IMPORTANT SAFETY INFORMATION

Anzemet® (dolasetron mesylate) Injection

WHAT IS ANZEMET INJECTION USED FOR?

Anzemet® (dolasetron mesylate) Injection is used to prevent and treat post-operative nausea and vomiting in adults and children 2 years and older.

WHEN SHOULD I NOT TAKE THE DRUG?

DO NOT USE ANZEMET INJECTION IF:

  • You have ever had a bad reaction to any form of Anzemet (injection or tablets) in the past
  • If you have a rapid heartbeat (prolonged QT interval)

WHAT WARNINGS SHOULD I KNOW ABOUT ANZEMET?

QT, PR and QRS Interval Prolongation

The QT, PR, and QRS intervals reflect separate measures of time on the heart’s electrical cycle.

QT Interval:  A lengthened QT interval can be associated with rapid/slow heartbeat and can increase your risk for sudden death.  Anzemet Injection can increase the QT Interval in a dose-dependent fashion.  If you have a prolonged QT Interval or low levels of potassium or magnesium in your bloodstream you should avoid receiving Anzemet Injection.  Low levels of potassium and magnesium in the bloodstream must be corrected prior to starting Anzemet Injection therapy and should be monitored once Anzemet Injection therapy has begun.  If you are prescribed Anzemet Injection and have congestive heart failure and very slow heart rate, your doctor may suggest ECG monitoring.

PR and QRS Interval:  Lengthened PR and QRS intervals are associated with heart block, heart attack, irregular heart beat, and serious slow heart rate in adults and children.  Anzemet Injection can increase these conditions and result in death.   Patients having underlying heart disease and heart abnormalities are at particular risk, as are elderly patients, patients with irregular heart beat, patients with atrial fibrillation (irregular or quivering heartbeat) with slow heart response, patients who have had heart attack or patients receiving drugs (such as verapamil, flecainide or quinidine) known to prolong the PR and/or QRS interval.  If you have one of these conditions, your doctor will prescribe Anzemet Injection with ECG monitoring.  If you have or are at risk for complete heart block, your doctor will only prescribe Anzemet Injection if you have an implanted pacemaker.

Serotonin Syndrome

Serotonin syndrome occurs when there is excess serotonin in the body.  This has been reported for drugs, such as Anzemet Injection, that are known as 5-HT3  receptor antagonists.  You can develop serotonin syndrome from use of a 5-HT3 receptor antagonist alone, or from use of other serotogenic drugs used for depression and migraine and other disorders such as serotonin reuptake inhibitors (SSRI’s), serotonin and norepinephrine reuptake inhibitors (SNRI’s), monoamine oxidase inhibitors (MAOI’s), mirtazepine, fentanyl, lithium, tramadol and intravenous methylene blue3, in combination with Anzemet Injection.

Serotonin syndrome can have serious, potentially life-threatening and sometimes fatal consequences.  If you are receiving Anzemet Injection and have any of the following symptoms, seek immediate medical attention: changes in your mental status (agitation, hallucinations, delirium and coma), changes in basic body functions (irregular heart beat, increased or decreased blood pressure, dizziness, flushing, sweating, high body temperature), neuromuscular symptoms (tremor, rigidity, unusual muscle jerking and/or spasms, in-coordination), seizures, nausea, vomiting, diarrhea.

ANZEMET INJECTION IS ADMINISTERED WITH CAUTION IN PATIENTS WHO HAVE OR MAY DEVELOP PROLONGED CARDIAC INTERVALS, PARTICULARLY PROLONGATION OF THE QT INTERVAL.  THIS INCLUDES PATIENTS WHO HAVE LOW BLOOD LEVELS OF POTASSIUM AND MAGNESIUM, PATIENTS TAKING DIURETICS WITH THE POTENTIAL OF CAUSING ELECTROLYTE ABNORMALITIES, PATIENTS WITH CONGENITAL QT SYNDROME (PROLONGED QT INTERVALS), PATIENTS TAKING ANTIARRHYTHMIC DRUGS OR OTHER DRUGS THAT CAN LEAD TO QT PROLONGATION, AND CUMULATIVE HIGH DOSE ANTHRACYCLINE THERAPY.

