Actonel
Risedronate Sodium · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE ACTONEL is a bisphosphonate indicated for: Treatment and prevention of postmenopausal osteoporosis ( 1.1 ) Treatment to increase bone mass in men with osteoporosis ( 1.2 ) Treatment and prevention of glucocorticoid-induced osteoporosis ( 1.3 ) Treatment of Paget’s disease ( 1.4 ) Limitations of Use Optimal duration of use has not been determined. For patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use. ( 1.5 ) 1.1 Postmenopausal Osteoporosis ACTONEL is indicated for the treatment and prevention of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, ACTONEL reduces the incidence of vertebral fractures and a composite endpoint of nonvertebral osteoporosis-related fractures [ see Clinical Studies ( 14.1 , 14.2 ) ] . 1.2 Osteoporosis in Men ACTONEL is indicated for treatment to increase bone mass in men with osteoporosis. 1.3 Glucocorticoid-Induced Osteoporosis ACTONEL is indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoid treatment (daily dosage of greater than or equal to 7.5 mg of prednisone or equivalent) for chronic diseases. Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D. 1.4 Paget’s Disease ACTONEL is indicated for treatment of Paget’s disease of bone in men and women. 1.5 Important Limitations of Use The optimal duration of use has not been determined. The safety and effectiveness of ACTONEL for the treatment of osteoporosis are based on clinical data of three years duration. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.
Dosage and administration
Treatment of Postmenopausal Osteoporosis: 5 mg daily, 35 mg once-a-week, 75 mg two consecutive days each month, 150 mg once-a-month ( 2.1 ) Prevention of Postmenopausal Osteoporosis: 5 mg daily, 35 mg once-a-week ( 2.2 ) Men with Osteoporosis: 35 mg once-a-week ( 2.3 ) Glucocorticoid-Induced Osteoporosis: 5 mg daily ( 2.4 ) Paget’s Disease: 30 mg daily for 2 months ( 2.5 ) Instruct patients to: Swallow tablet whole with 6 to 8 ounces of plain water, at least 30 minutes before the first food, beverage, or medication of the day Avoid lying down for 30 minutes ( 2 ) Take supplemental calcium and vitamin D if dietary intake is inadequate ( 2.7 ) 2.1 Treatment of Postmenopausal Osteoporosis [ see Indications and Usage (1.1 ) ] The recommended regimen is: one 5 mg tablet orally, taken daily or one 35 mg tablet orally, taken once-a-week or one 75 mg tablet orally, taken on two consecutive days for a total of two tablets each month or one 150 mg tablet orally, taken once-a-month 2.2 Prevention of Postmenopausal Osteoporosis [ see Indications and Usage ( 1.1 ) ] The recommended regimen is: one 5 mg tablet orally, taken daily or one 35 mg tablet orally, taken once-a-week or alternatively, one 75 mg tablet orally, taken on two consecutive days for a total of two tablets each month may be considered or alternatively, one 150 mg tablet orally, taken once-a-month may be considered 2.3 Treatment to Increase Bone Mass in Men with Osteoporosis [ see Indications and Usage ( 1.2 ) ] The recommended regimen is: one 35 mg tablet orally, taken once-a-week 2.4 Treatment and Prevention of Glucocorticoid-Induced Osteoporosis [ see Indications and Usage ( 1.3 ) ] The recommended regimen is: one 5 mg tablet orally, taken daily 2.5 Treatment of Paget’s Disease [ see Indications and Usage ( 1.4 ) ] The recommended treatment regimen is 30 mg orally once daily for 2 months. Retreatment may be considered (following post-treatment observation 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. No data are available on more than 1 course of retreatment. 2.6 Important Administration Instructions Instruct patients to do the following: Take ACTONEL at least 30 minutes before the first food or drink of the day other than water, and before taking any oral medication or supplementation, including calcium, antacids, or vitamins to maximize absorption and clinical benefit, [ see Drug Interactions ( 7.1 ) ] . Avoid the use of water with supplements, including mineral water, because they may have a higher concentration of calcium. Swallow ACTONEL tablets whole with a full glass of plain water (6 to 8 ounces). Avoid lying down for 30 minutes after taking the medication [ see Warnings and Precautions ( 5.1 ) ] . Do not chew or suck the tablet because of a potential for oropharyngeal ulceration. Do not eat or drink anything except plain water, or take other medications for at least 30 minutes after taking ACTONEL. 