Fosavance^® (Tablets) Instructions for Use

Marketing Authorization Holder

Merck Sharp & Dohme, B.V. (Netherlands)

Manufactured By

Frosst Iberica, S.A. (Spain)

ATC Code

M05BB03 (Alendronic acid and Colecalciferol)

Active Substances

Colecalciferol (Rec.INN registered WHO)

Alendronic acid (Rec.INN registered WHO)

Dosage Form

Fosavance®

Tablets 70 mg+70 mcg: 4 or 12 pcs.

Dosage Form, Packaging, and Composition

Tablets from white to almost white color, capsule-shaped, with an imprint “710” on one side and a drawing in the form of a bone – on the other.

Auxiliary substances : lactose anhydrous, cellulose microcrystalline, silicon dioxide colloidal, sodium croscarmellose, magnesium stearate.

* granules contain Colecalciferol (vit. D₃), triglycerides, gelatin, sucrose, starch modified food, butylated hydroxytoluene, sodium aluminosilicate.

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

Clinical-Pharmacological Group

Bone resorption inhibitor for osteoporosis

Pharmacotherapeutic Group

Osteoporosis treatment agent (bone resorption inhibitor + calcium-phosphorus metabolism regulator)

Indications

• Treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fractures. Fosavance^® is indicated in postmenopausal women with osteoporosis, defined as a low bone mineral density (BMD) with a T-score ≤ -2.5 SD, or in the presence of established osteoporosis, including existing vertebral or hip fractures.
• To increase bone mass in men with osteoporosis to reduce fracture risk. This is applicable in men with a confirmed diagnosis of osteoporosis, either by the presence of fragility fractures or by low BMD.
• Treatment of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoid therapy (≥ 7.5 mg/day prednisone or equivalent) for chronic diseases and are expected to remain on glucocorticoids for at least 12 months. This use is for patients with a low bone mineral density.

The combination of alendronic acid and colecalciferol is specifically designed to address both the excessive bone resorption and the vitamin D deficiency that are common contributors to osteoporosis.

Contraindications

• Hypersensitivity to alendronic acid, colecalciferol, or any of the excipients listed in the composition. This includes patients with a known allergy to any component of the tablet or its coating.
• Esophageal abnormalities and disorders which delay esophageal emptying, such as stricture or achalasia. The tablet formulation requires rapid transit to the stomach to minimize local irritation.
• Inability to stand or sit upright for at least 30 minutes after taking the tablet. This is a critical requirement to ensure the medication passes quickly into the stomach and to reduce the risk of esophageal ulceration.
• Hypocalcemia (low blood calcium levels). This condition must be corrected before initiating therapy with Fosavance^®, as the drug can lower serum calcium.
• Severe renal impairment (creatinine clearance < 35 mL/min). Alendronic acid is primarily excreted by the kidneys, and its use in this population has not been established. Colecalciferol requires renal hydroxylation for activation.
• Pregnancy and breastfeeding. There are no adequate and well-controlled studies in pregnant women, and it is not known if alendronic acid is excreted in human milk. Colecalciferol and its metabolites pass into breast milk, which may lead to hypercalcemia in the infant.

Patients with active upper gastrointestinal problems, such as dysphagia, gastritis, duodenitis, or ulcers, should be treated with caution.

Dosage Regimen

The recommended dosage for the treatment of osteoporosis is one Fosavance^® 70 mg/70 mcg tablet once weekly.

To ensure adequate absorption and to minimize the potential for esophageal adverse reactions, patients must adhere to the following administration instructions precisely. The tablet must be taken at least 30 minutes before the first food, beverage, or other medication of the day with plain water only. Other beverages (including mineral water, coffee, tea, milk, and juice) are not permitted as they can significantly reduce the absorption of alendronic acid.

The patient must swallow the tablet whole; it must not be sucked, chewed, or allowed to dissolve in the mouth due to the potential for oropharyngeal ulceration. To facilitate delivery to the stomach and thus reduce the potential for esophageal irritation and ulceration, the patient must take Fosavance^® immediately upon rising for the day with a full glass of plain water (180-240 mL).

After taking the tablet, the patient must not lie down and should remain in an upright position (sitting or standing) for at least 30 minutes and until after the first food of the day. The patient should not take the tablet at bedtime or before rising for the day. Failure to follow these instructions may increase the risk of esophageal adverse events.

