CLASSES
Oral Bisphosphonates
DESCRIPTION
Potent oral second-generation pyridinyl bisphosphonate; monthly, weekly, or daily regimens available for selected conditions
Used primarily for treatment and prevention of osteoporosis in both men and postmenopausal women; also used to treat and prevent corticosteroid-induced osteoporosis
Also used for the management of Paget's disease
COMMON BRAND NAMES
Actonel, Atelvia
HOW SUPPLIED
Actonel/Risedronate/Risedronate Sodium Oral Tab: 5mg, 30mg, 35mg, 150mg
Atelvia/Risedronate/Risedronate Sodium Oral Tab DR: 35mg
DOSAGE & INDICATIONS
For the treatment of osteoporosis.
Once daily regimen for postmenopausal osteoporosis.
Oral dosage (tablets for daily administration)
Adult postmenopausal females
5 mg PO once daily. Supplement calcium and vitamin D if dietary intake inadequate.The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Continue an oral bisphosphonate for up to 10 years in postmenopausal women who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk postmenopausal patients. For those patients at low or moderate risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Bisphosphonates are first-line therapy for the treatment of osteoporosis in postmenopausal women.[62806]
Once-weekly regimen for postmenopausal osteoporosis or osteoporosis in men.
Oral dosage (weekly tablets)
Adult men and postmenopausal females
35 mg PO once weekly. If dietary intake is not sufficient, supplement calcium and vitamin D daily. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Continue an oral bisphosphonate for up to 10 years in postmenopausal women who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk postmenopausal women. For those patients at low or moderate risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Bisphosphonates are first-line therapy for the treatment of osteoporosis in postmenopausal women; the drug is additionally effective in men with osteoporosis.[62806]
Oral dosage (weekly delayed-release tablets)
Adult postmenopausal females
35 mg PO once weekly. Supplement calcium and vitamin D if dietary intake inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Continue an oral bisphosphonate for up to 10 years in patients who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk patients. For those patients at low or moderate risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Bisphosphonates are first-line therapy for the treatment of osteoporosis in postmenopausal women.[62806]
Once daily regimen for corticosteroid-induced osteoporosis in men and women.
Oral dosage (tablets for daily administration)
Adults
5 mg PO once daily. Supplement calcium and vitamin D if dietary intake inadequate. For use in patients taking systemic corticosteroids (i.e., equivalent to prednisone 7.5 mg/day PO or more). The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.
Once monthly regimen for postmenopausal osteoporosis.
Oral dosage (monthly tablets)
Adult postmenopausal females
150 mg PO once monthly. Supplement with calcium and vitamin D if intake is inadequate. An alternative once-monthly regimen is 75 mg PO on 2 consecutive days each month (for a total of 150 mg each month). The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. Continue an oral bisphosphonate for up to 10 years in postmenopausal women who are initially at very high risk of fracture and remain at high risk. Consider discontinuation after 5 years of stability in high-risk postmenopausal patients. For those patients at low or moderate risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Bisphosphonates are first-line therapy for the treatment of osteoporosis in postmenopausal women.[62806]
For osteoporosis prophylaxis.
Once daily regimen for prevention of postmenopausal osteoporosis.
Oral dosage (tablets for daily administration)
Adult postmenopausal females
5 mg PO once daily. Supplement with calcium and vitamin D if intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Use of bisphosphonates to prevent bone loss can be considered in postmenopausal women with low bone mineral density (T-score less than -1) and other risk factors for fracture who do not meet criteria for osteoporosis treatment.
Once-weekly regimen for prevention of postmenopausal osteoporosis.
Oral dosage (weekly tablets or weekly delayed-release tablets)
Adult postmenopausal females
35 mg PO once weekly. Supplement with calcium and vitamin D if intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Use of bisphosphonates to prevent bone loss can be considered in postmenopausal women with low bone mineral density (T-score less than -1) and other risk factors for fracture who do not meet criteria for osteoporosis treatment.
Once monthly regimen for prevention of postmenopausal osteoporosis.
Oral dosage (monthly tablets)
Adult postmenopausal females
150 mg PO once monthly. Supplement with calcium and vitamin D if intake is inadequate. An alternative once-monthly regimen is 75 mg PO on 2 consecutive days each month (for a total of 150 mg each month). The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Use of bisphosphonates to prevent bone loss can be considered in postmenopausal women with low bone mineral density (T-score less than -1) and other risk factors for fracture who do not meet criteria for osteoporosis treatment.
