Actonel with Calcium
"March 7, 2013 -- An FDA panel voted to stop recommending calcitonin salmon for the treatment of osteoporosis in women who are at least five years past menopause.
The committee voted 12-9 against continued marketing of the drug, citing"...
Actonel with Calcium
Actonel has been studied in over 5700 patients enrolled in the Phase 3 glucocorticoid-induced osteoporosis clinical trials and in postmenopausal osteoporosis trials of up to 3-years duration. The overall adverse event profile of Actonel 5 mg in these studies was similar to that of placebo. Most adverse events were either mild or moderate and did not lead to discontinuation from the study. The incidence of serious adverse events in the placebo group was 24.9% and in the Actonel 5 mg group was 26.3%. The percentage of patients who withdrew from the study due to adverse events was 14.4% and 13.5% for the placebo and Actonel 5 mg groups, respectively. Table 4 lists adverse events from the Phase 3 osteoporosis trials reported in ≥ 2% of patients and in more Actonel-treated patients than placebo-treated patients. Adverse events are shown without attribution of causality.
Table 4 : Adverse Events Occurring at a Frequency ≥ 2%
and in More Actonel-Treated Patients than Placebo-Treated Patients Combined
Phase 3 Osteoporosis Trials
|Body System||Placebo %
(N = 1914)
|Actonel 5 mg
(N = 1916)
|Body as a Whole|
|Hemic and Lymphatic|
|Skin and Appendages|
|Urinary Tract Infection||9.7||10.9|
Laboratory Test Findings
Asymptomatic and small decreases were observed in serum calcium and phosphorus levels. Overall, mean decreases of 0.8% in serum calcium and of 2.7% in phosphorus were observed at 6 months in patients receiving Actonel. Throughout the Phase 3 studies, serum calcium levels below 8 mg/dL were observed in 18 patients, 9 (0.5%) in each treatment arm (Actonel and placebo). Serum phosphorus levels below 2 mg/dL were observed in 14 patients, 11 (0.6%) treated with Actonel and 3 (0.2%) treated with placebo.
Actonel clinical studies enrolled over 5700 patients, many with pre-existing gastrointestinal disease and concomitant use of NSAIDs or aspirin. Investigators were encouraged to perform endoscopies in any patients with moderate-to-severe gastrointestinal complaints, while maintaining the blind. These endoscopies were ultimately performed on equal numbers of patients between the treated and placebo groups [75 (14.5%) placebo; 75 (11.9%) Actonel]. Across treatment groups, the percentage of patients with normal esophageal, gastric, and duodenal mucosa on endoscopy was similar (20% placebo; 21% Actonel). The number of patients who withdrew from the studies due to the event prompting endoscopy was similar across treatment groups. Positive findings on endoscopy were also generally comparable across treatment groups. There was a higher number of reports of mild duodenitis in the Actonel group, however there were more duodenal ulcers in the placebo group. Clinically important findings (perforations, ulcers, or bleeding) among this symptomatic population were similar between groups (51% placebo; 39% Actonel).
In a 1-year, double-blind, multicenter study comparing Actonel 5 mg daily and Actonel 35 mg once-a-week in postmenopausal women, the overall safety and tolerability profiles of the 2 oral dosing regimens were similar. Table 5 lists the adverse events in ≥ 2% of patients from this trial. Events are shown without attribution of causality.
Table 5: Adverse Events Occurring in ≥ 2% of Patients
of Either Treatment Group in the Daily vs. Weekly Osteoporosis Treatment Study
in Postmenopausal Women
|Body System||5 mg Daily Actonel
(N = 480)
|35 mg Weekly Actonel
(N = 485)
|Body as a Whole|
|Metabolic and Nutritional Disorders|
|Traumatic Bone Fracture||5.0||6.4|
|Skin and Appendages|
|Urinary Tract Infection||2.9||5.2|
There were no deaths in a 1-year, double-blind, placebo-controlled study of Actonel 35 mg once-a-week for prevention of bone loss in 278 postmenopausal women without osteoporosis. More treated subjects on risedronate experienced arthralgia (risedronate 13.9%; placebo 7.8%), myalgia (risedronate 5.1%; placebo 2.1%), and nausea (risedronate 7.3%; placebo 4.3%) than subjects on placebo.
Very rare hypersensitivity and skin reactions have been reported, including angioedema, generalized rash and bullous skin reactions, some severe.
Musculoskeletal: bone, joint, or muscle pain, rarely described as severe or incapacitating (see PRECAUTIONS, Musculoskeletal Pain).
Calcium carbonate may cause gastrointestinal adverse effects such as constipation, flatulence, nausea, abdominal pain, and bloating. Administration of calcium may increase the risk of kidney stones, particularly in patients with a history of this condition (see PRECAUTIONS).
Read the Actonel with Calcium (risedronate sodium with calcium carbonate) Side Effects Center for a complete guide to possible side effects
No specific drug-drug interaction studies were performed. Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes (Cytochrome P450).
Co-administration of Actonel and calcium, antacids, or oral medications containing divalent cations will interfere with the absorption of Actonel.
Hormone Replacement Therapy
One study of about 500 early postmenopausal women has been conducted to date in which treatment with Actonel (5 mg/day) 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.
Aspirin/Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
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 Actoneltreated patients (24.5%) was similar to that in placebo-treated patients (24.8%).
H2 Blockers and Proton Pump Inhibitors (PPIs)
Of over 5700 patients enrolled in the Actonel Phase 3 osteoporosis studies, 21% used H2 blockers and/or PPIs. Among these patients, the incidence of upper gastrointestinal adverse experiences in the Actonel-treated patients was similar to that in placebo-treated patients.
Oral bisphosphonates (such as risedronate, alendronate, etidronate, ibandronate): Decreased absorption of the bisphosphonate may occur when the bisphosphonate and calcium are taken together.
Fluoroquinolones (such as ciprofloxacin, moxifloxacin, and ofloxacin): Concomitant administration of a fluoroquinolone and calcium carbonate may decrease the absorption of the fluoroquinolone.
Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic glucocorticoids.
Reduced urinary excretion of calcium has been reported during concomitant use of calcium carbonate and thiazide diuretics.
Vitamin D and vitamin D analogues (such as calcitriol, doxercalciferol, and paricalcitol): Absorption of calcium may be increased when calcium carbonate is given concomitantly with vitamin D analogues.
Calcium may interfere with the absorption of iron. Patients being treated for iron deficiency should take iron and calcium at different times of the day.
Drug/Laboratory Test Interactions
Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with Actonel have not been performed.
Read the Actonel with Calcium Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/18/2011
Additional Actonel with Calcium Information
- Actonel with Calcium Drug Interactions Center: risedronate-calcium oral
- Actonel with Calcium Side Effects Center
- Actonel with Calcium in detail including Side Effects and Drug Images
- Actonel with Calcium Overview including Precautions
- Actonel with Calcium FDA Approved Prescribing Information including Dosage
Actonel with Calcium - User Reviews
Actonel with Calcium User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get tips and advances in treatment.