[PDF] 160238 ACTONEL PLUS CALCIUM APM

160238 ACTONEL PLUS CALCIUM APM

Geriatrics: Of the patients receiving ACTONEL (risedronate) 5 mg daily in postmenopausal osteoporosis studies (see CLINICAL TRIALS), 43 were between 65 and 75 years of age, and 20 were over 75 In the 1-year study comparing daily versus weekly oral dosing regimens of ACTONEL in postmenopausal women, 41 of patients receiving ACTONEL 35 mg Once-a-

ACTIVATE Study Synopsis short1 - Sanofi

Actonel 5 mg bottle at least once as documented by the electronic cap Incidence tables were provided for this population for adverse events for all and possibly related treatment-emergent adverse events (TEAE), by system organ class, frequency, intensity, and type of event (eg, deaths, serious adverse events, withdrawals)

List of nationally authorised medicinal products

Actonel Combi D 35 mg + 1000 mg / 880 IU filmom obložene tablete + šumeće granule not available : UP/I-530-09/13-02/180 ACTAVIS GROUP PTC EHF HR Actonel 35 mg filmom obložene tablete : not available HR-H-350046678 : ACTAVIS GROUP PTC EHF HR : Actonel 35 mg filmtabletta SE/H/0192/003 : OGYI-T- 8738/01 ACTAVIS GROUP PTC EHF HU

Volume 22, Number 5 May 2008 Drugs & Therapy

Risedronate (Actonel® by Proctor & Gamble)‡‡ ‡‡Patients cannot use their home meds Risedronate with Calcium (Actonel® with Calcium by Proctor & Gamble)‡‡ ‡‡Patients cannot use their home meds Tiludronate (Skelid® by Sanofi-Synthelabo) Zoledronic Acid Injection 5 mg (Reclast® by Novartis) effects is minimized by the correct

Product Monograph Brand Safety Updates May 2017

Actonel, Actonel DR 200428 Risedronate Sodium Warner Chilcott Canada Co N/A √ N/A N/A N/A N/A N/A √ Advil Tablets, Advil Caplets, Advil Gel Caplets, Advil Extra Strength Caplets, Advil Muscle and Joint, Advil 12 Hour 203345 Ibuprofen Pfizer Consumer Healthcare A Division of Pfizer Canada Inc N/A N/A N/A N/A N/A N/A N/A √

Issue Brief: Value-based pricing for pharmaceuticals

Sanofi-Aventis) agreed to reimburse Health Alliance for medical costs of treating covered non-spinal, osteoporosis-related fractures in post-menopausal, Health Alliance eligible female members correctly taking Actonel prior to the fracture (maximum number per 1,000 us-

United States Court of Appeals for the Federal Circuit

osteoporosis drug Actonel® In August 2004, P&G sued Teva for infringement of the ’122 patent after Teva notified P&G that it planned to market risedronate as a generic equivalent of Actonel® Specifically, P&G alleged that Teva’s proposed drug infringed claim 4 of the ’122 patent for the compound risedronate, claim 16 for pharmaceutical

Dental management of patients receiving oral bisphosphonate

Actonel Boniva Didronel Fosamax Fosamax Plus D Skelid Aredia Bonefos Zometa Procter & Gamble Pharmaceuticals, Cincinnati/sanofi-aventis Group, New York Roche Pharmaceuticals, Basel, Switzerland/ GlaxoSmithKline, Philadelphia Procter & Gamble Pharmaceuticals Merck & Co , Whitehouse Station, N J Merck & Co sanofi-aventis Group Novartis, East

BISPHOSPHONATE-ASSOCIATEDOSTEOMYELITISOFTHEJAW

dronate,risedronate,andibandronate,arethemostfre- Risedronate Procter&Gamble Actonel Zoledronicacid Novartis Zometa Tiludronateb sanofi-aventis Skelid Clodronateb ScheringAG Bonefos

[PDF] Avis de transparence Forsteo, tériparatide, septembre - Lilly France

[PDF] Actonel et Actonel DR (risédronate) - Sanofi Canada

[PDF] MODE DE SOUSCRIPTION A « ONEF-JOB »

