Tevanate^® (Tablets) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

ATC Code

M05BA04 (Alendronic acid)

Active Substance

Alendronic acid (Rec.INN registered by WHO)

Dosage Forms

	Tevanate®	Tablets 10 mg: 30 pcs.
		Tablets 70 mg: 4 or 12 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, biconvex, without a score.

Excipients : low-substituted hydroxypropylcellulose, hydroxypropylcellulose, colloidal silicon dioxide, sodium stearyl fumarate.

10 pcs. – blisters (3) – cardboard packs.

Tablets white or almost white, round, flat, with a bevel, with an engraving “T” on one side and smooth on the other.

Excipients : microcrystalline cellulose, croscarmellose sodium, magnesium stearate.

4 pcs. – blisters (1) – cardboard packs.
4 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Bone resorption inhibitor for osteoporosis

Pharmacotherapeutic Group

Bone resorption inhibitor – bisphosphonate

Pharmacological Action

An inhibitor of bone resorption, it belongs to the group of aminobisphosphonates – synthetic analogs of pyrophosphate that bind to hydroxyapatite, which is part of bone tissue.

It increases the mineral density of the bones of the spine and other skeletal bones. The mechanism of the antiresorptive action is associated with the suppression of osteoclast function. It promotes the formation of bone tissue with a normal histological structure.

Pharmacokinetics

Absorption

When taken orally on an empty stomach in the dose range from 5 to 70 mg directly 2 hours before breakfast, the bioavailability of alendronic acid in women is 0.64%, in men – 0.6%. The bioavailability of alendronic acid decreases by 40% when taken on an empty stomach 1-1.5 hours before breakfast. After drinking coffee and orange juice, bioavailability decreases by approximately 60%.

Distribution

The binding of alendronic acid to plasma proteins is about 78%. The drug is distributed into soft tissues and then rapidly redistributes to the bones, where it is fixed, or is excreted in the urine.

The concentration of the drug in blood plasma after oral administration at a therapeutic dose is below the possible detection limit (<5 ng/ml).

Metabolism

It does not undergo biotransformation.

Excretion

It is excreted unchanged. The excretion process is characterized by a rapid decrease in the concentration of alendronic acid in the blood plasma and an extremely slow release from the bones.

The final T_1/2 exceeds 10 years, which reflects the release of the drug from bone tissue.

Indications

• Treatment of postmenopausal osteoporosis;
• Osteoporosis caused by the use of glucocorticoids.

ICD codes

Dosage Regimen

To ensure normal absorption of the drug and reduce the risk of side effects, it is necessary to strictly follow the recommendations for use and dosing.

The drug Tevanate^® is prescribed orally, 1 tab. 10 mg once/day or 1 tab. 70 mg once a week.

The tablet should be taken whole with a glass of water at least 30 minutes before the first meal, drinks, or other medications. The drug should be taken only with plain water, since other drinks (including mineral water), food, and some medications can reduce the bioavailability of alendronic acid. The tablets should not be chewed or dissolved.

After taking the drug, the patient must remain in an upright position (standing or sitting) for at least 30 minutes. The drug should not be taken before bedtime or before getting out of bed in the morning.

Adverse Reactions

The frequency of adverse events is indicated according to the following gradation: common (≥1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000).

From the digestive system common – stomach pain, dyspepsia, acid regurgitation, nausea, constipation, diarrhea, dysphagia, flatulence, gastritis, gastric ulcer, esophageal mucosal ulceration; uncommon – nausea, vomiting, gastritis, esophagitis, esophageal erosions, melena; rare – esophageal stricture, oropharyngeal ulceration, perforations, ulcers, bleeding in the upper gastrointestinal tract, although a causal relationship has not been established.

From the musculoskeletal system: common – bone, muscle and joint pain, muscle cramps; rare – osteonecrosis. There are reports of osteonecrosis of the jaw in patients taking bisphosphonates. Most reports concern cancer patients, but such cases have also been noted in patients undergoing therapy for osteoporosis.

From the nervous system: common – headache.

Dermatological reactions: uncommon – rash, itching, erythema; rare – rash with photosensitivity; in some cases – severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Allergic reactions rare – hypersensitivity reactions, including urticaria and angioedema.

From the organ of vision: rare – uveitis, scleritis, episcleritis.

From the body as a whole: rare – transient symptoms similar to those in the acute phase of the disease (myalgia, malaise and rarely fever), usually at the beginning of treatment; symptomatic hypocalcemia, usually associated with predisposing conditions.