Once daily regimen for prevention of corticosteroid-induced osteoporosis in men and women.
Oral dosage (tablets for daily administration)
Adults
5 mg PO once daily. Supplement with calcium and vitamin D if intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping risedronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.
For the treatment of Paget's disease.
Oral dosage (tablets for daily administration)
Adults
30 mg PO once daily for 2 months. Supplement calcium and vitamin D if dietary intake is inadequate. Consider retreatment (following an observation period of at least 2 months) if relapse occurs, or if treatment fails to normalize serum alkaline phosphatase. For retreatment, the dose and duration of therapy are the same as for initial treatment. Risedronate is associated with histologic and radiologic evidence of disease improvement, but guidelines suggest that retreatment with risedronate may be necessary within 1 to 5 years. Guidelines also recommend a single dose of zoledronic acid preferentially due to the rare need for retreatment within 5 years, but the risedronate regimen is also an acceptable option. There are long-term data for reducing pain and lytic lesions and improving quality of life.
For osteoporosis prophylaxis to preserve bone density in selected cancer patients and to reduce adverse skeletal events due to bone metastases†.
Oral dosage (weekly tablets)
Adult females
Use not established; not FDA-approved. 35 mg PO once weekly is a common regimen used in trials for adjuvant therapy in women with breast cancer taking aromatase inhibitors. This dosage has been to increase bone density / preserve bone mass. More data are needed, as trials have not been sufficiently powered to detect reduction in fractures or determine effects in breast cancer patients with bone metastases. More data are available for zoledronic acid and ibandronate in these patients.
Oral dosage (weekly tablets)
Adult males
Use not established; not FDA-approved. 35 mg PO once weekly is a common regimen used in trials for adjuvant therapy in men with prostate cancer receiving androgen deprivation therapy. This dosage has been to increase bone density / preserve bone mass. More data are needed, as trials have not been sufficiently powered to detect reduction in fractures or determine effects in prostate cancer patients with bone metastases. More data are available for zoledronic acid in these patients.
For the treatment of osteogenesis imperfecta†.
Oral dosage (daily)
Adults
5 mg PO once daily.
Children and Adolescents 4 to 17 years weighing more than 30 kg
5 mg PO once daily.
Children and Adolescents 4 to 17 years weighing 10 to 30 kg
2.5 mg PO once daily.
Oral dosage (weekly)
Adults
35 mg PO once weekly.
Children and Adolescents 4 to 17 years weighing 40 kg or more
30 mg PO once weekly.
Children and Adolescents 4 to 17 years weighing less than 40 kg
15 mg PO once weekly.
†Indicates off-label use
MAXIMUM DOSAGE
Adults
5 mg/day PO, 35 mg/week PO, or 150 mg/month PO for osteoporosis. For Paget's disease 30 mg/day PO for 2 months.
Geriatric
5 mg/day PO, 35 mg/week PO, or 150 mg/month PO for osteoporosis. For Paget's disease 30 mg/day PO for 2 months.
Adolescents
Weighing 40 kg or more: Safety and efficacy have not been established; however, 5 mg/day PO or 30 mg/week PO has been used off-label for osteogenesis imperfecta.
Weighing 31 to 39 kg: Safety and efficacy have not been established; however, 5 mg/day PO or 15 mg/week PO has been used off-label for osteogenesis imperfecta.
Weighing 10 to 30 kg: Safety and efficacy have not been established; however, 2.5 mg/day PO or 15 mg/week PO has been used off-label for osteogenesis imperfecta.
Children
4 to 12 years weighing 40 kg or more: Safety and efficacy have not been established; however, 5 mg/day PO or 30 mg/week PO has been used off-label for osteogenesis imperfecta.
4 to 12 years weighing 31 to 39 kg: Safety and efficacy have not been established; however, 5 mg/day PO or 15 mg/week PO has been used off-label for osteogenesis imperfecta.
4 to 12 years weighing 10 to 30 kg: Safety and efficacy have not been established; however, 2.5 mg/day PO or 15 mg/week PO has been used off-label for osteogenesis imperfecta.
1 to 3 years: Safety and efficacy have not been established.
Infants
Safety and efficacy have not been established.
