Fosavans Forte – combined formulation.
Alendronic acid, being a bisphosphonate is localized in areas of active bone resorption by osteoclasts inhibits resorption process without exerting a direct effect on new bone formation.
Since resorption and bone formation are interconnected, the formation is also reduced, but to a lesser extent than resorption which leads to increased bone mass. During treatment, normal bone tissue is formed, which is embedded in the matrix alendronic acid remaining pharmacologically inactive (at therapeutic doses alendronic acid does not cause osteomalacia).
Kolekaltsiferol increases intestinal absorption of Ca2 + and phosphate excretion by the kidneys regulates them, as well as regulates the concentration of Ca2 + plasma, forming bone and its resorption.
Alendronic acid, Colecalciferol
Merck Sharp & Dohme BV, USA
1 tablet contains:
alendronic acid 70 mg
Kolekaltsiferol 140 micrograms.
For the treatment of postmenopausal osteoporosis in patients who are not taking additional medications and vitamin D are in the group on the development of vitamin A deficiency risk D. The drug reduces the risk of vertebral fractures and hip; to increase bone mass in men with osteoporosis.
- Hypersensitivity to any component of the product;
- inability to sit or stand upright for 30 minutes;
- esophageal disease, delaying emptying, for example, a stricture or achalasia;
- severe renal failure (creatinine clearance < 35 ml / min);
- pregnancy and breastfeeding;
- children’s age (18 years);
- Heavy hypoparathyroidism;
- severe deficiency of vitamin D;
- calcium malabsorption;
- a hereditary deficiency of lactase deficiency sucrase / isomaltase, glucose-galactose malabsorption.
- an exacerbation of diseases of the upper gastrointestinal tract, such as dysphagia, oesophageal disease, gastritis, duodenitis or ulcer (including medical history information on peptic ulcer, active gastrointestinal bleeding, surgery on the upper parts of the gastrointestinal tract during the years before receiving the drug Fosavans forte).
- in diseases associated with overproduction of calcitriol (leukemia, lymphoma, sarcoidosis) and associated hypercalcemia and / or hypercalciuria.
The most frequently reported adverse reactions are unwanted reaction from the upper gastrointestinal tract, including abdominal pain, dyspepsia, esophageal ulcer, dysphagia, abdominal distension and acidic burps (≥ 1 / 100th, < 1/10).
The following adverse reactions were reported in clinical studies and / or post-marketing use of alendronate.
Additional adverse reactions to the drug Fosavans forte been established.
The frequency of adverse reactions set 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).
|Violations sostorony immune system||Rare: hypersensitivity reactions including urticaria and angioedema|
|Violations by the metabolism and nutrition||Rare: symptomatic hypocalcaemia, often in the background of predisposing risk factors 1|
|Disorders of the nervous system||Common: headache, dizziness 2 |
Infrequent: taste disturbance 2
|Violations by the authorities of||Infrequent: eye inflammation (uveitis, scleritis, episcleritis)|
|Violations by the ear and labyrinth disorders||Frequent: vertigo 2|
|Violations of the gastrointestinal tract||Common: abdominal pain, dyspepsia, constipation, diarrhea, flatulence, oesophageal ulcer 3 , dysphagia 3 , bloating, belching sour|
Uncommon: nausea, vomiting, gastritis, esophagitis 3 , esophageal erosion 3 , melena 2
Rare: oesophageal stricture 3 , ulceration of the esophagus 3 , perforation, ulcers, bleeding upper gastrointestinal 1 , gastroesophageal reflux disease
|Violations of the skin and subcutaneous tissue||Common: alopecia 2 , itching 2 |
Infrequent: skin rash, erythema
Rare: rash with photosensitivity, severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis 4
|Violations by musculoskeletal and connective tissue||Very common: musculoskeletal (bone, muscle or joint) pain, sometimes severe pain 1,2|
Common: joint swelling 2
Rare: osteonecrosis of the jaw 1,4 , 5 atypical, subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction)
|General disorders and injection site||Frequent: asthenia 2 , peripheral edema 2|
Uncommon: transient symptoms such as acute phase reaction (myalgia, malaise and rarely – fever), typically in association with initiation of treatment 2
1 See. See “Cautions”
2 In the clinical trials was similar frequency band for the drug and placebo groups.
3 See. Sections “Dosage and Administration” and “Cautions”
4 This adverse reaction was set during post-marketing surveillance. The frequency of “rare” has been set based on the respective clinical studies.
5 was found at post-marketing use.
How to accept, acceptance rate and dosage
1 tablet at least 30 minutes before the first meal, liquid or drugs (including antacids, calcium supplements and vitamins) with a full glass of plain water (no mineral water). Other beverages (including
mineral water), food and certain drugs may decrease the absorption of the drug Fosavans forte.
To reduce the risk of esophageal irritation drug Fosavans forte should be, follow these rules:
- Accept morning immediately after rising from the bed, not less than 30 minutes before the first meal, liquid or medicaments with a full glass of water (not mineral) to facilitate receipt of the tablet in the stomach.
