risedronate sodium 35 MG Oral Tablet
Generic Name: RISEDRONATE SODIUM
Brand Name: risedronate sodium
- Substance Name(s):
- RISEDRONATE SODIUM HEMI-PENTAHYDRATE
- RISEDRONATE SODIUM MONOHYDRATE
DRUG INTERACTIONS
7 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-treated patients (24.5%).
7.4 H2 Blockers and Proton Pump Inhibitors (PPIs) Of over 5700 patients enrolled in the risedronate sodium tablets Phase 3 osteoporosis studies, 21% used H2 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-treated patients.
OVERDOSAGE
10 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 risedronate sodium tablets 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/m2).
DESCRIPTION
11 Risedronate sodium tablets (risedronate sodium) is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism.
Each risedronate sodium 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: 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.
Chemical structure for risedronate sodium
CLINICAL STUDIES
14 14.1 Treatment of Osteoporosis in Postmenopausal Women The fracture efficacy of risedronate sodium tablets 5 mg daily in the treatment of postmenopausal osteoporosis was demonstrated in 2 large, randomized, placebo-controlled, double-blind studies that enrolled a total of almost 4000 postmenopausal women under similar protocols.
The Multinational study (VERT MN) (risedronate sodium tablets 5 mg, N = 408) was conducted primarily in Europe and Australia; a second study was conducted in North America (VERT NA) (risedronate sodium tablets 5 mg, N = 821).
Patients were selected on the basis of radiographic evidence of previous vertebral fracture, and therefore, had established disease.
The average number of prevalent vertebral fractures per patient at study entry was 4 in VERT MN, and 2.5 in VERT NA, with a broad range of baseline BMD levels.
All patients in these studies received supplemental calcium 1000 mg/day.
Patients with low 25-hydroxyvitamin D3 levels (approximately 40 nmol/L or less) also received supplemental vitamin D 500 international units/day.
Effect on Vertebral Fractures Fractures of previously undeformed vertebrae (new fractures) and worsening of pre-existing vertebral fractures were diagnosed radiographically; some of these fractures were also associated with symptoms (that is, clinical fractures).
Spinal radiographs were scheduled annually and prospectively planned analyses were based on the time to a patient’s first diagnosed fracture.
The primary endpoint for these studies was the incidence of new and worsening vertebral fractures across the period of 0 to 3 years.
Risedronate sodium tablets 5 mg daily significantly reduced the incidence of new and worsening vertebral fractures and of new vertebral fractures in both VERT NA and VERT MN at all time points (Table 3).
The reduction in risk seen in the subgroup of patients who had 2 or more vertebral fractures at study entry was similar to that seen in the overall study population.
Table 3 The Effect of Risedronate Sodium on the Risk of Vertebral Fractures VERT NA Proportion of Patients with Fracture (%)* Placebo N = 678 Risedronate sodium tablets 5 mg N = 696 Absolute Risk Reduction (%) Relative Risk Reduction (%) New and Worsening 0 – 1 Year 0 – 2 Years 0 – 3 Years 7.2 12.8 18.5 3.9 8.0 13.9 3.3 4.8 4.6 49 42 33 New 0 – 1 Year 0 – 2 Years 0 – 3 Years 6.4 11.7 16.3 2.4 5.8 11.3 4.0 5.9 5.0 65 55 41 VERT MN Placebo N = 346 Risedronate sodium tablets 5 mg N = 344 Absolute Risk Reduction (%) Relative Risk Reduction (%) New and Worsening 0 – 1 Year 0 – 2 Years 0 – 3 Years 15.3 28.3 34.0 8.2 13.9 21.8 7.1 14.4 12.2 50 56 46 New 0 – 1 Year 0 – 2 Years 0 – 3 Years 13.3 24.7 29.0 5.6 11.6 18.1 7.7 13.1 10.9 61 59 49 *Calculated by Kaplan-Meier methodology.
