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Drug Interactions between Adenocaine PF and Agamree

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

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Moderate

magnesium sulfate vamorolone

Applies to: Adenocaine PF (adenosine / lidocaine / magnesium sulfate) and Agamree (vamorolone)

MONITOR: The overuse or abuse of laxatives can cause significant loss of electrolytes and potentiate the risk of hypokalemia associated with corticosteroid therapy. Corticosteroids promote the retention of sodium and water and the excretion of potassium. Although these effects are primarily associated with mineralocorticoids like fludrocortisone, they may also occur with higher dosages of glucocorticoids or adrenocorticotropic agents, particularly if given systemically for longer than brief periods.

MANAGEMENT: In general, laxatives should only be used on a short-term, intermittent basis in recommended dosages. During concomitant therapy with corticosteroids, particularly if fludrocortisone or large doses of a glucocorticoid or adrenocorticotropic agent is given, patients should be counseled to recognize potential signs and symptoms of hypokalemia such as fatigue, myalgia, and muscle weakness. If maintenance of bowel regularity is required, patients should be advised to exercise and increase fiber in the diet and/or consider the use of bulk-forming laxatives.

References

  1. Seale JP, Compton MR (1986) "Side-effects of corticosteroid agents." Med J Aust, 144, p. 139-42
  2. Lieberman P, Patterson R, Kunske R (1972) "Complications of long-term steroid therapy for asthma." J Allergy Clin Immunol, 49, p. 329-36
  3. Ramsahoye BH, Davies SV, el-Gaylani N, Sandeman D, Scanlon MF (1995) "The mineralocorticoid effects of high dose hydrocortisone." BMJ, 310, p. 656-7
  4. Swartz SL, Dluhy RG (1978) "Corticosteroids: clinical pharmacology and therapeutic use." Drugs, 16, p. 238-55
  5. Brinckmann J, Blumenthal M, eds., Goldberg A (2000) "Herbal Medicine: Expanded Commission E Monographs." Newton, MA: Integrative Medicine Communications
  6. Chin RL (1998) "Laxative-induced hypokalemia." Ann Emerg Med, 32, p. 517-8
  7. Muller-Lissner SA (1993) "Adverse effects of laxatives: fact and fiction." Pharmacology, 47, p. 138-45
View all 7 references

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Drug and food interactions

Moderate

lidocaine food

Applies to: Adenocaine PF (adenosine / lidocaine / magnesium sulfate)

MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of lidocaine, which is primarily metabolized by the CYP450 3A4 and 1A2 isoenzymes to active metabolites (monoethylglycinexylidide (MEGX) and glycinexylidide). The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported with oral and/or intravenous lidocaine and potent CYP450 3A4 inhibitor, itraconazole, as well as moderate CYP450 3A4 inhibitor, erythromycin. A pharmacokinetic study of 9 healthy volunteers showed that the administration of lidocaine oral (1 mg/kg single dose) with itraconazole (200 mg daily) increased lidocaine systemic exposure (AUC) and peak plasma concentration (Cmax) by 75% and 55%, respectively. However, no changes were observed in the pharmacokinetics of the active metabolite MEGX. In the same study, when the moderate CYP450 3A4 inhibitor erythromycin (500 mg three times a day) was administered, lidocaine AUC and Cmax increased by 60% and 40%, respectively. By contrast, when intravenous lidocaine (1.5 mg/kg infusion over 60 minutes) was administered on the fourth day of treatment with itraconazole (200 mg once a day) no changes in lidocaine AUC or Cmax were observed. However, when lidocaine (1.5 mg/kg infusion over 60 minutes) was coadministered with erythromycin (500 mg three times a day) in the same study, the AUC and Cmax of the active metabolite MEGX significantly increased by 45-60% and 40%, respectively. The observed differences between oral and intravenous lidocaine when coadministered with CYP450 3A4 inhibitors may be attributed to inhibition of CYP450 3A4 in both the gastrointestinal tract and liver affecting oral lidocaine to a greater extent than intravenous lidocaine. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. While the clinical significance of this interaction is unknown, increased exposure to lidocaine may lead to serious and/or life-threatening reactions including respiratory depression, convulsions, bradycardia, hypotension, arrhythmias, and cardiovascular collapse.

