Drug Interaction Report
8 potential interactions and/or warnings found for the following 2 drugs:
- calcium / ferrous fumarate / vitamin d
- betamethasone / iodixanol / lidocaine
Interactions between your drugs
calcium carbonate ferrous fumarate
Applies to: calcium / ferrous fumarate / vitamin d, calcium / ferrous fumarate / vitamin d
ADJUST DOSING INTERVAL: The bioavailability of orally administered iron may be reduced by concomitant administration of antacids or other agents with acid-neutralizing effects. The exact mechanism is unknown but may involve reduced iron solubility due to increase in gastric pH and/or reduced absorption due to complexation or precipitation of the iron. Based on existing data, sodium bicarbonate and calcium carbonate appear to have greater effects than antacids containing magnesium and aluminum hydroxides. In a study of patients with mild iron deficiency anemia, coadministration of ferrous sulfate with sodium bicarbonate 1 gram and calcium carbonate 500 mg reduced iron absorption by 50% and 67%, respectively, while 5 mL of an antacid containing magnesium and aluminum hydroxides had little effect. Another study also found no effect on iron absorption when ferrous sulfate (equivalent to 10 mg/kg of elemental iron) was coadministered with magnesium hydroxide (1 mg for every 5 mg of elemental iron ingested) in a group of healthy, fasting male subjects. In contrast, absorption of iron from ferrous sulfate and ferrous fumarate tablets was reduced by 37% and 31%, respectively, following administration of an antacid containing magnesium carbonate, magnesium hydroxide, and aluminum hydroxide in a study of healthy, iron-replete volunteers. Similarly, in a study of nine patients, coadministration of 5 mg of ferrous sulfate with a 35 gram dose of magnesium trisilicate was found to reduce iron absorption by an average of more than 70%. The interaction reportedly does not occur in the presence of ascorbic acid, which may competitively bind with iron and prevent the interference with iron absorption.
MANAGEMENT: To minimize the potential for interaction, it may be appropriate to administer oral iron preparations at least two hours apart from antacids or other agents with acid-neutralizing effects.
References (12)
- O'Neil-Cutting MA, Crosby WH (1986) "The effect of antacids on the absorption of simultaneously ingested iron." JAMA, 255, p. 1468-70
- Hall GJ, Davis AE (1969) "Inhibition of iron absorption by magnesium trisilicate." Med J Aust, 2, p. 95-6
- Coste JF, de Bari VA, Keil LB, Needle MA (1977) "In-vitro interactions of oral hematinics." Curr Ther Res Clin Exp, 22, p. 205-15
- Corby DG, McCullen AH, Chadwick EW, Decker WJ "Effect of orally administered magnesium hydroxide in experimental iron intoxication." J Toxicol Clin Toxicol, 23, p. 489-99
- Gugler R, Allgayer H (1990) "Effects of antacids on the clinical pharmacokinetics of drugs. An update." Clin Pharmacokinet, 18, p. 210-9
- Rastogi SP, Padilla F, Boyd CM (1975) "Effect of aluminum hydroxide on iron absorption." Kidney Int, 8, p. 417
- Ekenved G, Halvorsen L, Solvell L (1976) "Influence of a liquid antacid on the absorption of different iron salts." Scand J Haematol, Suppl 28, p. 65-77
- Coste JF, De Barbi VA, Keil LB, Needle MA (1977) "In-vitro interactions of oral hemantics and antacid suspensions." Curr Ther Res Clin Exp, 22, p. 205-16
- Snyder BK, Clark RF (1999) "Effect of magnesium hydroxide administration on iron absorption after a supratherapeutic dose of ferrous sulfate in human volunteers: A randomized controlled trial." Ann Emerg Med, 33, p. 400-5
- Wallace KL, Curry SC, LoVecchio F, Raschke R (1999) "Effect of magnesium hydroxide on iron absorption after ferrous sulfate." Ann Emerg Med, 34, p. 685-6
- Pruchnicki MC, Coyle JD, Hoshaw-Woodard S, Bay WH (2002) "Effect of phosphate binders on supplemental iron absorption in healthy subjects." J Clin Pharmacol, 42, p. 1171-6
- (2010) "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories
betamethasone cholecalciferol
Applies to: betamethasone / iodixanol / lidocaine, calcium / ferrous fumarate / vitamin d
