Zofran ondansetron 4 mg

Zofran is the brand name for ondansetron, a prescription medication that is used to prevent nausea and vomiting. It is most often prescribed for cancer patients as a way to help prevent the nausea caused by chemotherapy, radiation and surgery. It is sometimes prescribed for pregnant women dealing with morning sickness.

Zofran is a serotonin 5-HT3 receptor antagonist that works by blocking serotonin’s function, which can cause nausea and vomiting.

“When chemotherapy is administered, it can release serotonin from various structures,” including the stomach, intestine and brain, said Dr. Nagashree Seetharamu, an oncologist at the North Shore Long Island Jewish Cancer Institute at Lake Success in New York. When serotonin is released, it can initiate a vomiting reflex.

“By interfering with that process, Zofran can prevent this,” she said.

Dosage

Zofran is available as an oral tablet, rapidly disintegrating tablet (ODT), as a liquid and occasionally given via injection. The first dose is usually taken 30 minutes before chemotherapy begins, one to two hours before radiation begins, or one hour before surgery begins. Sometimes, patients take additional doses one-to-three times a day during chemotherapy or radiation and for one or two days after finishing treatment.

Adults typically take one 8-mg tablet or rapidly disintegrating tablet or 10 mL of liquid twice a day. For patients ages 12 and older, the dosage is the same as for adults. For those ages 4 to 11, patients should take a 4-mg tablet or rapidly disintegrating tablet or 5 mL of liquid three times per day.

Zofran can be taken with or without food, and patients can continue their normal diet while taking Zofran. Patients should limit alcohol consumption.

In the case of a missed dose, patients should take Zofran as soon as possible — unless it is almost time for the next dose, in which case they should skip the missed dose. If a dose is missed and the patient feels nauseated or vomits, he or she should take the missed dose as soon as possible.

Zofran ODT

Zofran ODT is an oral rapidly disintegrating tablet that dissolves quickly on the tongue.

It’s important that Zofran can rapidly disintegrate on the tongue. Some cancer patients have difficulty swallowing pills, and it’s not always convenient for them to come into a medical center to receive injections, Seetharamu said.

Those taking rapidly disintegrating tablets should be careful in how they remove the tablet from the package. It is important to not push the tablet foil backing, but to use dry hands to peel back the foil backing. Remove the tablet gently and immediately place it on the top of the tongue. The tablet will then dissolve in a few seconds. It can be swallowed with saliva. Taking Zofran ODT with water may increase the risk of a headache.

Side effects

There are some side effects associated with Zofran. The National Institutes of Health lists the following as common side effects. If experienced severely or for a prolonged amount of time, a doctor should be consulted:

  • headache
  • diarrhea
  • constipation
  • weakness
  • tiredness
  • dizziness

The following are more serious side effects. If experienced, patients should consult their doctors immediately:

  • blurred vision or vision loss
  • rash
  • hives
  • itching
  • swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs
  • hoarseness
  • difficulty breathing or swallowing
  • shortness of breath
  • noisy, high pitched breathing

People taking antidepressants or other medications that involved with serotonin should not take Zofran. Mixing these medications can result in serotonin syndrome, which happens when large amounts of serotonin accumulate in the body. Symptoms range from shivering and diarrhea to muscle rigidity, fever and seizures, according to Seetharamu and the Mayo Clinic.

Symptoms of overdose from Zofran are:

  • sudden loss of vision for a short time
  • dizziness or lightheadedness
  • fainting
  • constipation
  • irregular heart beat

Those who suspect Zofran overdose should call emergency services or poison control immediately.

Zofran and pregnancy

Zofran may be prescribed to pregnant women experiencing morning sickness. It may be prescribed as a tablet, liquid or as an orally disintegrating tablet (ODT).

Though Zofran is often effective in curbing pregnant women’s nausea or vomiting, the safety of the drug for the fetus is still under study. A January 2012 study looked at more than 4,500 women who experienced nausea and vomiting during pregnancy and more than 5,800 controls. The researchers found that taking ondansetron during the first trimester of pregnancy was associated with a twofold risk of birth defects, such as a cleft lip or palate, compared with women who didn’t take the medication.

