Consumer medicine information

Risedro Once a Week

Risedronate sodium

BRAND INFORMATION

Brand name

Risedro Once A Week

Active ingredient

Risedronate sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Risedro Once a Week.

What is in this leaflet

This leaflet answers some common questions about RISEDRO ONCE A WEEK.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking RISEDRO ONCE A WEEK against the benefits they expect it will have for you.

Talk to your doctor or pharmacist if you have any concerns about taking this medicine.

Keep this leaflet with your medicine. You may need to read it again.

What RISEDRO ONCE A WEEK is used for

RISEDRO ONCE A WEEK is used to treat bone disease and belongs to a group of medicines called bisphosphonates.

It works directly on your bones to make them stronger and therefore less likely to break or fracture.

The tablets are used to treat:

  • osteoporosis (brittle or fragile bones that may easily fracture)
  • osteoporosis caused by taking steroids.

Osteoporosis is caused by changes in the way bone is normally maintained.

Understanding bone
Bone is living, growing tissue consisting of calcium and other minerals. Throughout life, our bodies are breaking down old bone and rebuilding new bone in a continuous cycle. Until our late 20s, while bones are still developing, we gain bone by building more than we lose. From then until about age 35 the process is usually in balance, so that the amount of bone lost is about equal to the amount that is replaced. After about age 35 this balance is disturbed, with bone loss occurring at a slightly faster rate than it can be replaced. In women, after menopause, hormonal changes cause bone loss at an even faster rate. When bone loss is excessive, bones can become thinner and weaker, and therefore are more likely to break.

Osteoporosis
"Osteo" means bone, and "porosis" means something that has holes in it, like a sponge. Therefore, osteoporosis is a disease which causes bones to become more porous, gradually making them weaker, more brittle and likely to break.

Osteoporosis is common in postmenopausal women. The menopause occurs when the ovaries virtually stop producing the female hormone, oestrogen, or are removed (which may occur, for example, at the time of a hysterectomy). At this time, bone is removed faster than it is formed, so bone loss occurs and bones become weaker. The earlier a woman reaches the menopause, the greater the risk of osteoporosis.

Osteoporosis also occurs in men but is less common than in women.

Early on, osteoporosis usually has no symptoms. However, if left untreated it can result in broken bones, also called fractures. Although fractures usually cause pain, fractures of the bones of the spine may go unnoticed until they cause height loss. Fractures may occur during normal, everyday activity, such as lifting, or from minor injury that would not ordinarily fracture normal bone. Fractures usually occur at the hip, spine, or wrist and can lead not only to pain, but also to considerable deformity and disability, such as stooped posture from curvature of the spine, and loss of mobility.

Long term steroid treatment can also lead to osteoporosis in both men and women.

RISEDRO ONCE A WEEK works by slowing down the process of old bone being removed, which allows the bone forming cells time to rebuild normal bone. It not only helps prevent the loss of bone but actually helps to rebuild bone and makes bone less likely to fracture. Thus, it reverses the progression of osteoporosis. Although it starts working on the bone cells immediately, measurable effects on bone mass may not be seen for several months or more.

Do not give RISEDRO ONCE A WEEK to children or adolescents under 18 years of age. There have been no studies of its effects in this age group.

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

There is no evidence that RISEDRO ONCE A WEEK is addictive.

Before you take it

When you must not take it

Do not take RISEDRO ONCE A WEEK if you are allergic to risedronate sodium or any of the ingredients listed at the end of this leaflet.

Do not take it if you:

  • have certain disorders of the food pipe (also called oesophagus), including those that cause difficulty swallowing
  • are unable to stand or sit upright for at least 30 minutes
  • have low levels of calcium in your blood (a condition called hypocalcaemia).

Do not take it if you are pregnant. It is not recommended for use during pregnancy, unless you and your doctor have discussed the risks and benefits.

Do not take it if you are breastfeeding. It is not known whether RISEDRO ONCE A WEEK passes into breast milk.

Do not take it if the expiry date (Exp.) printed on the pack has passed. If you take this medicine after the expiry date has passed, it may not work as well.

Do not take RISEDRO ONCE A WEEK if the packaging shows signs of tampering or the tablets do not look quite right.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

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

Tell your doctor if you have, or have had, any medical conditions, especially the following:

  • disturbances of bone and mineral metabolism (for example, vitamin D deficiency, parathyroid hormone abnormalities)
  • problems with the tube that takes food from your mouth to your stomach (oesophagus) such as ulcers.
  • Pain, swelling or numbness of the jaw or a “heavy jaw feeling” or loosening of a tooth

Check with your doctor or dentist to see if a dental check-up is required before starting RISEDRO ONCE A WEEK. This is especially important if you are receiving medicines or therapy used to treat cancer or taking corticosteroids, such as prednisone or cortisone.

Tell your doctor if you are planning to have any dental procedures or dental surgery. If you know that you need to have any dental work performed, make sure that you discuss this with your doctor as they may decide it is best to delay the commencement of RISEDRO ONCE A WEEK until the work has been completed.

If you have not told your doctor about any of the above, tell them before you start taking RISEDRO ONCE A WEEK.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop. Some medicines may affect the way other medicines work.

Some medicines are likely to interfere with the absorption of RISEDRO ONCE A WEEK if taken at the same time. These include:

  • antacids, used to treat indigestion eg Gaviscon, Mylanta
  • calcium supplements or products containing calcium
  • iron supplements.

Therefore, take RISEDRO ONCE A WEEK at least 30 minutes before taking any of these and other medicines to make sure there is no problem with absorption.

You can take aspirin while you are being treated with RISEDRO ONCE A WEEK. However, both aspirin and RISEDRO ONCE A WEEK can increase the chance of a stomach upset.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicine to be careful with or avoid while taking RISEDRO ONCE A WEEK.

How to take it

How much to take

Take RISEDRO ONCE A WEEK only when prescribed by your doctor.

For osteoporosis, the usual dose is one 35 mg tablet each week.

Follow all directions given to you by your doctor and pharmacist carefully.

When and how to take it

Take RISEDRO ONCE A WEEK after getting up for the day and before taking your first food, beverage, or other medication. Do not take it at bedtime.

