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Drug Interactions between budesonide / formoterol and Nydrazid

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

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Interactions between your drugs

Moderate

isoniazid budesonide

Applies to: Nydrazid (isoniazid) and budesonide / formoterol

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the systemic bioavailability of budesonide, which undergoes extensive first-pass and systemic metabolism via intestinal and hepatic CYP450 3A4. In pharmacokinetic studies, 6- to 8-fold increases in budesonide systemic exposure (AUC) have been observed during coadministration of the potent CYP450 3A4 inhibitor ketoconazole with different oral formulations of budesonide. When ketoconazole was administered 12 hours after budesonide in one study, the AUC increase was approximately half that reported during simultaneous administration. In a prospective study of a cystic fibrosis center patient population, 11 of 25 patients receiving high-dose itraconazole (400 to 600 mg/day) and budesonide oral inhalation therapy (800 to 1600 mcg/day) were found to have adrenal insufficiency, including one who developed Cushing's syndrome, compared to none in a group of 12 patients treated with itraconazole alone. There was also no adrenal insufficiency in a group of 30 cystic fibrosis patients retrospectively included as controls, 24 of whom had been treated with high-dose inhaled budesonide for several years. Adrenal function improved, but did not normalize, in 10 of the 11 patients during a follow-up of two to ten months after discontinuation of itraconazole and institution of hydrocortisone replacement therapy. Limited pharmacokinetic data indicate that itraconazole (200 mg once daily) may increase the plasma levels of budesonide by about 4-fold following inhalation of a single 1000 mcg dose, which may be mainly due to increased bioavailability of the swallowed portion of the dose.

MANAGEMENT: The possibility of increased systemic adverse effects of budesonide should be considered during coadministration with CYP450 3A4 inhibitors. If concomitant use cannot be avoided, the dosing times between budesonide and the CYP450 3A4 inhibitor should be separated by as much as possible. In addition, the lowest effective dosage of budesonide should be prescribed, and further adjustments made as necessary according to therapeutic response and tolerance. Patients should 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, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.

References

  1. Jonsson G, Astrom A, Andersson P "Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver." Drug Metab Dispos 23 (1995): 137-42
  2. "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc (2001):
  3. Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT "Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole." Clin Pharmacol Ther 72 (2002): 362-369
  4. Main KM, Skov M, Sillesen IB, et al. "Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient." Acta Paediatr 91 (2002): 1008-11
  5. Skov M, Main KM, Sillesen IB, Muller J, Koch C, Lanng S "Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide." Eur Respir J 20 (2002): 127-33
  6. De Wachter E, Vanbesien J, De Schutter I, Malfroot A, De Schepper J "Rapidly developing Cushing syndrome in a 4-year-old patient during combined treatment with itraconazole and inhaled budesonide." Eur J Pediatr (2003):
  7. Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN "Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole." Ann Pharmacother 38 (2004): 46-9
  8. Edsbacker S, Andersson T "Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease." Clin Pharmacokinet 43 (2004): 803-21
  9. De Wachter E, Malfroot A, De Schutter I, Vanbesien J, De Schepper J "Inhaled budesonide induced Cushing's syndrome in cystic fibrosis patients, due to drug inhibition of cytochrome P450." J Calif Dent Assoc 2 (2003): 72-5
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  11. Cerner Multum, Inc. "Australian Product Information." O 0
  12. Molimard M, Girodet PO, Pollet C, et al. "Inhaled corticosteroids and adrenal insufficiency: prevalence and clinical presentation." Drug Saf 31 (2008): 769-74
  13. Daveluy A, Raignoux C, Miremont-Salame G, et al. "Drug interactions between inhaled corticosteroids and enzymatic inhibitors." Eur J Clin Pharmacol (2009):
  14. Kedem E, Shahar E, Hassoun G, Pollack S "Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient." J Asthma 47 (2010): 830-1
  15. "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation (2011):
  16. "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals (2011):
View all 16 references

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Moderate

isoniazid formoterol

Applies to: Nydrazid (isoniazid) and budesonide / formoterol

MONITOR: Monoamine oxidase inhibitors (MAOIs) can potentiate the cardiovascular adverse effects of beta-2 adrenergic agonists such as hypertension, palpitation, tachycardia, and chest pain.