However, a February 2013 study found no significant risk of adverse fetal outcomes among mothers taking Zofran. In 2013, the FDA announced a potential safety issue for mothers taking Zofran, though was careful to note that, “listing of a drug and a potential safety issue … does not mean that FDA is suggesting prescribers should not prescribe the drug or that patients taking the drug should stop taking the medication.”

It is unknown whether Zofran transfers into breast milk. Pregnant women with questions about Zofran should talk to their doctors.

Additional reporting by Laura Geggel, staff writer. Follow her on Twitter @LauraGeggel. Follow Live Science @livescience, Facebook & Google+.

Additional resources

  • Learn more about the oral and injection routes of Zofran at the Mayo Clinic.
  • More lawsuits about alleged birth defects are being filed, according to Lawyers and Settlements.
  • Read about ondansetron at the National Institutes of Health.

Zofran

CLINICAL PHARMACOLOGY

Mechanism Of Action

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron’s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex.

Pharmacodynamics

In healthy subjects, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday administration of ondansetron has been shown to slow colonic transit in healthy subjects. Ondansetron has no effect on plasmaprolactin concentrations.

Cardiac Electrophysiology

QTc interval prolongation was studied in a double-blind, single-intravenous dose, placebo-and positive-controlled, crossover trial in 58 healthy subjects. The maximum mean (95% upper confidence bound) difference in QTcF from placebo after baseline correction was 19.5 (21.8) milliseconds and 5.6 (7.4) milliseconds after 15minute intravenous infusions of 32 mg and 8 mg of ondansetron injection, respectively. A significant exposure-response relationship was identified between ondansetron concentration and ΔΔQTcF. Using the established exposure-response relationship, 24 mg infused intravenously over 15 minutes had a mean predicted (95% upper prediction interval) ΔΔQTcF of 14.0 (16.3) milliseconds. In contrast, 16 mg infused intravenously over 15 minutes using the same model had a mean predicted (95% upper prediction interval) ΔΔQTcF of 9.1 (11.2) milliseconds. In this study, the 8-mg dose infused over 15 minutes did not prolong the QT interval to any clinically relevant extent.

Pharmacokinetics

Absorption

Ondansetron is absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, is approximately 56%.

Ondansetron systemic exposure does not increase proportionately to dose. The area under curve (AUC) from a 16-mg tablet was 24% greater than predicted from an 8-mg tablet dose. This may reflect some reduction of first-pass metabolism at higher oral doses.

Food Effects

Bioavailability is also slightly enhanced by the presence of food.

Distribution

Plasma protein binding of ondansetron as measured in vitro was 70% to 76% over the concentration range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.

Elimination

Metabolism and Excretion

Ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The metabolites are observed in the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation.

In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall ondansetron turnover, CYP3A4 played the predominant role. Because of the multiplicity of metabolic enzymes capable of metabolizing ondansetron, it is likely that inhibition or loss of one enzyme (e.g., CYP2D6 genetic deficiency) will be compensated by others and may result in little change in overall rates of ondansetron elimination.

Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron.

Specific Populations

Age

Geriatric Population

A reduction in clearance and increase in elimination half-life are seen in patients older than 75 years compared to younger subjects .

Sex

Gender differences were shown in the disposition of ondansetron given as a single dose. The extent and rate of absorption are greater in women than men. Slower clearance in women, a smaller apparent volume of distribution (adjusted for weight), and higher absolute bioavailability resulted in higher plasma ondansetron concentrations. These higher plasma concentrations may in part be explained by differences in body weight between men and women. It is not known whether these sex-related differences were clinically important. More detailed pharmacokinetic information is contained in Tables 5 and 6.