2.7 Recommendations for Calcium and Vitamin D Supplementation Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate; and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day as they interfere with the absorption of ACTONEL. 2. 8 Administration Instructions for Missed Doses Instruct patients about missing ACTONEL doses as follows: If a dose of ACTONEL 35 mg once-a-week is missed: Take 1 tablet on the morning after they remember and return to taking 1 tablet once-a-week, as originally scheduled on their chosen day. Do not take 2 tablets on the same day. If one or both tablets of ACTONEL 75 mg on two consecutive days per month are missed, and the next month’s scheduled doses are more than 7 days away: If both tablets are missed, take one ACTONEL 75 mg tablet in the morning after the day it is remembered and then the other tablet on the next consecutive morning. If only one ACTONEL 75 mg tablet is missed, take the missed tablet in the morning after the day it is remembered Return to taking their ACTONEL 75 mg on two consecutive days per month as originally scheduled. Do not take more than two 75 mg tablets within 7 days. If one or both tablets of ACTONEL 75 mg on two consecutive days per month are missed, and the next month's scheduled doses are within 7 days: Wait until their next month’s scheduled doses and then continue taking ACTONEL 75 mg on two consecutive days per month as originally scheduled. If the dose of ACTONEL 150 mg once-a-month is missed, and the next month’s scheduled dose is more than 7 days away: Take the missed tablet in the morning after the day it is remembered and then return to taking their ACTONEL 150 mg once-a-month as originally scheduled. Do not take more than one 150 mg tablet within 7 days. If the dose of ACTONEL 150 mg once-a-month is missed, and the next month's scheduled dose is within 7 days: Wait until their next month’s scheduled dose and then continue taking ACTONEL 150 mg once-a-month as originally scheduled.
Dosage forms and strengths
5 mg film-coated, oval, yellow tablet with RSN on 1 face and 5 mg on the other. 30 mg film-coated, oval, white tablet with RSN on 1 face and 30 mg on the other. 35 mg film-coated, oval, orange tablet with RSN on 1 face and 35 mg on the other. 75 mg film-coated, oval, pink tablet with RSN on 1 face and 75 mg on the other. 150 mg film-coated, oval, blue tablet with RSN on 1 face and 150 mg on the other. Tablets: 5, 30, 35, 75, and 150 mg ( 3 )
Contraindications
4 CONTRAINDICATIONS ACTONEL is 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 ACTONEL 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 , 5.3 ) Known hypersensitivity to any component of this product ( 4 , 6.2 )
Warnings and precautions
Products Containing Same Active Ingredient : Patients receiving Atelvia should not be treated with ACTONEL ( 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 J aw has been reported ( 5.4 ) S evere B one, J oint , M uscle P ain may occur. Discontinue use if severe symptoms develop ( 5.5 , 6.2 ) Atypical Fractures Including Femoral F ractures 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 ACTONEL contains the same active ingredient found in Atelvia ® . A patient being treated with Atelvia should not receive ACTONEL. 5. 2 Upper Gastrointestinal Adverse Reactions ACTONEL, 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 ACTONEL 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 ACTONEL 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 ACTONEL 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 ACTONEL. Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting ACTONEL 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 J aw 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 ACTONEL. 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 [ see Adverse Reactions ( 6.2 ) ] . 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 A dverse R eactions ( 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 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.