[PDF] communique du conseil des ministres du jeudi 13 juillet 2017

[PDF] Actualité 2016-2017 - Decitre

[PDF] l 'actualite du relais assistantes maternelles - Artigues-Près-Bordeaux

[PDF] ACUERDO 122 DE 2004 (Junio 28) Reglamentado por el Decreto

[PDF] Édito - ADA FRANCE

[PDF] STANDARDS OF MEDICAL CARE IN DIABETES #8212 2017

[PDF] STANDARDS OF MEDICAL CARE IN DIABETES #8212 2017

[PDF] West Ada School District 2017-2018 Traditional Student Calendar

[PDF] STANDARDS OF MEDICAL CARE IN DIABETES #8212 2017

[PDF] CODE DE COMMERCE

[PDF] La Main invisible d-Adam Smithpdf - Université Paris 1 Panthéon

[PDF] Adam Smith : richesse des nations / Courcelle-Seneuil - Gallica - BnF

PRODUCT MONOGRAPH

Pr

ACTONEL PLUS CALCIUM

Risedronate Sodium (as the hemi-pentahydrate) 35 mg Tablets USP

Bone Metabolism Regulator

and

Calcium Carbonate 1250 mg Tablets

USP

Mineral Supplement

Warner Chilcott Canada Co.

PO Box 4367, Station A

Toronto, ON

M5W 3N7

Marketed with sanofi-aventis Canada Inc.

Laval, QC H7L 4A8

Date of Revision:

February 19, 2013

Submission Control No: 160238

2

Table of Contents

Page PART I: HEALTH PROFESSIONAL INFORMATION .........................................................3

SUMMARY PRODUCT INFORMATION ............................................................................3

INDICATIONS AND CLINICAL USE ..................................................................................3

CONTRAINDICATIONS .......................................................................................................4

WARNINGS AND PRECAUTIONS ......................................................................................4

ADVERSE REACTIONS ........................................................................................................7

DRUG INTERACTIONS ......................................................................................................10

DOSAGE AND ADMINISTRATION ..................................................................................13

OVERDOSAGE .....................................................................................................................14

ACTION AND CLINICAL PHARMACOLOGY.................................................................15

STORAGE AND STABILITY ..............................................................................................19

DOSAGE FORMS, COMPOSITION AND PACKAGING .................................................19

PART II: SCIENTIFIC INFORMATION ...............................................................................20

PHARMACEUTICAL INFORMATION ..............................................................................20

CLINICAL TRIALS ..............................................................................................................22

DETAILED PHARMACOLOGY .........................................................................................28

TOXICOLOGY .....................................................................................................................28

REFERENCES .......................................................................................................................31

PART III: CONSUMER INFORMATION ..............................................................................34

3

ACTONEL PLUS CALCIUM

Risedronate Sodium (as the hemi-pentahydrate) 35 mg tablets and

Calcium Carbonate 1250 mg tablets

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of

Administration

Component of

Combination

Pack

Dosage Form/

Strength

Clinically Relevant Nonmedicinal

Ingredients

Oral ACTONEL

Once-a-Week

(risedronate sodium)

Tablet, 35 mg Lactose monohydrate

For a complete listing see Dosage

Forms, Composition and

Packaging Section.

Oral Calcium

carbonate

Tablet, 1250 mg;

elemental calcium 500 mg

For a complete listing see Dosage

Forms, Composition and

Packaging Section.

INDICATIONS AND CLINICAL USE

The ACTONEL (risedronate sodium) component of ACTONEL PLUS CALCIUM is indicated for the treatment and prevention of osteoporosis in postmenopausal women Treatment of Postmenopausal Osteoporosis: In postmenopausal women with osteoporosis, ACTONEL prevents vertebral and nonvertebral osteoporosis-related fractures and increases bone mineral density (BMD) at all measured skeletal sites of clinical importance for osteoporotic fractures, including spine, hip, and wrist. 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 Postmenopausal Osteoporosis: In postmenopausal patients at risk of developing osteoporosis, ACTONEL preserves or increases BMD at sites of clinical importance for 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 (particularly maternal history), previous fracture, smoking, moderately low BMD, high bone turnover, thin body frame, Caucasian or Asian race, 4 and early menopause are associated with an increased risk of developing osteoporosis and fractures. The calcium component of ACTONEL PLUS CALCIUM contains calcium carbonate which is a calcium supplement to dietary intake of calcium. The optimal duration of use has not been determined. Patients should have the need for continued therapy re-evaluated on a periodic basis. Geriatrics: Of the patients receiving ACTONEL (risedronate) 5 mg daily in postmenopausal osteoporosis studies (see CLINICAL TRIALS), 43% were between 65 and 75 years of age, and

20% were over 75. In the 1-year study comparing daily versus weekly oral dosing regimens of

ACTONEL in postmenopausal women, 41% of patients receiving ACTONEL 35 mg Once-a- Week were between 65 and 75 years of age and 23% were over 75. Based upon the above study populations, no overall differences in efficacy or safety were observed between these patients and younger patients (< 65 years). Pediatrics: Safety and efficacy of risedronate in children and growing adolescents have not been established. Important Limitations of Use: The optimal duration of use has not been determined. Patients should have the need for continued therapy re-evaluated on a periodic basis (see

DOSAGE AND ADMINISTRATION).

