Actonel

Name: Actonel

Actonel Interactions

Tell your doctor about all prescription, nonprescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially those listed in the Actonel Warnings section above, and any of the following:

  • Aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil or Motrin (ibuprofen) or Aleve (naproxen)
  • Chemotherapy for cancer
  • Oral steroids such as Medrol (methylprednisolone), Decadron or Dexone (dexamethasone), or Deltasone (prednisone)

Actonel and Alcohol

Your doctor will probably tell you to limit your alcohol intake — and not smoke — while taking Actonel.

Talk to your doctor about these and other restrictions.

What happens if I miss a dose?

If you take risedronate tablets once daily: If you forget to take this medicine first thing in the morning, do not take it later in the day. Wait until the following morning to take the medicine and skip the missed dose. Do not take two (2) tablets in one day.

If you take risedronate tablets once a week, or once or twice per month: If you forget to take risedronate on your scheduled day, take it first thing in the morning on the day after you remember the missed dose. Then return to your regular weekly schedule on your chosen dose day. Do not take two (2) tablets in one day.

Risedronate side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using risedronate and call your doctor at once if you have:

  • chest pain, new or worsening heartburn;

  • difficulty or pain when swallowing;

  • pain or burning under the ribs or in the back;

  • severe or ongoing indigestion;

  • severe joint, bone, or muscle pain;

  • new or unusual pain in your thigh or hip;

  • jaw pain, numbness, or swelling; or

  • severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

  • mild stomach pain or upset stomach;

  • flu symptoms, muscle pain;

  • diarrhea, constipation;

  • mild joint or back pain; or

  • headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1 800 FDA 1088.

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.1 2 4 5 6 8 9 12 13 14

Uses For Actonel

Risedronate delayed-release tablets and tablets are used to prevent and treat osteoporosis (thinning of the bone) in women after menopause. Risedronate tablets may also be used to increase bone mass in men who have osteoporosis, and in men and women to prevent and treat osteoporosis caused by long-term use of corticosteroids (cortisone-like medicine). Risedronate tablets are also used to treat Paget's disease of the bone. .

This medicine is available only with your doctor's prescription.

What are some things I need to know or do while I take Actonel?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Very bad swallowing tube (esophagus) problems like irritation, swelling, ulcers, and bleeding have happened with Actonel. Talk with the doctor.
  • Worsening of asthma has happened in people taking drugs like this one. Talk with the doctor.
  • This medicine may raise the chance of a broken leg. Talk with the doctor.
  • Have a bone density test as you have been told by your doctor. Talk with your doctor.
  • This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
  • This medicine works best when used with calcium/vitamin D and weight-bearing workouts like walking or PT (physical therapy).
  • Follow the diet and workout plan that your doctor told you about.
  • Have a dental exam before starting Actonel.
  • Take good care of your teeth. See a dentist often.
  • Talk with your doctor before you drink alcohol.
  • If you smoke, talk with your doctor.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
  • This medicine is not approved for use in children. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Actonel (risedronate tablets), please talk with the doctor, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Actonel. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Actonel.

Review Date: October 4, 2017

Actonel Dosage and Administration

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

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

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

Treatment and Prevention of Glucocorticoid-Induced Osteoporosis

[see Indications and Usage (1.3)]

The recommended regimen is:

  • one 5 mg tablet orally, taken daily

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.

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.

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.

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.

Adverse Reactions

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

Daily 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 H2 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 D3 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. Endoscopies were performed on equal numbers of patients between the placebo and treated groups [75 (14.5%) placebo; 75 (11.9%) Actonel]. Clinically important findings (perforations, ulcers, or bleeding) among this symptomatic population were similar between groups (51% placebo; 39% Actonel).

Once-a-Week Dosing

The safety of Actonel 35 mg once-a-week in the treatment of postmenopausal osteoporosis was assessed in a 1-year, double-blind, multicenter study comparing Actonel 5 mg daily and Actonel 35 mg once-a-week in postmenopausal women aged 50 to 95 years. The duration of the trials was one year, with 480 patients exposed to Actonel 5 mg daily and 485 exposed to Actonel 35 mg once-a-week. Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors, and H2 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 D3 level was below normal at baseline.

