Active ingredients: Alendronic acid
FOSAMAX 10 mg tablets
Fosamax package inserts are available for pack sizes:- FOSAMAX 10 mg tablets
- FOSAMAX 70 mg tablets
Why is Fosamax used? What is it for?
What is Fosamax
Fosamax contains the active substance alendronic acid and belongs to a group of medicines called bisphosphonates, which affect the structure and density (mineralization) of bones.
What Fosamax is used for
Fosamax is used to treat a disease that makes bones brittle and more prone to breaking (osteoporosis) in men and women after menopause. Fosamax is also used in men and women to treat and prevent osteoporosis caused by a particular class of medicines used to treat inflammation called glucocorticoids.
What is osteoporosis?
Osteoporosis is a disease that makes bones more fragile until they fracture. In menopause, the ovaries do not produce the female hormones, estrogen, which help keep a woman's skeleton healthy. As a result, tissue loss occurs. bone and bone becomes more fragile. The risk of osteoporosis is greater the earlier the woman reaches menopause. Osteoporosis can also occur in men. Glucocorticoids can also cause bone loss and osteoporosis in both men and women. In the early stages, osteoporosis usually has no symptoms. However, if no treatment is done, fractures can occur. Although fractures are usually painful, fractures of the bones of the spine may go unnoticed until a decrease in height is noted. Fractures can occur during normal daily activity, such as lifting weights and even minor injuries that do not normally cause bone fractures. Fractures occur most frequently in the hip, spine, or wrist and can be not only painful but can also be painful. lead to significant deformities and disabilities, such as "increased curvature of the back (kyphosis) and limitations in movement.
Contraindications When Fosamax should not be used
Do not take Fosamax
- if you are allergic to the active substance or any of the other ingredients of this medicine (listed in section 6)
- if you have problems with the esophagus (the tube that connects the mouth with the stomach) that delay its emptying such as narrowing (stricture) and changes in function (achalasia)
- if you are unable to stand or sit upright for at least 30 minutes
- if you have low blood calcium levels (hypocalcaemia)
- if you have severe kidney problems (severe kidney failure)
- if you are pregnant or breastfeeding
If you think that any of these apply to you, do not take the tablets. Consult your doctor and follow his instructions.
Precautions for use What you need to know before taking Fosamax
Talk to your doctor or pharmacist before taking Fosamax.
Tell your doctor before you start taking Fosamax:
- if you have difficulty swallowing (dysphagia), or if you have problems affecting the digestive system such as esophageal diseases, inflammation of the stomach (gastritis) or the first part of the intestine (duodenitis). If you have previously suffered from severe stomach or duodenal diseases such as ulcers, stomach or intestinal bleeding, which occurred within the last year, or have had stomach or esophageal surgery, as Fosamax can have irritating effects and potentially worsen gastrointestinal disease Basic.
- if you have been told that you have a disease associated with changes in the cells that line the lower part of the esophagus (Barrett's esophagus)
- if you have cancer
- if you are undergoing chemotherapy, radiotherapy or therapy with medicines that inhibit angiogenesis (development of new blood vessels from existing ones)
- if you are taking medicines to treat inflammation (glucocorticoids)
- if you smoke, as smoking can increase the risk of dental problems
You may be asked to have a check-up by your dentist (dental) before starting treatment with Fosamax.
It is important to maintain good oral hygiene while being treated with Fosamax. You should have periodic dental check-ups throughout your treatment and you should contact your doctor or dentist if you experience any kind of mouth or tooth problem such as loosening, pain or swelling.
If you are being treated by a dentist or are due to have a dental procedure or tooth extraction, please tell your dentist that you are taking Fosamax.
Stop taking Fosamax and tell your doctor immediately if you have difficulty swallowing (dysphagia), if you experience pain when swallowing (odynophagia), chest pain (retrosternal pain) or if you experience the onset or worsening of burning sensations in the chest (heartburn).
If you do not take Fosamax properly or if you continue to take it after you experience these symptoms, the risk of serious side effects in the esophagus may worsen.
It is very important that you know how to take this medicine (see section 3).
Treatment with Fosamax should only be started after your doctor has determined that the cause of your osteoporosis is lack of female hormones (estrogen) and / or age, excluding other causes.
Fosamax can irritate the mucosa of the upper gastrointestinal tract.
The risk of serious esophageal side effects appears to be greater in patients who do not take Fosamax properly or who continue to take it after symptoms of an "esophageal irritation." It is important to know that if certain precautions are not followed, it can increase the risk of esophageal problems.
