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Vandetanib (Vandetanib) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

CYP3A4 Inducers

Drugs that are CYP3A4 inducers can alter vandetanib plasma concentrations. The concomitant use of known strong CYP3A4 inducers should be avoided while receiving vandetanib therapy. St. John’s Wort may decrease vandetanib exposure unpredictably and should be avoided [see Dosage and Administration and Warnings and Precautions].

CYP3A4 Inhibitors

In healthy subjects, no clinically significant interaction was shown between vandetanib and the potent CYP3A4 inhibitor, itraconazole.

Drugs that Prolong the QT Interval

The administration of vandetanib with agents that may prolong the QT interval should be avoided [see Warnings and Precautions].

OVERDOSAGE

There is no specific treatment in the event of overdose with vandetanib and possible symptoms of overdose have not been established. Because of the 19-day half-life, adverse reactions may not resolve quickly. In phase 1 clinical trials, a limited number of patients were treated with daily doses of up to 600 mg and healthy volunteers with daily doses up to 1200 mg. An increase in the frequency and severity of some adverse reactions, like rash, diarrhea and hypertension, was observed at multiple doses at and above 300 mg in healthy volunteer studies and in patients. In addition the possibility of QTc prolongation and Torsades de pointes should be considered.

Adverse reactions associated with overdose are to be treated symptomatically; in particular, severe diarrhea must be managed appropriately. In the event of an overdose, further doses of vandetanib must be interrupted, and appropriate measures taken to assure that an adverse event has not occurred, i.e., ECG within 24 hours to determine QTc prolongation [see Dosage and Administration].

CONTRAINDICATIONS

Do not use in patients with congenital long QT syndrome [see Boxed Warning ].

REFERENCES

  1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004 165.

  2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

  3. American Society of Health-System Pharmacists. ASHP Guidelines on Handling Hazardous Drugs: Am J Health-Syst Pharm. (2006) 63:1172-1193.

  4. Polovich, M., White, J. M., & Kelleher, L. O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.

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