Effect on Osteoporosis-Related Nonvertebral Fractures In VERT MN and VERT NA, a prospectively planned efficacy endpoint was defined consisting of all radiographically confirmed fractures of skeletal sites accepted as associated with osteoporosis.
Fractures at these sites were collectively referred to as osteoporosis-related nonvertebral fractures.
Risedronate sodium tablets 5 mg daily significantly reduced the incidence of nonvertebral osteoporosis-related fractures over 3 years in VERT NA (8% versus 5%; relative risk reduction 39%) and reduced the fracture incidence in VERT MN from 16% to 11%.
There was a significant reduction from 11% to 7% when the studies were combined, with a corresponding 36% reduction in relative risk.
Figure 1 shows the overall results as well as the results at the individual skeletal sites for the combined studies.
Effect on Bone Mineral Density The results of 4 randomized, placebo-controlled trials in women with postmenopausal osteoporosis (VERT MN, VERT NA, BMD MN, BMD NA) demonstrate that risedronate sodium tablets 5 mg daily increases BMD at the spine, hip, and wrist compared to the effects seen with placebo.
Table 4 displays the significant increases in BMD seen at the lumbar spine, femoral neck, femoral trochanter, and midshaft radius in these trials compared to placebo.
In both VERT studies (VERT MN and VERT NA), risedronate sodium tablets 5 mg daily produced increases in lumbar spine BMD that were progressive over the 3 years of treatment, and were statistically significant relative to baseline and to placebo at 6 months and at all later time points.
Table 4 Mean Percent Increase in BMD from Baseline in Patients Taking Risedronate Sodium Tablets 5 mg or Placebo at Endpointa VERT MNb VERT NAb BMDc BMD NAc Placebo N = 323 5mg N = 323 Placebo N = 599 5 mg N = 606 Placebo N = 161 5 mg N = 148 Placebo N = 191 5 mg N = 193 Lumbar Spine Femoral Neck Femoral Trochanter Midshaft Radius 1.0 -1.4 -1.9 -1.5* 6.6 1.6 3.9 0.2* 0.8 -1.0 -0.5 -1.2* 5.0 1.4 3.0 0.1* 0.0 -1.1 -0.6 ND 4.0 1.3 2.5 ND 0.2 0.1 1.3 ND 4.8 2.4 4.0 ND a The endpoint value is the value at the study’s last time point for all patients who had BMD measuredat that time; otherwise the last post-baseline BMD value prior to the study’s last time point is used.
b The duration of the studies was 3 years.
c The duration of the studies was 1.5 to 2 years.
*BMD of the midshaft radius was measured in a subset of centers in VERT MN (placebo, N = 222; 5 mg, N = 214) and VERT NA (placebo, N = 310; 5 mg, N = 306).
ND = analysis not done Risedronate sodium tablets 35 mg once-a-week (N = 485) was shown to be non-inferior to risedronate sodium tablets 5 mg daily (N = 480) in a 1-year, double-blind, multicenter study of postmenopausal women with osteoporosis.
In the primary efficacy analysis of completers, the mean increases from baseline in lumbar spine BMD at 1 year were 4.0% (3.7, 4.3; 95% confidence interval [CI]) in the 5 mg daily group (N = 391) and 3.9% (3.6, 4.3; 95% CI) in the 35 mg once-a-week group (N = 387) and the mean difference between 5 mg daily and 35 mg once-a-week was 0.1% (-0.4, 0.6; 95% CI).
The results of the intent-to-treat analysis with the last observation carried forward were consistent with the primary efficacy analysis of completers.
The 2 treatment groups were also similar with regard to BMD increases at other skeletal sites.
In a double-blind, multicenter study of postmenopausal women with osteoporosis, treatment with risedronate sodium tablets 75 mg two consecutive days per month (N = 616) was shown to be non-inferior to risedronate sodium tablets 5 mg daily (N = 613).