Undesirable effects affecting the esophagus such as irritation (oesophagitis), lesions (ulcers and erosions) rarely followed by narrowing or perforation have been reported in patients taking Fosamax. Some of these undesirable effects occurred severely and required hospitalization.
In cancer patients taking bisphosphonates, mainly intravenously, bone death in the jaw (osteonecrosis), usually associated with tooth extraction or local infection (including osteomyelitis), has been reported. Many of these patients were also treated with chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis who took oral bisphosphonates.
Bone, joint and muscle pain have been reported in patients treated with bisphosphonates. Since the medicine has been marketed, these symptoms have rarely been severe or have caused disability (see section 4). The timing of symptom onset ranged from one day to several months after initiation of treatment. In most patients, discontinuation of treatment resulted in symptom improvement. Following re-administration of the same or another medicine of the same class, some patients have experienced a return of symptoms.
Unusual fractures of the femur have been reported, mainly in patients on long-term therapy with this class of drugs for osteoporosis. These fractures occur spontaneously or after minor trauma, and some patients experience pain in the thigh or groin.
X-rays often show this type of fracture (mechanical stress fracture) weeks or months before a complete femoral fracture occurs.
Fractures often occur in both femurs (bilateral fractures), so in bisphosphonate-treated patients who have fractured one femur, the other should also be examined.
Limited healing of these fractures has also been reported.In patients with suspected fracture of the femur, the physician will evaluate the discontinuation of bisphosphonate therapy pending evaluation of the benefit to the patient in relation to the risk.
During treatment with this type of medicine, any type of pain in the thigh, hip or groin should be reported to the doctor and, if such symptoms occur, they should be checked to exclude the presence of a fracture of the femur.
Since the medicine has been commercially available there have been rare reports of serious skin reactions including flaking (Stevens-Johnson syndrome) and breakdown of the skin (toxic epidermal necrolysis).
Before starting treatment with Fosamax and periodically thereafter, your doctor is likely to request that your blood calcium levels (calcaemia) be checked. Reduced blood calcium level (hypocalcaemia) must be corrected before starting Fosamax therapy (see section 2). Your doctor will need to monitor blood calcium levels and symptoms of hypocalcaemia while taking Fosamax and treat other disorders, such as vitamin D deficiency.
Rare cases of low calcium levels (hypocalcaemia), occasionally severe, have occurred during treatment with Fosamax, particularly in the presence of conditions that may promote hypocalcaemia, such as poor production of thyroid hormones (hypoparathyroidism), deficiency vitamin D and calcium malabsorption, particularly in patients taking glucocorticoids, medicines that reduce calcium absorption. It is recommended to ensure adequate calcium and vitamin D intake in patients on glucocorticoid therapy.
Children and adolescents
Fosamax is not recommended for children under the age of 18.
Interactions Which drugs or foods may change the effect of Fosamax
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, even those obtained without a prescription.
Calcium supplements, acid neutralizing medicines and some oral medicines are likely to interfere with the absorption of Fosamax when taken at the same time. At least 30 minutes should elapse after taking Fosamax before you can take any other medicines (see instructions provided in section 3 "How to take Fosamax").
Some medicines called NSAIDs (for example aspirin or ibuprofen) to treat inflammation of the joints and bones (rheumatism) or for long-term pain may cause digestive system problems. Therefore, caution should be exercised when these medicinal products are taken concomitantly with Fosamax.
Fosamax with food and drink
Food and drinks (including mineral water) are likely to make Fosamax less effective if taken at the same time. It is therefore important to follow the instructions given in section 3 "How to take Fosamax".
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Fosamax is only indicated for women after menopause.
Driving and using machines
Side effects (including blurred vision, dizziness and severe bone, muscle or joint pain) have been reported while taking Fosamax which may affect your ability to drive or use machines. The response to Fosamax may vary for each individual ( see paragraph 4).
Fosamax contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Fosamax: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose is 1 tablet of 10 mg once a day.
The optimal duration of osteoporosis treatment with this medicine has not been established.
The doctor will periodically evaluate the optimal duration of treatment according to the benefits obtained against the potential risks of Fosamax, particularly after 5 or more years of use.
Fosamax should be taken at least 30 minutes before any food, drink or medicine of the day together with tap water only. Other drinks (including mineral water), food and some medicines are likely to reduce the absorption of Fosamax (see section 2).
