Can you take Diovan and consume grapefruit. How does grapefruit juice interact with cardiovascular medications. What are the potential risks of combining grapefruit with valsartan. Is it safe to drink grapefruit juice while taking amlodipine-valsartan.

The Complexity of Grapefruit-Medication Interactions

Grapefruit and certain medications can interact in ways that may pose health risks. This is particularly true for some cardiovascular medications, including valsartan (brand name Diovan) and amlodipine-valsartan combinations. Understanding these interactions is crucial for patients taking these medications.

Grapefruit juice has been shown to inhibit specific enzymes in the body, particularly CYP3A4, which is responsible for metabolizing many drugs. This inhibition can lead to increased absorption of certain medications, potentially causing adverse effects or toxicity.

Why does grapefruit interact with some medications?

Grapefruit contains compounds called furanocoumarins, which interfere with the normal breakdown of certain drugs in the digestive system. This interference can result in higher levels of the medication in the bloodstream, effectively increasing the dose and potentially leading to side effects or toxicity.

Valsartan and Grapefruit: A Closer Look

Valsartan, an angiotensin receptor blocker (ARB) used to treat high blood pressure and heart failure, doesn’t appear to have a direct interaction with grapefruit juice. However, caution is still advised due to potential indirect effects and the combination of valsartan with other medications.

Does valsartan interact directly with grapefruit?

While there’s no strong evidence of a direct interaction between valsartan and grapefruit, healthcare providers often advise caution. This is because valsartan is frequently prescribed in combination with other medications that may interact with grapefruit juice.

Amlodipine-Valsartan Combination and Grapefruit

The combination of amlodipine and valsartan presents a more complex scenario. Amlodipine, a calcium channel blocker, has been shown to interact with grapefruit juice in ways similar to felodipine, another medication in the same class.

How does grapefruit juice affect amlodipine?

Grapefruit juice can increase the absorption of amlodipine, potentially leading to enhanced effects of the medication. This could result in a more significant drop in blood pressure than intended, causing symptoms like dizziness or fainting.

Potential Risks and Side Effects

The interaction between grapefruit and cardiovascular medications can lead to various risks and side effects. These may range from mild discomfort to more severe complications.

• Increased blood pressure-lowering effect
• Dizziness or lightheadedness
• Fainting
• Increased heart rate
• Headache
• Flushing

Can the interaction lead to serious complications?

In some cases, the interaction between grapefruit and cardiovascular medications can lead to more serious complications. These may include severe hypotension (low blood pressure), abnormal heart rhythms, or even kidney problems. It’s crucial to consult with a healthcare provider about potential risks.

Other Nutrients and Substances to Consider

While grapefruit is a primary concern, other nutrients and substances can also interact with valsartan and similar medications. Understanding these interactions is essential for comprehensive medication management.

How does potassium interact with valsartan?

Valsartan and other ARBs can cause increases in blood potassium levels. Patients taking these medications should be cautious with potassium supplements, potassium-containing salt substitutes, and high-potassium foods unless directed otherwise by their doctor.

What about DHEA and amlodipine?

Amlodipine has been shown to raise blood levels of DHEA-sulfate in certain patient populations, such as insulin-resistant, obese men with high blood pressure. The clinical significance of this interaction is not fully understood and may require further research.

Alternative Fruits and Juices

Given the potential risks associated with grapefruit consumption, patients may wonder about alternative fruits and juices that are safe to consume with their medications.

Is pomegranate juice a safe alternative?

Surprisingly, pomegranate juice has been shown to inhibit the same enzyme as grapefruit juice, potentially leading to similar interactions with medications like amlodipine. Therefore, it may not be a suitable alternative for patients taking these medications.

What fruits are generally safe with cardiovascular medications?

While individual cases may vary, many fruits are generally considered safe to consume with cardiovascular medications. These may include:

• Apples
• Berries (strawberries, blueberries, raspberries)
• Peaches
• Pears
• Plums

However, it’s always best to consult with a healthcare provider for personalized advice.