MONITOR: Use of systemic corticosteroids may reduce the effects of vitamin D and its analogs, though the exact mechanism is likely multifaceted. In general, corticosteroid use leads to increased excretion of calcium, whereas vitamin D promotes calcium absorption and is often administered with calcium to increase the absorption. Another potential mechanism involved is that long-term steroid use can contribute to weight gain and vitamin D is a fat-soluble vitamin; therefore, the bioavailability of vitamin D may be reduced in overweight and/or obese patients. Additionally, some studies have suggested that corticosteroid use increases the breakdown of 25-hydroxyvitamin D (25(OH)D), the active metabolite of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). However, several studies examining this theory found no significant differences when the levels of 25(OH)D in patients treated with corticosteroids were compared to the levels measured either pretreatment or in control groups. The results may be demonstrating a lack of effect on 25(OH)D or could be related to limitations in the studies themselves. Regardless of the exact mechanism, the 2001-2006 National Health and Nutrition Examination Survey from the United States reported that 25(OH)D deficiency (levels less than 25 nmol/L or 10 ng/mL) was more than twice as common among children and adults who reported oral steroid use (11%) than in nonusers (5%).
MANAGEMENT: Increased monitoring of calcium and vitamin D levels may be advisable in patients on systemic corticosteroids. Depending on the patient's levels, increased vitamin D supplementation may be required during coadministration. The severity of this interaction is likely impacted by the dosage and/or duration of the systemic corticosteroid. Consultation with relevant local and/or national guidelines may be helpful when deciding on vitamin D dosing as well as goal vitamin D levels.
References (10)
- (2024) "Product Information. Fultium-D3 (colecalciferol)." Internis Pharmaceuticals Ltd
- (2024) "Product Information. Ostelin Specialist Range Vitamin D (colecalciferol)." Sanofi-Aventis Healthcare Pty Ltd T/A Sanofi Consumer Healthcare
- (2021) "Product Information. Rocaltrol (calcitriol)." Atnahs Pharma UK Ltd
- (2019) "Product Information. Calcitriol (calcitriol)." Strides Pharma Inc.
- (2024) "Product Information. Calcitriol (GenRx) (calcitriol)." Apotex Pty Ltd
- Skversky AL, Kumar J, Abramowitz MK, Kaskel FJ, Melamed ML (2011) "Association of glucocorticoid use and low 25-hydroxyvitamin D levels: results from the National Health and Nutrition Examination Survey (NHANES): 2001-2006." J Clin Endocrinol Metab, 96, p. 3838-45
- Efird JT, Anderson EJ, Jindal C, et al. (2024) The interaction of vitamin d and corticosteroids: a mortality analysis of 26,508 veterans who tested positive for SARS-CoV-2. https://www.mdpi.com/1660-4601/19/1/447
- Wakeman M (2024) A literature review of the potential impact of medication on vitamin D status. https://www.dovepress.com/a-literature-review-of-the-potential-impact-of-medication-on-vitamin-d-peer-reviewed-fulltext-article-RMHP
- Davidson ZE, Walker KZ, Truby H (2012) "Clinical review: do glucocorticosteroids alter vitamin D status? A systematic review with meta-analyses of observations studies." J Clin Endocrinol Metab, 97, p. 738-44
- Alzohily B, AlMenhali A, Gariballa S, Munawar N, Yasin J, Shah I (2024) Unraveling the complex interplay between obesity and vitamin D metabolism. https://www.nature.com/articles/s41598-024-58154-z
calcium carbonate betamethasone
Applies to: calcium / ferrous fumarate / vitamin d, betamethasone / iodixanol / lidocaine
Antacids and agents with acid-neutralizing effects may impair the oral absorption of dexamethasone, prednisolone, prednisone, and other orally administered corticosteroids, although data from published studies are somewhat conflicting. The mechanism of interaction and clinical significance are unknown. No particular intervention is necessary during concomitant therapy with these agents, but clinicians should be aware of the potential for interaction.
