Alendronate, tablets 70 mg 4 pcs

The active ingredient in Alendronate Canon, alendronate sodium trihydrate, is a bisphosphonate (from the group of aminobisphosphonates – synthetic analogues of pyrophosphate binding hydroxyapatite present in bone) which inhibits osteoclast-mediated bone resorption without directly affecting new bone formation.

Alendronic acid predominantly localizes in areas of active bone resorption.

It inhibits osteoclast activity, but has no effect on osteoclast recruitment and attachment. During treatment with alendronic acid bone tissue with normal histological structure is formed.

Pharmacokinetics

Absorption

The bioavailability of alendronic acid when taken orally on an empty stomach in the morning two hours before a standard breakfast at a dose of 5-70 mg is 0.64% in women and 0.6% in men. When alendronic acid was taken on an empty stomach 0.5-1 hours before a standard breakfast, the bioavailability decreased to 0.46% and 0.39%, respectively.

The bioavailability of alendronic acid is significantly reduced if the drug is taken less than 30 minutes before meals or liquids, the bioavailability is minimal when taken with food or within two hours after meals.

If alendronic acid is taken concomitantly with coffee or orange juice, the bioavailability is reduced by approximately 60%.

Distribution

The average equilibrium volume of distribution, excluding bone, in humans is at least 28 liters. Plasma concentrations of alendronic acid after oral administration of a therapeutic dose are too low for analytical detection (< 5 ng/mL). Binding to plasma proteins in humans is approximately 78%.

Metabolism

There is no evidence that alendronic acid is metabolized in humans or animals.

Excretion

Excreted unchanged. Excretion is characterized by rapid reduction of alendronic acid concentration in blood plasma and extremely slow release from bones. When administered intravenously after 6 hours the plasma concentration decreases by more than 95%.

Alendronic acid absorbed but not embedded in bone tissue is rapidly excreted by the kidneys. After a single intravenous dose of [14C]alendronic acid, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no excretion in the feces.

The renal clearance of alendronic acid was 71 mL/min, and systemic clearance did not exceed 200 mL/min. Plasma concentrations decreased by more than 95% within six hours after intravenous administration. The end-phase elimination half-life in humans has been estimated to exceed ten years, reflecting the skeletal release of alendronic acid.

Alendronic acid is not excreted through the acid and basic kidney transport systems in rats; thus, it would not be expected to impair the excretion of other drugs through these systems in humans.

Pharmacokinetics in Special Patient Groups

Position

The bioavailability of alendronic acid is not significantly different in men and women.

Race

Pharmacokinetic differences by race have not been studied.

Elderly patients

The bioavailability and excretion of alendronic acid are similar in elderly and younger patients.

Patients with impaired liver function

In patients with impaired liver function there is no need to adjust the dose of alendronic acid because it is not metabolized and excreted with the bile.

Hepatic impairment

Preclinical studies have shown that the drug, which does not accumulate in bone tissue, is rapidly excreted in the urine. No evidence of saturation accumulation in bone tissue was found after repeated administration of cumulative intravenous doses up to 35 mg/kg in animals.

While no clinical data are available, it is likely that, as in animals, excretion of alendronic acid through the kidneys will be reduced in patients with impaired renal function.

Hence, slightly greater accumulation of alendronic acid in bone tissue can be expected in patients with impaired renal function (see section “Dosage and administration”).

Indications

Climax, Osteoporosis, Broken Bones

• Treatment of osteoporosis in postmenopausal women to prevent fractures, including hip fractures and compression fractures of the spine.
• Treatment of osteoporosis in men to prevent fractures.
  

Active ingredient

Alendronic acid

Composition

Alendronate sodium trihydrate 91.36 mg,

Translated into alendronic acid 70.00 mg.

Auxiliary substances:

Dose 70 mg:

Corn starch 50.00 mg,

lactose monohydrate 45.44 mg, <

Magnesium stearate 1.80 mg,

Microcrystalline cellulose 171.40 mg.

How to take, the dosage

Orally, 2 hours (but not less than 30 minutes) before the first meal, water or other medication. The recommended dose for osteoporosis in postmenopausal women and osteoporosis in men is 70 mg once a week or 10 mg once a day.

The optimal duration of osteoporosis therapy with bisphosphonates is not established. The need for continued bisphosphonate therapy should be evaluated by the treating physician on a regular basis based on the benefit/risk of Alendronate Canon for each patient, especially after 5 or more years of use.