Swallow the tablet whole with a full glass of plain water. It is important to take it with plain water only, not mineral water. Mineral water and other drinks, including fruit juices, coffee and tea, will reduce the effect of RISEDRO ONCE A WEEK by interfering with its absorption into the body.

Stay upright for at least 30 minutes after swallowing the tablet and do not take any food, medicines or drinks other than plain water during this time.

Do not lie down immediately after swallowing it. It is important to stay upright (sitting, standing or walking around) for at least 30 minutes after swallowing your tablet. It is also very important to stay upright until after you have eaten your first food of the day. These actions will help make sure your tablet reaches your stomach quickly and help reduce the potential for irritation to your food pipe (oesophagus).

How long to take it

Continue taking RISEDRO ONCE A WEEK for as long as recommended by your doctor. Do not stop taking it without checking with your doctor or pharmacist.

If you forget to take it

If you forget to take RISEDRO ONCE A WEEK, take your next dose the following morning. If you take the forgotten tablet after you have eaten or had a drink, it will not work as well as it should. Therefore, it is better to skip the dose that you missed.

Do not take two tablets on the same day to make up for the dose that you missed. Return to taking one tablet once a week, as originally scheduled on your chosen day.

Talk to your doctor or pharmacist if you are not sure what to do.

If you take too much RISEDRO ONCE A WEEK (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (13 11 26), or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much RISEDRO ONCE A WEEK. Do this even if there are no signs of discomfort or poisoning.

If you take too many tablets at one time, drink a full glass of milk or antacids. Do not induce vomiting. Do not lie down.

While you are taking RISEDRO ONCE A WEEK

Things you must do

Before starting any new medicine, tell your doctor or pharmacist that you are taking RISEDRO ONCE A WEEK.

Tell all the doctors, dentists, oral or facial surgeons and pharmacists who are treating you that you are taking the medicine. It may cause jaw-bone problems in some people. Jaw-bone problems may include infection, and delayed healing after teeth are pulled out or other work that involves drilling into the jaw.

Ensure that you maintain good oral hygiene while you are taking RISEDRO ONCE A WEEK, especially following any dental procedure.

Tell your doctor or dentist immediately if you develop a toothache, jaw pain, painful exposed bone or swelling, especially following dental work.

If you become pregnant while taking RISEDRO ONCE A WEEK, stop taking the tablets and tell your doctor.

If you develop difficulty or pain upon swallowing, chest pain, or new or worsening heartburn, stop taking RISEDRO ONCE A WEEK and tell your doctor.

Make sure you have an adequate intake of calcium in your diet.

Your doctor, dietician or pharmacist can tell you what foods you should eat.

Things you must not do

Do not use RISEDRO ONCE A WEEK to treat any other conditions unless your doctor tells you to.

Do not give RISEDRO ONCE A WEEK to anyone else, even if they have the same condition as you.

Do not lie down for 30 minutes after taking a dose.

Do not have any food or drink, except for plain water for 30 minutes after taking it.

Things that would be helpful for your osteoporosis

Some self help measures suggested below may help your osteoporosis. Talk to your doctor or pharmacist about these measures and for more information.

  • Exercise - can be helpful in building and maintaining strong bones. Regular exercise such as a brisk walk is a good idea. Talk to your doctor before you begin any exercise program.
  • Diet - eat a balanced diet. You may need to increase the amount of calcium in your diet by eating calcium-rich foods or taking a calcium supplement with vitamin D to aid calcium absorption. Your doctor will advise you.
  • Smoking - appears to increase the rate at which you lose bone and, therefore, may increase your risk of fracture. Your doctor may ask you to stop smoking or at least cut down.
  • Alcohol - your doctor may advise you to cut down the amount of alcohol you drink. If you drink excessively on a regular basis, you may increase your risk of developing osteoporosis.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking RISEDRO ONCE A WEEK.

Like all other medicines, it may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • stomach pain
  • diarrhoea
  • nausea
  • aching muscles, joints or bones
  • headache
  • runny nose
  • sore throat
  • dizziness.

Tell your doctor immediately if you notice any of the following:

  • skin rash or redness of the skin, sometimes made worse by sunlight, itchiness
  • mouth ulcers
  • blurred vision, pain or redness of the eyes
  • jaw or teeth problems, associated with delayed healing and/or infection, often following a tooth extraction or invasive dental procedure

Tell your dentist as well as your doctor if jaw problems develop.

These side effects are rare.

If any of the following happen, stop taking RISEDRO ONCE A WEEK and tell your doctor immediately:

  • difficulty or pain upon swallowing
  • chest pain
  • new or worsening heartburn.

These side effects may be due to irritation or ulceration of the food pipe. They may worsen if you continue taking the tablets. These side effects are rare.

If any of the following happen, stop taking the medicine and tell your doctor immediately, or go to Accident and Emergency at the nearest hospital:

  • swelling of the face, lips, mouth, throat or tongue which may cause difficulty in breathing or swallowing
  • severe skin reactions.

These may be serious side effects. You may need urgent medical attention.

Other side effects not listed above may also occur in some patients. Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

After using it

Storage

Keep RISEDRO ONCE A WEEK where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the blister pack, they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store RISEDRO ONCE A WEEK or any other medicine in the bathroom or near a sink.

Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking RISEDRO ONCE A WEEK, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

RISEDRO ONCE A WEEK is a white to off-white capsule shaped tablet with RE 35 on one side.

RISEDRO ONCE A WEEK comes in a blister pack of 4 tablets.

Ingredients

The active ingredient in RISEDRO ONCE A WEEK is risedronate sodium. Each tablet contains 35 mg of risedronate sodium.

The tablets also contain:

  • microcrystalline cellulose
  • sorbitol
  • colloidal anhydrous silica
  • croscarmellose sodium
  • sodium stearylfumarate.

The tablets do not contain gluten, sucrose, tartrazine or any other azo dyes.

Supplier

Arrow Pharma Pty Ltd
15 – 17 Chapel Street
Cremorne VIC 3121

Australian registration number:

RISEDRO ONCE A WEEK – AUST R 162455

Date of revision: March 2020

Published by MIMS April 2020

BRAND INFORMATION

Brand name

Risedro Once A Week

Active ingredient

Risedronate sodium

Schedule

S4

 

1 Name of Medicine

Risedronate sodium.

