Actonel Description

ACTONEL (risedronate sodium tablets) is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism. Each ACTONEL tablet for oral administration contains the equivalent of 5, 30, 35, or 75 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 C7 H10 NO7 P2 Na ?2.5 H2 O. The chemical name of risedronate sodium is [1-hydroxy-2-(3-pyridinyl)ethylidene]bis[phosphonic acid] monosodium salt. The chemical structure of risedronate sodium hemi-pentahydrate is the following:

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

Crospovidone, ferric oxide red (35 mg and 75 mg tablets only), ferric oxide yellow (5 mg and 35 mg tablets only), hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose monohydrate (5 mg, 30 mg and 35 mg tablets only), magnesium stearate, microcrystalline cellulose, polyethylene glycol, silicon dioxide, titanium dioxide.

Actonel Indications And Usage

Postmenopausal Osteoporosis

ACTONEL is indicated for the treatment and prevention of osteoporosis in postmenopausal women.

Treatment Of Osteoporosis

In postmenopausal women with osteoporosis, ACTONEL increases BMD and reduces the incidence of vertebral fractures and a composite endpoint of nonvertebral osteoporosis-related fractures (see CLINICAL STUDIES ). Osteoporosis may be confirmed by the presence or history of osteoporotic fracture, or by the finding of low bone mass (for example, at least 2 SD below the premenopausal mean).

Prevention Of Osteoporosis

ACTONEL may be considered in postmenopausal women who are at risk of developing osteoporosis and for whom the desired clinical outcome is to maintain bone mass and to reduce the risk of fracture.

Factors such as family history of osteoporosis, previous fracture, smoking, BMD (at least 1 SD below the premenopausal mean), high bone turnover, thin body frame, Caucasian or Asian race, and early menopause are associated with an increased risk of developing osteoporosis and fractures. The presence of these risk factors may be important when considering the use of ACTONEL for prevention of osteoporosis.

Osteoporosis In Men

ACTONEL is indicated for treatment to increase bone mass in men with osteoporosis.

Glucocorticoid-induced Osteoporosis

ACTONEL is indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoid treatment (daily dosage equivalent to 7.5 mg or greater of prednisone) for chronic diseases. Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.

Paget's Disease

ACTONEL is indicated for treatment of Paget's disease of bone in men and women. Treatment is indicated in patients with Paget's disease of bone (1) who have a level of serum alkaline phosphatase at least 2 times the upper limit of normal, or (2) who are symptomatic, or (3) who are at risk for future complications from their disease, to induce remission (normalization of serum alkaline phosphatase).

Actonel Contraindications

• Hypocalcemia (see PRECAUTIONS, Mineral Metabolism )
• Known hypersensitivity to any component of this product
• Inability to stand or sit upright for at least 30 minutes

Actonel Side Effects

Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer (see PRECAUTIONS ).

Actonel Precautions

Mineral Metabolism

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting ACTONEL therapy. 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. ACTONEL is not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min).

Upper Gastrointestinal Effects

Bisphosphonates have been associated with gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcers. This association has been reported for bisphosphonates in postmarketing experience, but has not been found in most pre-approval clinical trials, including those conducted with ACTONEL. Patients should be advised that taking the medication according to the instructions is important to minimize the risk of these events. They should take ACTONEL with sufficient plain water (6 to 8 oz) to facilitate delivery to the stomach, and should not lie down for 30 minutes after taking the drug.

Jaw Osteonecrosis

Osteonecrosis, primarily in the jaw, has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures such as tooth extraction, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally.

For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment, prior to the procedure, reduces the risk of osteonecrosis of the jaw. Clinical judgment should guide the management plan of each patient based on individual benefit/risk assessment.

Musculoskeletal Pain

In postmarketing experience, there have been infrequent reports of severe and occasionally incapacitating bone, joint, and/or muscle pain in patients taking bisphosphonates (see ADVERSE REACTIONS ). 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.

