Pronunciation
(pan oh BIN oh stat)
Index TermsFaridakLBH589Panobinostat LactateDosage Forms
Excipient information
presented when available (limited, particularly for generics); consult specific
product labeling.
Capsule, Oral:
Farydak: 10 mg [contains
brilliant blue fcf (fd&c blue #1)]
Farydak: 15 mg, 20 mg
Brand Names: U.S.FarydakPharmacologic CategoryAntineoplastic Agent, Histone Deacetylase (HDAC)
InhibitorPharmacology
Panobinostat is a histone
deacetylase (HDAC) inhibitor; inhibits enzymatic activity of HDACs resulting in
increased acetylation of histone proteins. Accumulation of acetylated histones
and other proteins induces cell cycle arrest and/or apoptosis of some
transformed cells. Panobinostat has minimal activity in multiple myeloma as a
single-agent; however, synergistic activity is demonstrated when combined with
bortezomib and dexamethasone (San-Miguel 2014).
Metabolism
Extensive via reduction,
hydrolysis, oxidation, and glucuronidation; CYP3A accounts for ~40 % of
elimination, CYP2D6 and CYP2C19 are minor pathways.
Excretion
Feces (44% to 77%; <4% as
unchanged drug); Urine (29% to 51%; <3% as unchanged drug)
Time to Peak
Within 2 hours
Half-Life Elimination
~37 hours
Protein Binding
~90%; to plasma proteins
Special Populations: Renal Function Impairment
In patients with mild,
moderate, and severe renal impairment, the AUC was 64%, 99%, and 59% of the
normal renal function group, respectively.
Special Populations: Hepatic Function Impairment
In patients with mild and
moderate hepatic impairment, the AUC was increased 43% and 105%, respectively
(compared with patients with normal hepatic function).
Use: Labeled Indications
Multiple myeloma: Treatment of multiple myeloma (in combination with
bortezomib and dexamethasone) in patients who have received at least 2 prior
regimens, including bortezomib and an immunomodulatory agent.
Contraindications
There are no contraindications
listed in the manufacturer’s labeling.
Dosing: Adult
Determine QTcF prior to the
start of therapy and verify that QTcF <450 msec prior to panobinostat
initiation. Baseline ANC should be at least 1,500/mm3 and
platelets at least 100,000/mm3 prior to treatment. Panobinostat
is associated with a moderate emetic potential; consider antiemetics to prevent
nausea and vomiting.
Multiple myeloma: Adults: Oral: 20 mg once every other day for 3 doses each
week during weeks 1 and 2 of a 21-day treatment cycle (eg, Monday, Wednesday,
and Friday of weeks 1 and 2 only, rest during week 3) for up to 8 cycles (in
combination with bortezomib and dexamethasone); treatment may continue (the
same schedule for panobinostat; bortezomib and dexamethasone schedules are
modified) for an additional 8 cycles in patients experiencing clinical benefit
and acceptable toxicity (San-Miguel 2014). The total duration of therapy may be
up to 16 cycles (48 weeks).
Missed doses: Missed doses may be taken up to 12 hours after the
scheduled time. Do not repeat the dose if vomiting occurs; patients should take
the next usual scheduled dose.
Dosage adjustment for
concomitant therapy:
CYP2D6 substrates: Avoid coadministration with sensitive CYP2D6 substrates
(eg, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol,
perphenazine, tolterodine, venlafaxine) or CYP2D6 substrates that have a narrow
therapeutic index (eg, thioridazine, pimozide).
Strong CYP3A inducers: Avoid concomitant use with strong CYP3A inducers.
Strong CYP3A inhibitors: Reduce the starting panobinostat dose to 10 mg with strong
CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptin, indinavir,
itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir,
posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Renal Impairment
CrCl <80 mL/minute: There
are no dosage adjustments provided in the manufacturer’s labeling. However,
based on a pharmacokinetic study of a single 30 mg dose, renal impairment does
not appear to impact panobinostat exposure in patients with mild, moderate, and
severe renal impairment (excluding dialysis patients), and initial dosage
adjustment is not necessary (Sharma 2015).