Side effects
The following clinically significant adverse drug reactions are described elsewhere in the labeling: Drug Products with the Same Active Ingredient [see Warnings and Precautions ( 5.1 ) ] Upper Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.2 ) ] Mineral Metabolism [see Warnings and Precautions ( 5.3 ) ] Jaw Osteonecrosis [see Warnings and Precautions ( 5.4 ) ] Musculoskeletal Pain [see Warnings and Precautions ( 5.5 ) ] Atypical Fractures Including Femoral Fractures [see Warnings and Precautions ( 5.6 ) ] Renal Impairment [see Warnings and Precautions ( 5.7 ) ] Glucocorticoid-Induced Osteoporosis [see Warnings and Precautions ( 5.8 ) ] Laboratory Test Interactions [see Warnings and Precautions ( 5.9 ) ] Most common adverse reactions reported in greater than 10% of patients treated with ACTONEL and with a higher frequency than placebo are: back pain, arthralgia, abdominal pain, and dyspepsia ( 6.1 ) Hypersensitivity reactions (angioedema, generalized rash, bullous skin reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis), and eye inflammation (iritis, uveitis) have been reported rarely ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Treatment of Postmenopausal Osteoporosis D aily Dosing The safety of ACTONEL 5 mg once daily in the treatment of postmenopausal osteoporosis was assessed in four randomized, double-blind, placebo-controlled multinational trials of 3232 women aged 38 to 85 years with postmenopausal osteoporosis. The duration of the trials was up to three years, with 1619 patients exposed to placebo and 1613 patients exposed to ACTONEL 5 mg. Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors, and H 2 antagonists were included in these clinical trials. All women received 1000 mg of elemental calcium plus vitamin D supplementation up to 500 international units per day if their 25-hydroxyvitamin D 3 level was below normal at baseline. The incidence of all-cause mortality was 2.0% in the placebo group and 1.7% in the ACTONEL 5 mg daily group. The incidence of serious adverse events was 24.6% in the placebo group and 27.2% in the ACTONEL 5 mg group. The percentage of patients who withdrew from the study due to adverse events was 15.6% in the placebo group and 14.8% in the ACTONEL 5 mg group. The most common adverse reactions reported in greater than 10 percent of subjects were: back pain, arthralgia, abdominal pain and dyspepsia. Table 1 lists adverse events from the Phase 3 postmenopausal osteoporosis trials reported in greater than or equal to 5% of patients. Adverse events are shown without attribution of causality. Table 1 Adverse Events Occurring at a Frequency greater than or equal to 5% in Either Treatment Group Combined Phase 3 Postmenopausal Osteoporosis Treatment Trials Body System Placebo N = 1619 5 mg ACTONEL N = 1613 % % Body as a Whole Infection 29.9 31.1 Back Pain 26.1 28.0 Accidental Injury 16.8 16.9 Pain 14.0 14.1 Abdominal Pain 9.9 12.2 Flu Syndrome 11.6 10.5 Headache 10.8 9.9 Asthenia 4.5 5.4 Neck Pain 4.7 5.4 Chest Pain 5.1 5.0 Allergic Reaction 5.9 3.8 Cardiovascular System Hypertension 9.8 10.5 Digestive System Constipation 12.6 12.9 Diarrhea 10.0 10.8 Dyspepsia 10.6 10.8 Nausea 11.2 10.5 Metabolic & Nutritional Disorders Peripheral Edema 8.8 7.7 Musculoskeletal System Arthralgia 22.1 23.7 Arthritis 10.1 9.6 Traumatic Bone Fracture 12.3 9.3 Joint Disorder 5.3 7.0 Myalgia 6.2 6.7 Bone Pain 4.8 5.3 Nervous System Dizziness 5.7 7.1 Depression 6.1 6.8 Insomnia 4.6 5.0 Respiratory System Bronchitis 10.4 10.0 Sinusitis 9.1 8.7 Rhinitis 5.1 6.2 Pharyngitis 5.0 6.0 Increased Cough 6.3 5.9 Skin and Appendages Rash 7.1 7.9 Special Senses Cataract 5.7 6.5 Urogenital System Urinary Tract Infection 10.4 11.1 Gastrointestinal Adverse Events: The incidence of adverse events in the placebo and ACTONEL 5 mg daily groups were: abdominal pain (9.9% versus 12.2%), diarrhea (10.0% versus 10.8%), dyspepsia (10.6% versus 10.8%), and gastritis (2.3% versus 2.7%). Duodenitis and glossitis have been reported uncommonly in the ACTONEL 5 mg daily group (0.1% to 1%). In patients with active upper gastrointestinal disease at baseline, the incidence of upper gastrointestinal adverse events was similar between the placebo and ACTONEL 5 mg daily groups. Musculoskeletal Adverse Events: The incidence of adverse events in the placebo and ACTONEL 5 mg daily groups were: back pain (26.1% versus 28.0%), arthralgia (22.1% versus 23.7%), myalgia (6.2% versus 6.7%), and bone pain (4.8% versus 5.3%). Laboratory Test Findings: Throughout the Phase 3 studies, transient decreases from baseline in serum calcium (less than 1%) and serum phosphate (less