6.7 Physicochemical Properties

The chemical name for risedronate sodium is [1-hydroxy-2-(3- pyridinyl)ethylidene]bis(phosphonic acid) monosodium salt.
Risedronate sodium is a fine, white to off white, odourless powder. It is soluble in water and aqueous solutions and essentially insoluble in common organic solvents.

Chemical structure.

The structural formula of risedronate sodium is:
Molecular formula: C7H10NO7P2Na.
Molecular weight: 305.10.

CAS number.

115436-72-1.

2 Qualitative and Quantitative Composition

Risedro Once A Week tablets contain 35 mg of risedronate sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White to off-white capsule shaped uncoated tablet, embossed with RE 35 on one side and plain on the other.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Risedronate is a potent pyridinyl bisphosphate that binds to bone hydroxyapatite and inhibits osteoclast mediated bone resorption. Risedronate is a third generation bisphosphonate. In preclinical studies risedronate demonstrated potent antiosteoclast and antiresorptive activity, increasing bone mass and biomechanical strength dose dependently. The activity of risedronate was confirmed by bone marker measurements during pharmacodynamic and clinical studies.
With risedronate 5 mg daily, decreases in biochemical markers of bone turnover were observed within one month of treatment and reached a maximum decrease in three to six months, remaining stable during the course of therapy. These data demonstrate that risedronate causes a moderate reduction in bone resorption and bone turnover. The new steady state approximates the rate of bone turnover seen in premenopausal women. Decreases in biochemical markers of bone turnover were similar with risedronate 35 mg once a week and risedronate 5 mg daily. In a study in men with osteoporosis, decreases in biochemical markers of bone turnover were observed at the earliest time point of three months and continued to be observed at 24 months.

Comparison of risedronate 5 mg daily dose and 35 mg once a week dose.

Based on a lumbar spine bone mineral density (BMD), risedronate 35 mg once a week (n = 485) was shown to be therapeutically equivalent to risedronate 5 mg daily (n = 480) in a one year, double blind multicentre study of postmenopausal women with osteoporosis. The two treatment groups were also similar at one year with regard to BMD increases at the total proximal femur, femoral neck and trochanter.

Clinical trials.

Treatment of osteoporosis.

The clinical program involved a wide range of early and late postmenopausal women with and without fracture, including those with a history of GI disease and those using aspirin, NSAIDs, proton pump inhibitors and H2-blockers.
The fracture efficacy of risedronate 5 mg daily in the treatment of postmenopausal osteoporosis was demonstrated in two large, randomised, placebo controlled, double blind studies which enrolled a total of almost 4,000 women under similar protocols. The multinational study (RVE) was conducted primarily in Europe and Australia; a second study was conducted in North America (RVN). Patients were selected on the basis of radiographic evidence of previous vertebral fracture and had established disease. The average number of prevalent vertebral fractures per patient at study entry was 4 in the multinational study and 2.5 in the North American study, with a broad range of baseline BMD levels. All patients in these studies received supplemental calcium 1,000 mg/day. Patients with low vitamin D levels also received supplemental vitamin D 500 IU/day.
The number of evaluable patients treated were:
RVN: risedronate 5 mg, n = 696; placebo, n = 678.
RVE: risedronate 5 mg, n = 344; placebo, n = 346.
RVN and RVE: n = 1,040; placebo, n = 1,024.

Effect on vertebral fracture.

The pivotal studies of risedronate in the treatment of postmenopausal osteoporosis clearly demonstrate that risedronate 5 mg daily reduces vertebral fracture incidence in patients with low bone mass and vertebral fractures, regardless of age, years since menopause or disease severity at baseline. Risedronate 5 mg daily significantly reduced the risk of new vertebral fractures in each of the two large treatment studies. In the multinational study, treatment with risedronate 5 mg daily for three years significantly reduced the risk of new vertebral fractures by 49% compared to treatment with placebo (p < 0.001). (See Figure 1.) A similar, significant reduction of 41% was seen in the North American study (p = 0.003). The effect of risedronate 5 mg daily on vertebral fracture incidence was seen as early as the end of the first year of treatment in each study. In the multinational study, the incidence of new vertebral fractures after one year was reduced from 13.3 to 5.6%, an absolute risk reduction of 8% and a relative risk reduction of 61% (p < 0.001). In the North American study, the incidence of new vertebral fractures after one year was reduced from 6.4 to 2.4%, an absolute risk reduction of 4% and a relative risk reduction of 65% (p < 0.001). At both one and three years, the reduction in risk seen in the subgroup of patients who had two or more vertebral fractures at study entry was similar to that seen in the overall study population. Treatment with risedronate 5 mg daily also significantly reduced the proportion of patients experiencing new and worsening vertebral fractures in each of the studies.

Effect on nonvertebral fractures.

In a prospectively planned analysis of pooled data from the multinational and North American studies, risedronate 5 mg daily significantly reduced the cumulative incidence of patients experiencing osteoporosis related nonvertebral fractures (wrist, humerus, clavicle, pelvis, hip and leg) over three years by 36% (p = 0.005). See Figure 2.
The incidence of nonvertebral fractures in the pooled analysis (RVN and RVE) was lower in the risedronate 5 mg group than in the placebo group for all fractures at these sites combined, as well as for the wrist, humerus, pelvis and leg separately. This difference was significant for all nonvertebral osteoporosis related fractures (p = 0.005), as well as for the humerus (p = 0.024) and pelvis (p = 0.044), while a trend was seen at the wrist (p = 0.075) (see Table 3).
These findings demonstrate a beneficial effect of risedronate in preventing nonvertebral, osteoporosis related fractures.

Effect on height.

In the two 3 year osteoporosis treatment studies, standing height was measured yearly by stadiometer. As shown in Figure 3, treatment with risedronate 5 mg daily was associated with a significant reduction of about 50% in the annual rate of height loss compared to treatment with placebo.

Effect on bone mineral density.

