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Drug Interactions between chlorothiazide / methyldopa and tizanidine

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

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Interactions between your drugs

Major

methyldopa tiZANidine

Applies to: chlorothiazide / methyldopa and tizanidine

GENERALLY AVOID: Tizanidine has alpha-2 adrenergic activity and may potentiate the hypotensive effects of other alpha-2 adrenergic agonists. Pharmacologic studies have found tizanidine to possess between 1/10 to 1/50 of the potency of clonidine, a structurally similar agent, in lowering blood pressure. In a single-dose study where blood pressure was monitored closely after dosing, two-thirds of patients treated with an 8 mg dose had a 20% reduction in either the diastolic or systolic blood pressure. The reduction was seen within 1 hour after dosing, peaked 2 to 3 hours after dosing, and was associated at times with bradycardia, orthostatic hypotension, lightheadedness, dizziness, and rarely, syncope. The hypotensive effect of tizanidine is dose-related and has been measured following single doses of 2 mg or more.

MANAGEMENT: Concomitant use of tizanidine with other alpha-2 adrenergic agonists should be avoided.

References

  1. (2001) "Product Information. Zanaflex (tizanidine)." Acorda Therapeutics

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Major

chlorothiazide tiZANidine

Applies to: chlorothiazide / methyldopa and tizanidine

ADJUST DOSE: Tizanidine may potentiate the hypotensive effect of some medications secondary to its alpha-2 adrenergic activity. Pharmacologic studies have found tizanidine to possess between 1/10 to 1/50 of the potency of clonidine, a structurally similar agent, in lowering blood pressure. The hypotensive effect of tizanidine is dose-related and has been measured following single doses of 2 mg or more. In a single-dose study where blood pressure was monitored closely after dosing, two-thirds of patients treated with an 8 mg dose had a 20% reduction in either diastolic or systolic blood pressure. The reduction was seen within 1 hour after dosing, peaked 2 to 3 hours after dosing, and was associated at times with bradycardia, orthostatic hypotension, lightheadedness, dizziness, and rarely, syncope. In clinical trials, the addition of tizanidine to antihypertensive therapy was associated with a 20% to 30% increase in the incidence of clinically significant decreases in systolic or diastolic blood pressure compared with placebo plus antihypertensive therapy or tizanidine alone. The incidence of orthostatic hypotension was also increased.

MANAGEMENT: A lower initial dosage and cautious dosage titration should be considered when tizanidine is initiated in patients receiving hypotensive medications. Although single doses of less than 8 mg of tizanidine have not been shown to be effective for spasticity in controlled clinical studies, some authorities recommend initiating treatment with single oral doses of 2 mg. The dose can then be gradually increased by 2 to 4 mg, with 1 to 4 days between dosage increases, until the optimum effect is achieved. The dose can be repeated at 6- to 8-hour intervals as needed, up to a maximum of three doses in 24 hours and a total daily dosage of 36 mg. Single doses greater than 16 mg have not been studied. Close monitoring for development of hypotension is recommended. 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. (2001) "Product Information. Zanaflex (tizanidine)." Acorda Therapeutics
  2. (2019) "Product Information. TiZANidine Hydrochloride (tiZANidine)." Advagen Pharma Limited
  3. (2023) "Product Information. Apo-TiZANidine (tizanidine)." AA Pharma Inc
  4. (2022) "Product Information. Tizagelan (tizanidine)." G.L. Pharma UK Ltd
View all 4 references

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Drug and food interactions

Moderate

methyldopa food

Applies to: chlorothiazide / methyldopa

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

chlorothiazide food

Applies to: chlorothiazide / methyldopa

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

methyldopa food

Applies to: chlorothiazide / methyldopa

ADJUST DOSING INTERVAL: The oral bioavailability and pharmacologic effects of methyldopa may be decreased during concurrent administration with iron-containing products. The proposed mechanism is chelation of methyldopa by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In one study, five hypertensive patients receiving chronic methyldopa therapy (250 mg to 1500 mg daily) all had elevated blood pressure following the addition of ferrous sulfate 325 mg three times daily for 2 weeks. The systolic pressure had increased by more than 15 mmHg in three of the patients and the diastolic pressure increased by more than 10 mmHg in two. Blood pressure returned to baseline within 7 days of discontinuing the iron. In 12 normal subjects, administration of methyldopa 500 mg with ferrous sulfate 325 mg or ferrous gluconate 600 mg resulted in an 88% and 79% reduction, respectively, in the renal excretion of unmetabolized, free methyldopa compared to administration of methyldopa alone. In another study, administration of ferrous sulfate simultaneously with methyldopa reduced the bioavailability of methyldopa by 83%, while administration one hour or two hours before methyldopa reduced its bioavailability by 55% and 42%, respectively.

MANAGEMENT: Until more information is available, patients receiving methyldopa in combination with iron-containing products should be advised to separate the times of administration by as much as possible. Patients should be monitored closely for altered hypertensive effect and methyldopa dosage increased as necessary. Selection of an alternative antihypertensive therapy may be necessary.

References

  1. Campbell N, Paddock V, Sundaram R (1988) "Alteration of methyldopa absorption, metabolism, and blood pressure control caused by ferrous sulfate and ferrous gluconate." Clin Pharmacol Ther, 43, p. 381-6
  2. Campbell NR, Campbell RR, Hasinoff BB (1990) "Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism." Clin Invest Med, 6, p. 329-32
  3. Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5

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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

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