Drug Interactions between Calcium 600 D and Razadyne ER

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

MONITOR: Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

MANAGEMENT: Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

ADJUST DOSING INTERVAL: The administration of galantamine with food and adequate fluid intake may reduce the impact of nausea, vomiting, diarrhea, anorexia, and weight loss that are commonly associated with acetylcholinesterase inhibitors (AChEIs). According to product labeling, the administration of food with various galantamine formulations (e.g., liquid, immediate-release tablets, modified/extended-release capsules) has no significant effect on the systemic absorption (AUC) of galantamine. While the presence of food has been shown to delay the rate of absorption (Tmax) and reduce peak concentration (Cmax), these changes are unlikely to be clinically significant. For example, when galantamine modified release was given after food, Tmax increased by approximately 30 minutes. Similarly, in 24 healthy elderly subjects, the presence of food with galantamine immediate release tablets (12 mg twice a day) delayed the Tmax by 1.5 hours and decreased the Cmax by about 25% without affecting the AUC.

MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of galantamine, which is partially metabolized by the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported with both moderate and potent CYP450 3A4 inhibitors. When study subjects (n=16) received the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 4 days) with galantamine (4 mg twice daily for 8 days), the systemic exposure (AUC) of galantamine increased by 30%. However, when study subjects (n=16) received the moderate CYP450 3A4 inhibitor erythromycin (500 mg 4 times daily for 4 days) with galantamine (4 mg twice daily for 6 days), the AUC of galantamine only increased by 10%. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. While the clinical significance of this interaction is unknown, increased exposure to galantamine may lead to AChEI related adverse effects such as vagotonic effects on the heart rate (e.g., bradycardia and heart block), neurologic side effects (e.g., seizure activity), respiratory distress, bladder outflow obstruction, dizziness or syncope, nausea, vomiting and/or diarrhea.

MANAGEMENT: According to product labeling, galantamine should be administered with food and adequate fluid intake to reduce the impact of cholinergic-related gastrointestinal adverse effects (e.g., nausea, vomiting, diarrhea, anorexia, and weight loss). Caution and closer monitoring for AChEI related adverse effects may advisable if galantamine is used in combination with grapefruit and/or grapefruit juice. Modified and/or extended-release formulations must also be swallowed whole and not crushed, chewed, or divided.