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Drug Interactions between guanfacine and vandetanib

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

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Interactions between your drugs

Moderate

guanFACINE vandetanib

Applies to: guanfacine and vandetanib

MONITOR: Coadministration with vandetanib may increase the plasma concentrations of drugs that are substrates of organic cation transporter 2 (OCT2). The mechanism is inhibition of OCT2-mediated renal tubular secretion by vandetanib. In healthy study subjects, single-dose coadministration of metformin and vandetanib increased metformin peak plasma concentration (Cmax) by 50% and systemic exposure (AUC) by 74%.

MANAGEMENT: Caution is advised when vandetanib is used with drugs that are substrates of OCT2, particularly those with a narrow therapeutic range such as metformin. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vandetanib is added to or withdrawn from therapy.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Vandetanib (vandetanib)." Astra-Zeneca Pharmaceuticals (2011):
View all 4 references

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Drug and food interactions

Major

guanFACINE food

Applies to: 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. "Product Information. Tenex (guanfacine)." Wyeth-Ayerst Laboratories PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. "Product Information. Intuniv (guanfacine)." Shire US Inc (2009):

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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.