than 3%) and compensatory increases in serum PTH levels (less than 30%) were observed within 6 months in patients in osteoporosis clinical trials treated with ACTONEL 5 mg once daily. There were no significant differences in serum calcium, phosphate, or PTH levels between placebo and ACTONEL 5 mg once daily at 3 years. Serum calcium levels below 8 mg/dL were observed in 18 patients, 9 (0.5%) in each treatment arm (placebo and ACTONEL 5 mg once daily). Serum phosphorus levels below 2 mg/dL were observed in 14 patients, 3 (0.2%) treated with placebo and 11 (0.6%) treated with ACTONEL 5 mg once daily. There have been rare reports (less than 0.1%) of abnormal liver function tests. Endoscopic Findings: In the ACTONEL clinical trials, endoscopic evaluation was encouraged in any patient with moderate-to-severe gastrointestinal complaints, while maintaining the blind.
Drug interactions
No specific drug-drug interaction studies were performed. Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes (for example, Cytochrome P450). Calcium, antacids, or oral medications containing divalent cations interfere with the absorption of ACTONEL ( 7.1 ) 7.1 Calcium Supplements/Antacids Co-administration of ACTONEL and calcium, antacids, or oral medications containing divalent cations will interfere with the absorption of ACTONEL. 7.2 Hormone Replacement Therapy One study of about 500 early postmenopausal women has been conducted to date in which treatment with ACTONEL 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, ACTONEL may be used concomitantly with hormone replacement therapy. 7.3 Aspirin/Nonsteroidal Anti-Inflammatory Drugs Of over 5700 patients enrolled in the ACTONEL 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 ACTONEL-treated patients (24.5%). 7.4 H 2 Blockers and Proton Pump Inhibitors (PPIs) Of over 5700 patients enrolled in the ACTONEL 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 ACTONEL-treated patients.
Use in specific populations
Pregnancy: Discontinue when pregnancy is recognized ( 8.1 ) ACTONEL is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/min) ( 5.6 , 8.6 , 12.3 ) ACTONEL is not indicated for use in pediatric patients ( 8.4 ) 8.1 Pregnancy Risk Summary Available data on the use of ACTONEL in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue ACTONEL when pregnancy is recognized. In animal reproduction studies, daily oral administration of risedronate to pregnant rats during organogenesis decreased neonatal survival and body weight at doses approximately 5 and 26 times, respectively, the highest recommended human daily dose of 30 mg (based on body surface area, mg/m 2 ). A low incidence of cleft palate was observed in fetuses of dams treated at doses approximately equal to the 30 mg human daily dose. Delayed skeletal ossification was observed in fetuses of dams treated at approximately 2.5 to 5 times the 30 mg human daily dose. Periparturient mortality due to maternal hypocalcemia occurred in dams and neonates upon daily oral administration of risedronate to pregnant rats during mating and/or gestation starting at doses equivalent to the 30 mg daily human dose. 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 available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on this risk has not been studied. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 - 4% and 15 - 20%, respectively. Data Animal Data In animal studies, pregnant rats received risedronate sodium during organogenesis at doses equivalent to 1 to 26 times the 30 mg human daily dose (based on body surface area, mg/m 2 ). Survival of neonates was decreased in dams treated during gestation with oral doses approximately 5 times the human dose, and body weight was decreased in neonates of dams treated with approximately 26 times the human dose. A low incidence of cleft palate was observed in fetuses of dams treated with oral doses approximately equal to the human dose. The number of fetuses exhibiting incomplete ossification of sternebrae or skull of dams treated with approximately 2.5 times the human dose was significantly increased compared to controls. Both incomplete ossification and unossified sternebrae were increased in fetuses of dams treated with oral doses approximately 5 times the human dose. No significant ossification effects were seen in fetuses of rabbits treated with oral doses approximately 7 times the human dose (the highest dose tested). However, 1 of 14 litters were aborted and 1 of 14 litters were delivered prematurely. Periparturient mortality due to maternal hypocalcemia occurred in dams and neonates when pregnant rats were treated daily during mating and/or gestation with oral doses equivalent to the human dose or higher. 