Glucocorticoid-induced Osteoporosis

The risk versus benefit of ACTONEL for the prevention and treatment of glucocorticoid-induced osteoporosis at daily doses of glucocorticoids <7.5 mg of prednisone or equivalent has not been established. Before initiating treatment, the hormonal status of both men and women should be ascertained and appropriate replacement considered.

The efficacy of ACTONEL for this indication has been established in studies of 1-year duration. The efficacy of ACTONEL beyond 1 year has not been studied.

Information For Patients

The patient should be informed to pay particular attention to the dosing instructions as clinical benefits may be compromised by failure to take the drug according to instructions. Specifically, ACTONEL should be taken at least 30 minutes before the first food or drink of the day other than water.

To facilitate delivery to the stomach, and thus reduce the potential for esophageal irritation, patients should take ACTONEL while in an upright position (sitting or standing) with a full glass of plain water (6 to 8 oz). Patients should not lie down for 30 minutes after taking the medication (see PRECAUTIONS, Upper Gastrointestinal Effects ). Patients should not chew or suck on the tablet because of a potential for oropharyngeal irritation.

Patients should be instructed that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or severe persistent or worsening heartburn) they should consult their physician before continuing ACTONEL.

Patients should be instructed that if they miss a dose of ACTONEL 35 mg once a week, they should take 1 tablet on the morning after they remember and return to taking 1 tablet once a week, as originally scheduled on their chosen day. Patients should not take 2 tablets on the same day.

If one or both tablets of ACTONEL 75 mg on two consecutive days/month are missed, and the next month's scheduled doses are more than 7 days away, the patient should be instructed as follows:

• If both tablets are missed, take one ACTONEL 75 mg tablet in the morning after the day it is remembered and then the other tablet on the next consecutive morning.
• If only one ACTONEL 75 mg tablet is missed, take the missed tablet in the morning after the day it is remembered.

Patients should then return to taking their ACTONEL 75 mg on two consecutive days/month as originally scheduled. Patients should not take more than two 75 mg tablets within 7 days.

If one or both tablets of ACTONEL 75 mg on two consecutive days/month are missed, and the next month's scheduled doses are within 7 days, patients should wait until their next month's scheduled doses and then continue taking ACTONEL 75 mg on two consecutive days/month as originally scheduled.

Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see PRECAUTIONS, Mineral Metabolism ). Calcium supplements or calcium-, aluminum-, and magnesium-containing medications may interfere with the absorption of ACTONEL and should be taken at a different time of the day, as with food.

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.

Physicians should instruct their patients to read the Patient Information before starting therapy with ACTONEL 5 mg, 35 mg, or 75 mg and to re-read it each time the prescription is renewed.

Patients should be reminded to give all of their health care providers an accurate medication history. Instruct patients to tell all of their health care providers that they are taking ACTONEL. Patients should be instructed that any time they have a medical problem they think may be from ACTONEL, they should talk to their doctor.

Drug Interactions

No specific drug-drug interaction studies were performed. Risedronate is not metabolized and does not induce or inhibit hepatic microsomal drug-metabolizing enzymes (Cytochrome P450).

Calcium Supplements/Antacids

Co-administration of ACTONEL and calcium, antacids, or oral medications containing divalent cations will interfere with the absorption of ACTONEL.

Hormone Replacement Therapy

One study of about 500 early postmenopausal women has been conducted to date in which treatment with ACTONEL (5 mg daily) plus estrogen replacement therapy was compared to estrogen replacement therapy alone. Exposure to study drugs was approximately 12 to 18 months and the primary endpoint was change in BMD. If considered appropriate, ACTONEL may be used concomitantly with hormone replacement therapy.

