Fosavans - instructions for use, dose, side effects, contraindications

Active substanceAlendronic acid + KololecalciferolAlendronic acid + Kololecalciferol

Similar drugsTo uncover

pills inwards

MERC SHARP and DOMA IDEA, Inc. Switzerland

Dosage form: & nbspPills

Composition:

For 1 tablet:

Active substances: sodium alendronate 91.37 mg (corresponding to 70 mg of alendronic acid) and vitamin D₃* 100,000 IU / g 26.67 (25.45-28) mg (corresponding to 70 μg (2800 ME) colcalciferol).

* in the form of granules containing, in addition to vitamin D₃, triglycerides, gelatin, sucrose, modified food starch, butylated hydroxytoluene and sodium aluminum silicate.

Excipients: lactose anhydrous 62,32 (60,99-63,54) mg, cellulose microcrystalline 131.0 mg, silicon dioxide colloid 0,812 mg, croscarmellose sodium 9,740 mg, magnesium stearate 3,087 mg.

Description:

Tablets from white to almost white, capsular form with an impression of "710" on one side and a figure in the form of a bone on the other side.

Pharmacotherapeutic group:osteoporosis remedy combined (bone resorption inhibitor + calcium-phosphorus exchange regulator).

ATX: & nbsp

M.05.B.B.03 Alendronic acid and colcalciferol

Pharmacodynamics:

Pharmacodynamics

The drug FOSAVANS® is a combined preparation containing two active substances: sodium alendronate and colcalciferol (vitamin D₃).

Alendronate

Sodium alendronate is a bisphosphonate that inhibits osteoclast-mediated bone resorption without directly affecting the formation of new bone tissue. Preclinical studies show that alendronate is predominantly localized in areas of active bone resorption. It suppresses the activity of osteoclasts, but does not affect the attraction and attachment of osteoclasts. During treatment with alendronate, normal bone tissue is formed.

Kolekaltsiferol (vitamin D3)

Vitamin D3 is formed in the skin by converting 7-dehydrocholesterol into a vitamin D3 under the influence of ultraviolet radiation. When there is a lack of sunlight, vitamin D3 is an indispensable component of food.

Vitamin D3 metabolized to 25-hydroxyvitamin D3 in the liver, where it accumulates. Conversion into active calcium-mobilizing hormone 1,25-dihydroxyvitamin D3 (calcitriol) occurs in the kidneys and is carefully regulated. The main effect of 1,25-dihydroxyvitamin D3 is to increase the intestinal absorption of calcium and phosphate, as well as in regulating the level of calcium in the plasma, excretion of calcium and phosphate by the kidneys, the formation of bone tissue and its resorption.

Vitamin D3 is necessary for the normal formation of bone tissue.Insufficient vitamin D3 develops in cases where sun exposure and vitamin intake D3 with food do not cover human needs. Hypovitaminosis causes a negative balance of calcium, loss of bone mass, an increased risk of fractures. In severe cases, vitamin deficiency leads to secondary hypoparathyroidism, hypophosphatemia, myasthenia, and osteomalacia, with a further increase in the risk of falls and fractures in patients with osteoporosis. Additional intake of vitamin D3 reduces these risks and their consequences.

Pharmacokinetics:

Alendronate
Suction

Bioavailability of alendronate in a dose of 5-70 mg when administered on an empty stomach no later than 2 hours before a standard breakfast is 0.64% in women and 0.6% in men from the intravenous dose. When taking alendronate on an empty stomach for an hour or half an hour before a standard breakfast, bioavailability decreased to 0.46% and 0.39%, respectively. In osteoporosis, alendronate is effective when applied on an empty stomach no later than 30 minutes before the first intake of food or liquid.

Bioavailability of alendronate in the combined preparation FOSAVANS® (70 mg / 2800 ME) is equivalent to its bioavailability in the alendronate 70 mg tablet.

Alendronate bioavailability is insignificant when administered concomitantly with food intake or within 2 hours after a standard breakfast. Simultaneous intake of alendronate with coffee or orange juice reduces its bioavailability by approximately 60%.

