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 ?
The SOLAR trial is designed to evaluate the safety and efficacy of cobomarsen given in 300 mg doses by intravenous (IV) infusion in an active control comparison trial versus Zolinza (vorinostat).
(1) In the Phase 3 trial, 372 adult patients with previously treated mycosis fungoides (MF) or Sezary syndrome (SS) stages IB to IV were randomized to either mogamulizumab (1 mg/kg dosed once weekly for the first 5 infusions, then once every 2 weeks) or vorinostat, dosed per prescribing information.
Four positive controls were used (vorinostat, geldanamycin, mitoxantrone, withaferin-a) each in final doses of 10, 3.33, and 1.00 [micro]M, respectively.
Algunos usan mecanismos de inhibicion selectiva de la metiltransferasa en dosis bajas (EC 2.1.1.43 Dacogen[R] (decitabina) y Vidaza[R] (azacitidina) para tratar el sindrome mielodisplasico; otros, inhibidores de la histona deacetilasa, Zolinza[R] (vorinostat) e Istodax[R] (romidepsina), para el tratamiento de linfoma de celulas T cutaneas.
On the basis of chemical structures and enzymatic activities, HDACIs are (Figure 3) (10) chemically classified as hydroxamates (vorinostat, panobinostat, givinostat, quisinostat, abexinostat, belinostat, tefinostat, resminostat, pracinostat), benzamides (entinostat, mocetinostat, chidamide), aliphatic acids (valproic acid), and cyclic peptides (romidepsin).
The combination of the histone deacetylase (HDAC) inhibitor suberanilo hydroxamic acid (vorinostat) with chemotherapeutics and/or radiation have shown much positive results.
Although this mutation has not been reported in choriocarcinoma, loss of function mutation sensitized ovarian cancer cells to targeted therapy of vorinostat, a histone deacetylase inhibitor used in the management of cutaneous T-cell lymphoma.
Preclinical experiments by researchers at University of Alabama at Birmingham (UAB) in the US suggest the cancer drugs vorinostat, belinostat and panobinostat might help treat HPVs.
Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation.
They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily.
The use of HDAC inhibitors, vorinostat and romidepsin, has been approved by the FDA for the treatment of cutaneous T-cell lymphoma.
The US FDA's approval was based on the company's clinical trial of 372 patients with relapsed MF or SS who received either Poteligeo or a type of chemotherapy called vorinostat. Progression-free survival (the amount of time a patient stays alive without the cancer growing) was longer for patients taking Poteligeo (median 7.6 months) compared to patients taking vorinostat (median 3.1 months).