Miacalcic密鈣息

Miacalcic

calcitonin

Manufacturer:

NT Pharma

Distributor:

Zuellig
/
Four Star
Full Prescribing Info
Contents
Synthetic salmon calcitonin.
Description
One international unit (IU) is equivalent to 0.2 mcg of synthetic salmon calcitonin. Excipients are: Benzalkonium chloride, sodium chloride, hydrochloric acid (for pH adjustment), water (purified, Eur.P.).
Action
Pharmacology: Pharmacodynamics: All calcitonin structures consist of 32 amino acids in a single chain with a ring of seven amino-acid residues at the N-terminus that differs in sequence from species to species. Salmon calcitonin is more potent and longer acting than calcitonins from mammalian species due to its greater affinity for receptor binding sites.
By inhibiting osteoclast activity via its specific receptors, salmon calcitonin markedly reduces bone turnover to a normal level in conditions with an increased rate of bone resorption such as osteoporosis. Salmon calcitonin has also been shown both in animal models and in humans to have analgesic activity, probably primarily via a direct effect on the central nervous system.
Miacalcic Nasal Spray produces a clinically relevant biological response in humans after only a single dose, as shown by an increase in the urinary excretion of calcium, phosphorus, and sodium (by reducing their tubular re-uptake) and a decrease in the urinary excretion of hydroxyproline. Long-term administration of Miacalcic Nasal Spray (up to 5 years of treatment) significantly suppresses biochemical markers of bone turnover such as serum C-telopeptides (sCTX) and skeletal isoenzymes of alkaline phosphatase.
Miacalcic Nasal Spray results in a statistically significant 1-2% increase in lumbar spine Bone Mineral Density (BMD) which is evident from year 1 and is sustained for up to 5 years. Hip BMD is preserved.
Administration of 200 IU/day Miacalcic Nasal Spray results in a statistically and clinically significant 36% decrease in the risk of developing new vertebral fractures relative to treatment with vitamin D and calcium alone (“placebo”). Additionally, the incidence of multiple new vertebral fractures is reduced by 35%, also compared to “placebo”.
Calcitonin reduces gastric and exocrine secretion pancreatic secretion.
Pharmacokinetics: The bioavailability of Miacalcic Nasal Spray relative to parenteral administration is between 3 and 5%. Miacalcic is absorbed rapidly through the nasal mucosa and peak plasma concentrations are attained within the 1st hour of administration (median about 10 minutes). The half-life of elimination has been calculated to be around 20 minutes and no evidence of accumulation was observed with multiple dosing. Doses higher than the recommended dose result in higher blood levels (as shown by an increase in AUC) but relative bioavailability does not increase. As is the case with other polypeptide hormones, there is very little value in monitoring plasma levels of salmon calcitonin since these are not directly predictive of the therapeutic response. Hence, Miacalcic activity should be evaluated by using clinical parameters of efficacy.
Toxicology: Preclinical Safety Data: Conventional long-term toxicity, reproduction, mutagenicity and carcinogenicity studies have been performed in laboratory animals.
Daily intranasal administration for 26 weeks of a placebo containing 0.01% benzalkonium chloride or of high doses of a calcitonin formulation containing 0.01% benzalkonium chloride was well tolerated by monkeys. No treatment-related changes to the respiratory tract were observed. Dogs receiving salmon calcitonin with 0.01% benzalkonium chloride daily by intranasal administration for 4 weeks did not reveal any relevant abnormal findings in the nasal cavity and upper respiratory tract. Miacalcic Nasal Spray with 0.01% benzalkonium chloride did not change the nasal ciliary beat frequency of guinea-pigs or of Pagetic patients over 4 weeks and 6 months of treatment, respectively.
Minor effects in toxicity studies are attributable to the pharmacological action of salmon calcitonin. Salmon calcitonin is devoid of embryotoxic, teratogenic and mutagenic potential. Toxicity and carcinogenicity studies have shown that salmon calcitonin increases the incidence of pituitary tumours in rats at exposures lower than those likely from clinical use. However, further preclinical studies, particularly a mouse carcinogenicity study, in which the maximum exposure was more than 7000 times greater than that in humans following a dose of 200 IU, suggested that pituitary tumor induction is specific to the rat. In vivo nonclinical safety data do not support an association of salmon calcitonin treatment with malignancies and do not provide any evidence for tumor progression.
Clinical data including for patients treated for up to 24 months in a study with matched controls, failed to show any pituitary-related changes. In addition, calcitonin receptors in the human pituitary have been shown to be very few in number or even to be completely absent.
Furthermore, there have been no reports of adverse events relating to pituitary tumors in patients.
There is therefore enough evidence to conclude that pituitary tumor induction is a rat-specific event and that rat pituitary tumors have no relevance for the clinical use of Miacalcic.
Indications/Uses
Bone pain associated with osteolysis and/or osteopenia.
Paget's disease of bone (osteitis deformans) only in patients who do not respond to alternative treatments or for whom such treatments are not suitable.
Neurodystrophic disorders (synonymous with algodystrophy or Sudeck's disease): Neurodystrophic disorders caused by various etiological and predisposing factors eg, posttraumatic painful osteoporosis, reflex dystrophy, shoulder-arm syndrome, causalgia, drug-induced neurotrophic disorders.