In the primary efficacy analysis of completers, the mean increases from baseline in lumbar spine BMD at 1 year were 3.6% (3.3, 3.9; 95% CI) in the 5 mg daily group (N = 527) and 3.4% (3.1, 3.7; 95% CI) in the 75 mg two days per month group (N = 524) with a mean difference between groups being 0.2% (-0.2, 0.6; 95% CI).
The results of the intent-to-treat analysis with the last observation carried forward were consistent with the primary efficacy analysis of completers.
The 2 treatment groups were also similar with regard to BMD increases at other skeletal sites.
Risedronate sodium tablets 150 mg once-a-month (N = 650) was shown to be non-inferior to risedronate sodium tablets 5 mg daily (N = 642) in a 1-year, double-blind, multicenter study of postmenopausal women with osteoporosis.
The primary efficacy analysis was conducted in all randomized patients with baseline and post-baseline lumbar spine BMD values (modified intent-to-treat population) using last observation carried forward.
The mean increases from baseline in lumbar spine BMD at 1 year were 3.4% (3.0, 3.8; 95% CI) in the 5 mg daily group (N = 561), and 3.5% (3.1, 3.9; 95% CI) in the 150 mg once-a-month group (N = 578) with a mean difference between groups being -0.1% (-0.5, 0.3; 95% CI).
The results of the completers analysis were consistent with the primary efficacy analysis.
The 2 treatment groups were also similar with regard to BMD increases at other skeletal sites.
Histology/Histomorphometry Bone biopsies from 110 postmenopausal women were obtained at endpoint.
Patients had received placebo or daily risedronate sodium tablets (2.5 mg or 5 mg) for 2 to 3 years.
Histologic evaluation (N = 103) showed no osteomalacia, impaired bone mineralization, or other adverse effects on bone in risedronate sodium-treated women.
These findings demonstrate that bone formed during risedronate sodium tablets administration is of normal quality.
The histomorphometric parameter mineralizing surface, an index of bone turnover, was assessed based upon baseline and post-treatment biopsy samples from 21 treated with placebo and 23 patients treated with risedronate sodium tablets 5 mg.
Mineralizing surface decreased moderately in risedronate sodium-treated patients (median percent change: placebo, -21%; risedronate sodium tablets 5 mg, -74%), consistent with the known effects of treatment on bone turnover.
Effect on Height In the two 3-year osteoporosis treatment studies, standing height was measured yearly by stadiometer.
Both risedronate sodium tablets and placebo-treated groups lost height during the studies.
Patients who received risedronate sodium tablets had a statistically significantly smaller loss of height than those who received placebo.
In VERT MN, the median annual height change was -2.4 mm/yr in the placebo group compared to -1.3 mm/yr in the risedronate sodium tablets 5 mg daily group.
In VERT NA, the median annual height change was -1.1 mm/yr in the placebo group compared to -0.7 mm/yr in the risedronate sodium tablets 5 mg daily group.
Figure 1 Nonvertebral Osteoporosis-Related Fractures 14.2 Prevention of Osteoporosis in Postmenopausal Women The safety and effectiveness of risedronate sodium tablets 5 mg daily for the prevention of postmenopausal osteoporosis were demonstrated in a 2-year, double-blind, placebo-controlled study of 383 postmenopausal women (age range 42 to 63 years) within three years of menopause (risedronate sodium tablets 5 mg, N = 129).
All patients in this study received supplemental calcium 1000 mg/day.
Increases in BMD were observed as early as 3 months following initiation of risedronate sodium tablets treatment.
Risedronate sodium tablets 5 mg daily produced significant mean increases in BMD at the lumbar spine, femoral neck, and trochanter compared to placebo at the end of the study (Figure 2).
Risedronate sodium tablets 5 mg daily was also effective in patients with lower baseline lumbar spine BMD (more than 1 SD below the premenopausal mean) and in those with normal baseline lumbar spine BMD.
Bone mineral density at the distal radius decreased in both risedronate sodium tablets and placebo-treated women following 1 year of treatment.
The safety and effectiveness of risedronate sodium tablets 35 mg once-a-week for the prevention postmenopausal osteoporosis were demonstrated in a 1-year, double-blind, placebo-controlled study of 278 patients risedronate sodium tablets 35 mg, N = 136).
All patients were supplemented with 1000 mg elemental calcium and 400 international units vitamin D per day.
The primary efficacy measure was the percent change in lumbar spine BMD from baseline after 1 year of treatment using LOCF (last observation carried forward).
Risedronate sodium tablets 35 mg once-a-week resulted in a statistically significant mean difference from placebo in lumbar spine BMD of +2.9% (least square mean for placebo -1.05%; risedronate +1.83%).
Risedronate sodium tablets 35 mg once-a-week also showed a statistically significant mean difference from placebo in BMD at the total proximal femur of +1.5% (placebo -0.53%; risedronate +1.01%), femoral neck of +1.2% (placebo -1.00%; risedronate +0.22%), and trochanter of +1.8% (placebo -0.74%; risedronate +1.07%).
Combined Administration with Hormone Replacement Therapy The effects of combining risedronate sodium tablets 5 mg daily with conjugated estrogen 0.625 mg daily (N = 263) were compared to the effects of conjugated estrogen alone (N = 261) in a 1-year, randomized, double-blind study of women ages 37 to 82 years, who were on average 14 years postmenopausal.
The BMD results for this study are presented in Table 5.
Table 5 Percent Change from Baseline in BMD After 1 Year of Treatment Estrogen 0.625 mg N = 261 Risedronate Sodium 5 mg + Estrogen 0.625 mg N = 263 Lumbar Spine 4.6 ± 0.20 5.2 ± 0.23 Femoral Neck 1.8 ± 0.25 2.7 ± 0.25 Femoral Trochanter 3.2 ± 0.28 3.7 ± 0.25 Midshaft Radius 0.4 ± 0.14 0.7 ± 0.17 Distal Radius 1.7 ± 0.24 1.6 ± 0.28 Values shown are mean (±SEM) percent change from baseline.
Histology/Histomorphometry Bone biopsies from 53 postmenopausal women were obtained at endpoint.
Patients had received risedronate sodium tablets 5 mg plus estrogen or estrogen-alone once daily for 1 year.
Histologic evaluation (N = 47) demonstrated that the bone of patients treated with risedronate sodium tablets plus estrogen was of normal lamellar structure and normal mineralization.
The histomorphometric parameter mineralizing surface, a measure of bone turnover, was assessed based upon baseline and post-treatment biopsy samples from 12 patients treated with risedronate sodium tablets plus estrogen and 12 treated with estrogen-alone.
Mineralizing surface decreased in both treatment groups (median percent change: risedronate sodium tablets plus estrogen, -79%; estrogen-alone, -50%), consistent with the known effects of these agents on bone turnover.
Figure 2 Change in BMD from Baseline 2-Year Prevention Study 14.3 Men with Osteoporosis The effects of risedronate sodium tablets 35 mg once-a-week on BMD were examined in a 2-year, double-blind, placebo-controlled, multinational study in 285 men with osteoporosis (risedronate sodium tablets, N = 192).
The patients had a mean age of 61 years (range 36 to 84 years) and 95% were Caucasian.
At baseline, mean lumbar spine T-score was -3.2 and mean femoral neck T-score was -2.4.
All patients in the study had either, 1) a BMD T-score less than or equal to -2 at the femoral neck and less than or equal to -1 at the lumbar spine, or 2) a BMD T-score less than or equal to -1 at the femoral neck and less than or equal to -2.5 at the lumbar spine.
All patients were supplemented with calcium 1000 mg/day and vitamin D 400 to 500 international units/day.