Aspirin/Nonsteroidal Anti-inflammatory Drugs (Nsaids)

Of over 5700 patients enrolled in the ACTONEL Phase 3 osteoporosis studies, aspirin use was reported by 31% of patients, 24% of whom were regular users (3 or more days per week). Forty-eight percent of patients reported NSAID use, 21% of whom were regular users. Among regular aspirin or NSAID users, the incidence of upper gastrointestinal adverse experiences in ACTONEL-treated patients (24.5%) was similar to that in placebo-treated patients (24.8%).

H Blockers and Proton Pump Inhibitors (Ppis)

Of over 5700 patients enrolled in the ACTONEL Phase 3 osteoporosis studies, 21% used H2 blockers and/or PPIs. Among these patients, the incidence of upper gastrointestinal adverse experiences in the ACTONEL-treated patients was similar to that in placebo-treated patients.

Drug/Laboratory Test Interactions

Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with ACTONEL have not been performed.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

In a 104-week carcinogenicity study, rats were administered daily oral doses up to 24 mg/kg/day (approximately 7.7 times the maximum recommended human daily dose of 30 mg based on surface area, mg/m2 ). There were no significant drug-induced tumor findings in male or female rats. The high dose male group of 24 mg/kg/day was terminated early in the study (Week 93) due to excessive toxicity, and data from this group were not included in the statistical evaluation of the study results. In an 80-week carcinogenicity study, mice were administered daily oral doses up to 32 mg/kg/day (approximately 6.4 times the 30 mg/day human dose based on surface area, mg/m2 ). There were no significant drug-induced tumor findings in male or female mice.

Mutagenesis

Risedronate did not exhibit genetic toxicity in the following assays: In vitro bacterial mutagenesis in Salmonella and E. coli (Ames assay), mammalian cell mutagenesis in CHO/HGPRT assay, unscheduled DNA synthesis in rat hepatocytes and an assessment of chromosomal aberrations in vivo in rat bone marrow. Risedronate was positive in a chromosomal aberration assay in CHO cells at highly cytotoxic concentrations (>675 mcg/mL, survival of 6% to 7%). When the assay was repeated at doses exhibiting appropriate cell survival (29%), there was no evidence of chromosomal damage.

Impairment Of Fertility

In female rats, ovulation was inhibited at an oral dose of 16 mg/kg/day (approximately 5.2 times the 30 mg/day human dose based on surface area, mg/m2 ). Decreased implantation was noted in female rats treated with doses ?7 mg/kg/day (approximately 2.3 times the 30 mg/day human dose based on surface area, mg/m2 ). In male rats, testicular and epididymal atrophy and inflammation were noted at 40 mg/kg/day (approximately 13 times the 30 mg/day human dose based on surface area, mg/m2 ). Testicular atrophy was also noted in male rats after 13 weeks of treatment at oral doses of 16 mg/kg/day (approximately 5.2 times the 30 mg/day human dose based on surface area, mg/m2 ). There was moderate-to-severe spermatid maturation block after 13 weeks in male dogs at an oral dose of 8 mg/kg/day (approximately 8 times the 30 mg/day human dose based on surface area, mg/m2 ). These findings tended to increase in severity with increased dose and exposure time.

Pregnancy

Pregnancy Category C: Survival of neonates was decreased in rats treated during gestation with oral doses ?16 mg/kg/day (approximately 5.2 times the 30 mg/day human dose based on surface area, mg/m2 ). Body weight was decreased in neonates from dams treated with 80 mg/kg (approximately 26 times the 30 mg/day human dose based on surface area, mg/m2 ). In rats treated during gestation, the number of fetuses exhibiting incomplete ossification of sternebrae or skull was statistically significantly increased at 7.1 mg/kg/day (approximately 2.3 times the 30 mg/day human dose based on surface area, mg/m2 ). Both incomplete ossification and unossified sternebrae were increased in rats treated with oral doses ?16 mg/kg/day (approximately 5.2 times the 30 mg/day human dose based on surface area, mg/m2 ). A low incidence of cleft palate was observed in fetuses from female rats treated with oral doses ?3.2 mg/kg/day (approximately 1 time the 30 mg/day human dose based on surface area, mg/m2 ). The relevance of this finding to human use of ACTONEL is unclear. No significant fetal ossification effects were seen in rabbits treated with oral doses up to 10 mg/kg/day during gestation (approximately 6.7 times the 30 mg/day human dose based on surface area, mg/m2 ). However, in rabbits treated with 10 mg/kg/day, 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 as low as 3.2 mg/kg/day (approximately 1 time the 30 mg/day human dose based on surface area, mg/m2 ) has resulted in periparturient hypocalcemia and mortality in pregnant rats allowed to deliver.