Table 5: Pharmacokinetics in Male and Female Healthy Subjects after a Single Dose of a ZOFRAN 8-mg Tablet

Table 6: Pharmacokinetics in Male and Female Healthy Subjects after a Single Dose of a ZOFRAN 24mg Tablet

Renal Impairment

Renal impairment is not expected to significantly influence the total clearance of ondansetron as renal clearance represents only 5% of the overall clearance. However, the mean plasma clearance of ondansetron was reduced by about 50% in patients with severe renal impairment (creatinine clearance less than 30 mL/min). The reduction in clearance was variable and not consistent with an increase in half-life .

Hepatic Impairment

In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared with 5.7 hours in healthy subjects. In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours .

Drug Interaction Studies

CYP 3A4 Inducers

Ondansetron elimination may be affected by cytochrome P-450 inducers. In a pharmacokinetic trial of 16 epileptic patients maintained chronically on CYP3A4 inducers, carbamazepine, or phenytoin, a reduction in AUC, Cmax, and t½ of ondansetron was observed. This resulted in a significant increase in the clearance of ondansetron. However, this increase is not thought to be clinically relevant .

Chemotherapeutic Agents

Carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron .

Antacids

Concomitant administration of antacids does not alter the absorption of ondansetron.

Clinical Studies

Prevention Of Chemotherapy-Induced Nausea And Vomiting

Highly Emetogenic Chemotherapy

In 2 randomized, double-blind, monotherapy trials, a single 24-mg oral dose of ZOFRAN was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2. Steroid administration was excluded from these clinical trials. More than 90% of patients receiving a cisplatin dose greater than or equal to 50 mg/m2 in the historical-placebo comparator, experienced vomiting in the absence of antiemetic therapy.

The first trial compared oral doses of ondansetron 24 mg as a single dose, 8 mg every 8 hours for 2 doses, and 32 mg as a single dose in 357 adult cancer patients receiving chemotherapy regimens containing cisplatin greater than or equal to 50 mg/m2. The first or single dose was administered 30 minutes prior to chemotherapy. A total of 66% of patients in the ondansetron 24-mg once-a-day group, 55% in the ondansetron 8-mg twice-aday group, and 55% in the ondansetron 32-mg once-a-day group, completed the 24-hour trial period with 0 emetic episodes and no rescue antiemetic medications, the primary endpoint of efficacy. Each of the 3 treatment groups was shown to be statistically significantly superior to a historical placebo control.

In the same trial, 56% of patients receiving a single 24-mg oral dose of ondansetron experienced no nausea during the 24-hour trial period, compared with 36% of patients in the oral ondansetron 8-mg twice-a-day group (P = 0.001) and 50% in the oral ondansetron 32-mg once-a-day group. Dosage regimens of ZOFRAN 8 mg twice daily and 32 mg once daily are not recommended for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy .

In a second trial, efficacy of a single 24-mg oral dose of ZOFRAN for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m2, was confirmed.

Moderately Emetogenic Chemotherapy

A randomized, placebo-controlled, double-blind trial was conducted in the US in 67 patients receiving a cyclophosphamide-based chemotherapy regimen containing doxorubicin. The first 8-mg dose of ZOFRAN was administered 30 minutes before the start of chemotherapy, with a subsequent dose 8 hours after the first dose, followed by 8 mg of ZOFRAN twice a day for 2 days after the completion of chemotherapy.

ZOFRAN was significantly more effective than placebo in preventing vomiting. Treatment response was based on the total number of emetic episodes over the 3-day trial period. The results of this trial are summarized in Table 7.

Table 7: Emetic Episodes – Treatment Response in Patients Receiving Moderately Emetogenic Chemotherapy (Cyclophosphamide-based Regimen Containing Doxorubicin)

ZOFRAN
(n = 33)
Placebo
(n = 34)
P Value
Treatment response
0 Emetic episodes 20 (61%) 2 (6%) <0.001
1 to 2 Emetic episodes 6 (18%) 8 (24%)
More than 2 emetic episodes/withdrawn 7 (21%) 24 (71%) <0.001
Median number of emetic episodes 0.0 Undefineda
Median time to first emetic episode (hours) Undefinedb 6.5
a Median undefined since at least 50% of the patients were withdrawn or had more than 2 emetic episodes.
b Median undefined since at least 50% of patients did not have any emetic episodes.

