Panobinostat

What is Panobinostat?

• Panobinostat (FARYDAK), a histone deacetylase inhibitor used, in combination with bortezomib and dexamethasone, to treat people with a type of cancer called multiple myeloma.

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What are the uses of this medicine?

• This medicine is used, in combination with bortezomib and dexamethasone, to treat people with a type of cancer called multiple myeloma after at least 2 other types of treatment have been tried.

How does this medicine work?

• Panobinostat (pan" oh bin' oh stat) is an oral small molecule inhibitor of histone deacetylases, thereby preventing removal of acetyl groups from histones.
• The accumulation of acetyl groups on histones causes cell cycle arrest and apoptotic cell death.
• Malignant cells are particularly sensitive to the effects of inhibition of histone deacetylases.
• In open label studies in patients with multiple myeloma, panobinostat in combination with bortezomib (a proteasome inhibitor) yielded overall response rates of up to 50% and some responders had long term remissions.
• A large, controlled trial in patients with advanced, refractory multiple myeloma demonstrated prolongation of progression-free survival by the addition of panobinostat to bortezomib and dexamethasone, but the overall survival was not different at the time of the initial analysis.
• Nevertheless, panobinostat was given accelerated approval for use in the United States in 2015 to be used in combination with bortezomib and dexamethasone in patients with refractory or relapsed multiple myeloma.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Reduce dose to 10 mg when coadministered with strong CYP3A inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole).
• Instruct patients to avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice because these foods are known to inhibit CYP3A enzymes.
• The concomitant use of strong CYP3A inducers should be avoided.
• Avoid coadministrating FARYDAK with sensitive CYP2D6 substrates (i.e., atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, and venlafaxine) or CYP2D6 substrates that have a narrow therapeutic index (i.e., thioridazine, pimozide). If concomitant use of CYP2D6 substrates is unavoidable, monitor patients frequently for adverse reactions.
• Concomitant use of anti-arrhythmic medicines (including, but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol) and other drugs that are known to prolong the QT interval (including, but not limited to chloroquine, halofantrine, clarithromycin, methadone, moxifloxacin, bepridil and pimozide) is not recommended.

Is this medicine FDA approved?

• It was approved for use in the United States in 2015.

How should this medicine be used?

Prior to the start of FARYDAK treatment and during treatment, monitoring should include:

• Complete Blood Count (CBC)
• ECG
• Serum Electrolytes

Recommended Dosage:

• The recommended starting dose of FARYDAK is 20 mg, taken orally once every other day for 3 doses per week in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles.
• Consider continuing treatment for an additional 8 cycles for patients with clinical benefit, unless they have unresolved severe or medically significant toxicity.

Dose Modifications for Use in Hepatic Impairment

• Reduce the starting dose of FARYDAK to 15 mg in patients with mild hepatic impairment and 10 mg in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

Dose Modifications for Use with Strong CYP3A Inhibitors

• Reduce the starting dose of FARYDAK to 10 mg when coadministered with strong CYP3A inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir).

Administration

• Take FARYDAK exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much FARYDAK to take and when to take it.
• Your healthcare provider may change your dose or stop treatment temporarily if you have side effects. Do not change your dose or stop taking FARYDAK without first talking with your healthcare provider.
• Take FARYDAK 1 time on each scheduled day at about the same time.
• FARYDAK can be taken with or without food.
• FARYDAK capsule should be swallowed whole with a cup of water. Do not open, crush, or chew FARYDAK.
• Avoid contact of the powder in the FARYDAK capsules. If you accidentally get powder from the FARYDAK capsule on your skin, wash the area with soap and water. If you accidentally get powder from the FARYDAK capsule in your eyes, flush your eyes with water.
• If you miss a dose of FARYDAK, take it as soon possible, up to 12 hours after the time the dose should have been taken.
• If you vomit after taking FARYDAK, do not take another capsule. Stay on your dosing schedule and take your next dose as usual.
• If you take too much FARYDAK, call your healthcare provider.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 10 mg, 15 mg, and 20 mg panobinostat (equivalent to 12.58 mg, 18.86 mg, and 25.15 mg respectively of panobinostat lactate)

This medicine is available in fallowing brand namesː

• FARYDAK

What side effects can this medication cause?

The most common side effects of this medicine include:

• tiredness
• nausea
• swelling in your arms or legs
• decreased appetite
• fever
• vomiting

FARYDAK may cause serious side effects, including:

• Diarrhea
• Heart problems
• Bleeding
• Low blood cell counts
• Infections
• Liver problems

What special precautions should I follow?

• Severe diarrhea occurred in 25% of patients treated with FARYDAK. Interrupt FARYDAK at the onset of moderate diarrhea (4 to 6 stools per day) . Ensure that patients initiating therapy with FARYDAK have anti-diarrheal medications on hand.
• Severe and fatal cardiac ischemic events, as well as severe arrhythmias, and electrocardiogram (ECG) changes occurred in patients receiving FARYDAK. Obtain ECG at baseline and periodically during treatment as clinically indicated. Monitor electrolytes during treatment with FARYDAK and correct abnormalities as clinically indicated.
• Fatal and serious hemorrhage occurred during treatment with FARYDAK. Monitor platelet counts and transfuse as needed.
• FARYDAK causes myelosuppression, including severe thrombocytopenia, neutropenia and anemia. Obtain a baseline CBC and monitor the CBC weekly during treatment (or more frequently if clinically indicated). Dose modifications are recommended for Myelosuppression.
• Localized and systemic infections, including pneumonia, bacterial infections, invasive fungal infections, and viral infections have been reported in patients taking FARYDAK. Monitor patients for signs and symptoms of infections during treatment; if a diagnosis of infection is made, institute appropriate anti-infective treatment promptly and consider interruption or discontinuation of FARYDAK.
• Hepatic dysfunction, primarily elevations in aminotransferases and total bilirubin, occurred in patients treated with FARYDAK. Monitor hepatic enzymes and adjust dosage if abnormal liver function tests are observed during FARYDAK therapy.
• FARYDAK can cause fetal harm. Advise women of the potential hazard to the fetus and to avoid pregnancy while taking FARYDAK.

What to do in case of emergency/overdose?

• Symptoms of overdosage including hematologic and gastrointestinal reactions such as thrombocytopenia, pancytopenia, diarrhea, nausea, vomiting and anorexia.

Management for overdosage:

• Monitor cardiac status including ECGs, and assess and correct electrolytes.
• Consider platelet transfusions for thrombocytopenic bleeding.
• It is not known if FARYDAK is dialyzable.

Can this medicine be used in pregnancy?

• FARYDAK can cause fetal harm when administered to a pregnant woman.

Can this medicine be used in children?

• The safety and efficacy of FARYDAK in children has not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: panobinostat
• Inactive ingredients: magnesium stearate, mannitol, microcrystalline cellulose, and pre-gelatinized starch

Capsule shell contains: gelatin, FD&C Blue 1 (10 mg capsules), yellow iron oxide (10 mg and 15 mg capsules), red iron oxide (15 mg and 20 mg capsules), and titanium dioxide

Who manufactures and distributes this medicine?

• Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

What should I know about storage and disposal of this medication?

• Store FARYDAK between 68°F to 77°F (20°C to 25°C). Store blister pack in original carton to protect from light.
• Keep FARYDAK and all medicines out of the reach of children.

• Dailymed label info on Panobinostat
• FDA Panobinostat

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