Fosamax is only effective when taken on an empty stomach.
To facilitate release in the stomach and thus reduce the possibility of local and esophageal irritation / side effects:
- take the Fosamax tablet in the morning, only after getting out of bed to start the day, with a glass of tap water (not mineral water, not less than 200 ml);
- swallow the Fosamax tablet whole. Do not chew, crush or let the tablet dissolve in the mouth, due to the potential risk of injury to the mouth and pharynx;
- do not lie down until you have eaten something and, before lying down, make sure that at least 30 minutes have passed since taking the Fosamax tablet;
- do not take the Fosamax tablet at bedtime or before getting out of bed at the beginning of the day;
- do not take Fosamax with coffee or tea
- do not take Fosamax with juice or milk
- if you experience difficulty or pain in swallowing, chest pain or develop or worsen heartburn, stop taking Fosamax and contact your doctor.
Your doctor will advise you to take calcium and vitamin D supplements if their intake with your normal diet is not adequate (see section 2).
Use in children and adolescents
Fosamax is not recommended for children under 18 years of age.
Use in the elderly
No dose adjustment is necessary in elderly patients.
Use in case of impaired kidney function
No dose adjustment is necessary in patients with mild to moderate degree of renal impairment (creatinine clearance greater than 35 ml / min). Fosamax should not be administered in patients with severe renal insufficiency (creatinine clearance <35 ml / min), as there is no information on this.
If you forget to take Fosamax
If you forget to take a Fosamax tablet, take one tablet the morning after the day you notice you have forgotten. Do not take a double dose to make up for a forgotten tablet. Resume taking the tablet daily as previously stated. If in doubt, contact your doctor.
If you stop taking Fosamax
It is important to continue taking Fosamax for as long as your doctor prescribes it. Fosamax is only effective for treating osteoporosis if you continue to take the tablets.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Fosamax
If you have taken too many tablets by mistake, drink a glass of milk or take antacid medicines and contact your doctor immediately or go to the nearest hospital. Do not induce vomiting and do not lie down to avoid irritation of the esophagus.
Side Effects What are the side effects of Fosamax
Like all medicines, this medicine 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 (occurs in at least 1 in 10 patients treated)
- Common (occurs in at least 1 in 100 and less than 1 in 10 patients treated)
- Uncommon (occurs in at least 1 in 1,000 and less than 1 in 100 patients treated)
- Rare (occurs in at least 1 in 10,000 and less than 1 in 1,000 patients treated)
- Very rare (occurs in less than 1 in 10,000 patients treated).
Very common:
- bone, muscle or joint pain, often severe in intensity
- slight and temporary decreases in calcium and phosphate values in the blood, generally within normal limits.
Common:
- headache, dizziness
- dizziness
- abdominal pain, unpleasant feeling in the stomach or belching after meals, constipation, feeling of fullness or bloating in the stomach, diarrhea, flatulence (gas), heartburn, difficulty swallowing, pain in swallowing, ulcers in the esophagus causing pain chest, burning or difficulty or pain in swallowing
- hair loss (alopecia), itching
- swelling of the joints
- tiredness, swelling of the hands or legs (peripheral edema)
Uncommon:
- taste disturbance (dysgeusia)
- blurred vision, pain or redness of the eyes. Inflammation of the eye (uveitis, scleritis, or episcleritis)
- nausea, vomiting, irritation or inflammation of the esophagus or stomach, black or dark stools
- rash, redness of the skin
- transient flu-like symptoms such as body aches, generally feeling unwell and sometimes with fever usually at the start of treatment
Rare:
- allergic reactions such as hives, swelling of the face, lips, tongue and / or throat, difficulty in breathing and swallowing
- symptoms of low blood calcium levels including muscle cramps or spasms and / or tingling in the fingers or around the mouth
- narrowing of the esophagus; mouth ulcers when the tablets are chewed or sucked; stomach or peptic ulcers (sometimes severe or with bleeding)
- rash worsened by exposure to sunlight, severe skin reactions such as flaking (Stevens-Johnson syndrome) and breakdown of the skin (toxic epidermal necrolysis)
- 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 bone damage in the jaw / jaw (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 may be an early indication. of a possible fracture of the femur.