Monitoring and Managing Medication Interactions

Proper management of potential interactions between medications and foods like grapefruit requires vigilance and communication with healthcare providers.

How can patients monitor for potential interactions?

Patients can monitor for potential interactions by:

1. Keeping a food diary, especially noting consumption of grapefruit or grapefruit juice
2. Regularly measuring blood pressure at home
3. Being aware of any unusual symptoms or side effects
4. Reporting any concerns to their healthcare provider promptly

When should patients consult their healthcare provider?

Patients should consult their healthcare provider:

• Before making any significant changes to their diet
• If they experience new or worsening side effects
• If they have questions about food-drug interactions
• During regular check-ups to review all medications and potential interactions

Future Research and Developments

The field of drug-nutrient interactions is continually evolving, with ongoing research providing new insights into the complex relationships between foods and medications.

What areas of research are currently being explored?

Current areas of research in grapefruit-medication interactions include:

• Identifying specific compounds in grapefruit responsible for interactions
• Developing new drug formulations that are less susceptible to grapefruit interactions
• Investigating potential beneficial interactions between foods and medications
• Exploring genetic factors that may influence individual susceptibility to these interactions

As research progresses, our understanding of these interactions will likely improve, potentially leading to more personalized recommendations for patients taking cardiovascular medications.

How might future developments impact patient care?

Future developments in this field could lead to:

• More precise guidelines for food and medication interactions
• Development of medications less prone to food interactions
• Improved methods for predicting individual patient risk for interactions
• Enhanced patient education tools and resources

These advancements could significantly improve patient safety and the effectiveness of cardiovascular treatments.

Practical Advice for Patients

For patients taking valsartan, amlodipine-valsartan, or similar cardiovascular medications, navigating potential food interactions can be challenging. Here are some practical tips to help manage these concerns:

How can patients safely enjoy citrus fruits while taking cardiovascular medications?

While grapefruit may pose risks, other citrus fruits are generally considered safe. Patients can:

• Opt for oranges, tangerines, or lemons instead of grapefruit
• Choose small portions of citrus fruits to minimize potential risks
• Consume citrus fruits at a different time of day from when they take their medication
• Always consult with their healthcare provider about specific dietary choices

What strategies can help patients remember their medication schedule and dietary restrictions?

To maintain a consistent medication schedule and adhere to dietary guidelines, patients can:

1. Use pill organizers to sort medications by day and time
2. Set reminders on smartphones or other devices
3. Keep a medication and food diary
4. Place notes or reminders in visible locations, such as on the refrigerator
5. Enlist the help of family members or caregivers to assist with medication management

By implementing these strategies, patients can better manage their medications and reduce the risk of potential interactions with foods like grapefruit.

The Role of Healthcare Providers

Healthcare providers play a crucial role in managing potential interactions between medications like valsartan and foods like grapefruit. Their expertise and guidance are essential for ensuring patient safety and optimizing treatment outcomes.

How do healthcare providers assess the risk of grapefruit-medication interactions?

Healthcare providers assess the risk of grapefruit-medication interactions by:

• Reviewing the patient’s complete medication list, including over-the-counter drugs and supplements
• Considering the patient’s dietary habits and preferences
• Evaluating the patient’s overall health status and any comorbidities
• Assessing the potential benefits and risks of the medication regimen
• Staying updated on the latest research and guidelines regarding food-drug interactions

What information should patients provide to their healthcare providers?

To help healthcare providers make informed decisions, patients should provide:

• A complete list of all medications, including prescription, over-the-counter, and herbal supplements
• Information about their typical diet, including consumption of grapefruit or grapefruit juice
• Any changes in their health status or the emergence of new symptoms
• Details about their lifestyle, including exercise habits and alcohol consumption
• Any concerns or questions about their medications or potential interactions

Open communication between patients and healthcare providers is essential for managing potential risks and ensuring the best possible outcomes from cardiovascular treatments.

Understanding Drug Metabolism and Interactions

To fully grasp the implications of grapefruit-medication interactions, it’s helpful to understand the basics of drug metabolism and how these interactions occur at a biological level.

