Zofran

Contraindications

Hypersensitivity

Coadministration with apomorphine; combination reported to cause profound hypotension and loss of consciousness

Cautions

Hypersensitivity reactions including anaphylaxis and bronchospasm may occur: discontinue therapy if suspected; monitor and treat promptly per standard of care until signs and symptoms resolve

Reduce dose with severe hepatic impairment

Use according to schedule, not PRN

Do not use instead of nasogastric suction

Ondansetron may mask progressive ileus or gastric distention in patients who are undergoing abdominal surgery or experiencing chemotherapy-induced nausea and vomiting; monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction

Ondansetron is not a drug that stimulates gastric or intestinal peristalsis; should not be used instead of nasogastric suction

Serotonin syndrome reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs including SSRIs, SNRIs, MAO inhibitors, lithium, tramadol, methylene blue IV, and mirtazapine; if concomitant use with other serotonergic drugs is clinically warranted, patients should be made aware of potential increased risk for serotonin syndrome

Cross-sensitivity among selective serotonin antagonists may occur

Zofran ODT contains phenylalanine (caution for phenylketonurics)

Dose-dependent QT prolongation; avoid in patients with congenital long QT syndrome; ECG monitoring recommended in patients who have electrolyte abnormalities, CHF, or bradyarrhythmias or who are also receiving other medications that cause QT prolongation

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There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Keep the medicine in the foil pouch until you are ready to use it. Store at room temperature, away from heat and direct light. Do not freeze.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep the unused soluble film in the foil pouch until you ready to use it.

Zofran is a prescription medication used to prevent nausea and vomiting caused by chemotherapy or surgery. Zofran belongs to a group of drugs called serotonin 5-HT3 antagonists, which block serotonin, a natural chemical in the body, from causing nausea and vomiting.

This medication comes in several oral forms: tablets and and solution (liquid). Zofran is also available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

The first oral dose of Zofran is usually taken 30 minutes before the start of chemotherapy, 1 to 2 hours before the start of radiation therapy, or 1 hour before surgery.

Common side effects include headache, tiredness, and constipation. Zofran can cause dizziness. Do not drive or operate heavy machinery until you know how it affects you.

Zofran is a prescription medication used for the:

• prevention of nausea and vomiting associated with chemotherapy
• prevention of nausea and vomiting caused by radiation therapy
• prevention of nausea and vomiting caused by surgery 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Before taking Zofran, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• or anyone in your family has or has ever had long QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause fainting or sudden death)
• have heart disease
• have liver disease
• have an electrolyte imbalance
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of ondansetron injection in children. However, safety and efficacy have not been established in children being treated for nausea and vomiting due to cancer treatments who are younger than 6 months of age for the prevention of nausea and vomiting from surgery in children younger than 1 month of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of ondansetron injection in the elderly.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Apomorphine
• Bepridil
• Cisapride
• Dronedarone
• Fluconazole
• Ketoconazole
• Mesoridazine
• Nelfinavir
• Pimozide
• Piperaquine
• Posaconazole
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Alfentanil
• Alfuzosin
• Amiodarone
• Amitriptyline
• Amoxapine
• Amphetamine
• Anagrelide
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azimilide
• Azithromycin
• Bedaquiline
• Benzphetamine
• Bretylium
• Buprenorphine
• Bupropion
• Buserelin
• Butorphanol
• Ceritinib
• Chloroquine
• Chlorpromazine
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dextroamphetamine
• Dihydrocodeine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Ebastine
• Efavirenz
• Enflurane
• Eribulin
• Erythromycin
• Escitalopram
• Famotidine
• Felbamate
• Fentanyl
• Fingolimod
• Flecainide
• Fluoxetine
• Foscarnet
• Fosphenytoin
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Idelalisib
• Iloperidone
• Imipramine
• Isoflurane
• Isradipine
• Itraconazole
• Ivabradine
• Lapatinib
• Leuprolide
• Levofloxacin
• Levorphanol
• Lisdexamfetamine
• Lopinavir
• Lumefantrine
• Mefloquine
• Meperidine
• Methadone
• Methamphetamine
• Methylene Blue
• Metronidazole
• Mifepristone
• Mirtazapine
• Mizolastine
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nafarelin
• Nalbuphine
• Netupitant
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olanzapine
• Oxycodone
• Oxymorphone
• Paliperidone
• Panobinostat
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Pentazocine
• Perphenazine
• Pimavanserin
• Pitolisant
• Pixantrone
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Remifentanil
• Ribociclib
• Rilpivirine
• Risperidone
• Ritonavir
• Salmeterol
• Sematilide
• Sertindole
• Sevoflurane
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sufentanil
• Sulpiride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Tapentadol
• Tedisamil
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Tolterodine
• Toremifene
• Tramadol
• Trazodone
• Trifluoperazine
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vinflunine
• Voriconazole
• Vorinostat
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cyclophosphamide