Very rare:
- talk to your doctor if you have ear pain, discharge from the ear and / or ear infection. These episodes could be symptoms of bone damage in the ear.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: www.agenziafarmaco.it/it/responsabili By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Deadline "> Other information
What Fosamax contains
- The active ingredient is alendronic acid sodium salt 13.05 mg, corresponding to alendronic acid 10 mg.
- The other ingredients are: microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, magnesium stearate, carnauba wax.
What Fosamax looks like and contents of the pack
Fosamax comes in tablet form.
The tablets are packed in opaque PVC and aluminum blisters.
Each blister contains 14 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 -
FOSAMAX 10 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
One tablet of FOSAMAX 10 mg tablets contains:
Active principle: alendronic acid sodium salt 13.05 mg corresponding to alendronic acid 10 mg.
Excipient with known effects: lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Tablets.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
FOSAMAX is indicated
• in the treatment of osteoporosis in postmenopausal women and men
• in the treatment and prevention of glycocorticoid-induced osteoporosis (GIOP) in men and women.
04.2 Posology and method of administration -
Dosage
The recommended dose is 10 mg once a day. 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.
Method of administration
To obtain adequate absorption of alendronate:
FOSAMAX should be swallowed at least 30 minutes before any food, drink or medicine of the day together with tap water only. Other beverages (including mineral water), food and some medicinal products are likely to reduce the absorption of alendronate (see section 4.5).
To facilitate gastric release and thus reduce the possibility of local and oesophageal irritation / adverse events (see section 4.4):
• FOSAMAX should be swallowed only after getting out of bed to start the day, with a full glass of tap water (not less than 200 ml).
• The patient should only swallow FOSAMAX whole. 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 FOSAMAX.
• FOSAMAX should not be taken at bedtime or before getting out of bed at the beginning of the day.
Patients should be advised that if they miss their daily dose of FOSAMAX 10 mg, they should take one tablet on the morning following the day they are aware of it. Two tablets should not be taken on the same day, but one tablet should be restarted per day as previously stated.
Patients should take calcium and vitamin D supplements if dietary intake is inadequate (see section 4.4).
Use in the elderly
In clinical studies, no age-related difference in the efficacy or safety profiles of alendronate was demonstrated. Therefore, no dose adjustment is necessary in elderly patients.
Use in case of renal impairment
No dose 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 population
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).
04.3 Contraindications -
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Disorders of the esophagus and other factors that delay oesophageal emptying, such as stricture and achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Severe renal insufficiency (see section 4.2).
• 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). In patients with esophagus Barrett already known, prescribers should weigh the potential benefits and risks of alendronate on an individual basis.
Undesirable reactions affecting the esophagus (some severe and requiring hospitalization) 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 medicine (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 treated with regimens including bisphosphonates administered primarily intravenously. Many of these patients were treated. also 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's risk of developing osteonecrosis of the jaw, the following risk factors should be considered:
• potency of bisphosphonate (maximum for zoledronic acid), route of administration (see above) and cumulative dose
• cancer, chemotherapy, radiotherapy, corticosteroids, angiogenesis inhibitors, smoking
• a 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 health, 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 develop osteonecrosis of the jaw during bisphosphonate therapy, dental surgery can exacerbate the condition. For patients requiring dental surgery, there are no data available to suggest that discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw.
The clinical judgment of the treating physician must guide the management program of each patient, based on the individual assessment of the risk / benefit ratio.
During treatment with bisphosphonates, 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 tooth mobility, pain or swelling.
Osteonecrosis of the external auditory canal has been reported in conjunction with the use of bisphosphonates, predominantly in association with long-term therapies. 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 present with ear symptoms such as pain or discharge, or chronic ear infections.
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 timing of symptom onset 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 medicine or another bisphosphonate, a subgroup of patients experienced a relapse of symptoms.
Atypical fractures of the femur
Atypical subtrochanteric and shaft 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 treatment with bisphosphonates, 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 fracture of the femur.
During post-marketing experience there have been rare reports of severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
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).
Before starting treatment, other causes of osteoporosis should be considered besides estrogen deficiency, age and use of glucocorticoids.
Hypocalcaemia should be corrected before starting alendronate therapy (see section 4.3). Other disorders of mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) should also be treated appropriately. In patients with these clinical conditions, serum calcium and symptoms of hypocalcaemia should be monitored during therapy with FOSAMAX.
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 reduced. Such 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.
Excipients
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
Food and beverages (including mineral water), calcium supplements, antacids and other oral medicines, 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 to elapse after taking alendronate before taking any other medicinal product orally (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.
