Risedronate

Generic Name: Risedronate
Full Name: Risedronate sodium
Brand Names: Actonel, Atelvia (US), Benet (EU), Risofos, Rispond, Risec, Risodonate
Drug Class: Bisphosphonate
Pharmaceutical Formulations:
– Oral tablets: 5 mg, 30 mg, 35 mg, 75 mg, 150 mg
– Delayed-release tablets (Atelvia): 35 mg
Route of Administration: Oral (swallowed whole with water)

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Therapeutic Indications and Clinical Use

Risedronate is a bisphosphonate drug indicated for the prevention and treatment of osteoporosis and other bone metabolism disorders characterized by excessive bone resorption.

Approved Indications:

1. Postmenopausal osteoporosis
   – Prevention and treatment
   – Reduces vertebral and non-vertebral fractures

2. Glucocorticoid-induced osteoporosis
   – In men and women on chronic systemic corticosteroids

3. Osteoporosis in men
   – Treatment of primary or hypogonadal osteoporosis

4. Paget’s disease of bone
   – For adults with active disease

5. Corticosteroid-associated bone loss
   – Prevention in high-risk patients

Off-label Uses (limited evidence):

• Prevention of bone loss in prostate or breast cancer patients undergoing hormone therapy

• Osteogenesis imperfecta (under research protocols)

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Mechanism of Action

Risedronate is a third-generation nitrogen-containing bisphosphonate. It inhibits osteoclast-mediated bone resorption by binding to hydroxyapatite in bone and interfering with osteoclast function.

Mechanism Details:

• Selectively adheres to bone mineral surfaces

• Once internalized by osteoclasts, inhibits farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway

• This disrupts prenylation of small GTPase signaling proteins essential for osteoclast activity and survival

• Result: Apoptosis of osteoclasts → reduced bone resorption → preservation of bone density

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Dosage and Administration

For Postmenopausal Osteoporosis (Treatment or Prevention):

• 5 mg once daily, or

• 35 mg once weekly, or

• 75 mg on two consecutive days per month, or

• 150 mg once monthly

Glucocorticoid-Induced Osteoporosis:

• 5 mg once daily (preferred)

Male Osteoporosis:

• 35 mg once weekly

Paget’s Disease:

• 30 mg once daily for 2 months

• Retreatment may be considered after biochemical relapse

Special Formulation: Atelvia (Delayed-Release Risedronate):

• 35 mg once weekly, taken immediately after breakfast (unlike immediate-release tablets which require fasting)

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Administration Guidelines (Standard Formulation)

• Take first thing in the morning, at least 30 minutes before any food, drink, or other medication

• Swallow whole with a full glass (6–8 oz) of plain water

• Do not lie down for at least 30 minutes after taking the dose

• Do not chew or suck the tablet

• Avoid taking with mineral water, coffee, tea, juice, or calcium supplements

Rationale: Increases bioavailability and minimizes esophageal irritation

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Pharmacokinetics

• Oral Bioavailability: 0.6% (fasted state); decreased with food or beverages

• Time to Peak Plasma Concentration: ~1 hour

• Plasma Protein Binding: ~24%

• Metabolism: Not metabolized

• Half-life: > 480 hours (due to binding in bone)

• Excretion:

  • Renal: ~50%

  • Fecal: minimal

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Contraindications

• Hypersensitivity to risedronate or any excipient

• Hypocalcemia (must be corrected prior to therapy)

• Inability to stand or sit upright for at least 30 minutes

• Esophageal abnormalities (e.g., stricture or achalasia) that delay emptying

• Severe renal impairment (CrCl < 30 mL/min)

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Warnings and Precautions

1. Esophageal irritation/ulceration
   – Avoid in patients with esophageal disorders
   – Follow exact administration instructions

2. Osteonecrosis of the Jaw (ONJ)
   – Rare, associated with invasive dental procedures and long-term therapy
   – More common in cancer patients receiving IV bisphosphonates

3. Atypical Femoral Fractures
   – Low-trauma subtrochanteric or diaphyseal fractures may occur
   – Monitor thigh/groin pain

