Drug Interactions between Advicor and methotrexate
This report displays the potential drug interactions for the following 2 drugs:
- Advicor (lovastatin/niacin)
- methotrexate
Interactions between your drugs
lovastatin niacin
Applies to: Advicor (lovastatin / niacin) and Advicor (lovastatin / niacin)
ADJUST DOSE: Severe myopathy and rhabdomyolysis have been reported with concomitant use of HMG-CoA reductase inhibitors (i.e., statins) and niacin. The mechanism is unknown; however, the development of myopathy has been associated with both the administration of statins alone and lipid-modifying dosages of niacin (1 g/day or more) alone. Certain populations may be more susceptible to the interaction. In a double-blind, randomized cardiovascular outcomes trial for simvastatin, the incidence of myopathy was found to be higher in patients of Chinese descent (0.43%) compared to patients not of Chinese descent (0.03%) taking 40 mg simvastatin and lipid-modifying dosages of a niacin-containing product. The cause of the increased risk is unknown, and it is also unknown if the increased risk applies to other Asian populations or to other statins when given to Chinese patients.
MANAGEMENT: Concomitant use of statins with lipid-modifying dosages of niacin (1 g/day or more) should be approached cautiously and only if the benefit of further alterations in lipid levels is anticipated to outweigh the potential risks. Addition of niacin to statin therapy typically provides little additional reduction in LDL cholesterol, but further reductions of triglycerides and increases in HDL cholesterol may be attained. If the combination is prescribed, lower dosages of the statin should be considered. Coadministration of simvastatin with high doses of niacin (1 g/day or more) is not recommended in Chinese patients due to an increased risk of myopathy. Lovastatin labeling recommends that the dosage not exceed 20 mg daily when prescribed with lipid-modifying dosages of niacin. All patients 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
- Mauro VF (1993) "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet, 24, p. 195-202
- Mauro VF, MacDonald JL (1991) "Simvastatin: a review of its pharmacology and clinical use." DICP, 25, p. 257-64
- Reaven P, Witztum JL (1988) "Lovastatin, nicotinic acid, and rhabdomyolysis." Ann Intern Med, 109, p. 597-8
- Norman DJ, Illingworth DR, Munson J, Hosenpud J (1988) "Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin." N Engl J Med, 318, p. 46-7
- Malloy MJ, Kane JP, Kunitake ST, Tun P (1987) "Complementarity of colestipol, niacin, and lovastatin in treatment of severe familial hypercholesterolemia." Ann Intern Med, 107, p. 616-23
- (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
- (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
- (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
- (2001) "Product Information. Baycol (cerivastatin)." Bayer
- (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
- (2004) "Product Information. Vytorin (ezetimibe-simvastatin)." Merck & Co., Inc
- FDA. U.S. Food and Drug Administration (2010) FDA drug safety communication: Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204882.htm
methotrexate lovastatin
Applies to: methotrexate and Advicor (lovastatin / niacin)
GENERALLY AVOID: Coadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher dosages or during prolonged treatment, has been associated with severe hepatotoxicity including acute hepatitis, chronic fibrosis, cirrhosis, and fatal liver failure.
MANAGEMENT: The risk of hepatic injury should be considered when methotrexate is used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Baseline and periodic monitoring of hepatic function is recommended, while liver biopsy may be warranted during long-term use of methotrexate. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, pale stools, and jaundice.
References
- (2002) "Product Information. Methotrexate (methotrexate)." Lederle Laboratories
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2023) "Product Information. Methotrexate (methotrexate)." Hospira Inc
methotrexate niacin
Applies to: methotrexate and Advicor (lovastatin / niacin)
GENERALLY AVOID: Coadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher dosages or during prolonged treatment, has been associated with severe hepatotoxicity including acute hepatitis, chronic fibrosis, cirrhosis, and fatal liver failure.
MANAGEMENT: The risk of hepatic injury should be considered when methotrexate is used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Baseline and periodic monitoring of hepatic function is recommended, while liver biopsy may be warranted during long-term use of methotrexate. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, pale stools, and jaundice.