Pediatric Use

Prevention of chemotherapy induced nausea and vomiting

ANZEMET INJECTION SHOULD NOT BE USED IN CHILDREN UNDERGOING CANCER CHEMOTHERAPY

Prevention and treatment of post-operative nausea and vomiting

ANZEMET INJECTION SHOULD NOT BE USED IN CHILDREN UNDER 2 YEARS OLD FOR POST-OPERATIVE NAUSEA AND VOMITING

Geriatric Use

Prevention of chemotherapy induced nausea and vomiting

ANZEMET INJECTION SHOULD NOT BE USED FOR GERIATRIC PATIENTS UNDERGOING CANCER CHEMOTHERAPY

Prevention and treatment of post-operative nausea and vomiting

There have been no studies of the use of Anzemet Injection for post-operative nausea and vomiting in older patients.

Older patients are at risk for prolongation of the PR, QRS and QT interval, so if you are an older patient and receiving Anzemet Injection, your doctor will exercise caution  and should require ECG monitoring.

WHAT SHOULD I TELL MY HEALTHCARE PROVIDER?

If you are prescribed Anzemet Injection and have congestive heart failure, very slow heart rate, QT syndrome, liver impairment, have hypokalemia (potassium deficiency in bloodstream) or hypomagnesemia (magnesium deficiency in bloodstream), take diuretics,  anti-arrhythmic drugs or other drugs which lead to QT prolongation, or take high doses of anthracycline, your doctor will monitor you closely.

You should tell your doctor if you are pregnant, thinking of becoming pregnant or nursing.

Anzemet Injection has been shown to  cause liver cancer in mice at 4,7, and 14 times the recommended doses.

Anzemet Injection does not have an effect on fertility and reproduction at up to 9 times the recommended dose.

There is no evidence of impaired fertility or harm to the fetus caused by Anzemet Injection in rats and rabbits. However, there have been no studies in pregnant women so your doctor will only prescribe Anzemet Injection if clearly needed.

It is not known whether Anzemet Injection passes through to human milk.   If you are nursing or considering nursing tell your doctor.

WHAT OTHER MEDICATIONS MIGHT INTREACT WITH ANZEMET INJECTION?

There are few drugs that interact with Anzemet Injection.  However, if you are going to receive Anzemet Injection with any other drugs make sure you tell your doctor.  Your doctor may monitor you if you are receiving Anzemet Injection in combination with certain chemotherapy drugs, drugs that may cause serotonin syndrome, or drugs that affect your QT Interval and/or cause low blood potassium or magnesium.

WHAT ARE THE SIDE EFFECTS OF ANZEMET INJECTION?

Get immediate medical help if you notice any of the following side effects:

  • Change in your heart rate
  • Lightheadedness
  • Irregular heartbeat, weak pulse, slow breathing
  • Swelling in your hands or feet
  • Headache with chest pain and severe dizziness, fainting, fast or slow pounding heartbeats
  • Urinating less than usual or not at all
  • Agitation, hallucinations, delirium, and coma
  • Dizziness
  • Tremors
  • Muscle stiffness, muscle spasms, overactive reflexes, lack of coordination
  • Seizures, with or without nausea, vomiting, diarrhea

Less serious side effects may include:

  • Mild headache
  • Tired feeling, mild dizziness
  • Diarrhea, constipation, upset stomach, loss of appetite
  • Chills, shivering, numbness or tingly feeling
  • Fever, sweating
  • Rash
  • Joint or muscle pain

The most common side effects reported in patients taking Anzemet Injection were headache, fatigue, diarrhea, abnormally slow heartbeat (bradycardia), dizziness, pain, abnormally rapid heartbeat (tachycardia), indigestion, and chills/shivering.

Very rapid heart rate and cardiac arrest have been reported following administration of Anzemet Injection.

THIS IS NOT A COMPLETE LIST OF SIDE EFFECTS AND OTHERS MAY OCCUR. TELL YOUR DOCTOR ABOUT ALL MEDICINES YOU USE.  THIS INCLUDES PRESCRIPTION, OVER-THE-COUNTER, VITAMIN AND HERBAL PRODUCTS.  DO NOT START A NEW MEDICATION WITHOUT TELLING YOUR DOCTOR. YOU MAY REPORT SIDE EFFECTS TO VALIDUS PHARMACEUTICALS LLC AT 1-866-982-5438 (1-866-9VALIDUS).

OVERDOSAGE:

There is no known specific antidote for Anzemet Injection, and patients with suspected overdose should be managed with supportive therapy.

Doses as large as 5 mg IV have safely been given to healthy volunteers and cancer patients.

Following a suspected overdose of Anzemet Injection, if a patient is found to have second-degree or higher heart block, he or she should undergo cardiac telemetry monitoring.