NutriStack
Calcium and Phenytoin, timing-sensitive.
Calcium can reduce phenytoin absorption if taken simultaneously. While calcium supplementation may be important for patients on phenytoin (which depletes calcium), timing must be managed to avoid impairing drug absorption and seizure control.
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At a glance
- Pair type
- Timing Sensitive
- Evidence (highest tier)
- Moderate
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored timing-sensitive row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Timing Sensitive · Moderate evidence
Timing Sensitive
What is happening. Calcium can reduce phenytoin absorption if taken simultaneously. While calcium supplementation may be important for patients on phenytoin (which depletes calcium), timing must be managed to avoid impairing drug absorption and seizure control.
Mechanism. Calcium can form complexes with phenytoin in the GI tract, reducing its dissolution and absorption. The interaction is most significant with calcium carbonate and other alkaline calcium forms that may also raise local pH, further affecting phenytoin solubility.
Recommendation. Separate phenytoin and calcium supplements by at least 2 hours to avoid absorption interference. Calcium supplementation is still recommended for bone health during phenytoin therapy, just not at the same time as the medication.
Minimum separation. 120
Sources (3)
- Carter BL et al. Effect of antacids on phenytoin bioavailability. Ther Drug Monit. 1981;3(4):333-340. PMID 7330692
- Liu C, Kuang X, Li K, Guo X, Deng Q, Li D. Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Food & Function. 2020. PMID 33237064
- Yao P, Bennett D, Mafham M et al.. Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis. JAMA Network Open. 2019. PMID 31860103
Stack Score
How this pair moves the number.
Effect on the composite score
If both Calcium and Phenytoin are in the same stack, this pair applies −5 to your Stack Score (per scored timing-sensitive row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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