8. 2 Lactation Risk Summary There are no data on the presence of risedronate in human milk, the effects on the breastfed infant, or the effects on milk production. A small degree of lacteal transfer occurred in nursing rats. The concentration of the drug in animal milk does not necessarily predict the concentration of drug in human milk. However, when a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ACTONEL and any potential adverse effects on the breast-fed child from ACTONEL or from the underlying maternal condition. Data Animal Data Risedronate was detected in neonates of lactating rats given a single oral dose of risedronate at 24-hours post-dosing, indicating a small degree of lacteal transfer. 8.4 Pediatric Use ACTONEL is not indicated for use in pediatric patients. The safety and effectiveness of risedronate was assessed in a one-year, randomized, double-blind, placebo-controlled study of 143 pediatric patients (94 received risedronate) with osteogenesis imperfecta (OI). The enrolled population was predominantly patients with mild osteogenesis imperfecta (85% Type-I), aged 4 to less than 16 years, 50% male and 82% Caucasian, with a mean lumbar spine BMD Z-score of -2.08 (2.08 standard deviations below the mean for age-matched controls). Patients received either a 2.5 mg (less than or equal to 30 kg body weight) or 5 mg (greater than 30 kg body weight) daily oral dose. After one year, an increase in lumbar spine BMD in the risedronate group compared to the placebo group was observed. However, treatment with risedronate did not result in a reduction in the risk of fracture in pediatric patients with osteogenesis imperfecta. In ACTONEL-treated subjects, no mineralization defects were noted in paired bone biopsy specimens obtained at baseline and month 12. The overall safety profile of risedronate in OI patients treated for up to 12 months was generally similar to that of adults with osteoporosis. However, there was an increased incidence of vomiting compared to placebo.
Pregnancy
8.1 Pregnancy Risk Summary Available data on the use of ACTONEL in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue ACTONEL when pregnancy is recognized. In animal reproduction studies, daily oral administration of risedronate to pregnant rats during organogenesis decreased neonatal survival and body weight at doses approximately 5 and 26 times, respectively, the highest recommended human daily dose of 30 mg (based on body surface area, mg/m 2 ). A low incidence of cleft palate was observed in fetuses of dams treated at doses approximately equal to the 30 mg human daily dose. Delayed skeletal ossification was observed in fetuses of dams treated at approximately 2.5 to 5 times the 30 mg human daily dose. Periparturient mortality due to maternal hypocalcemia occurred in dams and neonates upon daily oral administration of risedronate to pregnant rats during mating and/or gestation starting at doses equivalent to the 30 mg daily human dose. 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 available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on this risk has not been studied. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 - 4% and 15 - 20%, respectively. Data Animal Data In animal studies, pregnant rats received risedronate sodium during organogenesis at doses equivalent to 1 to 26 times the 30 mg human daily dose (based on body surface area, mg/m 2 ). Survival of neonates was decreased in dams treated during gestation with oral doses approximately 5 times the human dose, and body weight was decreased in neonates of dams treated with approximately 26 times the human dose. A low incidence of cleft palate was observed in fetuses of dams treated with oral doses approximately equal to the human dose. The number of fetuses exhibiting incomplete ossification of sternebrae or skull of dams treated with approximately 2.5 times the human dose was significantly increased compared to controls. Both incomplete ossification and unossified sternebrae were increased in fetuses of dams treated with oral doses approximately 5 times the human dose. No significant ossification effects were seen in fetuses of rabbits treated with oral doses approximately 7 times the human dose (the highest dose tested). However, 1 of 14 litters were aborted and 1 of 14 litters were delivered prematurely. Periparturient mortality due to maternal hypocalcemia occurred in dams and neonates when pregnant rats were treated daily during mating and/or gestation with oral doses equivalent to the human dose or higher.