To ensure adequate absorption of the drug:

Alendronate Canon should be taken at least 30 minutes before the first meal of food, drink, or daily medication, washed down with plain water only. Other drinks (including mineral water, coffee, tea, juices), food and some medicinal products can decrease absorption of Alendronate Canon.

To facilitate the entry of the tablet into the stomach and reduce the likelihood of local irritation and esophageal irritation/disorders:

• Alendronate Canon should be taken immediately after getting out of bed in the morning, with a full glass of plain water (at least 200 ml);
• Patients should swallow the Alendronate Canon tablet whole. The tablet should not be crumbled, chewed or mashed in the mouth because of the possible formation of ulcers in the mouth and pharynx;
• Patients should not lie down before their first meal, which should be at least 30 minutes after taking the tablet;
• Alendronate Canon should not be taken before bedtime or before getting up from bed.
• Patients should also take calcium and vitamin D supplements if their intake with food is insufficient.

If you accidentally miss a dose of 70 mg once a week, take one tablet the morning of the following day. You should not take two tablets on the same day but you should continue taking one tablet on the day of the week that you have chosen to take it since the start of treatment.

Children

Alendronate Canon should not be used in children under 18 years of age due to insufficient safety and efficacy data on diseases associated with childhood osteoporosis.

Use in elderly patients

No differences in the efficacy or safety profiles of alendronate have been observed in clinical trials depending on age. Therefore, no dose adjustment is required for elderly patients.

Administration in renal insufficiency

No dose adjustment is required for patients with mild to moderate renal insufficiency (with glomerular filtration rate (GFR) over 35 ml/min). The drug Alendronate Canon is not recommended for patients with renal impairment with a GFR less than 35 ml/min due to insufficient data on its use.

No studies were conducted on the use of alendronic acid in a dose of 70 mg once a week in the treatment of glucocorticosteroid-induced osteoporosis.

Interaction

Alendronic acid absorption may be impaired if the drug is taken simultaneously with food, beverages (including mineral water), calcium preparations, antacids and other medicinal products for oral administration.

In this regard, the interval between taking the drug Alendronate Canon and other drugs taken orally should be at least 30 minutes.

No other clinically significant drug-drug interactions are expected. In clinical trials, some patients received estrogen (intravaginally, transdermally, or orally) while taking alendronic acid. No adverse events associated with their concomitant use have been identified.

Because the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with the development of gastrointestinal erosive ulcers, caution should be exercised when using NSAIDs and alendronic acid concomitantly.

While no specific interaction studies have been conducted, alendronic acid has been used concomitantly with a wide range of commonly prescribed medications in clinical studies with no evidence of clinical adverse interactions.

Special Instructions

Alendronate should only be drunk with plain water, because other drinks (including mineral water, coffee, tea, orange juice) reduce absorption of alendronic acid.

The absorption of bisphosphonates is significantly reduced with simultaneous food intake.
To reduce the irritant effect on the esophagus, Alendronate should be taken immediately after rising in the morning, with a full glass of water.

After intake, stay upright (standing or sitting) for 30 minutes (it is dangerous to use the drug if the patient is unable to stand or sit upright for the specified time). Taking Alendronate before bedtime or while sitting upright increases the risk of esophagitis.

The patient should be informed to stop taking Alendronate and consult a physician if dysphagia, swallowing pain, sore throat pain, or heartburn develop.
If hypocalcemia is present, it should be corrected before starting treatment.

Mineral metabolism disorders leading to hypocalcemia must be eliminated (vitamin D deficiency, hypoparathyroidism, calcium malabsorption). Therapy should be carried out with a diet rich in calcium salts.

When taking bisphosphonates (especially with concomitant therapy with glucocorticosteroid drugs), adequate intake of calcium and vitamin D with food or in the form of medications should be provided.

In the course of treatment due to the positive effect of alendronic acid on bone mineral density a slight asymptomatic decrease in serum calcium and phosphate concentrations may be observed.

Patients with underlying risk factors (e.g., cancer, chemotherapy, radiation therapy, glucocorticosteroid drugs, poor oral hygiene) should have a dental workup with appropriate dental prophylaxis prior to bisphosphonate therapy.

Patients on bisphosphonate treatment should avoid invasive dental procedures if possible. Osteonecrosis of the jaw, usually associated with tooth extraction and/or local infection (including osteomyelitis), has been reported in cancer patients who received bisphosphonates intravenously (many of them also received chemotherapy and glucocorticosteroid drugs).

There have been reports of osteonecrosis of the jaw in patients with osteoporosis when bisphosonates were given orally.

In patients with osteonecrosis of the jaw who are on bisphosphonate therapy, dental surgery may worsen the condition.