The incidence of all-cause mortality was 0.4% in the Actonel 5 mg daily group and 1.0% in the Actonel 35 mg once-a-week group. The incidence of serious adverse events was 7.1% in the Actonel 5 mg daily group and 8.2% in the Actonel 35 mg once-a-week group. The percentage of patients who withdrew from the study due to adverse events was 11.9% in the Actonel 5 mg daily group and 11.5% in the Actonel 35 mg once-a-week group. The overall safety and tolerability profiles of the two dosing regimens were similar.

Gastrointestinal Adverse Events: The incidence of gastrointestinal adverse events was similar between the Actonel 5 mg daily group and the Actonel 35 mg once-a-week group: dyspepsia (6.9% versus 7.6%), diarrhea (6.3% versus 4.9%), and abdominal pain (7.3% versus 7.6%).

Musculoskeletal Adverse Events: Arthralgia was reported in 11.5% of patients in the Actonel 5 mg daily group and 14.2% of patients in the Actonel 35 mg once-a-week group. Myalgia was reported by 4.6% of patients in the Actonel 5 mg daily group and 6.2% of patients in the Actonel 35 mg once-a-week group.

Laboratory Test Findings: The mean percent changes from baseline at 12 months were similar between the Actonel 5 mg daily and Actonel 35 mg once-a-week groups, respectively, for serum calcium (0.4% versus 0.7%), phosphate (-3.8% versus -2.6%) and PTH (6.4% versus 4.2%).

Monthly Dosing

Two Consecutive Days per Month

The safety of Actonel 75 mg administered on two consecutive days per month for the treatment of postmenopausal osteoporosis was assessed in a double-blind, multicenter study in postmenopausal women aged 50 to 86 years. The duration of the trial was two years; 613 patients were exposed to Actonel 5 mg daily and 616 were exposed to Actonel 75 mg two consecutive days per month. Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors, and H2 antagonists were included in this clinical trial. All women received 1000 mg of elemental calcium plus 400 to 800 international units of vitamin D supplementation per day.

The incidence of all-cause mortality was 1.0% for the Actonel 5 mg daily group and 0.5% for the Actonel 75 mg two consecutive days per month group. The incidence of serious adverse events was 10.8% in the Actonel  5 mg daily group and 14.4% in the Actonel 75 mg two consecutive days per month group. The percentage of patients who withdrew from treatment due to adverse events was 14.2% in the Actonel 5 mg daily group and 13.0% in the Actonel 75 mg two consecutive days per month group. The overall safety and tolerability profiles of the two dosing regimens were similar.

Acute Phase Reactions: Symptoms consistent with acute phase reaction have been reported with bisphosphonate use. The overall incidence of acute phase reaction was 3.6% of patients on Actonel 5 mg daily and 7.6% of patients on Actonel 75 mg two consecutive days per month. These incidence rates are based on reporting of any of 33 acute phase reaction-like symptoms within 5 days of the first dose. Fever or influenza-like illness with onset within the same period were reported by 0.0% of patients on Actonel 5 mg daily and 0.6% of patients on Actonel 75 mg two consecutive days per month.

Gastrointestinal Adverse Events: The Actonel 75 mg two consecutive days per month group resulted in a higher incidence of discontinuation due to vomiting (1.0% versus 0.2%) and diarrhea (1.0% versus 0.3%) compared to the Actonel 5 mg daily group. Most of these events occurred within a few days of dosing.

Ocular Adverse Events: None of the patients treated with Actonel 75 mg two consecutive days per month reported ocular inflammation such as uveitis, scleritis, or iritis; 1 patient treated with Actonel 5 mg daily reported uveitis.

Laboratory Test Findings: When Actonel 5 mg daily and Actonel 75 mg two consecutive days per month were compared in postmenopausal women with osteoporosis, the mean percent changes from baseline at 24 months were 0.2% and 0.8% for serum calcium, -1.9% and -1.3% for phosphate, and -10.4% and -17.2% for PTH, respectively. Compared to the Actonel 5 mg daily group, Actonel 75 mg two consecutive days per month resulted in a slightly higher incidence of hypocalcemia at the end of the first month of treatment (4.5% versus 3.0%). Thereafter, the incidence of hypocalcemia with these regimens was similar at approximately 2%.