4. Hypocalcemia
   – Must be corrected before initiating
   – Ensure adequate calcium/vitamin D intake

5. Musculoskeletal Pain
   – Severe bone, joint, or muscle pain may occur (reversible upon discontinuation)

6. Renal Impairment
   – Not recommended if CrCl < 30 mL/min

7. Pregnancy and Lactation
   – Category C (US); use only if clearly needed
   – Excreted in small amounts in animal milk; avoid in lactating women

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Adverse Effects

Very Common (≥10%):
– Musculoskeletal pain (back pain, joint pain)
– Headache
– Upper abdominal pain or dyspepsia

Common (1–10%):
– Nausea, diarrhea, constipation
– Esophagitis, gastritis
– Dizziness
– Flu-like symptoms (especially after first dose)
– Hypocalcemia (especially if vitamin D deficient)

Uncommon to Rare (<1%):
– Osteonecrosis of the jaw
– Atypical femur fractures
– Visual disturbances (uveitis, scleritis)
– Rash
– Alopecia

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Drug Interactions

1. Calcium and Mineral Supplements (e.g., antacids):
   – Decrease absorption if taken within 30 minutes
   – Separate administration by ≥30–60 minutes

2. Iron and Magnesium Supplements:
   – Similar chelating interaction – avoid concurrent use

3. H2 blockers and Proton Pump Inhibitors (PPIs):
   – May affect calcium absorption, indirectly interfering with bone health
   – Long-term use associated with reduced bisphosphonate efficacy

4. NSAIDs:
   – Increased risk of GI irritation and ulceration

5. Estrogens / Hormone Replacement Therapy:
   – No direct interaction, but may be co-prescribed for synergistic benefit in menopausal osteoporosis

6. Aminoglycosides / Loop Diuretics:
   – Caution for enhanced hypocalcemic effect

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Monitoring Parameters

• Bone Mineral Density (BMD): via DEXA every 1–2 years

• Serum Calcium, Phosphate, and Vitamin D: at baseline and periodically

• Renal Function (eGFR/Creatinine): especially in elderly or comorbid patients

• Height and Posture: monitor for vertebral fracture signs

• Pain or swelling in femur/thigh: screen for atypical fractures

• Oral health assessment: before initiation in high-risk patients (especially oncology or steroid users)

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Patient Counseling Points

• Take on an empty stomach first thing in the morning with a full glass of water

• Do not eat, drink, or lie down for 30 minutes

• Report difficulty swallowing, chest pain, or new/worsening bone pain

• Ensure adequate calcium and vitamin D intake during treatment

• Notify dentist about bisphosphonate use before any dental procedures

• Do not take with other medications or supplements simultaneously

• Adherence to schedule is critical for fracture prevention

• Keep regular follow-up appointments for bone density monitoring

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Use in Special Populations

Elderly:
– Commonly used; ensure renal monitoring and fall prevention strategies

Pregnancy:
– Animal studies show fetal skeletal abnormalities; use only when benefits outweigh risks

Pediatrics:
– Not routinely used; off-label use under specialist guidance in severe bone disorders

Renal Impairment:
– Avoid use if CrCl <30 mL/min

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Comparison with Other Bisphosphonates

Drug	Dosing Frequency	GI Tolerability	Renal Cutoff (CrCl)	Unique Features
Risedronate	Daily/Weekly/Monthly	Moderate	<30 mL/min (avoid)	Multiple oral schedules
Alendronate	Daily/Weekly	More GI issues	<35 mL/min (avoid)	Lower cost, widely used
Ibandronate	Monthly oral or IV q3mo	Better GI profile	<30 mL/min	Only spine fracture benefit
Zoledronic Acid	Yearly IV	No GI side effects	<35 mL/min (avoid)	Most potent, injection only

Storage and Stability

• Store at room temperature (20–25°C)

• Protect from moisture and direct light

• Keep in original packaging until use

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Availability and Regulatory Status

• Prescription-only medication

• Approved by FDA, EMA, MHRA, and other regulatory bodies globally

• Included in national osteoporosis treatment guidelines

• Widely available under multiple brand and generic names