Zolinza (Vorinostat) is a chemotherapeutic drug. It inhibits the enzyme histone deacetylase and arrests cell growth.

Zolinza (Vorinostat) Uses:

It is used to treat cutaneous T-cell lymphoma (CTCL) in patients with a progressive, persistent, or recurrent disease on or following two systemic treatments.

Zolinza (Vorinostat) dose in Adults

Zolinza (Vorinostat) dose in the treatment of Cutaneous T-cell lymphoma (CTCL):

400 mg orally once a day until toxicity develops or the disease progresses.

Zolinza (Vorinostat) dose in Childrens

No recommended for use in children.

Zolinza (Vorinostat) Pregnancy Risk Factor: D

• Pregnancy with Vorinostat (Zolinza), has been linked to severe and fatal adverse fetal outcomes.
• However, if it is administered during pregnancy, the patient should be informed about the negative pregnancy outcomes.
• Before initiating therapy, it is important to evaluate your pregnancy status. Testing should be done within seven days.
• Reproductively-competent females should be advised not to get pregnant and to use a contraceptive for at least six months following the last vorinostat dose.
• Effective contraception should be used by males with female partners who have potential to conceive.

Use Zolinza (Vorinostat), while breastfeeding

• It is unknown if vorinostat can be found in breast milk.
• The manufacturer recommends against breastfeeding during therapy or for at least seven days following the last vorinostat dose.

Zolinza (Vorinostat) Dose in kidney disease:

• The manufacturer has not recommended any dose adjustment.
• Dose adjustment is not required because of minimal renal clearance. 

Zolinza (Vorinostat) dose in Liver disease:

• Mild to moderate impairment (total bilirubin 1 -  3 times the ULN or AST greater than the ULN):

  • 300 mg once a day initially.

• Severe impairment (total bilirubin greater than 3 times the ULN):

  • Limited data is available.
  • The maintenance dose in some studies was 100 - 200 mg, while the maximum dose is 200 mg once a day.

Common Side Effects of Zolinza (Vorinostat):

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Fatigue
  • Chills
  • Dizziness
  • Headache

• Dermatologic:

  • Alopecia
  • Pruritus

• Endocrine & Metabolic:

  • Hyperglycemia
  • Weight Loss
  • Dehydration

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Dysgeusia
  • Anorexia
  • Xerostomia
  • Constipation
  • Vomiting
  • Decreased Appetite

• Genitourinary:

  • Proteinuria

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Anemia

• Neuromuscular & Skeletal:

  • Muscle Spasm

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Cough
  • Upper Respiratory Tract Infection

• Miscellaneous:

  • Fever

Less Common Side Effects of Zolinza (Vorinostat):

• Cardiovascular:

  • Pulmonary embolism
  • Prolonged Q-T interval on ECG

• Hematologic & oncologic:

  • Squamous cell carcinoma of the skin

Contraindications to Zolinza (Vorinostat):

• Severe allergic reactions are possible to vorinostat and any component of this formulation.
• Severe/ advanced liver disease (total Bilirubin >=3x ULN).

Warnings and precautions

• Suppression of bone marrow

  • Anemia and thrombocytopenia have been reported as dose-related hematologic toxicities.
  • Some patients may need to reduce or stop taking the drug.
  • Every 2 weeks, blood counts should be checked for 2 months. Then every month.
  • If severe thrombocytopenia is combined with other histone deacetylase inhibitors, such as valproic acid, GI bleeding may occur.
  • Patients receiving concomitant histone-deacetylase inhibitor therapy should have their CBC and platelet count monitored more often.

• CNS effects

  • It can cause dizziness, vertigo, or fatigue.
  • Patients who are required to be alert for mental tasks should be warned about the dangers of taking this drug.

• Toxicities to the gastrointestinal tract:

  • It can cause nausea, vomiting, diarrhea, and gastrointestinal discomfort.
  • Antiemetics or antidiarrheals may be required by patients.
  • Avoid dehydration and replace electrolytes if necessary.
  • Patients who require bowel surgery or those who have had bowel surgery must be cautious about taking the drug. There have been adverse anastomotic healing reactions.

• Hyperglycemia

  • Rarely, severe hyperglycemia may result.
  • Monitor serum glucose every 2 weeks for 2 years, then every other month or as indicated by a physician.
  • Diabetes patients should be aware that the drug can cause complications.
  • Antiidiabetic medication may be necessary for patients with severe hyperglycemia.

• Extension of QT

  • It has been reported that QT prolongation can be achieved by its use.
  • It is important to check and correct serum electrolytes, especially potassium, calcium, magnesium, before you begin the therapy.
  • Patients who have had QT prolongation in the past or are taking QT prolonging medications should receive periodic ECGs.

• Events that are thromboembolic:

  • Patients who have had thrombotic events in the past should be closely monitored for signs and symptoms of Pulmonary embolism (PE) or deep vein thrombosis.

• Hepatic impairment

  • Patients suffering from liver disease should be cautious about taking the drug.
  • The liver is the main route of elimination so the dosage should be decreased.

Vorinostat: Drug Interaction

Monitor:

• CBC with differential counts
• Serum chemistries, including serum calcium, potassium, magnesium, glucose and creatinine at baseline, then every 2 weekly for 2 months, then every month, or as clinically indicated),
• Liver function,
• INR (if on concomitant warfarin therapy).
• Monitor fluid status and clinical features of thromboembolism.
• Monitor adherence to the treatment.
• Baseline and periodic ECGs were done in clinical trials (Duvic 2007; Olsen 2007). 

How to administer Zolinza (Vorinostat)?

• It is administered orally with food.
• The capsules should not be opened, crushed, broken, or chewed.
• Adequate hydration (≥2 L/day fluids) should be maintained during treatment. 

Mechanism of action of Zolinza (Vorinostat):

• Vorinostat blocks enzymes histone-deacetylase (HDAC1, HDAC2, HDAC3, HDAC6, and HDAC6), which catalyze the removal of acetyl groups from protein lysine (including histones)
• The accumulation of acetyl group causes inhibition of histone deacetylase, which leads to the alteration of transcription factors activation and chromatin structure. 
• This results in cell death and an arrest of cell growth.

Protein binding: About 71% of the drug is protein-bound.

Metabolism: Glucuronidated and hydrolyzed (followed by beta-oxidation) to inactive metabolites

Half-life elimination is about 2 hours

Time to reach peak plasma concentration: With a high-fat meal is 4 hours (ranging from 2 to 10 hours)

Excretion: About 52 % of the drug is excreted in the urine as inactive metabolites. 

International Brands of Zolinza (Vorinostat):

• Azinza
• Zolinza

Zolinza (Vorinostat) Brand Names in Pakistan:

Not available in Pakistan.