The results of four large, randomised, placebo controlled trials in women with postmenopausal osteoporosis demonstrate that risedronate 5 mg daily reverses the progression of disease, increasing BMD at the spine, hip and wrist compared to the effects seen with placebo. In the large multinational vertebral fracture treatment study previously described, risedronate 5 mg daily produced increases in lumbar spine BMD which were progressive over at least two years of treatment, and were statistically significant relative to baseline and to placebo at six months and at all later time points. The mean increase in BMD at the lumbar spine was 5.9%, compared to placebo at the end of three years. In the North American fracture trial, similarly progressive and significant increases were seen; the mean increase was 4.3%, compared to placebo. Risedronate 5 mg also produced significant mean increases in BMD at the hip (femoral neck and trochanter) in each trial, compared to losses in BMD in the placebo group. The increases compared to placebo were 3.1% at the femoral neck and 6.4% at the trochanter in the multinational study, and 2.8 and 3.9%, respectively, in the North American study. Significant mean increases in the BMD of the midshaft radius, a skeletal site high in cortical bone, were also observed in each study in patients receiving risedronate treatment. These findings indicate that risedronate treatment produces positive effects at all measured skeletal sites of clinical importance for osteoporotic fractures.
Positive effects of risedronate treatment on BMD were also demonstrated in each of two large, randomised, placebo controlled trials in which almost 1,200 postmenopausal women were recruited on the basis of low lumbar spine bone mass (more than 2 SD below the premenopausal mean) rather than a history of vertebral fracture. After 1.5 to 2 years, risedronate produced significant mean increases in BMD of the lumbar spine compared to placebo (5 and 4.1% in the two studies), femoral neck (2.8 and 2.3%) and trochanter (3.3 and 3.3%) in these women with low bone mass.

Histology/histomorphometry.

Histological evaluation of 278 bone biopsy samples from 204 postmenopausal women who received risedronate or placebo once daily for two to three years (including 74 pairs of biopsies, 43 from risedronate treated patients) showed a moderate decrease in bone turnover in risedronate treated women. Histological assessment showed no osteomalacia, impaired bone mineralisation or other adverse effects on bone in risedronate treated women. These findings demonstrate that the bone formed during risedronate administration is of normal quality.

Bone markers.

In clinical studies, dose dependent decreases in biochemical markers of bone turnover were observed with risedronate 5 mg treatment. These effects were seen within one month of treatment and reached a plateau, with levels about 40% below baseline values, by the sixth month of treatment which remained stable during continuous treatment for up to three years. These data demonstrate that risedronate 5 mg causes a moderate reduction in bone resorption without oversuppression of bone formation. This new steady state approximates the rate of bone turnover seen in premenopausal women.

Combined administration with hormone replacement therapy.

The effects of combining risedronate 5 mg daily with conjugated oestrogen treatment (0.625 mg daily) were compared to the effects of conjugated oestrogen alone in a one year, randomised, double blind study in more than 500 postmenopausal women (mean lumbar spine BMD 1.3 SD below the premenopausal mean). Risedronate 5 mg daily in postmenopausal women taking oestrogen produced significant mean increases from baseline in BMD of the femoral neck (2.7%) and the midshaft radius (0.7%) at 12 months. These increases were greater than the increases observed in the oestrogen alone group, and reached statistical significance in favour of the combined treatment at the femoral neck and midshaft radius.
Consistent with the changes in BMD, the reduction in bone turnover was significantly greater in the combined risedronate plus oestrogen group compared to the oestrogen alone group (40 to 47% versus 35 to 40%) and remained within the premenopausal range. Histological evaluation of 93 bone biopsy samples from 61 women on oestrogen therapy who received either placebo or risedronate once daily for one year (including 32 pairs of biopsies, 16 from risedronate treated patients) found decreases in bone turnover in the risedronate treated patients that were consistent with the changes in bone turnover markers. Bone histology demonstrated that the bone of patients treated with risedronate plus oestrogen was of normal lamellar structure and normal mineralisation.

Endoscopic findings.

Risedronate endoscopic findings from patients with moderate to severe GI complaints in both risedronate and control patients showed no evidence of treatment related gastric, duodenal or oesophageal ulcers. Duodenitis was rarely observed in the risedronate group. Four out of five patients with endoscopically diagnosed oesophageal strictures had been taking risedronate 5 mg for more than six months.

35 mg once a week dose.

Risedronate 35 mg once a week (n = 485) was shown to be therapeutically equivalent to risedronate 5 mg daily (n = 480) in a one year double blind multicentre study of postmenopausal women with osteoporosis. In the primary efficacy analysis of completers, the mean increases from baseline in lumbar spine BMD at one year were 4.0% (3.7, 4.3; 95% CI) in the 5 mg group (n = 391) and 3.9% (3.6, 4.3; 95% CI) in the 35 mg group (n = 387) and the mean difference between 5 mg daily and 35 mg once a week was 0.1% (-0.42, 0.55; 95% CI) (see Table 4). While once a week doses of risedronate resulted in slightly smaller increases in lumbar spine BMD compared to daily doses of 5 mg after six months, the two regimens are equivalent after 12 months. The clinical relevance of these six month BMD differences is unknown. The results of the intent to treat analysis with the last observation carried forward were consistent with the primary efficacy analysis of completers. The two treatment groups were also similar with regard to BMD increases at other skeletal sites.
Very few patients in any treatment group had new fractured vertebrae at month 12 (5 mg daily: 1.5%; 35 mg once a week: 1.3%). No patient had more than one new fractured vertebra. There were no statistically significant differences in the percentage of patients with new vertebral fractures among the two treatment groups.

Treatment of osteoporosis in men.

Risedronate 35 mg once a week demonstrated efficacy in men with osteoporosis (age range 36 to 84 years) in a two year, double blind, placebo controlled study in 284 patients (risedronate sodium 35 mg n = 191). All patients received supplemental calcium and vitamin D. The primary efficacy endpoint was assessed by the percentage change from baseline in lumbar spine BMD at endpoint (month 24 or last postbaseline observation). Secondary efficacy measures included lumbar spine and proximal femur BMD at 6, 12 and 24 months; BMD responders (defined as patients who had a positive lumbar spine BMD change at month 24); bone turnover markers at 6, 12 and 24 months; body height; incidence of new vertebral fractures and incidence of clinical fractures. Increases in BMD were observed as early as six months following initiation of risedronate sodium treatment. The primary analysis showed a statistically significant difference between risedronate and placebo in least squares mean percent change from baseline to endpoint (p < 0.0001). The estimated difference at endpoint between risedronate and placebo in the intention to treat (ITT) population was 4.53% (95% CI: 3.46%, 5.60%). Risedronate 35 mg once a week produced mean increases in BMD at the lumbar spine, femoral neck, trochanter and total hip compared to placebo after two years of treatment. The bone effect (BMD increase and bone turnover markers (BTM) decrease) of risedronate sodium is similar in males and females.

