vorinostat

(redirected from Suberoylanilide hydroxamic acid)
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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.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
Synthesis, Biological Evaluation, and Computer-Aided Drug Designing of New Derivatives of Hyperactive Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitors.
Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes.
Jin, "Suberoylanilide hydroxamic acid induces apoptosis and subG1 arrest of 320 HSR colon cancer cells," Journal of Biomedical Science, vol.
The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells.
More recently, the ability of suberoylanilide hydroxamic acid (SAHA/vorinostat) and trichostatin A to induce mammary gland differentiation of human breast cancer cells suggests that solid tumours are also susceptible to HDACi-dependent differentiation [17, 30].
Vorinostat (suberoylanilide hydroxamic acid) in relapsed or refractory Hodgkin lymphoma: SWOG 0517 [abstract].
"Suberoylanilide hydroxamic acid (SAHA) holds promise as a first-generation drug for the prevention and treatment of familial frontotemporal dementia (FTD), a progressive, inherited neurodegenerative disease for which there is no treatment," said Joachim Herz, professor of molecular genetics and neuroscience at UT Southwestern and the study's senior author.
Histone deacetylase inhibitors: development of suberoylanilide hydroxamic acid (SAHA) for the treatment of cancers.
Suberoylanilide hydroxamic acid (SOHA) is an agent developed at Sloan-Kettering, where it's under study for treatment of several different types of advanced malignancies.
Scientists at the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City, led by MSKCC president emeritus Paul Marks, have discovered that the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) causes cancer cells to stop growing and die.
and British colleagues added an HDAC inhibitor called suberoylanilide hydroxamic acid to the drinking water of young mice genetically engineered to make mutated huntingtin protein.
Low-dose exogenous carbon monoxide exposure protected against sepsis in animal models by inhibiting inflammatory responses and promoting host defense mechanism.[sup][32] [sz]-blockers could help maintain a favorable hemodynamic profile, reduce proinflammatory cytokines, and improve survival in clinical and animal studies.[sup][33],[34] Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, could attenuate cytokine levels and improve survival in CLP mice models.[sup][35] Our study found that 8-Br-cADPR is also a new potential antiseptic agent that reduces intracellular calcium overload, TNF-a production, and oxidative stress.