INTERACTIONS Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes (for example, Cytochrome P450). Calcium supplements, antacids, proton pump inhibitors (PPIs), H 2 blockers, magnesium-based supplements or laxatives, and iron preparations interfere with the absorption of risedronate sodium (7.1, 7.2)
7.1 Calcium Supplements/Antacids When risedronate sodium 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% [ see Clinical Pharmacology (12.3) ]. Calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations interfere with the absorption of risedronate sodium and should not be taken together.
7.2 Histamine 2 (H 2 ) Blockers and Proton Pump Inhibitors (PPIs) Drugs that raise stomach pH (for example, PPIs or H 2 blockers) may cause faster drug release from enteric coated (delayed-release) drug products such as risedronate sodium. Co-administration of risedronate sodium with the PPI, esomeprazole, increased risedronate bioavailability. The maximum plasma concentration (C max ) and the area under the plasma concentration (AUC) were increased by 60 percent and 22 percent, respectively. Concomitant administration of risedronate sodium and H 2 blockers or PPIs is not recommended.
7.3 Hormone Therapy Concomitant use of risedronate sodium with estrogens and estrogen agonist/antagonists has not been studied.
7.4 Aspirin/Nonsteroidal Anti-Inflammatory Drugs In the Phase 3 study comparing risedronate sodium 35 mg once-a-week immediately following breakfast and risedronate sodium 5 mg daily, 18% of NSAID users (any use) in both groups developed upper gastrointestinal adverse reactions. Among non-users, 13% of patients taking risedronate sodium 35 mg once-a-week immediately following breakfast developed upper gastrointestinal adverse reactions, compared to 12% taking risedronate sodium 5 mg daily.
Risedronate sodium tablets are contraindicated in patients with the following conditions:
- Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia [see Warnings and Precautions ( 5.1 )]
- Inability to stand or sit upright for at least 30 minutes [see Dosage and Administration ( 2 ), Warnings and Precautions ( 5.1 )]
- Hypocalcemia [see Warnings and Precautions ( 5.2 )]
- Known hypersensitivity to risedronate sodium tablets or any of its excipients. Angioedema, generalized rash, bullous skin reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported [see Adverse Reactions ( 6.2 )] Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia ( 4 , 5.1 ) Inability to stand or sit upright for at least 30 minutes ( 4 , 5.1 ) Hypocalcemia ( 4 , 5.2 ) Known hypersensitivity to any component of this product ( 4 , 6.2 )
AND PRECAUTIONS Products Containing Same Active Ingredient : Patients receiving Atelvia should not be treated with risedronate sodium tablets ( 5.1 )
Upper Gastrointestinal Adverse
Reactions can occur. Instruct patients to follow dosing instructions. Discontinue use if new or worsening symptoms occur ( 5.2 ) Hypocalcemia may worsen and must be corrected prior to use ( 5.3 ) Osteonecrosis of the Jaw has been reported ( 5.4 )
Severe
Bone, Joint, Muscle Pain may occur. Discontinue use if severe symptoms develop ( 5.5 , 6.2 )
Atypical Fractures Including Femoral
Fractures have been reported. Patients with new thigh or groin pain should be evaluated to rule out a femoral fracture. Risk/benefit of continuing bisphosphonate therapy should be re-evaluated in these patients and interruption of bisphosphonate therapy should be considered ( 5.6 )
5.1 Drug Products with the Same Active Ingredient Risedronate sodium tablets contain the same active ingredient found in Atelvia ® . A patient being treated with Atelvia should not receive risedronate sodium tablets.
5.2 Upper Gastrointestinal Adverse Reactions Risedronate, 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 risedronate is given to patients with active upper gastrointestinal problems (such as known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers) <span class="opacity-50 text-xs">[see Contraindications (4) , Adverse Reactions (6.1) , Information for Patients (17) ]</span> . Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. In some cases, these have been severe and required hospitalization. Physicians should therefore be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue risedronate and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. The risk of severe esophageal adverse experiences appears to be greater in patients who lie down after taking oral bisphosphonates and/or who fail to swallow it with the recommended full glass (6 to 8 ounces) of water, and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Therefore, it is very important that the full dosing instructions are provided to, and understood by, the patient <span class="opacity-50 text-xs">[see Dosage and Administration (2) ]</span> . In patients who cannot comply with dosing instructions due to mental disability, therapy with risedronate should be used under appropriate supervision. There have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications, although no increased risk was observed in controlled clinical trials.
5.3 Mineral Metabolism Hypocalcemia has been reported in patients taking risedronate. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting risedronate 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, especially in patients with Paget’s disease in whom bone turnover is significantly elevated <span class="opacity-50 text-xs">[see Contraindications (4) , Adverse Reactions (6.1) , Information for Patients (17) ]</span>.
5.4 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. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk for ONJ. Clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on individual benefit/risk assessment. Patients who develop osteonecrosis of the jaw while on bisphosphonate therapy should receive care by an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of bisphosphonate therapy should be considered based on individual benefit/risk assessment <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> .
5.5 Musculoskeletal Pain In postmarketing experience, there have been reports of severe and occasionally incapacitating bone, joint, and/or muscle pain in patients taking bisphosphonates <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> . 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.
5.6 Atypical Fractures Including Femoral Fractures Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported during treatment with bisphosphonates, including risedronate, in patients with osteoporosis. Atypical femur and other fractures most commonly occur with minimal or no trauma to the affected area. These fractures occurred 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. Atypical fractures of other bones have also been reported. They may be bilateral. These fractures can also occur in osteoporotic patients who have not been treated with bisphosphonates. Concomitant treatment with glucocorticoids may also induce these fractures. Prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs was reported by patients. Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Bony pain in other locations should also be considered for evaluation of atypical fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Risk/benefit of continuing bisphosphonate therapy should be re-evaluated in these patients and interruption of bisphosphonate therapy should be considered.
5.7 Renal Impairment Risedronate is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min).
5.8 Glucocorticoid-Induced Osteoporosis Before initiating risedronate treatment for the treatment and prevention of glucocorticoid-induced osteoporosis, the sex steroid hormonal status of both men and women should be ascertained and appropriate replacement considered.
5.9 Laboratory Test Interactions Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with risedronate have not been performed.