End-stage renal disease (ESRD)
and ESRD on dialysis: There are no dosage adjustments provided in the
manufacturer’s labeling (has not been studied). The dialyzability of
panobinostat is unknown.
Dosing: Hepatic Impairment
Hepatic impairment prior
to treatment:
Mild impairment (bilirubin ≤1
times ULN and AST >1 times ULN or bilirubin >1 to 1.5 times ULN and any
AST): Reduce initial dose to 15 mg; monitor frequently for adverse events and
adjust dose as needed for toxicity.
Moderate impairment (bilirubin
>1.5 to 3 times ULN and any AST): Reduce initial dose to 10 mg; monitor
frequently for adverse events and adjust dose as needed for toxicity.
Severe impairment: Avoid use.
Hepatic impairment during treatment:
If liver function tests are abnormal, consider dosage adjustments and monitor
until liver function returns to normal or baseline.
Dosing: Adjustment for Toxicity
If dose reductions are
necessary, keep the same treatment schedule and reduce panobinostat dose in
increments of 5 mg (from 20 mg to 15 mg, from 15 mg to 10 mg); if dose
reduction below 10 mg 3 times a week is necessary, discontinue treatment.
Hematologic toxicity:
Thrombocytopenia:
Grade 3 (platelets <50,000/mm3):
No dosage adjustments are necessary; monitor platelets weekly.
Grade 3 (platelets
<50,000/mm3) with bleeding: Interrupt panobinostat treatment,
monitor platelets weekly until platelets ≥50,000/mm3 and then
restart panobinostat at a reduced dose. (Interrupt bortezomib until platelets
≥50,000/mm3; if only 1 dose omitted, restart bortezomib at the same
dose; if ≥2 consecutive doses or doses within the same cycle are omitted, then
restart bortezomib at a reduced dose.)
Grade 4 (platelets
<25,000/mm3): Interrupt panobinostat treatment, monitor platelets
weekly until platelets ≥50,000/mm3 and then restart
panobinostat at a reduced dose. (Interrupt bortezomib until platelets
≥50,000/mm3; if only 1 dose omitted, restart bortezomib at the same
dose; if ≥2 consecutive doses or doses within the same cycle are omitted, then
restart bortezomib at a reduced dose.)
Severe thrombocytopenia:
Consider platelet transfusions. Discontinue panobinostat if thrombocytopenia
does not improve despite treatment modifications or if repeated platelet
transfusions are required.
Neutropenia:
Grade 3 (ANC 750 to 1,000/mm3):
No dosage adjustments are necessary.
Grade 3 (ANC 500 to 750/mm3 [2
or more occurrences]): Interrupt panobinostat treatment until ANC ≥1,000/mm3 and
then restart at the same dose. (Bortezomib dosage adjustment is not necessary.)
Grade 3 (ANC <1,000/mm3)
with neutropenic fever: Interrupt panobinostat treatment until neutropenic
fever resolves and ANC ≥1,000/mm3 and then restart at a reduced
dose. (Interrupt bortezomib until neutropenic fever resolves and ANC ≥1,000/mm3;
if only 1 dose omitted, restart bortezomib at the same dose; if ≥2 consecutive
doses or doses within the same cycle are omitted, then restart bortezomib at a
reduced dose.)
Grade 4 (ANC <500/mm3):
Interrupt panobinostat treatment until ANC ≥1,000/mm3 and then
restart at a reduced dose. (Interrupt bortezomib until ANC ≥1,000/mm3;
if only 1 dose omitted, restart bortezomib at the same dose; if ≥2 consecutive
doses or doses within the same cycle are omitted, then restart bortezomib at a
reduced dose.)
Neutropenia, grade 3 or 4:
Consider growth factor support or dose modification; if neutropenia does not
improve or if severe infection occurs despite dose modification or growth
factor support, discontinue panobinostat.
Anemia: Grade 3 (hemoglobin
<8 g/dL): Interrupt panobinostat until hemoglobin ≥10 g/dL and then restart
at a reduced dose.