CONTRAINDICATIONS

Patients who are hypersensitive to ACTONEL PLUS CALCIUM or to any ingredients in the formulation. For a complete listing, see DOSAGE FORMS, COMPOSITION AND

PACKAGING.

ACTONEL

Hypocalcemia (see WARNINGS AND PRECAUTIONS, General)

Calcium

Hypercalcemia from any cause including, but not limited to, hyperparathyroidism, hypercalcemia of malignancy, or sarcoidosis.

WARNINGS AND PRECAUTIONS

General

Before commencing ACTONEL PLUS CALCIUM, patients' calcium requirements should be assessed. It is recommended that patients receive at least 1200-1500 mg per day of calcium from all sources, as well as a daily vitamin D intake of at least 400-800 IU. The calcium carbonate 5 tablet in ACTONEL PLUS CALCIUM provides 500 mg elemental calcium per day and does not contain vitamin D. Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting ACTONEL PLUS CALCIUM combination pack therapy.

Osteonecrosis of the Jaw

In post-marketing reporting, osteonecrosis of the jaw has been reported in patients treated with bisphosphonates. The majority of reports occurred following dental procedures such as tooth extractions; and have involved cancer patients treated with intravenous bisphosphonates, but some occurred in patients receiving oral treatment for postmenopausal osteoporosis and other diagnoses. Many had signs of local infection, including osteomyelitis. Osteonecrosis has other

well documented multiple risk factors. It is not possible to determine if these events are related to

bisphosphonates, to concomitant drugs or other therapies, to the patient's underlying disease or to other co-morbid risk factors (e.g. anemia, infection, pre-existing oral disease). A dental examination with appropriate preventative dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, immune suppression, head and neck radiotherapy or poor oral hygiene). While on treatment, these patients should avoid invasive dental procedures if possible. 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, based on individual risk assessment, should guide the management of patients undergoing dental procedures. Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Atypical femur fractures most commonly occur with minimal or no impact trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. Poor healing of these fractures was also reported. Any patient with a history of bisphosphonate exposure who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical fracture should also be assessed for symptoms and signs of fracture in the contra-lateral limb. Interruption of bisphosphonate therapy should be considered, pending a risk/benefit assessment. Although causality has not been established, the role of bisphosphonates cannot be ruled out Concomitant use of calcium-containing antacids should be monitored to avoid excessive intake of calcium. Total daily intake of calcium above 1500 mg has not demonstrated additional bone benefits, however daily intake above 2000 mg has been associated with increased risk of adverse effects, including hypercalcemia and kidney stones. 6

Gastrointestinal

Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis, esophageal ulcer, and gastric ulcer (see ADVERSE REACTIONS). Since some bisphosphonates have been associated with esophagitis and esophageal ulcerations, to facilitate delivery to the stomach and minimize the risk of these events, patients should take the ACTONEL tablet while in an upright position (i.e., sitting or standing) and with sufficient plain water (>120 mL). Patients should not lie down for at least 30 minutes after taking the drug. Health professionals should be particularly careful to emphasize the importance of the dosing instructions to patients with a history of esophageal disorders (e.g., inflammation, stricture, ulcer, or disorders of motility). Patients with achlorhydria may have decreased absorption of calcium that may be attenuated by taking calcium with food. Taking calcium with food enhances absorption. See DOSAGE AND

ADMINISTRATION.

Musculoskeletal: In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported 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 the medication. A subset of patients had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate. Consider discontinuing use if severe symptoms develop.

Ophthalmologic:

Ocular disturbances including conjunctivitis, uveitis, episcleritis, iritis, and scleritis have been reported with Actonel therapy. Patients with ocular events other than uncomplicated conjunctivitis should be referred to an ophthalmologist for evaluation. If ocular inflammatory symptoms are observed, treatment may have to be discontinued. Renal The ACTONEL component of ACTONEL PLUS CALCIUM is not recommended for use in patients with severe renal impairment (creatinine clearance < 30 mL/min). Administration of calcium has been associated with a slight increase in the risk of kidney stones. In patients with a history of kidney stones or hypercalciuria, metabolic assessment to seek treatable causes of these conditions is warranted. If administration of calcium tablets should be needed in these patients, urinary calcium excretion and other appropriate testing should be monitored periodically.