MONITOR: Certain foods and behaviors that induce CYP450 1A2 may reduce the plasma concentrations of lidocaine. The proposed mechanism is induction of hepatic CYP450 1A2, one of the isoenzymes responsible for the metabolic clearance of lidocaine. Cigarette smoking is known to be a CYP450 1A2 inducer. In one pharmacokinetic study of 4 smokers and 5 non-smokers who received 2 doses of lidocaine (100 mg IV followed by 100 mg orally after a 2-day washout period), the smokers' systemic exposure (AUC) of oral lidocaine was 68% lower than non-smokers. The AUC of IV lidocaine was only 9% lower in smokers compared with non-smokers. Other CYP450 1A2 inducers include cruciferous vegetables (e.g., broccoli, brussels sprouts) and char-grilled meat. Therefore, eating large or variable amounts of these foods could also reduce lidocaine exposure. The clinical impact of smoking and/or the ingestion of foods that induce CYP450 1A2 on lidocaine have not been studied, however, a loss of efficacy may occur.

MANAGEMENT: Caution is recommended if lidocaine is to be used in combination with grapefruit and grapefruit juice. Monitoring for lidocaine toxicity and plasma lidocaine levels may also be advised, and the lidocaine dosage adjusted as necessary. Patients who smoke and/or consume cruciferous vegetables may be monitored for reduced lidocaine efficacy.

References

  1. Huet PM, LeLorier J (1980) "Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics" Clin Pharmacol Ther, 28, p. 208-15
  2. (2024) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Inc.
  3. (2015) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Healthcare Corporation
  4. (2022) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hameln Pharma Ltd
  5. (2022) "Product Information. Xylocaine HCl (lidocaine)." Aspen Pharmacare Australia Pty Ltd
  6. Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of oral lignocaine https://pubmed.ncbi.nlm.nih.gov/10193676/
  7. Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine https://pubmed.ncbi.nlm.nih.gov/9832299/
View all 7 references

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Moderate

adenosine food

Applies to: Adenocaine PF (adenosine / lidocaine / magnesium sulfate)

ADJUST DOSING INTERVAL: Caffeine and other xanthine derivatives (e.g., theophylline) are nonspecific, competitive antagonists of adenosine receptors and may interfere with the hemodynamic effects of adenosine. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort.

MANAGEMENT: Clinicians should be aware that adenosine may be less effective in the presence of xanthine derivatives including caffeine. Patients should avoid consumption of caffeine-containing products for at least 12 hours, preferably 24 hours, prior to administration of adenosine for myocardial perfusion imaging.

References

  1. Conti CR (1991) "Adenosine: clinical pharmacology and applications." Clin Cardiol, 14, p. 91-3
  2. Smits P, Schouten J, Thien T (1987) "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol, 24, p. 816-9
  3. Minton NA, Henry JA (1991) "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol, 10, p. 411-8
  4. (2001) "Product Information. Adenocard (adenosine)." Fujisawa
  5. "Multum Information Services, Inc. Expert Review Panel"
  6. (2001) "Product Information. Adenoscan (adenosine)." Fujisawa
View all 6 references

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Moderate

vamorolone food

Applies to: Agamree (vamorolone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of vamorolone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism in the gut wall by certain compounds present in grapefruit. The metabolism of vamorolone is mediated by the isoenzymes CYP450 3A4/5, and CYP450 2C8, and uridine diphosphate glucuronosyltransferases (UGT) 1A3, 2B7, and 2B17. In general, the effect of grapefruit juice is concentration-, dose-, and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to vamorolone may increase the risk of corticosteroid adverse effects such as hypercorticism, hyperglycemia, adrenal suppression, immunosuppression, hypertension, salt and water retention, electrolyte abnormalities, behavioral and mood disturbances, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.