Nonhematologic toxicity:
Cardiovascular: QTcF increase
to ≥480 msec: Interrupt panobinostat treatment; correct electrolyte
abnormalities. If QT prolongation does not resolve then permanently discontinue
panobinostat.
Diarrhea:
First sign of abdominal
cramping, loose stools, or onset of diarrhea: Begin antidiarrheal medication
(eg, loperamide).
Grade 2 (moderate diarrhea; 4
to 6 stools per day): Interrupt panobinostat until resolved and then restart at
the same dose. (Consider interruption of bortezomib until resolved and then
restart at the same dose.)
Grade 3 (severe diarrhea; ≥7
stools per day, IV fluids or hospitalization required): Interrupt panobinostat
treatment until resolved and then restart at a reduced dose. (Interrupt
bortezomib until resolved and then restart at a reduced dose.)
Grade 4 (life-threatening):
Permanently discontinue panobinostat. (Permanently discontinue bortezomib.)
Infection: Consider
interrupting or discontinuing panobinostat.
Nausea or vomiting
(panobinostat is associated with nausea and vomiting; consider prophylactic
antiemetics):
Severe nausea (grades 3/4):
Interrupt panobinostat treatment until resolved and then restart at a reduced
dose.
Severe/life-threatening
vomiting (grades 3/4): Interrupt panobinostat treatment until resolved and then
restart at a reduced dose.
Other toxicities:
Grade 3 or 4 toxicity or recurrent
grade 2 toxicity: Withhold panobinostat treatment until recovery to grade 1 or
less and then restart at a reduced dose.
Recurrent grade 3 or 4
toxicity: Withhold panobinostat treatment until recovery to grade 1 or less and
then restart at a reduced dose.
Administration
Panobinostat is associated
with a moderate emetic potential; consider antiemetics to prevent nausea and
vomiting. Administer orally at approximately the same time on scheduled days.
May administer with or without food. Swallow capsule whole with a cup of water.
Do not open, crush, or chew the capsules. Avoid exposure to crushed and/or
broken capsules. Avoid direct skin or mucous membrane contact with powder
inside the capsules; if contact occurs, wash thoroughly.
Dietary Considerations
Avoid star fruit, pomegranate
or pomegranate juice, and grapefruit or grapefruit juice.
Storage
Store at 20°C to 25°C (68°F to
77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Store
blister pack in original carton. Protect from light.
Drug Interactions
Aprepitant: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors).Monitor
therapy
BCG (Intravesical):
Immunosuppressants may diminish the therapeutic effect of BCG
(Intravesical). Avoid combination
Bosentan: May decrease the
serum concentration of CYP3A4 Substrates (High risk with Inducers).Monitor
therapy
Coccidioides immitis Skin
Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides
immitis Skin Test. Monitor therapy
Conivaptan: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors).Avoid
combination
CYP2D6 Substrates (High risk
with Inhibitors): Panobinostat may increase the serum concentration of CYP2D6
Substrates (High risk with Inhibitors). Management: Avoid concurrent use of
sensitive CYP2D6 substrates when possible, particularly those substrates with a
narrow therapeutic index. Consider therapy modification
CYP3A4 Inducers (Moderate):
May decrease the serum concentration of CYP3A4 Substrates (High risk with
Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May
decrease the serum concentration of Panobinostat. Avoid combination
CYP3A4 Inhibitors (Moderate):
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor
therapy
CYP3A4 Inhibitors (Strong):
May increase the serum concentration of Panobinostat. Management: Reduce the
panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Consider
therapy modification
Dabrafenib: May decrease the
serum concentration of CYP3A4 Substrates (High risk with Inducers). Management:
Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy
cannot be avoided, monitor clinical effects of the substrate closely (particularly
therapeutic effects). Consider therapy modification
Dasatinib: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors).Monitor
therapy
Deferasirox: May decrease the
serum concentration of CYP3A4 Substrates (High risk with Inducers).Monitor
therapy
Denosumab: May enhance the
adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious
infections may be increased. Monitor therapy
Dolasetron: May enhance the
arrhythmogenic effect of Panobinostat. Monitor therapy
Echinacea: May diminish the
therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants
may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the
concomitant use of fingolimod and other immunosuppressants when possible. If
combined, monitor patients closely for additive immunosuppressant effects (eg,
infections). Consider therapy modification
Fosaprepitant: May increase
the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).Monitor
therapy
Fusidic Acid (Systemic): May
increase the serum concentration of CYP3A4 Substrates (High risk with
Inhibitors). Avoid combination
Granisetron: May enhance the
arrhythmogenic effect of Panobinostat. Monitor therapy
Grapefruit Juice: May increase
the serum concentration of Panobinostat. Avoid combination
Hydroxychloroquine: May
enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid
combination
Idelalisib: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid
combination
Leflunomide:
Immunosuppressants may enhance the adverse/toxic effect of Leflunomide.