Risedronate sodium tablets 35 mg once-a-week produced significant mean increases in BMD at the lumbar spine, femoral neck, trochanter, and total hip compared to placebo after 2 years of treatment (treatment difference: lumbar spine, 4.5%; femoral neck, 1.1%; trochanter, 2.2%; total proximal femur, 1.5%).
14.4 Glucocorticoid-Induced Osteoporosis Bone Mineral Density Two 1-year, double-blind, placebo-controlled trials in patients who were taking greater than or equal to 7.5 mg/day of prednisone or equivalent demonstrated that risedronate sodium tablets 5 mg daily was effective in the prevention and treatment of glucocorticoid-induced osteoporosis in men and women who were either initiating or continuing glucocorticoid therapy.
The efficacy of risedronate sodium tablets therapy for glucocorticoid-induced osteoporosis beyond one year has not been studied.
The prevention study enrolled 228 patients (risedronate sodium tablets 5 mg, N = 76) (18 to 85 years of age), each of whom had initiated glucocorticoid therapy (mean daily dose of prednisone 21 mg) within the previous 3 months (mean duration of use prior to study 1.8 months) for rheumatic, skin, and pulmonary diseases.
The mean lumbar spine BMD was normal at baseline (average T-score -0.7).
All patients in this study received supplemental calcium 500 mg/day.
By the third month of treatment, and continuing through the year-long treatment, the placebo group experienced losses in BMD at the lumbar spine, femoral neck, and trochanter, while BMD was maintained or increased in the risedronate sodium tablets 5 mg group.
At each skeletal site there were statistically significant differences between the placebo group and the risedronate sodium tablets 5 mg group at all timepoints (Months 3, 6, 9, and 12).
The treatment differences increased with continued treatment.
Although BMD increased at the distal radius in the risedronate sodium tablets 5 mg group compared to the placebo group, the difference was not statistically significant.
The differences between placebo and risedronate sodium tablets 5 mg after 1 year were 3.8% at the lumbar spine, 4.1% at the femoral neck, and 4.6% at the trochanter, as shown in Figure 3.
The results at these skeletal sites were similar to the overall results when the subgroups of men and postmenopausal women, but not premenopausal women, were analyzed separately.
Risedronate sodium tablets was effective at the lumbar spine, femoral neck, and trochanter regardless of age (less than 65 vs.
greater than or equal to 65), gender, prior and concomitant glucocorticoid dose, or baseline BMD.
Positive treatment effects were also observed in patients taking glucocorticoids for a broad range of rheumatologic disorders, the most common of which were rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica.
The treatment study of similar design enrolled 290 patients (risedronate sodium tablets 5 mg, N = 100) (19 to 85 years of age) with continuing, long-term (greater than or equal to 6 months) use of glucocorticoids (mean duration of use prior to study 60 months; mean daily dose of prednisone 15 mg) for rheumatic, skin, and pulmonary diseases.
The baseline mean lumbar spine BMD was low (1.63 SD below the young healthy population mean), with 28% of the patients more than 2.5 SD below the mean.
All patients in this study received supplemental calcium 1000 mg/day and vitamin D 400 international units/day.
After 1 year of treatment, the BMD of the placebo group was within 1% of baseline levels at the lumbar spine, femoral neck, and trochanter.
Risedronate sodium tablets 5 mg increased BMD at the lumbar spine (2.9%), femoral neck (1.8%), and trochanter (2.4%).
The differences between risedronate sodium tablets and placebo were 2.7% at the lumbar spine, 1.9% at the femoral neck, and 1.6% at the trochanter as shown in Figure 4.
The differences were statistically significant for the lumbar spine and femoral neck, but not at the femoral trochanter.
Risedronate sodium tablets was similarly effective on lumbar spine BMD regardless of age (less than 65 vs.
greater than or equal to 65), gender, or pre-study glucocorticoid dose.
Positive treatment effects were also observed in patients taking glucocorticoids for a broad range of rheumatologic disorders, the most common of which were rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica.