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.

There are no adequate and well-controlled studies of ACTONEL in pregnant women. ACTONEL should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Nursing Women

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 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 bisphosphonates, 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.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the patients receiving ACTONEL in postmenopausal osteoporosis studies (see CLINICAL STUDIES ), 47% were between 65 and 75 years of age, and 17% were over 75. The corresponding proportions were 26% and 11% in glucocorticoid-induced osteoporosis trials, and 40% and 26% in Paget's disease trials. No overall differences in efficacy between geriatric and younger patients were observed in these studies. In the male osteoporosis trial, 28% of patients receiving ACTONEL were between 65 and 75 years of age and 9% were over 75. The lumbar spine BMD response for ACTONEL compared to placebo was 5.6% for subjects <65 years and 2.9% for subjects ?65 years. No overall differences in safety between geriatric and younger patients were observed in the ACTONEL trials, but greater sensitivity of some older individuals cannot be ruled out.

Actonel Overdosage

Decreases in serum calcium and phosphorus following substantial overdose may be expected in some patients. Signs and symptoms of hypocalcemia may also occur in some of these patients. Milk or antacids containing calcium should be given to bind ACTONEL and reduce absorption of the drug.

In cases of substantial overdose, gastric lavage may be considered to remove unabsorbed drug. Standard procedures that are effective for treating hypocalcemia, including the administration of calcium intravenously, would be expected to restore physiologic amounts of ionized calcium and to relieve signs and symptoms of hypocalcemia.

Lethality after single oral doses was seen in female rats at 903 mg/kg and male rats at 1703 mg/kg. The minimum lethal dose in mice and rabbits was 4000 mg/kg and 1000 mg/kg. These values represent 320 to 620 times the 30 mg human dose based on surface area (mg/m2 ).

Actonel Information For Patients

The patient should be informed to pay particular attention to the dosing instructions as clinical benefits may be compromised by failure to take the drug according to instructions. Specifically, ACTONEL should be taken at least 30 minutes before the first food or drink of the day other than water.

To facilitate delivery to the stomach, and thus reduce the potential for esophageal irritation, patients should take ACTONEL while in an upright position (sitting or standing) with a full glass of plain water (6 to 8 oz). Patients should not lie down for 30 minutes after taking the medication (see PRECAUTIONS, Upper Gastrointestinal Effects ). Patients should not chew or suck on the tablet because of a potential for oropharyngeal irritation.

Patients should be instructed that if they develop symptoms of esophageal disease (such as difficulty or pain upon swallowing, retrosternal pain or severe persistent or worsening heartburn) they should consult their physician before continuing ACTONEL.

Patients should be instructed that if they miss a dose of ACTONEL 35 mg once a week, they should take 1 tablet on the morning after they remember and return to taking 1 tablet once a week, as originally scheduled on their chosen day. Patients should not take 2 tablets on the same day.

If one or both tablets of ACTONEL 75 mg on two consecutive days/month are missed, and the next month's scheduled doses are more than 7 days away, the patient should be instructed as follows:

• If both tablets are missed, take one ACTONEL 75 mg tablet in the morning after the day it is remembered and then the other tablet on the next consecutive morning.
• If only one ACTONEL 75 mg tablet is missed, take the missed tablet in the morning after the day it is remembered.