Contraindications

• Hypocalcemia;
• Conditions leading to slow passage of food through the esophagus (including strictures or achalasia of the esophagus);
• Inability of the patient to stand or sit upright for at least 30 minutes;
• Severe renal failure (creatinine clearance less than 35 ml/min);
• Severe mineral metabolism disorders;
• Childhood;
• Pregnancy;
• Lactation period (breastfeeding);
• Hypersensitivity to the components of the drug.

With caution the drug should be used for gastrointestinal diseases in the acute phase (dysphagia, esophagitis, gastritis, duodenitis, gastric and duodenal ulcer), vitamin D deficiency.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance less than 35 ml/min).

Pediatric Use

Contraindicated: childhood.

Special Precautions

Special attention should be paid to any signs of side effects in the esophagus. The patient should be informed about the need to stop taking the drug and consult a doctor if dysphagia, pain when swallowing, chest pain, or the appearance or intensification of heartburn develops.

The patient must be informed about the possible risk of damage to the esophageal mucosa if the instructions for use are not followed.

Due to the risk of irritation of the upper gastrointestinal mucosa, as well as aggravation of the underlying disease, caution is recommended when prescribing the drug to patients with gastrointestinal diseases such as dysphagia, esophagitis, gastritis, duodenitis, gastric and duodenal ulcer in the acute stage, as well as with recently suffered (within the previous year) gastrointestinal diseases (gastric and duodenal ulcer, active gastrointestinal bleeding, surgery on the upper gastrointestinal tract, except pyloroplasty).

Patients should be informed that if a dose is missed, they should take 1 tablet in the morning after they remember it.

In patients with hypocalcemia, correction of mineral metabolism disorders, including vitamin D deficiency and hypoparathyroidism, must be carried out before starting treatment with Tevanate^®. During treatment, due to the positive effect of alendronic acid on bone mineral density, a slight asymptomatic decrease in the concentration of calcium and phosphates in the blood serum may be observed. In addition, there are rare reports of symptomatic hypocalcemia, sometimes severe, which is often found in patients with hypoparathyroidism, vitamin D deficiency and impaired calcium absorption.

When taking Tevanate^® (especially with concomitant glucocorticoid therapy), it is necessary to ensure adequate intake of calcium and vitamin D with food or in the form of medications.

The absorption of bisphosphonates is significantly reduced when taken simultaneously with food.

Osteonecrosis of the jaw has been reported, usually associated with tooth extraction and/or local infection (including osteomyelitis) in cancer patients receiving mainly intravenous bisphosphonates. Many of these patients also received chemotherapy and glucocorticoids. There are also reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral bisphosphonates.

Before prescribing bisphosphonate therapy, patients with concomitant risk factors (e.g., cancer, chemotherapy, radiation therapy, glucocorticoid use, poor oral hygiene) should undergo a dental examination with appropriate preventive dental treatment.

Patients undergoing treatment with bisphosphonates should avoid invasive dental procedures if possible. In patients on bisphosphonate therapy who have developed osteonecrosis of the jaw, dental surgical interventions may worsen the condition. If surgical interventions are necessary, it should be taken into account that there is no data on the possibility of reducing the risk of developing osteonecrosis of the jaw after discontinuation of the bisphosphonate.

The prescriptions and recommendations of the attending physician should be based on an individual assessment of the benefit/risk ratio for each patient.

Effect on the ability to drive vehicles and operate machinery

The drug does not affect the ability to drive vehicles and operate machinery.

Overdose

Symptoms hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis, erosive and ulcerative lesions of the gastrointestinal tract.

Treatment take milk or an antacid to bind alendronic acid. Due to the risk of esophageal irritation, vomiting should not be induced. The patient should be in an upright position.

Drug Interactions

Combined use of alendronic acid (but not simultaneous administration) with estrogen preparations is not accompanied by a change in their action and the development of side effects.

Simultaneous administration of alendronic acid with calcium-containing preparations, antacids or other oral medications is not allowed due to possible reduction in the absorption of alendronic acid. In this regard, it is necessary to maintain an interval of at least 30 minutes after taking alendronic acid and before taking other medications orally.

Oral administration of prednisone is not accompanied by clinically significant changes in the bioavailability of alendronic acid.

NSAIDs enhance the side effects of alendronic acid on the gastrointestinal tract.

Storage Conditions

List B. The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life of the drug in the form of 10 mg tablets is 3 years, in the form of 70 mg tablets – 2.5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.