Salost DR

Approved Indications:

• Postmenopausal Osteoporosis
• Treatment and prevention of osteoporosis in postmenopausal women.
• Reduces the risk of vertebral, non-vertebral, and hip fractures.
• Glucocorticoid-Induced Osteoporosis
• Treatment and prevention in men and women receiving systemic glucocorticoids (≥7.5 mg/day prednisone or equivalent) for at least 3 months.
• Paget’s Disease of Bone
• Treatment in patients with moderate to severe symptoms or risk of future complications, such as bone deformities, fractures, or joint issues.
• Osteoporosis in Men
• Treatment to increase bone mass and reduce the risk of fractures in men with primary or hypogonadal osteoporosis.

Important Off-Label (Clinically Accepted) Uses:

• Bone Loss due to Androgen Deprivation Therapy
• Used in prostate cancer patients to reduce skeletal-related events and preserve bone mineral density (BMD).
• Bone Loss in Organ Transplant Recipients
• Considered to manage post-transplant osteoporosis, especially with corticosteroid use.

Route of Administration: Oral
Important Administration Instructions:

• Must be taken with a full glass (180–240 mL) of plain water.
• Administer at least 30 minutes before the first food, drink, or other medications.
• Patients must remain upright (sitting or standing) for at least 30 minutes post-dose.

Adults:

• Postmenopausal Osteoporosis:
• 5 mg once daily
• OR 35 mg once weekly
• OR 150 mg once monthly
• Glucocorticoid-Induced Osteoporosis:
• 5 mg once daily
• Paget’s Disease of Bone:
• 30 mg once daily for 2 months
• Osteoporosis in Men:
• 35 mg once weekly

Pediatric Use:

• Safety and efficacy in children and adolescents have not been established.

Elderly:

• No dose adjustment is necessary based on age alone, but renal function should be assessed regularly.

Renal Impairment:

• Contraindicated in patients with creatinine clearance <30 mL/min.

Hepatic Impairment:

• No dose adjustment required; however, use with caution due to lack of specific data.

Risedronate Sodium is a nitrogen-containing bisphosphonate that selectively binds to hydroxyapatite crystals in bone. It inhibits osteoclast-mediated bone resorption by interfering with the mevalonate pathway, specifically blocking farnesyl pyrophosphate synthase (FPPS). This leads to impaired osteoclast function and induction of apoptosis. As a result, bone turnover is reduced, and bone mineral density is maintained or increased. Risedronate helps to restore skeletal strength, reduce microarchitectural deterioration, and ultimately decrease the risk of fractures in osteoporotic patients.

• Absorption: Rapid but low oral bioavailability (~0.63%) when taken under fasting conditions; negligible if taken with food.
• Distribution: Low plasma protein binding (~24%); rapidly distributed to bone.
• Metabolism: Not metabolized by the liver.
• Elimination: Primarily excreted unchanged via the kidneys; unabsorbed drug excreted in feces.
• Half-life: Prolonged terminal half-life (~480 hours) due to skeletal binding.
• Time to Peak Plasma Concentration (Tmax): ~1 hour (fasting state)

• Pregnancy: Category C (US FDA)
  Animal studies have shown skeletal toxicity; no well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
• Lactation:
  Unknown whether risedronate is excreted in human breast milk. Due to potential risk of harm to the infant (e.g., skeletal effects, hypocalcemia), breastfeeding is not recommended during treatment.
• Caution: Avoid use during pregnancy or breastfeeding unless absolutely necessary.

• Primary Class: Bisphosphonate
• Subclass: Nitrogen-containing (third-generation) bisphosphonate
• Indication Group: Anti-resorptive agent for metabolic bone disease

• Hypersensitivity to Risedronate Sodium or any component of the formulation
• Hypocalcemia
• Inability to sit or stand upright for at least 30 minutes
• Esophageal abnormalities (e.g., strictures, achalasia) that delay esophageal emptying
• Severe renal impairment (creatinine clearance <30 mL/min)

• Upper GI Effects: Risk of esophagitis, esophageal ulceration, and perforation—especially if dosing instructions are not followed.
• Osteonecrosis of the Jaw (ONJ): Mostly reported in cancer patients undergoing dental procedures. Dental examination and preventive care are recommended before treatment.
• Atypical Femoral Fractures: Rare but serious; may occur with long-term use. Evaluate any unexplained thigh or groin pain.
• Hypocalcemia and Mineral Metabolism Disorders: Correct before starting therapy; ensure adequate calcium and vitamin D intake.
• Musculoskeletal Pain: Severe, disabling bone, joint, or muscle pain has been reported.
• Renal Monitoring: Assess renal function periodically, especially in the elderly.

Common (≥1%):

• Gastrointestinal: Abdominal pain, nausea, dyspepsia, diarrhea, constipation
• Musculoskeletal: Arthralgia, back pain, myalgia
• Neurological: Headache, dizziness

Less Common:

• Skin rash, fatigue, visual disturbances, flu-like symptoms

Serious (Rare):

• Osteonecrosis of the jaw
• Atypical femoral fractures
• Severe esophageal irritation or bleeding
• Hypocalcemia (especially in predisposed individuals)

Timing: Most side effects are dose-related and occur early in therapy.

• Calcium, Magnesium, Aluminum, or Iron Supplements: Significantly reduce absorption. Administer at least 30–60 minutes apart.
• Antacids and Mineral Waters: Reduce drug absorption; avoid co-administration.
• NSAIDs: Concurrent use may increase risk of GI irritation or ulceration.
• H2 Blockers / PPIs: Chronic use may indirectly affect calcium metabolism; monitor bone health in long-term users.

Metabolic Pathways:

• Risedronate is not metabolized and does not affect cytochrome P450 enzymes (no CYP450 interactions).

• NOF and AACE Guidelines: Risedronate is a first-line option for the prevention and treatment of osteoporosis in postmenopausal women and men.
• Treatment Duration & Drug Holiday: Evaluation after 3–5 years of therapy for fracture risk is now recommended to determine the need for a “drug holiday” to reduce long-term adverse effects.
• Monitoring Recommendations Updated: Emphasis on regular BMD assessment and reassessment of fracture risk every 2–3 years during treatment.

• Storage Temperature: Store below 25°C (77°F)
• Humidity: Store in a dry place; protect from moisture
• Light Protection: Not required
• Handling Instructions:
• Store tablets in the original blister or container
• Do not break, crush, or chew the tablets
• Reconstitution: Not applicable (oral tablets only)