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Drug Interactions between atropine / edrophonium and Ziac

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

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Interactions between your drugs

Moderate

atropine edrophonium

Applies to: atropine / edrophonium and atropine / edrophonium

GENERALLY AVOID: Anticholinergic agents and other agents with significant anticholinergic activity (e.g., clozapine, class IA antiarrhythmics especially disopyramide) may antagonize the effects of cholinergic skeletal muscle stimulants (e.g., ambenonium, edrophonium, guanidine, neostigmine, pyridostigmine). Although this interaction may be desirable in some situations, such as when atropine is used to treat excessive muscarinic side effects and cholinergic crisis induced by anticholinesterase overdose, unintentional or indiscriminate use of anticholinergic agents in the treatment of myasthenia gravis may exacerbate symptoms. In addition, such use may mask the less serious, gastrointestinal signs of cholinergic overdose and lead to inadvertent induction of cholinergic crisis, which can produce respiratory paralysis and death.

MANAGEMENT: Agents with potent anticholinergic activity should preferably be avoided in patients receiving cholinergic skeletal muscle stimulants. If concurrent use is necessary, patients treated for myasthenia gravis should be monitored for potential exacerbation of symptoms. Caution is advised not only because anticholinergic agents may mask the signs of a cholinergic overdose, but also because increasing muscle weakness associated with disease aggravation may be difficult to distinguish from that due to cholinergic crisis.

References

  1. "Product Information. Mestinon (pyridostigmine)." ICN Pharmaceuticals Inc PROD (2001):

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Moderate

atropine bisoprolol

Applies to: atropine / edrophonium and Ziac (bisoprolol / hydrochlorothiazide)

MONITOR: Anticholinergic agents frequently cause drowsiness and other central nervous system-depressant effects that may be additive with those induced by beta blockers. In addition, these agents may increase heart rate and theoretically may counteract the bradycardic effects of beta blockers. Pharmacokinetically, anticholinergic agents may delay the gastrointestinal absorption of beta blockers and other drugs that are administered orally. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents. In healthy volunteers, pretreatment with propantheline has been shown to prolong the time to reach peak plasma concentration (Tmax) for both atenolol and metoprolol. Propantheline also decreased metoprolol peak plasma concentration (Cmax) but had no effect on its systemic exposure (AUC). In contrast, propantheline increased atenolol AUC but had no effect on its Cmax. The clinical relevance of these changes is probably minimal.

MANAGEMENT: Clinicians should be aware of the potential for diminished effects of beta blockers during coadministration with anticholinergic agents. Patients should also be monitored for potentially excessive CNS adverse effects (e.g., drowsiness, dizziness, lightheadedness, confusion, blurred vision) if these agents are used in combination. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Briant RH, Dorrington RE, Ferry DG, Paxton JW "Bioavailability of metoprolol in young adults and the elderly, with additional studies on the effects of metoclopramide and probanthine." Eur J Clin Pharmacol 25 (1983): 353-6
  2. Clark JM, Seager SJ "Gastric emptying following premedication with glycopyrrolate or atropine." Br J Anaesth 55 (1983): 1195-9
  3. Regardh CG, Lundborg P, Persson BA "The effect of antacid, metoclopramide, and propantheline on the bioavailability of metoprolol and atenolol." Biopharm Drug Dispos 2 (1981): 79-87
  4. 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):
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Australian Product Information." O 0
View all 6 references

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Moderate

hydroCHLOROthiazide bisoprolol

Applies to: Ziac (bisoprolol / hydrochlorothiazide) and Ziac (bisoprolol / hydrochlorothiazide)

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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Minor

atropine hydroCHLOROthiazide

Applies to: atropine / edrophonium and Ziac (bisoprolol / hydrochlorothiazide)

Anticholinergic agents may increase the absorption and oral bioavailability of thiazide diuretics. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents. In six healthy volunteers, pretreatment with propantheline prolonged the time to reach peak plasma concentration (Tmax) for hydrochlorothiazide from 2.4 to 4.8 hours and increased its total 48-hour urinary recovery by 36%. Similar results were reported for chlorothiazide in another study. The clinical significance of these changes is unknown.

References

  1. Osman MA, Welling PG "Influence of propantheline and metoclopramide on the bioavailability of chlorothiazide." Curr Ther Res Clin Exp 34 (1983): 404-8
  2. Beermann B, Groschinsky-Grind M "Enhancement of the gastrointestinal absorption of hydrochlorothiazide by propantheline." Eur J Clin Pharmacol 13 (1978): 385-7

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Drug and food interactions

Moderate

atropine food

Applies to: atropine / edrophonium

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Moderate

hydroCHLOROthiazide food

Applies to: Ziac (bisoprolol / hydrochlorothiazide)

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

bisoprolol food

Applies to: Ziac (bisoprolol / hydrochlorothiazide)

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

bisoprolol food

Applies to: Ziac (bisoprolol / hydrochlorothiazide)

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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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.