In a double-blind, US trial in 336 patients receiving a cyclophosphamide-based chemotherapy regimen containing either methotrexate or doxorubicin, ZOFRAN 8 mg administered twice a day, was as effective as ZOFRAN 8 mg administered 3 times a day in preventing nausea and vomiting. ZOFRAN 8 mg three times daily is not a recommended regimen for the treatment of moderately emetogenic chemotherapy .

Treatment response was based on the total number of emetic episodes over the 3-day trial period. See Table 8 for the details of the dosage regimens studied and results of this trial.

Table 8: Emetic Episodes – Treatment Response after ZOFRAN Tablets Administered Twice a Day and Three Times a Day

ZOFRAN Tablets
8 mg Twice Dailya
(n = 165)
8 mg Three Times a Dayb
(n = 171)
Treatment response
0 Emetic episodes 101 (61%) 99 (58%)
1-2 Emetic episodes 16 (10%) 17 (10%)
More than 2 emetic episodes/withdrawn 48 (29%) 55 (32%)
Median number of emetic episodes 0.0 0.0
Median time to first emetic episode (h) Undefinedc Undefinedc
Median nausea scores (0-100)d 6 6
a The first 8-mg dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent 8-mg dose 8 hours after the first dose, followed by 8 mg administered twice a day for 2 days after the completion of chemotherapy.
b The first 8-mg dose was administered 30 minutes before the start of emetogenic chemotherapy, with subsequent 8-mg doses at 4 hours and 8 hours after the first dose, followed by 8 mg administered 3 times a day for 2 days after the completion of chemotherapy.
c Median undefined since at least 50% of patients did not have any emetic episodes.
d Visual analog scale assessment: 0 = no nausea, 100 = nausea as bad as it can be.

Re-Treatment

In single-arm trials, 148 patients receiving cyclophosphamide-based chemotherapy were re-treated with ZOFRAN 8 mg three times daily during subsequent chemotherapy for a total of 396 re-treatment courses. No emetic episodes occurred in 314 (79%) of the re-treatment courses, and only 1 to 2 emetic episodes occurred in 43 (11%) of the re-treatment courses.

Pediatric Trials

Three open-label, single-arm, non-US trials have been performed with 182 pediatric patients aged 4 to 18 years with cancer who were given a variety of cisplatin or noncisplatin regimens. The initial dose of ZOFRAN injection ranged from 0.04 to 0.87 mg per kg (total dose of 2.16 mg to 12 mg) followed by the administration of oral doses of ZOFRAN ranging from 4 to 24 mg daily for 3 days. In these trials, 58% of the 170 evaluable patients had a complete response (no emetic episodes) on Day 1. In 2 trials, the response rates to ZOFRAN 4 mg three times a day in patients younger than 12 years was similar to ZOFRAN 8 mg three times daily in patients 12 to 18 years. Prevention of emesis in these pediatric patients was essentially the same as for adults.

Radiation-Induced Nausea And Vomiting

Total Body Irradiation

In a randomized, placebo-controlled, double-blind trial in 20 patients, 8 mg of ZOFRAN administered 1.5 hours before each fraction of radiotherapy for 4 days was significantly more effective than placebo in preventing vomiting induced by total body irradiation. Total body irradiation consisted of 11 fractions (120 cGy per fraction) over 4 days for a total of 1,320 cGy. Patients received 3 fractions for 3 days, then 2 fractions on Day 4.

Single High-Dose Fraction Radiotherapy

In an active-controlled, double-blind trial in 105 patients receiving single high-dose radiotherapy (800 to 1,000 cGy) over an anterior or posterior field size of greater than or equal to 80 cm2 to the abdomen, ZOFRAN was significantly more effective than metoclopramide with respect to complete control of emesis (0 emetic episodes). Patients received the first dose of ZOFRAN (8 mg) or metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, 8 mg of ZOFRAN or 10 mg of metoclopramide was administered in the late afternoon and repeated again before bedtime. If radiotherapy was given in the afternoon, patients took 8 mg of ZOFRAN or 10 mg of metoclopramide only once before bedtime. Patients continued the doses of oral medication three times daily for 3 days.