MANAGEMENT: Until further information is available, it may be advisable for patients to avoid the consumption of large amounts of grapefruit and grapefruit juice during vamorolone therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation. If coadministration is considered necessary, patients should be closely monitored for signs and symptoms of corticosteroid adverse effects. Patients should also be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, and depression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as an inability to respond to stress (e.g., illness, infection, surgery, trauma). Consultation with product labeling for specific recommendations is advisable.

References

  1. Zurcher RM, Frey BM, Frey FJ (1989) "Impact of ketoconazole on the metabolism of prednisolone." Clin Pharmacol Ther, 45, p. 366-72
  2. Yamashita SK, Ludwig EA, Middleton E Jr, Jusko WJ (1991) "Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone." Clin Pharmacol Ther, 49, p. 558-70
  3. Ulrich B, Frey FJ, Speck RF, Frey BM (1992) "Pharmacokinetics/pharmacodynamics of ketoconazole-prednisolone interaction." J Pharmacol Exp Ther, 260, p. 487-90
  4. Kandrotas RJ, Slaughter RL, Brass C, Jusko WJ (1987) "Ketoconazole effects on methylprednisolone disposition and their joint suppression of endogenous cortisol." Clin Pharmacol Ther, 42, p. 465-70
  5. Glynn AM, Slaughter RL, Brass C, et al. (1986) "Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion." Clin Pharmacol Ther, 39, p. 654-9
  6. Itkin IH, Menzel ML (1970) "The use of macrolide antibiotic substances in the treatment of asthma." J Allergy Clin Immunol, 45, p. 146-62
  7. LaForce CF, Szefler SJ, Miller MF, Ebling W, Brenner M (1983) "Inhibition of methylprednisolone elimination in the presence of erythromycin therapy." J Allergy Clin Immunol, 72, p. 34-9
  8. Finkenbine RD, Frye MD (1998) "Case of psychosis due to prednisone-clarithromycin interaction." Gen Hosp Psychiat, 20, p. 325-6
  9. Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ (1998) "Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole." Clin Pharmacol Ther, 64, p. 363-8
  10. Hillebrand-Haverkort ME, Prummel MF, ten Veen JH (1999) "Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone." AIDS, 13, p. 1803
  11. Varis T, Kivisto KT, Neuvonen PJ (2000) "The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone." Eur J Clin Pharmacol, 56, p. 57-60
  12. Varis T, Backman JT, Kivisto KT, Neuvonen PJ (2000) "Diltiazem and mibefradil increase the plasma concentrations and greatly enhance the adrenal-suppressant effect of oral methylprednisolone." Clin Pharmacol Ther, 67, p. 215-21
  13. Garey KW, Rubinstein I, Gotfried MH, Khan IJ, Varma S, Danziger LH (2000) "Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma." Chest, 118, p. 1826-7
  14. Lebrun-Vignes B, Archer VC, Diquest B, et al. (2001) "Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects." Br J Clin Pharmacol, 51, p. 443-50
  15. Couturier J, Steele M, Hussey L, Pawliuk G (2001) "Steroid-induced mania in an adolescent: risk factors and management." Can J Clin Pharmacol, 8, p. 109-12
  16. Gupta SK, Dube MP (2002) "Exogenous Cushing syndrome mimicking human immunodeficiency virus lipodystrophy." Clin Infect Dis, 35, E69-71
  17. Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT (2002) "Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole." Clin Pharmacol Ther, 72, p. 362-369
  18. Main KM, Skov M, Sillesen IB, et al. (2002) "Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient." Acta Paediatr, 91, p. 1008-11
  19. Skov M, Main KM, Sillesen IB, Muller J, Koch C, Lanng S (2002) "Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide." Eur Respir J, 20, p. 127-33
  20. Kotlyar M, Brewer ER, Golding M, Carson SW (2003) "Nefazodone inhibits methylprednisolone disposition and enhances its adrenal-suppressant effect." J Clin Psychopharmacol, 23, p. 652-6
  21. Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN (2004) "Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole." Ann Pharmacother, 38, p. 46-9
  22. Edsbacker S, Andersson T (2004) "Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease." Clin Pharmacokinet, 43, p. 803-21
  23. Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA (2005) "Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in HIV-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases." J Clin Endocrinol Metab, 90, p. 4394-8
  24. Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J (2005) "Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction." Intern Med J, 35, p. 67-8
  25. Penzak SR, Formentini E, Alfaro RM, Long M, Natarajan V, Kovacs J (2005) "Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral prednisone administration to healthy volunteers." J Acquir Immune Defic Syndr, 40, p. 573-80
  26. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  27. Bhumbra NA, Sahloff EG, Oehrtman SJ, Horner JM (2007) "Exogenous Cushing syndrome with inhaled fluticasone in a child receiving lopinavir/ritonavir." Ann Pharmacother, 41, p. 1306-9
  28. Busse KH, Formentini E, Alfaro RM, Kovacs JA, Penzak SR (2008) "Influence of antiretroviral drugs on the pharmacokinetics of prednisolone in HIV-infected individuals." J Acquir Immune Defic Syndr, 48, p. 561-6
  29. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  30. (2023) "Product Information. Agamree (vamorolone)." Santhera Pharmaceuticals (US)
View all 30 references