Neonates
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
No dosage adjustment is needed.
Renal Impairment
CrCl 30 mL/minute or more: No dosage adjustment is needed.
CrCl less than 30 mL/minute: Use is not recommended.
ADMINISTRATION
Oral Administration
Immediate-release tablets (i.e., Actonel):
Administer after the patient has risen for the day. Administer whole and on an empty stomach; the patient should not chew or suck the tablet. The patient should be sitting or standing. Do not administer to the patient while the patient is lying down.
Administer in the morning with a full glass (180 to 240 mL or 6 to 8 ounces) of plain water only and at least 30 minutes before the first food, beverage, or other medications of the day. Do not administer with mineral water, coffee, tea, soda, or juice.
At least 30 minutes should elapse after the dose before the patient eats, drinks beverages other than water, or is administered any other drugs or supplements.
Calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations should be taken at a different time of the day as they interfere with the absorption of risedronate.
To avoid esophageal irritation, the patient should not lie down for at least 30 minutes after the dose and until after their first food of the day.
Missed doses:
Once daily dosage: If a once-daily dose is missed, do not administer it later in the day. Administer the missed dose the next morning and then return to the normal schedule. The patient should not take 2 doses at the same time.
Once weekly dosage: If a once-weekly dose is missed, instruct the patient to take the weekly dose on the morning after they remember. They should not take 2 doses on the same day but should return to taking 1 dose once a week, as originally scheduled on their chosen day.
Once monthly dosage: Do not administer more than one 150 mg tablet within a 7-day period. If the monthly dose is missed, and the next month's scheduled dose is more than 7 days away, administer the dose the morning after it is remembered. The patient should then return to taking their dose as originally scheduled. If the next month's scheduled dose is 1 to 7 days away, the missed dose should be skipped and the regular schedule resumed.
Ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia.
Delayed-release tablets (i.e., Atelvia):
Administer immediately after breakfast with at least 4 ounces of plain water. Administer the tablets whole; do not chew, cut, or crush. The patient should be sitting or standing. Do not administer to the patient while the patient is lying down.
To avoid esophageal irritation, the patient should not lie down for at least 30 minutes after the dose.
Calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations should be taken at a different time of the day as they interfere with the absorption of risedronate.
Missed dose: If a once-weekly dose is missed, instruct the patient to take the weekly risedronate dose on the morning after they remember. They should not take 2 doses on the same day but should return to taking 1 dose once a week, as originally scheduled on their chosen day.
Ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia.
STORAGE
Actonel:
- Store at controlled room temperature (between 68 and 77 degrees F)
Atelvia:
- Store at controlled room temperature (between 68 and 77 degrees F)
CONTRAINDICATIONS / PRECAUTIONS
Phosphonate hypersensitivity
Risedronate is contraindicated in patients with a known hypersensitivity to risedronate or any component of the product. Angioedema, generalized serious rash, bullous skin reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, and other hypersensitivity reactions have been reported. Angioedema, generalized rash, bullous skin reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.[29352] Risedronate should be used cautiously in patients with known phosphonate hypersensitivity.
Hypocalcemia, vitamin D deficiency
Risedronate therapy is contraindicated in patients with hypocalcemia. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting risedronate therapy. Similarly, correct vitamin D deficiency. Adequate intake of calcium and vitamin D is important in all patients, especially in patients with Paget's disease in whom bone turnover is significantly elevated.
Achalasia, dysphagia, esophageal stricture, esophagitis, gastritis, gastroesophageal reflux disease (GERD), GI disease, hiatal hernia, inability to stand or sit upright
As oral bisphosphonates are known to cause local irritation to gastric mucosa with prolonged contact, use of risedronate is contraindicated in patients with an inability to stand or sit upright for at least 30 minutes after dose administration (see Administration) and in those with delayed esophageal emptying due to achalasia, esophageal stricture, or other cause. Risedronate should be used with caution in patients with other upper GI disease. Bisphosphonates may cause or worsen symptoms of dysphagia, esophagitis, gastroesophageal reflux disease (GERD), hiatal hernia, gastritis, and esophageal and gastric ulcers. Additionally, exercise caution when administering NSAIDs and aspirin with risedronate, due to the potential for additive GI toxicity. Prescribers and health care professionals should closely monitor patients for any signs or symptoms an esophageal reaction. Advise patients to discontinue risedronate and seek medical attention if they develop dysphagia, odynophagia, or retrosternal pain. The risk of esophageal reactions increases in patients who do not follow the administration instructions. It is very important that patients understand and follow these instructions; direct observation may be required in those who cannot independently follow dosing instructions due to mental disability. In 2011, the FDA announced an ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of esophageal cancer. There have been conflicting findings from studies evaluating this risk. At the time of the announcement, FDA states that the benefits of oral bisphosphonate drugs in reducing the risk of serious fractures in people with osteoporosis continue to outweigh their potential risks.
Children, infants, neonates
Safe and effective use of risedronate in pediatric patients (children, infants, neonates) less than 18 years of age has not been established. Bisphosphonates have been used successfully in children and adolescents for treatment of specific disease states (i.e., hypercalcemia of malignancy, idiopathic or glucocorticoid induced osteoporosis, osteogenesis imperfecta, Paget's disease). However, extreme caution must be used to ensure appropriate use in children; excessive doses of bisphosphonates may compromise skeletal quality during growth, despite concomitant increases in bone density. In a case report, inappropriate and excessive doses of pamidronate in a child resulted in osteopetrosis (abnormally dense and misshapen bone predisposed to fracture). It may be advisable to monitor biochemical markers of skeletal turnover when bisphosphonates are used in children to help assure clinicians that skeletal resorption is not excessively suppressed.
Pregnancy
There are no studies of risedronate use during human pregnancy. It is prudent to avoid the use of risedronate during pregnancy. There is a theoretical risk of fetal harm (predominantly skeletal) if a woman becomes pregnant during or after completing a course of bisphosphonate therapy. After a bisphosphonate is incorporated into bone matrix it is gradually released from the bone, over a period of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into systemic circulation, is directly related to the total dose and duration of bisphosphonate use. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration on this risk has not been established. Bisphosphonates do cause fetal harm in animals, suggesting the uptake of bisphosphonates into fetal bone is greater than into maternal bone. Animal reproductive studies indicate risedronate may induce fetal skeletal changes, decrease maternal calcium and cause protracted parturition, and may have a possible effect on fetal viability.[29352]
Breast-feeding
Risedronate should be used with caution during breast-feeding. It is not known whether risedronate is excreted in human milk; there are no data regarding the effect on the breastfed infant or the effect on lactation physiology or breast milk composition. Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount available for release back into the systemic circulation for potential excretion into breast milk, is directly related to the dose and duration of bisphosphonate use. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[29352]
Renal failure, renal impairment
It is recommended that patients with renal failure or severe renal impairment with a creatinine clearance < 30 ml/min not receive risedronate. Renal excretion is substantially decreased in patients with a creatinine clearance < 30 ml/min. Patients with a creatinine clearance >= 30 ml/min do not require dosage adjustments.
Geriatric
Dosage adjustments of risedronate are not necessary in geriatric patients based on age alone. Controlled clinical trials of postmenopausal osteoporosis included a good proportion of elderly patients 65 to 75 years of age, as well as patients over 75 years of age. No overall differences in efficacy or safety were observed between older patients and younger adults during these trials. In the male osteoporosis trial, 28% of patients receiving risedronate were aged 65 to 75 years and 9% were over 75 years of age. The lumbar spine bone mineral density change for risedronate compared to placebo was 5.6% for subjects less than 65 years of age and 2.9% for subjects 65 years and older. No overall differences in safety were observed between elderly and younger patients in this trial. Per the manufacturer, however, greater sensitivity of some older individuals cannot be ruled out. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of medications in residents of long-term care facilities. The OBRA guidelines state that bisphosphonates must be taken according to very specific directions, including time of day, position, and timing relative to other medications and food. Patients receiving these medications should be monitored closely for GI complications (e.g., esophageal or gastric erosion). Potential adverse effects of bisphosphonates include dysphagia, esophagitis, gastritis, or esophageal and gastric ulcers, particularly when used in combination with oral corticosteroids, aspirin, or other NSAIDs.
