ATELVIA® (risedronate sodium)

ATELVIA® (risedronate sodium)

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ATELVIA® (risedronate sodium)

Atelvia (risedronate sodium) delayed-release tablets contain a pH-sensitive enteric coating and a chelating agent (EDTA).

Risedronate is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism. Each Atelvia tablet for oral administration contains the equivalent of 35 mg of anhydrous risedronate sodium in the form of the hemi-pentahydrate with small amounts of monohydrate. The empirical formula for risedronate sodium hemi-pentahydrate is C7H10NO7P2Na •2.5 H2O. The chemical name of risedronate sodium is [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid] monosodium salt.

Risedronate sodium is a fine, white to off-white, odorless, crystalline powder. It is soluble in water and in aqueous solutions, and essentially insoluble in common organic solvents.

Inactive Ingredients: Edetate disodium, ferric oxide yellow, magnesium stearate, methacrylic acid copolymer, polysorbate 80, silicified microcrystalline cellulose (ProSolv SMCC90), simethicone, sodium starch glycolate, stearic acid, talc, and triethyl citrate.

Indications and usage

Atelvia is a bisphosphonate in a delayed-release formulation and is indicated for treatment of postmenopausal osteoporosis

Limitations of Use: Optimal duration of use has not been determined. For patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use.

Mechanism of Action

Risedronate has an affinity for hydroxyapatite crystals in bone and acts as an antiresorptive agent. At the cellular level, risedronate inhibits osteoclasts. The osteoclasts adhere normally to the bone surface, but show evidence of reduced active resorption (for example, lack of ruffled border). Histomorphometry in rats, dogs, and minipigs showed that risedronate treatment reduces bone turnover (activation frequency, that is, the rate at which bone remodeling sites are activated) and bone resorption at remodeling sites.

Dosage and administration

The recommended regimen is:

  • one 35 mg delayed-release tablet orally, taken once-a-week

Administration instructions

  • Take Atelvia in the morning immediately following breakfast. Atelvia should be taken immediately following breakfast and not under fasting conditions because of a higher risk of abdominal pain if taken before breakfast when fasting.
  • Swallow Atelvia whole while in an upright position and with at least 4 ounces of plain water to facilitate delivery to the stomach. Avoid lying down for 30 minutes after taking the medication
  • Do not chew, cut, or crush Atelvia tablets.

Contraindications

  • Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia
  • Inability to stand or sit upright for at least 30 minutes
  • Hypocalcemia
  • Known hypersensitivity to any component of this product

Adverse reactions

Most common adverse reactions (greater than 5%) include: diarrhea, influenza, arthralgia, back pain, and abdominal pain

Hypersensitivity reactions (angioedema, generalized rash, bullous skin reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis), and eye inflammation (iritis, uveitis) have been reported rarely

Warnings and precautions

Drug Products with the Same Active Ingredient: Atelvia contains the same active ingredient found in Actonel®. A patient being treated with Actonel should not receive Atelvia.

Upper Gastrointestinal Adverse Reactions: Atelvia, like other bisphosphonates administered orally, may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Atelvia is given to patients with active upper gastrointestinal problems (such as known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers)

Mineral Metabolism: Hypocalcemia has been reported in patients taking Atelvia. Treat hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Atelvia therapy. Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate. Adequate intake of calcium and vitamin D is important in all patients

Jaw Osteonecrosis: Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates, including risedronate. Known risk factors for osteonecrosis of the jaw include invasive dental procedures (for example, tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (for example, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders (for example, periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures). The risk of ONJ may increase with duration of exposure to bisphosphonates.

Musculoskeletal Pain: In postmarketing experience, there have been reports of severe and occasionally incapacitating bone, joint, and/or muscle pain in patients taking bisphosphonates. The time to onset of symptoms varied from one day to several months after starting the drug. Most patients had relief of symptoms after stopping medication. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate. Consider discontinuing use if severe symptoms develop.

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Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are traverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates.

Renal Impairment: Atelvia is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min) because of lack of clinical experience.

Drug interactions

Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drugmetabolizing enzymes (for example, Cytochrome P450).

Calcium Supplements/Antacids: When Atelvia was administered following breakfast, the co-administration of a tablet containing 600 mg of elemental calcium and 400 international units vitamin D reduced risedronate bioavailability by approximately 38%. Calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations interfere with the absorption of Atelvia and should not be taken together.

Histamine 2 (H2) Blockers and Proton Pump Inhibitors (PPIs): Drugs that raise stomach pH (for example, PPIs or H2 blockers) may cause faster drug release from enteric coated (delayed-release) drug products such as Atelvia. Co-administration of Atelvia with the PPI, esomeprazole, increased risedronate bioavailability.

Use in specific populations

Pregnancy: Available data on use of Atelvia in pregnant women are insufficient to inform drug-associated risk of adverse maternal or fetal outcomes. Discontinue Atelvia when pregnancy is recognized.

Lactation: There are no data to assess the presence of risedronate in human milk, the effects on the breastfed infant, or the effects on milk production. A small degree of lacteal transfer occurred in nursing rats. The concentration of the drug in animal milk does not necessarily predict the concentration of drug in human milk. However, when a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Atelvia and any potential adverse effects on the breast-fed child from Atelvia or from the underlying maternal condition.

Pediatric Use: Atelvia is not indicated for use in pediatric patients.

Renal Impairment: Atelvia is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min) because of lack of clinical experience. No dosage adjustment is necessary in patients with a creatinine clearance greater than or equal to 30 mL/min.

Overdosage

Decreases in serum calcium and phosphorus following substantial overdose may be expected in some patients. Signs and symptoms of hypocalcemia may also occur in some of these patients. While milk or antacids containing calcium may be given to bind risedronate sodium immediaterelease and reduce absorption of the drug, the impact of this intervention for Atelvia delayedrelease tablets has not been evaluated.

In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed drug. Standard procedures that are effective for treating hypocalcemia, including the administration of calcium intravenously, would be expected to restore physiologic amounts of ionized calcium and to relieve signs and symptoms of hypocalcemia.

Lethality after single oral doses of risedronate was seen in female rats at 903 mg/kg and male rats at 1703 mg/kg. The minimum lethal dose in mice and rabbits was 4000 mg/kg and 1000 mg/kg, respectively. These values represent 320 to 620 times the human Paget’s disease dose of 30 mg/day based on surface area (mg/m2 ).

Storage

Store at controlled room temperature 20° to 25° C (68° to 77° F) [see USP].

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