Version July 2025
Severe diarrhea occurred in 25% of panobinostat treated patients. Monitor for symptoms, institute antidiarrheal treatment, interrupt panobinostat, and then reduce dose or discontinue panobinostat.
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.
Note: In December 2021, the manufacturer voluntarily withdrew the approval of panobinostat for the treatment of relapsed or refractory multiple myeloma (in combination with bortezomib and dexamethasone) from the US market.
Baseline ANC should be ≥1,500/mm3 and platelets ≥100,000/mm3 prior to treatment. Do not initiate panobinostat in patients with a QTcF >450 msec, clinically significant baseline ST-segment depression or T-wave abnormalities, or a history of recent myocardial infarction or unstable angina.
Multiple myeloma, relapsed/refractory: 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 (Ref). The total duration of therapy may be up to 16 cycles (48 weeks) or
Heavily pretreated bortezomib-refractory patients: Oral: 20 mg three days/week on weeks 1 and 2 of a 3-week treatment cycle 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) until disease progression or unacceptable toxicity (Ref).
Off-label combinations: Oral: 20 mg on days 1, 3, 5, 15, 17, and 19 of a 28-day cycle (in combination with carfilzomib) until disease progression or unacceptable toxicity (Berdeja 2021) or 20 mg on days 1, 3, 5, 15, 17, and 19 of a 28-day cycle (in combination with lenalidomide and dexamethasone) (Ref).
Missed doses: A missed dose may be taken up to 12 hours after the scheduled time. If vomiting occurs, do not repeat the dose; resume with the next usual scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.
CrCl <80 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling. However, no need for dosage adjustment is expected (Ref). 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 (Ref).
End-stage renal disease (ESRD) and ESRD on dialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). No need for dosage adjustment is expected (Ref). Per the manufacturer, the dialyzability of panobinostat is unknown.
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.
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.
|
Adverse reaction |
Severity |
Dose modification |
|---|---|---|
|
Hematologic toxicity | ||
|
Thrombocytopenia |
Grade 3 (platelets <50,000/mm3) |
No dosage adjustments are necessary; monitor platelets at least weekly. |
|
Grade 3 (platelets <50,000/mm3) with bleeding |
Interrupt panobinostat treatment, monitor platelets at least weekly until ≥50,000/mm3 and then restart panobinostat at a reduced dose. Interrupt bortezomib until platelets ≥50,000/mm3; if only 1 bortezomib 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 at least weekly until ≥50,000/mm3 and then restart panobinostat at a reduced dose. Interrupt bortezomib until platelets ≥50,000/mm3; if only 1 bortezomib 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 bortezomib 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 bortezomib 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 and/or dose modification; if neutropenia does not improve despite dose modification or growth factor support, or if severe infection occurs, 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, 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 |
Any |
Consider interrupting or discontinuing panobinostat. Do not initiate panobinostat if active infection is present. |
|
Severe |
Discontinue panobinostat. | |
|
Nausea or vomiting |
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. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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 QT 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%)
There are no contraindications listed in the manufacturer’s labeling.
Concerns related to adverse events:
• Bone marrow suppression: Hematologic toxicities, including severe thrombocytopenia, neutropenia, and anemia have occurred. Patients >65 years of age may require more frequent monitoring.
• 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. ECG abnormalities, including ST-segment depression and T-wave abnormalities, have been observed. Panobinostat may prolong the QT interval. Concomitant use with medications known to prolong the QT interval is not recommended.
• GI events: Severe diarrhea occurred in one-fourth of panobinostat-treated patients. Diarrhea (of any grade) was reported in over two-thirds of patients and may occur at any time. Patients should have antidiarrheal medications available for use; begin antidiarrheal medications at the first sign of diarrhea, loose stools, or abdominal cramping. If antiemetics are needed, some antiemetics known to prolong the QT interval (eg, dolasetron, ondansetron) may be used with frequent ECG monitoring.
• Hemorrhage: Serious and fatal hemorrhage has occurred, including grade 3 or higher hemorrhage. All patients with hemorrhage also experienced thrombocytopenia at the time of hemorrhage.
• Hepatotoxicity: Hepatic dysfunction (transaminase and total bilirubin elevations) has been reported.
• Infection: Localized and systemic infections (including pneumonia, bacterial infections, invasive fungal infections, and viral infections) have been observed; infections may be severe (or fatal).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Farydak: 10 mg [DSC] [contains fd&c blue #1 (brilliant blue)]
Farydak: 15 mg [DSC], 20 mg [DSC]
No
Capsules (Farydak Oral)
10 mg (per each): $2,816.50
15 mg (per each): $2,816.50
20 mg (per each): $2,816.50
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Oral: Administer 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.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM436377.pdf, must be dispensed with this medication.
Multiple myeloma, relapsed or refractory: 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.
Note: In December 2021, the manufacturer voluntarily withdrew the approval of panobinostat for the treatment of relapsed or refractory multiple myeloma (in combination with bortezomib and dexamethasone) from the US market.
Panobinostat may be confused with belinostat, palbociclib, pazopanib, ponatinib, tazemetostat, vorinostat
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP2C19 (Minor), CYP2D6 (Minor), CYP3A4 (Major), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Conivaptan: May increase serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with conivaptan. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Panobinostat. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Panobinostat. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider Therapy Modification
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Panobinostat. Risk X: Avoid
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Pomegranate: May increase serum concentration of Panobinostat. Risk X: Avoid
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Star Fruit: May increase serum concentration of Panobinostat. Risk X: Avoid
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Taurursodiol: Histone Deacetylase Inhibitors may increase adverse/toxic effects of Taurursodiol. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Thioridazine: CYP2D6 Inhibitors (Weak) may increase serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider Therapy Modification
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice may interfere with panobinostat metabolism. Management: Avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice.
Verify pregnancy status prior to use in patients who may become pregnant; pregnancy testing is recommended prior to use and intermittently during panobinostat therapy. Patients who may become pregnant should avoid pregnancy and use an effective contraceptive during therapy and for at least 3 months after the last panobinostat dose. Patients with partners who may become pregnant should use condoms during therapy and for at least 6 months after the last dose of panobinostat.
Based on data from animal reproduction studies, in utero exposure to panobinostat may cause fetal harm.
It is not known if panobinostat is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the person who is breastfeeding.
Avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice.
CBC with differential and platelets (prior to treatment initiation then weekly or more often if clinically indicated during treatment; monitor more frequently in patients ≥65 years of age); 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. Evaluate pregnancy status in patients who may become pregnant (rule out pregnancy prior to and intermittently during treatment). ECG (prior to treatment initiation and periodically as clinically indicated during treatment); monitor frequently if using concomitant medications known to prolong the QT interval). Monitor hydration status; monitor for gastrointestinal toxicity (eg, diarrhea, nausea, vomiting), signs/symptoms of hemorrhage and/or infection.
The American Society of Clinical Oncology hepatitis B virus screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Panobinostat is a histone deacetylase (HDAC) inhibitor; it 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).
Protein binding: ~90% to plasma proteins.
Metabolism: Extensive via reduction, hydrolysis, oxidation, and glucuronidation; CYP3A accounts for ~40 % of elimination, CYP2D6 and CYP2C19 are minor pathways.
Bioavailability: ~21%; AUC is 16% lower (compared with fasting) when administered with a high-fat meal.
Half-life elimination: ~37 hours.
Time to peak: Within 2 hours.
Excretion: Feces (44% to 77%; <4% as unchanged drug); Urine (29% to 51%; <3% as unchanged drug).
Clearance: ~160 L/hour.
Altered kidney function: In patients with mild, moderate, and severe renal impairment, the AUC was 64%, 99%, and 59% of the normal renal function group, respectively.
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).