When taking prednisone orally (20 mg 3 times a day for 5 days), a clinically significant change in the bioavailability of alendronate does not occur in healthy individuals (the average increase in bioavailability was 20-44%).

Distribution

Studies in rats show that after intravenous administration at a dose of 1 mg / kg, alendronate is distributed into soft tissues, and then quickly redistributed into bones or excreted in the urine. In humans, the average volume of distribution in the equilibrium state, with the exception of bone tissue, is at least 28 liters. When administered orally at therapeutic doses, the concentration of alendronate in the blood plasma can not be determined analytically (less than 5 ng / ml). The binding to plasma proteins is approximately 78%.

Metabolism

There is no evidence that alendronate is metabolized in humans or animals.

Excretion

After a single intravenous injection of alendronate labeled ¹⁴C, approximately 50% of radioactive alendronate is excreted in the urine within 72 hours. The excretion of labeled alendronate with feces is insignificant or not determined. After a single intravenous injection of alendronate in a dose 10 mg its renal clearance is 71 ml / min, systemic clearance does not exceed 200 ml / min. Across 6 hours after intravenous administration, the concentration in the blood plasma is reduced by more than 95%. The final half-life in humans exceeds 10 years, which reflects the release of alendronate from the bones of the skeleton. Alendronate is not excreted through acid or basic renal transport in rats, its effect on the excretion of other drugs in this way in humans is not expected.

Kolekaltsiferol

Suction

When using the drug FOSAVANS® 70 mg / 2800 ME in healthy volunteers (male and female) after a morning sleep on an empty stomach for 2 hours before meals, the average area under the concentration-time curve (AUCo-120 _h) for the vitamin D3 (without adjustment for endogenous vitamin D3) is 296.4 ng * h / ml. The mean maximum concentration in the serum (C max) of the vitamin D3 is 5.9 ng / ml, and the mean time to reach the maximum serum concentration (Tmax) is 12 h. Bioavailability 2800 ME vitamin A D3 in the preparation of FOSAVANS® is similar to the bioavailability of 2800 ME vitamin A D3 at isolated reception.

Distribution

After absorption, the vitamin D3 enters the blood in the composition of chylomicrons and is quickly distributed mainly to the liver, where it is metabolized to its basic form of accumulation of 25-hydroxyvitamin D3. Smaller amounts are distributed into adipose and muscle tissue, where they are accumulated as a vitamin D3 for further gradual release into the bloodstream. Vitamin D3 circulates in the bloodstream associated with vitamin- Dbinding protein.
Metabolism

Vitamin D₃ It is rapidly metabolized by hydroxylation in the liver to 25-hydroxyvitamin D3, which in turn is metabolized in the kidneys to 1,25-dihydroxyvitamin D3, which is a biologically active form of vitamin. Before excretion of the vitamin, its further hydroxylation takes place. A small amount of vitamin D3 It is glucuronized before excretion.

Excretion

When taking radioactive vitamin D3 in healthy individuals, the average excretion of radioactive colcalciferol in the urine was 2.4% after 48 hours, with feces 4.9% after 4 days. In both cases, radioactive colcalciferol was excreted mainly in the form of metabolites.

The average half-life of the vitamin D3 after oral administration of the drug FOSAVANS® 70 mg / 2800 ME is approximately 24 hours.

Renal insufficiency

Preclinical studies show that alendronate not ingested in bone tissue is rapidly excreted in the urine. After repeated intravenous administration in a total dose of up to 35 mg / kg in animals, evidence of the deposition of the drug in the bones was not found. Despite the lack of clinical data, it is likely that, like in animals, the excretion of alendronate with urine worsens if there is a violation of renal function in patients. If the renal function is impaired, it is possible to increase the accumulation of alendronate in bone tissue.

Indications:

- The drug is intended for the treatment of postmenopausal osteoporosis in patients at risk for developing vitamin deficiency D. The drug reduces the risk of vertebral and hip fractures.