Patients should also be informed that if they miss a weekly dose, they should take one tablet on the morning after they remember. They should not take two tablets on the same day but should return to taking one tablet once a week, as originally scheduled on their chosen day. Supplemental calcium and vitamin D should be considered if the dietary intake is inadequate. The need for continued therapy should be re-evaluated periodically based on the patient’s clinical status and fracture risk.

Adverse Reactions

As with all bisphosphonates, Fosavance^® can cause adverse reactions, some of which can be serious. The most common adverse reactions are related to the gastrointestinal tract.

Very common (≥1/10) adverse reactions include dyspepsia. Common (≥1/100 to <1/10) adverse reactions include abdominal pain, nausea, vomiting, constipation, diarrhea, flatulence, esophageal ulcer, dysphagia, abdominal distension, acid regurgitation, gastritis, duodenitis, musculoskeletal pain (bone, muscle, or joint pain), headache, and dizziness.

Uncommon (≥1/1,000 to <1/100) adverse reactions include esophagitis, esophageal erosions, stomatitis, melena, rash, pruritus, erythema, photosensitivity, transient acute-phase reaction (myalgia, malaise, and fever) typically at the initiation of treatment, eye inflammation (uveitis, scleritis, episcleritis), and taste disturbance. Rare but serious adverse reactions include osteonecrosis of the jaw, which is primarily associated with tooth extraction and/or local infection, often in cancer patients receiving chemotherapy and corticosteroids, and atypical femoral fractures, which are low-energy or low-trauma fractures of the femoral shaft.

Hypersensitivity reactions, including urticaria and angioedema, have been reported. Severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely. Colecalciferol can lead to vitamin D intoxication and hypercalcemia if dosed inappropriately, though this is unlikely at the recommended dosage. Patients should be advised to report any unusual thigh, hip, or groin pain, as this may be indicative of an atypical fracture, or any jaw pain, tooth mobility, or signs of oral infection.

Drug Interactions

The bioavailability of alendronic acid is negligible when taken with food or beverages other than plain water. Therefore, food, beverages (including mineral water, coffee, tea, milk, and juice), and other oral medications must be taken at least 30 minutes after Fosavance^® to avoid a significant reduction in absorption.

Calcium supplements, antacids, and other polyvalent cation-containing products (such as iron, magnesium, and aluminum) can interfere with the absorption of alendronic acid. Patients must take these supplements or medications at a different time of the day, at least several hours after taking Fosavance^®.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal irritation. Since bisphosphonates can also cause gastrointestinal irritation, caution should be used when they are co-administered, especially in patients with a history of upper GI disorders.

Colecalciferol may increase the risk of hypercalcemia when used concomitantly with high doses of calcium supplements, thiazide diuretics (which reduce calcium excretion), or other vitamin D analogs. Serum calcium levels should be monitored in patients taking such combinations. Drugs that induce liver enzymes (e.g., phenytoin, carbamazepine, barbiturates) may increase the catabolism of vitamin D and reduce its efficacy, potentially requiring a higher dose of colecalciferol.

Caution is advised when bisphosphonates are used with angiogenesis inhibitors (e.g., bevacizumab) or systemic corticosteroids, as these combinations may increase the risk of osteonecrosis of the jaw. Patients should inform their healthcare provider about all the medications they are taking, including prescription, over-the-counter, and herbal products.

Overdose

Overdose with Fosavance^® may lead to hypocalcemia, hypophosphatemia, and upper gastrointestinal adverse effects, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer.

No specific antidote is known. Milk or antacids should be given to bind alendronic acid. Due to the risk of esophageal irritation, the patient should remain fully upright. Inducing vomiting is not recommended. Esophageal irritation or ulceration should be considered if the patient experiences symptoms such as dysphagia, odynophagia, or retrosternal pain. Gastric lavage may be considered if performed within 60 minutes of ingestion to remove unabsorbed drug, but this must be done with the patient upright to protect the airway.

Treatment should be supportive and symptomatic. Serum calcium and electrolyte levels should be monitored, and intravenous calcium gluconate may be administered if clinically significant hypocalcemia occurs. Hemodialysis would not be beneficial for alendronic acid removal due to its high binding affinity for bone. Medical supervision should be sought immediately in case of suspected overdose.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.