Patients should then return to taking their ACTONEL 75 mg on two consecutive days/month as originally scheduled. Patients should not take more than two 75 mg tablets within 7 days.

If one or both tablets of ACTONEL 75 mg on two consecutive days/month are missed, and the next month's scheduled doses are within 7 days, patients should wait until their next month's scheduled doses and then continue taking ACTONEL 75 mg on two consecutive days/month as originally scheduled.

Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate (see PRECAUTIONS, Mineral Metabolism ). Calcium supplements or calcium-, aluminum-, and magnesium-containing medications may interfere with the absorption of ACTONEL and should be taken at a different time of the day, as with food.

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.

Physicians should instruct their patients to read the Patient Information before starting therapy with ACTONEL 5 mg, 35 mg, or 75 mg and to re-read it each time the prescription is renewed.

Patients should be reminded to give all of their health care providers an accurate medication history. Instruct patients to tell all of their health care providers that they are taking ACTONEL. Patients should be instructed that any time they have a medical problem they think may be from ACTONEL, they should talk to their doctor.

Actonel Patient Information

ACTONEL ® (AK-toh-nel) Tablets

ACTONEL (risedronate sodium tablets) 5 mg,
ACTONEL (risedronate sodium tablets) 35 mg, and
ACTONEL (risedronate sodium tablets) 75 mg
for Osteoporosis

Read this information carefully before you start to use your medicine. Read the information you get every time you get more medicine. There may be new information. This information does not take the place of talking with your health care provider about your medical condition or your treatment. If you have any questions or are not sure about something, ask your health care provider or pharmacist.

What is the most important information I should know about ACTONEL?

ACTONEL may cause problems in your stomach and esophagus (the tube that connects the mouth and the stomach), such as trouble swallowing (dysphagia), heartburn (esophagitis), and ulcers. You might feel pain in your bones, joints, or muscles (See ?What are the Possible Side Effects of ACTONEL??).

You must follow the instructions exactly for ACTONEL to work and to lower the chance of serious side effects. (See ?How should I take ACTONEL??).

What is ACTONEL?

ACTONEL is a prescription medicine used:

• to prevent and treat osteoporosis in postmenopausal women (See ?What is Osteoporosis??).
• to increase bone mass in men with osteoporosis
• to prevent and treat osteoporosis in men and women that is caused by treatment with steroid medicines such as prednisone.
• to treat Paget's disease of bone in men and women. The treatment for Paget's disease is very different than for osteoporosis and uses a different type of ACTONEL. This leaflet does not cover using ACTONEL for Paget's disease. If you have Paget's disease, ask your health care provider how to use ACTONEL.

ACTONEL may reverse bone loss by stopping more loss of bone and increasing bone strength in most people who take it, even though they won't be able to see or feel a difference. ACTONEL helps lower the risk of breaking bones (fractures). Your health care provider may measure the thickness (density) of your bones or do other tests to check your progress.

See the end of this leaflet for information about osteoporosis.

Who should not take ACTONEL?

Do not take ACTONEL if you:

• have low blood calcium (hypocalcemia)
• cannot sit or stand up for 30 minutes
• have kidneys that work poorly
• have an allergy to ACTONEL. The active ingredient in ACTONEL is risedronate sodium. (See the end of this leaflet for a list of all the ingredients in ACTONEL.)

Tell your doctor before using ACTONEL if:

• you are pregnant or may become pregnant. We do not know if ACTONEL can harm your unborn child.
• you are breast-feeding or plan to breast-feed. We do not know if ACTONEL can pass through your milk and if it can harm your baby.
• you have kidney problems. ACTONEL may not be right for you.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. ACTONEL can interact with other medicines. Keep a list of all the medicines you take. Show it to all your health care providers, including your dentist and pharmacist, each time you get a new medicine.

How should I take ACTONEL?