How do drugs like valsartan and amlodipine get metabolized in the body?

Drug metabolism typically occurs in two phases:

1. Phase I: This often involves the cytochrome P450 enzyme system, particularly CYP3A4, which modifies the drug molecule.
2. Phase II: The modified drug molecule is conjugated with another substance to make it more water-soluble and easier to excrete.

Valsartan is primarily eliminated unchanged via biliary excretion, while amlodipine is extensively metabolized in the liver, primarily by CYP3A4.

What mechanisms are involved in grapefruit-medication interactions?

Grapefruit-medication interactions primarily occur through:

• Inhibition of CYP3A4 enzymes in the intestinal wall, leading to increased drug absorption
• Interference with drug transport proteins, potentially affecting how drugs enter and leave cells
• Additive effects on blood pressure or heart rate when combined with certain medications

Understanding these mechanisms helps explain why some medications are more susceptible to grapefruit interactions than others.

Global Perspectives on Grapefruit Consumption and Medication Safety

The issue of grapefruit-medication interactions is not confined to a single region or country. It’s a global concern that affects patients worldwide, though awareness and approaches to managing these interactions may vary.

How do different countries approach the issue of grapefruit-medication interactions?

Different countries may approach this issue in various ways:

• In the United States, the FDA requires some medications to carry warnings about grapefruit interactions
• European countries often include grapefruit interaction information in patient leaflets
• Japan has conducted extensive research on grapefruit juice interactions and provides detailed guidance to healthcare providers
• Some countries may have less awareness or fewer regulations regarding these interactions

These differences highlight the need for global collaboration and standardization in addressing food-drug interactions.

How does grapefruit consumption vary around the world?

Grapefruit consumption patterns differ globally:

• The United States is one of the largest producers and consumers of grapefruit
• Mediterranean countries often incorporate grapefruit in their diets
• Some Asian countries have seen an increase in grapefruit consumption in recent years
• In some regions, grapefruit may be less common or considered a luxury fruit

These variations in consumption patterns can impact the prevalence and significance of grapefruit-medication interactions in different populations.

As our understanding of these interactions grows, it becomes increasingly important to consider global perspectives and develop internationally applicable guidelines for managing potential risks associated with grapefruit consumption and cardiovascular medications.

Amlodipine-Valsartan – Health Information Library

Summary of Interactions with Vitamins, Herbs, & Foods

What Are Nutrient Interactions

Types of interactions:
Beneficial
Adverse
Check

Replenish Depleted Nutrients

• none

Reduce Side Effects

• none

Support Medicine

• none

Reduces Effectiveness

• none

Potential Negative Interaction

• Potassium

  Angiotensin receptor blocker drugs such as valsartan have caused significant increases in blood potassium levels. Potassium supplements, potassium-containing salt substitutes (No Salt, Morton Salt Substitute, and others), and even high-potassium foods (including Noni juice) should be avoided by those taking valsartan, unless directed otherwise by their doctor.

Explanation Required 

• DHEA

  Amlodipine has been shown to raise blood levels of DHEA-sulfate in insulin-resistant, obese men with high blood pressure.

• Ingestion of grapefruit juice has been shown to increase the absorption of felodipine (a drug similar in structure and action to that of amlodipine) and to increase the adverse effects of the medication in patients with hypertension. Until more is known, it seems that grapefruit juice should not be ingested by people taking amlodipine or similar drugs. The same effects might be seen from eating grapefruit as from drinking its juice.

• Pleurisy Root

  As pleurisy root and other plants in the Aesclepius genus contain cardiac glycosides, it is best to avoid use of pleurisy root with heart medications such as calcium channel blockers.

  The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

• Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice. The degree of inhibition is about the same for each of these juices. Therefore, it would be reasonable to expect that pomegranate juice might interact with amlodipine in the same way that grapefruit juice does.

