Active ingredients: Alendronic acid (Alendronate sodium trihydrate)
ASTON 70 mg film-coated tablets
Why is Aston used? What is it for?
What is ASTON?
ASTON belongs to a group of non-hormonal medicines called bisphosphonates. ASTON prevents bone loss that occurs in postmenopausal women and promotes bone reconstruction. It reduces the risk of vertebral and hip fractures.
What is ASTON for?
The doctor prescribed ASTON for the treatment of osteoporosis. ASTON reduces the risk of vertebral and hip fractures.
ASTON is a once a week treatment.
What is osteoporosis?
Osteoporosis is a thinning and weakening of the bones. It is common in women after menopause. In menopause, the ovaries stop producing the female hormone, estrogen, which helps keep a woman's skeleton healthy. As a result, bone loss occurs and the bone becomes weaker. The risk of osteoporosis is greater the earlier a woman reaches menopause.
In the early stages, osteoporosis usually has no symptoms. However, if treatment is not taken, fractures can occur. Although fractures are usually painful, fractures of the bones of the spine may not be felt until they are found. in a decrease in stature. Fractures can occur during daily activities such as lifting weights, or with minor injuries that would not be able to cause fractures in normal bone. Fractures normally occur in the hip, spine or wrist and can be not only painful, but can lead to significant deformities and disabilities, such as a bowed back (hump) and limitations in movement.
How can osteoporosis be treated?
It is important to remember that osteoporosis can be treated and that it is never too late to start. ASTON not only prevents bone loss but helps rebuild bone that may have been lost and reduces the risk of vertebral and hip fractures.
Along with treatment with ASTON, your doctor may suggest lifestyle changes to improve the condition of the disease, such as:
Quitting smoking: Smoking appears to increase the rate at which bone is lost and, therefore, may increase the risk of fractures.
Exercise: Like muscles, bones need exercise to stay strong and healthy. Consult your doctor before starting any exercise program.
Balanced diet: your doctor will be able to give you information on your diet or on the possible need to take food supplements (especially calcium and vitamin D).
Contraindications When Aston should not be used
Do not take ASTON:
- If you are allergic (hypersensitive) to alendronate sodium trihydrate or any of the other ingredients.
- If you have certain diseases of the esophagus (the tube that connects your mouth with your stomach), such as narrowing and difficulty swallowing.
- If you cannot stand or sit upright for at least 30 minutes. 4. If your doctor has told you that you have low blood calcium levels.
If you think that any of these apply to you, do not take the tablets. Consult your doctor and follow the advice given.
Precautions for use What you need to know before taking Aston
Before taking ASTON it is important to tell your doctor if you have:
- Kidney problems.
- Allergies.
- Difficulty swallowing or problems with the digestive system.
- Low levels of calcium in the blood. There have been rare reports of symptomatic hypocalcaemia, occasionally severe and often in patients with predisposing conditions (eg hypoparathyroidism, vitamin D deficiency and calcium malabsorption), particularly in patients taking glucocorticoids, which reduce the absorption of Calcium It is particularly important to ensure adequate calcium and vitamin D intake in patients on glucocorticoid therapy.
- You have poor dental health, have gum disease, have a "tooth extraction planned" or don't have regular dental checkups.
- He is planning dental surgery.
- Barrett's esophagus (a condition associated with changes in the cells that line the lower portion of the esophagus).
- He has cancer.
- He is undergoing chemotherapy or radiotherapy.
- You are taking corticosteroids (such as prednisone or dexamethasone).
- He is or has been a smoker.
- He underwent invasive dental procedures and poorly fitting dentures.
Jaw or jaw problems may occur while using alendronate, usually in cancer patients, often after tooth extraction and / or local infection. Many of these patients were being treated with chemotherapy and corticosteroids.
You should consider having a dental examination before starting treatment with ASTON.
During bisphosphonate treatment, all patients should be encouraged to maintain good oral hygiene, to undergo periodic dental check-ups, and to report any type of oral symptoms such as mobility, pain or dental swelling.
There may be irritation, inflammation or ulceration of the esophagus (the tube that connects the mouth to the stomach) often with symptoms of chest pain, heartburn, difficulty or pain in swallowing, especially if patients do not drink a full glass. d "water and / or if they spread during the first 30 minutes after taking ASTON. These side effects may worsen if patients continue to take ASTON after experiencing these symptoms. If you notice any of the side effects described above, stop taking the medicine and contact your doctor.
