INTERACTIONS No specific drug-drug interaction studies were performed. Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes (for example, Cytochrome P450). Calcium, antacids, or oral medications containing divalent cations interfere with the absorption of risedronate sodium tablets ( 7.1 )
7.1 Calcium Supplements/Antacids Co-administration of risedronate sodium tablets and calcium, antacids, or oral medications containing divalent cations will interfere with the absorption of risedronate sodium tablets.
7.2 Hormone Replacement Therapy One study of about 500 early postmenopausal women has been conducted to date in which treatment with risedronate sodium tablets 5 mg daily plus estrogen replacement therapy was compared to estrogen replacement therapy alone. Exposure to study drugs was approximately 12 to 18 months and the primary endpoint was change in BMD. If considered appropriate, risedronate sodium tablets may be used concomitantly with hormone replacement therapy.
7.3 Aspirin/Nonsteroidal Anti-Inflammatory Drugs Of over 5700 patients enrolled in the risedronate sodium tablets Phase 3 osteoporosis studies, aspirin use was reported by 31% of patients, 24% of whom were regular users (3 or more days per week). Forty-eight percent of patients reported NSAID use, 21% of whom were regular users. Among regular aspirin or NSAID users, the incidence of upper gastrointestinal adverse experiences in placebo-treated patients (24.8%) was similar to that in risedronate sodium tablets-treated patients (24.5%). 7.4 H 2 Blockers and Proton Pump Inhibitors (PPIs) Of over 5700 patients enrolled in the risedronate sodium tablets Phase 3 osteoporosis studies, 21% used H 2 blockers and/or PPIs. Among these patients, the incidence of upper gastrointestinal adverse experiences in the placebo-treated patients was similar to that in risedronate sodium tablets-treated patients.
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 risedronate sodium delayed-release tablets 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 Femur
Fractures have been reported. Patients with new thigh or groin pain should be evaluated to rule out a femoral fracture ( 5.6 )
5.1 Drug Products with the Same Active Ingredient Risedronate sodium tablets contain the same active ingredient found in risedronate sodium delayed-release tablets. A patient being treated with risedronate sodium delayed-release tablets should not receive risedronate sodium tablets.
5.2 Upper Gastrointestinal Adverse Reactions Risedronate sodium, 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 sodium is given to patients with active upper gastrointestinal problems (such as known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers) [ see Contraindications ( 4 ), Adverse Reactions ( 6.1 ), Information for Patients ( 17 ) ]. 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 sodium 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 [ see Dosage and Administration ( 2 ) ]. In patients who cannot comply with dosing instructions due to mental disability, therapy with risedronate sodium should be used under appropriate supervision. There have been postmarketing 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 sodium tablets. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting risedronate sodium tablet 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 [ see Contraindications ( 4 ), Adverse Reactions ( 6.1 ), Information for Patients ( 17 ) ].
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 sodium. 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 preexisting 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 [ see Adverse Reactions ( 6.2 ) ]. 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 Subtrochanteric and Diaphyseal Femoral Fractures Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are traverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates. Atypical femur fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (for example, prednisone) at the time of fracture. 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. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment, on an individual basis.
5.7 Renal Impairment Risedronate sodium 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 sodium 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 sodium have not been performed.