Vertebral Fractures In the prevention study of patients initiating glucocorticoids, the incidence of vertebral fractures at 1 year was reduced from 17% in the placebo group to 6% in the risedronate sodium tablets group.
In the treatment study of patients continuing glucocorticoids, the incidence of vertebral fractures was reduced from 15% in the placebo group to 5% in the risedronate sodium tablets group (Figure 5).
The statistically significant reduction in vertebral fracture incidence in the analysis of the combined studies corresponded to an absolute risk reduction of 11% and a relative risk reduction of 70%.
All vertebral fractures were diagnosed radiographically; some of these fractures also were associated with symptoms (that is, clinical fractures).
Histology/Histomorphometry Bone biopsies from 40 patients on glucocorticoid therapy were obtained at endpoint.
Patients had received placebo or daily risedronate sodium tablets (2.5 mg or 5 mg) for 1 year.
Histologic evaluation (N = 33) showed that bone formed during treatment with risedronate sodium tablets was of normal lamellar structure and normal mineralization, with no bone or marrow abnormalities observed.
The histomorphometric parameter mineralizing surface, a measure of bone turnover, was assessed based upon baseline and post-treatment biopsy samples from 10 patients treated with risedronate sodium tablets 5 mg.
Mineralizing surface decreased 24% (median percent change) in these patients.
Only a small number of placebo-treated patients had both baseline and post-treatment biopsy samples, precluding a meaningful quantitative assessment.
Figure 3 Change in BMC from Baseline Patients Recently Initiating Glucocorticoid Therapy Figure 4 Change in BMD from Baseline Patients on Long-Term Glucocorticoid Therapy Figure 5 Incidence of Vertebral Fractures in patients Initiating or Continuing Glucocorticoid Therapy 14.5 Treatment of Paget’s Disease The efficacy of risedronate sodium tablets was demonstrated in 2 clinical studies involving 120 men and 65 women.
In a double-blind, active-controlled study of patients with moderate-to-severe Paget’s disease (serum alkaline phosphatase levels of at least 2 times the upper limit of normal), patients were treated with risedronate sodium tablets 30 mg daily for 2 months or Didronel (etidronate disodium) 400 mg daily for 6 months.
At Day 180, 77% (43/56) of risedronate sodium-treated patients achieved normalization of serum alkaline phosphatase levels, compared to 10.5% (6/57) of patients treated with Didronel (p less than 0.001).
At Day 540, 16 months after discontinuation of therapy, 53% (17/32) of risedronate sodium-treated patients and 14% (4/29) of Didronel-treated patients with available data remained in biochemical remission.
During the first 180 days of the active-controlled study, 85% (51/60) of risedronate sodium-treated patients demonstrated a greater than or equal to 75% reduction from baseline in serum alkaline phosphatase excess (difference between measured level and midpoint of the normal range) with 2 months of treatment compared to 20% (12/60) in the Didronel-treated group with 6 months of treatment (p less than 0.001).
Changes in serum alkaline phosphatase excess over time (shown in Figure 6) were significant following only 30 days of treatment, with a 36% reduction in serum alkaline phosphatase excess at that time compared to only a 6% reduction seen with Didronel treatment at the same time point (p less than 0.01).
Response to risedronate sodium tablets therapy was similar in patients with mild to very severe Paget’s disease.
Table 6 shows the mean percent reduction from baseline at Day 180 in excess serum alkaline phosphatase in patients with mild, moderate, or severe disease.
Table 6 Mean Percent Reduction from Baseline at Day 180 in Total Serum Alkaline Phosphatase Excess by Disease Severity Subgroup: Baseline Disease Severity (AP) Risedronate Sodium Tablets 30 mg Didronel 400 mg n Baseline Serum AP (U/L)* Mean % Reduction n Baseline Serum AP (U/L)* Mean % Reduction greater than 2, less than 3x ULN greater than or equal to 3, less than 7x ULN greater than or equal to 7x ULN 32 271.6 ± 5.3 -88.1 22 277.9 ± 7.45 -44.6 14 475.3 ± 28.8 -87.5 25 480.5 ± 26.44 -35.0 8 1336.5 ± 134.19 -81.8 6 1331.5 ± 167.58 -47.2 *Values shown are mean ± SEM; ULN = upper limit of normal.