Specifically, the risk for hematologic toxicity such as pancytopenia,
agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider
not using a leflunomide loading dose in patients receiving other
immunosuppressants. Patients receiving both leflunomide and another
immunosuppressant should be monitored for bone marrow suppression at least
monthly. Consider therapy modification
MiFEPRIStone: May enhance the
QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk).Avoid
combination
Natalizumab:
Immunosuppressants may enhance the adverse/toxic effect of Natalizumab.
Specifically, the risk of concurrent infection may be increased. Avoid
combination
Netupitant: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors).Monitor
therapy
Nivolumab: Immunosuppressants
may diminish the therapeutic effect of Nivolumab. Consider therapy
modification
Ocrelizumab: May enhance the
immunosuppressive effect of Immunosuppressants. Monitor therapy
Ondansetron: May enhance the
arrhythmogenic effect of Panobinostat. Monitor therapy
Palbociclib: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors).Monitor
therapy
Pidotimod: Immunosuppressants
may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the
adverse/toxic effect of Immunosuppressants. Avoid combination
Pitolisant: May decrease the
serum concentration of CYP3A4 Substrates (High risk with Inducers). Management:
Combined use of pitolisant with a CYP3A4 substrate that has a narrow
therapeutic index should be avoided. Other CYP3A4 substrates should be
monitored more closely when used with pitolisant. Consider therapy
modification
Pomegranate: May increase the
serum concentration of Panobinostat. Avoid combination
Probucol: May enhance the
QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid
combination
Promazine: May enhance the
QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid
combination
QTc-Prolonging Agents (Highest
Risk): QTc-Prolonging Agents (Moderate Risk) may enhance the QTc-prolonging
effect of QTc-Prolonging Agents (Highest Risk). Avoid combination
QTc-Prolonging Agents
(Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect
of QTc-Prolonging Agents (Moderate Risk). Monitor therapy
QTc-Prolonging Agents
(Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging
Agents (Moderate Risk). Management: Avoid such combinations when possible. Use
should be accompanied by close monitoring for evidence of QT prolongation or
other alterations of cardiac rhythm. Consider therapy modification
Roflumilast: May enhance the
immunosuppressive effect of Immunosuppressants. Consider therapy
modification
Sarilumab: May decrease the
serum concentration of CYP3A4 Substrates (High risk with Inducers).Monitor
therapy
Siltuximab: May decrease the
serum concentration of CYP3A4 Substrates (High risk with Inducers).Monitor
therapy
Simeprevir: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors).Monitor
therapy
Sipuleucel-T:
Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor
therapy
St John's Wort: May decrease
the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Management: Consider an alternative for one of the interacting drugs. Some
combinations may be specifically contraindicated. Consult appropriate
manufacturer labeling. Consider therapy modification
Star Fruit: May increase the
serum concentration of Panobinostat. Avoid combination
Stiripentol: May increase the
serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management:
Use of stiripentol with CYP3A4 substrates that are considered to have a narrow
therapeutic index should be avoided due to the increased risk for adverse
effects and toxicity. Any CYP3A4 substrate used with stiripentol requires
closer monitoring. Consider therapy modification
Tacrolimus (Topical): May
enhance the adverse/toxic effect of Immunosuppressants. Avoid
combination
Tertomotide:
Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor
therapy
Tocilizumab: May decrease the serum
concentration of CYP3A4 Substrates (High risk with Inducers).Monitor therapy
Tofacitinib:
Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
Management: Concurrent use with antirheumatic doses of methotrexate or
nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and
this warning seems particularly focused on more potent immunosuppressants. Consider
therapy modification
Trastuzumab: May enhance the
neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated):
Immunosuppressants may diminish the therapeutic effect of Vaccines
(Inactivated). Management: Vaccine efficacy may be reduced. Complete all
age-appropriate vaccinations at least 2 weeks prior to starting an
immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate
at least 3 months after immunosuppressant discontinuation.Consider therapy
modification
Vaccines (Live):
Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live).
