Treatment of postmenopausal osteoporosis

Alendronate reduces the risk of vertebral and hip fractures

Dosage

The recommended dosage is one film-coated tablet, 70 mg ALTERRONIC ACID ALTER once a week orally.


In order to allow sufficient absorption of alendronate

· ALENDRONIC ACID ALTER should be taken on an empty stomach at least 30 minutes before the first intake of food, drinks or medications of the day and only with tap water. Other drinks (including plain or gaseous mineral water) and foods, as well as certain medicines, may reduce the absorption of alendronate (see section Interactions with other medicinal products and other forms; Of interactions).

In order to facilitate the passage to the stomach and reduce the potential for irritation or local and esophageal adverse effects (see section 4.4), the recommendations Should be observed

· The ALTERRONIC ACID ALTER tablet should be swallowed in the morning when getting up, accompanied by a glass of whole water (not less than 200 ml). >

Patients should not chew the tablet or let it dissolve in their mouth due to a risk of oropharyngeal ulceration

· Patients should not lie down before taking their first dose, which should be taken at least 30 minutes after taking the tablet. >
· Patients should not lie down for at least 30 minutes after taking ACID ALENDRONIQUE ALTER.

· ALTERRONIC ACID ALTER should not be taken at bedtime or before getting up in the morning

Patients should receive an additional calcium and vitamin D intake if there is insufficient dietary intake (see Warnings and Precautions for Use).
Use in the elderly

In clinical studies, no differences related to the age of efficacy or safety profiles of alendronic acid were observed. Therefore, no dosage adjustment is necessary in the elderly.


No dosage adjustment is necessary in patients with glomerular filtration (FG) greater than 35 ml / min. Due to insufficient experience, alendronate is not recommended in patients with renal impairment where FG is less than 35 ml / min.

Use in children (under 18 years of age)

Alendronate has been studied in a small number of patients with osteogenesis imperfecta and aged under 18 years. The results are insufficient to support its use in the child

Alendronate has not been studied in the treatment of glucocorticoid-induced osteoporosis

White, round and biconvex film-coated tablets marked "M14".

Pharmaco-therapeutics: drugs affecting mineralization and bone structure, biphosphonate, code; ATC: M05BA04.

The active substance, alendronate, is a bisphosphonate which inhibits bone resorption, osteoclastic with no direct effect on osteogenesis. Preclinical studies have shown a preferential localization of alendronate at sites where active resorption occurs Osteoclast activity is inhibited but osteoclast recruitment or anchorage is not affected . The bone formed during treatment with alendronate is of normal quality.

Treatment of osteoporosis, postmenopausal

Osteoporosis corresponds to a BMD of the spine or hip of 2.5 SD lower than the mean value of a normal young adult population or corresponds to a history of fracture fracture independently of BMD. >

The therapeutic equivalence of alendronate 70 mg once weekly (n = 519) and alendronate 10 mg daily (n = 370) was demonstrated in a multicentre study of One year in postmenopausal women with osteoporosis. The mean increases in lumbar spine BMD compared with the initial BMD were 5.1% after one year (95% CI 4.8, 5.4%) in the 70 mg group Times per week and 5.4% (CI, 95%: 5.0, 5.8%) in the 10 mg group per day. Mean increases in BMD were 2.3% and 2.9% at the femoral neck and 2.9% and 3.1% at the total hip level in the 70 mg one Times per week and 10 mg per day respectively. The two treatment groups also showed similar increases in BMD at other sites in the skeleton.

The effects of alendronate on bone mass and the incidence of fractures in postmenopausal women were examined in two initial efficacy studies of identical design (n '= 994) FIT trial (Fracture, Intervention Trial: n '= 6,459).
In the initial efficacy studies, mean increases in bone mineral density (BMD) with alendronate 10 mg / day compared to placebo at three years were 8.8%, 5, 9% and 7.8% at the level of the spine, femoral neck and trochanter, respectively. Total body BMD also significantly increased. There was a 48% (alendronate, 3.2% versus placebo: 6.2%) reduction in the proportion of patients treated with alendronate with one or more vertebral fractures compared to placebo patients. During the two-year extension of these studies, BMD at the spine and trochanter levels continued to increase and BMD at the femoral neck and total body BMD remained. Br>

The FIT study consisted of two studies: placebo-controlled studies using alendronate daily (5 mg daily for two years and 10 mg / day for one or two additional years)
< Br>

· FIT 1: a three-year study of 2,027 patients with at least one vertebral fracture prior to treatment. In this study, the daily administration of alendronate reduced the incidence of 1 new vertebral fracture by 47% (alendronate: 7.9% versus placebo: 15.0%). In addition, a statistically significant decrease was detected in the incidence of hip fractures (1.1% versus 2.2%, a reduction of 51%).

· FIT 2: a four-year study of 4,432 patients with bone loss but no fracture, initial vertebral. In this study, a significant difference was observed in the analysis of the subgroup of women with osteoporosis (37% of the overall population corresponding to the above definition of osteoporosis). The incidence of hip fractures (alendronate 1.0% versus placebo 2.2%, a decrease of 56%) and incidence of vertebral fracture (2.9% versus 5.8% , Or a decrease of 50%).