Anemia, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, dental work, infection
Osteonecrosis of the jaw has been reported in patients with cancer receiving treatment regimens which included bisphosphonates (most commonly pamidronate and zoledronic acid), but also occasionally in patients receiving chronic oral bisphosphonate therapy for osteoporosis, including risedronate. The risk may increase with duration of exposure to the bisphosphonate. In patients with cancer receiving intravenous bisphosphonates, many patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures, such as tooth extraction, and many of these patients had signs of local infection including osteomyelitis; however, cases have appeared spontaneously. It would be prudent for all patients including those with concomitant risk factors (e.g. anemia, cancer, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, infection, poor oral hygiene) initiating bisphosphonate therapy to receive a dental examination with appropriate preventive dentistry and correction of dental complications prior to beginning treatment. Preventive measures such as these as well as continued regular follow-up with a dentist during bisphosphonate therapy are recommended by the American Academy of Oral Medicine as the best way to minimize the risk of osteonecrosis. Invasive dental procedures should be avoided, if possible, during treatment, but if they are necessary, should be performed by an experienced dentist with close patient follow-up. If osteonecrosis of the jaw does develop during bisphosphonate therapy, it should be noted that dental surgery may exacerbate the condition. For patients requiring dental work, no data are available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Discontinuing the bisphosphonate once osteonecrosis develops is controversial as the estimated half-life of bisphosphonates in the bone is years.
Laboratory test interference
Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with risedronate regarding this laboratory test interference have not been performed.
ADVERSE REACTIONS
Severe
prostatic hypertrophy / Delayed / 5.0-5.0
toxic epidermal necrolysis / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
uveitis / Delayed / 0-0.1
arrhythmia exacerbation / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
esophageal ulceration / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
visual impairment / Early / Incidence not known
osteonecrosis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
bone fractures / Delayed / Incidence not known
Moderate
constipation / Delayed / 2.9-12.9
hypertension / Early / 10.5-10.5
bone pain / Delayed / 5.3-10.0
peripheral edema / Delayed / 7.7-8.2
depression / Delayed / 6.8-6.8
chest pain (unspecified) / Early / 5.0-6.6
cataracts / Delayed / 6.5-6.5
hypocalcemia / Delayed / 0.2-4.5
nephrolithiasis / Delayed / 3.0-3.0
gastritis / Delayed / 1.0-2.7
glossitis / Early / 0.1-1.0
hypophosphatemia / Delayed / 0.6-0.6
iritis / Delayed / 0-0.1
dysphagia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
ocular inflammation / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known
bullous rash / Early / Incidence not known
Mild
arthralgia / Delayed / 6.8-32.8
infection / Delayed / 2.6-31.1
back pain / Delayed / 5.9-28.0
headache / Early / 2.6-20.0
diarrhea / Early / 4.7-19.7
vomiting / Early / 1.6-15.0
nausea / Early / 3.6-13.2
abdominal pain / Early / 2.3-12.2
rash / Early / 7.9-11.5
dyspepsia / Early / 3.9-10.8
sinusitis / Delayed / 8.7-8.7
influenza / Delayed / 6.2-7.2
dizziness / Early / 2.6-7.1
myalgia / Early / 1.0-6.7
rhinitis / Early / 6.2-6.2
pharyngitis / Delayed / 6.0-6.0
asthenia / Delayed / 5.4-5.4
insomnia / Early / 5.0-5.0
musculoskeletal pain / Early / 1.6-2.0
gastroesophageal reflux / Delayed / 1.0-1.6
pyrosis (heartburn) / Early / Incidence not known
ocular pain / Early / Incidence not known
DRUG INTERACTIONS
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aluminum Hydroxide: (Moderate) Separate administration of oral risedronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral risedronate.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of oral risedronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral risedronate.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Magnesium hydroxide will interfere with the absorption of risedronate. Do not take magnesium hydroxide within 2 hours of taking risedronate. (Moderate) Separate administration of oral risedronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral risedronate.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Magnesium hydroxide will interfere with the absorption of risedronate. Do not take magnesium hydroxide within 2 hours of taking risedronate. (Moderate) Separate administration of oral risedronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral risedronate.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of oral risedronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral risedronate.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Aspirin, ASA: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product. (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Dipyridamole: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Omeprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively. (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Oxycodone: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Pravastatin: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Calcium (oral): (Moderate) Separate administration of oral risedronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral risedronate.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Cimetidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including risedronate.
Dexlansoprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Esomeprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Famotidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Food: (Major) Any food, including milk products, will decrease the bioavailability of risedronate, and may also increase the risk of esophageal irritation from the medication. Patients should be informed to take risedronate at least 30 minutes before their first food or drink of the day, other than plain water.