- not chew tablets or dissolve them in the mouth due to the possible formation of ulcers in the mouth and throat. Patients should not go before the first meal, which should be done at least 30 minutes after taking the drug Fosavans forte.
- The preparation Fosavans Forte should not be taken at bedtime or before getting up from the bed.
The recommended dose is one tablet of the preparation Fosavans forte 1 time per week.
Patients should take additional calcium preparations, if it is received with inadequate food. Preparation Fosavans forte week satisfies the need for vitamin D, based on a daily dose of 800 ME.
For elderly patients and patients with mild and moderate renal impairment (creatinine clearance of 35 to 60 ml / min) dose adjustment is required. The recommended dose is one tablet of the preparation Fosavans forte 1 time per week.
If you accidentally missed doses should take 1 tablet in the morning the next day. Do not take 2 doses on the same day, but in the future it is necessary to go back to using the drug 1 time per week on the day of the week, which was selected at the beginning of treatment.
In a dry place, protected from light at a temperature not higher than 25 ° C
Alendronic acid, Colecalciferol
Absorption of Alendronate may be violated if the drug is taken together with food, beverages (including mineral water), calcium preparations, antacids and other drugs for oral administration.
In this regard, the interval between administration of the drug Fosavans forte and other drugs taken by mouth, should be at least 30 minutes.
Since the use of NSAIDs is associated with the development of erosive-ulcerous lesions of the gastrointestinal tract, caution should be exercised while the use of NSAIDs and alendronate.
Olestra, mineral oils, orlistat and bile acid sequestrants (cholestyramine, colestipol) may hinder the absorption of vitamin D.
Anticonvulsants, cimetidine, thiazide diuretics can accelerate the catabolism of vitamin D.
Gastrointestinal adverse reactions
from the top departments
Alendronate can cause local irritation of the mucosa of the upper gastrointestinal tract. Due to the possibility of deterioration underlying disease while receiving alendronate, caution should be exercised when administering the drug to patients with diseases of the upper gastrointestinal tract, such as dysphagia, oesophageal disease, gastritis, duodenitis, gastric, and also under severe gastrointestinal disease, migrated in the preceding 12 months, e.g., peptic ulcer, gastro-intestinal haemorrhage, surgery, operations on the upper gastrointestinal tract, except piroloplastiki. For patients diagnosed with Barrett’s esophagus the appointment of alendronate should be decided individually on the basis of an estimate of the expected benefit to the possible risk.
When alendronate known cases of adverse reactions on the part of the esophagus (esophagitis, esophageal ulcer, or erosion) sometimes be severe requiring hospital treatment, and in rare cases complicated by stricture formation. Therefore, physicians need to pay special attention to any signs or symptoms suggestive of possible violations of the esophagus, and patients should be advised to discontinue alendronate and seek medical attention at the appearance of esophageal irritation symptoms such as dysphagia, pain on swallowing or chest pain, new or worsening heartburn.
The risk of severe adverse events from the esophagus is higher in those patients who violate the guidelines for receiving alendronate and / or continue to take it at the appearance of symptoms of irritation of the esophagus. It is extremely important to fully inform patients about the importance of compliance with the rules of the drug and make sure that they understand this. It is necessary to warn them that the risk of developing esophageal increases in case of failure of these recommendations.
Although in extensive clinical trials, alendronate increased risk were observed in post-marketing reports of rare cases reported razvitiya.yazvy gastric and duodenal ulcers, sometimes severe and complicated.
Osteonecrosis of the jaw
In cancer patients treated by intravenous administration of bisphosphonates conducted, there were cases of osteonecrosis of the jaw due primarily preceding tooth extraction and / or local infection. (Including osteomyelitis). Many of them also receiving chemotherapy and corticosteroids.
Also, there are cases of osteonecrosis of the jaw in patients with ostsoporozom when administered bisphosphonates.
When an individual risk assessment of necrosis of the jaw following risk factors should be considered:
– bisphosphonate force action (at the highest zoledronic acid), route of administration (see above.) And a total dose;
– cancer, chemotherapy, radiotherapy, corticosteroids, smoking;
– dental diseases in history, poor oral hygiene, periodontal disease, invasive dental procedures and poorly selected prosthesis
Before therapy with oral bisphosphonates in patients with poor dental status recommended dental examination and preventive therapeutic measures.
During the course of bisphosphonates in these patients is recommended as far as possible, avoid invasive dental procedures. If the patient developed osteonecrosis during bisphosphonate therapy, surgical dental treatment can worsen his condition. It is unknown whether the reduced risk of discontinuation of bisphosphonate osteonecrosis of the jaw in patients requiring dental procedures. In each case, the decision should be made by the attending physician on the basis of an estimate of the expected benefit to the possible risk for the individual patient.
During bisphosphonate therapy should explain to patients the importance of proper oral hygiene, preventive examinations, and warn them of the need for communication of any symptoms of the oral cavity, such as loose teeth, pain or swelling appears.
