Calcium Orotate

Approved Indications:

• Calcium Deficiency States:
• Osteopenia and osteoporosis (postmenopausal, age-related, corticosteroid-induced)
• Rickets and osteomalacia
• Chronic hypocalcemia
• Hypoparathyroidism
• Supportive Therapy in Pregnancy & Lactation:
• For prevention of gestational hypertension and fetal skeletal development
• Pediatric Calcium Supplementation:
• For children with poor dietary calcium intake or during rapid growth phases
• Fracture Healing Support:
• Promotes bone remodeling and mineralization during recovery

Clinically Accepted Off-Label Uses:

• Adjunct therapy in premenstrual syndrome (PMS) for musculoskeletal symptoms
• Supportive supplement in dental health (reduces demineralization)
• Possible adjuvant therapy in muscle cramps due to hypocalcemia

General Administration:

• Route: Oral
• Formulations: Tablets, capsules, and powder
• Recommended to be taken with food to enhance absorption

Adult Dosage:

• Osteoporosis/Osteopenia: 500 mg to 1000 mg elemental calcium daily in divided doses
• Calcium Deficiency: 500 mg once or twice daily
• Pregnancy & Lactation: 500 mg to 1000 mg daily (individualized)

Pediatric Dosage:

• 1–3 years: 250 mg elemental calcium daily
• 4–8 years: 500 mg elemental calcium daily
• 9–18 years: 1000 mg elemental calcium daily

Geriatric Dosage:

• Similar to adult dosing (typically 1000 mg/day), considering renal function

Special Populations:

• Renal Impairment: Use with caution; monitor calcium levels regularly
• Hepatic Impairment: No dosage adjustment typically needed

Duration of Use:

• Long-term use may be required in chronic calcium deficiency states
• Intermittent reassessment of calcium levels recommended every 6 months

Calcium Orotate delivers elemental calcium bound to orotic acid, which facilitates better transport of calcium ions across cell membranes. The orotate moiety enhances cellular calcium uptake and retention by increasing membrane permeability, especially in bone and neuronal tissues. Once absorbed, calcium participates in vital physiological processes such as bone mineralization, neuromuscular function, cardiac excitability, blood coagulation, and enzymatic activities. Its superior bioavailability promotes effective correction of hypocalcemia and supports bone remodeling.

• Absorption: Approximately 40% of ingested calcium orotate is absorbed from the gastrointestinal tract, higher than calcium carbonate or citrate
• Bioavailability: High due to orotic acid-mediated transport
• Distribution: Widely distributed to bone, plasma, and soft tissues; about 50% protein-bound
• Metabolism: Calcium is not metabolized; orotic acid is partially metabolized in the liver
• Half-life: Calcium itself does not have a conventional half-life; systemic levels depend on absorption and bone turnover
• Elimination: Excreted primarily through urine (renal route) and feces (unabsorbed fraction)

• Pregnancy: Considered safe in recommended doses during pregnancy. No FDA pregnancy category defined for calcium orotate, but calcium supplementation is often recommended during pregnancy to support fetal skeletal growth.
• Lactation: Calcium is excreted into breast milk in low quantities and is generally considered safe for use during breastfeeding. No adverse effects reported in breastfed infants when maternal supplementation is within recommended limits.
• Caution: Avoid excessive dosing due to potential risk of maternal hypercalcemia.

• Primary Class: Mineral Supplement
• Sub-Class: Calcium Salt (Chelated Form)
• Generation/Form: Third-generation calcium salt (enhanced absorption via orotic acid chelation)

• Known hypersensitivity to calcium salts or orotic acid
• Hypercalcemia (e.g., from hyperparathyroidism, vitamin D toxicity, malignancy)
• Severe renal impairment with risk of calcium accumulation
• Nephrolithiasis (renal stones with calcium origin)
• Sarcoidosis or other granulomatous diseases with hypercalcemia

• Use caution in patients with renal impairment due to risk of calcium accumulation
• Monitor serum calcium regularly in long-term use or high doses
• Avoid use with high-dose vitamin D therapy unless supervised
• May interfere with absorption of iron, zinc, and certain antibiotics
• Use cautiously in individuals with history of kidney stones
• Avoid excessive calcium intake (>2000 mg/day) due to risk of vascular calcification

Common Side Effects:

• Gastrointestinal: Constipation, bloating, flatulence, nausea
• Neurological: Headache, fatigue (rare)

Serious or Rare Side Effects:

• Hypercalcemia (symptoms: vomiting, weakness, confusion, arrhythmia)
• Kidney stones (long-term high doses)
• Hypophosphatemia (in rare cases due to calcium-phosphate imbalance)

Onset & Dose-Dependence:

• GI effects typically occur within first few days of dosing and may be dose-related
• Hypercalcemia risk increases with doses >1000 mg/day

• Decreased Absorption of Other Drugs:
• Tetracyclines, Quinolones, Levothyroxine: Take at least 2 hours apart
• Vitamin D: Enhances calcium absorption; may increase hypercalcemia risk
• Thiazide Diuretics: Decrease urinary calcium excretion → risk of hypercalcemia
• Iron/Zinc Supplements: Compete for absorption; separate by several hours

Enzyme Systems: Not significantly involved in CYP450 metabolism

• Recent clinical preference trends show increased use of chelated calcium forms like calcium orotate for enhanced gastrointestinal tolerance and better absorption.
• Nutritional recommendations from several global guidelines now support calcium supplementation during pregnancy, menopause, and elderly care—emphasizing formulations with higher bioavailability like orotate salts.
• No recent FDA or EMA regulatory warnings specific to calcium orotate.

• Temperature: Store below 30°C (room temperature)
• Humidity: Store in a dry place; protect from moisture
• Light Exposure: Keep in original container to protect from light
• Handling: No special handling; do not freeze
• Shelf Life: Check individual product labeling; typically 24–36 months unopened