H2-blockers: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Ibuprofen; Famotidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Iron: (Moderate) Separate administration of oral risedronate and iron supplements by at least 2 hours. Iron will interfere with the absorption of oral risedronate.
Lansoprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Lansoprazole; Naproxen: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Lanthanum Carbonate: (Moderate) To limit absorption problems, the oral bisphosphonates should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like the oral bisphosphonates, may also be bound by lanthanum carbonate. Separating times of administration will maximize absorption and clinical benefit of the bisphosphonate. Separate the times of administration appropriately. Monitor the patient's clinical status and bone density as recommended to ensure the appropriate response to bisphosphonate therapy is obtained.
Magnesium Citrate: (Moderate) Do not administer oral magnesium-containing products within 2 hours of oral bisphosphonates; oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g., alendronate, etidronate, ibandronate, risedronate, or tiludronate). All medications should be administered at least 30 minutes after an alendronate or risedronate dose, and at least 1 hour after an ibandronate dose to help prevent absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after these drugs or at a different time of day.
Magnesium Hydroxide: (Moderate) Magnesium hydroxide will interfere with the absorption of risedronate. Do not take magnesium hydroxide within 2 hours of taking risedronate.
Magnesium Salts: (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day.
Magnesium: (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day.
Naproxen; Esomeprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Nizatidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Nonsteroidal antiinflammatory drugs: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Omeprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Omeprazole; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product. (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Pantoprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Polycarbophil: (Moderate) Coadministration of risedronate with calcium polycarbophil can interfere with the oral absorption of risedronate; do not administer calcium polycarbophil within 30 minutes of risedronate. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
Proton pump inhibitors: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Rabeprazole: (Moderate) Use of proton pump inhibitors (PPIs) with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. In healthy subjects who received esomeprazole for 6 days, the Cmax and AUC of a single dose of risedronate delayed-release tablets (Atelvia) increased by 60% and 22%, respectively. PPIsare widely used and are frequently coadministered in users of oral bisphosphonates. A national register-based, open cohort study of 38,088 elderly patients suggests that those who use PPIs in conjunction with alendronate have a dose-dependent loss of protection against hip fracture. While causality was not investigated, the dose-response relationship noted during the study suggested that PPIs may reduce oral alendronate efficacy, perhaps through an effect on absorption or other mechanism, and therefore PPIs may not be optimal agents to control gastrointestinal complaints. Study results suggest that the interaction may occur across the class; however, other interactions have not been confirmed and data suggest that fracture protection is not diminished when risedronate is used with PPIs. A post hoc analysis of patients who took risedronate 5 mg daily during placebo-controlled clinical trials determined that risedronate significantly reduced the risk of new vertebral fractures compared to placebo, regardless of concomitant PPI use. PPI users (n = 240) and PPI non-users (n = 2489) experienced fracture risk reductions of 57% (p = 0.009) and 38% (p < 0.001), respectively.
Ranitidine: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g. risedronate). All medications should be administered at least 30 minutes after a risedronate dose to help prevent these absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after oral bisphosphonates or at a completely different time of day.