Once-a-Month

The safety of Actonel 150 mg administered once-a-month for the treatment of postmenopausal osteoporosis was assessed in a double-blind, multicenter study in postmenopausal women aged 50 to 88 years. The duration of the trial was one year, with 642 patients exposed to Actonel 5 mg daily and 650 exposed to Actonel 150 mg once-a-month. Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors, and H2 antagonists were included in this clinical trial. All women received 1000 mg of elemental calcium plus up to 1000 international units of vitamin D supplementation per day.

The incidence of all-cause mortality was 0.5% for the Actonel 5 mg daily group and 0.0% for the Actonel 150 mg once-a-month group. The incidence of serious adverse events was 4.2% in the Actonel 5 mg daily group and 6.2% in the Actonel 150 mg once-a-month group. The percentage of patients who withdrew from treatment due to adverse events was 9.5% in the Actonel 5 mg daily group and 8.6% in the Actonel 150 mg once-a-month group. The overall safety and tolerability profiles of the two dosing regimens were similar.

Acute Phase Reactions: Symptoms consistent with acute phase reaction have been reported with bisphosphonate use. The overall incidence of acute phase reaction was 1.1% in the Actonel 5 mg daily group and 5.2% in the Actonel 150 mg once-a-month group. These incidence rates are based on reporting of any of 33 acute phase reaction-like symptoms within 3 days of the first dose and for a duration of 7 days or less. Fever or influenza-like illness with onset within the same period were reported by 0.2% of patients on Actonel 5 mg daily and 1.4% of patients on Actonel 150 mg once-a-month.

Gastrointestinal Adverse Events: A greater percentage of patients experienced diarrhea with Actonel 150 mg once-a-month compared to 5 mg daily (8.2% versus 4.7%, respectively). The Actonel 150 mg once-a-month group resulted in a higher incidence of discontinuation due to abdominal pain upper (2.5% versus 1.4%) and diarrhea (0.8% versus 0.0%) compared to the Actonel 5 mg daily regimen. All of these events occurred within a few days of the first dose. The incidence of vomiting that led to discontinuation was the same in both groups (0.3% versus 0.3%).

Ocular Adverse Events: None of the patients treated with Actonel 150 mg once-a-month reported ocular inflammation such as uveitis, scleritis, or iritis; 2 patients treated with Actonel 5 mg daily reported iritis.

Laboratory Test Findings: When Actonel 5 mg daily and Actonel 150 mg once-a-month were compared in postmenopausal women with osteoporosis, the mean percent changes from baseline at 12 months were 0.1% and 0.3% for serum calcium, -2.3% and -2.3% for phosphate, and 8.3% and 4.8% for PTH, respectively. Compared to the Actonel 5 mg daily regimen, Actonel 150 mg once-a-month resulted in a slightly higher incidence of hypocalcemia at the end of the first month of treatment (0.2% versus 2.2%). Thereafter, the incidence of hypocalcemia with these regimens was similar at approximately 2%.

Prevention of Postmenopausal Osteoporosis

Daily Dosing

The safety of Actonel 5 mg daily in the prevention of postmenopausal osteoporosis was assessed in two randomized, double-blind, placebo-controlled trials. In one study of postmenopausal women aged 37 to 82 years without osteoporosis, the use of estrogen replacement therapy in both placebo- and Actonel-treated patients was included. The duration of the trial was one year, with 259 exposed to placebo and 261 patients exposed to Actonel 5 mg. The second study included postmenopausal women aged 44 to 63 years without osteoporosis. The duration of the trial was one year, with 125 exposed to placebo and 129 patients exposed to Actonel 5 mg. All women received 1000 mg of elemental calcium per day.

In the trial with estrogen replacement therapy, the incidence of all-cause mortality was 1.5% for the placebo group and 0.4% for the Actonel 5 mg group. The incidence of serious adverse events was 8.9% in the placebo group and 5.4% in the Actonel 5 mg group. The percentage of patients who withdrew from treatment due to adverse events was 18.9% in the placebo group and 10.3% in the Actonel 5 mg group. Constipation was reported by 1.9% of the placebo group and 6.5% of Actonel 5 mg group.

