Risedronate (Actonel) is an orally available bisphosphonate that is used to increase bony matrix and prevent bone loss. It is indicated for the treatment of osteoporosis in postmenopausal women, men on androgen deprivation therapy, individuals on glucocorticoids (daily doses exceeding 7.5 per day), and paget's disease. see Glucocorticoid-induced Osteoporosis Treatment Guidelines

Risedronate (Actonel) Uses:

• Actonel:

  • Osteoporosis:
    • Treatment and prevention of osteoporosis in postmenopausal women.
    • Treatment of osteoporosis in men.
    • Treatment and prevention of glucocorticoid-induced osteoporosis (daily dosage of ≥7.5 mg prednisone or equivalent)
  • Paget disease: Treatment of Paget disease of the bone

• Atelvia, Actonel DR [Canadian product]:

  • Osteoporosis: Treatment of osteoporosis in postmenopausal women

• Off Label Use of Risedronate in Adults:

  • For the prevention of bone loss associated with androgen deprivation therapy in prostate cancer.

Risedronate (Actonel) Dose in Adults:

Note:

• The optimal duration of osteoporosis treatment has not been determined.
• In postmenopausal women with low fracture risk, consider a drug holiday after 5 years of oral bisphosphonate therapy however in postmenopausal women who remain at high fracture risk, consider extending treatment for up to 10 years.
• Although evidence is limited, these recommendations may be considered in older men.
• Patients should receive supplemental calcium and vitamin D if dietary intake is not adequate.

Risedronate (Actonel) Dose in the treatment of Osteoporosis (postmenopausal): Oral:

• Immediate-release tablet:

  • Prevention and treatment:
    • 5 mg once daily or 35 mg once weekly or 150 mg once monthly

• Delayed-release tablet:

  • Treatment:
    • 35 mg once weekly

Risedronate (Actonel) Dose in the treatment of Osteoporosis (males): Oral:

• Immediate-release tablet:

  • 35 mg once weekly

Risedronate (Actonel) Dose in the prevention and treatment of glucocorticoid-induced osteoporosis: Oral:

• Immediate-release tablet:

  • 5 mg once daily.

Risedronate (Actonel) Dose in the treatment of Paget disease of bone: Oral:

• Immediate-release tablet:

  • 30 mg once daily for 2 months

Note:

• Re-treatment may be considered (following posttreatment observation of at least 2 months) if relapse occurs, or if treatment fails to normalize serum alkaline phosphatase.
• For re-treatment, the dose and duration of therapy are the same as for initial treatment. Retreatment may be required between 1 and 5 years.

• Missed doses:

  • Immediate-release tablet:

    • Once-weekly:
      • If a once-weekly dose is missed, it should be given the next morning;
      • The dose may then be continued as per the original once-weekly schedule (original scheduled day of the week), however, do not administer 2 doses on the same day.
    • Monthly (150 mg once monthly):
      • If 150 mg once-monthly dose is missed, it should be given the next morning after remembered if the next month's scheduled dose is more than 7 days away.
      • If the next month's scheduled dose is within 7 days, wait until the next month's scheduled dose.
      • For either scenario, may then continue with the original monthly schedule (original scheduled day of the month).
      • Do not administer >150 mg within 7 days.

Risedronate (Actonel) Dose in the prevention of bone loss associated with androgen deprivation therapy in prostate cancer (off-label):

• Oral: 35 mg once weekly.

Dose in Children:

Not indicated.

Pregnancy Risk Factor C

• Some animal reproduction studies showed adverse events.
• Although it is not clear if bisphosphonates cross into the placenta or not, it is possible that fetal exposure may occur.
• Bisphosphonates are integrated into bone matrix and slowly released over time.
• The dose and duration of therapy will determine how much is available in the systemic circulation.
• Theoretically, there could be a risk to fetal harm if therapy is completed during pregnancy. However, data available do not support this claim.
• Bisphosphonate therapy should be stopped in women of reproductive potential immediately before the planned pregnancy. Premenopausal women should only use it in exceptional circumstances where rapid bone loss is taking place.
• Hypocalcemia has been reported in infants exposed to in utero bisphosphonate. Therefore, it is important that hypocalcemia be checked after birth.

Use of risedronate while breastfeeding

• It is unknown if breast milk contains risedronate.
• The manufacturer suggests that the mother decide whether to stop nursing her infant or discontinue using the drug. This is in consideration of the risk of serious adverse reactions.

Risedronate (Actonel) Dose in Kidney Disease:

• CrCl ≥30 mL/minute:
  • No dosage adjustment necessary.
• CrCl <30 mL/minute:
  • Use is not recommended

Dose in Liver disease:

• There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
• However, dosage adjustment not likely because risedronate is not metabolized by the liver.