Corticosteroid induced osteoporosis.

Bone mineral density.

Two one year, double blind, placebo controlled trials demonstrated that risedronate 5 mg once daily was effective in maintaining or increasing BMD in men and women initiating or continuing corticosteroid therapy.
The first study enrolled 228 patients, each of whom had initiated corticosteroid therapy (greater than or equal to 7.5 mg/day of prednisone or equivalent) within the previous three months for rheumatic, skin and pulmonary diseases. The mean lumbar spine BMD was normal at baseline. All patients in this study received supplemental calcium 500 mg/day. After one year of treatment, the placebo group lost BMD at the lumbar spine, femoral neck and trochanter, as shown in Figure 4. Risedronate 5 mg once daily prevented this bone loss with a statistically significant difference from placebo of 3.8% at the lumbar spine, 4.1% at the femoral neck and 4.6% at the trochanter. The results at these three sites were also statistically significant when the subgroups of men or postmenopausal women were analysed separately. Risedronate prevented bone loss regardless of underlying disease, age, race, gender, corticosteroid dose or baseline BMD.
The effect of risedronate discontinuation on BMD was studied in a double blind, placebo controlled study in postmenopausal women with glucocorticoid dependent rheumatoid arthritis. Women were treated for two years with risedronate 2.5 mg daily, cyclic risedronate (averaged 2.5 mg of risedronate per day over the 96 week active period), or placebo and then followed without treatment for one more year. Patients continued glucocorticoid treatment during the third year of the study. Risedronate discontinuation resulted in bone loss at all skeletal sites (proximal femur and lumbar spine) during the third year. The rate of bone loss, however, was similar to the placebo group indicating that bone loss was not accelerated after risedronate was discontinued. The study supports the use of continuous treatment with risedronate to prevent bone loss.
A second study of similar design enrolled 290 patients with continuing, long-term use (greater than or equal to six months) of corticosteroids for rheumatic, skin and pulmonary diseases. The baseline mean lumbar spine BMD was low (1.64 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 1,000 mg/day. Patients also received supplemental vitamin D 400 IU/day. After one year of treatment, the BMD of the placebo group remained near baseline levels at the lumbar spine, femoral neck and trochanter. Risedronate 5 mg once daily improved bone mass with a statistically significant mean increase compared to placebo of 2.7% at the lumbar spine and 1.9% at the femoral neck as shown in Figure 5. At the trochanter, a statistically significant increase from baseline was demonstrated (2.4%). Risedronate was effective regardless of age, race, gender, underlying disease, corticosteroid dose or baseline BMD.

Vertebral fractures.

Vertebral fractures were monitored for safety in the two placebo controlled studies. The incidence of vertebral fractures in each study was 15 to 17% in the placebo patients. The risk of vertebral fractures was reduced approximately 70% in the patients treated with risedronate 5 mg compared to patients treated with placebo. This decrease reached statistical significance when the studies were pooled, but not when analysed individually.

Bone marker data.

Risedronate 5 mg daily produced significant reductions in biochemical markers of bone turnover relative to placebo. Deoxypyridinoline/ creatinine and bone specific alkaline phosphatase (SAP) were significantly reduced by approximately 20% relative to placebo after one and three months of treatment, respectively, and remained reduced (maximum 35 and 26%, respectively) for the duration of the treatment period.

Histology/histomorphometry.

Histological evaluation of 70 bone biopsy samples from 48 women on corticosteroid therapy who received either placebo or risedronate once daily for one year (including 22 pairs of biopsies, 16 from risedronate treated patients) showed that bone formed during treatment with risedronate was of normal lamellar structure and normal mineralisation, with no bone or marrow abnormalities observed. Histomorphometric evaluation indicated that risedronate reduces bone resorption and produces a mild to moderate decrease in the rate of bone turnover. The rate of bone formation was preserved or increased and there was no evidence of impaired mineralisation. The structure of the cortical bone (cortical thickness and porosity) was maintained in the risedronate treated patients; cortical porosity increased, however, in the placebo group. These findings indicate that bone formed during risedronate treatment is of normal quality.

5.2 Pharmacokinetic Properties

Absorption.

Risedronate is relatively rapidly absorbed (Tmax ≈ 1 hour) throughout the upper gastrointestinal (GI) tract. Absorption is independent of dose over the range studied (single dose study, 2.5 to 30 mg; multiple dose studies, 2.5 to 5 mg daily and up to 50 mg dosed weekly). In a 13 week pharmacokinetic study with 5 mg daily and 35 mg weekly and 50 mg weekly dosing (n ~ 19/group), a comparison of the average serum concentration (Cavg) for 35 mg/week and 5 mg/day was not statistically significantly different. The 95% confidence interval for Cavg was 57.1 to 101.2, with a point estimate of 76.0% for the 35 mg dose compared to the 5 mg dose. Steady-state conditions in the serum are observed within 57 days of daily dosing. Mean oral bioavailability of the tablet is 0.63% and is decreased when risedronate is administered with food. Bioavailability was similar in men and women. Although administration of risedronate either 30 minutes prior to breakfast or two hours after dinner reduces absorption of risedronate by 55% compared to administration in the fasting state (i.e. no food or beverages for ten hours prior to, or four hours after dosing), and administration one hour prior to breakfast reduces absorption by 30%, risedronate has been shown to be effective in clinical trials when administered 30 minutes (or longer) before the first meal or beverage of the day (e.g. breakfast) and also when administered two hours (or longer) prior to and following food or beverages at other times of the day.
In a crossover, randomised comparative bioavailability study, 60 healthy male and female volunteers were enrolled for treatment. Volunteers were administered a single dose of 35 mg Risedro Once A Week risedronate tablet or the Australian reference risedronate tablet. Results demonstrated bioequivalence of Risedro Once A Week with the Australian reference risedronate (Table 5).

Distribution.