In the second trial, the incidence of all-cause mortality was 0.0% for both groups. The incidence of serious adverse events was 17.6% in the placebo group and 9.3% in the Actonel 5 mg group. The percentage of patients who withdrew from treatment due to adverse events was 6.4% in the placebo group and 5.4% in the Actonel 5 mg group. Nausea was reported by 6.4% of patients in the placebo group and 13.2% of patients in the Actonel 5 mg group.

Once-a-Week Dosing

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 Actonel reported arthralgia (placebo 7.8%; Actonel 13.9%), myalgia (placebo 2.1%; Actonel 5.1%), and nausea (placebo 4.3%; Actonel 7.3%) than subjects on placebo.

Treatment to Increase Bone Mass in Men with Osteoporosis

In a 2-year, double-blind, multicenter study, 284 men with osteoporosis were treated with placebo (N = 93) or Actonel 35 mg once-a-week (N = 191). The overall safety and tolerability profile of Actonel in men with osteoporosis was similar to the adverse events reported in the Actonel postmenopausal osteoporosis clinical trials, with the addition of benign prostatic hyperplasia (placebo 3%; Actonel 35 mg 5%), nephrolithiasis (placebo 0%; Actonel 35 mg 3%), and arrhythmia (placebo 0%; Actonel 35 mg 2%).

Treatment and Prevention of Glucocorticoid-Induced Osteoporosis

The safety of Actonel 5 mg daily in the treatment and prevention of glucocorticoid-induced osteoporosis was assessed in two randomized, double-blind, placebo-controlled multinational trials of 344 patients [male (123) and female (221)] aged 18 to 85 years who had recently initiated oral glucocorticoid therapy (less than or equal to 3 months, prevention study) or were on long-term oral glucocorticoid therapy (greater than or equal to 6 months, treatment study). The duration of the trials was one year, with 170 patients exposed to placebo and 174 patients exposed to Actonel 5 mg daily. Patients in one study received 1000 mg elemental calcium plus 400 international units of vitamin D supplementation per day; patients in the other study received 500 mg calcium supplementation per day.

The incidence of all-cause mortality was 2.9% in the placebo group and 1.1% in the Actonel 5 mg daily group. The incidence of serious adverse events was 33.5% in the placebo group and 30.5% in the Actonel 5 mg daily group. The percentage of patients who withdrew from the study due to adverse events was 8.8% in the placebo group and 7.5% in the Actonel 5 mg daily group. Back pain was reported in 8.8% of patients in the placebo group and 17.8% of patients in the Actonel 5 mg daily group. Arthralgia was reported in 14.7% of patients in the placebo group and 24.7% of patients in the Actonel 5 mg daily group.

Treatment of Paget’s Disease

Actonel has been studied in 392 patients with Paget’s disease of bone. As in trials of Actonel for other indications, the adverse experiences reported in the Paget’s disease trials have generally been mild or moderate, have not required discontinuation of treatment, and have not appeared to be related to patient age, gender, or race.

The safety of Actonel was assessed in a randomized, double-blind, active-controlled study of 122 patients aged 34 to 85 years. The duration of the trial was 540 days, with 61 patients exposed to Actonel and 61 patients exposed to Didronel®. The adverse event profile was similar for Actonel and Didronel: 6.6% (4/61) of patients treated with Actonel 30 mg daily for 2 months discontinued treatment due to adverse events, compared to 8.2% (5/61) of patients treated with Didronel 400 mg daily for 6 months. Table 2 lists adverse events reported in greater than or equal to 5% of Actonel-treated patients in Phase 3 Paget's disease trials. Adverse events shown are considered to be possibly or probably causally related in at least one patient.

Table 2 Adverse Events Reported in greater than or equal to 5% of Actonel-Treated Patients* in Phase 3 Paget's Disease Trials
 Body System  30 mg/day
x 2 months Actonel
%
(N = 61)
 400 mg/day
x 6 months Didronel
%
(N = 61)
 

*Considered to be possibly or probably causally related in at least one patient.