Dosage/Direction for Use
Bone Pain Associated with Osteolysis and/or Osteopenia: 200-400 IU daily. Up to 200 IU may be administered as a single dose; in cases where a higher dosage is required, it should be given in individual doses.
Dosage should be adjusted to the individual patient's needs.
It may take several days of treatment until the analgesic effect is fully developed. For continuing therapy, the initial daily dosage can usually be reduced and/or the interval between administrations is prolonged.
Paget's Disease: 200 IU daily in single dose or divided doses. In some cases 400 IU in divided doses may be necessary at the beginning of therapy.
The duration of treatment depends on the therapeutic indication and the patient’s response. Dosage should be adjusted to the individual patient’s needs.
Treatment with Miacalcic markedly reduces serum alkaline phosphatase and urinary hydroxyproline excretion, often to normal levels. However, in rare cases, alkaline phosphatase and hydroxyproline excretion levels may rise after an initial fall; the physician must then judge from the clinical picture whether treatment should be discontinued and when it may be resumed.
Disorders of bone metabolism may recur one or several months after treatment has been discontinued, necessitating a new course of Miacalcic therapy.
Neurodystrophic disorders: Early diagnosis of neurodystrophic disorders is essential and treatment should start as soon as the diagnosis is confirmed.
The recommended dose is 200 IU daily in a single dose over a period of 2-4 weeks. An additional 200 IU may be administered every 2nd day for up to 6 weeks depending on clinical progress.
Development of antibodies:
Treatment should be limited to the shortest duration possible. Antibodies to calcitonins may develop in patients under long-term therapy; clinical efficacy is usually not affected, however. Escape phenomena, which occur in particular in patients with Paget’s disease receiving long-term therapy, may be due to saturation of the binding sites and are apparently not related to the development of antibodies. Following interruption of treatment, the therapeutic response to Miacalcic is restored.
Special Population: Use in children:
There is limited experience with the use of Miacalcic Nasal Spray in children, therefore no recommendations can be given for this patient population.
Use in elderly:
Extensive experience with the use of Miacalcic Nasal Spray in the elderly has shown no evidence of reduced tolerance or altered dosage requirements. The same applies to patients with altered renal or hepatic function, although no formal studies have been carried out in this specific patient population.
Administration: It is recommended to administer Miacalcic Nasal Spray per actuation to alternating nostrils.
Due to the association between occurence 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.
Overdosage
Nausea, vomiting, flushing and dizziness are known to be dose dependent when Miacalcic is administered parenterally. Such events might therefore also be expected to occur in association with an overdose of Miacalcic Nasal Spray. However, Miacalcic Nasal Spray has been administered at up to 1600 IU as a single dose and up to 800 IU per day for three days without causing any serious adverse event. Isolated cases of overdose have been reported. Treatment would be symptomatic.
Contraindications
Hypersensitivity to Miacalcic or to any of the excipients.
Special Precautions
Because salmon calcitonin is a peptide, the possibility of systemic allergic reactions exists and allergic-type reactions including single cases of anaphylactic shock have been reported in patients receiving Miacalcic Nasal Spray. Skin testing with diluted sterile solution from Miacalcic Ampoules should be considered prior to treatment with Miacalcic in patients with suspected sensitivity to salmon calcitonin.
Meta-analyses of randomized 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 Reactions). 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 6-12 months of therapy. A mechanism for this observation has not been identified. Patients in these trials were treated with oral or intra-nasal formulations. The benefits for the individual patient should be carefully evaluated against possible risks (see Adverse Reactions).
Use in Pregnancy: Since no studies have been carried out in pregnant women, Miacalcic should not be administered to such patients. Animal studies have, however, shown that Miacalcic is devoid of embryotoxic and teratogenic potential.
Use in Lactation: Since no studies have been carried out in nursing mothers and it is not known whether salmon calcitonin is excreted into human milk, breast-feeding during treatment is not recommended.
Effects on Ability to Drive and Use Machines: No studies exist on the effects of Miacalcic on the ability to drive and use machines. Miacalcic may cause fatigue, dizziness and visual disturbances (see Adverse Reactions), 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 use machines.
Use In Pregnancy & Lactation
Use in Pregnancy: Since no studies have been carried out in pregnant women, Miacalcic should not be administered to such patients. Animal studies have, however, shown that Miacalcic is devoid of embryotoxic and teratogenic potential.
Use in Lactation: Since no studies have been carried out in nursing mothers and it is not known whether salmon calcitonin is excreted into human milk, breast-feeding during treatment is not recommended.
Adverse Reactions
Local adverse events are generally mild (in about 80% of reports) and require discontinuation of the treatment in less than 5% of cases.
Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥ 1/10); common (≥1/100, < 1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000), including isolated reports (see table).