MANAGEMENT: Cardiovascular status should be closely monitored when beta-2 agonists are coadministered with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). Preferably, at least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with beta-2 agonists.

References

  1. Finch JS "Cardiovascular toxicity: clinical evaluation of albuterol, isoproterenol and placebo in rising dose tolerance trial." Ann Allergy 47 (1981): 402-4
  2. "Adverse effects and complications of treatment with beta-adrenergic agonist drugs. Committee on drugs, the American Academy of Allergy and Immunology." J Allergy Clin Immunol 75 (1985): 443-9
  3. "Product Information. Proventil (albuterol)." Schering Corporation PROD (2002):
  4. "Product Information. Brethaire (terbutaline)." Novartis Pharmaceuticals PROD (2001):
  5. "Product Information. Isuprel (isoproterenol)." Sanofi Winthrop Pharmaceuticals PROD (2001):
  6. "Product Information. Serevent (salmeterol)." Glaxo Wellcome PROD
  7. "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals PROD (2001):
  8. Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Prichard BN "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J 1 (1973): 311-5
  9. Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31
  10. "Product Information. Alupent (metaproterenol)." Boehringer-Ingelheim PROD (2001):
  11. "Product Information. Tornalate (bitolterol)." Apothecon Inc (2022):
  12. "Product Information. Xopenex (levalbuterol)." Sepracor Inc PROD (2001):
  13. "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals PROD (2001):
  14. "Product Information. Brovana (arformoterol)." Sepracor Inc (2006):
  15. "Product Information. S2 Inhalant (racepinephrine)." Nephron Pharmaceuticals (2010):
  16. "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals (2011):
  17. "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline (2013):
  18. "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim (2014):
View all 18 references

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Minor

budesonide formoterol

Applies to: budesonide / formoterol and budesonide / formoterol

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.

References

  1. "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
View all 4 references

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Drug and food interactions

Moderate

isoniazid food

Applies to: Nydrazid (isoniazid)

GENERALLY AVOID: Concurrent use of isoniazid (INH) in patients who ingest alcohol daily may result in an increased incidence of both hepatotoxicity and peripheral neuropathy. The increase in hepatotoxicity may be due to an additive risk as both alcohol and INH are individually associated with this adverse reaction. INH-associated hepatotoxicity is believed to be due to an accumulation of toxic metabolites and may also be partly immune mediated, though the exact mechanisms are not universally agreed upon. INH is metabolized by N-acetyltransferase and CYP450 2E1. The rate of acetylation is genetically determined and generally classified as slow or rapid. Slow acetylators have been identified by some studies as having a higher risk of hepatotoxicity; therefore, this interaction may be more significant for patients who fall into this category. Other studies have postulated that alcohol-mediated CYP450 2E1 induction may play a role, as this isoenzyme is involved in INH metabolism and may be responsible for producing hepatotoxic metabolites. However, available literature is conflicting. The labeling for some INH products lists daily alcohol use or chronic alcoholism as a risk factor for hepatitis, but not all studies have found a significant association between alcohol use and INH-induced hepatotoxicity. Additionally, INH and alcohol are both associated with pyridoxine (B6) deficiency, which may increase the risk of peripheral neuropathy.

GENERALLY AVOID: Concomitant administration of isoniazid (INH) with foods containing tyramine and/or histamine may increase the risk of symptoms relating to tyramine- and/or histamine toxicity (e.g., headache, diaphoresis, flushing, palpitations, and hypotension). The proposed mechanism is INH-mediated inhibition of monoamine oxidase (MAO) and diamine oxidase (DAO), enzymes responsible for the metabolism of tyramine and histamine, respectively. Some authors have suggested that the reactions observed are mainly due to INH's effects on DAO instead of MAO or the amounts of histamine instead of tyramine present in the food. A Japanese case report recorded an example in 8 out of 25 patients on the tuberculosis ward who developed an accidental histamine poisoning after ingesting a fish paste (saury). Patients developed allergy-like symptoms, which started between 20 minutes and 2 hours after ingesting the food. A high-level of histamine (32 mg/100 g of fish) was confirmed in the saury paste and all 8 patients were both on INH and had reduced MAO concentrations. The 17 remaining patients were not on INH (n=5) or reported not eating the saury paste (n=12).