Fractures of the femur with or without minimal injury (stress fractures) have been reported in patients treated with alendronate for long periods. If you feel pain, weakness or discomfort in your leg, hip or groin please report this to your doctor as this could be an early indication of a possible fracture of the femur (see section POSSIBLE SIDE EFFECTS).
Your doctor will decide if treatment with ASTON needs to be stopped.
Rare cases of gastric and duodenal ulcers, some serious and associated with complications, have been reported while using alendronate.
In patients treated with bisphosphonates, including alendronate, there have been cases of bone, joint and / or muscle pain which on rare occasions have been severe and have resulted in disability. The onset of symptoms has been variable since one day. several months after starting treatment. In most patients, discontinuation of treatment resulted in symptom relief.
Rare cases of severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with the use of alendronate.
Interactions Which drugs or foods may change the effect of Aston
Calcium supplements, antacids, and some oral medications are likely to interfere with the absorption of ASTON if taken at the same time.
It is therefore important to follow the instructions given in the section HOW TO TAKE ASTON.
Other medicines for rheumatism or long-term pain called NSAIDs (e.g. aspirin or ibuprofen) could cause digestive problems. Therefore, caution should be used when these medicines are taken at the same time as ASTON.
Always tell your doctor about all medicines you are taking or plan to take, including those that you can buy without a prescription
Taking ASTON with food and drink
Food and drinks (including mineral water) are likely to make ASTON less effective if taken at the same time. It is therefore important to follow the instructions given in section 3. HOW TO TAKE ASTON.
Warnings It is important to know that:
Children and adolescents
Alendronate should not be given to children and adolescents.
Pregnancy and breastfeeding
ASTON is for postmenopausal women only. Do not take ASTON if you are pregnant or think you may be or are breastfeeding.
Driving and using machines
No studies on the ability to drive and use machines have been performed. However, some adverse reactions reported with ASTON may affect the ability of some patients to drive or use machines. Individual responses to ASTON may vary (see section POSSIBLE SIDE EFFECTS).
Dose, Method and Time of Administration How to use Aston: Posology
Take the ASTON tablet once a week.
To benefit from treatment with ASTON, it is necessary to act as described below.
1) Choose the day of the week that best matches your activities. Take ASTON once a week on your chosen day.
It is very important to follow instructions 2), 3), 4), and 5) to facilitate the quick entry of the ASTON tablet into the stomach and to help reduce the possibility of irritating the esophagus (the tube that connects the mouth to the stomach).
2) After getting out of bed to start the day, and before taking any food, drink or other medication of the day, swallow your ASTON tablet with a full glass of water only (not mineral water) (not less than 200ml ).
- Do not take with mineral water (still or sparkling).
- Do not take with coffee or tea.
- Do not take with juice or milk.
The ASTON tablet should only be swallowed whole. Do not crush, chew or let the tablet dissolve in the mouth.
3) Do not lie down - keep your torso upright (whether sitting, standing or walking) - for at least 30 minutes after swallowing the tablet. Don't lie down until you've eaten something.
4) ASTON should not be taken at bedtime or before getting out of bed at the beginning of the day.
5) If you experience difficulty or pain in swallowing, chest pain or develop or worsen upper stomach burn, stop taking ASTON and contact your doctor.
6) After swallowing your ASTON tablet, wait at least 30 minutes before eating, drinking or taking any other medicines of the day, including antacids, calcium supplements and vitamins. ASTON is only effective when taken on an empty stomach.
Overdose What to do if you have taken too much Aston
If you take more ASTON than you should
If you take too many tablets by mistake, drink a full glass of milk and contact your doctor immediately. Do not induce vomiting and do not lie down.
If you forget to take ASTON
If you forget to take your tablet, simply take one ASTON tablet the next morning. Do not take two tablets on the same day. Thereafter, resume taking the tablet on the chosen day of the week.
If you stop taking ASTON
It is important to continue taking ASTON for as long as your doctor prescribes it. ASTON is only effective for treating osteoporosis if you continue to take the tablets.
If you have any further questions on the use of this drug, ask your doctor or pharmacist.
Side Effects What are the side effects of Aston
Like all medicines, ASTON can cause side effects, although not everybody gets them.