 Body as a Whole    
      Flu Syndrome  9.8  1.6
      Chest Pain  6.6  3.3
 Gastrointestinal    
      Diarrhea  19.7  14.8
      Abdominal Pain  11.5  8.2
      Nausea  9.8  9.8
      Constipation  6.6  8.2
 Metabolic and Nutritional Disorders    
      Peripheral Edema  8.2  6.6
 Musculoskeletal    
      Arthralgia  32.8  29.5
 Nervous    
      Headache  18.0  16.4
      Dizziness  6.6  4.9
 Skin and Appendages    
      Rash  11.5  8.2

Gastrointestinal Adverse Events: During the first year of the study (treatment and nontreatment follow-up), the proportion of patients who reported upper gastrointestinal adverse events was similar between the treatment groups; no patients reported severe upper gastrointestinal adverse events. The incidence of diarrhea was 19.7% in the Actonel group and 14.8% in the Didronel group; none were serious or resulted in withdrawal.

Ocular Adverse Events: Three patients who received Actonel 30 mg daily experienced acute iritis in 1 supportive study. All 3 patients recovered from their events; however, in 1 of these patients, the event recurred during Actonel treatment and again during treatment with pamidronate. All patients were effectively treated with topical steroids.

Postmarketing Experience

Because these adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity Reactions

Hypersensitivity and skin reactions have been reported, including angioedema, generalized rash, bullous skin reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Gastrointestinal Adverse Events

Events involving upper gastrointestinal irritation, such as esophagitis and esophageal or gastric ulcers, have been reported [see Warnings and Precautions (5.1)].

Musculoskeletal Pain

Bone, joint, or muscle pain, described as severe or incapacitating, have been reported rarely [see Warnings and Precautions (5.4)].

Eye Inflammation

Reactions of eye inflammation including iritis and uveitis have been reported rarely.

Jaw Osteonecrosis

Osteonecrosis of the jaw has been reported rarely [see Warnings and Precautions (5.3)].

Pulmonary

Asthma exacerbations

Actonel and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Actonel falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

 

Pregnancy & Lactation

Pregnancy category: C

Lactation: Unknown whether drug crosses into breast milk; avoid using

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

What is Actonel?

Actonel (risedronate) is in a group of medicines called bisphosphonates (bis FOS fo nayts). It alters the cycle of bone formation and breakdown in the body. Risedronate slows bone loss while increasing bone mass, which may prevent bone fractures.

Actonel is used to treat or prevent osteoporosis in men and women.

Actonel is also used to treat Paget's disease of bone.

Before taking this medicine

You should not use Actonel if you are allergic to risedronate, or if you have:

  • low levels of calcium in your blood (hypocalcemia); or

  • a problem with the movement of muscles in your esophagus.

Do not take a Actonel tablet if you cannot sit upright or stand for at least 30 minutes. Risedronate can cause serious problems in the stomach or esophagus (the tube that connects your mouth and stomach). You will need to stay upright for at least 30 minutes after taking this medication.

To make sure Actonel is safe for you, tell your doctor if you have:

  • low blood calcium (hypocalcemia);

  • a vitamin D deficiency;

  • kidney disease; or

  • an ulcer in your stomach or esophagus.

In rare cases, risedronate may cause bone loss (osteonecrosis) in the jaw. Symptoms include jaw pain or numbness, red or swollen gums, loose teeth, or slow healing after dental work. The longer you use Actonel, the more likely you are to develop this condition.

Osteonecrosis of the jaw may be more likely if you have cancer or received chemotherapy, radiation, or steroids. Other risk factors include blood clotting disorders, anemia (low red blood cells), and a pre existing dental problem.

Talk with your doctor about the risks and benefits of using Actonel.

It is not known whether Actonel will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether risedronate passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

What should I avoid while taking Actonel?

Avoid taking any other medicines including vitamins, calcium, or antacids for at least 30 minutes after taking a risedronate tablet. Some medicines can make it harder for your body to absorb risedronate.

In Summary

Common side effects of Actonel include: abdominal pain, arthralgia, and ostealgia. Other side effects include: bone fracture, arthropathy, and myalgia. See below for a comprehensive list of adverse effects.

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