

Immune system disorders.

Rare: hypersensitivity+. Very rare: anaphylactic and anaphylactoid reactions^, anaphylactic shock.

Nervous system disorders.

Common: dizziness, headache, dysgeusia. Uncommon: paraesthesia.

Eye disorders.

Uncommon: visual impairment.

Vascular disorders.

Common: flushing*. Uncommon: hypertension.

Gastrointestinal disorders.

Common: nausea, diarrhoea, abdominal pain. Uncommon: vomiting.

Skin and subcutaneous tissue disorders.

Rare: pruritus, rash generalised (including maculopapular eruption urticaria).

Musculoskeletal and connective tissue disorders.

Common: arthralgia. Uncommon: musculoskeletal pain, muscle spasms.

Renal and urinary disorders.

Rare: polyuria.

General disorders and administration site conditions.

Common: fatigue. Uncommon: injection site reaction (including pain on injection), influenza-like illness (including chills and fever), oedema (facial, peripheral and generalised).
^Reactions resulting in tachycardia, hypotension and collapse.
*Facial flushing accompanied by a sensation of heat.
+Allergic reactions manifested in some cases by rash, hypertension or peripheral oedema.
The gastrointestinal disorder may include nausea, abdominal pain, diarrhoea and vomiting and is usually a transient, dose related phenomenon, and occurs more frequently after i.v. than i.m. or s.c. administration. This problem may be overcome either by concomitant antiemetic therapy or by subdividing the daily dose. A temporary dose reduction may be necessary in a few cases.

Immunological.

Salcatonin binding antibodies may develop in some patients after several months (generally of low titre and more likely to occur with higher doses). However, the development of antibodies does not necessarily cause clinical resistance but may do so in a small number of cases.

Malignancies.

Meta-analyses of randomised controlled trials conducted in patients with osteoarthritis and osteoporosis have shown that long-term calcitonin use is associated with a small but statistically significant increase in the incidence of malignancies compared to patients treated with placebo. A mechanism for this observation has not been identified (see Precautions).

Postmarketing experience.

The following reactions have been identified through postmarketing reporting and literature review. Because this adverse drug reaction has been reported voluntarily from a population of uncertain size, it is not possible to reliably estimate its frequency which is therefore categorised as not known.

Central and peripheral nervous system.

Tremor.

Metabolism and nutrition disorders.

Hypocalcaemia.

Skin and subcutaneous tissue disorders.

Urticaria.

Dosage and Administration

Note.

1 IU = 1 MRC unit. One unit corresponds to 0.2 microgram of the pure peptide.
Miacalcic may be administered subcutaneously, intramuscularly or intravenously; local and systemic tolerance is generally good with all 3 routes of administration at recommended dosages.
Due to the association between occurrence of malignancies and long-term calcitonin use (see Precautions), the treatment duration in all indications should be limited to the shortest period of time possible and using the lowest effective dose.

Hypercalcaemia.

Treatment should be limited to the shortest duration possible. The recommended dose is 5-10 IU per kg daily, administered by slow i.v. infusion in 500 mL normal saline over at least six hours, or by slow intravenous injection in 2 to 4 divided doses spread over the day.
Alternatively, the same daily dose may be given by one or more s.c. or i.m. injections. If the volume of Miacalcic for injection exceeds 2 mL, i.m. injection is preferable and multiple sites of injection should be used.
Rehydration should be considered. Emergency treatment is followed by specific treatment of the underlying disease, if required.

Paget's disease.

80-100 IU daily by s.c. or i.m. injection. In some cases the injections may be given only every second day. In particular, after improvement of the objective and subjective symptoms, an injection of 50 IU per day may be sufficient.
The duration of treatment depends on the therapeutic indication and the patient's response. The need for ongoing therapy should be assessed by a health practitioner on a regular basis.
Following cessation of chronic treatment, return of biochemical values to pretreatment levels may take weeks or years.

Mode of administration.

For intramuscular or subcutaneous use.

The solution requires no further dilution. (See Presentation.)
Patients who are instructed in the self administration of subcutaneous injections must receive precise directions from the physician or the nurse.

For intravenous infusion.

Intravenous infusion is the most effective method of administration and should always be used in emergency or severe cases of hypercalcaemia. Dilute the required amount of salcatonin in 500 mL of 0.9% sodium chloride and infuse over at least 6 hours.

Geriatric.

Use adult dosage with care. It should be noted that most patients with Paget's disease are elderly.

With impaired liver function.

No information available.

With impaired renal function.

A smaller dose may be required in renal impairment, as calcitonin is metabolised and excreted predominantly by the kidneys.

Overdosage

Clinical features.

Nausea, vomiting, flushing and dizziness are known to be dose dependent when Miacalcic is administered parenterally. Nausea and vomiting have occurred following administration of Miacalcic as a parenteral overdose, but severe adverse reactions due to overdosage have so far not been reported.
Contact the Poison Information Centre on 131 126 for advice on management.

Presentation

Solution for injection, 50 IU/1 mL, 100 IU/1 mL: 5's (ampoule).

Storage

Store between 2 to 8°C. Refrigerate. Do not freeze.

Poison Schedule

S4.