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Moderate

adenosine food

Applies to: Adenocaine PF (adenosine / lidocaine / magnesium sulfate)

ADJUST DOSING INTERVAL: Methylxanthines (e.g., caffeine, theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the pharmacologic effects of adenosine and other adenosine receptor agonists such as dipyridamole and regadenoson. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort. Similarly, caffeine has been found to reduce the hemodynamic response to dipyridamole, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole. In a placebo-controlled study that assessed the effects of oral caffeine on regadenoson-induced increase in coronary flow reserve (CFR), healthy subjects who took caffeine 200 mg orally two hours prior to regadenoson administration exhibited a median CFR that was 92% that of subjects who took placebo. The study was done using positron emission tomography with radiolabeled water.

MANAGEMENT: Clinicians should be aware that adenosine and other adenosine receptor agonists may be less effective in the presence of methylxanthines. Methylxanthines including caffeine should be withheld for 12 to 24 hours (or five half-lives) prior to administration of adenosine receptor agonists for myocardial perfusion imaging. However, parenteral aminophylline should be readily available for treating severe or persistent adverse reactions to adenosine receptor agonists such as bronchospasm or chest pain.

References

  1. Conti CR (1991) "Adenosine: clinical pharmacology and applications." Clin Cardiol, 14, p. 91-3
  2. Smits P, Aengevaeren WR, Corstens FH, Thien T (1989) "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med, 30, p. 1723-6
  3. Smits P, Schouten J, Thien T (1987) "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol, 24, p. 816-9
  4. Minton NA, Henry JA (1991) "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol, 10, p. 411-8
  5. (2002) "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim
  6. (2001) "Product Information. Adenocard (adenosine)." Fujisawa
  7. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group (1990) "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation, 81, p. 1205-9
  8. (2001) "Product Information. Adenoscan (adenosine)." Fujisawa
  9. (2008) "Product Information. Lexiscan (regadenoson)." Astellas Pharma US, Inc
View all 9 references

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Minor

adenosine food

Applies to: Adenocaine PF (adenosine / lidocaine / magnesium sulfate)

Nicotine may enhance adenosine-associated tachycardia and chest pain. The mechanism is not known. No special precautions appear to be necessary.

References

  1. Smits P, Eijsbouts A, Thien T (1989) "Nicotine enhances the circulatory effects of adenosine in human beings." Clin Pharmacol Ther, 46, p. 272-8
  2. Sylven C, Beermann B, Kaijser L, Jonzon B (1990) "Nicotine enhances angina pectoris-like chest pain and atriovenricular blockade provoked by intravenous bolus of adenosine in healthy volunteers." J Cardiovasc Pharmacol, 16, p. 962-5

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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.