- The drug is designed to increase bone mass in men with osteoporosis.

Contraindications:

- Diseases of the esophagus slowing its emptying, for example, stricture or achalasia.

- Inability to sit or stand straight for 30 minutes.

- Hypersensitivity to any component of the drug.

- Hypocalcemia.

- Severe renal insufficiency (creatinine clearance <35 ml / min).

- Pregnancy and breastfeeding.

- Children's age (up to 18 years).

- Severe hypoparathyroidism.

- Severe Vitamin Deficiency D.

- Malabsorption of calcium.

- Hereditary lactase deficiency, sugarase / isomaltase deficiency, glucose galactose malabsorption.

Carefully:

- In case of exacerbation of diseases of the upper gastrointestinal tract (GI tract), such as dysphagia, esophageal diseases, gastritis, duodenitis or stomach ulcer (including anamnestic information about peptic ulcer, active gastrointestinal bleeding, surgical intervention in the upper gastrointestinal tract during the year before taking the drug FOSAVANS®).

- In diseases associated with hyperproduction of calcitriol (leukemia, lymphoma, sarcoidosis) and concomitant hypercalcemia and / or hypercalciuria.

Pregnancy and lactation:

The drug FOSAVANS® is intended for the treatment of women only in the post-menopausal period and is contraindicated in pregnancy and during breastfeeding.

Pregnancy

Data on the use of the drug FOSAVANS ® in pregnancy are absent. Studies of alendronate in animals have not revealed a direct damaging effect on pregnancy, embryo / fetus development, or postnatal development. The use of alendronate in rats during pregnancy caused disruption of labor due to hypocalcemia. Studies in animals have revealed hypercalcemia and reproductive toxicity in the use of vitamin A D in high doses.

Breast-feeding

It is not known whether alendronate passes into breast milk. Kolekaltsiferol and some of its active metabolites penetrate into breast milk.

Fertility

Bisphosphonates are embedded in the bone tissue, from which they are gradually released over many years. The amount of bisphosphonate that can build into the bone and, thus, get back into the systemic bloodstream, is directly proportional to the dose and duration of bisphosphonate.Data on the risk for the fetus in humans are not available, but there is a theoretical risk of damage to the fetus, especially the bone skeleton, if pregnancy occurs after the bisphosphonate course. The effect of variables such as the length of the period between discontinuing bisphosphonate therapy and conception, the specific form of the bisphosphonate and the route of administration (intravenous or oral) for this risk have not been studied.

Dosing and Administration:

1 tablet at least 30 minutes before the first meal, liquid or medicines (including antacids, preparations of calcium and vitamins), drinking down full glass of plain water (not mineral water). Other drinks (including mineral water), food and some medicines may reduce absorption of the drug FOSAVANS®.

To reduce the risk of irritation of the esophagus FOSAVANS should be accepted by the following rules:

1. Take in the morning immediately after lifting with bed at least 30 minutes before first meal, liquid, or medicines, drink full a glass of water (not mineral) for facilitate the receipt of the pill in stomach.

2. Do not chew the tablets and dissolve them in the mouth because of the possible formation of ulcers in the mouth and throat. Patients should not take a horizontal position until the first meal, which should be made at least 30 minutes after taking the drug FOSAVANS®.

3. FOSAVANS® should not be taken before going to bed or before going to bed. The recommended dose is 1 tablet 70 mg / 70 mcg once a week. The optimal duration of the drug is not established. The need to continue therapy with bisphosphonates should be evaluated on a regular basis. Patients should additionally take calcium supplements if their intake with food is insufficient. The need for additional vitamin intake D should be considered on an individual basis, given the amount of vitamin D, coming with vitamins or food. The drug FOSAVANS® satisfies the weekly requirement for a vitamin D, based on a daily dose of 400 ME.

For elderly patients and patients with mild and moderate renal failure (creatinine clearance from 35 to 60 ml / min), dose adjustments are not required.

