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Drug Interactions between atenolol / chlorthalidone and lithium

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

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Interactions between your drugs

Major

lithium chlorthalidone

Applies to: lithium and atenolol / chlorthalidone

GENERALLY AVOID: Thiazide diuretics may cause a rapid increase in serum lithium levels and potentiate the risk of lithium toxicity. The exact mechanism is unknown but may be related to the sodium loss induced by thiazide diuresis, which produces a compensatory increase in proximal tubular reabsorption of sodium along with lithium. In a study of 22 patients receiving bendroflumethiazide 2.5 mg or hydroflumethiazide 25 mg daily for the treatment of edema, mean renal clearance of a single 600 mg dose of lithium carbonate was reduced by 24% during thiazide diuretic therapy compared to before or after diuretic therapy. A similar reduction in renal lithium clearance has been reported in studies with chlorothiazide. There have also been case reports of patients developing lithium toxicity shortly after initiation of various thiazide diuretics including bendroflumethiazide, chlorothiazide, chlorthalidone, hydrochlorothiazide and indapamide, either alone or in combination with other diuretics. Up to severalfold increases in serum lithium levels have been observed, usually within several days to 2 weeks but occasionally longer. The risk for lithium toxicity may be further increased during concomitant sodium restriction.

MANAGEMENT: Thiazide diuretics should generally not be prescribed to patients receiving lithium unless close monitoring of serum lithium levels and electrolytes can be rendered. Lithium dose reductions may be required. Patients should be advised to notify their physician if they experience potential signs and symptoms of lithium toxicity such as drowsiness, dizziness, muscle weakness, vomiting, diarrhea, thirst, polyuria, tinnitus, tremor, ataxia, and blurred vision. Some investigators have suggested that loop diuretics are safer with lithium than thiazide diuretics, although supporting data are limited.

References

  1. Crabtree BL, Mack JE, Johnson CD, Amyx BC "Comparison of the effects of hydrochlorothiazide and furosemide on lithium disposition." Am J Psychiatry 148 (1991): 1060-3
  2. MacNeil S, Hanson-Nortey E, Paschalis C, et al. "Diuretics during lithium therapy." Lancet 06/07/75 (1975): 1295-6
  3. Boer WH, Koomans HA, Mees EJ "Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man." Clin Sci 76 (1989): 539-45
  4. Hanna ME, Lobao CB, Stewart JT "Severe lithium toxicity associated with indapamide therapy." J Clin Psychopharmacol 10 (1990): 379-80
  5. Dorevitch A, Baruch E "Lithium toxicity induced by combined amiloride HCl- hydrochlorothiazide administration." Am J Psychiatry 143 (1986): 257-8
  6. Gammon GD, Docherty JP "Thiazide-induced hypercalcemia in a manic-depressive patient." Am J Psychiatry 137 (1980): 1453-5
  7. Levy ST, Forrest JN, Jr Heninger GR "Lithium-induced diabetes insipidus: manic symptoms, brain and electrolyte correlates, and chlorothiazide treatment." Am J Psychiatry 130 (1973): 1014-8
  8. Poust RI, Mallinger AG, Mallinger J, Himmelhoch JM, Neil JF, Hanin I "Effect of chlorothiazide on the pharmacokinetics of lithium in plasma and erythrocytes." Psychopharmacol Commun 2 (1976): 273-84
  9. Solomon JG "Lithium toxicity precipitated by a diuretic." Psychosomatics 21 (1980): 425, 429
  10. Macfie AC "Lithium poisoning precipitated by diuretics." Br Med J 1 (1975): 516
  11. Nurnberger JI Jr "Diuretic-induced lithium toxicity presenting as mania." J Nerv Ment Dis 173 (1985): 316-8
  12. Mehta BR, Robinson BH "Lithium toxicity induced by triamterene-hydrochlorothiazide." Postgrad Med J 56 (1980): 783-4
  13. Hurtig HI, Dyson WL "Lithium toxicity enhanced by diuresis." N Engl J Med 290 (1974): 748-9
  14. Petersen V, Hvidt S, Thomsen K, Schou M "Effect of prolonged thiazide treatment on renal lithium clearance." Br Med J 3 (1974): 143-5
  15. Himmelhoch JM, Poust RI, Mallinger AG, Hanin I, Neil JF "Adjustment of lithium dose during lithium-chlorothiazide therapy." Clin Pharmacol Ther 22 (1977): 225-7
  16. Kerry RJ, Ludlow JM, Owen G "Diuretics are dangerous with lithium." Br Med J 281 (1980): 371
  17. "Product Information. Eskalith (lithium)." SmithKline Beecham PROD (2002):
  18. Aronson JK, Reynolds DJM "ABC of monitoring drug therapy. Lithium." Br Med J 305 (1992): 1273-6
  19. Jefferson JW, Kalin NH "Serum lithium levels and long-term diuretic use." JAMA 241 (1979): 1134-6
  20. Finley PR, Warner MD, Peabody CA "Clinical relevance of drug interactions with lithium." Clin Pharmacokinet 29 (1995): 172-91
  21. Bennett WM "Drug interactions and consequences of sodium restriction." Am J Clin Nutr 65 (1997): S678-81
  22. Vipond AJ, Bakewell S, Telford R, Nicholls AJ "Lithium toxicity." Anaesthesia 51 (1996): 1156-8
View all 22 references

