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 ?
Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.
This center confirmed that the clinical picture and histopathological specimen were most consistent with AITL and recommended a chemotherapy regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and vorinostat.
According to Mehar news agency, Bortezomib, Cytarabine, Capecitabine, Erlotinib, Vorinostat, and Irinotecan are some of the drugs which were unveiled.
Others may be less well-known but equally valuable: Remicade, a therapy for rheumatoid arthritis (NYU), Gardasil, the cervical cancer vaccine (multiple inventors), Somavert, for the treatment of acromegaly (Ohio University), Vorinostat, for T-cell lymphoma, Latanoprost, for glaucoma, and Palivizumab, for respiratory syncytial virus (all Columbia University).
Furthermore, the HDACi vorinostat has been used in clinical trials for reducing the severity of graft-versus-host disease in patients with bone marrow transplants (Choi and Reddy 2011), and the HDACi givinostat has been studied for the treatment of several other inflammatory conditions.
In its experiment, the team gave a one-time dose of the cancer drug Vorinostat to eight patients on antiretroviral therapy.
Researchers at the University of North Carolina at Chapel Hill, working in collaboration with scientists from the Harvard School of Public Health, National Cancer Institute, Merck, and the University of California at San Diego, undertook a series of experiments designed to evaluate the potential of the drug vorinostat, a deacetylase inhibitor that is used to treat some types of lymphoma, to activate and disrupt the dormant virus.
Led by researchers at the University of North Carolina, the small study on eight HIV-positive men taking antiretrovirals probed how a lymphoma drug, vorinostat, could activate and disrupt the dormant virus.
Valproic acid, a relatively weak and non-toxic HDACi, showed promising effects in a small pilot study however, further retrospective studies failed to demonstrate any benefit from valproic acid in reducing the number of latently infected resting CD4+ T cells A far more potent HDACi, vorinostat (also called SAHA), is licensed for the treatment of cutaneous T-cell lymphoma, is relatively well tolerated in humans and has significant potency in promoting HIV replication from latently infected cells in vitro.
Hoffmann-La Roche AG, Basel, Switzerland); and (4) the epigenetic modification of histones in cutaneous T-cell lymphoma, which can be targeted by the histone deacetylase inhibitor vorinostat (Zonlinza, Merck & Co).
The second trial, sponsored by the comprehensive cancer center at Ohio State University in Columbus, is a phase I study of the side effects and best dose of vorinostat when given together with cisplatin and radiation therapy in patients with stage III or stage IVA squamous cell cancer of the oropharynx, either unreseccable or borderline resectable.
Ileri evre hastalarda bu tedavi yaklasimlari vakit kaybi olmakta, ilk etepta interferonalfa (INF-[alpha]), psoralen+UVA (PUVA) dusunulmeli, duruma gore yeni sentetik retinoid olan Beksaroten ya da daha once hematolojik malinitelerde kullanilan histon deasetilaz inhibitoru, Vorinostat gibi yeni tedavi yaklasimlari goz onunde bulundurulmalidir.