Immunosuppressants may diminish the therapeutic effect of Vaccines (Live).
Management: Avoid use of live organism vaccines with immunosuppressants;
live-attenuated vaccines should not be given for at least 3 months after
immunosuppressants. Avoid combination
Vinflunine: May enhance the
QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid
combination
Xipamide: May enhance the
QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor
therapy
Adverse Reactions
Frequency not always defined.
>10%:
Cardiovascular: Abnormal T
waves on ECG (40%), peripheral edema (29%; grades 3/4: 2%), depression of ST
segment on ECG (22%), cardiac arrhythmia (12%; grades 3/4: 3%)
Central nervous system:
Fatigue (≤60%, grades 3/4: ≤25%), lethargy (≤60%; grades 3/4: ≤25%), malaise
(≤60%; grades 3/4: ≤25%)
Endocrine & metabolic:
Hypocalcemia (67%; grades 3/4: 5%), hypoalbuminemia (63%; grades 3/4: 2%),
hypophosphatemia (63%; grades 3/4: 20%), hypokalemia (52%; grades 3/4: 18%),
hyponatremia (49%; grades 3/4: 13%), hyperphosphatemia (29%; grades 3/4: 2%),
hypermagnesemia (27%; grades 3/4: 5%), weight loss (12%; grades 3/4: 2%)
Gastrointestinal: Diarrhea
(68%; grades 3/4: 25%), nausea (36%; grades 3/4: 6%), decreased appetite (28%;
grades 3/4: 3%), vomiting (26%; grades 3/4: 7%)
Hematologic & oncologic:
Thrombocytopenia (97%; grades 3/4: 67%), lymphocytopenia (82%; grades 3/4:
53%), leukopenia (81%; grades 3/4: 23%), neutropenia (75%; grades 3/4: 34%),
anemia (62%; grades 3/4: 18%)
Hepatic: Hyperbilirubinemia
(21%; grades 3/4: 1%)
Infection: Severe infection
(31%; includes bacterial, fungal, and viral infections)
Neuromuscular & skeletal:
Weakness (≤60%; grades ≥3: ≤25%)
Renal: Increased serum
creatinine (41%; grades 3/4: 1%)
Miscellaneous: Fever (26%)
1% to 10%:
Cardiovascular: Hypertension
(>2% to <10%), hypotension (>2% to <10%), orthostatic hypotension
(>2% to <10%), palpitations (>2% to <10%), syncope (>2% to
<10%), ischemic heart disease (4%), ECG changes, prolonged Q-T interval on
ECG
Central nervous system: Chills
(>2% to <10%), dizziness (>2% to <10%), headache (>2% to
<10%), insomnia (>2% to <10%)
Dermatologic: Cheilitis
(>2% to <10%), erythema (>2% to <10%), skin lesion (>2% to
<10%), skin rash (>2% to <10%)
Endocrine & metabolic:
Dehydration (>2% to <10%), fluid retention (>2% to <10%),
hyperglycemia (>2% to <10%), hyperuricemia (>2% to <10%),
hypomagnesemia (>2% to <10%), hypothyroidism (>2% to <10%)
Gastrointestinal: Abdominal
distention (>2% to <10%), abdominal pain (>2% to <10%), colitis
(>2% to <10%), dysgeusia (>2% to <10%), dyspepsia (>2% to
<10%), flatulence (>2% to <10%), gastritis (>2% to <10%),
gastrointestinal pain (>2% to <10%), xerostomia (>2% to <10%),
gastrointestinal toxicity
Genitourinary: Urinary
incontinence (>2% to <10%)
Hematologic & oncologic:
Hemorrhage (grades 3/4: 4%)
Hepatic: Hepatitis B (>2%
to <10%), increased serum alkaline phosphatase (>2% to <10%),
increased serum transaminases, increased serum bilirubin
Infection: Sepsis (6%)
Neuromuscular & skeletal:
Joint swelling (>2% to <10%), tremor (>2% to <10%)
Renal: Increased blood urea