If you miss an appointment, you must take 1 pill in the morning the next day.Do not take 2 doses on the same day, but in the future you should return to taking the drug 1 time a week on the day of the week that was chosen at the beginning of treatment.

Side effects:

The most frequently reported adverse reactions are unwanted reactions from the upper gastrointestinal tract, including abdominal pain, dyspepsia, ulcer of the esophagus, dysphagia, bloating and acid burp (>= 1/100, < 1/10).

The following adverse reactions were reported during clinical trials and / or post-marketing use of alendronate.

There were no additional undesirable reactions for the drug FOSAVANS.

The frequency of unwanted reactions is established as follows: very frequent (> 1/10); Frequent (> = 1/100, < 1/10); infrequent (> = 1/1000, < 1/100); rare (> = 1/10000, < 1/1000); very rare (< 1/10000).

Immune system disorders	Rare: hypersensitivity reactions, including hives and angioedema
Disorders from the metabolism and nutrition	Rare: symptomatic hypocalcemia, often against the background of factors predispositions
Disturbances from the nervous system	Frequent: headache, dizziness²Infrequent: violation of taste sensations²
Violations from the authorities view	Infrequent: inflammation of the eye (uveitis, scleritis, episcleritis)



Violations from	Frequent: systemic dizziness²
the sides of the ears
and labyrinthine
violations
Violations from	Frequent: abdominal pain, indigestion, constipation, diarrhea, flatulence, ulcer
side of the gastro-	esophagus³, dysphagia³, bloating, acidic eructation
intestinal tract	Infrequent: nausea, vomiting, gastritis, esophagitis³, erosion of the esophagus³, melena² Rare: esophageal stricture³, ulceration of the esophagus³, perforation, ulcers, upper gastrointestinal bleeding¹, gastroesophageal reflux
Violations from	Frequent: alopecia², itching²
the skin and	Infrequent: skin rash, erythema
subcutaneous tissue	Rare: skin rash with photosensitivity, severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis⁴
Violations from	Very Frequent: musculoskeletal (bones, muscles or joints)
side of the skeletal-	pain, sometimes severe pain^1,2
muscular and	Frequent: swelling of the joints2
connective	Rare: osteonecrosis of the jaw^1,4, atypical susceptible and
fabrics	diaphyseal hip fractures (unwanted bisphosphonate class reaction)³
General disorders	Frequent: asthenia, peripheral edema
and violations in place	Infrequent: transient symptoms as acute phase reaction
introduction of	(myalgia, malaise and rarely - fever), usually in connection with the onset of treatment²

See section "Special instructions".

²In clinical trials, the frequency was comparable for the drug group and the placebo group.

³See the section "Dosage and administration" and "Special instructions".

⁴This unwanted reaction was established during post-marketing surveillance. The frequency of "rare" was established on the basis of relevant clinical studies.

⁵Established in postmarketing applications.

Overdose:

Alendronate

When an overdose is possible hypocalcemia, hypophosphatemia and undesirable reactions from the upper part of the digestive tract: dyspepsia, heartburn, esophagitis, gastritis, stomach and esophagus ulcer.

There is no specific treatment for alendronate overdose. When an overdose of the drug FOSAVANS ® should be taken milk or antacids for the binding of alendronate. To avoid irritation of the esophagus, do not induce vomiting.Patients should maintain their vertical position.

Kolekalcisewol

Toxicity of the Vitamin D was not observed in healthy adults in chronic doses below 10,000 IU / day. In clinical trials involving healthy adults, vitamin intake D3 in a daily dose of 4000 ME within 5 months did not cause hypercalciuria and hypercalcemia.

Interaction:

Alendronate

Absorption of alendronate may be impaired if the drug is taken concomitantly with food, beverages (including mineral water), calcium preparations, antacids and other medications for oral use. In this regard, the interval between taking the drug FOSAVANS and other medicinal drugs taken orally should be at least 30 minutes.

