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Risedronate Sodium

Pronunciation

Pronunciation: RIS-e-DROE-nate SOE-dee-um
Class: Bisphosphonate

Trade Names

Actonel
- Tablets, oral 5 mg
- Tablets, oral 30 mg
- Tablets, oral 35 mg
- Tablets, oral 150 mg

Atelvia
- Tablets, delayed-release, oral 35 mg

Pharmacology

Inhibits osteoclast-mediated bone resorption and modulates bone metabolism, resulting in decreased rate of bone turnover.

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Pharmacokinetics

Absorption

Relatively rapid and occurs in upper GI tract (oral). T max is approximately 1 h for immediate release and 3 h for delayed release. Steady state is approximately 57 days. Bioavailability is 0.63%. Food decreases absorption of the immediate-release tablet by 55% when taken 30 min before breakfast and decreases by 30% when the delayed-release tablet is taken immediately after a high-fat breakfast.

Distribution

60% of dose is distributed to bone. Protein binding is approximately 24%.

Steady-state Vd is 13.8 L/kg.

Metabolism

No evidence of systemic metabolism.

Elimination

Approximately 50% is eliminated in urine in 24 h. Mean renal Cl is 52 to 105 mL/min. Mean total Cl is 73 to 122 mL/min. Terminal exponential half-life is approximately 561 h.

Special Populations

Renal Function Impairment

Cl decreased approximately 70% with CrCl 30 mL/min. Not recommended for use in patients with severe renal impairment. Dosage adjustment is not necessary in patients with CrCl at least 30 mL/min.

Hepatic Function Impairment

Pharmacokinetics have not been studied.

Elderly

Bioavailability and disposition are similar in elderly and younger patients. Dosage adjustment is not necessary.

Gender

Bioavailability and pharmacokinetics are similar in men and women.

Race

Pharmacokinetics have not been studied.

Indications and Usage

Treatment and prevention of osteoporosis in postmenopausal women (delayed-release tablet is indicated only for treatment); treatment and prevention of glucocorticoid-induced osteoporosis (immediate release); treatment of Paget disease of the bone (immediate release); treatment to increase bone mass in men with osteoporosis (immediate release).

Contraindications

Hypocalcemia; inability to stand or sit upright for at least 30 min; abnormalities of the esophagus (eg, stricture, achalasia) that delay esophageal emptying; hypersensitivity to any component of the product.

Dosage and Administration

Glucocorticoid-Induced Osteoporosis
Adults

PO 5 mg daily.

Osteoporosis in Men
Adults

PO 35 mg once weekly.

Paget Disease
Adults

PO 30 mg once daily for 2 mo.

Postmenopausal Osteoporosis
Adults Delayed release

PO 35 mg once per week.

Immediate release

PO 5 mg daily, 35 mg once per week, 75 mg taken on 2 consecutive days (2 tablets per month), or 150 mg once monthly.

General Advice

  • Administer immediate-release tablet at least 30 min before the first food or drink of the day other than water and delayed-release tablet immediately following breakfast.
  • To facilitate delivery to the stomach, medication should be swallowed while the patient is in an upright position (with a full glass of water).
  • Patient should not lie down for 30 min after taking the medication.
  • Tablets should not be chewed or allowed to melt or dissolve in the mouth. Delayed-release tablet should not be chewed, cut, or crushed.
  • Patients should take supplemental calcium and vitamin D if dietary intake is inadequate.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

Aluminum and/or magnesium supplements/antacids, calcium supplements/antacids, oral medications containing divalent cations (eg, iron salts)

May decrease risedronate absorption, which may decrease activity. Advise patients to take risedronate at least 30 min before any oral medications containing divalent cations.

Aspirin, NSAIDs (eg, ibuprofen, indomethacin)

NSAIDs and risedronate may be synergistic with respect to causing gastric ulcers. Use with caution. Closely monitor patients for possible GI adverse reactions, especially gastric irritation.

Food

Food decreases absorption of risedronate immediate-release tablets compared with dosing in the fasting state. Advise patient to take risedronate immediate-release tablets at least 30 min before the first food or beverage of the day other than water. Bioavailability of risedronate delayed-release tablets is decreased approximately 30% when given immediately after a high-fat breakfast compared with administration 4 hours before a meal. The bioavailability of risedronate delayed-release tablets after a high-fat breakfast is similar to risedronate immediate-release tablets given 4 hours before a meal and approximately 2- to 4-fold greater than the immediate-release tablet administered 30 minutes prior to a high-fat breakfast. Risedronate delayed-release tablets should be taken immediately after breakfast.

Histamine H 2 antagonists (eg, cimetidine), proton pump inhibitors (eg, omeprazole)

These agents may affect the enteric coating on risedronate delayed-release tablets, decreasing bioavailability. Coadministration of histamine H 2 antagonists or proton pump inhibitors and risedronate delayed-release tablets is not recommended.