nitrogen (>2% to <10%), mean glomerular filtration rate decreased (>2%
to <10%), renal failure (>2% to <10%)
Respiratory: Cough (>2% to
<10%), dyspnea (>2% to <10%), rales (>2% to <10%), respiratory
failure (>2% to <10%), wheezing (>2% to <10%)
ALERT: U.S. Boxed Warning
Gastrointestinal
events:
Severe diarrhea occurred in
25% of panobinostat treated patients. Monitor for symptoms, institute
antidiarrheal treatment, interrupt panobinostat, and then reduce dose or discontinue
panobinostat.
Cardiovascular events:
Severe and fatal cardiac
ischemic events, severe arrhythmias, and ECG changes have occurred in patients
receiving panobinostat. Arrhythmias may be exacerbated by electrolyte
abnormalities. Obtain ECG and electrolytes at baseline and periodically during
treatment as clinically indicated.
Warnings/Precautions
Concerns related to adverse
events:
• Bone marrow suppression:
Severe thrombocytopenia, neutropenia and anemia have occurred. May require
treatment interruption, dosage modification, discontinuation, transfusion or
granulocyte colony-stimulating factor support. Monitor CBC with differential at
baseline and during treatment. Patients >65 years may require more frequent
monitoring.
• Cardiovascular events: [US
Boxed Warning]: Severe and fatal cardiac ischemic events, severe arrhythmias,
and ECG changes have occurred in patients receiving panobinostat. Arrhythmias
may be exacerbated by electrolyte abnormalities. Obtain ECG and electrolytes at
baseline and periodically during treatment as clinically indicated. ECG
abnormalities including ST-segment depression and T-wave abnormalities have
been observed. Monitor and correct electrolyte abnormalities as needed.
Panobinostat may prolong the QT interval. Do not initiate treatment in patients
with a QTcF >450 msec or with clinically significant baseline ST-segment or
T-wave abnormalities. Interrupt treatment if QTcF increases to ≥480 msec;
correct electrolyte abnormalities; if QT prolongation does not resolve, permanently
discontinue panobinostat. Concomitant use with medications known to prolong the
QT interval is not recommended. Do not initiate panobinostat treatment in
patients with a history of recent MI or unstable angina.
• Gastrointestinal
events: [US Boxed Warning]: Severe diarrhea occurred in one-fourth of
panobinostat treated patients. Monitor for symptoms, institute antidiarrheal
treatment, interrupt panobinostat, and then reduce dose or discontinue
panobinostat. Any grade diarrhea was reported in over two-thirds of
patients and may occur at any time. Monitor hydration status and serum
electrolytes (including magnesium, potassium, and phosphate). Patients should
have antidiarrheal medications available for use; begin antidiarrheal
medications at the first sign of diarrhea, loose stools, or abdominal cramping.
Interrupt panobinostat treatment for moderate diarrhea (4 to 6 stools per day).
Panobinostat is associated with nausea and vomiting (moderate emetic
potential); consider antiemetics to prevent nausea and vomiting. Some
antiemetics known to prolong the QT interval (eg, dolasetron or ondansetron)
may be used with frequent ECG monitoring.