The mean steady-state volume of distribution is 6.3 L/kg in humans. Human plasma protein binding of risedronate is about 24%. Preclinical studies in rats and dogs dosed intravenously with single doses of 14C-risedronate indicate that 40 to 45% of the dose was distributed in the bone after 72 hours. At the same time, risedronate levels in soft tissues of rats and dogs were at least 40 and 16 times lower than those in bone, respectively. The remainder of the dose was mainly excreted in the urine. This is likely to be considerably lower in humans who excrete 65% of an intravenously administered dose in the urine in 24 hours. After multiple oral dosing in rats, accumulation of risedronate was observed in bone but not in soft tissues.

Metabolism.

There is no evidence of systemic metabolism of risedronate.

Excretion.

Approximately half the absorbed dose is excreted in the urine within 24 hours. 85% of an intravenous dose is recovered in the urine over 28 days. Mean renal clearance is 105 mL/min and mean total clearance is 122 mL/min. The difference primarily reflects nonrenal clearance or clearance due to adsorption to bone. The renal clearance is not concentration dependent and there is a linear relationship between renal clearance and creatinine clearance. In the same pharmacokinetic study mentioned (see Section 5.2 Pharmacokinetic Properties, Absorption), the percent of dose excreted in urine was measured. The point estimate for the 35 mg versus 5 mg doses was 66.8% (95% CI, 48.0 to 95.8). Although this was statistically significantly different, the clinical relevance is unknown.
Unabsorbed risedronate is eliminated unchanged in the faeces.
Following absorption, the serum concentration time profile is multiphasic with an initial half-life of about 1.5 hours and a terminal exponential half-life of 480 hours. Although the elimination rate from human bone is unknown, the 480 hour half-life is hypothesised to represent the dissociation of risedronate from the surface of the bone.

Special population.

Paediatric.

Safety and efficacy of risedronate have not been established in patients under 18 years of age.

Gender.

Bioavailability and pharmacokinetics following oral administration are similar in men and women.

Geriatric.

Risedronate pharmacokinetics are similar in older subjects (age 45 to 76 years) with normal renal function (creatinine clearance 80 to 120 mL/min) to that observed in young subjects (age 18 to 45 years). No dosage adjustment is necessary (see Section 4.2 Dose and Method of Administration).

Ethnicity.

Pharmacokinetic differences due to ethnicity have not been studied.

Renal insufficiency.

Risedronate is excreted intact primarily via the kidney. There is limited clinical data in patients with severe renal impairment (creatinine clearance < 30 mL/min) and, therefore, risedronate is not recommended for this patient group.
No dosage adjustment is necessary in patients with a creatinine clearance ≥ 30 mL/min.

Hepatic insufficiency.

No studies have been performed to assess the safety or efficacy of risedronate in patients with hepatic impairment. Risedronate is not metabolised in rat, dog and human liver preparations. Insignificant amounts (< 0.1% of intravenous dose) of risedronate are excreted in the bile in rats. Therefore, dosage adjustment is unlikely to be needed in patients with hepatic impairment.

5.3 Preclinical Safety Data

Genotoxicity.

Risedronate did not cause gene mutations in bacterial or mammalian cells in vitro, nor did it cause DNA damage in rat hepatocytes in vitro. In clastogenicity assays, risedronate was positive in an in vitro assay using Chinese hamster ovary cells at cytotoxic concentrations (7 to 18% cell survival), but there was no evidence of chromosomal damage when the assay was repeated at concentrations leading to 48 to 74% cell survival. Risedronate was negative at oral doses up to 1,336 mg/kg in an in vivo assay (chromosomal aberrations in rat bone marrow).

Carcinogenicity.

No evidence of carcinogenicity was observed in either rats (treated for 104 weeks with up to 24 mg/kg/day) or mice (treated for 80 weeks with up to 32 mg/kg/day). Systemic exposure (serum AUC 0-24 hours) at the high dose in rats was 160 times greater than that in humans dosed at 30 mg/day. Systemic exposure was not assessed in mice, but the highest dose in the carcinogenicity study was at least 30 times higher than the dose required for pharmacological effects on bone. Thus, risedronate sodium appears to have no carcinogenic potential at therapeutic dose levels.

4 Clinical Particulars

4.1 Therapeutic Indications

Risedro Once A Week 35 mg tablets are indicated for the:
Treatment of osteoporosis.
Treatment of glucocorticoid induced osteoporosis.
Preservation of bone mineral density in patients on long-term corticosteroid therapy.

4.3 Contraindications

Known hypersensitivity to the active substance or any of the excipients listed, see Section 6.1 List of Excipients.
Hypocalcaemia (see Section 4.4 Special Warnings and Precautions for Use).
Inability to stand or sit upright for at least 30 minutes.

4.4 Special Warnings and Precautions for Use

General.

Food, certain medications containing polyvalent cations (such as calcium, magnesium, iron and aluminium) and beverages (except plain water) can interfere with the absorption of bisphosphonates and should not be taken at the same time as Risedro Once A Week uncoated tablet.
Bisphosphonates have been associated with oesophagitis, gastritis, oesophageal ulcerations and gastroduodenal ulcerations. Thus, caution should be used:
In patients who have a history of oesophageal disorders which delay oesophageal transit or emptying e.g. stricture or achalasia.
In patients who are unable to stay in the upright position for at least 30 minutes after taking the tablet.
If risedronate sodium is given to patients with active or recent oesophageal or upper gastrointestinal problems (including known Barrett's oesophagus).
For patients to gain maximum benefit, doctors must stress the importance of taking Risedro Once A Week as per the dosage instructions (see Section 4.2 Dose and Method of Administration). This is especially important in the case of patients with a history of oesophageal disorders.
Hypocalcaemia must be corrected before starting risedronate sodium therapy.
Bone and mineral metabolism dysfunction (e.g. vitamin D deficiency and parathyroid abnormalities) should be effectively treated before starting risedronate therapy.
Patients should receive supplemental calcium and vitamin D if dietary intake is inadequate.

Gastrointestinal.

Risedronate sodium, like other bisphosphonates, may cause local irritation of the upper GI mucosa. Since some bisphosphonates have been associated with oesophagitis and oesophageal ulcerations, and gastroduodenal ulceration doctors should, therefore, be alert to any signs or symptoms signalling a possible oesophageal reaction, especially in patients with a history of upper GI disease or who are using NSAIDs or aspirin concomitantly. Doctors should be particularly careful to emphasise the importance of taking Risedronate sodium as per the dosage instructions to patients who have a history of oesophageal disorders.
There is very little experience with risedronate in patients with inflammatory bowel disease.