ADJUST DOSING INTERVAL: Administration with food significantly reduces oral isoniazid (INH) absorption, increasing the risk of therapeutic failure or resistance. The mechanism is unknown. Pharmacokinetic studies completed in both healthy volunteers (n=14) and tuberculosis patients (n=20 treatment-naive patients during days 1 to 3 of treatment) have resulted in almost doubling the time to reach INH's maximum concentration (tmax) and a reduction in isoniazid's maximum concentration (Cmax) of 42%-51% in patients who consumed high-fat or high-carbohydrate meals prior to INH treatment.

MANAGEMENT: The manufacturer of oral forms of isoniazid (INH) recommends administration on an empty stomach (i.e., 30 minutes before or 2 hours after meals). Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and INH concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with INH. Concomitant pyridoxine (B6) administration is also recommended to reduce the risk of peripheral neuropathy, with some authorities suggesting a dose of at least 10 mg/day. Patients should be advised to avoid foods containing tyramine (e.g., aged cheese, cured meats such as sausages and salami, fava beans, sauerkraut, soy sauce, beer, or red wine) or histamine (e.g., skipjack, tuna, mackerel, salmon) during treatment with isoniazid. Consultation of product labeling for combination products containing isoniazid and/or relevant guidelines may be helpful for more specific recommendations.

References

  1. Smith CK, Durack DT "Isoniazid and reaction to cheese." Ann Intern Med 88 (1978): 520-1
  2. Dimartini A "Isoniazid, tricyclics and the ''cheese reaction''." Int Clin Psychopharmacol 10 (1995): 197-8
  3. Uragoda CG, Kottegoda SR "Adverse reactions to isoniazid on ingestion of fish with a high histamine content." Tubercle 58 (1977): 83-9
  4. Self TH, Chrisman CR, Baciewicz AM, Bronze MS "Isoniazid drug and food interactions." Am J Med Sci 317 (1999): 304-11
  5. "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India) 2 (2021):
  6. "Product Information. Isoniazid (isoniazid)." Chartwell RX, LLC. (2023):
  7. "Product Information. Isoniazid (Arrotex) (isoniazid)." Arrotex Pharmaceuticals Pty Ltd (2023):
  8. "Product Information. Isoniazid (isoniazid)." RPH Pharmaceuticals AB (2023):
  9. Saukkonen JJ, Cohn DL, Jasmer RM, et al. "An official ATS statement: hepatotoxicity of antituberculosis therapy." Am J Respir Crit Care Med 174 (2006): 935-52
  10. Bouazzi OE, Hammi S, Bourkadi JE, et al. "First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326068/" (2024):
  11. Wang P, Pradhan K, Zhong XB, Ma X "Isoniazid metabolism and hepatoxicity." Acta Pharm Sin B 6 (2016): 384-92
  12. Saktiawati AM, Sturkenboom MG, Stienstra Y, et al. "Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment naive TB patients: a randomized cross-over trial." J Antimicrob Chemother 71 (2016): 703-10
  13. Hahn JA, Ngabirano C, Fatch R, et al. "Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use." AIDS 37 (2023): 1535-43
  14. Huang YS, Chern HD, Su WJ, et al. "Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis." Hepatology 37 (2003): 924-30
  15. Sousou JM, Griffith EM, Marsalisi C, Reddy P "Pyridoxine deficiency and neurologic dysfunction: an unlikely association. https://www.cureus.com/articles/188310-pyridoxine-deficiency-and-neurologic-dysfunction-an-unlikely-association?score_article=true#!/" (2024):
  16. Miki M, Ishikawa T, Okayama H "An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward." Intern Med 44 (2005): 1133-6
  17. "Product Information. Isotamine (isoniazid)." Bausch Health, Canada Inc. (2021):
View all 17 references

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Moderate

budesonide food

Applies to: budesonide / formoterol

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

MANAGEMENT: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

References

  1. "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc (2001):

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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.

See also

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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

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