vorinostat

(redirected from Zolinza)

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 ?
Additional medications now available to patients being treated for cancer through Walgreens Specialty Pharmacy are Afinitor and Votrient (kidney cancer), Sprycel and Tasigna (leukemia), and Targretin and Zolinza (lymphoma).
26 September 2011 - US Merck & Co Inc (NYSE:MRK) said last week that a Phase III trial of ZOLINZA (vorinostat) for an investigational use in patients with advanced malignant pleural mesothelioma who previously have been treated with systemic chemotherapy containing pemetrexed did not meet its primary endpoint of demonstrating an improvement in overall survival.
Healthcare company Merck (NYSE:MRK)(MSD outside the US and Canada) announced on Friday that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved for use in Japan three of its products, GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant], ZOLINZA (vorinostat) and CUBICIN (daptomycin for injection).
Vicky led the team that discovered Zolinza at Memorial Sloan Kettering and was a co-founder of Aton, which was subsequently acquired by Merck.
Approved drugs that operate by an epigenetic mechanism include two that inhibit methylation (Vidaza in 2004 and Dacogen in 2006) that were approved to treat myelodysplastic syndrome, a blood disorder that can progress to leukemia, and one drug that enhances acetylation, Zolinza, which was approved in 2006 to treat T cell lympboma.
In the United States, the tablet is sold under the trade name ZOLINZA (vorinostat).
Merck began selling two new oncology products in the past year, Zolinza for a form of lymphoma and the Gardisil cervical cancer vaccine.
The FDA has approved Zolinza (vorinostat) capsules for the treatment of cutaneous T-cell lymphoma (CTCL), a type of skin cancer, to be used when the disease persists, gets worse, or comes back during or after treatment with other medicines.
Drugs affected by the revisions include: Cozaar, Crixivan, Hyzaar, Isentress, Janumet, Januvia, Mevacor, Noroxin, Prinivil, Prinizide, Propecia, Proscar, Singulair, Zocor, and Zolinza.
Merck and Multiple Myeloma Research Consortium (MMRC) initiated a Phase IIb study of Zolinza (Merck's vorinostat), an oral histone deacetylase (HDAC) inhibitor, in combination with Velcade (Millennium's bortezomib) for Injection, a proteasome inhibitor, in patients with relapsed and refractory multiple myeloma.
These preclinical data clearly demonstrate the potential advantage of HDAC6-selective inhibitors such as ACY-1215 versus currently available pan-HDAC inhibitors such as Zolinza, also called vorinostat or SAHA.
The expected launch of NGR-hTNF (combination of a tumour homing peptide (NGR) with the human tumour necrosis factor (hTNF), Onconase(ranpirnase) and Zolinza (vorinostat) for the second-line treatment in 2014 will drive the market.