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Grapefruit juice and its interaction with warfarin

Poster · September 2017


DOI: 10.13140/RG.2.2.36010.72647

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Ana Baltazar João José Joaquim


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Grapefruit juice and its interaction with Warfarin
Neto Inês1, Serra Mariana1, Coelho Núria1, Mendes Pedro1, Baltazar Ana2, Joaquim João3, Matos Cristiano3
1) Students of Dietetics and Nutrition Degree, Coimbra Health School/IPC, Coimbra, Portugal
2) Department of Dietetics and Nutrition, Coimbra Health School/IPC, Coimbra, Portugal
3) Department of Pharmacy, Coimbra Health School/IPC, Coimbra, Portugal

Background ⇨Type of flavonoid; It has several isoforms, with CYP3A4


being responsible for the
⇨ High number of metabolism of more than 50% of
pharmacological effects drugs, including warfarin
Naringenin recognized;
⇨ Inhibition of CYP 450 enzymes.

CYP450
Furanocumarins ⇨Organic chemical compounds Responsible for the first Inhibition will increase the oral
produced by plants; phase metabolism of bioavailability of drugs that
⇨ Strong and irreversible binding with drugs, toxins and other
substances
went through an extensive 1st
the same enzymatic superfamily as passage effect
naringenin, the CYP 450.

Warfarin

Oral anticoagulant for the prevention and treatment of deep vein


thrombosis and pulmonary thromboembolism and prevention of
thromboembolism in patients with atrial fibrillation or undergoing
heart valve surgery.
Enantiomers R and S – metabolized by cytochrome P450 (CYP)

CYP2C9, CYP1A2 and CYP3A4


Responsible for Warfarin’s metabolism

Schematic representation of transporters acting together to eliminate drugs from


Warfarin and grapefruit juice the organism. (Dolton et al., 2012).

CYP2C9, CYP1A2  Warfarin’s * International Normalized Ratio


and CYP3A4 - plasmatic  Enantiomer’s Hemorrhagic Laboratory measures to evaluate the
 INR * extrinsic coagulation / Exam used to
when inhibited concentration depuration complications
determine blood’s coagulation tendency.

Aim Highlight, under a bibliographic review, the interaction between grapefruit juice and warfarin.

Other studies found were not


It was conduced a research on Single case studies, case reports considered because results were
Material & Methods PubMed, using the keywords: warfarin, and revision articles in PT and either inconclusive or the quantity of
juice provided was to litle to obtain a
grapefruit juice, oral anticoagulants. EN between 2009 and 2016.
significant conclusion

Results
Bodiford et al. (2013) Mouly et al. (2017) PL-Detailed
Document (2013)
Norwood et al. (2015) Di Minno et al. (2017) Conclusion
The pharmacokinetic
• 65mg/week “ An interval of three days • 50 fl oz “scientific evidence is “Components of profile and effect of
INR = 1,7 between the ingestion of (≈1500 ml)/day : scarce. Until further grapefruit and grapefruit juice, especially
grapefruit and drug intake information is available, grapefruit juice, in large quantities, on
• 10mg/day + grapefruit completely offsets this risk,  INR clinicians may want to mainly the CYP3A4 makes plausible an
(for 2 weeks) because this is the time encourage patients to furanocoumarins, interaction with warfarin.
INR = 4,77 required for the total consume cranberry inhibit CYP3A4
renewal of intestinal CYP3A4 • 24 fl oz products activity [… ]minor
Therefore, is crucial
• 8mg/day activity”. (≈700ml)/day and grapefruit juice in small hematomas have considering close follow-up
INR = 2,1 For 1 week: to moderate quantities (…) been reported” in patients on warfarin
when taking a dietary who drink grapefruit juice.
• 65mg/weeK No significant history or when assessing
INR = therapeutic range effect possible causes for
over the following 4 months international normalized
ratio (INR) instability.”

References
 Mouly S, Lloret-Linares C, Sellier PO, Sene D, Bergmann JF. “Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort?”. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/27693910
 Norwood DA, Parke CK, Rappa LR. “A Comprehensive Review of Potential Warfarin-Fruit Interactions”. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25112306
 Bodiford AB, Kessler FO, Fermo JD, Ragucci KR. “Elevated international normalized ratio with the consumption of grapefruit and use of warfarin”. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27489634
 Rosane Maria Salvi, Caroline de Oliveira Riella, Cristine Saldanha Souto, Juliana Krunitzki Bueno, Rosane Ramos Guimarães, Carolina Mariante de Abreu. “Fruit juices influence in the bioavailability and half-life of
drugs”. Available at: http://revistaseletronicas.pucrs.br/ojs/index.php/faenfi/article/viewFile/6380/5914
 PL Detail-Document, Potential Drug Interactions with Grapefruit. Pharmacist’s Letter/Prescriber’s Letter. January 2013
 Di Minno, A., Frigerio, B., Spadarella, G., Ravani, A., Sansaro, D., Amato, M., Baldassarre, D. Old and new oral anticoagulants: Food, herbal medicines and drug interactions. Available at: Corresponding author: jjj@estescoimbra.pt
http://www.sciencedirect.com/science/article/pii/S0268960X16300352
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