  The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

• Top of the page

• Next Section:

Health Information Library

Interactions of grapefruit juice and cardiovascular medications: A potential risk of toxicity

1. Statistics Canada Per Capita Consumption of Selected Fruits and Vegetables, Canada, 1997 to 2000 (kg/yr)(May 14, 2002) <http://www.gov.on.ca/OMAFRA/english/stats/food/vegpcc.html> (Version current at October 8, 2003).

2. Lesser PF.Florida grapefruit-juice developments October71997. <http://www.fred.ifas.ufl.edu/citrus/pubs/misc/am.html> (Version current at October 8, 2003).

3. Fuhr U. Drug interactions with grapefruit juice: Extent, probable mechanism and clinical relevance. Drug Safety. 1998;18:251–72. [PubMed] [Google Scholar]

4. Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Pharmacokinet. 1997;33:103–21. [PubMed] [Google Scholar]

5. Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc. 2000;75:933–42. [PubMed] [Google Scholar]

6. Bailey DG, Spence JD, Edgar B, Bayliff CD, Arnold JMO. Ethanol enhances the hemodynamic effects of felodipine. Clin Invest Med. 1989;12:357–62. [PubMed] [Google Scholar]

7. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: Comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther. 2001;69:14–23. [PubMed] [Google Scholar]

8. Guo LQ, Fukuda K, Ohta T, Yamazoe Y. Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metab Dispos. 2000;28:766–71. [PubMed] [Google Scholar]

9. Bailey DG, Dresser GK, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68:468–77. [PubMed] [Google Scholar]

10. Lundahl J, Regardh CG, Edgar B, Johnsson G. The interaction effect of grapefruit juice is maximal after the first glass. Eur J Clin Pharmacol. 1998;54:75–81. [PubMed] [Google Scholar]

11. Edwards DJ, Bernier SM. Naringin and naringenin are not the primary CYP3A inhibitors in grapefruit juice. Life Sci. 1996;59:1025–30. [PubMed] [Google Scholar]

12. Fukuda K, Ohta T, Yamazoe Y. Grapefruit component interacting with rat and human P450 CYP3A: Possible involvement of non-flavonoid components in drug interaction. Biol Pharm Bull. 1997;20:560–4. [PubMed] [Google Scholar]

13. Guo LQ, Taniguchi M, Xiao YQ, Baba K, Ohta T, Yamazoe Y. Inhibitory effect of natural furanocoumarins on human microsomal cytochrome P450 3A activity. Jpn J Pharmacol. 2000;82:122–9. [PubMed] [Google Scholar]

14. Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, et al. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab Dispos. 1997;25:1228–33. [PubMed] [Google Scholar]

15. Ho PC, Saville DJ, Wanwimolruk S. Inhibition of human CYP3A4 activity by grapefruit flavanoids, furanocoumarins and related compounds. J Pharm Pharm Sci. 2001;4:217–27. [PubMed] [Google Scholar]

16. Bourian M, Runkel M, Krisp A, Tegtmeier M, et al. Naringenin and interindividual variability in interaction of coumarin with grapefruit juice. Exp Toxicol Pathol. 1999;51:289–93. [PubMed] [Google Scholar]

17. Mangano NG, Cutli VM, Caruso A, De Bernardis E, Amico-Roxas A. Grapefruit juice effects on the bioavailability of cyclosporin-A in rats. Eur Rev Med Pharmacol Sci. 2001;5:1–6. [PubMed] [Google Scholar]

18. Honig PK, Wortham DC, Lazarev A, Cantilena LR. Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine. J Clin Pharmacol. 1996;36:345–51. [PubMed] [Google Scholar]

19. George J, Byth K, Farrell GC. Age but not gender selectively affects expression of individual cytochrome P450 proteins in human liver. Biochem Pharmacol. 1995;50:727–30. [PubMed] [Google Scholar]

20. Schmucker DL. Liver function and phase I drug metabolism in the elderly: A paradox. Drugs Aging. 2001;18:837–51. [PubMed] [Google Scholar]