Special Populations

Pediatrics: The safety and efficacy of ACTONEL in children and growing adolescents have not been established. Pregnant Women: ACTONEL PLUS CALCIUM is not intended for use during pregnancy. There are no studies of ACTONEL PLUS CALCIUM in pregnant women. Calcium crosses the placenta, reaching higher levels in fetal blood than in maternal blood. 7 Nursing Women: ACTONEL PLUS CALCIUM is not intended for use with nursing mothers. It is not known whether risedronate is excreted in human milk. Risedronate was detected in feeding pups exposed to lactating rats for a 24-hour period post-dosing, indicating a small degree of lacteal transfer. Since 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.

Calcium is excreted in breast milk.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis, esophageal ulcer, and gastric ulcer. It is therefore important to follow the recommended dosing instructions (see DOSAGE AND ADMINISTRATION). Musculoskeletal pain, rarely severe, has been reported as a common side effect in patients who received the ACTONEL component of ACTONEL PLUS CALCIUM. In osteoporosis studies with ACTONEL, the most commonly reported adverse reactions were abdominal pain, dyspepsia and nausea. Most adverse events (AEs) reported in the Phase III trials with ACTONEL were mild or moderate in severity and did not generally lead to discontinuation of ACTONEL. Calcium carbonate may cause gastrointestinal adverse effects such as constipation, flatulence, nausea, abdominal pain, and bloating.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and approximate rates of occurrence. Treatment of Postmenopausal Osteoporosis: ACTONEL 5 mg daily has been studied for up to 3 years in over 5000 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 distribution of severe adverse events was similar across treatment groups. In addition, the overall incidence of AEs was found to be comparable amongst ACTONEL and placebo-treated patients. Table 1 lists adverse events considered possibly or probably drug related, reported in 1% of ACTONEL 5 mg daily-treated patients, in Phase III postmenopausal osteoporosis trials. 8 Discontinuation of therapy due to serious clinical adverse events occurred in 5.5 % of ACTONEL 5 mg daily-treated patients and 6.0% of patients treated with placebo.

Table 1

Drug-Related* Adverse Events Reported in 1% of ACTONEL 5 mg Daily-Treated Patients in Combined Phase III Postmenopausal Osteoporosis Trials

Adverse Event

ACTONEL 5 mg

N = 1742

Placebo Control

N = 1744

Body as a Whole

Abdominal Pain

Headache

Asthenia

4.1 2.5 1.0 3.3 2.3 0.7

Digestive System

Dyspepsia

Nausea

Constipation

Diarrhea

Flatulence

Gastritis

5.2 4.8 3.7 2.9 2.1 1.1 4.8 5.0 3.6 2.5 1.8 0.9

Skin and Appendages

Rash

Pruritus

1.4 1.0 0.9 0.5 * Considered to be possibly or probably causally related by clinical study Investigators. Once a Week Dosing: In the 1-year, double-blind, multicentre study comparing ACTONEL 35 mg Once-a-Week (the same formulation as the risedronate in ACTONEL PLUS CALCIUM) to ACTONEL 5 mg daily for the treatment of osteoporosis in postmenopausal women, the overall safety and tolerability profiles of the 2 oral dosing regimens were similar. Patients with active or a history of upper gastrointestinal disorders at baseline and those taking ASA, non-steroidal anti-inflammatory drugs (NSAIDs) or drugs traditionally used for the treatment of peptic ulcers were not specifically excluded from participating in the ACTONEL once-a-week dosing study. The proportion of patients who experienced an upper gastrointestinal adverse event and the pattern of those events were found to be similar between the ACTONEL

35 mg Once-a-Week and ACTONEL 5 mg daily-treated groups.

In the 1-year, double-blind, multicentre study comparing ACTONEL 35 mg Once-a-Week to placebo for the prevention of osteoporosis in postmenopausal women, the overall safety and tolerability profiles of the two groups were comparable with the exception of "arthralgia". Specifically, 13.9% of patients taking ACTONEL 35 mg Once-a-Week experienced arthralgia compared to 7.8% of placebo patients. The overall safety profile observed in this study showed no substantive difference from that observed in the ACTONEL 5 mg daily versus ACTONEL 35 mg Once-a-Week treatment study 9 Endoscopic Findings: ACTONEL 5 mg daily clinical studies enrolled over 5700 patients for the treatment and prevention of postmenopausal and glucocorticoid-induced osteoporosis, many with pre-existing gastrointestinal disease and concomitant use of NSAIDs or ASA. 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 ACTONEL; 75 placebo). Across treatment groups, the percentage of patients with normal esophageal, gastric, and duodenal mucosa on endoscopy was similar (21% ACTONEL; 20% placebo). Positive findings on endoscopy were also generally comparable across treatment groups. There were a higherquotesdbs_dbs22.pdfusesText_28