Pediatric use
8.4 Pediatric Use ACTONEL is not indicated for use in pediatric patients. The safety and effectiveness of risedronate was assessed in a one-year, randomized, double-blind, placebo-controlled study of 143 pediatric patients (94 received risedronate) with osteogenesis imperfecta (OI). The enrolled population was predominantly patients with mild osteogenesis imperfecta (85% Type-I), aged 4 to less than 16 years, 50% male and 82% Caucasian, with a mean lumbar spine BMD Z-score of -2.08 (2.08 standard deviations below the mean for age-matched controls). Patients received either a 2.5 mg (less than or equal to 30 kg body weight) or 5 mg (greater than 30 kg body weight) daily oral dose. After one year, an increase in lumbar spine BMD in the risedronate group compared to the placebo group was observed. However, treatment with risedronate did not result in a reduction in the risk of fracture in pediatric patients with osteogenesis imperfecta. In ACTONEL-treated subjects, no mineralization defects were noted in paired bone biopsy specimens obtained at baseline and month 12. The overall safety profile of risedronate in OI patients treated for up to 12 months was generally similar to that of adults with osteoporosis. However, there was an increased incidence of vomiting compared to placebo. In this study, vomiting was observed in 15% of children treated with risedronate and 6% of patients treated with placebo. Other adverse events reported in greater than or equal to 10% of patients treated with risedronate and with a higher frequency than placebo were: pain in the extremity (21% with risedronate versus 16% with placebo), headache (20% versus 8%), back pain (17% versus 10%), pain (15% versus 10%), upper abdominal pain (11% versus 8%), and bone pain (10% versus 4%).
Geriatric use
8.5 Geriatric Use Of the patients receiving ACTONEL in postmenopausal osteoporosis studies [ see C linical S tudies ( 14 ) ] , 47% were between 65 and 75 years of age, and 17% were over 75. The corresponding proportions were 26% and 11% in glucocorticoid-induced osteoporosis trials, and 40% and 26% in Paget’s disease trials. No overall differences in efficacy between geriatric and younger patients were observed in these studies. In the male osteoporosis trial, 28% of patients receiving ACTONEL were between 65 and 75 years of age and 9% were over 75. The lumbar spine BMD response for ACTONEL compared to placebo was 5.6% for subjects less than 65 years and 2.9% for subjects greater than or equal to 65 years. No overall differences in safety between geriatric and younger patients were observed in the ACTONEL trials, but greater sensitivity of some older individuals cannot be ruled out.
Overdosage
Decreases in serum calcium and phosphorus following substantial overdose may be expected in some patients. Signs and symptoms of hypocalcemia may also occur in some of these patients. Milk or antacids containing calcium should be given to bind ACTONEL and reduce absorption of the drug. In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed drug. Standard procedures that are effective for treating hypocalcemia, including the administration of calcium intravenously, would be expected to restore physiologic amounts of ionized calcium and to relieve signs and symptoms of hypocalcemia. Lethality after single oral doses was seen in female rats at 903 mg/kg and male rats at 1703 mg/kg. The minimum lethal dose in mice and rabbits was 4000 mg/kg and 1000 mg/kg, respectively. These values represent 320 to 620 times the 30 mg human dose based on surface area (mg/m 2 ).
