RISOFOS (RISEDRONATE SODIUM TABLETS)

Indications

• Osteoporosis in postmenopausal women
• Osteoporosis in men
• Paget's disease of bone
• Glucocorticoid-induced osteoporosis

Dosage

Children: Use in children and adolescents is not well established; refer to the BNF for Children for guidance on dosing.

Adults: The usual dose for adults is 35 mg once weekly, or 5 mg once daily, depending on the specific indication.

Mechanism of action

Risedronate binds to bone hydroxyapatite, which causes local acidification during bone resorption. This releases risedronic acid, which is taken up by osteoclasts through fluid-phase endocytosis. Inside the osteoclasts, risedronic acid inhibits farnesyl pyrophosphate synthase, leading to apoptosis of osteoclasts. This results in decreased bone resorption and reduced bone turnover, ultimately contributing to increased bone mineral density.

Pharmacodynamics

As a bisphosphonate, risedronate inhibits bone resorption caused by osteoclasts, which are responsible for bone degradation. By reducing the activity and number of osteoclasts, risedronate helps to preserve bone mass and strength, making it particularly beneficial in conditions characterized by increased bone turnover.

Pharmacokinetics

Risedronate is absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 1 to 2 hours after oral administration. Its bioavailability is low due to poor absorption and significant first-pass metabolism. The drug is highly bound to bone tissue, and its elimination half-life is prolonged due to this binding, although the biological effects continue long after the drug has been cleared from circulation. It is primarily excreted unchanged in the urine.

Interactions

• oral iron + risedronate: Unknown (decreases absorption)
• oral magnesium + risedronate: Unknown (decreases absorption)
• oral zinc + risedronate: Unknown (decreases absorption)

Pregnancy

Risedronate is not recommended during pregnancy due to potential risks to the fetus.

Breast-feeding

It is unknown whether risedronate is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store below 25 degrees Celsius. Keep the container tightly closed.

Formulations

• Risedronate sodium 5 mg tablets
• Risedronate sodium 30 mg tablets
• Risedronate sodium 150 mg tablets

Indications

• Osteoporosis in postmenopausal women
• Paget's disease of bone
• Prevention of osteoporosis in individuals at high risk
• Bone metastases associated with malignancies

Dosage

Children: Refer to the BNF for Children for specific dosing information, as pediatric dosages may vary based on specific conditions and individual patient factors.

Adults: The usual dose for osteoporosis is 35 mg once weekly or 5 mg once daily. For Paget's disease, the recommended dose is 30 mg daily for 2 months. For prevention of osteoporosis, 5 mg daily or 35 mg once weekly is typically used. Dosing may need adjustment for renal impairment.

Mechanism of action

Risedronate sodium works by binding to hydroxyapatite in the bone and inhibiting the activity of osteoclasts, the cells responsible for bone resorption. This leads to a decrease in bone turnover and an increase in bone mineral density. It also reduces the risk of fractures in patients with osteoporosis and other conditions leading to bone loss.

Pharmacodynamics

The primary pharmacodynamic action of risedronate sodium is the inhibition of bone resorption. This results in decreased serum calcium levels and reduced bone turnover rates. Clinical studies have demonstrated its effectiveness in increasing bone mineral density in postmenopausal women and in preventing fractures in patients with osteoporosis.

Pharmacokinetics

Risedronate sodium is absorbed in the gastrointestinal tract with a bioavailability of approximately 0.63% when taken on an empty stomach. Its peak plasma concentrations occur about 1-2 hours after administration. The drug is predominantly eliminated via urine, with a half-life of approximately 10 hours. Renal function significantly affects its clearance; thus, caution is advised in patients with renal impairment.

Contra-indications

• Hypocalcemia
• Severe renal impairment (creatinine clearance less than 30 mL/min)
• Pregnancy
• Breastfeeding

Adverse effects

• Drowsiness
• Muscle pain
• Agitation
• Hypotension
• Seizures
• Decreased leukocytes
• Heartburn
• Pain on swallowing
• Retrosternal pain
• Confusion
• Oedema

Interactions

• Calcium supplements
• Antacids
• Other bisphosphonates may increase the risk of adverse effects

Precautions

• Monitor serum electrolytes, calcium, and phosphate levels
• Assess renal function before each dose
• Caution in patients with a history of gastrointestinal disorders

Pregnancy

Avoid due to potential toxicity observed in animal studies.

Breast-feeding

Manufacturer advises to avoid, as no information is available on safety.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Risedronate sodium 5mg tablets
• Risedronate sodium 30mg tablets
• Risedronate sodium oral solution 100 mL

Mechanism of action

Risedronatic acid binds to bone hydroxyapatite. Bone resorption causes local acidification, releasing risedronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing risedronic acid to the cytosol of osteoclasts where they induce apoptosis through inhbition of farnesyl pyrophosphate synthase. Inhibition of osteoclasts results in decreased bone resorption. Risedronate binds to bone hydroxyapatite and, at the cellular level, inhibits osteoclasts. Although the osteoclasts adhere normally to the bone surface, they show evidence of reduced active resorption (e.g., lack of ruffled border). Evidence from studies in rats and dogs indicates that risedronate treatment reduces bone turnover (activation frequency, i.e., the number of sites at which bone is remodeled) and bone resorption at remodeling sites. /Risedronate/ Risedronate sodium, a synthetic pyridinyl bisphosphonate analog of pyrophosphate, is an inhibitor of osteoclast-mediated bone resorption. / Risedronate sodium/ ... Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. Loss of bone-resorptive activity and osteoclast apoptosis is due primarily to loss of geranylgeranylated small GTPases. Identification of FPP synthase as the target of nitrogen-containing bisphosphonates has also helped explain the molecular basis for the adverse effects of these agents in the GI tract and on the immune system. /Risedronate/

Pharmacodynamics

Risedronate is a pyridine-based bisphosphonate that inhibits bone resorption caused by osteoclasts.