References
- (2002) "Product Information. Methotrexate (methotrexate)." Lederle Laboratories
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2023) "Product Information. Methotrexate (methotrexate)." Hospira Inc
Drug and food interactions
lovastatin food
Applies to: Advicor (lovastatin / niacin)
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
- Richter WO, Jacob BG, Schwandt P (1991) "Interaction between fibre and lovastatin." Lancet, 338, p. 706
- (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
- (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
- 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
- Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
- 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
- Thompson PD, Clarkson P, Karas RH (2003) "Statin-associated myopathy." JAMA, 289, p. 1681-90
- 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
- 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
- Werba JP, Misaka S, Giroli MG, et al. (2014) "Overview of Green Tea Interaction with Cardiovascular Drugs." Curr Pharm Des
- Roth M, Timmermann BN, Hagenbuch B (2011) "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos, 39, p. 920-6
- 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
methotrexate food
Applies to: methotrexate
MONITOR: Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine. In a study of 39 patients treated with MTX 7.5 mg/week (without folate supplementation) for 3 months, patients with high caffeine intake (more than 180 mg/day) experienced significantly less improvement in morning stiffness and joint pain from baseline than patients with low caffeine intake (less than 120 mg/day). There were no significant differences between the responses of patients with moderate caffeine intake (120 to 180 mg/day) and those of the other 2 groups. In an interview of 91 patients treated with MTX, 26% of patients who discontinued the drug were regular coffee drinkers compared to only 2% of those still receiving the drug. Because treatment failure was the reason for MTX discontinuation in 80% of patients who discontinued, the investigators suggested that caffeine may have interfered with MTX efficacy.
MANAGEMENT: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.
References
- Nesher G, Mates M, Zevin S (2003) "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum, 48, p. 571-572
methotrexate food
Applies to: methotrexate
GENERALLY AVOID: Coadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Methotrexate, especially at higher dosages or during prolonged treatment, has been associated with severe hepatotoxicity including acute hepatitis, chronic fibrosis, cirrhosis, and fatal liver failure.
MANAGEMENT: The risk of hepatic injury should be considered when methotrexate is used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Baseline and periodic monitoring of hepatic function is recommended, while liver biopsy may be warranted during long-term use of methotrexate. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, pale stools, and jaundice.
References
- (2002) "Product Information. Methotrexate (methotrexate)." Lederle Laboratories
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2023) "Product Information. Methotrexate (methotrexate)." Hospira Inc
lovastatin food
Applies to: Advicor (lovastatin / niacin)
MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.
MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.
References
- (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
- (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
- (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
- (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
- (2002) "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals
- (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
niacin food
Applies to: Advicor (lovastatin / niacin)
GENERALLY AVOID: Ethanol can exacerbate the cutaneous flushing that is a common side effect of niacin. At least one case of delirium and lactic acidosis has been reported with coadministration of these drugs, although data are limited.
MANAGEMENT: Coadministration should probably be discouraged, particularly since chronic consumption of large amounts of alcohol is associated with hyperlipidemia.
References
- Schwab RA, Bachhuber BH (1991) "Delirium and lactic acidosis caused by ethanol and niacin coingestion." Am J Emerg Med, 9, p. 363-5
methotrexate food
Applies to: methotrexate
MONITOR: Limited data suggest that consumption of greater than 180 mg/day of caffeine may interfere with the efficacy of methotrexate (MTX) in patients with rheumatoid arthritis. The exact mechanism of interaction is unknown but may be related to the antagonistic effect of caffeine on adenosine receptors, as anti-inflammatory properties of MTX is thought to result from the accumulation of adenosine. In a study of 39 patients treated with MTX 7.5 mg/week (without folate supplementation) for 3 months, patients with high caffeine intake (more than 180 mg/day) experienced significantly less improvement in morning stiffness and joint pain from baseline than patients with low caffeine intake (less than 120 mg/day). There were no significant differences between the responses of patients with moderate caffeine intake (120 to 180 mg/day) and those of the other 2 groups. In an interview of 91 patients treated with MTX, 26% of patients who discontinued the drug were regular coffee drinkers compared to only 2% of those still receiving the drug. Because treatment failure was the reason for MTX discontinuation in 80% of patients who discontinued, the investigators suggested that caffeine may have interfered with MTX efficacy.
MANAGEMENT: Until further information is available, the potential for interaction should be considered in patients who consume substantial amounts of caffeine and caffeine-containing foods and are prescribed methotrexate for rheumatoid arthritis. It may be appropriate to limit caffeine intake if an interaction is suspected in cases of treatment failure.
References
- Nesher G, Mates M, Zevin S (2003) "Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis." Arthritis Rheum, 48, p. 571-572
niacin food
Applies to: Advicor (lovastatin / niacin)
A single case has been reported in which cutaneous flushing and tremors were noted in a woman who was taking niacin while wearing a nicotine patch. The mechanism is suspected to be synergistic cutaneous vasodilatory effects. The clinical significance of this possible interaction is not known.
References
- Rockwell KA Jr (1993) "Potential interaction between niacin and transdermal nicotine." Ann Pharmacother, 27, p. 1283-8
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
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