Osteonecrosis of the jaw.

Osteonecrosis of the jaw generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.
A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids and poor oral hygiene).
While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgment of the treating doctor should guide the management plan of each patient based on individual benefit/ risk assessment.

Osteonecrosis of the external auditory canal.

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

Atypical stress fractures.

A small number of patients on long-term bisphosphonate therapy (usually longer than three years), mostly in connection with the use of alendronate have developed stress fractures of the proximal femoral shaft (also known as insufficiency or atypical fractures), some of which occurred in the absence of apparent trauma. Some of these patients experienced prodromal pain in the affected area, often associated with imaging features of stress fracture, weeks to months before a complete fracture occurred.
Approximately one third of these fractures were bilateral; therefore, the contralateral femur should be examined in patients who have sustained a femoral shaft stress fracture. The number of reported cases of this condition is very low (some 40 reported cases world-wide in connection with alendronate as of 2009).
It is not known to what extent other agents of the aminobisphosphonate class, including Risedronate sodium, may be associated with this adverse event. Prior treatment with alendronate should be a cause for added vigilance. Patients with suspected stress fractures should be evaluated, including evaluation for known causes and risk factors (e.g. vitamin D deficiency, malabsorption, glucocorticoid use, previous stress fracture, lower extremity arthritis or fracture, extreme or increased exercise, diabetes mellitus, chronic alcohol abuse), and receive appropriate orthopaedic care.
During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.
Discontinuation of bisphosphonate therapy in patients with stress fractures is advisable pending evaluation of the patient, based on individual benefit/risk assessment. Causality has not been excluded in regard to bisphosphonate use and stress fractures.

Osteomalacia.

The potential for risedronate to induce osteomalacia was investigated in the Schenk rat assay. This assay is based on histological examination of the epiphyses of the growing rats after drug treatment. Risedronate did not interfere with bone mineralisation even at the highest dose tested (5 mg/kg/day, subcutaneously) which was > 3,000 times the lowest antiresorptive dose (1.5 microgram/kg/day). These data indicate that risedronate administered at therapeutic doses is unlikely to induce osteomalacia.

Use in hepatic impairment.

See Section 5.2 Pharmacokinetic Properties, Special population, Hepatic insufficiency.

Use in renal impairment.

Risedronate sodium is not recommended for use in patients with severe renal impairment (creatinine clearance < 30 mL/minute). See Section 5.2 Pharmacokinetic Properties, Special population, Renal insufficiency; Section 4.2 Dose and Method of Administration, Renal impairment.

Use in the elderly.

Of the patients receiving Risedronate sodium in postmenopausal osteoporosis studies, 59% were 65 and over, while 13% were 75 and over. No overall differences in safety or efficacy were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out and also see Section 4.2 Dose and Method of Administration, Use in the elderly.

Paediatric use.

See Section 5.2 Pharmacokinetic Properties, Special population, Paediatric use; Section 4.2 Dose and Method of Administration, Use in children.

Effects on laboratory tests.

Bisphosphonates are known to interfere with the use of bone imaging agents. However, specific studies with risedronate have not been performed.
Small asymptomatic decreases in serum calcium and phosphorus levels have been observed in some patients.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No specific drug interactions studies have been performed. However, risedronate is not systemically metabolised, does not induce or inhibit hepatic microsomal drug metabolising enzymes (cytochrome P450) and has low protein binding.
Concomitant intake of medications containing polyvalent cations (e.g. calcium, magnesium, iron, aluminium, antacids) will interfere with the absorption of risedronate and should be taken at a different time of the day.
Risedronate may be used concomitantly with hormone replacement therapy or the contraceptive pill.
During clinical trials, patients were exposed to a wide variety of commonly used concomitant medication while taking risedronate. No clinically relevant interactions were noted. The medications included NSAIDs, aspirin, H2-blockers, proton pump inhibitors, antacids, calcium channel blockers, beta-blockers, thiazides, glucocorticoids, anticoagulants, anticonvulsants and cardiac glycosides. There are no clinical data concerning the concomitant medication with two or more bisphosphonates and such concomitant medication is not recommended.
In the phase III postmenopausal trials with 5 mg daily dosing, 29 and 37% of patients used aspirin and NSAIDs respectively. The incidence of upper GI adverse events in risedronate patients (aspirin/ NSAIDs taken greater than or equal to 3 days/week) was similar to that in placebo treated patients. In the phase III Once a Week study, 57 and 40% of patients used aspirin and NSAIDs respectively.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A fertility study in male and female rats showed no adverse effects at oral doses up to 16 mg/kg/day, corresponding to systemic exposure (serum AUC 0-24 hours) about 30 times higher than that in humans dosed at 30 mg/day. At higher dose levels, systemic toxicity, testicular atrophy and reduced fertility were seen in male rats, but these effects are unlikely to have clinical relevance.
(Category B3)
Risedronate has not been studied in pregnant women. It should only be used during pregnancy if the potential benefit justifies the potential risk to mother and fetus. If administration during pregnancy is contemplated, serum calcium levels should be monitored and calcium supplementation (with vitamin D to aid calcium absorption) provided in late gestation. Animal studies suggest that periparturient maternal hypocalcaemia and fetal ossification effects may occur.
Animal studies have shown that risedronate sodium crosses the placenta to a minimal extent in rats. The drug had no teratogenic activity in rats or rabbits at oral doses up to 80 and 10 mg/kg/day respectively. However, suppression of fetal growth and retardation of ossification were observed at the highest dose level in rats. When administered to rats during late gestation, maternal deaths and parturition failure were observed at oral dose levels greater than 2 mg/kg/day. These effects were probably secondary to maternal hypocalcaemia. Systemic exposure (AUC 0-24 hours) at the no-effect level in rats was similar to that in patients with Paget's disease, and about six times higher than that in patients with corticosteroid induced osteoporosis. Systemic exposure in rabbits was not measured.
 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. Due to the potential for serious adverse reactions in breastfed infants from bisphosphonates, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother.
As with other bisphosphonates in preclinical models, fetuses from risedronate treated dams showed ossification changes in sternebrae and/or skull at doses as low as 3.2 mg/kg/day. This is equivalent to the human 30 mg dose and six times the human 5 mg dose based on surface area, mg/m2. Treatment with risedronate during mating and gestation with doses of 3.2 mg/kg/day has resulted in periparturient hypocalcaemia and mortality in rats allowed to deliver.

