Calcin-O Kit

Approved Medical Uses:

• Postmenopausal Osteoporosis
• Treatment and prevention of osteoporosis in postmenopausal women to reduce the risk of vertebral fractures.
• Ibandronic Acid inhibits bone resorption, while Calcium Orotate helps restore calcium levels necessary for bone mineralization.

Off-Label and Clinically Accepted Uses:

• Corticosteroid-Induced Osteoporosis
• Prevents or treats bone loss in patients receiving long-term corticosteroid therapy.
• Osteoporosis in Men
• Occasionally used in elderly men with low bone mineral density or high fracture risk.
• Bone Metastases (Ibandronic Acid only)
• Ibandronic Acid is used intravenously to reduce skeletal-related events in patients with bone metastases.
• Hypocalcemia and Calcium Deficiency (Calcium Orotate)
• Used to treat or prevent calcium deficiency in conditions such as pregnancy, lactation, or postmenopausal states.

Adults (Postmenopausal Osteoporosis):

• Ibandronic Acid: 150 mg orally once a month, on the same date each month.
• Calcium Orotate: 400 mg to 800 mg daily, in 1–2 divided doses (depending on the patient's calcium requirement).

Important Administration Instructions:

• Take Ibandronic Acid with a full glass of plain water only, first thing in the morning, on an empty stomach, at least 60 minutes before food, beverages, or other medications.
• Remain upright (sitting or standing) for at least 60 minutes after taking Ibandronic Acid.
• Do not take Calcium Orotate at the same time—administer at least 6 hours apart to prevent reduced absorption.
• Calcium Orotate should be taken with or after meals to minimize gastrointestinal side effects.

Elderly:

• No dosage adjustment required; monitor renal function periodically.

Renal Impairment:

• Ibandronic Acid: Contraindicated in severe renal impairment (creatinine clearance <30 mL/min).
• Use with caution in moderate renal impairment (30–50 mL/min).

Hepatic Impairment:

• No dosage adjustment necessary for either component.

Pediatrics:

• Not recommended; safety and efficacy have not been established in children.

Ibandronic Acid is a bisphosphonate that binds to hydroxyapatite in bone and specifically inhibits osteoclast-mediated bone resorption. By reducing osteoclast activity, it decreases bone turnover and increases bone density, ultimately reducing fracture risk.

Calcium Orotate is a mineral salt where elemental calcium is bound to orotic acid, which acts as a carrier to improve calcium transport into bone cells. This enhances calcium availability for bone mineralization and helps correct systemic calcium deficiency.

Ibandronic Acid:

• Absorption: Low (approximately 0.6%) when taken orally under fasting conditions.
• Time to Peak: 1 to 2 hours.
• Distribution: High affinity for bone; minimal distribution in soft tissues.
• Metabolism: Not metabolized; remains unchanged.
• Half-Life: Terminal half-life is 10 to 60 hours; functional half-life extends due to prolonged skeletal binding.
• Elimination: Primarily renal excretion of unchanged drug.

Calcium Orotate:

• Absorption: High bioavailability due to orotate chelation.
• Distribution: Deposits in bone and teeth; supports systemic calcium levels.
• Metabolism: Orotic acid may undergo minor hepatic metabolism.
• Elimination: Absorbed calcium is excreted via urine; unabsorbed calcium is eliminated in feces.

Pregnancy:

• Ibandronic Acid: Category C (FDA)
• Animal studies have shown fetal harm; there are no adequate human studies. Use only when clearly necessary.
• Calcium Orotate: Generally regarded as safe when used in recommended doses for dietary supplementation.

Lactation:

• Ibandronic Acid: Unknown whether it is excreted in human milk. Use with caution.
• Calcium Orotate: Safe in breastfeeding; calcium is naturally present in breast milk and does not harm infants at normal doses.

• Ibandronic Acid: Bisphosphonate (Anti-resorptive agent)
• Calcium Orotate: Calcium supplement (Bone mineral support)

Combination Classification: Osteoporosis treatment agent (Bisphosphonate + Calcium)

• Known hypersensitivity to Ibandronic Acid, Calcium Orotate, or any excipient
• Hypocalcemia (must be corrected before starting therapy)
• Severe renal impairment (creatinine clearance <30 mL/min)
• Esophageal abnormalities or conditions delaying esophageal emptying
• Inability to remain upright for at least 60 minutes post-dosing
• Active gastrointestinal disorders (e.g., esophagitis, ulcers)

• Esophageal Irritation or Ulcers: May occur with improper administration. Discontinue if dysphagia or retrosternal pain develops.
• Osteonecrosis of the Jaw (ONJ): Reported rarely, especially in cancer patients undergoing dental surgery. Perform dental evaluation prior to initiation.
• Atypical Femoral Fractures: Occur rarely with long-term use; consider discontinuation if unexplained thigh pain occurs.
• Hypocalcemia: Monitor calcium and vitamin D levels before and during therapy.
• Renal Function: Monitor serum creatinine in patients with moderate renal impairment.
• Severe Musculoskeletal Pain: May occur; discontinue if pain is disabling.

Common Side Effects:

• Gastrointestinal: Abdominal pain, nausea, dyspepsia, constipation, esophagitis (Ibandronic Acid)
• Musculoskeletal: Back pain, joint pain, muscle cramps
• General: Headache, fatigue, flu-like symptoms (especially after the first dose)

Serious or Rare Side Effects:

• Osteonecrosis of the jaw (ONJ)
• Atypical subtrochanteric or femoral shaft fractures
• Severe hypocalcemia
• Anaphylactic or allergic reactions (rare)

Calcium Orotate Specific:

• Constipation
• Hypercalcemia, especially with overdose or renal dysfunction
• Bloating or flatulence (mild)

• Calcium-containing products: Reduce absorption of Ibandronic Acid. Must be administered at least 6 hours apart.
• Antacids, iron, magnesium, multivitamins: Decrease absorption of Ibandronic Acid. Administer separately.
• NSAIDs: Increase gastrointestinal irritation risk when used with Ibandronic Acid.
• Diuretics:
• Thiazides: May increase risk of hypercalcemia with calcium supplements.
• Loops: May increase urinary calcium loss.

Enzyme Interaction:

• Ibandronic Acid is not metabolized via CYP450, reducing risk of hepatic drug interactions.

• Osteoporosis Treatment Duration: Clinical guidelines recommend reassessing fracture risk after 3 to 5 years of bisphosphonate therapy to consider discontinuation or continuation based on risk level.
• Safety Warnings: Updated alerts emphasize the importance of monitoring for ONJ and atypical fractures during long-term use.
• Combination Use: Endorsed in updated clinical guidelines to improve treatment adherence and calcium balance.

Ibandronic Acid:

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture, heat, and light
• Keep in original blister pack until administration

Calcium Orotate:

• Store at 15°C to 30°C (59°F to 86°F)
• Protect from humidity and direct sunlight
• Keep container tightly closed