Version May 2024
Cutaneous T-cell lymphoma (CTCL): Oral: 400 mg once daily until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, based on the minimal renal elimination, adjustment not likely required.
Mild to moderate impairment (total bilirubin 1 to 3 times ULN or AST > ULN): Initial: 300 mg once daily.
Severe impairment (total bilirubin >3 times ULN): There are no dosage adjustments provided in the manufacturer's labeling (evidence is insufficient for a starting dose recommendation). Doses of 100 to 200 mg once daily were studied in a limited number of patients with severe impairment (Ref); according to the manufacturer, the maximum dose used was 200 mg once daily.
Intolerance: Reduce dose to 300 mg once daily; if needed, may further reduce to 300 mg daily for 5 consecutive days per week.
In clinical trials, treatment was withheld for grade 4 anemia or thrombocytopenia or other grade 3 or 4 drug-related toxicity, until resolved to ≤ grade 1 and then was reinitiated with dose reduction (Ref). Vorinostat was discontinued in patients requiring more than 2 dose modifications or if a toxicity did not resolve within 2 weeks (Ref).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (13%)
Central nervous system: Fatigue (52%), chills (16%), dizziness (15%), headache (12%)
Dermatologic: Alopecia (19%), pruritus (12%)
Endocrine & metabolic: Hyperglycemia (8% to 69%; grade 3: 5%), weight loss (21%), dehydration (1% to 16%)
Gastrointestinal: Diarrhea (52%), nausea (41%), dysgeusia (28%), anorexia (24%), xerostomia (16%), constipation (15%), vomiting (15%), decreased appetite (14%)
Genitourinary: Proteinuria (51%)
Hematologic & oncologic: Thrombocytopenia (26%; grades 3/4: 6%), anemia (14%; grades 3/4: 2%)
Neuromuscular & skeletal: Muscle spasm (20%)
Renal: Increased serum creatinine (16% to 47%)
Respiratory: Cough (11%), upper respiratory tract infection (11%)
Miscellaneous: Fever (11%)
1% to 10%:
Cardiovascular: Pulmonary embolism (5%), prolonged QT interval on ECG (3% to 4%)
Hematologic & oncologic: Squamous cell carcinoma of skin (4%)
<1%, postmarketing, and/or case reports: Abdominal pain, acute ischemic stroke, angioedema, bacteremia (streptococcal), blurred vision, chest pain, cholecystitis, deafness, deep vein thrombosis, diverticulitis, dysphagia, exfoliative dermatitis, gastrointestinal hemorrhage, Guillain-Barre syndrome, hemoptysis, hypertension, hypokalemia, hyponatremia, infection, infection due to enterococcus, lethargy, leukopenia, myocardial infarction, neutropenia, pneumonia, renal failure, sepsis, spinal cord injury, syncope, T-cell lymphoma, tumor hemorrhage, ureteral obstruction, obstructive uropathy (ureteropelvic junction), urinary retention, vasculitis, weakness
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to vorinostat or any component of the formulation; severe hepatic impairment (total bilirubin ≥3 times ULN)
Concerns related to adverse effects:
• Bone marrow suppression: Dose-related anemia and thrombocytopenia may occur; may require dosage reduction or discontinuation. Monitor blood counts (every 2 weeks for 2 months, then monthly). Gastrointestinal bleeding due to severe thrombocytopenia has been reported in patients receiving vorinostat in combination with other histone deacetylase inhibitors (eg, valproic acid); monitor platelet counts more frequently in patients receiving concomitant histone deacetylase inhibitor therapy.
• CNS effects: May cause dizziness or fatigue; caution patients about performing tasks which require mental alertness (eg, operating machinery or driving).
• Gastrointestinal toxicities: Nausea, vomiting, and diarrhea may occur; antiemetics and antidiarrheals may be required. Replace fluids and electrolytes to avoid dehydration. Control preexisting nausea, vomiting, and diarrhea prior to treatment initiation. Adverse anastomotic healing events have occurred in patients recovering from bowel surgery; use with caution in the perioperative period in patients requiring bowel surgery.
• Hepatitis B virus screening: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) 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.
• Hyperglycemia: May cause hyperglycemia (may be severe). Monitor serum glucose every 2 weeks for 2 months, then monthly, or as clinically necessary. Use with caution in patients with diabetes; may require diet and/or antidiabetic therapy modifications.
• QTc prolongation: QTc prolongation has been observed. Correct electrolyte abnormalities prior to treatment and monitor and correct potassium, calcium, and magnesium levels during therapy. Use caution in patients with a history of QTc prolongation or with medications known to prolong the QT interval. Baseline and periodic ECGs were done in clinical trials (Duvic 2007; Olsen 2007).
• Thromboembolic events: Pulmonary embolism and deep vein thrombosis (DVT) have been reported; monitor for signs/symptoms, especially in patients with a history of thrombotic events.
Disease-related issues:
• Hepatic impairment: Use with caution in patients with hepatic impairment; dose reductions are recommended (elimination is predominantly hepatic).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zolinza: 100 mg
No
Capsules (Zolinza Oral)
100 mg (per each): $150.10
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zolinza: 100 mg
Oral: Administer with food. Do not open, crush, break, or chew capsules. Maintain adequate hydration (≥2 L/day fluids) during treatment.
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).
Cutaneous T-cell lymphoma: Treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or recurrent disease on or following two systemic treatments.
Vorinostat may be confused with belinostat, panobinostat, venetoclax, Votrient
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
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
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). 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
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) 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
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
Taurursodiol: Histone Deacetylase Inhibitors may enhance the adverse/toxic effect of Taurursodiol. Risk X: Avoid combination
Valproate Products: May enhance the thrombocytopenic effect of Vorinostat. This may increase the risk of gastrointestinal bleeding. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Vorinostat may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Evaluate pregnancy status prior to treatment. Pregnancy testing should be conducted within 7 days prior to treatment in females of reproductive potential. Females of reproductive potential should avoid pregnancy and use an effective contraceptive during therapy and for at least 6 months after the last vorinostat dose. Males with female partners of reproductive potential should use effective contraception during therapy and for at least 3 months after the last vorinostat dose.
Based on the mechanism of action and data from animal reproduction studies, vorinostat may cause fetal harm if administered during pregnancy. Inform patient of potential hazard if used during pregnancy or if pregnancy occurs during treatment.
It is not known if vorinostat is present in breast milk.
Due to the potential for serious adverse reactions, the manufacturer does not recommend breastfeeding during therapy and for at least 7 days after the last vorinostat dose.
CBC with differential and serum chemistries, including calcium, magnesium, potassium, glucose and creatinine (baseline, then every 2 weeks for 2 months, then monthly, or as clinically necessary), hepatic function, INR (if on concomitant warfarin therapy). Hepatitis B virus (HBV) screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]). Monitor fluid status and for signs/symptoms of thromboembolism. Monitor adherence.
Baseline and periodic ECGs were done in clinical trials (Duvic 2007; Olsen 2007).
Vorinostat inhibits histone deacetylase enzymes, HDAC1, HDAC2, HDAC3, and HDAC6, which catalyze acetyl group removal from protein lysine residues (including histones and transcription factors). Histone deacetylase inhibition results in accumulation of acetyl groups, which alters chromatin structure and transcription factor activation; cell growth is terminated and apoptosis occurs.
Protein binding: ~71%
Metabolism: Glucuronidated and hydrolyzed (followed by beta-oxidation) to inactive metabolites
Half-life elimination: ~2 hours
Time to peak, plasma: With high-fat meal: 4 hours (range: 2 to 10 hours)
Excretion: Urine: ~52% (~52% as inactive metabolites; <1% as unchanged drug)
Hepatic function impairment: In a single 400 mg dose pharmacokinetic study in cancers other than cutaneous T-cell lymphoma, the AUC was increased by 50% in patients with mild (bilirubin >1 to 1.5 times ULN or AST > ULN with bilirubin ≤ ULN) and moderate (bilirubin 1.5 to ≤3 times ULN) impairment, and increased by 66% in patients with severe impairment (bilirubin >3 times ULN), compared to patients with normal hepatic function.
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