Response to risedronate sodium tablets therapy was similar between patients who had previously received anti-pagetic therapy and those who had not.
In the active-controlled study, 4 patients previously non-responsive to 1 or more courses of anti-pagetic therapy (calcitonin, Didronel) responded to treatment with risedronate sodium tablets 30 mg daily (defined by at least a 30% change from baseline).
Each of these patients achieved at least 90% reduction from baseline in serum alkaline phosphatase excess, with 3 patients achieving normalization of serum alkaline phosphatase levels.
Histomorphometry of the bone was studied in 14 patients with bone biopsies: 9 patients had biopsies from pagetic bone lesions and 5 patients from non-pagetic bone.
Bone biopsy results in non-pagetic bone did not reveal osteomalacia, impairment of bone remodeling, or induction of a significant decline in bone turnover in patients treated with risedronate sodium tablets.
Figure 6 Mean Percent Change from Baseline in Serum Alkaline Phosphatase Excess by Visit
HOW SUPPLIED
16 /STORAGE AND HANDLING Risedronate sodium tablets is available as follows: 5 mg film-coated, oval, yellow tablets with RSN on 1 face and 5 mg on the other.
NDC 0591-2102-30 bottle of 30 30 mg film-coated, oval, white tablets with RSN on 1 face and 30 mg on the other.
NDC 0591-2109-30 bottle of 30 35 mg film-coated, oval, orange tablets with RSN on 1 face and 35 mg on the other.
NDC 0591-2075-04 dose pack of 4 NDC 0591-2075-39 dose pack of 12 75 mg film-coated, oval, pink tablets with RSN on 1 face and 75 mg on the other.
NDC 0591-2067-02 dose pack of 2 150 mg film-coated, oval, blue tablets with RSN on 1 face and 150 mg on the other.
NDC 0591-2044-54 dose pack of 1 NDC 0591-2044-03 dose pack of 3 Store at controlled room temperature 20° to 25° C (68° to 77° F) [see USP].
GERIATRIC USE
8.5 Geriatric Use Of the patients receiving Risedronate Sodium in postmenopausal osteoporosis studies [see Clinical Studies (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 Risedronate Sodium were between 65 and 75 years of age and 9% were over 75.
The lumbar spine BMD response for Risedronate Sodium 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 risedronate sodium tablets trials, but greater sensitivity of some older individuals cannot be ruled out.
DOSAGE FORMS AND STRENGTHS
3 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
MECHANISM OF ACTION
12.1 Mechanism of Action Risedronate sodium has an affinity for hydroxyapatite crystals in bone and acts as an antiresorptive agent.
At the cellular level, risedronate sodium 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 risedronate sodium tablets treatment reduces bone turnover (activation frequency, that is, the rate at which bone remodeling sites are activated) and bone resorption at remodeling sites.
INDICATIONS AND USAGE
1 Risedronate sodium tablets 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 Risedronate sodium tablets is indicated for the treatment and prevention of osteoporosis in postmenopausal women.
In postmenopausal women with osteoporosis, risedronate sodium tablets 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 Risedronate sodium tablets is indicated for treatment to increase bone mass in men with osteoporosis.
1.3 Glucocorticoid-Induced Osteoporosis Risedronate sodium tablets 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 Risedronate sodium tablets 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 risedronate sodium tablets 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.
PEDIATRIC USE
8.4 Pediatric Use Risedronate sodium tablets 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 than16 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 risedronate sodium-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%).
PREGNANCY
8.1 Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies of risedronate sodium tablets in pregnant women.