References (3)
- Albin H, Vincon G, Demotes-Mainard F, et al. (1984) "Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone." Eur J Clin Pharmacol, 26, p. 271-3
- Naggar VF, Khalil SA, Gouda MW (1978) "Effect of concomitant administration of magnesium trisilicate on GI absorption of dexamethasone in humans." J Pharm Sci, 67, p. 1029-30
- Tanner AR, Caffin JA, Halliday JW, Powell LW (1979) "Concurrent administration of antacids and prednisone: effect on serum levels of prednisolone." Br J Clin Pharmacol, 7, p. 397-400
Drug and food interactions
lidocaine food
Applies to: betamethasone / iodixanol / lidocaine
MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of lidocaine, which is primarily metabolized by the CYP450 3A4 and 1A2 isoenzymes to active metabolites (monoethylglycinexylidide (MEGX) and glycinexylidide). 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 oral and/or intravenous lidocaine and potent CYP450 3A4 inhibitor, itraconazole, as well as moderate CYP450 3A4 inhibitor, erythromycin. A pharmacokinetic study of 9 healthy volunteers showed that the administration of lidocaine oral (1 mg/kg single dose) with itraconazole (200 mg daily) increased lidocaine systemic exposure (AUC) and peak plasma concentration (Cmax) by 75% and 55%, respectively. However, no changes were observed in the pharmacokinetics of the active metabolite MEGX. In the same study, when the moderate CYP450 3A4 inhibitor erythromycin (500 mg three times a day) was administered, lidocaine AUC and Cmax increased by 60% and 40%, respectively. By contrast, when intravenous lidocaine (1.5 mg/kg infusion over 60 minutes) was administered on the fourth day of treatment with itraconazole (200 mg once a day) no changes in lidocaine AUC or Cmax were observed. However, when lidocaine (1.5 mg/kg infusion over 60 minutes) was coadministered with erythromycin (500 mg three times a day) in the same study, the AUC and Cmax of the active metabolite MEGX significantly increased by 45-60% and 40%, respectively. The observed differences between oral and intravenous lidocaine when coadministered with CYP450 3A4 inhibitors may be attributed to inhibition of CYP450 3A4 in both the gastrointestinal tract and liver affecting oral lidocaine to a greater extent than intravenous lidocaine. 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 lidocaine may lead to serious and/or life-threatening reactions including respiratory depression, convulsions, bradycardia, hypotension, arrhythmias, and cardiovascular collapse.
MONITOR: Certain foods and behaviors that induce CYP450 1A2 may reduce the plasma concentrations of lidocaine. The proposed mechanism is induction of hepatic CYP450 1A2, one of the isoenzymes responsible for the metabolic clearance of lidocaine. Cigarette smoking is known to be a CYP450 1A2 inducer. In one pharmacokinetic study of 4 smokers and 5 non-smokers who received 2 doses of lidocaine (100 mg IV followed by 100 mg orally after a 2-day washout period), the smokers' systemic exposure (AUC) of oral lidocaine was 68% lower than non-smokers. The AUC of IV lidocaine was only 9% lower in smokers compared with non-smokers. Other CYP450 1A2 inducers include cruciferous vegetables (e.g., broccoli, brussels sprouts) and char-grilled meat. Therefore, eating large or variable amounts of these foods could also reduce lidocaine exposure. The clinical impact of smoking and/or the ingestion of foods that induce CYP450 1A2 on lidocaine have not been studied, however, a loss of efficacy may occur.
