ACTONEL® (risedronate sodium)

ACTONEL® (risedronate sodium)

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ACTONEL® (risedronate sodium)

ACTONEL (risedronate sodium) tablets is a pyridinyl bisphosphonate that inhibits osteoclast mediated bone resorption and modulates bone metabolism. Each ACTONEL tablet for oral administration contains the equivalent of 5, 30, 35, 75, or 150 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: All dose strengths contain: crospovidone, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, silicon dioxide, titanium dioxide. Dose strength-specific ingredients include: 5 mg—ferric oxide yellow, lactose monohydrate; 30 mg—lactose monohydrate; 35 mg—ferric oxide red, ferric oxide yellow, lactose monohydrate; 75 mg—ferric oxide red; 150 mg—FD&C blue #2 aluminum lake.

Indications and usage

ACTONEL is a bisphosphonate indicated for:
Treatment and prevention of postmenopausal osteoporosis
Treatment to increase bone mass in men with osteoporosis
Treatment and prevention of glucocorticoid-induced osteoporosis
Treatment of Paget’s disease

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

ACTONEL has an affinity for hydroxyapatite crystals in bone and acts as an antiresorptive agent. At the cellular level, ACTONEL 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 ACTONEL 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

Treatment of Postmenopausal Osteoporosis: 5 mg daily, 35 mg once-a-week, 75 mg two consecutive days each month, 150 mg once-a-month

Prevention of Postmenopausal Osteoporosis: 5 mg daily, 35 mg once-a-week

Men with Osteoporosis: 35 mg once-a-week
Glucocorticoid-Induced Osteoporosis: 5 mg daily
Paget’s Disease: 30 mg daily for 2 months

Instruct patients to:
Swallow tablet whole with 6 to 8 ounces of plain water, at least 30 minutes before the first food, beverage, or medication of the day
Avoid lying down for 30 minutes
Take supplemental calcium and vitamin D if dietary intake is inadequate

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

Warnings and precautions

  • Products Containing Same Active Ingredient: Patients receiving Atelvia should not be treated with
  • Upper Gastrointestinal Adverse Reactions can occur. Instruct patients to follow dosing instructions. Discontinue use if new or worsening symptoms occur
  • Hypocalcemia may worsen and must be corrected prior to use
  • Osteonecrosis of the Jaw has been reported
  • Severe Bone, Joint, Muscle Pain may occur. Discontinue use if severe symptoms develop
  • Atypical Femur Fractures have been reported. Patients with new thigh or groin pain should be evaluated to rule out a femoral fracture
  • Renal Impairment: ACTONEL is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min).
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  • Glucocorticoid-Induced Osteoporosis: Before initiating ACTONEL treatment for the treatment and prevention of glucocorticoidinduced osteoporosis, the sex steroid hormonal status of both men and women should be ascertained and appropriate replacement considered.

Adverse drug reactions

Most common adverse reactions reported in greater than 10% of patients treated with ACTONEL and with a higher frequency than placebo are: back pain, arthralgia, abdominal pain, and dyspepsia.

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

Drug interactions

No specific drug-drug interaction studies were performed. Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes (for example, Cytochrome P450).

Calcium Supplements/Antacids: Co-administration of ACTONEL and calcium, antacids, or oral medications containing divalent cations will interfere with the absorption of ACTONEL.

Use in special populations

Pregnancy Category C: There are no adequate and well-controlled studies of ACTONEL in pregnant women. ACTONEL should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Nursing Mothers: Risedronate was detected in feeding pups exposed to lactating rats for a 24-hour period postdosing, indicating a small degree of lacteal transfer. It is not known whether ACTONEL is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ACTONEL, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

Renal Impairment: ACTONEL 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.

Hepatic Impairment: No studies have been performed to assess risedronate’s safety or efficacy in patients with hepatic impairment. Risedronate is not metabolized in human liver preparations. Dosage adjustment is unlikely to be needed in patients with hepatic impairment.

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. Milk or antacids containing calcium should be given to bind ACTONEL and reduce absorption of the drug.

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 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 30 mg human dose based on surface area (mg/m2 ).

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