Veprena^® (Spray) Instructions for Use

Marketing Authorization Holder

Nativa, LLC (Russia)

ATC Code

H05BA01 (Calcitonin (synthetic salmon))

Active Substance

Calcitonin (Rec.INN registered by WHO)

Dosage Form

Veprena®

Metered nasal spray 200 IU/1 dose: 2 ml bottle 1 or 2 pcs.

Dosage Form, Packaging, and Composition

* 1 IU corresponds to approximately 0.2 mcg of synthetic salmon calcitonin.

2 ml (14 doses) – bottles with a dosing device (1) – cardboard packs.
2 ml (14 doses) – bottles with a dosing device (2) – cardboard packs.

Clinical-Pharmacological Group

Drug affecting phosphorus-calcium metabolism, used for the treatment of osteoporosis

Pharmacotherapeutic Group

Calcium-phosphorus metabolism regulator

Pharmacological Action

Calcitonin is a hormone produced by the C-cells of the thyroid gland, is an antagonist of parathyroid hormone and, together with it, participates in the regulation of calcium metabolism in the body.

The structure of all calcitonins is represented by a single chain of 32 amino acids and a ring of 7 amino acid residues at the N-terminus, the sequence of which is not the same in different species. Salmon calcitonin has a higher affinity for receptors (compared to mammalian calcitonins), its action is most pronounced both in strength and duration.

Salmon calcitonin suppresses osteoclast activity by acting on specific receptors, significantly reduces the rate of bone turnover to a normal level in conditions with an increased rate of resorption (in osteoporosis).

Calcitonin has analgesic activity in bone pain, which is due to a direct effect on the central nervous system.

Already after a single application of the drug, a clinically significant response is noted, which is manifested by an increase in the urinary excretion of calcium, phosphorus and sodium (due to a decrease in their tubular reabsorption) and a decrease in the excretion of hydroxyproline.

According to available data, with prolonged use of calcitonin, a significant and persistent decrease in the level of biochemical markers of bone metabolism, such as serum C-telopeptides (sCTX) and bone isoenzymes of alkaline phosphatase, is achieved.

The use of the drug leads to a statistically significant increase in bone mineral density in the lumbar vertebrae, which is determined already in the first year of treatment and persists for up to 5 years; ensures the maintenance of mineral density in the femur.

The use of the drug at a dose of 200 IU per day in combination with vitamin D and calcium preparations leads to a statistically and clinically significant reduction in the risk of developing new vertebral fractures and a reduction in the frequency of multiple vertebral fractures.

Calcitonin reduces gastric secretion and the exocrine function of the pancreas.

Pharmacokinetics

Absorption. The drug is rapidly absorbed through the nasal mucosa, its C_max in plasma is reached within the first hour (on average about 10 minutes). Bioavailability is 3-5%. When using the drug in doses exceeding the recommended ones, the AUC increases, while bioavailability does not increase.

Determination of the concentration of salmon calcitonin in plasma, as well as the concentrations of other polypeptide hormones, seems to be of little value, since the level of concentrations cannot predict the therapeutic efficacy of the drug. The activity of the drug is assessed by clinical efficacy indicators.

Salmon calcitonin does not cross the placental barrier.

Metabolism. T_1/2 is about 20 minutes. With repeated use of drugs based on calcitonin, no accumulation is noted.

Indications

• Treatment of postmenopausal osteoporosis;
• Bone pain associated with osteolysis and/or osteopenia;
• Paget’s disease (osteitis deformans);
• Neurodystrophic diseases (synonyms: algoneurodystrophy, Sudeck’s atrophy) of various etiologies, caused by various predisposing factors, including such as post-traumatic osteoporosis, reflex dystrophy, shoulder-scapular syndrome, causalgia, drug neurotrophic disorders.

ICD codes

Dosage Regimen

The drug is used intranasally.

It is recommended to administer the nasal spray alternately: first in one, then in the other nostril.

For the treatment of osteoporosis 200 IU per day is recommended.

For the prevention of progressive bone loss, adequate doses of calcium and vitamin D are recommended simultaneously with the use of the nasal spray. Treatment should be carried out for a long time.

For bone pain associated with osteolysis and/or osteopenia the daily dose of the drug is 200 – 400 IU daily. The daily dose of 200 IU can be administered at one time. Higher doses should be divided into several administrations. The dose should be adjusted according to the individual needs of the patient. It may take several days to achieve the full analgesic effect. During long-term therapy, the initial daily dose is usually reduced and/or the interval between administrations is increased.

The duration of treatment is at least 3 months, if necessary it can be longer. The daily dose should be adjusted according to the individual needs of the patient.

Paget’s disease the daily dose of the drug is 200 IU. In some cases, at the beginning of treatment, a dose of 400 IU per day may be required, administered in several doses.

In Paget’s disease, the duration of treatment should be from several months to several years. Against the background of treatment, a significant decrease in the concentration of alkaline phosphatase in the blood and the excretion of hydroxyproline in the urine is noted, sometimes to normal values. In some cases, after an initial decrease in the values of these indicators, their increase may occur again. In these cases, the doctor, guided by the clinical picture, should decide whether to stop treatment and when it can be resumed. One or several months after discontinuation of treatment, bone metabolism disorders may reappear; in this case, a new course will be required.

Neurodystrophic diseases the daily dose of the drug is 200 IU, daily for 2-4 weeks. An additional prescription of 200 IU every other day for 6 weeks is possible, depending on the dynamics of the patient’s condition.

