Drug interactions - summary-

Vorinostat + coumarin -derivative anticoagulant eg. Warfarin

  prolongation of prothrobin time and international normalized ratio INR  observed
in patients receiving vorinostat concomittantly with coumarin -derivative anticoagulant
eg warfarin. Carefully monitor PT and INR in patients coadministered vorinostat and coumarin derivatives

Vorinostat + valproic acid

severe thrombocytopenia and  GI bleeding reported with concomittant use of vorinostat
with HDAC inhibitors eg, valproic acid.
Monitor platelet count every 2 weeks after the first 2 months

Cutaneous T-cell lymphoma ( CTCL )

Common adverse reactions-

GI symptoms eg anorexia, diarrhea, constipation, nausea, vomiting, weight decrease
constitutional symptoms - eg chills, fatigue,
hematological abnormalites eg anemia, thrombocytopenia,
taste disorders - dry mouth, dyspeusia
Pulmonary embolism

CNS- dizziness   12%    fatigue    42%   headache  8%

Dermatologic -  alopecia    14%     pruritus   8%

GI -     anorexia    20%   constipation  11%    decreaed appetite   10%    diarrhea   42%
           dry mouth   12%  dysgeusia    22%     nausea      32%         vomiting   11%

Hematologic      anemia      10%     thrombocytopenia   20%

Musculoskeletal -     muscle spasms   15%

Respiratory -    cough    7%    upper respiratory tract infection 7%

Miscellaneous -     blood creatinine  increased    12%     chills 12%  
                                peripheral edema   10%    pyrexia   7%
                                weight decreased    17%

Not known

Special Precautions/Warnings-

Cardiac effects - administer vorinostat with particular caution in patients with congenital
long QT syndrome and patients taking antiarrhthmic medicines or other products that lead
to QT prolongation

GI effects- GI disturbances inculding nausea ,vimiting and diarrhea  have been reported
and may require the use of antiemetic and antidiarrheal medications
Replace fluid and electrolytes to prevent dehydration.
Patients instructed to drink at least 2L/day of fluids for adequate hydration.

Hematologic effects - if platelet count and/or hemoglobin are reduced during treatment with vorinostat , modify the dosage or discontinue therapy

Hyperglycemia - as pulmonary embolism and deep vein thrombosis have been reported,
be alert to the signs and symptoms in patients with prior history of thromboembolic reactions

Thromboembolism- be alert to the signs and sypmtoms of pulmonary embolism and deep
vein thrombosis particularly in patients with a prior  history of thromboembolic reactions

Renal function impairment - treat patients with preexising renal function impairment  with caution.

Hepatic function impairment - treat patients with  hepatic function impairment with caution

Pregnancy - if the drug is used during pregnancy of if the patient becomes pregnant while taking the drug, appraise the patient of the potential hazard to the fetus.

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

Children- safety and efficacy of verinostat in children have not been established

Elderly- no overall differences in responses between the elderly and younger patients ,
but greater sensitivity of some of the older individuals cannot be ruled out.

Laboratory test abnormalites- increased glucose was reported with 400mg once
daily dosage. Transcient increases in serum creatinine were also detected

Indication-

Cutaneous T-cell lymphoma ( CTCL )

Dosage -

Recommended dose - 400mg orally once daily with food. treatment may continued  as there is no evidence of progressive disease or unacceptable toxicity

Dose modification - If a patient is intolrent to therapy, the dose may be reduced to 300mg orally with food. The dose may be further reduced to 300mg once daily with food for 5 consecutive days each week, as necessary

Storage- store at 20 to 25C ( 68 to 77F )

1. Instruct patients to drink at least 2L/day of fluid to prevent dehydration and to promptly report
excessive vomiting or diarrhea to their Doctor.

2. Instruct patients about the signs of deep vein thrombosis and to consult their doctor, should
any deep vein thrombosis develop.

3. Patients receiving verinostat should seek immdiate medical attention if any unusual bleeding
occurs.

4. Do not open or crush vorinostat capsules.

5. Instruct patients to read the patient insert carefully.

To be taken with food.

Pregnancy -
If the drug is used during pregnancy of if the patient becomes pregnant while taking
the drug, appraise the patient of the potential hazard to the fetus.

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

Children-
Safety and efficacy of verinostat in children have not been established

Elderly-
No overall differences in responses between the elderly and younger patients ,
but greater sensitivity of some of the older individuals cannot be ruled out.