The following terms are used to describe how often side effects have been reported.
Very common (occurring in at least 1 in 10 patients treated)
Common (occurring in at least 1 in 100 and less than 1 in 10 treated patients)
Uncommon (occurring in at least 1 in 1,000 and less than 1 in 100 patients treated)
Rare (occurring in at least 1 in 10,000 and less than 1 in 1,000 patients treated)
Very rare (occurring in less than 1 in 10,000 patients treated)
Disorders of the immune system
Rare: allergic reactions such as hives, swelling of the face, lips, tongue and / or throat, possibly causing difficulty in breathing and swallowing.
Metabolism and nutrition disorders
Rare: symptoms of low blood calcium levels including muscle cramps or spasms and / or tingling in the fingers or around the mouth.
Nervous system disorders
Common: headache, dizziness.
Uncommon: dysgeusia (taste disturbances).
Eye disorders
Uncommon: blurred vision, pain or redness of the eyes. Inflammation of the eye (uveitis, scleritis, episcleritis).
Ear and labyrinth disorders
Common: dizziness.
Gastrointestinal disorders
Common: abdominal pain, uncomfortable feeling in the stomach or belching after meals, constipation, feeling of fullness or bloating in the stomach, diarrhea, flatulence, heartburn, difficulty swallowing, pain in swallowing, ulcers of the esophagus (the tube that connects the mouth to the stomach) which cause chest pain, burning or difficulty or pain in swallowing.
Uncommon: nausea, vomiting, irritation or inflammation of the esophagus (the tube that connects your mouth to your stomach) or stomach, black or dark stools.
Rare: narrowing of the esophagus (the tube that connects the mouth to the stomach), mouth ulcers when the tablets are chewed or sucked, stomach or peptic ulcers (sometimes severe or with bleeding).
Skin and subcutaneous tissue disorders
Common: alopecia (hair loss), itching.
Uncommon: rash, erythema.
Rare: rash worsened by exposure to sunlight, severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders
Very common: muscle, bone and / or joint pains, sometimes severe.
Common: joint swelling.
Rare: Pain in the mouth, and / or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw or loosening of teeth. These may be signs of damage to the jaw / jaw bone. (osteonecrosis) generally associated with delayed healing and infection, often following tooth extraction. Contact your doctor or dentist if you experience these symptoms.
Rarely, an unusual fracture of the femur may occur, particularly in patients on long-term treatment for osteoporosis.
Contact your doctor if you experience pain, weakness or discomfort in the thigh, hip or groin as this could be an early indication of a possible fracture of the femur.
Systemic pathologies
Common: fatigue, peripheral edema (swelling of the hands or legs).
Uncommon: transient flu-like symptoms such as muscle aches, generally feeling unwell and sometimes with fever usually at the start of treatment.
Diagnostic tests
Very common: slight and transient decreases in calcium and phosphate values in the blood, generally within normal limits.
It is good to take note of any symptoms that may occur, the time of their onset and their duration.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep ASTON out of the reach and sight of children.
Do not use ASTON after the expiry date which is stated on the label
Do not remove the tablets from the blister before it is time to take them.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What ASTON contains
Active principle
The active ingredient is alendronate sodium trihydrate. Each tablet contains the equivalent of 70 mg alendronic acid, as alendronate sodium trihydrate.
Excipients
Core: microcrystalline cellulose, croscarmellose sodium, anhydrous colloidal silica, sodium stearyl fumarate. Coating: hypromellose, talc.
Description of what ASTON looks like and contents of the pack
Film-coated tablets: pack of 4 tablets.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ASTON 70 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains:
Active principle: alendronic acid 70 mg (as alendronate sodium trihydrate).
For excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of postmenopausal osteoporosis. ASTON reduces the risk of vertebral and hip fractures.
04.2 Posology and method of administration
The recommended dosage is one 70 mg tablet once weekly.
The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be reassessed in each individual patient periodically based on the potential benefits and risks, particularly after 5 or more years of use.
To obtain adequate absorption of alendronate
ASTON should be swallowed at least 30 minutes before any food, drink or medication of the day together with plain water only. Other beverages (including mineral water), food and some medications are likely to reduce the absorption of alendronate (see section 4.5).