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to selective 5-HT3 receptor antagonists (such as alosetron [Lotronex®], dolasetron [Anzemet®], granisetron [Kytril®], or palonosetron [Aloxi®])—Use with caution. It is likely you will also be allergic to ondansetron.

• Bowel blockage or
• Gastric distension (enlarged abdomen)—May cover up symptoms of these stomach or bowel problems, especially in patients who had a recent abdominal or stomach surgery.

• Bradyarrhythmia (slow heartbeat) or
• Congestive heart failure or
• Electrolyte imbalance (e.g., low potassium or magnesium in the blood)—Patients with these conditions should be monitored while using this medicine.

• Heart rhythm problems (e.g., congenital long QT syndrome, Torsade de Pointes)—Use is not recommended in patients with this condition.

• Heart rhythm problems (e.g., prolonged QT interval)—Use with caution. May make this condition worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Zofran is contraindicated in patients:

Clinical Trials Experience

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

The following adverse reactions have been reported in clinical trials of patients treated with ondansetron, the active ingredient of Zofran. A causal relationship to therapy with Zofran was unclear in many cases.

Prevention of Chemotherapy‑induced Nausea and Vomiting

The most common adverse reactions reported in greater than or equal to 4% of 300 adults receiving a single 24-mg dose of Zofran orally in 2 trials for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy (cisplatin greater than or equal to 50 mg/m2) were: headache (11%) and diarrhea (4%).

The most common adverse reactions reported in 4 trials in adults for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy (primarily cyclophosphamide-based regimens) are shown in Table 3.

aReported in greater than or equal to 5% of patients treated with Zofran and at a rate that exceeded placebo.

Less Common Adverse Reactions

Central Nervous System: Extrapyramidal reactions (less than 1% of patients).

Hepatic: Aspartate transaminase (AST) and/or alanine transaminase (ALT) values exceeded twice the upper limit of normal in approximately 1% to 2% of 723 patients receiving Zofran and cyclophosphamide‑based chemotherapy in US clinical trials. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur. The role of cancer chemotherapy in these biochemical changes is unclear.

Liver failure and death has been reported in cancer patients receiving concurrent medications, including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.

Integumentary: Rash (approximately 1% of patients).

Other (less than 2%): Anaphylaxis, bronchospasm, tachycardia, angina, hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures. Except for bronchospasm and anaphylaxis, the relationship to Zofran is unclear.

Prevention of Radiation‑induced Nausea and Vomiting

The most common adverse reactions (greater than or equal to 2%) reported in patients receiving Zofran and concurrent radiotherapy were similar to those reported in patients receiving Zofran and concurrent chemotherapy and were headache, constipation, and diarrhea.

Prevention of Postoperative Nausea and Vomiting

The most common adverse reactions reported in adults in trial(s) of prevention of postoperative nausea and vomiting are shown in Table 4. In these trial(s) patients were receiving multiple concomitant perioperative and postoperative medications in both treatment groups.