21. Benet LZ, Kroetz DL, Sheiner LB. Pharmacokinetics: The dynamics of drug absorption, distribution, and elimination. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 1999. pp. 3–28. [Google Scholar]

22. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38:41–57. [PubMed] [Google Scholar]

23. Wacher VJ, Silverman JA, Zhang Y, Benet LZ. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J Pharm Sci. 1998;87:1322–30. [PubMed] [Google Scholar]

24. Thummel KE, Wilkinson GR. In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol. 1998;38:389–430. [PubMed] [Google Scholar]

25. Wang EJ, Casciano CN, Clement RP, Johnson WW. Inhibition of P-glycoprotein transport function by grapefruit juice psoralen. Pharm Res. 2001;18:432–8. [PubMed] [Google Scholar]

26. He K, Iyer KR, Hayes RN, et al. Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol. 1998;11:252–9. [PubMed] [Google Scholar]

27. Yu DK. The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions. J Clin Pharmacol. 1999;39:1203–11. [PubMed] [Google Scholar]

28. Tassaneeyakul W, Guo LQ, Fukuda K, Ohta T, Yamazoe Y. Inhibition selectivity of grapefruit juice components on human cytochromes P450. Arch Biochem Biophys. 2000;378:356–63. [PubMed] [Google Scholar]

29. Chan WK, Nguyen LT, Miller VP, Harris RZ. Mechanism-based inactivation of human cytochrome P450 3A4 by grapefruit juice and red wine. Life Sci. 1998;62:PL135–42. [PubMed] [Google Scholar]

30. Lown KS, Bailey DG, Fontana RJ, et al. Grapefruit juice increase felopdipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest. 1997;99:2545–53. [PMC free article] [PubMed] [Google Scholar]

31. Eagling VA, Profit L, Back DJ. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999;48:543–52. [PMC free article] [PubMed] [Google Scholar]

32. Spahn-Langguth H, Langguth P. Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol. Eur J Pharm Sci. 2001;12:361–7. [PubMed] [Google Scholar]

33. Matheny CJ, Lamb MW, Brouwer KL, Pollack GM. Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation. Pharmacotherapy. 2001;21:778–96. [PubMed] [Google Scholar]

34. Gersh BJ, Braunwald E, Bonow RO. Chronic coronary artery disease. In: Braunwald E, Zipes DP, Libby P, editors. Heart Disease: A Textbook of Cardiovascular Medicine. New York: WB Saunders and Co; 2001. pp. 1272–363. [Google Scholar]

35. American Society of Health-System Pharmacists . AHFS Drug Information. Bethesda: American Society of Health-Syst Pharmacists, Inc; 2002. [Google Scholar]

36. Zaidenstein R, Dishi V, Gips M, et al. The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil. Eur J Clin Pharmacol. 1998;54:337–40. [PubMed] [Google Scholar]

37. Miniscalco A, Lundahl J, Regardh CG, Edgar B, Eriksson UG. Inhibition of dihydropyridine in rat and human liver microsomes by flavonoids found in grapefruit juice. J Pharmacol Exp Ther. 1992;261:1195–9. [PubMed] [Google Scholar]

38. Dresser GK, Bailey DG, Carruthers SG. Grapefruit juice-felodipine interaction in the elderly. Clin Pharmacol Ther. 2000;68:28–34. [PubMed] [Google Scholar]

39. Takanaga H, Ohnishi A, Murakami H, et al. Pharmacokinetics analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Br J Clin Pharmacol. 2000;49:49–58. [PMC free article] [PubMed] [Google Scholar]

40. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit juice-felodipine interaction: Effect of naringin and 6′,7′-dihydrobergamottin in humans. Clin Pharmacol Ther. 1998;64:248–56. [PubMed] [Google Scholar]

41. Lundahl J, Regardh CG, Edgar B, Johnsson G. Effect of grapefruit juice ingestion – pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol. 1997;52:139–45. [PubMed] [Google Scholar]

42. Lundahl J, Regardh CG, Edgar B, Johnsson G. Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol. 1995;49:61–7. [PubMed] [Google Scholar]

43. Ho PC, Ghose K, Saville D, Wanwimolruk S. Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers. Eur J Clin Pharmacol. 2000;56:693–8. [PubMed] [Google Scholar]

44. Fuhr U, Muller-Peltzer H, Kern R, et al. Effect of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol. 2002;58:45–53. [PubMed] [Google Scholar]

45. Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A. Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Pharmazie. 1994;49:675–9. [PubMed] [Google Scholar]

46. Mohri K, Uesawa Y. Effects of furanocoumarin derivatives in grapefruit juice on nifedipine pharmacokinetics in rats. Pharm Res. 2001;18:177–82. [PubMed] [Google Scholar]

47. Grundy JS, Eliot LA, Kulmatycki KM, Foster RT. Grapefruit juice and orange juice effects on the bioavailability of nifedipine in the rat. Biopharm Drug Dispos. 1998;19:175–83. [PubMed] [Google Scholar]

48. Mohri K, Uesawa Y, Sagawa K. Effects of long-term grapefruit juice ingestion in nifedipine pharmacokinetics: Induction of rat hepatic P-450 by grapefruit juice. Drug Metab Dispos. 2000;28:482–6. [PubMed] [Google Scholar]

49. Takanaga H, Ohnishi A, Murakami H, et al. Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin Pharmacol Ther. 2000;67:201–14. [PubMed] [Google Scholar]

50. Ohtani M, Kawabata S, Kariya S, et al. Effect of grapefruit pulp on the pharmacokinetics of the dihydropyridine calcium antagonists nifedipine and nisoldipine. Yakugaku Zasshi. 2002;122:323–9. [PubMed] [Google Scholar]

51. Fuhr U, Maier-Bruggemann A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol. 1998;36:126–32. [PubMed] [Google Scholar]

52. Uno T, Ohkubo T, Sugawara K, Higashiyama A, Motomura S, Ishizaki T. Effect of grapefruit juice on the stereoselective disposition of nicardipine in humans: Evidence for dominant presystemic elimination at the gut site. Eur J Clin Pharmacol. 2000;5:643–9. [PubMed] [Google Scholar]

53. Hashimoto K, Shirafuji T, Sekino H, et al. Interaction of citrus juices with pranidine, a new 1,4-dihydropyridine calcium antagonist, in health subjects. Eur J Clin Pharmacol. 1998;54:753–60. [PubMed] [Google Scholar]

54. Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlopdipine in healthy volunteers. Eur J Clin Pharmacol. 1996;51:189–93. [PubMed] [Google Scholar]

55. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL. Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Br J Clin Pharmacol. 2000;50:455–63. [PMC free article] [PubMed] [Google Scholar]

56. Klotz U. Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium channel antagonist. Arzneimittelforschung. 2002;52:155–61. [PubMed] [Google Scholar]

57. Lilja JJ, Kivisto KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther. 2000;68:384–90. [PubMed] [Google Scholar]

58. Rogers JD, Zhao J, Liu L, et al. Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Clin Pharmacol Ther. 1999;66:358–66. [PubMed] [Google Scholar]

59. Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998;63:397–402. [PubMed] [Google Scholar]

60. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther. 1999;66:118–27. [PubMed] [Google Scholar]

61. Zaidenstein R, Soback S, Gips M, et al. Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in health volunteers. Ther Drug Monit. 2001;23:369–73. [PubMed] [Google Scholar]

62. Kelly R, Smith TW. Pharmacological treatment of heart failure. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 1996. pp. 814–9. [Google Scholar]

63. Xu H, Rashkow A. Clarithromycin-induced digoxin toxicity: A case report and a review of the literature. Conn Med. 2000;65:527–9. [PubMed] [Google Scholar]

64. Becquemont L, Verstuyft C, Kerb R, et al. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther. 2001;70:311–6. [PubMed] [Google Scholar]

65. Ha HR, Chen J, Leuenberger PM, et al. In vitro inhibition of midazolam and quinidine metabolism by flavonoids. Eur J Clin Pharmacol. 1995;48:367–71. [PubMed] [Google Scholar]

66. Min DI, Ku YM, Geraets DR, Lee H. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in health volunteers. J Clin Pharmacol. 1996;36:469–76. [PubMed] [Google Scholar]

67. Damkier P, Hansen LL, Brøsen K. Effect of diclofenac, disulfram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol. 1999;48:829–38. [PMC free article] [PubMed] [Google Scholar]

68. Libersa CC, Brique SA, Motte KB, et al. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol. 2000;49:373–8. [PMC free article] [PubMed] [Google Scholar]

69. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther. 2002;71:21–9. [PubMed] [Google Scholar]

70. Lee M, Min DI. Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate. Ther Drug Monit. 2001;23:21–6. [PubMed] [Google Scholar]

71. Sullivan DM, Ford MA, Boyden TW. Grapefruit juice and the response to warfarin. Am J Health Syst Pharm. 1998;55:1581–3. [PubMed] [Google Scholar]

72. Health Canada Advisory: Health Canada is advising Canadians not to take certain drugs with grapefruit juice. Health Canada – Warnings/Advisories June212002. <http://www.hc-sc.gc.ca/english/protection/warnings/2002/2002_49e.htm> (Version current at October 20, 2003).

73. Australian Adverse Drug Reaction Bulletin December2002. <http://www.health.gov.au/tga/adr/aadrb/aadr0212.htm> (Version current at October 20, 2003)

74. Bailey DG. Compendium of Pharmaceuticals and Specialties. The Canadian Drug Reference for Health Professionals. Published by the Canadian Pharmacists Association; Ottawa, Ontario, Canada: 2002. Drug administration and grapefruit juice; pp. L88–90. [Google Scholar]

Valodip film-coated tablets 10 mg + 160 mg blister №30

Valodip tablets are indicated for essential hypertension in adult patients whose blood pressure is not regulated by amlodipine or valsartan monotherapy.

Composition

Active ingredient: amlodipine in the form of amlodipine besylate, valsartan;

1 film-coated tablet contains 5 mg of amlodipine as amlodipine besilate and 80 mg of valsartan, or 5 mg of amlodipine as amlodipine besilate and 160 mg of valsartan, or 10 mg of amlodipine as amlodipine besilate and 160 mg of valsartan;

Excipients: microcrystalline cellulose, mannitol (E 421), magnesium stearate, croscarmellose sodium, povidone, colloidal silicon dioxide, sodium lauryl sulfate;

Film coat: polyvinyl alcohol (partially hydrolyzed), titanium dioxide (E 171), polyethylene glycol 3000, talc, iron oxide yellow (E 172).

Contraindications

Hypersensitivity to the active substance, dihydropyridine derivatives or any of the excipients of the medicinal product. Severe liver dysfunction, biliary cirrhosis or cholestasis. Simultaneous use of angiotensin receptor antagonists (ARA), including valsartan, or ACE inhibitors (ACE) with aliskiren in patients with diabetes mellitus or with impaired renal function (glomerular filtration rate. Contraindicated in pregnant women and women planning pregnancy. Severe hypotension. Shock (including cardiogenic shock) Left ventricular outflow tract obstruction (eg, hypertrophic obstructive cardiomyopathy and severe aortic stenosis) Hemodynamically unstable heart failure after acute myocardial infarction.

Route of administration

Patients whose blood pressure is not adequately controlled with amlodipine or valsartan alone can be treated with drug combination therapy. The recommended dose is 1 tablet per day. The tablets can be taken with or without food, with a small amount of water.

Patients taking valsartan and amlodipine alone can be given a drug that contains the same doses of the components.

Before using the combination, it is recommended to individually adjust the doses of the individual components (ie amplodipine and valsartan). In case of clinical need, direct replacement of monotherapy with a combination of fixed doses can be considered.

Application features

Pregnant women

Contraindicated.

Children

Not recommended.

Drivers

Use with caution, dizziness may occur.

Overdose

Symptoms. At present, there is no experience of drug overdose. The main symptom of an overdose of valsartan is probably severe arterial hypotension with dizziness. An overdose of amlodipine can lead to progressive peripheral vasodilation and possibly reflex tachycardia. Significant prolonged systemic hypotension, up to shock and death, has been reported.

Treatment. If the drug has been used recently, induce vomiting or gastric lavage. The absorption of amlodipine is significantly reduced when activated charcoal is used immediately or within two hours after taking amlodipine.

Side effects

Adverse reactions that were observed most often or were significant or severe: nasopharyngitis, influenza, hypersensitivity, headache, syncope, orthostatic hypotension, edema, soft tissue edema, facial edema, peripheral edema, increased fatigue, redness of the face , asthenia and hot flashes.

Interactions

Interactions with other medicinal products have not been studied.

Grapefruit or grapefruit juice. The use of amlodipine with grapefruit juice or with grapefruit is not recommended, since in some patients the bioavailability may be increased, which will lead to an increase in the hypotensive effect of the drug.

Storage conditions

Store below 30°C.

Keep out of reach of children.

Shelf life – 3 years.

The number of drugs interacting with grapefruit is growing – Russian Association of Gynecologists and Endocrinologists

Drugs That Interact With Grapefruit on the Rise

The chemicals that make up drugs can react with some drinks and foods, as a result of which not only the effectiveness of treatment may decrease, but also damage to health.

The results of a recent review showed that the number of drugs that can become dangerous when combined with grapefruit juice is on the rise, in large part due to the introduction of more and more new drugs into the market. Currently, there are 85 drugs that, when interacting with grapefruit, may be accompanied by side effects; over the past 4 years, their number has increased from 17 to 43, i.e. Approximately 6 new drugs of this kind appear annually. This list includes a number of statins (such as atorvastatin, lovastatin, and simvastatin), some antibiotics, cancer treatments, and cardiovascular drugs. Older people who use a wide variety of medications and try to consume more “vitamins”, including grapefruits, are most at risk.

Grapefruit contains furanocoumarins, which block enzymes that break down certain drugs in the body. In this regard, although in rare cases, the accumulation of the drug in the body can have a toxic effect. Not only grapefruit, but also other citrus fruits and bitter orange (Seville oranges) often used in marmalade, lime and pamello contain these active ingredients, although their potential negative interactions with individual drugs have not yet been well studied.

Grapefruit and some drugs: a dangerous combination

The researchers searched medical articles regarding grapefruit-drug interactions using keywords. They also reviewed the instructions for use of recently approved medicines in Canada. The findings were published in the Journal of the Canadian Medical Association ( Canadian Medical Association Journal ).

It is clear that drugs that interact with grapefruit are oral agents, while the degree of influence of this fruit on the absorption of individual drugs in the body varies. For a small number of drugs, even a single intake of grapefruit can lead to its dose being many times over. This adverse interaction may occur even if the grapefruit was eaten many hours before the medication was taken. For example, if simvastatin is taken with about 7 ounces (28.3 g) of grapefruit juice once a day for three days, the excess concentration of this drug can reach 330% compared to what would be observed when washed down with water, as a result of this life-threatening acute necrosis of skeletal muscle (rhabdomyolysis) may develop.

“Grapefruit and grapefruit products can interact with a wide range of medications, from cardiovascular agents to hormones,” said Dr. Tara Narula, director of the Heart Center at Lenox Hill Hospital in New York. In some cases, the effect may be stronger, the shorter the time interval between taking the medicine and drinking grapefruit juice, in other cases, this interaction persists even with a significant increase in this period of time, for example, if the patient takes the pill at night and drank the juice 12 hours ago ” she added.

Dr. Narula warns, “If you are in need of a medicine for which there is no adequate substitute, and yet regularly consume grapefruit juice or the fruit itself, be careful.” However, the researchers note that although grapefruit may interact with certain medications, it does not necessarily interact with the entire class of these drugs, so you should never stop taking a medication without talking to your doctor.

Source:

Bailey, D.