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Drug Interactions between Dolophine and formoterol

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

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Interactions between your drugs

Moderate

methadone formoterol

Applies to: Dolophine (methadone) and formoterol

MONITOR: Beta-2 adrenergic agonists can cause dose-related prolongation of the QT interval and potassium loss. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Clinically significant prolongation of QT interval and hypokalemia occur infrequently when beta-2 agonists are inhaled at normally recommended dosages. However, these effects may be more common when the drugs are administered systemically or when recommended dosages are exceeded.

MANAGEMENT: Caution is recommended if beta-2 agonists are used in combination with other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Whyte KF, Addis GJ, Whitesmith R, Reid JL (1987) "The mechanism of salbutamol-induced hypokalaemia." Br J Clin Pharmacol, 23, p. 65-71
  2. Larsson S, Svedmyr N (1977) "Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol inasthmatics." Am Rev Respir Dis, 116, p. 861-9
  3. Hastwell G, Lambert BE (1978) "The effect of oral salbutamol on serum potassium and blood sugar." Br J Obstet Gynaecol, 85, p. 767-9
  4. (1981) "Hypokalaemia due to salbutamol overdosage." Br Med J (Clin Res Ed), 283, p. 500-1
  5. Kantola I, Tarssanen L (1986) "Hypokalemia from usual salbutamol dosage ." Chest, 89, p. 619-20
  6. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE (1990) "Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma." Lancet, 336, p. 1396-9
  7. Gross TL, Sokol RJ (1980) "Severe hypokalemia and acidosis: a potential complication of beta- adrenergic treatment." Am J Obstet Gynecol, 138, p. 1225-6
  8. Clifton GD, Hunt BA, Patel RC, Burki NK (1990) "Effects of sequential doses of parenteral terbutaline on plasma levels of potassium and related cardiopulmonary responses." Am Rev Respir Dis, 141, p. 575-9
  9. Hurlbert BJ, Edelman JD, David K (1981) "Serum potassium levels during and after terbutaline." Anesth Analg, 60, p. 723-5
  10. Bengtsson B, Fagerstrom PO (1982) "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther, 31, p. 726-32
  11. Gelmont DM, Balmes JR, Yee A (1988) "Hypokalemia induced by inhaled bronchodilators." Chest, 94, p. 763-6
  12. Sanders JP, Potter DE, Ellis S, Bee DE, Grant JA (1977) "Metabolic and cardiovascular effects of carbuterol and metaproterenol." J Allergy Clin Immunol, 60, p. 174-9
  13. (2002) "Product Information. Proventil (albuterol)." Schering Corporation
  14. Windom H, Grainger J, Burgess C, Crane J, Pearce N, Beasley R (1990) "A comparison of the haemodynamic and hypokalaemic effects of inhaled pirbuterol and salbutamol." N Z Med J, 103, p. 259-61
  15. "Product Information. Serevent (salmeterol)." Glaxo Wellcome
  16. (2001) "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals
  17. Dickens GR, Mccoy RA, West R, Stapczynski JS, Clifton GD (1994) "Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease." Pharmacotherapy, 14, p. 729-33
  18. Tveskov C, Djurhuus MS, Klitgaard NAH, Egstrup K (1994) "Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta(2)-adrenergic stimulation with terbutaline in healthy subjects." Chest, 106, p. 1654-9
  19. Braden GL, vonOeyen PT, Germain MJ, Watson DJ, Haag BL (1997) "Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences." Kidney Int, 51, p. 1867-75
  20. Rakhmanina NY, Kearns GL, Farrar HC (1998) "Hypokalemia in an asthmatic child from abuse of albuterol metered dose inhaler." Pediatr Emerg Care, 14, p. 145-7
  21. (2001) "Product Information. Xopenex (levalbuterol)." Sepracor Inc
  22. (2001) "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals
  23. Ferguson GT, Funck-Brentano C, Fischer T, Darken P, Reisner C (2003) "Cardiovascular Safety of Salmeterol in COPD." Chest, 123, p. 1817-24
  24. Milic M, Bao X, Rizos D, Liu F, Ziegler MG (2006) "Literature review and pilot studies of the effect of qt correction formulas on reported beta(2)-agonist-induced QTc prolongation." Clin Ther, 28, p. 582-90
  25. (2006) "Product Information. Brovana (arformoterol)." Sepracor Inc
  26. Lowe MD, Rowland E, Brown MJ, Grace AA (2001) "Beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium." Heart, 86, p. 45-51
  27. Sun ZH, Swan H, Vitasalo M, Toivonen L (1998) "Effects of epinephrine and phenylephrine on QT interval dispersion in congenital long QT syndrome." J Am Coll Cardiol, 31, p. 1400-5
  28. (2011) "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals
  29. (2013) "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline
  30. (2014) "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim
View all 30 references

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Drug and food interactions

Moderate

methadone food

Applies to: Dolophine (methadone)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of methadone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 8 study subjects stabilized on methadone maintenance treatment, ingestion of regular strength grapefruit juice (200 mL one-half hour before and 200 mL simultaneously with the daily methadone dose) for five days resulted in an approximately 17% mean increase in methadone peak plasma concentration (Cmax) and systemic exposure (AUC) and a 14% mean decrease in apparent clearance for both the R(+) and S(-) enantiomers. Grapefruit juice did not affect the time to peak level (Tmax), terminal half-life, or apparent volume of distribution of methadone. No signs or symptoms of methadone toxicity or changes in intensity of withdrawal symptoms were reported in the study.

MANAGEMENT: Given the interindividual variability in the pharmacokinetics of methadone, a more significant interaction with grapefruit juice in certain patients cannot be ruled out. Patients treated with methadone should preferably avoid or limit the consumption of grapefruit juice, particularly during the induction of maintenance treatment.

References

  1. Iribarne C, Berthou F, Baird S, Dreano Y, Picart D, Bail JP, Beaune P, Menez JF (1996) "Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes." Chem Res Toxicol, 9, p. 365-73
  2. Oda Y, Kharasch ED (2001) "Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation." J Pharmacol Exp Ther, 298, p. 1021-32
  3. Benmebarek M, Devaud C, Gex-Fabry M, et al. (2004) "Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone." Clin Pharmacol Ther, 76, p. 55-63
  4. Foster DJ, Somogyi AA, Bochner F (1999) "Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4." Br J Clin Pharmacol, 47, p. 403-12
View all 4 references

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Moderate

methadone food

Applies to: Dolophine (methadone)

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
  2. Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
  4. Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
  6. Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
  7. Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
  9. Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80
View all 9 references

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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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