The following instructions are for ACTONEL 5 mg (daily), ACTONEL 35 mg (Once-a-Week), and ACTONEL 75 mg (Two Consecutive Days each Month):

• Take ACTONEL first thing in the morning before you eat or drink anything except plain water.
• Take ACTONEL while you are sitting up or standing.
• Take ACTONEL with 6 to 8 ounces (about 1 cup) of plain water. Do not take it with any other drink besides plain water. Do not take it with coffee, tea, juice, milk, or other dairy drinks.
• Swallow ACTONEL whole. Do not chew the tablet or keep it in your mouth to melt or dissolve.
• After taking ACTONEL you must wait at least 30 minutes BEFORE :
  • lying down. You may sit, stand, or do normal activities like read the newspaper or take a walk.
  • eating or drinking anything except plain water.
  • taking vitamins, calcium, or antacids. Take vitamins, calcium, and antacids at a different time of the day from when you take ACTONEL.
• Keep taking ACTONEL for as long as your health care provider tells you.
• For ACTONEL to treat your osteoporosis or keep you from getting osteoporosis, you have to take it exactly as prescribed.
• Your health care provider may tell you to take calcium and vitamin D supplements and to exercise.

What is my ACTONEL schedule?

If your doctor has prescribed ACTONEL 5 mg daily (a yellow tablet):

• Take 1 ACTONEL 5 mg tablet every day in the morning.
• If you miss a dose of your ACTONEL 5 mg in the morning, do not take it later in the day. Take only 1 ACTONEL 5 mg tablet the next morning and continue your usual schedule of 1 tablet a day. Do not take 2 tablets on the same day.

If your doctor has prescribed ACTONEL 35 mg Once-a-Week (an orange tablet) :

• Choose 1 day of the week that you will remember and that best fits your schedule to take your ACTONEL 35 mg. Every week, take 1 ACTONEL 35 mg tablet in the morning on your chosen day.
• If you miss a dose of your ACTONEL 35 mg in the morning, do not take it later in the day. Take only 1 ACTONEL 35 mg tablet the next morning and continue your usual schedule of 1 tablet on your chosen day of the week. Do not take 2 tablets on the same day.

If your doctor has prescribed ACTONEL 75 mg Two Consecutive Days each Month (a pink tablet) :

• Choose 2 days in a row during the month that best fits your schedule and that you will remember to take your ACTONEL 75 mg. Take 1 ACTONEL 75 mg tablet in the morning of your first chosen day. Take the second tablet in the morning of the following day. ACTONEL 75 mg tablets should be taken on the same two consecutive days each month.
• If you miss one or both tablets of your dose of ACTONEL 75 mg in the morning, do not take it later in the day.
  
  
  • If the next month's scheduled doses are more than 7 days away do the following:
    
  • If both tablets were missed, take the first ACTONEL 75 mg tablet on the morning after the day it is remembered and the second tablet on the next consecutive morning.
    
    
  • If only one tablet is missed, take the missed tablet on the morning after the day it is remembered.
    
    
  • You should then continue your usual schedule of ACTONEL 75 mg on two consecutive days each month.
    
    
  • Do not take more than two 75 mg tablets within 7 days.
    
    
  • If the next month's scheduled doses are 1 to 7 days away, you should wait until next month's scheduled doses and then resume taking ACTONEL 75 mg on two consecutive days each month as originally scheduled.
    
    
• If you are not sure what to do if you miss a dose, contact your health care provider who will be able to advise you.

What should I avoid while taking ACTONEL?

• Do not eat or drink anything except water before you take ACTONEL and for at least 30 minutes after you take it.
• Do not lie down for at least 30 minutes after you take ACTONEL.
• Foods and some vitamin supplements and medicines can stop your body from absorbing (using) ACTONEL. Therefore, do not take anything other than plain water at or near the time you take ACTONEL. (See "How should I take ACTONEL?").

What are the possible side effects of ACTONEL?