Common Side Effects of Risedronate (Actonel):

• Cardiovascular:

  • Hypertension

• Central Nervous System:

  • Headache

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Gastrointestinal Disease
  • Diarrhea
  • Nausea
  • Abdominal Pain

• Genitourinary:

  • Urinary Tract Infection

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain

Less Common Side Effects Of Risedronate (Actonel):

• Cardiovascular:

  • Peripheral Edema
  • Chest Pain
  • Cardiac Arrhythmia

• Central Nervous System:

  • Depression
  • Dizziness

• Endocrine & Metabolic:

  • Increased Parathyroid Hormone
  • Hypocalcemia
  • Hypophosphatemia

• Gastrointestinal:

  • Dyspepsia
  • Constipation
  • Vomiting
  • Gastritis
  • Gastroesophageal Reflux Disease
  • Duodenitis
  • Glossitis

• Genitourinary:

  • Benign Prostatic Hyperplasia
  • Nephrolithiasis

• Hypersensitivity:

  • Acute Phase Reaction-Like Symptoms

• Infection:

  • Influenza

• Neuromuscular & Skeletal:

  • Arthropathy
  • Myalgia
  • Limb Pain
  • Musculoskeletal Pain
  • Muscle Spasm

• Ophthalmic:

  • Cataract

• Respiratory:

  • Flu-Like Symptoms
  • Pharyngitis
  • Rhinitis
  • Bronchitis
  • Upper Respiratory Tract Infection

Contraindications to Risedronate (Actonel):

• Hypersensitivity to risedronate and any component of the formula
• hypocalcemia;
• Inability to stand or sit straight for more than 30 minutes.
• Achalasia, stricture, and other abnormalities in the esophagus can delay emptying.

Warnings and precautions

• Bone fractures:

  • Patients who have taken bisphosphonates have had atypical femur fractures (AFF).
  • These fractures are the subtrochanteric and diaphyseal Femurs (the bones just below the hip joint), as well as the subtrochanteric and diaphyseal Femurs (the long segment in the thigh bone).
  • Prodromal pain can occur weeks or months before a fracture occurs.
  • These fractures may be caused by bisphosphonate therapy. However, atypical fractures of the femur have been seen in patients who do not take bisphosphonates and those who receive glucocorticoids.
  • Long-term bisphosphonate therapy for osteoporosis may increase the risk. However, the relative benefits of the therapy (when used to treat osteoporosis) usually outweigh the risk of AFF in the first five years.
  • A femur fracture should be considered for patients who present with groin or thigh pain and have had bisphosphonate treatment in the past.
  • Patients who have a fracture of the femoral shaft should be treated with bisphosphonate therapy. Also, check for fractures in the contralateral leg.

• Bone/ joint/ muscle pain:

  • Bisphosphonate treatment can sometimes cause severe, debilitating, or even fatal, bone, joint, and/or muscular pain.
  • The time it took to feel pain was anywhere from one day to several years.
  • Patients with severe symptoms should consider quitting therapy. Symptoms usually disappear once treatment is stopped.
  • Patients who have had recurrences with one bisphosphonate or another may experience them again.

• Irritation of the gastrointestinal mucosa

  • It can cause irritation of the upper gastrointestinal mucosa.
  • Patients who do not follow the dosing instructions may experience a higher risk of developing dysphagia, gastric ulcers, esophagitis or esophageal stricture.
  • Patients with dysphagia or esophageal diseases, gastritis, duodenitis, and ulcers should be cautious.
  • If you experience new or worsening symptoms, discontinue use.

• Osteonecrosis in the jaw:

  • Patients who have received bisphosphonates have been known to develop osteonecrosis (ONJ) or medication-induced osteonecrosis (MRONJ).
  • MRONJ is a condition that can be caused by invasive dental procedures, such as tooth extractions, dental implants, or boney surgery), and concomitant treatment (eg chemotherapy, corticosteroids. angiogenesis inhibitors), poor dental hygiene, ill fitting dentures, and other conditions (anemia.coagulopathy. infection.
  • Increased use of bisphosphonate may increase the risk.
  • According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonate and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy; risk of MRONJ is significantly more in cancer patients receiving antiresorptive therapy compared to patients receiving osteoporosis treatment (regardless of medication used or dosing schedule).
  • MRONJ risk is also higher with IV antiresorptive treatment than with oral bisphosphonate therapy. However, the risk seems to rise with oral bisphosphonate therapy if the treatment lasts more than 4 years.
  • According to the manufacturer's labeling, patients who require invasive dental procedures may need to discontinue bisphosphonates. Clinical judgment should be used to guide this decision.
  • The AAOMS says that there is no evidence to suggest that stopping oral bisphosphonate treatment increases the risk of ONJ after a tooth is extracted. It also suggests that patients who have been receiving oral bisphosphonate for less than 4 years and have not developed any clinical risk factors should undergo no delay or alternations in any procedure. This is especially true for patients who are receiving dental implants.
  • However, patients who have been receiving oral bisphosphonates more than 4years or patients who have taken antiangiogenic or corticosteroids concomitantly should be given a 2-month drug-free period. This recommendation is based on theoretical benefits. Patients with ONJ that develop during therapy should be seen by an oral surgeon.
  • According to the manufacturer of the bisphosphonate treatment, patients with ONJ should consider discontinuing it (based on the risk/benefit analysis).