Since the use of NSAIDs is associated with gastrointestinal irritation, caution should be exercised during concomitant treatment with alendronate.
Although specific interaction studies have not been conducted, alendronate has been used in combination with a wide range of commonly prescribed medicinal products in clinical studies without giving rise to evidence of adverse clinical reactions.
04.6 Pregnancy and breastfeeding -
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).
Feeding time
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 effects on the ability to drive and use machines have been performed. However, some adverse reactions that have been reported with FOSAMAX (including blurred vision, dizziness and severe bone, muscle or joint pain) may affect the ability of some patients to drive or use machines. Individual responses to FOSAMAX 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 substantially 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 medicinal product:
Very common (≥1 / 10), Common (≥1 / 100,
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
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 erect.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Medicinal products acting on bone structure and mineralization, bisphosphonates.
ATC code: M05BA04.
Alendronate is a bisphosphonate which, in animal studies, acts as a specific inhibitor of osteoclast-mediated bone resorption. Bisphosphonates are synthetic analogues of pyrophosphate, which have a "high affinity for" hydroxyapatite present in bone. From what emerges from animal studies, alendronate is preferentially localized in sites where bone resorption occurs, specifically beyond under osteoclasts, and inhibits osteoclastic bone resorption without any direct effect on bone formation. Since bone resorption and bone formation are associated, there is also a reduction in bone formation but to a lesser extent than resorption, which leads to an increase in bone mass. Upon exposure to alendronate, it is incorporated into the matrix of newly formed normal bone, where it is pharmacologically inactive.
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 1).
In the initial efficacy studies, the 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. Also the organism's DMO in full it increased significantly. C "was a reduction of 48% (alendronate 3.2% vs placebo 6.2%) in the proportion of alendronate-treated patients with one or more vertebral fractures compared to those treated with placebo. In 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. in full.
In a three-year placebo-controlled study (FIT 1), alendronate once daily (5 mg once daily for two years and 10 mg once daily for one year) was used in 2,027 patients with at least one vertebral fracture (from compression) 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%).
Treatment of osteoporosis in men
The efficacy of FOSAMAX 10 mg once daily in men with osteoporosis was demonstrated in a two-year, placebo-controlled, double-blind, multicenter study in which a total of 241 men aged 31 to 87 were enrolled. age (mean, 63). At two years, mean increases in BMD compared to placebo in men treated with FOSAMAX 10 mg daily were: lumbar spine, 5.3%; femoral neck, 2.6%; trochanter , 3.1%; and organism in full, 1.6% (p = 0.001 for each comparison). FOSAMAX was effective regardless of age, race, gonad function, baseline bone turnover rate, or baseline BMD. In accordance with much larger studies conducted in postmenopausal women, FOSAMAX in these men 10 mg per day reduced the incidence of new vertebral fractures (ascertained by quantitative radiography) compared to placebo (0.8% vs 7.1%, respectively; p = 0.017) and, in parallel, also decreased the reduction in height (-0.6 vs -2.4 mm, respectively; p = 0.022).
Glycocorticoid-induced osteoporosis
Prolonged use of glucocorticoids is commonly associated with the development of osteoporosis which can cause fractures (particularly vertebral, hip and rib fractures). It occurs in both men and women of all ages. Although the study was not designed. with such potency to allow comparison between the different doses of alendronate, the 10 mg dose seemed capable of producing numerically superior effects compared to
5 mg at all sites in 24 months. In the overall patient population, alendronate 10 mg once daily increased BMD in the spine bone by 4.6% compared with 3.6% in patients treated with 5 mg once daily. Corresponding values for the increases at the other sites were: total hip 4.3%, femoral neck 3.5%, trochanter 5.1%, and organism in full 1.5%, compared to 3.2%, 3.0%, 3.4% and 1.1% in the 5 mg group. Therefore, alendronate 10 mg once daily showed consistent numerical increases in BMD greater than those of the 5 mg dose, with differences of between 0.3% at the organism level. in full and 1.7% at the level of the trochanter.
Laboratory data
In clinical trials, transient and mild asymptomatic reductions 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 population
Alendronate sodium has been studied in a small number of patients with osteogenesis imperfecta under the age of 18. The 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 oral bioavailability of alendronate in women is approximately 0.7% for doses of 5 to 40 mg, administered after an overnight fast and 2 hours before a standardized breakfast. oral in men (0.6%) was similar to that in women. Similarly, bioavailability was reduced (by approximately 40%) when alendronate was administered an "hour or half" before a standardized breakfast. In osteoporosis studies, FOSAMAX was effective when administered at least 30 minutes before the first food or drink of the day.