Daily Fractionated Radiotherapy

In an active-controlled, double-blind trial in 135 patients receiving a 1-to 4-week course of fractionated radiotherapy (180 cGy doses) over a field size of greater than or equal to 100 cm2 to the abdomen, ZOFRAN was significantly more effective than prochlorperazine with respect to complete control of emesis (0 emetic episodes). Patients received the first dose of ZOFRAN (8 mg) or prochlorperazine (10 mg) 1 to 2 hours before the first daily radiotherapy fraction, with subsequent 8-mg doses approximately every 8 hours on each day of radiotherapy.

Postoperative Nausea And Vomiting

In 2 placebo-controlled, double-blind trials (one conducted in the US and the other outside the US) in 865 females undergoing inpatient surgical procedures, ZOFRAN 16 mg as a single dose or placebo was administered one hour before the induction of general balanced anesthesia (barbiturate, opioid, nitrous oxide, neuromuscular blockade, and supplemental isoflurane or enflurane), ZOFRAN tablets was significantly more effective than placebo in preventing postoperative nausea and vomiting.

No trials have been performed in males.

Nausea and Vomiting

Anti Nausea Meds in Pregnancy

Nausea is common in the first three months of pregnancy. Occasional vomiting is also common. Many women find their morning sickness tolerable, however if becomes too much to handle there are medications available. All anti nausea and vomiting medications have side effects, so it may not be worth taking medicine if the predominant symptoms is nausea alone.

Vomiting, especially, throwing up multiple times each day, can be treated. There are three common and safe medicines used to treat nausea with vomiting, in pregnancy. Each of these medications is safe, and each has its own side effect. Luckily though, not all patients will experience the side effects.

Treatment Options

Drug Name

Active Ingredient

Dosage

Side Effect

Compazine Prochlorperazine 10 mg every 6 hours Jittery, neck spasm
Phenergan Promenthazine 25 mg every 6 hours Sleepy
Zofran Ondansetron 4-8 mg every 6 hours Constipation

These medicines are safe and effective and each has been used in pregnancy for years, including in the first trimester. Keep in mind that side effects do not happen to everyone. And the side effects are not always severe.

Managing Side Effects

Treat With

Compazine Jittery, neck spasm diphenhydramine
(Benadryl)
25 or 50 mg
stop and switch
Phenergan Sleepy No Treatment switch
Zofran Constipation Docusate 100 mg
Twice Per Day

How and When to Take These Medications

Patients can take these medicines every 6, 8, 12 hours; 1-4 times per day. You can start or stop the medicines as needed or wanted. Patients can switch between these meds, also.

  • Take the medicine every 6 hours.
  • If its working, try taking the medicine every 8 hours.
  • Decrease to every 12 hours, or as needed, if feeling better.
  • Increase to every 6 hours, 4 scheduled doses each day, if feeling worse.
  • If you are taking the medicine every 6 hours and not feeling better you may switch to another medication.
  • Begin taking the new medicine every 6 hours.
  • If there is still No Relief then contact the office.

Intravenous Fluids

Sometimes, if the medications don’t work a patient may need intravenous fluids. Fluids can be given in the office. Some patients only need to come in for one round, others need to come for IV fluids daily. We can schedule IV fluids based on your needs. It is always best to call the office to arrange for IV fluids. The ER should be used as a LAST RESORT. It’s much better to call the office, so we can arrange IV fluids without going to the ER. Contact the office…

Zofran is a brand name for the drug ondansetron, prescribed to treat or prevent nausea and vomiting.

Doctors sometimes prescribe Zofran to treat nausea and vomiting caused by cancer treatments such as chemotherapy and radiation therapy.

Zofran also can treat nausea and vomiting after surgery.

The drug may also help prevent the common complication of shivering in people who have had anesthesia.

Some doctors have prescribed Zofran off-label to treat nausea and vomiting caused by morning sickness in pregnant women, though the drug has never been approved for this use.

