Interacting drugs -summary

+ Nilotinib

CYP450 3A4 inducers eg. carbamazepine, dexemethasone, phenobarbital, rifabutin,
rifampin, rifapentine, St Johns wart
Avoid concomittant use . If coadministration is necessary, the dose of nilotinib
need to reduced

CYP450 3A4 inhibitors eg. atazanavir, clarithromycin, indinavir, itraconazole,
ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin,
voriconazole
Avoid concomittant use. If coadministration is necessary reduce the dose of nilotinib
to half the original daily dose

P-glycoprotein + Nilotinib or Nilotinib + p-glycoprotein
Nilotinib is a substrate of P-glycoprotein. If nilotinib is coadministered with drugs
that inhibit P-glycoprotein increased concentration of nilotinib are necessary.
Excercise caution

Nilotinib +

CYP3A4 substrate eg cyclosporine.idazolam, pimozide
coadmininstration of nilotinib and midazolam increased exposure.
Use caution when administering nilotinib with CYP3A4 substrates

Warfarin
avoid concurrent use if possible

Serious adverse drug reactions-
electrolyte abnormalites, elevated serum lipase, hepatotoxicity, myelosuppression,
and QT prolongation andsuden deaths

Most commonly reported adverse drug reactions-
febrile neutropenia, intracranial hemorrhage, leukopenia, neutropenia, pneumonia,
pyrexia and thrombocytopenia

Sudden death and QT prolongation reported

CNS -  asthenia  12%   fatigue  26%   headache  30%

Dermatologic -  pruriitus  26%    rash 30%

GI -         abdominal pain  10%     constipation 20%   diarrhea  20% nausea   28%
               vomiting  19%

Musculoskeletal -   arthalgia   16%    back pain 8%   bone pain 9% 
                                muscle spasms 10%       myalgia  12% 
                                pain in extremity  12%

Respiratory -         cough  15%    dyspnea  10%   nasopharyngitis   14%

Miscellaneous -      peripheral edema  10%      pyrexia   12%   

Hypokalemia, hypomaganesemia, or long QT syndrome

Special Precautions/Warnings-

QT prolongation ad suden deaths- nitotinib prolongs QT interval. Sudden death have reported in patients receiving nilotinib

Do not use nilotinib in patients with hypokalemia, hypomaganesemia or long QT syndrome
Hyopkalemia and hypomaganesemia should be corrected prior to administration of nilotinib
and should be periodically monitored.

Myelosuppresion- myelosuppression was generally reversible and usually managed by
 withholding  nilotinib temporarily or reducing the dose

Elevated serum lipase - use of nilotinib can cause increases in serum lipase . Caution is
recomended in patients with a history of pancreatitis. Check serum lipase periodically

Hepatoxicity -  use of nilotinib may result in elevation of alkaline phosphatase,
AST/ALT  and bilirubin. Check hepatic function tests periodically

Electrolyte imbalance - use of nilotinib can cause hyperkalemia, hypocalcemia,
hypokalemia, hyponatremia, and hypophosphatemia. Electrolye imbalance corrected prior to initiating treatment with nilotinib. Monitor electrolytes periodically during treatment

Renal function impairment - because nilotinib and its metabolites are not renally excreted
 a decrease in renal clarance is not anticipated in patients with renal function impairment

Hepatic function impairment - caution is recommended in patients with hepatic function
impairment. Closely monitor these patients for QT interval prolongation

Pregnancy- nilotinib can cause fetal harm when administered to a pregnant woman.

Lactation- decide whether to discontinue breast feeding or the drug taking into account
the importance of the drug to the mother.

Children- safety and effectiveness  in children have not been established

Elderly- no major differences were observed for safety in patients 65 years of age
and older compared to younger than 65 years of age.

Monitoring-  perform complete blod dell counts every 2 weeks for the first 2 months and then monthly therafter.
Obtain ECG at baseline 7 days after initiation and periodically thereafter.
Monitor patients with hepatic function impairment closely for QT prolongation

Indication-

Chronic Myelogenous leukemia  ( CML )

Dosage -
400mg twice daily . Treatment should continue as long as the patient does not show evidence of progression or unacceptable toxicity

If the dose is missed the patient should not take a make-up but should resume             taking the next prescribed dose.

1. Nilotinib doses should be taken twice daily, approximately 12 hours apart, and should not be taken with food.

2. Swallow capsules whole with water

3.  Advice patients to take nilotinib on an empty stomach at least 2 hours after a meal

4.Advice patients that no food should be consumed for atleast 1 hour after the dose is taken.

5. Advice patients not to consume grapefruit juice and other food that are known to inhibit
CYP3A at any time during the treatment

6. Advice patients that use of nilotinib during pregnancy may cause harm to the fetus and
should not be taken during pregnancy, unless necessary.

7.Instruct women of child bearing potential to use contraceptives if taking nilotinib.

8. Sexually active women taking nioltinib should use adequate contraceptives

Should not be taken with food

To be taken an empty stomach at least 2 hours after a meal. No food should be consumed
for atleast 1 hour after the dose is taken.

Pregnancy-
Nilotinib can cause fetal harm when administrated to a pregnant woman.

Lactation-
Decide whether to discontinue breast feeding or the drug taking into account
the importance of the drug to the mother.

Children-
Safety and effectiveness  in children have not been established

Elderly-
No major differences were observed for safety in patients 65 years of age
and older compared to younger than 65 years of age.