To facilitate gastric release and reduce the potential for local and oesophageal irritation / undesirable events (see section 4.4):
• ASTON should only be swallowed after getting out of bed to start the day, with a full glass of water (not less than 200 ml).
• The patient should swallow the ASTON tablet whole only. The patient should not crush or chew or dissolve the tablet in the mouth due to the potential risk of oropharyngeal ulceration.
• The patient should not lie down until after something has been eaten, which should be at least 30 minutes after taking the tablet.
• The patient should not lie down for at least 30 minutes after taking ASTON.
• ASTON should not be taken at bedtime or before getting out of bed at the beginning of the day.
Patients should take calcium and vitamin D supplements if dietary intake is inadequate (see section 4.4).
Use in the elderlyNo age-related difference in the efficacy or safety profiles of alendronate was demonstrated in clinical trials. Therefore, no dosage adjustment is necessary in elderly patients.
Use in case of impaired renal function: No dosage adjustment is necessary in patients with GFR (glomerular filtration rate) greater than 35 mL / min. Alendronate is not recommended in patients with impaired renal function when the GFR is less than 35 ml / min, as no information is available.
Pediatric patients: the use of alendronate sodium is not recommended in children below 18 years of age due to insufficient data on safety and efficacy in conditions associated with pediatric osteoporosis (see also section 5.1).
ASTON 70 mg has not been studied in the treatment of glucocorticoid-induced osteoporosis.
04.3 Contraindications
• Disorders of the esophagus and other factors that delay esophageal emptying, such as stricture and
achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Hypersensitivity to alendronate or to any of the excipients.
• Hypocalcemia
• See also section 4.4.
04.4 Special warnings and appropriate precautions for use
Alendronate may cause local irritation of the upper gastrointestinal mucosa. Due to the potential for worsening of the underlying disease, caution should be exercised when administering alendronate to patients with active upper gastrointestinal disease such as dysphagia. , esophageal disease, gastritis, duodenitis, ulcers or with a recent history (within the previous year) of major gastrointestinal disorders such as peptic ulcer or active gastrointestinal bleeding or upper gastrointestinal surgery excluding pyloroplasty (see section 4.3). Barrett's esophagus known, physicians should consider the benefits and potential risks of alendronate in individual patients
Undesirable reactions (some severe and requiring hospitalization) affecting the esophagus such as esophagitis, esophageal ulcers and esophageal erosions, rarely followed by esophageal strictures, have been reported in patients receiving alendronate. of any signs or symptoms that indicate a possible oesophageal reaction and advise the patient to discontinue alendronate and seek medical attention if symptoms of esophageal irritation such as dysphagia, odynophagia, retrosternal pain, onset or worsening of heartburn occur.
The risk of serious oesophageal adverse events appears to be greater in patients who do not take alendronate properly and / or who continue to take alendronate after developing symptoms suggestive of oesophageal irritation. It is very important that the patient knows and understands how to take the drug (see section 4.2). The patient should be advised that if these precautions are not followed, the risk of esophageal problems may increase.
While no increased risk was observed in large clinical trials, rare (post-marketing) cases of gastric and duodenal ulcers, some serious and associated with complications, have been reported.
Osteonecrosis of the jaw, usually associated with tooth extraction and / or local infection (including osteomyelitis), has been reported in cancer patients receiving regimens including bisphosphonates administered primarily intravenously. Many of these patients they were also treated with chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis being treated with oral bisphosphonates.
When assessing the individual risk of developing osteonecrosis of the jaw, the following risk factors should be considered:
• Potency of bisphosphonates (highest for zoledronic acid), route of administration (see above) and cumulative dose;
• cancer, chemotherapy, radiotherapy, corticosteroids, smoking;
• history of dental disease, poor oral hygiene, periodontal disease, invasive dental procedures and poorly fitting dentures.
Before initiating treatment with oral bisphosphonates in patients with poor dental hygiene the need for a dental examination with appropriate preventive dental procedures should be considered.
During treatment, these patients should, if possible, avoid invasive dental procedures. In patients who have developed osteonecrosis of the jaw during bisphosphonate therapy, dental surgery can exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest that discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw and / or jaw.
The clinical judgment of the physician must guide the management program of each patient, based on the individual assessment of the risk / benefit ratio.
During treatment with bisphosphonates, patients are recommended to maintain good oral hygiene, have routine dental checkups and report any oral symptoms such as tooth mobility, pain or swelling.