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Moderate

atenolol lithium

Applies to: atenolol / chlorthalidone and lithium

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Moderate

atenolol chlorthalidone

Applies to: atenolol / chlorthalidone and atenolol / chlorthalidone

MONITOR: Although they are often combined in clinical practice, diuretics and beta-blockers may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in patients with diabetes or latent diabetes. In addition, the risk of QT interval prolongation and arrhythmias (e.g. torsades de pointes) due to sotalol may be increased by potassium-depleting diuretics.

MANAGEMENT: Monitoring of serum potassium levels, blood pressure, and blood glucose is recommended during coadministration. Patients should be advised to seek medical assistance if they experience dizziness, weakness, fainting, fast or irregular heartbeats, or loss of blood glucose control.

References

  1. Dornhorst A, Powell SH, Pensky J "Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion." Lancet 1 (1985): 123-6
  2. Roux A, Le Liboux A, Delhotal B, Gaillot J, Flouvat B "Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination." Eur J Clin Pharmacol 24 (1983): 801-6
  3. Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33
  4. "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer PROD (2002):
  5. Marcy TR, Ripley TL "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm 63 (2006): 49-58
View all 5 references

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Drug and food interactions

Moderate

atenolol food

Applies to: atenolol / chlorthalidone

GENERALLY AVOID: Orange juice may moderately reduce the bioavailability of atenolol by interfering with its absorption from the gastrointestinal tract. In a pharmacokinetic study, subjects ingested 200 mL orange juice 3 times daily for 3 days and twice daily on the fourth day, and took 50 mg atenolol with 200 mL orange juice on day 3. The average peak plasma concentration (Cmax) of atenolol fell by 49% and the area under the concentration-time curve (AUC) fell by 40% in comparison to subjects who drank only water. In addition, the presence of food may reduce the bioavailability of atenolol by 20%. The clinical significance is unknown.

MANAGEMENT: Patients treated orally with atenolol should be advised to take atenolol at the same time each day and to avoid consumption of large amounts of orange juice to prevent any undue fluctuations in serum drug levels. Monitoring for altered efficacy of atenolol may be advisable.

References

  1. Lilja JJ, Raaska K, Neuvonen PJ "Effects of orange juice on the pharmacokinetics of atenolol." Eur J Clin Pharmacol (2005):

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Moderate

lithium food

Applies to: lithium

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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Moderate

atenolol food

Applies to: atenolol / chlorthalidone

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Moderate

chlorthalidone food

Applies to: atenolol / chlorthalidone

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Moderate

atenolol food

Applies to: atenolol / chlorthalidone

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther 30 (1981): 429-35

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Moderate

lithium food

Applies to: lithium

MONITOR: One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

MANAGEMENT: When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.

References

  1. Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A "Caffeine withdrawal increases lithium blood levels." Biol Psychiatry 37 (1995): 348-50

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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.