Bioavailability was negligible when alendronate was administered within two hours after a standardized breakfast. Concomitant administration of coffee or orange juice with alendronate reduced its bioavailability by approximately 60%.
In healthy individuals, oral administration of prednisone (20 mg three times daily for five days) did not result in clinically significant changes in the oral bioavailability of alendronate (a mean increase range of 20 to 40%).
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. The plasma concentrations of the drug following therapeutic oral doses are too low to be detected (plasma protein is approximately 78%.
Biotransformation
In both humans and animals, there is no evidence that alendronate is metabolised.
Elimination
Following an 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 intravenous administration of 10 mg la clearance of alendronate was 71 mL / min. Plasma concentrations fell by more than 95% within 6 hours after intravenous administration.
In rats, renal excretion of alendronate does not occur via acid or base transport systems and therefore is not expected to interfere at this level with the excretion of other medicinal products in humans.
Preclinical studies show that the drug that is not deposited in bone is rapidly excreted in the urine. There is no evidence in animals of bone absorption saturation after chronic treatment with cumulative intravenous doses up to 35 mg / kg. 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, increased accumulation of alendronate in bone might be expected in patients with impaired renal function (see section 4.2).
05.3 Preclinical safety data -
Animal toxicology
The oral LD of alendronate in female rats and mice is 552 mg / kg (3256 mg / m²) and 966 mg / kg (2898 mg / m²), respectively (2760 and 4830 times the recommended dose for the treatment of osteoporosis. in postmenopausal women considering a body weight of 50 kg). In males these values are slightly higher: 626 and 1280 mg / kg respectively. In dogs, doses up to 200 mg / kg (4000 mg / m²) (1000 times the recommended dose for the treatment of osteoporosis in postmenopausal women considering a body weight of 50 kg) were not lethal.
No evidence of a carcinogenic effect was observed in a 105-week study in rats receiving oral doses up to 3.75 mg / kg / day and in a 92-week study in mice receiving oral doses up to 10 mg / kg. / day.
Alendronate did not show genotoxicity in the microbial mutagenesis test in vitro with or without metabolic activation. Similarly, no evidence of mutagenicity was observed in a mutagenesis test in vitro on mammalian cells, in an alkaline elution test in vitro on rat hepatocytes and in a chromosomal aberration test in vivo in mice at intravenous doses up to 25 mg / kg / day (75 mg / m²). In a chromosomal aberration test in vitro on Chinese hamster ovary cells, however, alendronate showed mild positivity at concentrations greater than or equal to 5 mM in the presence of cytotoxicity.
This data is of no relevance in terms of human safety, since similar concentrations are not achievable in vivo at therapeutic doses.
Furthermore, the clear negativity of the results of 4 of the 5 genotoxicity studies, which include the most relevant studies for the evaluation of the carcinogenic potential in humans (the chromosomal aberration test in vivo and the microbial mutagenesis test) and the negativity of carcinogenicity studies in rats and mice leads to the conclusion that with alendronate in humans there is no evidence of risk of carcinogenicity and genotoxicity.
Development and Reproduction Toxicity
Alendronate had no effect on fertility and reproductive capacity (male and female) in rats up to oral doses of 5 mg / kg / day. The only effect attributed to the drug observed in these studies was dystocia in rats. which is directly related to iatrogenic hypocalcaemia. This effect can be prevented in rats with calcium supplements. Furthermore, 1.25 mg / kg / day has been shown to be the dose level at which clearly no effect is observed. In developmental toxicology studies, no undesirable effects occurred in rats and rabbits up to doses of 25 mg / kg / day and 35 mg / kg / day, respectively.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, magnesium stearate, carnauba wax.
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
In intact packaging: 2 years.
06.4 Special precautions for storage -
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package -
The tablets are contained in an opaque PVC and aluminum blister.
Fosamax 10 mg tablets: pack of 14 tablets.
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
MERCK SHARP & DOHME LIMITED
Hertford Road, Hoddesdon
Hertfordshire, United Kingdom
08.0 MARKETING AUTHORIZATION NUMBER -
Fosamax 10 mg tablets - 14 tablets AIC n.029052038
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
July 2003
10.0 DATE OF REVISION OF THE TEXT -
June 9, 2016