Use in elderly patients and specific patient groups: according to available data, there is no need to change the dosing regimen for elderly patients and patients with reduced renal or hepatic function.

Instructions for use

• Never shake the bottle, as this may cause air bubbles to form inside the bottle and, as a result, incorrect dosing of the drug.
• First use: Remove the protective cap, then, holding the device with one or two hands strictly vertically, press the plunger three times, which will allow air to escape from the tube. Possible splashing of the solution is provided for and does not affect the subsequent number of doses.
• Subsequent use: Remove the protective cap. Tilt your head slightly forward and insert the tip into the nostril. For more even distribution of the solution, the tip should be in line with the nasal passage. Press the plunger once. Remove the tip from the nose and take several vigorous breaths through the nose to prevent the drug from leaking out. You should not clean your nose immediately after using the drug. If two administrations are prescribed at one time, the second administration should be made into the other nostril.

Gently wipe the tip with a clean, dry cloth, be sure to put on the protective cap.

Adverse Reactions

Adverse effects such as nausea, vomiting, dizziness, mild facial flushing, arthralgia have been reported. Polyuria and chills may develop, which usually disappear on their own, and only in some cases require a temporary reduction in the dose of the drug. The frequency of adverse events, possibly associated with the use of the drug, is estimated as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000), including isolated reports.

Immune system disorders rare – hypersensitivity; very rare – anaphylactic or anaphylactoid reactions, anaphylactic shock.

Nervous system disorders common – headache, dizziness, taste disorders.

Sensory organ disorders uncommon – visual disturbances.

Cardiovascular system disorders common – flushing; uncommon – arterial hypertension.

Respiratory system disorders very common – nasal pain, congestion, nasal mucosal edema, sneezing, rhinitis, nasal dryness, allergic rhinitis, nasal mucosal erythema, irritation, unpleasant odor, excoriation in the nasal cavity; common – nosebleeds, sinusitis, ulcerative rhinitis, pharyngitis; uncommon – cough.

Digestive system disorders common – nausea, abdominal pain, diarrhea; uncommon – vomiting.

Skin disorders rare – generalized rash.

Musculoskeletal system disorders common – arthralgia; uncommon – bone and muscle pain.

Urinary system disorders rare – polyuria.

General disorders and administration site conditions common – increased fatigue; uncommon – flu-like syndrome, facial edema, peripheral and generalized edema, rare – chills; reactions at the site of drug administration – itching.

Contraindications

Hypersensitivity to synthetic salmon calcitonin or any other component of the drug.

The drug is not recommended for use in children under 18 years of age due to the lack of data on efficacy and safety. Use during pregnancy and breastfeeding: Calcitonin does not have embryotoxic or teratogenic effects, does not cross the placental barrier.

There are no clinical data on the safety of the drug during pregnancy. In this regard, the drug should not be used in women during pregnancy.

During therapy with the drug, it is recommended to stop breastfeeding, as it is not known whether salmon calcitonin passes into breast milk.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding: Calcitonin does not have embryotoxic or teratogenic effects, does not cross the placental barrier.

There are no clinical data on the safety of the drug during pregnancy. In this regard, the drug should not be used in women during pregnancy.

During therapy with the drug, it is recommended to stop breastfeeding, as it is not known whether salmon calcitonin passes into breast milk

Use in Hepatic Impairment

Patients with reduced liver function do not need to change the dosing regimen of the drug.

Use in Renal Impairment

Patients with reduced renal function do not need to change the dosing regimen of the drug.

Pediatric Use

The drug is not recommended for use in children under 18 years of age due to the lack of data on efficacy and safety.

Geriatric Use

Elderly patients do not need to change the dosing regimen of the drug.

Special Precautions

Salmon calcitonin is a peptide, so there is a possibility of systemic allergic reactions. There are reports of allergic reactions, including isolated cases of anaphylactic shock, which occurred in patients receiving calcitonin in the form of a nasal spray.

If hypersensitivity to salmon calcitonin is suspected, a doctor should be consulted before starting treatment with the drug.

With long-term therapy, the formation of antibodies to calcitonin is possible, but this, as a rule, does not affect clinical efficacy.

In patients with Paget’s disease receiving long-term therapy, the phenomenon of tolerance may be a consequence of saturation of binding sites and is apparently not related to the formation of antibodies. The therapeutic effect of the drug is restored after a break in treatment.

Influence on the ability to drive vehicles and work with moving mechanisms. Currently, there is no data on the possible effect of Veprena on the ability to drive a car and operate machinery. Nevertheless, given that the use of the drug may lead to the development of such side effects as dizziness, increased fatigue and visual disturbances, it is recommended to be careful when driving a car or working with machinery.

Overdose

In case of overdose, one can expect – nausea, vomiting, flushing and dizziness. There are reports of the use of calcitonin at a dose of up to 1600 IU once and at a dose of 800 IU per day for 3 days, while no serious adverse events were noted. There are reports of isolated cases of overdose. Treatment is symptomatic.

In case of overdose, hypocalcemia may develop with symptoms such as paresthesia, muscle twitching.

Treatment administration of calcium gluconate.

Drug Interactions

With the simultaneous appointment of calcitonin and lithium preparations, it may be necessary to adjust the dose of the latter, since a decrease in the plasma concentration of lithium is possible.

Storage Conditions

In a place protected from light at a temperature of 2 to 8°C (46.4°F). Keep out of the reach of children.

Shelf Life

Shelf life . 2 years. Do not use after the expiration date indicated on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.