In a crossover study with 25 subjects, headache was reported in 6 subjects administered Zofran ODT with water (24%) as compared with 2 subjects administered Zofran ODT without water (8%).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ondansetron. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular

Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions, and atrial fibrillation), bradycardia, electrocardiographic alterations (including second‑degree heart block, QT/QTc interval prolongation, and ST segment depression), palpitations, and syncope. Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.

General

Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylactic reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported. Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable ondansetron.

Hepatobiliary

Liver enzyme abnormalities.

Lower Respiratory

Hiccups.

Neurology

Oculogyric crisis, appearing alone, as well as with other dystonic reactions.

Skin

Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Eye Disorders

Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.

The active ingredient in Zofran tablets and Zofran oral solution is ondansetron hydrochloride as the dihydrate, the racemic form of ondansetron and a selective blocking agent of the serotonin 5‑HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate. It has the following structural formula:

The empirical formula is C18H19N3O•HCl•2H2O, representing a molecular weight of 365.9.

Ondansetron hydrochloride dihydrate is a white to off‑white powder that is soluble in water and normal saline.

The active ingredient in Zofran ODT orally disintegrating tablets is ondansetron base, the racemic form of ondansetron, and a selective blocking agent of the serotonin 5‑HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one. It has the following structural formula:

The empirical formula is C18H19N3O representing a molecular weight of 293.4.

Each 4-mg Zofran tablet for oral administration contains ondansetron hydrochloride dihydrate equivalent to 4 mg of ondansetron. Each 8‑mg Zofran tablet for oral administration contains ondansetron hydrochloride dihydrate equivalent to 8 mg of ondansetron. Each tablet also contains the inactive ingredients hypromellose, iron oxide yellow (8-mg tablet only), lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, triacetin, and titanium dioxide.

Each 4-mg Zofran ODT orally disintegrating tablet for oral administration contains 4 mg ondansetron base. Each 8-mg Zofran ODT orally disintegrating tablet for oral administration contains 8 mg ondansetron base. Each Zofran ODT tablet also contains the inactive ingredients aspartame, gelatin, mannitol, methylparaben sodium, propylparaben sodium, and strawberry flavor. Zofran ODT tablets are a freeze‑dried, orally administered formulation of ondansetron which disintegrates on the tongue and does not require water to aid dissolution or swallowing.

Each 5 mL of Zofran oral solution contains 5 mg of ondansetron hydrochloride dihydrate equivalent to 4 mg of ondansetron. Zofran oral solution contains the inactive ingredients citric acid anhydrous, purified water, sodium benzoate, sodium citrate, sorbitol, and strawberry flavor.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 mg/kg per day and 30 mg/kg per day, respectively (approximately 4 and 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area).

Ondansetron was not mutagenic in standard tests for mutagenicity.

Oral administration of ondansetron up to 15 mg/kg per day (approximately 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.

Zofran (ondansetron) blocks the actions of chemicals in the body that can trigger nausea and vomiting.

Zofran is used to prevent nausea and vomiting that may be caused by surgery, cancer chemotherapy, or radiation treatment.

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

You should not use Zofran if you are also using apomorphine (Apokyn).

You should not use Zofran if you are allergic to ondansetron or to similar medicines such as dolasetron (Anzemet), granisetron (Kytril), or palonosetron (Aloxi).

Zofran orally disintegrating tablets may contain phenylalanine. Tell your doctor if you have phenylketonuria (PKU).

Serious side effects include blurred vision or temporary vision loss (lasting from only a few minutes to several hours), slow heart rate, trouble breathing, anxiety, agitation, shivering, feeling like you might pass out, and urinating less than usual or not at all. Stop taking Zofran and call your doctor at once if you have any of these side effects. Ondansetron may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Get emergency medical help if you have signs of an allergic reaction to Zofran: rash, hives; fever, chills, difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe constipation, stomach pain, or bloating;

• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;

• fast or pounding heartbeats;

• jaundice (yellowing of the skin or eyes);

• blurred vision or temporary vision loss (lasting from only a few minutes to several hours);

• high levels of serotonin in the body--agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Common Zofran side effects may include:

• diarrhea or constipation;

• headache;

• drowsiness; or

• tired feeling.

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.