• Bariatric surgery

  • Risk of altered absorption or ulceration:
    • Avoid taking oral bisphosphates following bariatric surgery. Inadequate oral absorption, and possible anastomotic pressure may result.
  • If therapy is required, IV-administered bisphosphonates should be considered.

• Glucocorticoid-induced osteoporosis:

  • Before starting treatment, assess your sex steroid hormonal condition.
  • Consider appropriate hormone replacement if required.

• Hypocalcemia:

  • Hypocalcemia must first be treated before you can start therapy.
  • For patients suffering from Paget disease, ensure adequate calcium intake and vitamin D intake.

• Renal impairment

  • Patients with kidney impairment should be cautious (not recommended for patients with CrCl 30mL/minute).

Risedronate: Drug Interaction

Monitoring parameters:

• Osteoporosis:
  • Bone mineral density (BMD) should be evaluated 1 to 2 years after initiating therapy and every 1 to 2 years (or less frequently if stable) thereafter
  • In patients with combined risedronate and glucocorticoid treatment, evaluate BMD at the initiation of glucocorticoid therapy and after 6 to 12 months, then every 2 to 3 years if the patient continues to have significant osteoporosis risk factors.
  • Annual measurements of height and weight, assessment of chronic back pain;
  • Serum calcium and 25(OH)D;
  • Consider measuring biochemical markers of bone turnover

Paget disease:

• Serum total alkaline phosphatase at 6 to 12 weeks for initial response to treatment (when bone turnover will have shown a substantial decline) and potentially at 6 months (maximal suppression of high bone turnover);
• following treatment completion, monitor at ~6- to 12-month intervals.
• Monitoring more specific biochemical markers of bone turnover (eg, serum P1NP, NTX, serum beta-CTx) is generally only warranted in patients with Paget disease who have abnormal liver or biliary tract function or when the early assessment of response to treatment is needed (eg, spinal compression, very active disease).
• Serum calcium and 25(OH)D;
• Pain (posttreatment pain) may not strictly correlate with increased biochemical markers.

How to administer Risedronate (Actonel)?

Oral: Note: Avoid administration of oral calcium supplements, antacids, magnesium supplements/laxatives, and iron preparations for at least 30 minutes after risedronate administration.

Immediate-release tablet:

• Risedronate immediate-release tablets must be taken on an empty stomach with a full glass (6 to 8 oz) of plain water (not mineral water) at least 30 minutes before any food, drink, or other medications orally to avoid interference with absorption.
• The patient must remain sitting upright or standing for at least 30 minutes after taking (to reduce esophageal irritation).
• The tablet should be swallowed whole; do not crush or chew.

Delayed-release tablet:

• Risedronate delayed-release tablets must be taken with at least 4 oz of plain water (not mineral water) immediately after breakfast.
• The patient must remain sitting upright or standing for at least 30 minutes after taking (to reduce esophageal irritation).
• The tablet should be swallowed whole; do not cut, split, crush, or chew.

Mechanism of action of Risedronate (Actonel):

• It is a bisphosphonate which inhibits bone loss via osteoclasts and osteoclast precursors.
• This decreases bone resorption rate, leading to an indirect increase of bone mineral density.
• Paget's disease is characterized by disordered bone formation and resorption.
• However, the inhibition of resorption results in an indirect decrease of bone formation.
• The newly formed bone however, has a more normal structure.

The onset of action:

• May require weeks

Absorption:

• Rapid

Protein binding:

• About 24%

Metabolism:

• None

Bioavailability:

• Poor, ~0.54% to 0.75%

Half-life elimination:

• Initial: 1.5 hours;
• Terminal: 480 to 561 hours

Time to peak serum:

• 1 to 3 hours

Excretion:

• Urine (up to 85%);
• feces (as unabsorbed drug)

International Brand Names of Risedronate:

• Actonel
• Atelvia
• Actonel
• Actonel DR
• APO-Risedronate
• Auro-Risedronate
• DOM-Risedronate
• JAMP-Risedronate
• MYLAN-Risedronate
• PMS-Risedronate
• RATIO-Risedronate
• Risedronate-35
• RIVA Risedronate
• SANDOZ Risedronate
• TEVA-Risedronate
• Acrel
• Actoday
• Actonel
• Actonel Once A Month
• Actonel once A Week
• Actonel Once A Week
• Actoril
• Avestra
• Benet
• Boncret
• Dronagi
• Dronel
• Droriate
• Droserid
• Gemfos
• Gusong
• Kantonel
• Merval
• Norifaz
• Optinate
• Osteoclax
• Osteonate OD
• Osteorise
• Osteral
• Residron
• Retonel
• Ribastamin
• Ribone
• Ridate
• Ridbone
• Ridbone Month
• Ridroqueen
• Risedreenos
• Risedro
• Risemylan
• Risendros
• Risenel
• Risenoros
• Riseto
• Risnel
• Risofos
• Risonate
• Risonato
• Risonet
• Risontel
• Risopage
• Ristonat
• Rosenax
• Salost
• Sedron
• Valetta

Risedronate Brand Names in Pakistan: