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Drug Interactions between Prevpac and red yeast rice

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

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Major

clarithromycin red yeast rice

Applies to: Prevpac (amoxicillin / clarithromycin / lansoprazole) and red yeast rice

ADJUST DOSE: Some macrolide antibiotics inhibit CYP450 3A4 and may elevate the plasma concentrations of HMG-CoA reductase inhibitors that are metabolized by the isoenzyme. Macrolides that may significantly inhibit CYP450 3A4 include troleandomycin, erythromycin, and clarithromycin. There have been case reports of patients treated with lovastatin or simvastatin who developed severe myopathy or rhabdomyolysis following the addition of a macrolide, usually erythromycin. Plasma levels of HMG-CoA reductase inhibitory activity were significantly elevated in these patients, up to severalfold in many cases. Similar pharmacokinetic changes have been reported in studies with erythromycin and simvastatin and, to a lesser extent, with clarithromycin or erythromycin and atorvastatin. The interaction was also suspected in a patient treated with atorvastatin (more than 1 year) and esomeprazole (6 weeks) who developed rhabdomyolysis with AV block two days after the addition of clarithromycin. The patient reported experiencing symptoms of increased fatigue, mild chest pain, and shortness of breath that coincided with the initiation of esomeprazole approximately six weeks prior to admission.

MANAGEMENT: The benefits of using HMG-CoA reductase inhibitors that are metabolized by CYP450 3A4 in combination with medications that can inhibit the isoenzyme such as clarithromycin and erythromycin should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. A lower dosage of the HMG-CoA reductase inhibitor should be considered if concomitant use is required. Atorvastatin labeling recommends that the dosage not exceed 20 mg/day when used in combination with clarithromycin. Fluvastatin, pitavastatin, and rosuvastatin may be safer alternatives, since they are not metabolized by CYP450 3A4. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References

  1. Spach DH, Bauwens JE, Clark CD, Burke WG (1991) "Rhabdomyolysis associated with lovastatin and erythromycin use." West J Med, 154, p. 213-5
  2. Ayanian JZ, Fuchs CS, Stone RM (1988) "Lovastatin and rhabdomyolysis." Ann Intern Med, 109, p. 682-3
  3. Corpier CL, Jones PH, Suki WN, et al. (1988) "Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients." JAMA, 260, p. 239-41
  4. East C, Alivizatos PA, Grundy SM, Jones PH, Farmer JA (1988) "Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation." N Engl J Med, 318, p. 47-8
  5. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  6. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  7. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  8. (2001) "Product Information. Baycol (cerivastatin)." Bayer
  9. Grunden JW, Fisher KA (1997) "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother, 31, p. 859-63
  10. Wong PW, Dillard TA, Kroenke K (1998) "Multiple organ toxicity from addition of erythromycin to long-term lovastatin therapy." South Med J, 91, p. 202-5
  11. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations." Clin Pharmacol Ther, 64, p. 177-82
  12. Siedlik PH, Olson SC, Yang BB, Stern RH (1999) "Erythromycin coadministration increases plasma atorvastatin concentrations." J Clin Pharmacol, 39, p. 501-4
  13. Westphal JF (2000) "Macrolide - induced clinically relevant drug interactions with cytochrome P-450 (CYP) 3A4: an update focused on clarithromycin, azithromycin, and dirithromycin." Br J Clin Pharmacol, 50, p. 285-95
  14. Lee AJ, Maddix DS (2001) "Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin." Ann Pharmacother, 35, p. 26-31
  15. Garnett WR (1995) "Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors." Am J Health Syst Pharm, 52, p. 1639-45
  16. Omar MA, Wilson JP (2002) "FDA adverse event reports on statin-associated rhabdomyolysis." Ann Pharmacother, 36, p. 288-95
  17. Amsden GW, Kuye O, Wei GC (2002) "A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers." J Clin Pharmacol, 42, p. 444-9
  18. Williams D, Feely J (2002) "Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors." Clin Pharmacokinet, 41, p. 343-70
  19. Huynh T, Cordato D, Yang F, et al. (2002) "HMG coA reductase-inhibitor-related myopathy and the influence of drug interactions." Intern Med J, 32(9-10), p. 486-90
  20. Sipe BE, Jones RJ, Bokhart GH (2003) "Rhabdomyolysis Causing AV Blockade Due to Possible Atorvastatin, Esomeprazole, and Clarithromycin Interaction." Ann Pharmacother, 37, p. 808-11
  21. Chouhan UM, Chakrabarti S, Millward LJ (2005) "Simvastatin interaction with clarithromycin and amiodarone causing myositis." Ann Pharmacother, 39, p. 1760-1
  22. Neuvonen PJ, Backman JT, Niemi M (2008) "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet, 47, p. 463-74
  23. Cooper JM, Jones AL (2009) "Neuroleptic malignant syndrome or a statin drug reaction? A case report." Clin Neuropharmacol, 32, p. 348-9
View all 23 references

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Moderate

clarithromycin lansoprazole

Applies to: Prevpac (amoxicillin / clarithromycin / lansoprazole) and Prevpac (amoxicillin / clarithromycin / lansoprazole)

MONITOR: Coadministration with clarithromycin may increase the plasma concentrations of lansoprazole. The proposed mechanism is clarithromycin inhibition of intestinal (first-pass) and hepatic metabolism of lansoprazole via CYP450 3A4. Although lansoprazole is primarily metabolized by CYP450 2C19 in the liver, 3A4-mediated metabolism is the predominant pathway in individuals who are 2C19-deficient (approximately 3% to 5% of the Caucasian and 17% to 20% of the Asian population). Additionally, inhibition of P-glycoprotein intestinal efflux transporter by clarithromycin may also contribute to the interaction, resulting in increased bioavailability of lansoprazole. In 18 healthy volunteers--six each of homozygous extensive metabolizers (EMs), heterozygous EMs, and poor metabolizers (PMs) of CYP450 2C19--clarithromycin (400 mg orally twice a day for 6 days) increased the peak plasma concentration (Cmax) of a single 60 mg oral dose of lansoprazole by 1.47, 1.71- and 1.52-fold, respectively, and area under the concentration-time curve (AUC) by 1.55-, 1.74- and 1.80-fold, respectively, in each of these groups compared to placebo. The AUC ratio of lansoprazole to lansoprazole sulphone, which is considered an index of CYP450 3A4 activity, was significantly increased by clarithromycin in all three groups. However, elimination half-life of lansoprazole was prolonged by 1.54-fold only in PMs. Mild diarrhea was reported in two subjects and mild abdominal disturbance in six subjects during clarithromycin coadministration. These side effects continued until day 6 and ameliorated the day after discontinuation of clarithromycin, whereas no adverse events were reported during placebo administration or after lansoprazole plus placebo. In another study, clarithromycin induced dose-dependent increases in the plasma concentration of lansoprazole in a group of 20 patients receiving treatment for H. pylori eradication. Mean 3-hour plasma lansoprazole concentration was 385 ng/mL for the control subjects who received lansoprazole 30 mg and amoxicillin 750 mg twice a day for 7 days; 696 ng/mL for patients coadministered clarithromycin 200 mg twice a day; and 947 ng/mL for patients coadministered clarithromycin 400 mg twice a day.

MANAGEMENT: Although lansoprazole is generally well tolerated, caution may be advised during coadministration with clarithromycin, particularly if higher dosages of one or both drugs are used. Dosage adjustment may be necessary in patients who experience excessive adverse effects of lansoprazole.

References

  1. Ushiama H, Echizen H, Nachi S, Ohnishi A (2002) "Dose-dependent inhibition of CYP3A activity by clarithromycin during Helicobacter pylori eradication therapy assessed by changes in plasma lansoprazole levels and partial cortisol clearance to 6beta-hydroxycortisol." Clin Pharmacol Ther, 72, p. 33-43
  2. Saito M, Yasui-Furukori N, Uno T, et al. (2005) "Effects of clarithromycin on lansoprazole pharmacokinetics between CYP2C19 genotypes." Br J Clin Pharmacol, 59, p. 302-9
  3. Miura M, Tada H, Yasui-Furukori N, et al. (2005) "Effect of clarithromycin on the enantioselective disposition of lansoprazole in relation to CYP2C19 genotypes." Chirality, 17, p. 338-344

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Moderate

lansoprazole red yeast rice

Applies to: Prevpac (amoxicillin / clarithromycin / lansoprazole) and red yeast rice

MONITOR: A case report suggests that coadministration with esomeprazole may increase the plasma concentrations of atorvastatin and the associated risk of myopathy. The proposed mechanism is competitive inhibition of intestinal P-glycoprotein, resulting in decreased drug secretion into the intestinal lumen and increased drug bioavailability. Another, perhaps minor mechanism is competitive inhibition of CYP450 3A4 metabolism. The interaction was suspected in a patient treated with atorvastatin (more than 1 year) and esomeprazole (6 weeks) who developed rhabdomyolysis with AV block two days after the addition of clarithromycin. The patient reported experiencing symptoms of increased fatigue, mild chest pain, and shortness of breath that coincided with the initiation of esomeprazole approximately six weeks prior to admission. Theoretically, the interaction may also occur with other proton pump inhibitors like lansoprazole, omeprazole, and pantoprazole and HMG-CoA reductase inhibitors like lovastatin and simvastatin, since these drugs are all substrates of P-glycoprotein and CYP450 3A4.

MANAGEMENT: Because of the increased risk of musculoskeletal toxicity associated with high levels of HMG-CoA reductase inhibitory activity in plasma, patients treated with atorvastatin, lovastatin, simvastatin, and red yeast rice (which contains lovastatin) should be monitored more closely during concomitant use of proton pump inhibitors. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report to their physician any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated or if myopathy is suspected or diagnosed.

References

  1. Bogman K, Peyer AK, Torok M, Kusters E, Drewe J (2001) "HMG-CoA reductase inhibitors and P-glycoprotein modulation." Br J Pharmacol, 132, p. 1183-92
  2. Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF (2001) "Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein." Naunyn Schmiedebergs Arch Pharmacol, 364, p. 551-7
  3. Sipe BE, Jones RJ, Bokhart GH (2003) "Rhabdomyolysis Causing AV Blockade Due to Possible Atorvastatin, Esomeprazole, and Clarithromycin Interaction." Ann Pharmacother, 37, p. 808-11

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Minor

amoxicillin clarithromycin

Applies to: Prevpac (amoxicillin / clarithromycin / lansoprazole) and Prevpac (amoxicillin / clarithromycin / lansoprazole)

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

References

  1. Strom J (1961) "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother, 11, p. 694-7
  2. Cohn JR, Jungkind DL, Baker JS (1980) "In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens." Antimicrob Agents Chemother, 18, p. 872-6
  3. Penn RL, Ward TT, Steigbigel RT (1982) "Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of listeria monocytogenes." Antimicrob Agents Chemother, 22, p. 289-94

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Drug and food interactions

Major

red yeast rice food

Applies to: red yeast rice

GENERALLY AVOID: Coadministration with grapefruit juice may significantly increase the plasma concentrations of lovastatin and simvastatin and their active acid metabolites. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 60 mg dose of simvastatin was coadministered with 200 mL of double-strength grapefruit juice three times a day, simvastatin systemic exposure (AUC) increased by 16-fold and simvastatin acid AUC increased by 7-fold. Administration of a single 20 mg dose of simvastatin with 8 ounces of single-strength grapefruit juice increased the AUC of simvastatin and simvastatin acid by 1.9-fold and 1.3-fold, respectively. The interaction has also been reported with lovastatin, which has a similar metabolic profile to simvastatin. Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

Coadministration with green tea may increase the plasma concentrations of simvastatin. The mechanism of interaction has not been established, but may involve inhibition of organic anion transporting polypeptide (OATP) 1B1- and/or 2B1-mediated hepatic uptake of simvastatin by catechins in green tea. The interaction was suspected in a 61-year-old man who experienced muscle intolerance during treatment with simvastatin while drinking an average of 3 cups of green tea daily. He also experienced similar muscle intolerance (leg cramps without creatine phosphokinase elevation) during treatments with atorvastatin and rosuvastatin while drinking green tea. Pharmacokinetic studies performed during his usual green tea intake demonstrated an approximately two-fold higher exposure to simvastatin lactone (the administered form of simvastatin) than that observed after stopping green tea intake for a month. He was also able to tolerate simvastatin after discontinuing green tea consumption. The authors of the report subsequently conducted two independent studies to assess the effect of different green tea preparations on simvastatin pharmacokinetics. One study was conducted in 12 Italian subjects and the other in 12 Japanese subjects. In the Italian study, administration of a single 20 mg dose of simvastatin following pretreatment with 200 mL of a hot green tea standardized infusion 3 times daily for 14 days (estimated daily intake of 335 mg total catechins and 173 mg epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea) was found to have no significant effect on mean peak plasma concentration (Cmax) or systemic exposure (AUC) of simvastatin lactone and simvastatin acid relative to administration with water. However, green tea increased simvastatin lactone AUC (0-6h) by about two-fold in 3 of the study subjects. In the Japanese study, administration of a single 10 mg dose of simvastatin following pretreatment with 350 mL of a commercial green tea beverage twice daily for 14 days (estimated daily intake of 638 mg total catechins and 322 mg EGCG) did not affect mean simvastatin lactone Cmax or AUC to a statistically significant extent compared to administration with water, but increased mean simvastatin acid Cmax and AUC by 42% and 22%, respectively. Similar to the first study, green tea increased simvastatin lactone AUC (0-6h) by two- to three-fold in 4 of the study subjects. Although not studied, the interaction may also occur with lovastatin due to its similar metabolic profile to simvastatin.

MANAGEMENT: Patients receiving therapy with lovastatin, simvastatin, or red yeast rice (which contains lovastatin) should be advised to avoid the consumption of grapefruit and grapefruit juice. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are metabolized by other enzymes and may be preferable alternatives in some individuals. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. Also, patients should either refrain from the use of oat bran and pectin, or separate the administration times by at least 2 to 4 hours if concurrent use cannot be avoided. Caution may be advisable when coadministered with green tea or green tea extracts. Dosing reduction of the statin and/or limiting consumption of green tea and green tea products may be required if an interaction is suspected.

References

  1. Richter WO, Jacob BG, Schwandt P (1991) "Interaction between fibre and lovastatin." Lancet, 338, p. 706
  2. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  3. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  4. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  5. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  7. Thompson PD, Clarkson P, Karas RH (2003) "Statin-associated myopathy." JAMA, 289, p. 1681-90
  8. Neuvonen PJ, Backman JT, Niemi M (2008) "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet, 47, p. 463-74
  9. Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L (2008) "The effect of green tea on simvastatin tolerability." Ann Intern Med, 149, p. 286-7
  10. Werba JP, Misaka S, Giroli MG, et al. (2014) "Overview of Green Tea Interaction with Cardiovascular Drugs." Curr Pharm Des
  11. Roth M, Timmermann BN, Hagenbuch B (2011) "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos, 39, p. 920-6
  12. Knop J, Misaka S, Singer K, et al. (2015) "Inhibitory effects of green tea and (-)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein." PLoS One, 10, e0139370
View all 12 references

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Minor

clarithromycin food

Applies to: Prevpac (amoxicillin / clarithromycin / lansoprazole)

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References

  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.