Since the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with the development of erosive-ulcerative lesions of the gastrointestinal tract, caution should be exercised while using NSAIDs and alendronate. Kolekalishchefuel Olestra, mineral oils, orlistat, as well as sequestrants of bile acids (colestramine, colestipol) can obstruct suction vitamin A D.

Anticonvulsants, cimetidine, thiazide diuretics can accelerate the catabolism of the vitamin D.

Special instructions:

Alendronate

Undesirable reactions from the upper gastrointestinal tract

Alendronate can cause local irritation of the mucous membrane of the upper gastrointestinal tract. In connection with the possibility of worsening of the underlying disease during the administration of alendronate, caution should be exercised in prescribing patients with diseases of the upper gastrointestinal tract, for example, with dysphagia, esophageal disease, gastritis, duodenitis, ulcers, and serious gastrointestinal disease transferred to previous 12 months, for example, with peptic ulcer, gastrointestinal bleeding, surgical operation on the upper gastrointestinal tract, with the exception of pyloroplasty. For patients with a diagnosed Barrett's esophagus, the question of the appointment of alendronate should be decided on an individual basis by assessing the relationship between the expected benefit and the potential risk.

In the treatment of alendronate, there are cases of adverse reactions from the side of the esophagus (esophagitis, ulcer or erosion of the esophagus), sometimes occurring in severe form, requiring hospital treatment, and in rare cases complicated by the formation of stricture.In this regard, doctors need to pay special attention to any signs or symptoms that indicate possible abnormalities on the part of the esophagus, and patients should be warned about the need to stop taking alendronate and consult a doctor if symptoms of esophageal irritation such as dysphagia, swallowing pain or pain behind the sternum, the appearance or intensification of heartburn.

The risk of severe adverse events on the side of the esophagus is higher in those patients who violate the recommendations for alendronate and / or continue to take it when symptoms of esophageal irritation appear. It is extremely important to fully inform patients about the importance of compliance with the rules of taking the drug and make sure that they understand this. It should be warned that the risk of developing an esophageal lesion increases if these recommendations are not followed.

Although there was no increased risk in the extended clinical trial of alendronate, post-marketing reports reported rare cases of stomach and duodenal ulcer, sometimes severe and complicated.

Osteonecrosis of the jaw

In patients with cancer, with the treatment of which intravenous bisphosphonates were administered, there were cases of osteonecrosis of the jaw, mainly due to previous extraction of the tooth and / or local infection (including osteomyelitis). Many of them also received chemotherapy and glucocorticosteroids. There are also cases of osteonecrosis of the jaw in patients with osteoporosis when ingested bisphosphonates. When assessing the individual risk of developing necrosis of the jaw, the following risk factors should be considered:
- the action strength of the bisphosphonate (highest in zoledronic acid), the route of administration (see above), and the total dose;
- cancer, chemotherapy, radiotherapy, glucocorticosteroids, smoking;
- dental disease in history, poor oral hygiene, periodontal disease, invasive dental procedures and poorly selected dentures.

Before starting oral bisphosphonate therapy, patients with unsatisfactory dental status are recommended to have a dental examination and preventive medical measures.

During the course of bisphosphonates, it is recommended that such patients avoid invasive dental procedures whenever possible.If a patient develops osteonecrosis during bisphosphonate therapy, surgical dental treatment may worsen his condition. It is not known whether the discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw in patients who require dental procedures. In each case, the decision should be made by the attending physician on the basis of an estimate of the relationship between the expected benefit and the possible risk for the particular patient.

During therapy with bisphosphonates, patients should be told the importance of proper oral hygiene, preventive examinations, and warn them about reporting any symptoms from the oral cavity, such as tooth mobility, pain, or swelling.

Pain in the bones and muscles

It is known about cases of pain in the bones, joints and / or muscles during the course of bisphosphonates. In rare cases, post-marketing use of these symptoms has been severe and / or caused disability. The time of onset of symptoms varied from one day to several months after the start of treatment. In most patients, symptoms were resolved after discontinuation of treatment.In some of them, the symptoms appeared again with the resumption of the same drug or other bisphosphonate.