MANAGEMENT: Caution is recommended if lidocaine is to be used in combination with grapefruit and grapefruit juice. Monitoring for lidocaine toxicity and plasma lidocaine levels may also be advised, and the lidocaine dosage adjusted as necessary. Patients who smoke and/or consume cruciferous vegetables may be monitored for reduced lidocaine efficacy.
References (7)
- Huet PM, LeLorier J (1980) "Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics" Clin Pharmacol Ther, 28, p. 208-15
- (2024) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Inc.
- (2015) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Healthcare Corporation
- (2022) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hameln Pharma Ltd
- (2022) "Product Information. Xylocaine HCl (lidocaine)." Aspen Pharmacare Australia Pty Ltd
- Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of oral lignocaine https://pubmed.ncbi.nlm.nih.gov/10193676/
- Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine https://pubmed.ncbi.nlm.nih.gov/9832299/
calcium carbonate food
Applies to: calcium / ferrous fumarate / vitamin d
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.
References (6)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
- Mangels AR (2014) "Bone nutrients for vegetarians." Am J Clin Nutr, 100, epub
- Davies NT (1979) "Anti-nutrient factors affecting mineral utilization." Proc Nutr Soc, 38, p. 121-8
cholecalciferol food
Applies to: calcium / ferrous fumarate / vitamin d
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.
References (10)
- (2023) "Product Information. Drisdol (ergocalciferol)." Validus Pharmaceuticals LLC
- (2024) "Product Information. Fultium-D3 (colecalciferol)." Internis Pharmaceuticals Ltd
- (2024) "Product Information. Ostelin Specialist Range Vitamin D (colecalciferol)." Sanofi-Aventis Healthcare Pty Ltd T/A Sanofi Consumer Healthcare
- (2021) "Product Information. Rocaltrol (calcitriol)." Atnahs Pharma UK Ltd
- (2019) "Product Information. Calcitriol (calcitriol)." Strides Pharma Inc.
- (2024) "Product Information. Calcitriol (GenRx) (calcitriol)." Apotex Pty Ltd
- (2022) "Product Information. Ergocalciferol (ergocalciferol)." RPH Pharmaceuticals AB
- (2020) "Product Information. Sandoz D (cholecalciferol)." Sandoz Canada Incorporated
- Fischer V, Haffner-Luntzer M, Prystaz K, et al. (2024) Calcium and vitamin-D deficiency marginally impairs fracture healing but aggravates posttraumatic bone loss in osteoporotic mice. https://www.nature.com/articles/s41598-017-07511-2
- National Institutes of Health Office of Dietary Supplements (2024) Vitamin D https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h37
ferrous fumarate food
Applies to: calcium / ferrous fumarate / vitamin d
ADJUST DOSING INTERVAL: Concomitant use of some oral medications may reduce the bioavailability of orally administered iron, and vice versa.
Food taken in conjunction with oral iron supplements may reduce the bioavailability of the iron. However, in many patients intolerable gastrointestinal side effects occur necessitating administration with food.
MANAGEMENT: Ideally, iron products should be taken on an empty stomach (i.e., at least 1 hour before or 2 hours after meals), but if this is not possible, administer with meals and monitor the patient more closely for a subtherapeutic effect. Some studies suggest administration of iron with ascorbic acid may enhance bioavailability. In addition, administration of oral iron products and some oral medications should be separated whenever the bioavailability of either agent may be decreased. Consult the product labeling for specific separation times and monitor clinical responses as appropriate.
References (2)
- "Product Information. Feosol (ferrous sulfate)." SmithKline Beecham
- (2021) "Product Information. Accrufer (ferric maltol)." Shield Therapeutics
lidocaine food
Applies to: betamethasone / iodixanol / lidocaine
MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.
MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.
References (4)
- (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
- jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
- Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
- Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38
Therapeutic duplication warnings
No duplication warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
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