Bone, joint and / or muscle pain has been reported in patients treated with bisphosphonates. In post-marketing experience these symptoms have rarely been severe and / or have caused disability (see section 4.8). The time to onset of symptoms ranged from one day to several months after initiation of treatment. Discontinuation of treatment resulted in symptom relief in most patients. Following re-administration of the same drug or another bisphosphonate, a subset of patients experienced relapse of symptoms.
Atypical subtrochanteric and diaphyseal fractures of the femur have been reported, mainly in patients on long-term bisphosphonate therapy for osteoporosis. These short transverse or oblique fractures can occur anywhere in the femur from just below the lesser trochanter to above the supracondylar line. These fractures occur spontaneously or after minimal trauma and some patients experience thigh or groin pain, often associated with imaging findings and radiographic evidence of stress fractures, weeks or months before the onset of stress fractures. a complete femoral fracture. Fractures are often bilateral; therefore in bisphosphonate-treated patients who have sustained a femoral shaft fracture, the contralateral femur should be examined. Limited healing of these fractures has also been reported. In patients with suspected atypical femoral fracture, consideration should be given to discontinuing bisphosphonate therapy pending an assessment of the patient based on the individual benefit-risk ratio.
During bisphosphonate treatment, patients should be advised to report any pain in the thigh, hip or groin and any patient who exhibits such symptoms should be evaluated for the presence of an incomplete femur fracture.
During post-marketing experience, there have been rare reports of serious skin reactions, including Stevens-Johnson Syndrome and toxic epidermal necrolysis.
Patients should be advised that if they miss their weekly dose of ASTON 70 mg, they should take one tablet on the morning following the day they are aware of it. You should not take two tablets on the same day but you should restart taking one tablet once a week, on the chosen day as previously established.
The use of alendronate is not recommended in patients with renal impairment when the GFR is less than 35 ml / min (see section 4.2).
Causes of osteoporosis other than estrogen deficiency and age must be carefully considered.
Hypocalcaemia should be corrected prior to initiation of alendronate therapy (see section 4.3). Other disorders affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) should also be treated appropriately. In patients with these clinical conditions, monitoring of serum calcium levels and hypocalcaemia was performed during treatment with ASTON.
Due to the positive effect of alendronate on increased bone mineralization, decreases in serum calcium and phosphate levels may occur, especially in patients taking glucocorticoids, in whom calcium absorption may be decreased. decreases are usually limited and asymptomatic, however there have been rare reports of symptomatic hypocalcaemia, occasionally severe and often in patients with predisposing conditions (eg, hypoparathyroidism, vitamin D deficiency and calcium malabsorption).
It is particularly important to ensure adequate calcium and vitamin D intake in patients on glucocorticoid therapy.
Osteonecrosis of the external auditory canal
Osteonecrosis of the external auditory canal has been reported in conjunction with the use of bisphosphonates, predominantly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include the use of steroids and chemotherapy and / or local risk factors such as infection or trauma. Osteonecrosis of the external auditory canal should be considered in patients treated with bisphosphonates who have ear symptoms, including chronic ear infections.
04.5 Interactions with other medicinal products and other forms of interaction
Food and beverages (including mineral water), calcium supplements, antacids and other oral medications, when taken at the same time as alendronate, are likely to interfere with the absorption of alendronate. Consequently, patients should allow at least 30 minutes after "taking" alendronate before taking any other oral medication (see sections 4.2 and 5.2).
No other drug interactions of clinical relevance are expected. In clinical studies, some patients were given estrogen (intravaginal, transdermal or oral) during treatment with alendronate. No undesirable events attributable to the use of estrogen during treatment with alendronate were identified.
Caution should be exercised when alendronate and NSAIDs are co-administered as the latter are associated with the risk of gastrointestinal irritation.
Although specific interaction studies have not been conducted, alendronate has been used in clinical studies with a wide range of commonly prescribed drugs without resulting in clinically relevant adverse events.
04.6 Pregnancy and lactation
Use during pregnancy
Alendronate should not be used in pregnancy. There are no adequate data from the use of alendronate in pregnant women. Animal studies do not indicate direct harmful effects with respect to pregnancy, embryo / fetal development or postnatal development. Alendronate caused dystocia due to hypocalcaemia in pregnant rats (see section 5.3).