Description
(risedronate sodium) tablets is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism. Each ACTONEL tablet for oral administration contains the equivalent of 5, 30, 35, 75, or 150 mg of anhydrous risedronate sodium in the form of the hemi-pentahydrate with small amounts of monohydrate. The empirical formula for risedronate sodium hemi-pentahydrate is C 7 H 10 NO 7 P 2 Na
• 2.5 H 2 O. The chemical name of risedronate sodium is [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid] monosodium salt. The chemical structure of risedronate sodium hemi-pentahydrate is the following: Molecular Weight: Anhydrous: 305.10 Hemi-pentahydrate: 350.13 Risedronate sodium is a fine, white to off-white, odorless, crystalline powder. It is soluble in water and in aqueous solutions, and essentially insoluble in common organic solvents. Inactive Ingredients All dose strengths contain: crospovidone, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, silicon dioxide, titanium dioxide. Dose strength-specific ingredients include: 5 mg—ferric oxide yellow, lactose monohydrate; 30 mg—lactose monohydrate; 35 mg—ferric oxide red, ferric oxide yellow, lactose monohydrate; 75 mg—ferric oxide red; 150 mg—FD&C blue #2 aluminum lake. ACTONEL (risedronate sodium) tablets is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism. Each ACTONEL tablet for oral administration contains the equivalent of 5, 30, 35, 75, or 150 mg of anhydrous risedronate sodium in the form of the hemi-pentahydrate with small amounts of monohydrate. The empirical formula for risedronate sodium hemi-pentahydrate is C7H10NO7P2Na
• 2.5 H2O. The chemical name of risedronate sodium is [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid] monosodium salt. The chemical structure of risedronate sodium hemi-pentahydrate is the following:
Mechanism of action
12.1 Mechanism of Action ACTONEL has an affinity for hydroxyapatite crystals in bone and acts as an antiresorptive agent. At the cellular level, ACTONEL inhibits osteoclasts. The osteoclasts adhere normally to the bone surface, but show evidence of reduced active resorption (for example, lack of ruffled border). Histomorphometry in rats, dogs, and minipigs showed that ACTONEL treatment reduces bone turnover (activation frequency, that is, the rate at which bone remodeling sites are activated) and bone resorption at remodeling sites.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING ACTONEL ® is available as follows: 5 mg film-coated, oval, yellow tablets with RSN on 1 face and 5 mg on the other. NDC 0430-0471-15 bottle of 30 30 mg film-coated, oval, white tablets with RSN on 1 face and 30 mg on the other. NDC 0430-0470-15 bottle of 30 35 mg film-coated, oval, orange tablets with RSN on 1 face and 35 mg on the other. NDC 0430-0472-03 dose pack of 4 NDC 0430-0472-07 dose pack of 12 75 mg film-coated, oval, pink tablets with RSN on 1 face and 75 mg on the other. NDC 0430-0477-02 dose pack of 2 150 mg film-coated, oval, blue tablets with RSN on 1 face and 150 mg on the other. NDC 0430-0478-01 dose pack of 1 NDC 0430-0478-02 dose pack of 3 Store at controlled room temperature 20° to 25° C (68° to 77° F) [see USP].
Patient information
See FDA-approved patient labeling ( Medication Guide ) Instruct patients to read the Medication Guide before starting therapy with ACTONEL and to re-read it each time the prescription is renewed. Instruct patients that Atelvia and ACTONEL contain the same active ingredient and if they are taking Atelvia, they should not take ACTONEL [ see Warnings and Precautions ( 5.1 ) ] . Instruct patients to pay particular attention to the dosing instructions as clinical benefits may be compromised by failure to take the drug according to instructions. Specifically, ACTONEL should be taken at least 30 minutes before the first food or drink of the day other than water. Instruct patients to take ACTONEL while in an upright position (sitting or standing) with a full glass of plain water (6 to 8 ounces) to facilitate delivery to the stomach, and thus reduce the potential for esophageal irritation. Instruct patients not to lie down for 30 minutes after taking the medication [ see Warnings and Precautions ( 5.1 ) ] . Instruct patients not to chew or suck on the tablet because of a potential for oropharyngeal irritation. Instruct patients that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or severe persistent or worsening heartburn) they should consult their physician before continuing ACTONEL. Instruct patients about missing