Drug interaction -summary

+Sunitinib

CYP-4503A4 inducers- eg carbamzapine, dexamethasone, phenobarbital, phenytoin,
rifabutin, rifampin, rifapentine, St.johns Wart

Coadministration is not recommended. Consider a dose increase of suminitab to
a maximum of 87.5mg daily , if it  siminitib must be coadminstered with a CYP3A4
inducer.

CYP-4503A4  inhibitors eg atazanavir,clarithromycin, indinavir, itraconazole, ketoconazole,nefazodone, nelfinavir, saquinavir, telitromycin , voriconazole

Consider a dose decrease of sunitinib to  a minimum of  37.5mg daily if suninitib must be
coadministered. with a CYP3A4 inhibitor.

Advanced renal cell carcinoma

GI stromal tumor (GIST )

Most common adverse reactions-
abdominal pain, altered taste, anorexia, asthenia, bleeding, constipation, diarrhea, dyspepsia, fatigue, hand- foot syndrome, hypertension,mucositosis/stomatitis, nausea, rash, skin discoloration and vomiting

Cardiovascular - hypertension  14%

CNS -    asthenia  20%

Dermatologic -    hand-foot syndrome   13%    rash  12%   skin discoloration 28%

GI -          altered taste  20%   anorexia   30%   constipation 18%   diarrhea   38%
                mucositis/stomatitis  26%

Miscellaneous -   myalgia/limb pain    13%

Lab/test abnormalites-

 Cardiovascular -     decreased LVEF   10%

GI -                             amylase  15%        lipase  24%

Drug/food interaction- grape fruit may increase plasma concentrations of sunitinib

Hematologic/lymphatic -     anemia    25%    lymphoma  35%   neutropenia    50%
                                               thrombocytopenia     35%

Hepatic -    alkaline phosphatase   23%      AST/ALT   35%  indirect bilirubin  8%
                    total bilirubin  14%

Metabolic/renal -      creatinine   10%    hypernatremia   8%    hypokalemia   10%  

Special precautions/Warnings-

Left ventricular dysfuntion- interupt and or reduce the dose of sunitinib in patients without
clinical eveidence of CHF but the ejection fraction of less than the baseline .
Weigh the potential benefits of the sunitinib.

QT interval prolongation-  use sunitinib with caution in patients who have a history of
QT interval prolongation, are taking antiarrhythmias or have preexisting cardiac disease,
bradycardia, or electrolyte disturbances.

Pregnancy - Advice women of childbearing potential to avoid becoming pregnant while
receiving treatment with sunitinib.

Lactation- decide whether to discontinue breast feeding or the drug depending on
the importance to the mother.

Children- Safety and efficacy of sunitinib in children have not been studied

Elderly- No overall difference in efficacy were observed between younger and older patients

Monitoring- perform complete blood counts with platelet count and serum chemistries,
including phosphates at the beginning of each treatment cycle

Monitor patients for hypertension and treat as needed.

Indication-

Advanced renal cell carcinoma
GI stromal tumor (GIST )

Dosage-
The recommended dose for GIST and advanced renal cell carcinoma is one 50mg oral dose once daily on a schedule of 4 weeks on treatment followed by 2 weeks off.
It may taken with or without food.

Dose mdification- dose increase or reduction in 12.5mg increments is recommended based on individual safety and toleralibity.

Storage - store at 25C( 77F) excursions are permitted to 15 to 30C ( 59 to 86F)

1. Advice patients about GI disorders. Diarrhea, dyspepsia, nausea, stomatitis, and vomiting
are most commonly reported GI reactions occuring in patients receiving sunitinib. Supporting care for  GI adverse reactions requiring treatment may include antiemtic or antidiarrheal medication.

2. Advice patients of possible skin discoloration is due to the color ( yellow ) which occurs
approximately one-third of the patients .

Advice patients that pigmentation of the hair or skin may occur during treatment with sunitinib

Other possible dermatological effects include dryness, thickness, or cracking of the skin,
blister on the palms of the hands and soles of the feet.

3. Advice patients that other commonly adverse reactions include bleeding,fatigue,
 high blood pressure, mouth pain/irritation, swelling, and taste disturbance.

4. Advice patients in inform their health care providers of all concomittant medications,
including nonprescription medications and dietary supplements
  

It may taken with or without food.

Pregnancy -
Advice women of childbearing potential to avoid becoming pregnant while
receiving treatment with sunitinib.

Lactation-
Decide whether to discontinue breast feeding or the drug depending on
the importance to the mother.

Children-
Safety and efficacy of sunitinib in children have not been studied

Elderly-
No overall difference in efficacy were observed between younger and older patients