Use while breastfeeding
It is not known whether alendronate is excreted in human milk. Alendronate should not be used during breastfeeding.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed.
However, some adverse reactions reported with ASTON may affect some patients' ability to drive or use machines. Individual responses to ASTON may vary (see section 4.8).
04.8 Undesirable effects
In a one-year clinical study in postmenopausal women with osteoporosis, the overall safety profiles of alendronate 70 mg once weekly (n = 519) and alendronate 10 mg / day (n = 370) were found to be similar.
In two three-year studies of essentially identical design, in postmenopausal women (alendronate 10 mg: n = 196, placebo: n = 397) the overall safety profiles of alendronate 10 mg / day and placebo were similar. .
Adverse events reported by investigators as possibly, probably or definitely drug related are presented in the table below if they occurred in ≥ 1% for each treatment group in the one-year study, or if they occurred in ≥ 1% of the patients treated with alendronate 10 mg / day and at an incidence greater than placebo in the three-year studies:
The following adverse experiences have also been reported in clinical trials and / or with commercial use of the drug:
[Very common (≥1 / 10), Common (≥1 / 100,
04.9 Overdose
Hypocalcaemia, hypophosphataemia and upper gastrointestinal adverse events such as gastric disturbances, heartburn, oesophagitis, gastritis or ulcer may be the consequence of oral overdose.
No specific information is available on the treatment of overdose with alendronate. Give milk or antacids that bind to alendronate. Due to the risk of esophageal irritation, do not induce vomiting and keep the patient strictly with the torso erect.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: bisphosphonate, for the treatment of bone diseases.
ATC code: M05BA04.
The active substance in ASTON, alendronate sodium trihydrate, is a bisphosphonate that acts as a specific inhibitor of osteoclast-mediated bone resorption with no direct effect on bone formation.
Preclinical studies have shown that alendronate is preferentially localized to sites of active resorption. The activity is inhibited, but recruitment and adhesion of osteoclasts are not altered. The bone tissue formed during treatment with alendronate is qualitatively normal.
Treatment of postmenopausal osteoporosis
Osteoporosis is defined as the BMD of the spine or hip that is 2.5 SD less than the mean value in a normal young population or as a history of pathological fracture, regardless of the BMD.
Therapeutic equivalence of alendronate 70 mg once weekly (n = 519) and alendronate 10 mg / day (n = 370) was demonstrated in a one-year multicenter study of postmenopausal women with osteoporosis. Mean increases in BMD. lumbar spine baseline at one year were 5.1% (95% CI: 4.8, 5.4%) in the 70 mg once weekly group and 5.4% (95 % CI: 5.0, 5.8%) in the 10 mg / day group. Mean increases in BMD were 2.3% and 2.9% at the femoral neck and 2.9% % and 3.1% across the hip, for the 70 mg once weekly and 10 mg once daily groups, respectively. The two groups were also similar with regard to increases in DMO in other bone districts.
The effects of alendronate on bone mass and fracture incidence in postmenopausal women were investigated in two initial efficacy studies of identical design (n = 994), and in the Fracture Intervention Trial (FIT: n = 6,459).
In the initial efficacy studies, mean increases in bone mineral density (BMD) with alendronate 10 mg / day compared with placebo at three years were 8.8%, 5.9% and 7.8% at the level spine, femoral neck and trochanter, respectively. The BMD of the whole organism also increased significantly. C was a 48% reduction (alendronate 3.2% vs placebo 6.2%) in the proportion of alendronate-treated patients with one or more vertebral fractures compared with to those treated with placebo. Over the two-year extension of these studies, BMD continued to increase in the spine and trochanter and remained stable in the femoral neck and body as a whole.
The FIT (Fracture Intervention Trial) consisted of two placebo-controlled studies of alendronate once daily (5 mg per day for two years and 10 mg per day for one or two additional years):
• FIT 1: A three-year study of 2,027 patients with at least one vertebral (compression) fracture at baseline. In this study, alendronate once daily reduced the incidence of ≥1 new vertebral fracture by 47% (alendronate 7.9% vs placebo 15.0%). There was also a statistically significant reduction in the incidence of hip fractures (1.1% vs 2.2%, a reduction of 51%).