Zofran blocks serotonin, a natural substance in the brain that may contribute to nausea and vomiting.

It belongs to a class of drugs called serotonin 5-HT3 receptor antagonists. These drugs are antiemetics, meaning they block nausea and vomiting.

The Food and Drug Administration (FDA) approved ondansetron in 1992 under the brand name Zofran for GlaxoSmithKline.

In 2007, the FDA approved generic ondansetron for several drug companies.

One form of ondansetron is a rapidly dissolving tablet (Zofran ODT). If you use Zofran ODT, do not remove the tablet from its foil pocket until just before you take it.

You should not take Zofran if you take a drug called apomorphine, which is an injectable drug used to treat Parkinson’s disease. The combination of apomorphine and ondansetron can cause dangerously low blood pressure.

You also should not use Zofran if you’ve had an allergic reaction to a different serotonin 5-HT3 receptor antagonist. Brand names of these include Lotronex, Anzemet, Kytril, and Aloxi.

In 2011, the FDA issued a warning that ondansetron may increase the risk for abnormal changes in the electrical activity of the heart.

These changes could trigger serious abnormal heart rhythms, including torsade de pointes, a type of life-threatening rapid heartbeat that starts in the bottom chambers of the heart.

People with underlying heart conditions, such as long QT syndrome, already are at increased risk for developing torsade de pointes. Taking Zofran may increase that risk.

Tell your doctor if you have this syndrome or a family history of the syndrome or if you’ve ever had fainting spells because of an irregular heartbeat.

If you have phenylketonuria (PKU), you should know that taking the rapidly dissolving tablet form of ondansetron (Zofran ODT) may increase your level of phenylalanine, which can be dangerous for you.

If you have certain health conditions, you need to use caution when taking ondansetron. Let your doctor know if you have or every had:

  • Inherited phenyketonuria, PKU
  • Heart rhythm problems including congenital long QT syndrome
  • History of congestive heart failure
  • Low magnesium or low potassium
  • Liver disease

Zofran and Pregnancy

There is some evidence that suggests Zofran may not be safe to take during pregnancy because of the risk of birth defects.

Some research has linked the use of Zofran during pregnancy to cleft palates, according to a 2012 report in the journal Canadian Family Physician.

Additionally, Zofran was never approved to treat nausea and vomiting from morning sickness in pregnant women.

Despite that fact, in 2012 GlaxoSmithKline pleaded guilty to illegally promoting the use of Zofran to prevent morning sickness (among other charges), and paid a $3 billion fine.

A number of lawsuits have been filed against GlaxoSmithKline over the safety of Zofran.

Research is continuing into the risk of birth defects when Zofran is taken by pregnant women. According to the Zofran prescribing information, “this drug should be used during pregnancy only if clearly needed.”

Though Zofran has been detected in the breast milk of laboratory animals, experts don’t know whether Zofran passes into human breast milk.

Because of these risks, be sure to tell your doctor if you are pregnant or breastfeeding before taking Zofran. Also, tell your doctor if you become pregnant or are considering breastfeeding while taking Zofran.

For additional Zofran information, visit our other Zofran pages: Zofran Lawsuits, Zofran studies, Should I Take Zofran While Pregnant?, or What Types of Birth Defects are Associated with Zofran Use?

It is extremely important that doctors do not prescribe medications to pregnant mothers that could be dangerous to the infant. It is even more important for healthcare providers and medication manufacturers to properly address the risk of medications and birth defects and not recommend medications that could be harmful.

One of the most concerning medications commonly prescribed to pregnant women is Zofran (ondansetron). Doctors most often prescribe Zofran to individuals who are undergoing chemotherapy, who have recently undergone surgery or who are suffering from nausea, including pregnant women. Pregnant women experiencing severe symptoms of morning sickness often take anti-nausea medication during the first trimester.

Although Zofran has shown effectiveness in treating nausea and vomiting, recent studies indicate that it also comes with a serious risk of side effects to both mother and infant. What’s more, the U.S. Food and Drug Administration (FDA) has not approved this medication for use during pregnancy.