Risedronate sodium tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over periods of weeks to years.
The amount of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the dose and duration of bisphosphonate use.
There are no data on fetal risk in humans.
However, there is a theoretical 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.
In animal studies, pregnant rats received risedronate sodium tablets during organogenesis at doses 1 to 26 times the human dose of 30 mg/day.
Survival of neonates was decreased in rats treated during gestation with oral doses approximately 5 times the human dose and body weight was decreased in neonates from dams treated with approximately 26 times the human dose.
The number of fetuses exhibiting incomplete ossification of sternebrae or skull from 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 rats treated with oral doses approximately 5 times the human dose.
A low incidence of cleft palate was observed in fetuses from female rats treated with oral doses approximately equal to the human dose.
The relevance of this finding to human use of risedronate sodium tablets is unclear.
No significant fetal ossification effects were seen in 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.
Similar to other bisphosphonates, treatment during mating and gestation with doses of risedronate sodium tablets approximately the same as the 30 mg/day human dose resulted in periparturient hypocalcemia and mortality in pregnant rats allowed to deliver.
Dosing multiples provided above are based on the recommended human dose of 30 mg/day and normalized using body surface area (mg/m2).
Actual animal doses were 3.2, 7.1 and 16 mg/kg/day in the rat and 10 mg/kg/day in the rabbit.
NUSRING MOTHERS
8.3 Nursing Mothers Risedronate was detected in feeding pups exposed to lactating rats for a 24-hour period post-dosing, indicating a small degree of lacteal transfer.
It is not known whether risedronate sodium tablets is excreted in human milk.
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from risedronate sodium tablets a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
WARNING AND CAUTIONS
5 WARNINGS 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 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 contains 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 sodium tablets, 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 tablets 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 (17.1)]. 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 tablets 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 tablets 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 sodium tablets.
Treat hypocalcemia and other disturbances of bone and mineral metabolism before starting risedronate sodium tablets 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 (17.1)].
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 tablets.
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), 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 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 tablets 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 tablets 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 tablets have not been performed.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Medication Guide) Instruct patients to read the Medication Guide before starting therapy with risedronate sodium tablets and to re-read it each time the prescription is renewed.
Instruct patients that Atelvia and risedronate sodium tablets contain the same active ingredient and if they are taking Atelvia, they should not take risedronate sodium tablets [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, risedronate sodium tablets should be taken at least 30 minutes before the first food or drink of the day other than water.
Instruct patients to take risedronate sodium tablets 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 lie down for 30 minutes after taking the medication [see Warnings and Precautions (5.1)].
Instruct patients not 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 risedronate sodium tablets.
Instruct patients about missing risedronate sodium tablets doses as follows: If a dose of risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 75 mg on two consecutive days per month as originally scheduled.
If the dose of risedronate sodium tablets 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 risedronate sodium 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 risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets as these medications may interfere with the absorption of risedronate sodium tablets.
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 risedronate sodium tablets.
Patients should be instructed that any time they have a medical problem they think may be from risedronate sodium tablets, they should talk to their doctor.
Content updated: October 2014
DOSAGE AND ADMINISTRATION
2 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 risedronate sodium tablets 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 risedronate sodium 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 risedronate sodium tablets.
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 risedronate sodium tablets.
2.8 Administration Instructions for Missed Doses Instruct patients about missing risedronate sodium tablets doses as follows: If a dose of risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 75 mg tablet is missed, take the missed tablet in the morning after the day it is remembered Return to taking their risedronate sodium tablets 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 risedronate sodium tablets 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 risedronate sodium tablets 75 mg on two consecutive days per month as originally scheduled.
If the dose of risedronate sodium tablets 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 risedronate sodium tablets 150 mg once-a-month as originally scheduled.
Do not take more than one 150 mg tablet within 7 days.
If the dose of risedronate sodium tablets 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 risedronate sodium tablets 150 mg once-a-month as originally scheduled.