Vitamin A: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of risedronate therapy.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan with delayed-release risedronate tablets (Atelvia). Concomitant use of drugs that raise gastric pH, such as vonoprazan, increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of vonoprazan with delayed-release risedronate tablets (Atelvia). Concomitant use of drugs that raise gastric pH, such as vonoprazan, increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
PREGNANCY AND LACTATION
Pregnancy
There are no studies of risedronate use during human pregnancy. It is prudent to avoid the use of risedronate during pregnancy. There is a theoretical risk of fetal harm (predominantly skeletal) if a woman becomes pregnant during or after completing a course of bisphosphonate therapy. After a bisphosphonate is incorporated into bone matrix it is gradually released from the bone, over a period of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into systemic circulation, is directly related to the total dose and duration of bisphosphonate use. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration on this risk has not been established. Bisphosphonates do cause fetal harm in animals, suggesting the uptake of bisphosphonates into fetal bone is greater than into maternal bone. Animal reproductive studies indicate risedronate may induce fetal skeletal changes, decrease maternal calcium and cause protracted parturition, and may have a possible effect on fetal viability.[29352]
Risedronate should be used with caution during breast-feeding. It is not known whether risedronate is excreted in human milk; there are no data regarding the effect on the breastfed infant or the effect on lactation physiology or breast milk composition. Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount available for release back into the systemic circulation for potential excretion into breast milk, is directly related to the dose and duration of bisphosphonate use. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[29352]
MECHANISM OF ACTION
Risedronate is a potent antiresorptive agent that does not affect bone mineralization. The inclusion of an amino group within the heterocyclic ring makes risedronate one of the most potent antiresorptive bisphosphonates. Risedronate binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts, the bone-resorbing cells. Risedronate reduces bone resorption with no direct effect on bone formation. At the cellular level, risedronate shows preferential localization to sites of bone resorption, specifically inhibiting osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Histomorphometry in rats, dogs, and minipigs showed that risedronate reduces bone turnover (i.e., the rate at which bone remodeling sites are activated) and bone resorption at remodeling sites, leading to progressive gains in bone mass. [26651] [50514]
Like other bisphosphonates, the exact mechanism of risedronate's therapeutic effect in patients with Paget's disease has not been established. Paget's disease is a progressive, idiopathic disease of bone. Increasing numbers of unusually large osteoclasts are produced at affected sites. Increased osteoclastic bone resorption follows, which is compensated for by an increase in osteoblastic bone formation, leading to the replacement of the normal bone architecture by disorganized, enlarged, and weakened bone structure. This new bone architecture is inferior and often deformed, and can fracture easily. Bisphosphonates are believed to reduce the solubility of the mineralized bone matrix by adsorption to hydroxyapatite crystals in the matrix. The matrix becomes less soluble and resistant to osteoclastic resorption, which helps stabilize osteolytic lesions. Risedronate and other bisphosphonates can also block the formation of mature osteoclasts by affecting the attachment of osteoclast precursors to the mineralized matrix. In patients with Paget's disease, risedronate directly decreases bone resorption, resulting in a significant decrease in serum alkaline phosphatase and urinary markers of bone collagen degradation. Bisphosphonates cause histological and radiological evidence of Paget's disease improvement and also reduce pain. [50514]
Some bisphosphonates cause a significant decrease in serum calcium and urinary calcium levels in patients with hypercalcemia of malignancy, and some bisphosphonate agents in selected cancer patients may reduce osteopenia related to cancer treatment and thus help reduce skeletal events.[50514]
PHARMACOKINETICS
Risedronate is administered orally. Approximately 60% of the absorbed dose is distributed to the bone with the remainder of the dose excreted in the urine. Unabsorbed drug is eliminated in the feces. Risedronate is not metabolized in the liver and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes. Approximately 50% of the absorbed dose is excreted in the urine within 24 hours. Risedronate elimination is biphasic with an initial half-life of 1.5 hours and a terminal half-life of 220 hours. The extended terminal half-life is thought to be due to risedronate release from bone.
Oral Route
Risedronate is absorbed throughout the upper GI tract after oral administration. Differences in time to peak plasma concentration and bioavailability exist between the immediate-release and delayed-release dosage forms; both forms are significantly affected by administration with food. Immediate release tablets achieve Tmax approximately 1 hour after administration, while the Tmax of delayed-release tablets occurs approximately 3 hours after the dose. Bioavailability of 35 mg delayed-release tablets given after a high-fat breakfast and 35 mg immediate-release tablets given 4 hours prior to a meal are similar; however, the bioavailability of the delayed-release tablet is 2- to 4-fold higher than that of the immediate-release tablet administered as indicated (at least 30 minutes prior to breakfast). The average bioavailability of immediate-release risedronate taken 4 hours prior to a meal is 0.63%. Absorption of the immediate-release tablet is decreased by 55% if this dosage form is taken either 0.5 hours prior to breakfast or 2 hours after dinner as compared to absorption in the fasting state, while absorption is decreased by 30% when given 1 hour prior to breakfast as compared to the fasting state. The bioavailability of delayed-release risedronate is decreased by approximately 30% when administered 30 minutes after a high-fat breakfast as compared to when administered 4 hours prior to the morning meal; however, in clinical trials, administration of delayed-release risedronate prior to breakfast, resulted in a higher incidence of abdominal pain. Risedronate is considered effective when immediate-release tablets are given at least 30 minutes prior to breakfast and when delayed-release tablets are given after breakfast. Unabsorbed drug is eliminated in the feces.