Click on icon to see table/diagram/image

Meta-analyses of randomized controlled trials conducted in patients with osteoarthritis and osteoporosis have shown that long term calcitonin 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).
Adverse drug reactions from spontaneous reports and literature cases (frequency not known): The following reaction has been identified through post-marketing 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 categorized as not known.
Central and peripheral nervous system: Tremor.
Drug Interactions
Concomitant use of calcitonin and lithium may lead to a reduction in plasma lithium concentrations. The dose of lithium may need to be adjusted.
Caution For Usage
Instructions for Use and Handling: The instructions for use and handling of the Miacalcic Nasal Spray included in the section Information for patients must be read carefully before the spray is used for the first time.
The pump must be primed before first use: Pull up the protective cap, holding the bottle in an upright position, press down the upper part until it clicks. Repeat twice. After the first time the dose counter window shows white and red lines, after the second time white, and after the third time green. It is now ready for use.
Note:
Miacalcic Nasal Spray must be kept out of the reach and sight of children.
Information for Patients: When and How to Use Miacalcic Nasal Spray: This medicine is for administration into the nostrils only. Switch between each nostril should be observed in every use of Miacalcic Nasal Spray.
Micalcic is stored in a refrigerator. Before using it, the spray should reach room temperature.
Instructions for use/handling of Miacalcic Nasal Spray: If the spray mechanism should become blocked, this may be resolved by pressing down firmly on the pump; do not attempt to unblock it by using a sharp pointed object as this may cause damage.
Preparing a New Nasal Spray Bottle for Use: Never shake the nasal spray bottle as this could cause air bubbles, which may affect your dose.
The dose counter window of a new nasal spray bottle is in the position marked red. First, remove the protective cap. Hold the nasal spray upright in 1 or 2 hands and press down firmly on the pump 3 times.
This primes the new spray by clearing air out of the dip tube. Priming is done only once when starting a new spray. Do not worry if a little solution sprays out; this is normal.
As the pump is pressed, the dose counter window changes. When green is showing in the dose counter window, the new nasal spray is ready to use.
Using the Nasal Spray: With the protective cap removed, bend the head slightly forward and insert the nozzle into 1 of the nostrils. Try to hold the nasal spray upright.
Press the pump firmly once only.
Remove the nasal spray from the nose and breathe in deeply through the nostrils to help keep the solution in the nose.
If told to take 2 puffs at a time, repeat procedure in the other nostril.
After use, clean the nozzle with a dry tissue and replace the protective cap.
Checking the Counter: In every use the nasal spray, the number in the dose counter window will change. The number displayed tells how many puffs have been taken. Miacalcic Nasal Spray is guaranteed to deliver 14 metered doses. One may be able to obtain 2 extra doses.
When the dose counter window a red "16" mark, 16 puffs have been used and the nasal spray finished. A little liquid may be left in the nasal spray bottle, but this is normal.
Storage
Unopened nasal spray bottles should be stored in a refrigerator (2-8°C). Once opened, the nasal spray bottle must be kept at room temperature; it should be kept in the upright position and used for a maximum of 4 weeks.
Keep the bottle upright at all times to reduce the risk of air bubbles entering the dip tube.
ATC Classification
H05BA01 - calcitonin (salmon synthetic) ; Belongs to the class of anti-parathyroid hormones, calcitonin preparations. Used in the management of calcium homeostasis.
Presentation/Packing
Inj 50 IU/mL x 1 mL x 5's. 100 IU/mL x 1 mL x 5's. Nasal spray 50 IU x 14 actuations. 100 IU x 14 actuations. 200 IU x 14 actuations.
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