Stop taking ACTONEL and tell your health care provider right away if:

• swallowing is difficult or painful
• you have chest pain
• you have very bad heartburn or it doesn't get better

ACTONEL may cause:

• pain or trouble swallowing (dysphagia)
• heartburn (esophagitis)
• ulcers in your stomach and esophagus (the tube that connects the mouth and the stomach)
• pain in bones, joints or muscles, sometimes severe. Pain may start as soon as one day or up to several months after starting ACTONEL.

The most common side effects with ACTONEL include back pain, joint pain, upset stomach, abdominal (stomach area) pain, constipation, diarrhea, gas, and headache. Tell your health care provider if you have pain or discomfort in your stomach or esophagus. Rarely, severe skin reactions may occur. Patients may get allergic reactions such as rash, hives, or in rare cases, swelling that can be of the face, lips, tongue, or throat, which may cause trouble breathing or swallowing.

In rare cases, patients taking ACTONEL may get eye inflammation, usually with pain, redness and sensitivity to light.

Rarely, patients had jaw problems associated with delayed healing and infection, often following tooth extraction.

These are not all the possible side effects of ACTONEL. You can ask your health care provider or pharmacist about other side effects. Any time you have a medical problem you think may be from ACTONEL, talk to your doctor.

What is osteoporosis?

Osteoporosis is a disease that causes bones to become thinner. Thin bones can break easily. Most people think of their bones as being solid like a rock. Actually, bone is living tissue, just like other parts of the body?your heart, brain, or skin, for example. Bone just happens to be a harder type of tissue. Bone is always changing. Your body keeps your bones strong and healthy by replacing old bone with new bone.

Osteoporosis causes the body to remove more bone than it replaces. This means that bones get weaker. Weak bones are more likely to break. Osteoporosis is a bone disease that is quite common, especially in older women. However, young people and men can develop osteoporosis, too. Osteoporosis can be prevented, and with proper therapy it can be treated.

How can osteoporosis affect me?

• You may not have any pain or other symptoms when osteoporosis begins.
• You are more likely to break (fracture) a bone especially if you fall because osteoporosis makes your bones weaker. You are most likely to break a bone in your back (spine), wrist, or hip.
• You may ?shrink? (get shorter).
• You may get a ?hump? (curve) in your back.
• You may have bad back pain that makes you stop some activities.

Who is at risk for osteoporosis?

Many things put people at risk for osteoporosis. The following people have a higher chance of getting osteoporosis:

Women who

• are going through or who are past menopause ("the change")
• are white (Caucasian) or Asian

People who

• are thin
• have a family member with osteoporosis
• do not get enough calcium or vitamin D
• do not exercise
• smoke
• drink alcohol often
• take bone thinning medicines (like prednisone or other corticosteroids) for a long time

General information about ACTONEL:

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use ACTONEL for a condition for which it was not prescribed. Do not give ACTONEL to other people, even if they have the same symptoms you have. It may harm them.

What if I have other questions about ACTONEL?

This leaflet summarizes the most important information about ACTONEL for osteoporosis. If you have more questions about ACTONEL, ask your health care provider or pharmacist. They can give you information written for health care professionals. For more information, call 1-877- ACTONEL (toll-free) or visit our web site at www.actonel.com.

What are the ingredients of ACTONEL?

ACTONEL (active ingredient): risedronate sodium.

ACTONEL (inactive ingredients): crospovidone, ferric oxide red (35 mg and 75 mg tablets only), ferric oxide yellow (5 mg and 35 mg tablets only), hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose monohydrate (5 mg, 30 mg and 35 mg tablets only), magnesium stearate, microcrystalline cellulose, polyethylene glycol, silicon dioxide, and titanium dioxide.

ACTONEL® is marketed by:
Procter & Gamble Pharmaceuticals, Inc.
Cincinnati, OH 45202
and
sanofi-aventis U.S. LLC
Bridgewater, NJ 08807

May 2007

© 2007 Procter & Gamble Pharmaceuticals, Inc.