Pain in the bones and muscles
Known cases of the appearance of pain in the bones, joints and / or muscles during the course of bisphosphonates. During post-marketing use in rare cases, these symptoms are severe and / or lead to disability. Time of onset of symptoms varied from one day to several months after starting treatment. In most patients, symptoms resolved after cessation of treatment. Some of these symptoms occur again when you resume receiving the same drug or another bisphosphonate.
Atypical fractures of the femur
Known cases of subtrochanteric or diaphyseal femur fractures with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or oblique fractures can occur along the entire length of the femur lesser trochanter of the femur to the supracondylar extension. These fractures occur posle.neznachitelnoy injury or not, some patients experience severe pain in the hip or groin, which is often combined with radiological signs of stress fractures, weeks to months before the appearance of a complete picture of hip fracture. Fractures are often bilateral, so patients with a hip fracture who take bisphosphonates, should be examined second (contralateral) thigh. It is known that these fractures are bad fuse. If you suspect that an atypical femur fracture should consider discontinuation of therapy with bisphosphonates prior to the individual assessment of the relationship of the expected benefits to the possible risk.
During bisphosphonate therapy patients should be advised to report any pain in the hip or groin. All patients admitted with such complaints should be examined for hip fracture.
Fosavans forte drug is contraindicated in patients with renal failure at the glomerular filtration rate of less than 35 ml per minute.
Bone and mineral metabolism
It is necessary to take into account other causes of osteoporosis, in addition to age and estrogen deficiency.
In the presence gikaltsiemii blood calcium concentration must be normalized prior to treatment with Fosavans forte.
Other disorders of mineral metabolism (for example, deficiency of vitamin D and hypoparathyroidism) should also be effectively treated before beginning treatment with Fosavans forte. The content of vitamin D in the preparation Fosavans forte insufficient correction hypovitaminosis D. Patients with these disorders during treatment with Fosavans forte necessary to control the concentration of calcium in serum and symptoms of hypocalcemia.
Since alendronate increases mineral content in bones, reducing the level of calcium and phosphate in the serum can be observed, especially when taking glucocorticosteroids reducing calcium absorption. Typically, such a decline is small and asymptomatic. However, known rare cases symptomatic hypocalcemia, which sometimes reaches and developed severe patients with a corresponding predisposition (e.g., hypoparathyroidism, hypovitaminosis D and calcium malabsorption).
Vitamin D3 can increase the severity of hypercalcemia and / or hypercalciuria when used in patients with diseases that cause an uncontrolled overproduction of calcitriol (e.g., leukemia, lymphoma, sarcoidosis). In these patients, it is necessary to control the content of calcium in the urine and serum.
Patients with malabsorption may experience malabsorption of vitamin D3.
This drug contains lactose and sucrose. Patients with rare hereditary disorders of fructose and galactose intolerance, lactase deficiency, glucose-galactose malabsorption and saharazno-izomaltaznoy insufficiency should not take this medicine.
Effects on ability to drive and use other mechanisms
There is no evidence that the drug Fosavans forte directly affects the ability to drive or use other mechanisms. Some adverse events; such as blurred vision, dizziness, severe pain in the joints or muscles (see. section “Side effects”), observed while taking the drug Fosavans forte, may affect the ability to drive and other mechanisms.
Pregnancy and lactation
The drug Fosavans fort designed to treat only women in the postmenopausal and is contraindicated in pregnancy and during breastfeeding.
Data on the use of the drug Fosavans fort in pregnancy. Alendronate studies in animals have revealed no direct damaging action against pregnancy, embryo / fetal or postnatal development.
The use of alendronate in rats during pregnancy caused the violation of labor due to hypocalcemia. Animal studies indicate hypercalcemia and reproductive toxicity with vitamin D in high doses.
It is not known whether alendronate passes into breast milk. Kolekaltsiferol and some active metabolites into breast milk.
Bisphosphonates are incorporated into the bone tissue from which they are gradually released over the years. The number of bisphosphonate which can integrate into the bone and, therefore, fall back into the systemic circulation, is directly proportional to the dose and duration of application of the bisphosphonate.
Data about the risk to the fetus in humans are not available, but there is a theoretical risk of fetal damage, especially the skeleton, if pregnancy occurs at the end of a course of the bisphosphonate. The influence of such variables as length of the period between termination and bisphosphonate therapy conception, the specific type of bisphosphonate and route of administration (oral or intravenous) have not been investigated in respect of this risk.
When possible overdose hypocalcemia, hypophosphatemia and unwanted reaction from the upper GI: dyspepsia, heartburn, esophagitis, gastritis, gastric ulcer and esophageal.
No specific treatment of alendronate overdose. If overdose Fosavans forte should take milk or antacids to bind alendronate. To avoid irritation of the esophagus should not induce vomiting. Patients should maintain an upright position.
Vitamin D toxicity has not been reported in healthy adults with chronic reception at doses below 10,000 IU per day. In clinical studies involving healthy adults taking vitamin D3 at a daily dose of 4000 ME for 5 months did not cause hypercalciuria and hypercalcemia.