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Panobinostat (United States: Withdrawn from market): Drug information

Panobinostat (United States: Withdrawn from market): Drug information
(For additional information see "Panobinostat (United States: Withdrawn from market): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US 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.

Brand Names: US
  • Farydak [DSC]
Pharmacologic Category
  • Antineoplastic Agent, Histone Deacetylase (HDAC) Inhibitor
Dosing: Adult

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

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 (San-Miguel 2014). 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 (Richardson 2013).

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) (Chari 2017).

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.

Dosing: Kidney Impairment: Adult

CrCl <80 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling. However, no need for dosage adjustment is expected (Krens 2019). 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). No need for dosage adjustment is expected (Krens 2019). Per the manufacturer, the dialyzability of panobinostat is unknown.

Dosing: Hepatic Impairment: Adult

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: Adult

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.

Panobinostat Recommended Dose Modifications for Adverse Reactions

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.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

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%)

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Warnings/Precautions

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).

Dosage Forms: US

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]

Generic Equivalent Available: US

No

Pricing: US

Capsules (Farydak Oral)

10 mg (per each): $2,816.50

15 mg (per each): $2,816.50

20 mg (per each): $2,816.50

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

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 Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 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 2016; USP-NF 2020).

Medication Guide and/or Vaccine Information Statement (VIS)

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.

Use: Labeled Indications

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Panobinostat may be confused with belinostat, palbociclib, pazopanib, ponatinib, tazemetostat, vorinostat

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 the 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 (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Panobinostat. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Panobinostat. Risk C: 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. 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 enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect 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 enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Dolasetron: May enhance the arrhythmogenic effect of Panobinostat. Risk C: Monitor therapy

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Granisetron: May enhance the arrhythmogenic effect of Panobinostat. Risk C: Monitor therapy

Grapefruit Juice: May increase the serum concentration of Panobinostat. Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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

Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Ondansetron: May enhance the arrhythmogenic effect of Panobinostat. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 the serum concentration of Panobinostat. Risk X: Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect 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 therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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 enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Star Fruit: May increase the serum concentration of Panobinostat. Risk X: Avoid combination

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination

Taurursodiol: Histone Deacetylase Inhibitors may enhance the adverse/toxic effect of Taurursodiol. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Thioridazine: CYP2D6 Inhibitors (Weak) may increase the 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 enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Food Interactions

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.

Reproductive Considerations

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.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to panobinostat may cause fetal harm.

Breastfeeding Considerations

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.

Dietary Considerations

Avoid star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice.

Monitoring Parameters

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.

Mechanism of Action

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).

Pharmacokinetics (Adult Data Unless Noted)

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.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Farydak;
  • (BE) Belgium: Farydak;
  • (CH) Switzerland: Farydak;
  • (CZ) Czech Republic: Farydak;
  • (DE) Germany: Farydak;
  • (EE) Estonia: Farydak;
  • (FI) Finland: Farydak;
  • (FR) France: Farydak;
  • (GB) United Kingdom: Farydak;
  • (GR) Greece: Farydak;
  • (HU) Hungary: Farydak;
  • (IN) India: Ixapana;
  • (JP) Japan: Farydak;
  • (KR) Korea, Republic of: Farydak;
  • (LT) Lithuania: Farydak;
  • (NL) Netherlands: Farydak;
  • (NO) Norway: Farydak;
  • (PR) Puerto Rico: Farydak;
  • (RO) Romania: Farydak;
  • (RU) Russian Federation: Farydak;
  • (SE) Sweden: Farydak;
  • (SG) Singapore: Farydak;
  • (SI) Slovenia: Farydak
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Berdeja JG, Gregory TK, Faber EA, et al. A phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma: final analysis of second dose-expansion cohort. Am J Hematol. 2021;9(4):428-435. doi:10.1002/ajh.26088 [PubMed 33421178]
  3. Berdeja JG, Hart LL, Mace JR, et al. Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Haematologica. 2015;100(5):670-676. doi:10.3324/haematol.2014.119735 [PubMed 25710456]
  4. Chari A, Cho HJ, Dhadwal A, et al. A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma. Blood Adv. 2017;1(19):1575-1583. doi:10.1182/bloodadvances.2017007427 [PubMed 29296798]
  5. Farydak (panobinostat) [prescribing information]. Las Vegas, NV: Secura Bio, Inc; September 2019.
  6. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  7. Krens SD, Lassche G, Jansman FGA, et al. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol. 2019;20(4):e200-e207. doi:10.1016/S1470-2045(19)30145-7 [PubMed 30942181]
  8. Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013;122(14):2331-2337. doi:10.1182/blood-2013-01-481325 [PubMed 23950178]
  9. San-Miguel JF, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014;15(11):1195-1206. [PubMed 25242045]
  10. Sharma S, Witteveen PO, Lolkema MP, et al. A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of renal function. Cancer Chemother Pharmacol. 2015;75(1):87-95. [PubMed 25377157]
  11. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 5, 2016.
Topic 100045 Version 206.0

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