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Drug Interactions between AK-Beta and Tenex

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

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Interactions between your drugs

Moderate

guanFACINE levobunolol ophthalmic

Applies to: Tenex (guanfacine) and AK-Beta (levobunolol ophthalmic)

MONITOR: Use of central alpha-2 adrenergic agonists, such as clonidine or guanfacine, with beta-blockers may have synergistic pharmacodynamic effects resulting in AV block, bradycardia, and hypotension. In addition, sinus node dysfunction may also be enhanced. Abrupt withdrawal of an alpha-2 agonist or both the alpha-2 agonist and the beta-blocker may also result in rebound hypertensive effects. Increased blood pressure, hypertensive crisis, hypertensive encephalopathy, strokes, and fatalities have been reported after clonidine withdrawal. The proposed mechanism is related to increased catecholamine release after alpha-2 agonist withdrawal which, when combined with concurrent beta-blockade, results in unopposed vasoconstriction. Data are available for clonidine; however, the manufacturer of guanfacine states that beta-blockers and guanfacine have been given concomitantly without evidence of any interactions in long-term safety studies. Patients who discontinued clonidine while taking noncardioselective beta blockers appeared to be at a higher risk of developing rebound hypertension.

MANAGEMENT: Until more information is available, caution and close monitoring of blood pressure are recommended for patients receiving guanfacine with a beta-blocker. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some patients. 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, headaches, or reduced or irregular heart rate.

References

  1. Perks D, Fisher GC (1992) "Esmolol and clonidine: a possible interaction." Anaesthesia, 47, p. 533-4
  2. Jounela AJ, Lilja M (1984) "Interactions between beta-blockers and clonidine." Ann Clin Res, 16, p. 181-2
  3. Lilja M, Jounela AJ, Juustila H, Mattila MJ (1980) "Interaction of clonidine and beta-blockers." Acta Med Scand, 207, p. 173-6
  4. Bailey RR, Neale TJ (1976) "Rapid clonidine withdrawal with blood pressure overshoot exaggerated by beta-blockage." Br Med J, 1, p. 942-3
  5. Strauss FG, Franklin SS, Lewin AJ, Maxwell MH (1977) "Withdrawal of antihypertensive therapy. Hypertensive crisis in renovascular hypertension." JAMA, 238, p. 1734-6
  6. (2001) "Product Information. Tenex (guanfacine)." Wyeth-Ayerst Laboratories
  7. (2001) "Product Information. Zanaflex (tizanidine)." Acorda Therapeutics
  8. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  9. (2009) "Product Information. Intuniv (guanfacine)." Shire US Inc
View all 9 references

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Drug and food interactions

Major

guanFACINE food

Applies to: Tenex (guanfacine)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of guanfacine. The risk of adverse reactions such as hypotension, bradycardia, and sedation may increase. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Ketoconazole, a potent CYP450 3A4 inhibitor, has been reported to increase guanfacine peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 2- and 3-fold, respectively. A computer simulation suggests that fluconazole, a moderate CYP450 3A4 inhibitor, would increase guanfacine Cmax and AUC by about 1.5- and 2-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

GENERALLY AVOID: Alcohol may enhance the sedative and hypotensive effects of guanfacine.

GENERALLY AVOID: Administration of extended-release guanfacine with a high-fat meal may increase the bioavailability of guanfacine. When a single 4 mg dose of extended-release guanfacine was administered to adult volunteers with a high-fat breakfast, mean guanfacine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 75% and 40%, respectively, compared to dosing in a fasted state.

MANAGEMENT: Patients treated with guanfacine should avoid consumption of grapefruit and grapefruit juice. In addition, it is preferable to avoid or limit the use of alcohol during treatment. Patients should be advised against driving or operating hazardous machinery until they know how the medication affects them. The extended-release formulation of guanfacine should not be taken together with a high-fat meal.

References

  1. (2001) "Product Information. Tenex (guanfacine)." Wyeth-Ayerst Laboratories
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. (2009) "Product Information. Intuniv (guanfacine)." Shire US Inc

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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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