Laboratory Test Interactions

Interferes with bone-imaging agents.

Adverse Reactions

Cardiovascular

Hypertension (11%); arrhythmia (2%).

CNS

Headache (18%); depression, dizziness (7%); asthenia, insomnia (5%).

Dermatologic

Rash (12%); bullous skin reactions, generalized rash (postmarketing).

EENT

Cataract (7%); pharyngitis (6%); iritis, uveitis (postmarketing).

GI

Diarrhea (20%); constipation (13%); abdominal pain (12%); dyspepsia, nausea (11%); vomiting (5%); gastritis, upper abdominal pain (3%); gastroesophageal reflux disease (2%); duodenitis, glossitis (1%); upper GI irritation including esophagitis and esophageal or gastric ulcer (postmarketing).

Genitourinary

UTI (11%); benign prostatic hyperplasia (5%); nephrolithiasis (3%).

Hypersensitivity

Allergic reactions (4%); angioedema, hypersensitivity (postmarketing).

Lab Tests

Increased serum parathyroid hormone (less than 30%); hypocalcemia (5%); decreased serum phosphate (less than 3%).

Metabolic-Nutritional

Peripheral edema (8%).

Musculoskeletal

Arthralgia (33%); back pain (28%); arthritis (10%); traumatic bone fracture (9%); joint disorder, myalgia (7%); bone pain, neck pain (5%); pain in extremity (4%); musculoskeletal pain, muscle spasms (2%); incapacitating bone, joint, and muscle pain; osteonecrosis of the jaw (postmarketing).

Respiratory

Bronchitis (10%); sinusitis (9%); influenza (7%); increased cough, rhinitis (6%); upper respiratory tract infection (4%).

Miscellaneous

Infection (31%); pain (14%); flu syndrome (11%); acute-phase reaction (8%); chest pain (7%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Not indicated in children.

Renal Function

Not recommended in patients with CrCl less than 30 mL/min.

Hormone status

Before beginning therapy for prevention or treatment of glucocorticoid-induced osteoporosis, determine the sex steroid hormonal status and consider appropriate replacement.

Hypocalcemia

Effectively treat hypocalcemia and other disturbances of bone and mineral metabolism prior to starting risedronate.

Musculoskeletal pain

Severe and incapacitating bone, joint, and muscle pain has been reported.

Osteonecrosis of the jaw

Has been reported with bisphosphonates. May occur spontaneously and is generally associated with tooth extraction and/or local infection with delayed healing.

Upper GI disorders

Bisphosphonates may cause upper GI disorders, such as dysphagia, esophageal ulcer, esophagitis, and esophageal erosions (occasionally with bleeding and rarely followed by esophageal stricture or perforation). Use with caution in patients with active upper GI problems (eg, Barrett esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis, ulcers).

Overdosage

Symptoms

Hypocalcemia, hypophosphatemia.

Patient Information

  • Advise patient to read the patient information leaflet before using product the first time and with each refill.
  • Instruct patient to take the medication exactly as directed because clinical benefits may be negatively affected by failure to take the drug according to instructions.
  • Instruct patient to take medication in an upright position with a full (6 to 8 oz) glass of water 30 min or more before the first food or liquid of the day for immediate-release tablets and immediately following breakfast for the delayed-release tablets. Instruct patient not to chew tablets or allow them to melt or dissolve in the mouth.
  • Remind patient to avoid lying down for 30 min after taking this medication.
  • Instruct the patient that if a dose of 150 mg once monthly is missed and the next month's dose is more than 7 days away, to take the missed dose in the morning after the day it is remembered. Instruct patients to return to taking their once-monthly dose as originally scheduled. Advise patients to not take more than one 150 mg tablet within 7 days. If the once-monthly dose is missed and the next month's dose is within 7 days, instruct patients to wait until their next month's scheduled dose and then continue taking the once-monthly dose as originally scheduled.
  • Instruct patient that if a dose of risedronate 35 mg weekly is missed, to take 35 mg on the morning after they remember and return to taking 35 mg weekly, as originally scheduled, on their chosen day. Advise patients not to take two 35 mg tablets on the same day.
  • Instruct patient to take supplemental calcium and vitamin D if dietary intake is inadequate.
  • Instruct patient to take any supplement containing calcium or antacids containing magnesium or aluminum 1 h or more before or 2 h after taking risedronate tablets to prevent interference with absorption.
  • Instruct patient to report any symptoms of esophageal disease (eg, difficulty or pain upon swallowing; retrosternal pain; severe, persistent, or worsening heartburn) to health care provider before continuing treatment.
  • Warn breast-feeding women to decide in collaboration with their primary health care provider whether to discontinue the drug or breast-feeding.
  • Inform patients that osteonecrosis of the jaw has been reported rarely and that severe bone, joint, or muscle pain may occur. If any of these symptoms occur, instruct patients to report them immediately to their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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