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Drug Interactions between Caltrate 600+D and Di-Phen

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

phenytoin calcium carbonate

Applies to: Di-Phen (phenytoin) and Caltrate 600+D (calcium / vitamin d)

ADJUST DOSING INTERVAL: Concurrent administration of antacids may decrease the bioavailability of phenytoin. The mechanism of interaction is unknown. In eight healthy volunteers, coadministration of a single 600 mg dose of phenytoin and an antacid containing either aluminum-magnesium hydroxide or calcium carbonate (dose equal to 160 mEq of neutralizing capacity) given one and three hours after meals and at bedtime on the same day resulted in an approximately 25% reduction in the total area under the concentration-time curve (AUC) of phenytoin compared to administration alone. An antacid containing aluminum hydroxide-magnesium trisilicate given in an equivalent dose also reduced the AUC of phenytoin, but the difference was not statistically significant. In another study, aluminum hydroxide-magnesium trisilicate caused a 12% reduction in steady-state serum phenytoin levels in six epileptic patients, but seizure frequency was not affected. There have also been isolated case reports of patients with low serum phenytoin levels or inadequate seizure control attributed to concurrent antacid administration. In a few of the patients, serum phenytoin levels rose two to threefold when antacid administration was delayed by 2 to 3 hours. However, some studies have failed to find a significant interaction with these antacids.

MANAGEMENT: Given the narrow therapeutic index and the large interindividual variability in the pharmacokinetics of phenytoin, patients requiring concomitant antacid therapy should consider separating the times of administration by at least two to three hours if possible. Serum phenytoin levels and seizure activity should be monitored.

References

  1. D'Arcy PF, McElnay JC "Drug-antacid interactions: assessment of clinical importance." Drug Intell Clin Pharm 21 (1987): 607-17
  2. O'Brien LS, Orme ML, Breckenridge AM "Failure of antacids to alter the pharmacokinetics of phenytoin." Br J Clin Pharmacol 6 (1978): 176-7
  3. Kulshrestha K, Thomas M, Wadsworth J, Richens A "Interaction between phenytoin and antacids." Br J Clin Pharmacol 6 (1978): 177-9
  4. Carter BL, Garnett WR, Pellock JM, et al. "Effects of antacids on phenytoin bioavailability." Ther Drug Monit 3 (1981): 333-40
  5. "Product Information. Dilantin (phenytoin)." Parke-Davis PROD (2001):
  6. Kutt H "Interactions of antiepileptic drugs." Epilepsia 16 (1975): 393-402
  7. Chapron DJ, Kramer PA, Mariano SL, Hohnadel DC "Effect of calcium and antacids on phenytoin bioavailability." Arch Neurol 36 (1979): 436-8
View all 7 references

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Moderate

phenytoin ergocalciferol

Applies to: Di-Phen (phenytoin) and Caltrate 600+D (calcium / vitamin d)

MONITOR: Coadministration with CYP450 inducers such as rifampin, isoniazid, barbiturates, and certain anticonvulsants may decrease the pharmacologic effects of vitamin D analogs. These agents are thought to induce the hepatic conversion of vitamin D to inactive metabolites and have been shown to reduce circulating levels of active vitamin D, sometimes accompanied by reduced serum calcium and increased parathyroid hormone levels. Patients on long-term anticonvulsant therapy have occasionally developed osteomalacia, presumably due to interference with vitamin D and calcium metabolism. There have also been isolated reports of patients who responded poorly to vitamin D supplements during treatment with phenytoin and/or primidone.

MANAGEMENT: Patients receiving vitamin D analogs with CYP450 inducers should be monitored for potentially reduced vitamin D effects. Dosage adjustments may be necessary.

References

  1. "Product Information. Rocaltrol (calcitriol)." Roche Laboratories PROD (2001):
  2. "Product Information. Zemplar (paricalcitol)." Abbott Pharmaceutical PROD (2001):
  3. "Product Information. Hectorol (doxercalciferol)." Genzyme Corporation (2004):
  4. "Product Information. One-Alpha (alfacalcidol)." Pharmel Inc (2004):
View all 4 references

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Drug and food interactions

Moderate

phenytoin food

Applies to: Di-Phen (phenytoin)

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

  1. Sandor P, Sellers EM, Dumbrell M, Khouw V "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther 30 (1981): 390-7
  2. Holtz L, Milton J, Sturek JK "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr 11 (1987): 183-6
  3. Sellers EM, Holloway MR "Drug kinetics and alcohol ingestion." Clin Pharmacokinet 3 (1978): 440-52
  4. "Product Information. Dilantin (phenytoin)." Parke-Davis PROD (2001):
  5. Doak KK, Haas CE, Dunnigan KJ, et al. "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy 18 (1998): 637-45
  6. Rodman DP, Stevenson TL, Ray TR "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy 15 (1995): 801-5
  7. Au Yeung SC, Ensom MH "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother 34 (2000): 896-905
  8. Ozuna J, Friel P "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs 16 (1984): 289-91
  9. Faraji B, Yu PP "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs 30 (1998): 55-9
  10. Marvel ME, Bertino JS "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr 15 (1991): 316-8
  11. Fleisher D, Sheth N, Kou JH "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr 14 (1990): 513-6
  12. Haley CJ, Nelson J "Phenytoin-enteral feeding interaction." DICP 23 (1989): 796-8
  13. Guidry JR, Eastwood TF, Curry SC "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med 150 (1989): 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia 28 (1987): 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  16. Cerner Multum, Inc. "Australian Product Information." O 0
View all 16 references

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Moderate

calcium carbonate food

Applies to: Caltrate 600+D (calcium / 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

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  5. Mangels AR "Bone nutrients for vegetarians." Am J Clin Nutr 100 (2014): epub
  6. Davies NT "Anti-nutrient factors affecting mineral utilization." Proc Nutr Soc 38 (1979): 121-8
View all 6 references

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Therapeutic duplication warnings

No 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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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