vorinostat


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vorinostat

(vor-in-o-stat ) ,

Zolinza

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzyme inhibitors
Pregnancy Category: D

Indications

Treatment of skin manifestations cutaneous T-cell lymphoma (CTCL) that has not responded to two systemic therapies.

Action

Acts as a histone deacetylase inhibitor which decreases gene transcription resulting in cell cycle arrest.

Therapeutic effects

Decreased progression of CTCL.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Crosses the placenta.
Metabolism and Excretion: Mostly metabolized, <1% excreted unchanged in urine.
Half-life: 2 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown4 hr24 hr

Contraindications/Precautions

Contraindicated in: Severe hepatic impairment; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Renal impairment; Mild or moderate hepatic impairment; Geriatric: May be more sensitive to drug effects; Pre-existing nausea, vomiting, diarrhea (treat symptomatically before initiating therapy); Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness
  • headache

Cardiovascular

  • pulmonary embolism (life-threatening)
  • deep vein thrombosis
  • QTc interval prolongation

Respiratory

  • cough

Gastrointestinal

  • anorexia (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • dry mouth (most frequent)
  • dysgeusia (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Genitourinary

  • proteinuria

Dermatologic

  • alopecia
  • itching

Endocrinologic

  • hyperglycemia (most frequent)

Hematologic

  • anemia (most frequent)
  • thrombocytopenia (most frequent)

Metabolic

  • weight loss (most frequent)

Musculoskeletal

  • muscle spasms

Miscellaneous

  • chills (most frequent)
  • fever (most frequent)

Interactions

Drug-Drug interaction

↑ risk of thrombocytopenia and GI bleeding with valproic acid.May ↑ risk of bleeding with warfarin.

Route/Dosage

Oral (Adults) 400 mg daily; if intolerance occurs dose may be ↓ to 300 mg daily or 300 mg daily for 5 consecutive days/wk.

Availability

Capsules: 100 mg

Nursing implications

Nursing assessment

  • Monitor ECG prior to and periodically during therapy.
  • Assess for nausea, vomiting, and diarrhea during therapy. Administer anti-emetic and antidiarrheal medications as needed. Maintain fluid and electrolyte balances to prevent adverse effects.
  • Lab Test Considerations: Monitor CBC and blood chemistry tests, including electrolytes (potassium, magnesium, calcium), glucose, and serum creatinine, every 2 wks during first 2 mo of therapy and monthly thereafter. Correct hypokalemia and hypomagnesemia before initiating therapy.
    • May cause thrombocytopenia and anemia requiring dose reduction or discontinuation.
    • May cause hyperglycemia requiring diet or insulin modification.
    • May cause proteinuria.

Potential Nursing Diagnoses

Risk for injury (Adverse Reactions)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Oral: Administer once daily with food. Capsules should be swallowed whole; do not open, crush, or chew.

Patient/Family Teaching

  • Instruct patient to take vorinostat as directed. Take missed doses as soon as remembered. If almost time for next dose, skip dose and take next dose at regular time; do not double doses.
  • Advise patient to drink at least 2 L of fluid/day to prevent dehydration and to report vomiting or diarrhea to health care professional promptly.
  • Instruct patient to notify health care professional immediately if signs of deep vein thrombosis (sudden swelling in leg, pain or tenderness in leg (may only be felt when standing or walking), increased warmth in the area of swelling, skin redness or change in skin color) or pulmonary embolus (sudden sharp chest pain, shortness or breath, cough with bloody secretions, sweating, rapid pulse, fainting, feeling anxious) occur. Also notify health care professional if unusual bleeding or bruising, or unusual tiredness occur.
  • Advise diabetic patients to monitor blood glucose frequently as directed and notify health care professional if blood sugar is higher than normal.
  • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • May have teratogenic effects. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Improvement in or decreased progression of CTCL.
References in periodicals archive ?
ATLANTA -- Intravenous treatment with mogamulizumab, an investigational antibody targeting CC chemokine receptor 4, more than doubled progression-free survival (PFS), compared with oral vorinostat in a phase 3 trial of 372 patients with heavily pretreated cutaneous T-cell lymphoma (CTCL).
Vorinostat (SAHA)[sup][42] and panobinostat (LBH-589)[sup][43] are histone deacetylase (HDAC) inhibitors that have been approved for the treatment of advanced hematologic malignancies such as lymphoma and multiple myeloma.
A vaccine is used to help the body identify the HIV-infected cells so it can clear it out, while a drug called Vorinostat activates the dormant T-cells so they can be spotted by the immune system.
This is then followed by a course of the drug Vorinostat that awakens the dormant T-cells, which then begin producing HIV proteins that act as a homing beacon to the immune system.
The epigenetics drugs market report estimates the market size (Revenue USD million - 2013 to 2020) for key market segments based on the drug type (ChIP technology, DNA methylation), and their mechanism of action such as DNMT inhibitors - Azacitidine (vidaza) and Decitabine (dacogen); and HDAC inhibitors or HDIs - Romidepsin (istodax), Vorinostat (zolinza), and forecasts growth trends (CAGR% - 2016 to 2020).
Algunos de los inhibidores de HDAC reportados como farmacos para el tratamiento del cancer de pulmon son: butirato de sodio, vorinostat y panobinostat.
A randomized phase II study of two doses of vorinostat in combination with 5-FU/LV in patients with refractory colorectal cancer.
Las interacciones farmacocineticas de los AD son poco probables con busulfan, clorambucil, melfalan, tioguanina, cisplatino, carboplatino, oxaliplatino, mercaptopurina, 5-fluorouracilo, estramustina, daunorubicin, temozolomida, mecloretamina, doxorubicina, epirubicina, vorinostat.
Besides, a previous study demonstrated that combining topotecan and vorinostat induced apoptosis of two small cell lung cancer (SCLC) cell lines (H209 and H526 cell) through increasing endogenous ROS [49].
It combines the DNA damaging effect of bendamustine with the pan-histone deacetylase inhibitor (HDACi), vorinostat, with the aim of increasing the efficacy of the alkylator through the HDACi-mediated chromatin relaxation.
Potential mechanism of positive effect for histone deacetylases inhibitors (valproic acid, vorinostat and givinostat) directly relates with reduction of pro-inflammatory cytokine release, increased apoptosis of immune competent cells, and regulation of transcription factors.
Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.