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Drug Interactions between Rimactane and Timolide

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

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Interactions between your drugs

Moderate

rifAMPin timolol

Applies to: Rimactane (rifampin) and Timolide (hydrochlorothiazide / timolol)

MONITOR: Rifampin may decrease serum levels and effects of some oral beta-blockers. The proposed mechanism is increased CYP450 oxidative metabolism of beta-blockers that are hepatically metabolized. Renally excreted beta-blockers such as atenolol, carteolol, nadolol, or sotalol are not expected to interact.

MANAGEMENT: Patients should be monitored for clinical response and tolerance when rifampin is added to or discontinued from a beta-blocker regimen. The beta-blocker dosage may require adjustment.

References

  1. Venkatesan K (1992) "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet, 22, p. 47-65
  2. Borcherding SM, Baciewicz AM, Self TH (1992) "Update on rifampin drug interactions." Arch Intern Med, 152, p. 711-6
  3. Branch RA, Herman RJ (1984) "Enzyme induction and beta-adrenergic receptor blocking drugs." Br J Clin Pharmacol, 17, s77-84
  4. Bennett PN, John VA, Whitmarsh VB (1982) "Effect of rifampicin on metoprolol and antipyrine kinetics." Br J Clin Pharmacol, 13, p. 387-91
  5. Stagni G, Davis PJ, Ludden TM (1991) "Human pharmacokinetics of betaxolol enantiomers." J Pharm Sci, 80, p. 321-4
  6. Janku I, Perlik F, Tkaczykova M, Brodanova M (1992) "Disposition kinetics and concentration-effect relationship of metipranolol in patients with cirrhosis and healthy subjects." Eur J Clin Pharmacol, 42, p. 337-40
  7. Piquette-Miller M, Foster RT, Kappagoda CT, Jamali F (1992) "Effect of aging on the pharmacokinetics of acebutolol enantiomers." J Clin Pharmacol, 32, p. 148-56
  8. Smith RL (1985) "Polymorphic metabolism of the beta-adrenoreceptor blocking drugs and its clinical relevance." Eur J Clin Pharmacol, 28, p. 77-84
  9. McGourty JC, Silas JH, Fleming JJ, McBurney A, Ward JW (1985) "Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin." Clin Pharmacol Ther, 38, p. 409-13
  10. Kirch W, Rose I, Klingmann I, Pabst J, Ohnhaus EE (1986) "Interaction of bisoprolol with cimetidine and rifampicin." Eur J Clin Pharmacol, 31, p. 59-62
  11. Le Coz F, Sauleman P, Poirier JM, Cuche JL, Midavaine M, Rames A, Lecocq B, Jaillon P (1991) "Oral pharmacokinetics of bisoprolol in resting and exercising healthy volunteers." J Cardiovasc Pharmacol, 18, p. 28-34
  12. Amemiya M, Tabei K, Furuya H, Sakairi Y, Asano Y (1992) "Pharmacokinetics of carteolol in patients with impaired renal function." Eur J Clin Pharmacol, 43, p. 417-21
  13. Collste P, Seideman P, Borg K, Haglund K, Von Bahr C (1979) "Influence of pentobarbital on effect and plasma levels of alprenolol and 4-hydroxy-alprenolol." Clin Pharmacol Ther, 25, p. 423-7
  14. Shaheen O, Biollaz J, Koshakji R, Wilkinson GR, Wood AJ (1987) "Effect of debrisoquine (D) phenotype on the inducibility of propranolol (P) metabolism." Clin Pharmacol Ther, 41, p. 158
  15. (2002) "Product Information. Tenormin (atenolol)." ICN Pharmaceuticals Inc
  16. (2002) "Product Information. Normodyne (labetalol)." Schering Corporation
  17. (2002) "Product Information. Corgard (nadolol)." Bristol-Myers Squibb
  18. (2001) "Product Information. Inderal (propranolol)." Wyeth-Ayerst Laboratories
  19. (2001) "Product Information. Blocadren (timolol)." Merck & Co., Inc
  20. (2001) "Product Information. Brevibloc (esmolol)." DuPont Pharmaceuticals
  21. (2001) "Product Information. Cartrol (carteolol)." Abbott Pharmaceutical
  22. (2001) "Product Information. Betapace (sotalol)." Berlex Laboratories
  23. (2001) "Product Information. Levatol (penbutolol)." Reed and Carnrick
  24. Morgan T (1994) "Clinical pharmacokinetics and pharmacodynamics of carvedilol." Clin Pharmacokinet, 26, p. 335-46
  25. McTavish D, Campoli-Richards D, Sorkin EM (1993) "Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy." Drugs, 45, p. 232-58
  26. Seffart G ed. (1991) "Drug Dosage in Renal Insufficiency." Dordrecht, South Holland, : Kluwer Academic Publishers
  27. Limbird LE eds., Gilman AG, Hardman JG (1995) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill
  28. Strayhorn VA, Baciewicz AM, Self TH (1997) "Update on rifampin drug interactions, III." Arch Intern Med, 157, p. 2453-8
View all 28 references

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Moderate

timolol hydroCHLOROthiazide

Applies to: Timolide (hydrochlorothiazide / timolol) and Timolide (hydrochlorothiazide / timolol)

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

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Drug and food interactions

Moderate

rifAMPin food

Applies to: Rimactane (rifampin)

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 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 rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References

  1. (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
  2. (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
  3. (2023) "Product Information. Rifadin (rifampicin)." Sanofi
  4. (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE (2024) Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/
  6. (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.
View all 6 references

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Moderate

timolol food

Applies to: Timolide (hydrochlorothiazide / timolol)

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

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Moderate

hydroCHLOROthiazide food

Applies to: Timolide (hydrochlorothiazide / timolol)

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

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Moderate

timolol food

Applies to: Timolide (hydrochlorothiazide / timolol)

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 (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35

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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.

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