Atypical Hip Fractures

It is known about cases of susceptible or diaphyseal fractures of the thigh during treatment with bisphosphonates, mainly in patients receiving long-term therapy for osteoporosis. These transverse or oblique fractures may occur throughout the

length of the thigh from the small trochanter of the femur to the supracondylar dilatation. These fractures occur after or without minor trauma, some patients experience severe pain in the thigh or inguinal region, which is often combined with the radiologic symptoms of stress fractures, weeks or months before the full pattern of hip fracture appears. Fractures are often bilateral, so in patients with a hip fracture, taking bisphosphonates, the second (contralateral) thigh should be examined. It is known that these fractures are poorly fused. If an atypical hip fracture is suspected, consideration should be given to stopping bisphosphonate therapy before an individual assessment of the relationship between expected benefit and possible risk occurs.

During therapy with bisphosphonates, patients should be advised to report any pain in the thigh or in the groin. All patients who have received such complaints should be examined for fracture of the hip.

Renal insufficiency

The drug FOSAVANS® is contraindicated in patients with renal failure at a glomerular filtration rate of less than 35 ml / min.

Bone and mineral metabolism

Other causes of osteoporosis should be taken into account, in addition to estrogen deficiency and age.

In the presence of hypocalcemia, the concentration of calcium in the blood should be normalized before starting treatment with the drug FOSAVANS®.

Other disorders of mineral metabolism (eg, vitamin deficiency D and hypoparathyroidism) should also be effectively treated before starting treatment with the drug FOSAVANS®. Vitamin content D in the preparation of FOSAVANS® is not enough to correct hypovitaminosis D. In patients with these disorders during treatment with the drug FOSAVANS®, it is necessary to monitor the concentration of calcium in the serum and the symptoms of hypocalcaemia.

Since alendronate increases the mineral content of bones,can be observed a decrease in the level of calcium and phosphate in the blood serum, especially when taking glucocorticosteroids that reduce calcium absorption. Usually, this decrease is small and asymptomatic. Nevertheless, there are rare cases of symptomatic hypocalcemia, which sometimes reached a severe degree and developed in patients with a corresponding predisposition (eg, hypoparathyroidism, hypovitaminosis D and calcium malabsorption).

Kolekalischferol

Vitamin D3 may contribute to an increase in the severity of hypercalcemia and / or hypercalciuria when used in patients with diseases that cause uncontrolled hyperproliferation of calcitriol (eg, leukemia, lymphoma, sarcoidosis). In such patients it is necessary to control the calcium content in urine and serum.

In patients with malabsorption, there may be a violation of absorption of the vitamin D3. Excipients

This drug contains lactose anhydrous and sucrose. Patients with rare hereditary diseases of intolerance to fructose and galactose, lactase deficiency,glucose-galactose malabsorption and sucrose-isomaltase insufficiency, this medication should not be taken.

Effect on the ability to drive transp. cf. and fur:There is no evidence that the drug FOSAVANS® directly affects the ability to drive or use other mechanisms. Some undesirable effects, such as blurred vision, dizziness, severe joint or muscle pain (see "Side effect"), observed with the drug FOSAVANS®, can affect the ability to drive and other mechanisms.

Form release / dosage:

Tablets 70 mg + 70 mcg.

Packaging:By 2 or 4 Tablets in a blister of PVC / aluminum foil. By 1, 2, 3 or 10 blisters together with instructions for medical use in a cardboard box.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

18 months.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002619/07

Date of registration:07.09.2007 / 27.03.2014

Date of cancellation:2016-03-25

The owner of the registration certificate:MERC SHARP and DOMA IDEA, Inc. MERC SHARP and DOMA IDEA, Inc. Switzerland

Manufacturer: & nbsp

FROSST IBERICA, S.A. Spain

Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.

Information update date: & nbsp29.07.2016

Illustrated instructions

Instructions

Fosavans® (Fosavance®)