• Hemorrhage: Serious and
fatal hemorrhage has occurred, including grade 3 and 4 hemorrhage. All patients
with hemorrhage also experienced thrombocytopenia at the time of hemorrhage.
• Hepatotoxicity: Hepatic
dysfunction (transaminase and total bilirubin elevations) has been reported.
Monitor liver function prior to and during treatment. If liver function tests
are abnormal, consider dosage adjustments and monitor until liver function
returns to normal or baseline. Initial dose should be reduced in patients with
mild-to-moderate hepatic impairment; avoid use in patients with severe
impairment.
• Infection: Localized and
systemic infections (including pneumonia, bacterial infections, invasive fungal
infections, and viral infections) have been observed; infections may be severe
(or fatal). Do not initiate treatment in patients with active infections.
Monitor for sings/symptoms of infections during treatment. If infection occurs,
begin appropriate management and consider interrupting or discontinuing
panobinostat.
Concurrent drug therapy
issues:
• Drug-drug interactions:
Potentially significant interactions may exist, requiring dose or frequency
adjustment, additional monitoring, and/or selection of alternative therapy.
Consult drug interactions database for more detailed information.
Monitoring Parameters
CBC with differential and
platelets (prior to treatment initiation then weekly or more often if
clinically indicated during treatment); serum electrolytes, including potassium
and magnesium prior to treatment and during treatment (in the clinical trial, electrolytes
were monitored prior to the start of each cycle, after the fifth panobinostat
dose in week 2 through cycle 8 and then at the beginning of cycles 9 to 16);
liver function tests at baseline and regularly during treatment; pregnancy test
(in women of reproductive potential, rule out pregnancy prior to and
intermittently during treatment); ECG (prior to treatment initiation and
periodically as clinically indicated during treatment); hydration status;
monitor for gastrointestinal toxicity (eg, diarrhea, nausea, vomiting),
signs/symptoms of hemorrhage and/or infection.
Pregnancy Considerations
Adverse events were observed
in animal reproduction studies. Pregnancy should be ruled out prior to
treatment. Women of reproductive potential should avoid pregnancy and use an
effective contraceptive during therapy and for at least 3 months after the last
panobinostat dose. Males should use condoms during therapy and for at least 6
months after the last dose of panobinostat.
Patient Education
• Discuss specific use of drug
and side effects with patient as it relates to treatment. (HCAHPS: During this
hospital stay, were you given any medicine that you had not taken before?
Before giving you any new medicine, how often did hospital staff tell you what
the medicine was for? How often did hospital staff describe possible side
effects in a way you could understand?)
• Patient may experience, lack
of appetite, or weight loss. Have patient report immediately to prescriber
severe diarrhea, severe abdominal pain, arrhythmia, signs of infection, signs
of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing
up blood; blood in the urine; black, red, or tarry stools; bleeding from the
gums; abnormal vaginal bleeding; bruises without a reason or that get bigger;
or any bleeding that is very bad or that will not stop), signs of fluid and
electrolyte problems (mood changes, confusion, muscle pain or weakness,
abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more
thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine
or change in the amount of urine produced, dry mouth, dry eyes, or nausea or
vomiting), signs of liver problems (dark urine, feeling tired, lack of
appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow
skin or eyes), signs of severe cerebrovascular disease (change in strength on
one side is greater than the other, trouble speaking or thinking, change in
balance, or change in eyesight), skin discoloration, angina, bradycardia,
tachycardia, dizziness, passing out, pale skin, severe headache, severe nausea,
vomiting, shortness of breath, swelling of arms or legs, or loss of strength
and energy (HCAHPS).
• Educate patient about signs
of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad
cough; blue skin color; seizures; or swelling of face, lips, tongue, or
throat). Note: This is not a comprehensive list of all side
effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This
information is intended to serve as a concise initial reference for health care
professionals to use when discussing medications with a patient. You must
ultimately rely on your own discretion, experience, and judgment in diagnosing,
treating, and advising patients.