ACTONEL doses as follows: If a dose of ACTONEL 35 mg once-a-week is missed, they should take 1 tablet on the morning after they remember and return to taking 1 tablet once-a-week, as originally scheduled on their chosen day. Patients should not take 2 tablets on the same day. If one or both tablets of ACTONEL 75 mg on two consecutive days per month are missed, and the next month’s scheduled doses are more than 7 days away, the patient should be instructed as follows: If both tablets are missed, take one ACTONEL 75 mg tablet in the morning after the day it is remembered and then the other tablet on the next consecutive morning. If only one ACTONEL 75 mg tablet is missed, take the missed tablet in the morning after the day it is remembered. Patients should then return to taking their ACTONEL 75 mg on two consecutive days per month as originally scheduled. Patients should not take more than two 75 mg tablets within 7 days. If one or both tablets of ACTONEL 75 mg on two consecutive days per month are missed, and the next month's scheduled doses are within 7 days, patients should wait until their next month’s scheduled doses and then continue taking ACTONEL 75 mg on two consecutive days per month as originally scheduled. If the dose of ACTONEL 150 mg once-a-month is missed, and the next month’s scheduled dose is more than 7 days away, the patient should be instructed to take the missed tablet in the morning after the day it is remembered. Patients should then return to taking their ACTONEL 150 mg once-a-month as originally scheduled. Patients should not take more than one 150 mg tablet within 7 days. If the dose of ACTONEL 150 mg once-a-month is missed, and the next month's scheduled dose is within 7 days, patients should wait until their next month’s scheduled dose and then continue taking ACTONEL 150 mg once-a-month as originally scheduled. Instruct patients to take supplemental calcium and vitamin D if dietary intake is inadequate [ see Warnings and Precautions ( 5.3 ) ] . Weight-bearing exercise should be considered along with the modification of certain behavioral factors, such as excessive cigarette smoking, and/or alcohol consumption, if these factors exist. Instruct patients to take calcium supplements or calcium-, aluminum-, and magnesium-containing medications at a different time of the day than ACTONEL as these medications may interfere with the absorption of ACTONEL. Remind patients to give all of their healthcare providers an accurate medication history. Instruct patients to tell all of their healthcare providers that they are taking ACTONEL. Patients should be instructed that any time they have a medical problem they think may be from ACTONEL, they should talk to their doctor. Distributed by: AbbVie Inc. North Chicago, Illinois 60064 © 2026 AbbVie. All rights reserved. ACTONEL and its design are trademarks of Allergan Pharmaceuticals International Limited, an AbbVie company. 133169 R2
Label text from the FDA structured product label by Allergan, Inc. (revised Feb 4, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Risedronate Sodium Hemipentahydrate in 2 products
- Risedronate Sodium Monohydrate in 2 products
Actonel NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0430-0472 | Risedronate Sodium Hemipentahydrate 30.1 mg/1; Risedronate Sodium Monohydrate 4.9 mg/1 Tablet, Film Coated | Allergan, Inc. | NDA |
| 0430-0478 | Risedronate Sodium Hemipentahydrate 129 mg/1; Risedronate Sodium Monohydrate 21 mg/1 Tablet, Film Coated | Allergan, Inc. | NDA |
Frequently asked questions
What is Actonel used for?
1 INDICATIONS AND USAGE ACTONEL is a bisphosphonate indicated for: Treatment and prevention of postmenopausal osteoporosis ( 1.1 ) Treatment to increase bone mass in men with osteoporosis ( 1.2 ) Treatment and prevention of glucocorticoid-induced osteoporosis ( 1.3 ) Treatment of Paget’s disease ( 1.4 ) Limitations of Use Optimal duration of use has not been determined. For patients at low-risk…
What are the side effects of Actonel?
The following clinically significant adverse drug reactions are described elsewhere in the labeling: Drug Products with the Same Active Ingredient [see Warnings and Precautions ( 5.1 ) ] Upper Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.2 ) ] Mineral Metabolism [see Warnings and Precautions ( 5.3 ) ] Jaw Osteonecrosis [see Warnings and Precautions ( 5.4 ) ]… See the full label for the complete list.
Who makes Actonel?
Actonel is listed by 1 labeler in the FDA NDC directory, including Allergan, Inc..