Pediatric population

Sodium alendronate was tested on a small number of patients, less than 18 years of age, suffering from bone fragility, congenital. The results are insufficient to allow the use of sodium alendronate in children with congenital bone fragility

No studies have been carried out on the effects on the ability to drive or use machines. However, some adverse reactions have been reported, and during ALTERINE ALENDRONIC ACID therapy in some patients these effects may impair ability to drive or use machines. The reaction to ALTERNATE ACID ALTER may vary from one individual to another (see section Effects, undesirable).

· Abnormalities of the esophagus and other factors, delaying oesophageal transit such as stenosis or achalasia

· Inability to stand or sit upright for at least 30 minutes.

· Hypersensitivity to the active substance or to any of the excipients

· Hypocalcaemia.

(See also Warnings and precautions for use)

Undesirable effects of the upper part of the tract, gastrointestinal

Alendronate may cause local irritation of the upper gastrointestinal mucosa. Because of the worsening potential of the underlying pathology, caution is recommended when alendronate is administered to patients with evolving high-functioning gastrointestinal disorders such as dysphagia, lesions, esophageal , Gastritis, duodenitis, ulcers, or recent history (during the preceding year) of major gastrointestinal tract such as ulcer, gastroduodenal or gastrointestinal hemorrhage, or surgery on the Upper gastrointestinal tract other than pyloroplasty (see Contraindications). For patients in whom Barrett's esophagus has been diagnosed, prescribers should evaluate the benefits and risks of alendronate on a case-by-case basis. >
Esophageal reactions (sometimes severe and requiring hospitalization), such as esophagitis, esophagus ulcers, and esophageal erosions, followed in rare cases by oesophageal stenosis, have been reported Of patients receiving alendronate. Doctors should therefore remain vigilant in case of signs or symptoms indicating a possible oesophageal reaction and should be ordered to interrupt the use of alendronate and to consult a doctor in the event of symptoms; Oesophageal irritation such as dysphagia, pain in swallowing or retrosternal pain, onset or aggravation of heartburn

The risk of severe adverse events in the esophagus appears to be greater in patients who do not take alendronate correctly and / or continue to take alendronate after the onset of symptoms; Of an esophageal irritation. It is very important that complete dosing instructions are provided to patients and that they are well understood by the patient (see Dosage and Mode of Administration) Patients should be informed that they are Increased risk of esophageal problems, failure to follow these instructions

Although no increased risk has been observed in large clinical studies, gastric and duodenal ulcers have been reported in rare cases (after placing on the market), some of which are severe and With complications.

Osteonecrosis of the jaw

Osteonecrosis of the jaw, usually associated with dental extraction and / or local infection (including osteomyelitis), has been reported in cancer patients receiving treatment with bisphosphonates mainly administered intravenously. Many of these patients also received chemotherapy and corticordes. Osteonecrosis of the jaw has also been reported in patients with osteoporosis and oral bisphosphonates.

The following risk factors should be taken into consideration during the assessment: the individual risk of developing osteonecrosis of the jaw

· Strength of bisphosphonate (higher for zoledronic acid), route of administration (see above) and cumulative dose
· Cancer, chemotherapy, radiotherapy, steroids and smoking

History of dental disease, poor oral hygiene, periodontal disease, interventions, invasive dental and dental prostheses poorly adjusted

Dental examination, accompanied by appropriate preventive dentistry, should be considered prior to any treatment with bisphosphonates in patients with poor dental status
< Code>
During treatment, these patients should avoid invasive dental procedures where possible. Dental surgery can aggravate the condition of patients developing osteonecrosis of the jaw during bisphosphonate treatment. For patients requiring dental procedures, there are no available data suggesting that discontinuation of bisphosphonate therapy reduces the risk of osteonecrosis of the jaw.
< Br>

The clinical evaluation of the attending physician should guide the conduct to be taken for each patient based on the evaluation of the report, individual benefit / risk

During bisphosphonate therapy, all patients should be encouraged to maintain good oral hygiene, to have their teeth regularly checked and to report any oral symptoms such as dental mobility, pain or swelling. Code>
Musculoskeletal pain

Bone, joint and / or muscle pain have been reported in patients taking bisphosphonates. As a result of post-marketing use, these symptoms have rarely been severe and / or disabling (see side effects). The time to onset of symptoms varied from one day to several months after starting treatment. These symptoms disappeared in most patients after discontinuation of therapy. They reappeared in a subgroup after reintroduction of the same drug or another bisphosphonate.


Atypical, subtrochanteric and diaphyseal femoral fractures have been reported under bisphosphonates, mainly in long-term patients for osteoporosis. These short transverse or oblique fractures may occur on any part of the femur from below the trochanter to the supracondylar zone. These fractures occur after minimal trauma or trauma, and some patients have pain, in the thigh or groin, often associated with radiological signs of stress fractures, weeks or months before the femoral fracture . Fractures are often bilateral, therefore, the contralateral femur should be examined in patients treated with bisphosphonates having had a diaphyseal femoral fracture. Poor consolidation of these fractures has also been reported: Discontinuation of bisphosphonate therapy in patients in whom an atypical femoral fracture is suspected should be considered in terms of the benefit / risk assessment for Patient.