If surgical interventions are necessary, consider that there is no data on the possibility of reducing the risk of jaw osteonecrosis after bisphosphonate withdrawal. Prescriptions and recommendations from the treating physician must be based on an individual assessment of the benefit/risk ratio for each patient.

Contraindications

• High sensitivity to components of Alendronate;
• hypocalcemia;
• Inability to stand upright (stand or sit upright) for at least 30 min;
• severe renal insufficiency (creatinine clearance less than 35 ml/min);
• severe mineral metabolism disorders;
• strictures or achalasia of the esophagus and other conditions that lead to difficulty in the movement of food through the esophagus;
• severe hypoparathyroidism;
• calcium malabsorption;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• pregnancy;
• lactation period;
• childhood.

With caution

Diseases of the gastrointestinal tract (GIT) in the acute phase (dysphagia, esophagitis, gastritis, duodenitis, peptic ulcer and duodenal ulcer), vitamin D deficiency.

Side effects

The following adverse events have been reported during clinical studies and/or post-registration use.

The frequency of adverse events has been established as follows: Very common (≥ 1/10), common (≥ 1/100, < 1/10),

infrequent (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000),

very rare (< 1/10000, including individual cases).

Immune system disorders
Rare: hypersensitivity reactions, including urticaria and Quincke’s edema

Metabolic and nutritional disorders
Rare: Symptomatic hypocalcemia, often with a background of predisposition factors¹

Nervous system disorders
Often: Headache, dizziness²
Infrequent: taste disturbance²

Visual organ disorders
Infrequent: Visual inflammation (uveitis, scleritis, episcleritis)

Hearing organ disorders and labyrinth disorders
Frequent: systemic vertigo²
Very rare: osteonecrosis of the external auditory canal (adverse bisphosphonate class reaction)

Gastrointestinal tract disorders
Often: abdominal pain, dyspepsia, constipation, diarrhea, flatulence, esophageal ulcer, dysphagia, abdominal bloating, acidic belching
Infrequent: Nausea, vomiting, gastritis, esophagitis³, esophageal erosion, melena²
Rarely: esophageal stricture³, esophageal ulceration³, upper gastrointestinal tract disorders (perforation, ulcers, bleeding)¹

Skin and subcutaneous tissue disorders
Often: Alopecia², itching²
Infrequent: skin rash, erythema,
Rarely: Skin rash with photosensitivity, severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis⁴

Skeletal-muscular and connective tissue disorders
Very common: Skeletal-muscular pain (in bones, muscles, or joints), sometimes severe pain^1,2
Frequently: joint swelling²

Rarely: Local osteonecrosis of the jaw associated primarily with prior tooth extraction and/or local infection (including osteomyelitis), often with slow recovery^1,4, atypical subjacent and diaphyseal fractures of the femur (adverse reaction class of bisphosphonates)⁵

General disorders and disorders at the site of administration
Often: Asthenia², peripheral edema²
Infrequent: Transient symptoms as an acute phase reaction (myalgia, malaise, and rarely fever), usually in association with initiation of treatment²

1 See Special Indications.

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

3 See sections “Administration and Doses” and “Special Precautions”.

4 This adverse reaction was established during post-registration follow-up.

5 Established during post-registration use.

Overdose

Symptoms: hypocalcemia, hypophosphatemia, adverse reactions from the gastrointestinal tract (GIT) – heartburn, esophagitis, erosive and ulcerative lesions of the GIT, diarrhea.

Treatment: milk or calcium-containing antacids to bind alendronic acid. Because of the risk of esophageal irritation, vomiting should not be induced. The patient should be in an upright position.

Pregnancy use

The use of alendronic acid during pregnancy is contraindicated.

No data on the use of alendronic acid in pregnant women.

Animal studies indicate no direct adverse effects during pregnancy, embryonic and fetal development or postnatal development. Alendronic acid administered to rats during pregnancy caused dystocia due to hypocalcemia.

Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over several years. The amount of bisphosphonate incorporated into a woman’s bone tissue and released from it into the systemic bloodstream is directly related to the doses and duration of treatment.

There is a theoretical risk of effects on the fetus (particularly on bone tissue) if pregnancy occurs after bisphosphonate therapy. There are no data on direct embryotoxic or teratogenic effects. The effect of such risk factors on the fetus, such as the time between discontinuation of bisphosphonates therapy and the onset of pregnancy, routes of administration (intravenous, oral), has not been studied.

Breast-feeding

No data on penetration into breast milk; administration of alendronic acid during breast-feeding is contraindicated.

Similarities

Foroza, Osterepar