• FIT 2: A four-year study of 4,432 patients with low bone mass but without vertebral fractures at baseline. In this study, a significant difference was observed in the subgroup analysis of osteoporotic women (37% of the overall study population, with osteoporosis as defined above) in the incidence of hip fractures (alendronate 1.0% vs placebo 2.2%, a reduction of 56%) and in the incidence of ≥1 vertebral fracture (2.9% vs 5.8%, a reduction of 50%).
Laboratory data :
In clinical trials, asymptomatic, mild and transient decreases in serum calcium and phosphate were reported in approximately 18% and 10% of patients treated with alendronate 10 mg / day, respectively, compared with approximately 12% and 3% of those treated with placebo. . However, the incidences of serum calcium decreases up to
Pediatric patients: Alendronate sodium has been studied in a limited number of patients less than 18 years of age with osteogenesis imperfecta. Results are insufficient to support the use of alendronate sodium in pediatric patients with osteogenesis imperfecta.
05.2 "Pharmacokinetic properties
Absorption
Compared to an intravenous reference dose, the mean oral bioavailability of alendronate in women was 0.64% for doses ranging from 5 to 70 mg administered after an overnight fast and 2 hours before a standardized breakfast. Similarly, bioavailability decreased to approximately 0.46% and 0.39% when alendronate was administered an "hour or half" before a standardized breakfast. In osteoporosis studies alendronate was effective when given at least 30 minutes before the first food or drink of the day.
Bioavailability was negligible when alendronate was administered with or within two hours of a standardized breakfast. Concomitant administration of coffee or orange juice with alendronate reduced its bioavailability by approximately 60%.
In healthy subjects, prednisone administered orally (20 mg three times daily for five days) did not produce clinically relevant changes in the oral bioavailability of alendronate (a mean increase of 20% to 44%).
Distribution
Studies in rats show that following intravenous administration of 1 mg / kg l "alendronate, initially distributed in soft tissues, is rapidly redistributed to bone or excreted in the urine. In humans, the mean volume of distribution at steady state, exclusive of bone, is at least 28 liters. Plasma drug concentrations following therapeutic oral doses are too low to be analytically detected (plasma protein is approximately 78%.
Biotransformation
In both humans and animals, there is no evidence that alendronate is metabolised.
Elimination
Following a single intravenous dose of 14C-labeled alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the faeces. After single intravenous administration of 10 mg, the renal clearance of alendronate was 71 ml / min and the systemic clearance did not exceed 200 ml / min. Plasma concentrations fell by more than 95% within 6 hours of intravenous administration. The terminal half-life in humans has been estimated to exceed ten years, reflecting the release of alendronate from the skeleton.
In rats, renal excretion of alendronate does not occur via acid-base transport systems and therefore is not expected to interfere at this level with the excretion of other drugs in humans.
Characteristics in patients
Preclinical studies show that non-bone-depositing drug is rapidly excreted in the urine. There was no evidence of saturation of bone uptake following chronic administration of cumulative intravenous doses up to 35 mg / kg in patients. animals.
Although no clinical information is available, it is likely that, as in animals, renal elimination of alendronate is reduced in patients with impaired renal function. Consequently, slightly greater accumulation of alendronate in bone might be expected in patients. with impaired renal function (see section 4.2 "Posology and method of administration").
05.3 Preclinical safety data
Non-clinical data indicate no specific risk in humans based on conventional studies of safety, repeated dose toxicity, genotoxicity and carcinogenic potential. Studies in rats showed that treatment with alendronate during pregnancy was associated with dystocia related to pregnancy. hypocalcemia in mothers. In studies, rats given the highest doses showed a higher incidence of incomplete fetal ossification. The relevance of these finds to man is not known.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core: microcrystalline cellulose;
croscarmellose sodium;
anhydrous colloidal silica;
sodium stearyl fumarate.
Coating: hypromellose;
talc.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
No special storage precautions.
06.5 Nature of the immediate packaging and contents of the package
Cardboard box and PVC + PVdC / Al blister containing 4 tablets.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
BENEDETTI & Co. S.p.A., via Bolognese n.250 - 51020 Pistoia (Italy)
08.0 MARKETING AUTHORIZATION NUMBER
ASTON 70 mg film-coated tablets - 4 tablets: AIC n. 037444015
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
08/11/2008
10.0 DATE OF REVISION OF THE TEXT
March 2016