During bisphosphonate therapy, patients should be advised that any pain in the thigh, hip or groin should be reported and all patients with such symptoms should be examined for a fracture Atypical femoral.
Rare cases of severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported since marketing.


Patients should be instructed in case of forgetting a dose of ALTERNATE ALTERRONIC ACID, to take one tablet the morning after they become conscious of their oblivion. They should not take two tablets on the same day and should resume a rhythm, one tablet per week, as originally scheduled on the day of their choice. >
Renal insufficiency

Alendronate is not recommended, in patients with renal insufficiency, where FG is less than 35 ml / min (see section Posology and method of administration). >

Bone and mineral metabolism

The causes of osteoporosis other than oestrogenic deficiency and aging should be considered.
Due to the positive effects of alendronate on the increased mineralization of the bone substance, decreases in serum calcium and phosphate concentrations may occur, especially in patients treated with glucocorticoids, Calcium can be decreased. These are generally mild and asymptomatic. However, symptomatic hypocalcaemia has been reported in rare cases, which have sometimes been severe and have often occurred in patients with predisposing factors (eg, hypoparathyroidism, vitamin D deficiency, and calcium malabsorption).

It is particularly important to ensure adequate intake of calcium and vitamin D. In patients receiving corticosteroids

In the case of concomitant use, it is likely that foods and beverages (including mineral water), calcium supplements, antacids and certain medications taken orally, interferes with the absorption of alendronate. Therefore, patients should wait at least 30 minutes after taking alendronate before taking any other oral medicinal product (see section 4.2 and Method of administration and Pharmacokinetic Properties). >

No other clinically significant interaction with drugs is expected. A number of patients in clinical trials received estrogens (intravaginally, transdermally or orally) while taking alendronate. No adverse effect attributable to their concomitant use has been identified

As the use of NSAIDs is associated with gastrointestinal irritation, caution should be exercised when concomitant use with alendronate.
No interaction studies have been performed. However, in clinical studies, alendronate has been used concomitantly with a wide range of commonly prescribed drugs without any indication of undesirable clinical interactions.

Without object.

Hypocalcaemia, hypophosphatemia and high gastrointestinal adverse reactions such as disturbed stomach, heartburn, esophagitis, gastritis or ulcer may result from oral overdosage Br>

No specific information is available on the treatment of an overdose of alendronate. Milk or antacids should be administered to fix alendronate. Due to the risk of irritation of the esophagus, vomiting should not be induced and the patient should remain straight (standing or sitting).
< Code>
Use during pregnancy

Alendronate should not be used during pregnancy. There are no sufficiently relevant data regarding the use of alendronate in pregnant women. Animal studies have not shown any direct deleterious effects on gestation, embryonic / fetal development or postnatal development. In the rat, alendronate administered during pregnancy resulted in dystocia associated with hypocalcaemia (see section Preclinical safety data).

Use in period of breastfeeding

It is not known whether alendronate is excreted in human milk. Due to its indication, ACID ALENDRONIQUE ALTER should not be used in lactating women.

In a one-year study, in postmenopausal women with osteoporosis, overall safety profiles, alendronate 70 mg / week (n = 519) and alendronate 10 mg / Day (n '= 370) were similar.
In two postmenopausal studies (alendronate 10 mg, n '= 196, placebo: n' = 397), the safety profiles of alendronate 10 Mg / day and placebo were similar.
The undesirable events reported by the investigators as possibly, probably or undoubtedly related to the drug are presented, below if they occurred in 1% of one of the groups, treated in the one-year study, Or in 1% of patients treated with alendronate 10 mg / day and at a higher incidence than patients receiving placebo in the three-year studies
>
One-year study

Three-year study

Alendronate 70 mg (n '= 519)

Alendronate 10 mg / day (n '= 370)

Alendronate 10 mg / day (n '= 196)

Placebo (n '= 397)

%

%

%

%

Gastrointestinal

Pain, abdominal
3.7

3.0

6,6

4.8

Dyspepsia

2.7

2.2

3.6

3,5

Acid regurgitation

1.9

2.4

2.0

4.3

Nausea

1.9

2.4

3.6

4.0

Bloating, abdominal

1.0

1,4

1.0

0.8

Constipation

0.8

1.6

3.1

1.8

Diarrhea

0.6

0.5

3.1

1.8

Dysphagia

0.4

0.5

1.0

0.0

Flatulence

0.4

1.6

2.6

0.5

Gastritis

0.2

1.1

0.5

1.3

Ulcer, gastric

0.0

1.1

0.0

0.0

Ulcer, oesophageal

0.0

0.0

1.5

0.0

Musculoskeletal system

Pain, musculoskeletal (bone, muscle or joint)

2.9

3.2

4.1

2.5

Cramp muscle

0.2

1.1

0.0

1.0

Neurological

Headache

0.4

0.3

2.6

1.5

The following adverse events have also been reported during clinical studies and / or post-marketing: very common (≥ 1/10), frequent (≥ 1/100,