4.8 Adverse Effects (Undesirable Effects)

Osteoporosis - 5 mg daily dosing.

The phase IIIA clinical trials were designed to include patients with a history of upper gastrointestinal (GI) disorder. Patients were permitted concomitant use of NSAIDs and aspirin. In these patients the incidence of upper GI adverse reactions in the risedronate group was similar to that in the placebo control group.
Abdominal and musculoskeletal pain were commonly reported (1 to 10%). Glossitis, iritis and duodenitis were reported uncommonly (0.1% to 1%). There were rare reports (< 0.1%) of abnormal liver function tests.

Laboratory test findings.

Asymptomatic, small decreases in serum calcium and phosphorus levels have been observed in some patients.
Risedronate has been studied for up to three years in over 5,000 women enrolled in phase III clinical trials for treatment or prevention of postmenopausal osteoporosis. Most adverse events reported in these trials were either mild or moderate in severity, and did not lead to discontinuation from the study. The incidence of serious adverse events in the placebo group was 24.9% and in the risedronate group 26.3%. The percentage of patients who withdrew from the study due to adverse events was 14.4 and 13.5% for the placebo and risedronate groups respectively.
Table 1 lists adverse events reported in ≥ 5% of risedronate treated patients and at an incidence higher than in the placebo group in phase III postmenopausal osteoporosis trials. Adverse events are shown without attribution of causality.

Endoscopic findings.

Risedronate clinical studies enrolled over 5,000 postmenopausal women and included patients with pre-existing gastrointestinal disease and concomitant use of NSAIDs or aspirin. Investigators were encouraged to perform endoscopies in any patients with moderate to severe gastrointestinal complaints while maintaining the blind. These endoscopies were ultimately performed on equal numbers of patients between the treated and placebo groups (75 (11.9%) risedronate; 75 (14.5%) placebo). Across treatment groups, the percentage of patients with normal oesophageal, gastric and duodenal mucosa on endoscopy was similar (20% placebo and 21% risedronate). Positive findings on endoscopy were also generally comparable across treatment groups (58 (82.9%) placebo and 57 (81.4%) risedronate).

Gastrointestinal adverse events.

There was a higher number of reports of mild duodenitis in the risedronate group (11 (15.7%); placebo 7 (10%)), however, there were more duodenal ulcers in the placebo group (33 (47.1%); risedronate (26 (37.1%)). The number of patients who had positive findings and withdrew from the studies was similar across treatment groups (placebo 26 (37.1%) and risedronate 27 (38.6%)) and there was no evidence of treatment related oesophageal, gastric or duodenal ulcers/ erosions.
Risedronate has been studied in phase III corticosteroid induced osteoporosis trials enrolling more than 500 patients. The adverse event profile in this population was similar to that seen in postmenopausal osteoporosis trials, except for musculoskeletal events, which were reported by > 10% of patients and occurred at a greater frequency in the risedronate 5 mg treatment group (75 (43.1%)) compared to the placebo group (57 (33.5%)). The adverse experiences reported (165 placebo and 167 risedronate) have usually been mild or moderate and generally have not required discontinuation of treatment. The occurrence of adverse events does not appear to be related to patient age, gender or race.

Osteoporosis - 35 mg once a week dosing.

In a one year, double blind multicentre study comparing 5 mg risedronate daily and 35 mg risedronate once a week in postmenopausal women with osteoporosis, the overall safety and tolerability profiles were similar. Table 2 lists the adverse events in greater than or equal to 5% of patients from this trial. Events are shown without attribution of causality.
In a two year study in men with osteoporosis, the overall safety and tolerability were similar between the treatment and the placebo groups. Adverse experiences were consistent with those previously observed in women.

Risedronate postmarketing data.

The following additional adverse reactions have been very rarely reported during postmarketing use.

Eye disorders.

Iritis, uveitis.

Musculoskeletal and connective tissue disorders.

Osteonecrosis of the jaw.

Skin and subcutaneous tissue disorders.

Hypersensitivity and skin reactions, including angioedema, generalised rash and bulbous skin reactions, some severe.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Risedro Once A Week must only be taken with plain water. Please note that some mineral waters or water from regional areas may have a higher concentration of calcium and therefore should not be used.
Risedro Once A Week must be taken 30 minutes before the first food or drink other than water. To facilitate delivery to the stomach, it should be taken in an upright position and the patient should avoid lying down for 30 minutes.
Patients should not chew or suck on the tablet because of the potential for oropharyngeal irritation.

Osteoporosis.

The recommended dose is 35 mg once a week, taken on the same day each week.

Use in the elderly.

No dose adjustment is necessary.

Renal impairment.

No dose adjustment is necessary in patients with mild to moderate renal insufficiency (creatinine clearance 30 to 60 mL/minute). Risedronate is not recommended in patients with severe renal impairment (creatinine clearance < 30 mL/minute) due to limited clinical data.

Use in children.

Safety and efficacy of risedronate has not been established in patients under 18 years of age.

Compatibility with other drugs.

Calcium, antacids, aluminium and some oral medications will interfere with the absorption of risedronate and therefore should be taken at a different time of the day.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Signs and symptoms.

No specific information is available on the treatment of overdose with risedronate. Decreases in serum calcium following substantial overdose may be expected in some patients. Signs and symptoms of hypocalcaemia may also occur in some of these patients. Administration of milk or antacids (containing magnesium, calcium or aluminium) to chelate risedronate may be helpful.
Standard procedures that are effective for treating hypocalcaemia, including the administration of calcium intravenously, would be expected to restore physiological amounts of ionised calcium and to relieve signs and symptoms of hypocalcaemia.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the following excipients: microcrystalline cellulose, sorbitol, colloidal anhydrous silica, croscarmellose sodium and sodium stearylfumarate. The tablets are gluten free.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store the tablets below 25°C.

6.5 Nature and Contents of Container

Available in blister packs (PVC/PVDC/Al) of 4 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes