Drugs Details

Drugs Info of Zolinza
Drugs Details
  • Drugs Type  : Multum
  • Date : 8th Jul 2015 07:29 am
  • Brand Name : Zolinza
  • Generic Name : vorinostat (Pronunciation: vor IN o stat)
Descriptions

ZOLINZA contains vorinostat, which is described chemically as N-hydroxy-N'-phenyloctanediamide. The empirical formula is C14H20N2O3. The molecular weight is 264.32 and the structural formula is:

 

ZOLINZA® (vorinostat) Structural Formula Illustration

 

Vorinostat is a white to light orange powder. It is very slightly soluble in water, slightly soluble in ethanol, isopropanol and acetone, freely soluble in dimethyl sulfoxide and insoluble in methylene chloride. It has no chiral centers and is non-hygroscopic. The differential scanning calorimetry ranged from 161.7 (endotherm) to 163.9°C. The pH of saturated water solutions of vorinostat drug substance was 6.6. The pKa of vorinostat was determined to be 9.2.

Each 100 mg ZOLINZA capsule for oral administration contains 100 mg vorinostat and the following inactive ingredients: microcrystalline cellulose, sodium croscarmellose and magnesium stearate. The capsule shell excipients are titanium dioxide, gelatin and sodium lauryl sulfate.

 

What are the possible side effects of vorinostat (Zolinza)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using vorinostat and call your doctor at once if you have a serious side effect such as:

  • chest pain, sudden cough, wheezing, rapid breathing;
  • pain, swelling, warmth, or redness in one or both legs;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • easy bruising,...

Read All Potential Side Effects and See Pictures of Zolinza »

What are the precautions when taking vorinostat (Zolinza)?

Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, certain mineral imbalances (such as low levels of potassium or magnesium in the blood), blood clots.

This drug may cause dizziness. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Vorinostat may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can...

Read All Potential Precautions of Zolinza »

Indications

ZOLINZA is indicated for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent orrecurrent disease on or following two systemic therapies.

Dosage Administration

Dosing Information

The recommended dose is 400 mg orally once daily with food.

Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.

ZOLINZA capsules should not be opened or crushed [see HOW SUPPLIED/Storage and Handling].

Dose Modifications

If a patient is intolerant to therapy, the dose may be reduced to 300 mg orally once daily with food. The dose may be further reduced to 300 mg once daily with food for 5 consecutive days each week, as necessary.

Dosing in Special Populations

ZOLINZA is contraindicated in patients with severe hepatic impairment [seeCONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, Use in Specific Populations and CLINICAL PHARMACOLOGY].

No information is available in patients with renal impairment [see CLINICAL PHARMACOLOGY].

How Supplied

Dosage Forms And Strengths

100 mg white, opaque, hard gelatin capsules with “568” over “100 mg” printed within radial bar in black ink on the capsule body.

ZOLINZA capsules, 100 mg, are white, opaque hard gelatin capsules with “568” over “100 mg” printed within the radial bar in black ink on the capsule body. They are supplied as follows:

NDC 0006-0568-40.

Each bottle contains 120 capsules.

Storage and Handling

Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F). [See USP Controlled Room Temperature.]

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-5There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

ZOLINZA (vorinostat) capsules should not be opened or crushed. Direct contact of the powder in ZOLINZA capsules with the skin or mucousmembranes should be avoided. If such contact occurs, wash thoroughly as outlined in the references. Personnel should avoid exposure to crushed and/or broken capsules [see Nonclinical Toxicology].

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

3. NIH [2002]. 1999 recommendations for the safe handling of cytotoxic drugs. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, NIH Publication No. 92-2621.

4. American Society of Health-System Pharmacists. (2006) ASHP Guidelines on Handling Hazardous Drugs.

5. Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.

Manuf for : Merck Sharp & Dohme Corp., a subsidiary of MERCK & CO., INC., Whitehouse Station, NJ 08889, USA. Manufactured by: Patheon, Inc. Mississauga, Ontario, Canada L5N 7K9

Side Effects

The most common drug-related adverse reactions can be classified into 4 symptom complexes: gastrointestinal symptoms (diarrhea, nausea, anorexia, weight decrease, vomiting, constipation), constitutional symptoms (fatigue,chills), hematologic abnormalities (thrombocytopenia, anemia), and taste disorders (dysgeusia, dry mouth). The most common serious drug-related adverse reactions were pulmonary embolism and anemia.

Clinical Trials Experience

The safety of ZOLINZA was evaluated in 107 CTCL patients in two single arm clinical studies in which 86 patients received 400 mg once daily.

The data described below reflect exposure to ZOLINZA 400 mg once daily in the 86 patients for a median number of 97.5 days on therapy (range 2 to 480+ days). Seventeen (19.8%) patients were exposed beyond 24 weeks and 8 (9.3%) patients were exposed beyond 1 year. The population of CTCL patients studied was 37 to 83 years of age, 47.7% female, 52.3% male, and 81.4% white, 16.3% black, and 1.2% Asian or multi-racial.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Common Adverse Reactions

Table 1 summarizes the frequency of CTCL patients with specific adverse events, regardless of causality, using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCICTCAE, version 3.0).

Table 1 : Clinical or Laboratory Adverse Events Occurring in CTCL Patients (Incidence ≥ 10% of patients) 

ADVERSE EVENTS ZOLINZA 400 MG ONCE DAILY (N=86)
ALL GRADES GRADES 3-5*
N % N %
Fatigue 45 52.3 3 3.5
Diarrhea 45 52.3 0 0.0
Nausea 35 40.7 3 3.5
Dysgeusia 24 27.9 0 0.0
Thrombocytopenia 22 25.6 5 5.8
Anorexia 21 24.4 2 2.3
Weight Decreased 18 20.9 1 1.2
Muscle Spasms 17 19.8 2 2.3
Alopecia 16 18.6 0 0.0
Dry Mouth 14 16.3 0 0.0
Blood Creatinine Increased 14 16.3 0 0.0
Chills 14 16.3 1 1.2
Vomiting 13 15.1 1 1.2
Constipation 13 15.1 0 0.0
Dizziness 13 15.1 1 1.2
Anemia 12 14.0 2 2.3
Decreased Appetite 12 14.0 1 1.2
Peripheral Edema 11 12.8 0 0.0
Headache 10 11.6 0 0.0
Pruritus 10 11.6 1 1.2
Cough 9 10.5 0 0.0
Upper Respiratory Infection 9 10.5 0 0.0
Pyrexia 9 10.5 1 1.2
* No Grade 5 events were reported.

 

The frequencies of more severe thrombocytopenia, anemia [see WARNINGS AND PRECAUTIONS] and fatigue were increased at doses higher than 400 mg once daily of ZOLINZA.

Serious Adverse Reactions

The most common serious adverse events, regardless of causality, in the 86 CTCL patients in two clinical studies were pulmonary embolism reported in 4.7% (4/86) of patients, squamous cell carcinoma reported in 3.5% (3/86) of patients and anemia reported in 2.3% (2/86) of patients. There were single events of cholecystitis, death (of unknown cause), deep vein thrombosis, enterococcal infection, exfoliative dermatitis, gastrointestinal hemorrhage, infection, lobar pneumonia, myocardial infarction, ischemic stroke, pelvi-ureteric obstruction, sepsis, spinal cord injury, streptococcal bacteremia,syncope, T-cell lymphoma, thrombocytopenia and ureteric obstruction.

Discontinuations

Of the CTCL patients who received the 400-mg once daily dose, 9.3% (8/86) of patients discontinued ZOLINZA due to adverse events. These adverse events, regardless of causality, included anemia, angioneurotic edema,asthenia, chest pain, exfoliative dermatitis, death, deep vein thrombosis, ischemic stroke, lethargy, pulmonary embolism, and spinal cord injury.

Dose Modifications

Of the CTCL patients who received the 400-mg once daily dose, 10.5% (9/86) of patients required a dose modification of ZOLINZA due to adverse events. These adverse events included increased serum creatinine, decreased appetite, hypokalemia, leukopenia, nausea, neutropenia, thrombocytopenia and vomiting. The median time to the first adverse event resulting in dose reduction was 42 days (range 17 to 263 days).

Laboratory Abnormalities

Laboratory abnormalities were reported in all of the 86 CTCL patients who received the 400-mg once-daily dose.

Increased serum glucose was reported as a laboratory abnormality in 69% (59/86) of CTCL patients who received the 400-mg once daily dose; only 4 of these abnormalities were severe (Grade 3). Increased serum glucose was reported as an adverse event in 8.1% (7/86) of CTCL patients who received the 400-mg once daily dose. [See WARNINGS AND PRECAUTIONS.]

Transient increases in serum creatinine were detected in 46.5% (40/86) of CTCL patients who received the 400-mg once daily dose. Of these laboratory abnormalities, 34 were NCI CTCAE Grade 1, 5 were Grade 2, and 1 was Grade 3.

Proteinuria was detected as a laboratory abnormality (51.4%) in 38 of 74 patients tested. The clinical significance of this finding is unknown.

Dehydration

Based on reports of dehydration as a serious drug-related adverse event in clinical trials, patients were instructed to drink at least 2 L/day of fluids for adequate hydration. [See WARNINGS AND PRECAUTIONS.]

Adverse Reactions in Non-CTCL Patients

The frequencies of individual adverse events were substantially higher in the non-CTCL population. Drug-related serious adverse events reported in the non-CTCL population which were not observed in the CTCL population included single events of blurred vision, asthenia, hyponatremia, tumor hemorrhage, Guillain-Barré syndrome, renal failure, urinary retention, cough,hemoptysis, hypertension, and vasculitis.

Interactions

Coumarin-Derivative Anticoagulants

Prolongation of prothrombin time (PT) and International Normalized Ratio(INR) were observed in patients receiving ZOLINZA concomitantly with coumarin-derivative anticoagulants. Physicians should carefully monitor PT and INR in patients concurrently administered ZOLINZA and coumarin derivatives.

Other HDAC Inhibitors

Severe thrombocytopenia and gastrointestinal bleeding have been reported with concomitant use of ZOLINZA and other HDAC inhibitors (e.g., valproic acid). Monitor platelet count every 2 weeks for the first 2 months. [SeeWARNINGS AND PRECAUTIONS.]

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Thromboembolism

As pulmonary embolism and deep vein thrombosis have been reported as adverse reactions, physicians should be alert to the signs and symptoms of these events, particularly in patients with a prior history of thromboembolic events [see ADVERSE REACTIONS].

Hematologic

Treatment with ZOLINZA can cause dose-related thrombocytopenia andanemia. If platelet counts and/or hemoglobin are reduced during treatment with ZOLINZA, the dose should be modified or therapy discontinued. [SeeDOSAGE AND ADMINISTRATION and ADVERSE REACTIONS.]

Gastrointestinal

Gastrointestinal disturbances, including nausea, vomiting and diarrhea, have been reported [see ADVERSE REACTIONS] and may require the use of antiemetic and antidiarrheal medications. Fluid and electrolytes should be replaced to prevent dehydration [see ADVERSE REACTIONS]. Pre-existing nausea, vomiting, and diarrhea should be adequately controlled before beginning therapy with ZOLINZA.

Hepatic

ZOLINZA was studied in a limited number of patients with hepatic impairment. Based on these results, patients with mild and moderate hepatic impairment should be treated with caution. [See CONTRAINDICATIONS, Use In Specific Populations and CLINICAL PHARMACOLOGY.]

Hyperglycemia

Hyperglycemia has been observed in patients receiving ZOLINZA [seeADVERSE REACTIONS]. Serum glucose should be monitored, especially in diabetic or potentially diabetic patients. Adjustment of diet and/or therapy for increased glucose may be necessary.

Monitoring: Laboratory Tests

Careful monitoring of blood cell counts and chemistry tests, including electrolytes, glucose and serum creatinine, should be performed every 2 weeks during the first 2 months of therapy and monthly thereafter. Electrolytemonitoring should include potassium, magnesium and calcium. Hypokalemiaor hypomagnesemia should be corrected prior to administration of ZOLINZA, and consideration should be given to monitoring potassium and magnesium in symptomatic patients (e.g., patients with nausea, vomiting, diarrhea, fluid imbalance or cardiac symptoms).

Other Histone Deacetylase (HDAC) Inhibitors

Severe thrombocytopenia and gastrointestinal bleeding have been reported with concomitant use of ZOLINZA and other HDAC inhibitors (e.g., valproic acid). Monitor platelet count every 2 weeks during the first 2 months. [SeeDRUG INTERACTIONS].

Pregnancy

Pregnancy Category D

ZOLINZA can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of ZOLINZA in pregnant women. Results of animal studies indicate that vorinostat crosses theplacenta and is found in fetal plasma at levels up to 50% of maternalconcentrations. Doses up to 50 and 150 mg/kg/day were tested in rats and rabbits, respectively (~0.5 times the human exposure based on AUC0-24 hours). Treatment-related developmental effects including decreased mean live fetal weights, incomplete ossifications of the skull, thoracic vertebra, sternebra, and skeletal variations (cervical ribs, supernumerary ribs, vertebral count and sacral arch variations) in rats at the highest dose of vorinostat tested. Reductions in mean live fetal weight and an elevatedincidence of incomplete ossification of the metacarpals were seen in rabbits dosed at 150 mg/kg/day. The no observed effect levels (NOELs) for these findings were 15 and 50 mg/kg/day ( < 0.1 times the human exposure based on AUC) in rats and rabbits, respectively. A dose-related increase in the incidence of malformations of the gall bladder was noted in all drug treatment groups in rabbits versus the concurrent control. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Patient Counseling Information

[See FDA-Approved Patient Labeling]

Instructions

Patients should be instructed to drink at least 2 L/day of fluid to prevent dehydration and should promptly report excessive vomiting or diarrhea to their physician. Patients should be instructed about the signs of deep vein thrombosis and should consult their physician should any evidence of deep vein thrombosis develop. Patients receiving ZOLINZA should seek immediate medical attention if unusual bleeding occurs. ZOLINZA capsules should not be opened or crushed.

Patients should be instructed to read the patient insert carefully.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with vorinostat.

Vorinostat was mutagenic in vitro in the bacterial reverse mutation assays (Ames test), caused chromosomal aberrations in vitro in Chinese hamster ovary (CHO) cells and increased the incidence of micro-nucleated erythrocytes when administered to mice (Mouse Micronucleus Assay).

Effects on the female reproductive system were identified in the oral fertility study when females were dosed for 14 days prior to mating through gestational day 7. Doses of 15, 50 and 150 mg/kg/day to rats resulted in approximate exposures of 0.15, 0.36 and 0.70 times the expected clinical exposure based on AUC. Dose dependent increases in corpora lutea were noted at ≥ 15 mg/kg/day, which resulted in increased peri-implantation losses were noted at ≥ 50 mg/kg/day. At 150 mg/kg/day, there were increases in the incidences of dead fetuses and in resorptions.

No effects on reproductive performance were observed in male rats dosed (20, 50, 150 mg/kg/day; approximate exposures of 0.15, 0.36 and 0.70 times the expected clinical exposure based on AUC), for 70 days prior to mating with untreated females. [See WARNINGS AND PRECAUTIONS.]

Use In Specific Populations

Pregnancy

Pregnancy Category D [See WARNINGS AND PRECAUTIONS]

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ZOLINZA, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of ZOLINZA in pediatric patients have not been established.

Geriatric Use

Of the total number of patients with CTCL in trials (N=107), 46 percent were 65 years of age and over, while 15 percent were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Use in Patients with Hepatic Impairment

ZOLINZA was studied in a limited number of patients with hepatic impairment. Based on these limited data, ZOLINZA is contraindicated in patients with severe hepatic impairment and should be used with caution in patients with mild and moderate hepatic impairment. [See CONTRAINDICATIONS,WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY.]

Use in Patients with Renal Impairment

Vorinostat was not evaluated in patients with renal impairment. However, renal excretion does not play a role in the elimination of vorinostat. Patients with pre-existing renal impairment should be treated with caution. [SeeCLINICAL PHARMACOLOGY.]

OverDose

No specific information is available on the treatment of overdosage of ZOLINZA.

In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required. It is not known if vorinostat is dialyzable.

ContrainDications

Severe hepatic impairment [See WARNINGS AND PRECAUTIONS, Use in Specific Populations and CLINICAL PHARMACOLOGY.]

Clinical Pharamacology

Mechanism of Action

Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations (IC50 < 86 nM). These enzymes catalyze the removal of acetyl groups from the lysine residues of proteins, including histones andtranscription factors. In some cancer cells, there is an overexpression of HDACs, or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. Hypoacetylation of histones is associated with a condensed chromatinstructure and repression of gene transcription. Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In vitro, vorinostat causes the accumulation of acetylated histones and inducescell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat has not been fully characterized.

Pharmacodynamics

Cardiac Electrophysiology

A randomized, partially-blind, placebo-controlled, 2-period crossover studywas performed to assess the effects of a single 800-mg dose of vorinostat on the QTc interval in 24 patients with advanced cancer. This study was conducted to assess the impact of vorinostat on ventricular repolarization. The upper bound of the 90% confidence interval of the placebo-adjusted mean QTc interval change-from-baseline was less than 10 msec at every time point through 24 hours. Based on these study results, administration of a single supratherapeutic 800-mg dose of vorinostat does not appear to prolong the QTc interval in patients with advanced cancer; however the study did not include a positive control to demonstrate assay sensitivity. In the fasted state, oral administration of a single 800-mg dose of vorinostat resulted in a mean AUC and Cmax and median Tmax of 8.6±5.7 μM•hr and 1.7±0.67 μM and 2.1 (0.5-6) hours, respectively.

In clinical studies in patients with CTCL, three of 86 CTCL patients exposed to 400 mg once daily had Grade 1 ( > 450-470 msec) or 2 ( > 470-500 msec or increase of > 60 msec above baseline) clinical adverse events of QTc prolongation. In a retrospective analysis of three Phase 1 and two Phase 2 studies, 116 patients had a baseline and at least one follow-up ECG. Four patients had Grade 2 ( > 470-500 msec or increase of > 60 msec above baseline) and 1 patient had Grade 3 ( > 500 msec) QTc prolongation. In 49 non-CTCL patients from 3 clinical trials who had complete evaluation of QT interval, 2 had QTc measurements of > 500 msec and 1 had a QTc prolongation of > 60 msec.

Pharmacokinetics

Absorption

The pharmacokinetics of vorinostat were evaluated in 23 patients with relapsed or refractory advanced cancer. After oral administration of a single 400-mg dose of vorinostat with a high-fat meal, the mean ± standard deviation area under the curve (AUC) and peak serum concentration (Cmax) and the median (range) time to maximum concentration (Tmax) were 5.5±1.8 μM•hr, 1.2±0.62 μM and 4 (2-10) hours, respectively.

In the fasted state, oral administration of a single 400-mg dose of vorinostat resulted in a mean AUC and Cmax and median Tmax of 4.2±1.9 μM•hr and 1.2±0.35 μM and 1.5 (0.5-10) hours, respectively. Therefore, oral administration of vorinostat with a high-fat meal resulted in an increase (33%) in the extent of absorption and a modest decrease in the rate of absorption (Tmax delayed 2.5 hours) compared to the fasted state. However, these small effects are not expected to be clinically meaningful. In clinical trials of patients with CTCL, vorinostat was taken with food.

At steady state in the fed-state, oral administration of multiple 400-mg doses of vorinostat resulted in a mean AUC and Cmax and a median Tmax of 6.0±2.0 μM•hr, 1.2±0.53 μM and 4 (0.5-14) hours, respectively.

Distribution

Vorinostat is approximately 71% bound to human plasma proteins over the range of concentrations of 0.5 to 50 μg/mL.

Metabolism

The major pathways of vorinostat metabolism involve glucuronidation and hydrolysis followed by β-oxidation. Human serum levels of two metabolites, O-glucuronide of vorinostat and 4-anilino4-oxobutanoic acid were measured. Both metabolites are pharmacologically inactive. Compared to vorinostat, the mean steady state serum exposures in humans of the O-glucuronide of vorinostat and 4-anilino-4-oxobutanoic acid were 4-fold and 13-fold higher, respectively.

In vitro studies using human liver microsomes indicate negligible biotransformation by cytochromes P450 (CYP).

Excretion

Vorinostat is eliminated predominantly through metabolism with less than 1% of the dose recovered as unchanged drug in urine, indicating that renalexcretion does not play a role in the elimination of vorinostat. The meanurinary recovery of two pharmacologically inactive metabolites at steady state was 16±5.8% of vorinostat dose as the O-glucuronide of vorinostat, and 36±8.6% of vorinostat dose as 4-anilino-4-oxobutanoic acid. Total urinary recovery of vorinostat and these two metabolites averaged 52±13.3% of vorinostat dose. The mean terminal half-life (t½) was ~2.0 hours for both vorinostat and the O-glucuronide metabolite, while that of the 4-anilino-4-oxobutanoic acid metabolite was 11 hours.

Special Populations

Based upon an exploratory analysis of limited data, gender, race and age do not appear to have meaningful effects on the pharmacokinetics of vorinostat.

Pediatric

Vorinostat was not evaluated in patients < 18 years of age.

Hepatic Insufficiency

Vorinostat is contraindicated in patients with severe hepatic impairment and should be used with caution in patients with mild and moderate hepatic impairment. This recommendation is based on preliminary data from an ongoing pharmacokinetic study, which suggests that following administration of vorinostat, patients with severe hepatic dysfunction have a higherincidence and severity of adverse experiences compared with patients with no hepatic dysfunction. [See CONTRAINDICATIONS, WARNINGS ANDPRECAUTIONS and Use In Specific Populations.]

Renal Insufficiency

Vorinostat was not evaluated in patients with renal impairment. However, renal excretion does not play a role in the elimination of vorinostat. [See Use in Specific Populations.]

Pharmacokinetic effects of vorinostat with other agents

Vorinostat is not an inhibitor of CYP drug metabolizing enzymes in human liver microsomes at steady state Cmax of the 400 mg dose (Cmax of 1.2 μM vs IC50 of > 75 μM). Gene expression studies in human hepatocytes detected some potential for suppression of CYP2C9 and CYP3A4 activities by vorinostat at concentrations higher ( ≥ 10 μM) than pharmacologically relevant. Thus, vorinostat is not expected to affect the pharmacokinetics of other agents. As vorinostat is not eliminated via the CYP pathways, it is anticipated that vorinostat will not be subject to drug-drug interactions when co-administered with drugs that are known CYP inhibitors or inducers. However, no formal clinical studies have been conducted to evaluate drug interactions with vorinostat.

In vitro studies indicate that vorinostat is not a substrate of human P-glycoprotein (P-gp). In addition, vorinostat has no inhibitory effect on human P-gp-mediated transport of vinblastine (a marker P-gp substrate) at concentrations of up to 100 μM. Thus, vorinostat is not likely to inhibit P-gp at the pharmacologically relevant serum concentration of 2 μM (Cmax) in humans.

Clinical Studies

Cutaneous T-cell Lymphoma

In two open-label clinical studies, patients with refractory CTCL have been evaluated to determine their response rate to oral ZOLINZA. One study was a single-arm clinical study and the other assessed several dosing regimens. In both studies, patients were treated until disease progression or intolerabletoxicity.

Study 1

In an open-label, single-arm, multicenter non-randomized study, 74 patients with advanced CTCL were treated with ZOLINZA at a dose of 400 mg once daily. The primary endpoint was response rate to oral ZOLINZA in the treatment of skin disease in patients with advanced CTCL (Stage IIB and higher) who had progressive, persistent, or recurrent disease on or following two systemic therapies. Enrolled patients should have received, been intolerant to or not a candidate for bexarotene. Extent of skin disease was quantitatively assessed by investigators using a modified Severity Weighted Assessment Tool (SWAT). The investigator measured the percentage totalbody surface area (%TBSA) involvement separately for patches, plaques, and tumors within 12 body regions using the patient's palm as a “ruler”. The total %TBSA for each lesion type was multiplied by a severity weighting factor (1=patch, 2=plaque and 4=tumor) and summed to derive the SWAT score. Efficacy was measured as either a Complete Clinical Response (CCR) defined as no evidence of disease, or Partial Response (PR) defined as a ≥ 50% decrease in SWAT skin assessment score compared to baseline. Both CCR and PR had to be maintained for at least 4 weeks.

Secondary efficacy endpoints included response duration, time to progression, and time to objective response.

The population had been exposed to a median of three prior therapies (range 1 to 12).

Table 2 summarizes the demographic and disease characteristics of the Study 1 population.

Table 2 : Baseline Patient Characteristics (All Patients As Treated) 

CHARACTERISTICS VORINOSTAT (N=74)
Age (year)
Mean (SD) 61.2 (11.3)
Median (Range) 60.0 (39.0, 83.0)
Gender, n (%)
Male 38 (51.4%)
Female 36 (48.6%)
CTCL stage, n (%)
IB 11 (14.9%)
IIA 2 (2.7%)
IIB 19 (25.7%)
III 22 (29.7%)
IVA 16 (21.6%)
IVB 4 (5.4%)
Racial Origin, n (%)
Asian 1 (1.4%)
Black 11 (14.9%)
Other 1 (1.4%)
White 61 (82.4%)
Time from Initial CTCL Diagnosis (year)
Median (Range) 2.6 (0.0, 27.3)
Clinical Characteristics
Number of prior systemic treatments, median (range) 3.0 (1.0, 12.0)

 

The overall objective response rate was 29.7% (22/74, 95% CI [19.7 to 41.5%]) in all patients treated with ZOLINZA. In patients with Stage IIB and higher CTCL, the overall objective response rate was 29.5% (18/61). One patient with Stage IIB CTCL achieved a CCR. Median times to response were 55 and 56 days (range 28 to 171 days), respectively in the overall population and in patients with Stage IIB and higher CTCL. However, in rare cases it took up to 6 months for patients to achieve an objective response to ZOLINZA.

The median response duration was not reached since the majority of responses continued at the time of analysis, but was estimated to exceed 6 months for both the overall population and in patients with Stage IIB and higher CTCL. When end of response was defined as a 50% increase in SWAT score from the nadir, the estimated median response duration was 168 days and the median time to tumor progression was 202 days.

Using a 25% increase in SWAT score from the nadir as criterion for tumor progression, the estimated median time-to-progression was 148 days for the overall population and 169 days in the 61 patients with Stage IIB and higher CTCL.

Response to any previous systemic therapy does not appear to be predictive of response to ZOLINZA.

Study 2

In an open-label, non-randomized study, ZOLINZA was evaluated to determine the response rate for patients with CTCL who were refractory or intolerant to at least one treatment. In this study, 33 patients were assigned to one of 3 cohorts: Cohort 1, 400 mg once daily; Cohort 2, 300 mg twice daily 3 days/week; or Cohort 3, 300 mg twice daily for 14 days followed by a 7-day rest (induction). In Cohort 3, if at least a partial response was not observed then patients were dosed with a maintenance regimen of 200 mg twice daily. The primary efficacy endpoint, objective response, was measured by the 7-point Physician's Global Assessment (PGA) scale. The investigator assessed improvement or worsening in overall disease compared to baseline based on overall clinical impression. Index and non-index cutaneous lesions as well as cutaneous tumors, lymph nodes and all other disease manifestations were also assessed and included in the overall clinical impression. CCR required 100% clearing of all findings, and PR required at least 50% improvement in disease findings.

The median age was 67.0 years (range 26.0 to 82.0). Fifty-five percent of patients were male, and 45% of patients were female. Fifteen percent of patients had Stage IA, IB, or IIA CTCL and 85% of patients had Stage IIB, III, IVA, or IVB CTCL. The median number of prior systemic therapies was 4 (range 0.0 to 11.0).

In all patients treated, the objective response was 24.2% (8/33) in the overall population, 25% (7/28) in patients with Stage IIB or higher disease and 36.4% (4/11) in patients with Sezary syndrome. The overall response rates were 30.8%, 9.1% and 33.3% in Cohort 1, Cohort 2 and Cohort 3, respectively. The 300 mg twice daily regimen had higher toxicity with no additional clinical benefit over the 400 mg once daily regimen. No CCR was observed.

Among the 8 patients who responded to study treatment, the median time to response was 83.5 days (range 25 to 153 days). The median response duration was 106 days (range 66 to 136 days). Median time to progression was 211.5 days (range 94 to 255 days).

Patient Information

ZOLINZA®
(zo LINZ ah)
(vorinostat) Capsules

Read the patient information that comes with ZOLINZA* before you start taking it and each time you get a refill. There may be new information. This leaflet is a summary of the information for patients. Your doctor or pharmacistcan give you additional information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is ZOLINZA?

ZOLINZA is a prescription medicine used to treat a type of cancer called cutaneous T-cell lymphoma (CTCL) in patients when the CTCL gets worse, does not go away, or comes back after treatment with other medicines.

ZOLINZA has not been studied in children under the age of 18.

What should I tell my doctor before taking ZOLINZA?

Tell your doctor about all of your medical conditions, including if you:

  • Have any allergies
  • Have had a blood clot in your lung (pulmonary embolus)
  • Have had a blood clot in a vein (a blood vessel) anywhere in your body (deep vein thrombosis)
  • Have nausea, vomiting, or diarrhea
  • Have high blood sugar or diabetes
  • Are pregnant or plan to become pregnant. ZOLINZA may harm your unborn baby. ZOLINZA has not been studied in pregnant women. If you use ZOLINZA during pregnancy, tell your doctor immediately.
  • Are breast-feeding or plan to breast-feed. It is not known if ZOLINZA will pass into your breast milk. Talk to your doctor about the best way to feed your baby while you are taking ZOLINZA.

Tell your doctor about all of the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Some medicines may affect how ZOLINZA works, or ZOLINZA may affect how your other medicines work. Especially tell your doctor if you take:

  • Valproic acid: a medicine used to treat seizures. Your doctor will decide if you should continue to take valproic acid and may want to test your blood more frequently.
  • COUMADIN®: (warfarin) or any other blood thinner. Ask your doctor if you are not sure if you are taking a blood thinner. Your doctor may want to test your blood more frequently.

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

How should I take ZOLINZA?

  • Take ZOLINZA exactly as your doctor tells you to.
  • Your doctor will tell you how many ZOLINZA capsules to take and when to take them.
  • Swallow each capsule whole. Do not chew or break open the capsule. If you can't swallow ZOLINZA capsules whole, tell your doctor. You may need a different medicine.
  • Take ZOLINZA with food.
  • If ZOLINZA capsules are accidentally opened or crushed, do not touch the capsules or the powder contents of the capsules. If the powder from an open or crushed capsule gets on your skin or in your eyes, wash the contacted area well with plenty of plain water. Call your doctor.
  • Drink at least eight 8-ounce glasses of liquids every day while taking ZOLINZA. Drinking enough fluids may help to decrease the chances of losing too much fluid from your body (dehydration) especially if you are having symptoms such as nausea, vomiting or diarrhea while taking ZOLINZA.
  • If you miss a dose, take it as soon as you remember. If you do not remember until it is almost time for your next dose, just skip the missed dose. Just take the next dose at your regular time. Do not take two doses of ZOLINZA at the same time.
  • If you take too much ZOLINZA, call your doctor, local emergency room, or poison control center right away.
  • Your doctor will check your blood cell counts, blood sugar, blood electrolytes, and other chemistries every two weeks for the first two months of your treatment with ZOLINZA and then monthly. Your doctor may decide to do other tests to check your health as needed.
  • If you have high blood sugar (hyperglycemia) or diabetes, continue to monitor your blood sugar as your doctor tells you to. Your doctor may need to change your diet or medicine to help control your blood sugar while you take ZOLINZA. Be sure to tell your doctor if you are unable to eat or drink normally due to nausea, vomiting or diarrhea.

What are the possible side effects of ZOLINZA?

ZOLINZA may cause serious side effects. Tell your doctor right away if you have any of the following symptoms:

  • Blood clots in the legs (deep vein thrombosis)
    • sudden swelling in a leg
    • pain or tenderness in the leg. The pain may only be felt when standing or walking.
    • increased warmth in the area where the swelling is.
    • skin redness or change in skin color
  • Blood clots that travel to the lungs (pulmonary embolus)
  • sudden sharp chest pain
  • shortness of breath
  • cough with bloody secretions
  • sweating
  • rapid pulse
  • fainting
  • feeling anxious

 

  • Dehydration (loss of too much fluid from the body). This can happen if you are having nausea, vomiting or diarrhea and can not drink fluids well.
  • Changes in blood tests: Your doctor will periodically do blood tests to check your blood counts and electrolytes.
    • Low red blood cells. Low red blood cells may make you feel tiredand get tired easily. You may look pale, and feel short of breath.
    • Low platelets. Low platelets can cause unusual bleeding or bruising under the skin. Talk to your doctor right away if this happens.
  • High blood sugar (blood glucose). If you have high blood sugar or diabetes, monitor your blood sugar frequently as directed by your doctor. Tell your doctor right away if your blood sugar is higher than normal.

In addition, the most common side effects with ZOLINZA include:

  • Stomach and intestinal problems, including diarrhea, nausea, vomiting, loss of appetite, constipation and weight loss
  • Tiredness
  • Dizziness
  • Headache
  • Changes in the way things taste and dry mouth
  • Muscle aches
  • Hair loss
  • Chills
  • Fever
  • Upper respiratory infection
  • Cough
  • Increase in blood creatinine
  • Swelling in the foot, ankle and leg
  • Itching

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of ZOLINZA. For more information, ask your doctor or pharmacist.

General information about ZOLINZA

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use ZOLINZA for a condition for which it was not prescribed. Do not give ZOLINZA to other people, even if they have the same symptoms you have. It may harm them.

Keep ZOLINZA and all medicines out of the reach of children.

This leaflet summarizes the most important information about ZOLINZA. If you would like to know more information, talk to your doctor. You can ask your doctor or pharmacist for information about ZOLINZA that is written for health professionals.

What are the ingredients in ZOLINZA?

Active ingredient: vorinostat
Inactive ingredients: microcrystalline cellulose, sodium croscarmellose and magnesium stearate. The inactive ingredients in the capsule shell are titanium dioxide, gelatin, and sodium lauryl sulfate.

How should I store ZOLINZA?

Store ZOLINZA at room temperature, 68° F to 77° F (20° C to 25°C).

Issued: October 2010

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

VORINOSTAT - ORAL

 

(vor-IN-oh-stat)

 

COMMON BRAND NAME(S): Zolinza

 

USES: Vorinostat is used to treat a certain type of cancer (CTCL-cutaneous T-cell lymphoma). It works by slowing or stopping the growth of cancer cells.

 

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking vorinostat and each time you get a refill. If you have any questions regarding the information, ask your doctor or pharmacist.

Take this medication by mouth with food as directed by your doctor, usually once daily. Swallow the capsules whole. Do not crush, chew, or open the capsules.

Do not use capsules that are opened or crushed. If your skin or eyes come in contact with the powder inside the capsule, wash the area well with plenty of water and call your doctor.

The dosage is based on your medical condition and response to treatment.

To prevent dehydration while taking this medication, drink at least 8 glasses of water (8 ounces/240 milliliters each) throughout the day unless your doctor directs you otherwise.

Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and the risk of serious side effects may be increased.

Since this drug can be absorbed through the skin and lungs, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the capsules.

Tell your doctor if your condition does not improve or if it worsens.

Consumer Overview Side Effect

SIDE EFFECTS: Tiredness, loss of appetite, weight loss, dizziness, dry mouth, change in the sense of taste, hair loss, headache, or cough may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Nausea, vomiting, and diarrhea can also occur and may be severe. Tell your doctor right away if these effects occur. In some cases, your doctor may prescribe medication to prevent or relieve them. Eating several small meals, not eating before treatment, or limiting activity may help to lessen the nausea and vomiting.

Many people using this medication have serious side effects. However, your doctor has prescribed this drug because he or she has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.

Persistent vomiting/diarrhea may result in a serious loss of body water (dehydration). Contact your doctor promptly if you notice any symptoms of dehydration, such as unusual decreased urination, unusual dry mouth/thirst, fast heartbeat, or dizziness/lightheadedness.

This medication may infrequently make your blood sugar level rise, which can cause or worsen diabetes. Tell your doctor immediately if you develop symptoms of high blood sugar, such as increased thirst and urination. If you already have diabetes, be sure to check your blood sugars regularly. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

This medication decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising/bleeding. You may be at an increased risk for stomach/intestine bleeding if you are taking certain medications (see also Drug Interaction section). Tell your doctor right away if you develop any of the following unlikely symptoms: unusual tiredness, pale skin, signs of infection (such as fever, chills, persistent sore throat), easy bruising/bleeding, signs of stomach/intestine bleeding (such as black/bloody stools, vomit that contains blood or looks like coffee grounds, dizziness).

Tell your doctor right away if you have any serious side effects, including: signs of low levels of magnesium/potassium/calcium in the blood (such as severe muscle spasms/cramps, irregular heartbeat, mental/mood changes, seizures).

This medication may rarely cause blood clots (such as pulmonary embolism and deep vein thrombosis). You may be at increased risk for blood clots if you have a history of blood clots. Get medical help right away if any of these side effects occur: chest pain, pain/redness/swelling usually in the leg, trouble breathing.

Get medical help right away if any of these rare but serious side effects occur: fast/irregular heartbeat, severe dizziness, fainting.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Zolinza (vorinostat) Side Effects Center for a complete guide to possible side effects

Learn More »
 

PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, certain mineral imbalances (such as low levels of potassium or magnesium in the blood), blood clots.

This drug may cause dizziness. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Vorinostat may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using vorinostat, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using vorinostat safely.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially QT prolongation.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details.

It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: "blood thinners" (such as warfarin), valproic acid.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as complete blood count, kidney function, blood glucose levels, blood mineral levels including potassium/magnesium/calcium) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised July 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Zolinza

Generic Name: vorinostat (Pronunciation: vor IN o stat)

  • What is vorinostat (Zolinza)?
  • What are the possible side effects of vorinostat (Zolinza)?
  • What is the most important information I should know about vorinostat (Zolinza)?
  • What should I discuss with my health care provider before taking vorinostat (Zolinza)?
  • How should I take vorinostat (Zolinza)?
  • What happens if I miss a dose (Zolinza)?
  • What happens if I overdose (Zolinza)?
  • What should I avoid while taking vorinostat (Zolinza)?
  • What other drugs will affect vorinostat (Zolinza)?
  • Where can I get more information?

What is vorinostat (Zolinza)?

 

Vorinostat is used to treat skin problems caused by cutaneous T-cell lymphoma.

Vorinostat is usually given after other treatments have been tried without successful treatment.

Vorinostat may also be used for purposes not listed in this medication guide.

What are the possible side effects of vorinostat (Zolinza)?

 

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using vorinostat and call your doctor at once if you have a serious side effect such as:

  • chest pain, sudden cough, wheezing, rapid breathing;
  • pain, swelling, warmth, or redness in one or both legs;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • severe or ongoing vomiting or diarrhea;
  • bloody, black, or tarry stools;
  • coughing up blood or vomit that looks like coffee grounds;
  • feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin; or
  • high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision).

Less serious side effects may include:

  • nausea, constipation, diarrhea;
  • loss of appetite, weight loss;
  • headache, tired feeling;
  • itching, chills;
  • dry mouth;
  • hair loss;
  • altered sense of taste;
  • muscle spasms; or
  • cold symptoms such as stuffy nose, sneezing, cough, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Zolinza (vorinostat) Side Effects Center for a complete guide to possible side effects

Learn More »
 

What is the most important information I should know about vorinostat (Zolinza)?

 

You should not use this medication if you are allergic to vorinostat, or if you have severe liver disease.

Do not use vorinostat if you are pregnant. It could harm the unborn baby.

You should not breast-feed while you are using vorinostat.

Drink at least 2 liters of water each day to keep from getting dehydrated while you are taking vorinostat. Tell your doctor if you have severe vomiting or diarrhea during treatment.

Do not crush or open a vorinostat capsule. Swallow it whole. The medicine inside the capsule can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If this occurs, wash your skin with soap and water or rinse your eyes with water. Ask your doctor or pharmacist how to safely handle and dispose of a broken tablet or capsule.

You may need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly.

Stop using vorinostat and call your doctor at once if you have chest pain, sudden cough, wheezing, rapid breathing, coughing up blood, swelling or warmth in one or both legs, fever, chills, mouth sores, easy bruising or bleeding, bloody or tarry tools, or severe vomiting or diarrhea.

Patient Detailed How Take

What should I discuss with my health care provider before taking vorinostat (Zolinza)?

 

You should not use this medication if you are allergic to vorinostat, or if you have severe liver disease.

To make sure vorinostat is safe for you, tell your doctor if you have any of these other conditions:

  • diabetes;
  • liver disease;
  • kidney disease;
  • anemia (low red blood cells);
  • an electrolyte imbalance (such as high or low potassium levels in your blood);
  • a personal or family history of Long QT syndrome;
  • a history of stroke or blood clot; or
  • if you have recently been ill with vomiting or diarrhea.

FDA pregnancy category D. Do not use vorinostat if you are pregnant.It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether vorinostat passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using vorinostat.

How should I take vorinostat (Zolinza)?

 

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Your doctor may occasionally change your dose to make sure you get the best results. Follow the directions on your prescription label.

Vorinostat is usually taken once daily with food.

Drink at least 2 liters of water each day to keep from getting dehydrated while you are taking vorinostat. Tell your doctor if you have severe vomiting or diarrhea during treatment.

Do not crush or open a vorinostat capsule. Swallow it whole. The medicine inside the capsule can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If this occurs, wash your skin with soap and water or rinse your eyes with water. Ask your doctor or pharmacist how to safely handle and dispose of a broken capsule.

You will need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

Patient Detailed Avoid Taking

What happens if I miss a dose (Zolinza)?

 

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Zolinza)?

 

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking vorinostat (Zolinza)?

 

Avoid becoming overheated or dehydrated during exercise and in hot weather.

What other drugs will affect vorinostat (Zolinza)?

 

Tell your doctor about all other medicines you use, especially:

  • a blood thinner such as warfarin (Coumadin, Jantoven); or
  • valproic acid (Depakene, Stavzor).

This list is not complete and other drugs may interact with vorinostat. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

 

Your pharmacist can provide more information about vorinostat.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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