How Zofran Works

Zofran works by blocking chemicals in the body responsible for nausea and vomiting. The main function of the medication is to treat patients with cancer, who have surgery, or who are undergoing chemotherapy or radiation. These patients often experience severe nausea.

Patients take Zofran orally via a rapidly disintegrating tablet (ODT), or through injections. Pregnant women experiencing nausea and/or vomiting usually take the oral tablet, which typically starts around 8 mg per tablet.

Although no one knows exactly why pregnant women experience nausea and/or vomiting, research suggests that more 50 percent of all pregnant women will experience a bout of nausea during pregnancy. In instances in which nausea is severe and home remedies fail to work, women may be prescribed Zofran or similar medications.

Zofran Warnings

According to the FDA, taking Zofran while pregnant can potentially lead to serious birth defects. Yet many doctors still frequently prescribe it. Even worse, since morning sickness is most common during the first trimester of pregnancy, women taking Zofran do so during an infant’s most crucial development period.

It is important to note that despite its potential risks, the FDA has not stopped Zofran from being prescribed. However, doctors have the legal duty to inform all pregnant women of the risks associated with Zofran prior to prescribing it.

Common Types of Birth Defects

The most common types of birth defects that can potentially result from Zofran use include:

  • Cleft Lip / Cleft Palate – Cleft lip and palate occur as a result of an incomplete formation of the front of the upper jaw and upper portion of the roof of the mouth.
  • Jaundice – A buildup of bilirubin (the substance that develops after red blood cells break down). Jaundice causes the skin and eyes to turn yellow. Severe jaundice can lead to kernicterus, a dangerous condition with the potential to cause liver damage, seizures or brain damage.
  • Musculoskeletal Anomalies – Deformity or malformation of the musculoskeletal system present at birth.
  • Heart Murmurs – A heart murmur is a condition often attributed to structural issues of the heart. The “murmur” sound refers to the sound of abnormal blood flow.
  • Atrial Septal Defect, or ASD – ASD occurs when the wall between the two upper heart chambers fails to fully close. Because of the incomplete closure between the two chambers, the infant is born with a gap in the heart. This “hole” could take multiple surgeries to repair and can lead to long term disabilities due to the lack of oxygen supply to the infant’s brain and body.
  • Ventricular Septal Defect, or VSD – VSD is similar to ASD except that the lower two heart chambers experience an incomplete closure of the wall.

Because of the controversial side effects of Zofran, there are numerous studies that aim to gather more substantial results. A Danish study monitoring 600,000 women taking Zofran found that there isn’t a high risk. However, the same day that Danish doctors presented their evidence, another group of Danish doctors presented evidence to the contrary. That study indicates that after following over 900,000 pregnant women who took Zofran, there was a two-fold increase in infant heart defects.

Zofran Complaints and Lawsuits

Some pregnant women find that Zofran eases their nausea and vomiting significantly. Yet, numerous other women experience tragic adverse events. There are numerous birth injury lawsuits against GlaxoSmithKline (GSK), the manufacturer of Zofran. In July 2015, GSK filed a motion to consolidate all Zofran birth defect lawsuits pursuant to Multidistrict Litigation (MDL). In October 2015, the cases were consolidated into MDL No. 2657.

The motion to consolidate the Zofran pregnancy lawsuits was filed before the U.S. Judicial Panel on Multidistrict Litigation. The initial consolidation included at least twelve lawsuits alleging that fetal exposure to Zofran led to the development of various birth defects.

In anticipation of other lawsuits for the same general complaints, GSK requested that all current and future Zofran pregnancy lawsuits be consolidated before a single judge to ensure consistency and uniformity. The filing of this motion to consolidate is somewhat common practice in cases involving mass torts that involve similar allegations and issues.

Zofran Complaints Related to Off-Label Use

In 2012, the United States Department of Justice filed a lawsuit against GSK, which eventually ended in a $3 billion settlement. According to court documents, the government filed a claim against GSK after it engaged in promoting off-label use of several drugs, including Zofran.

GSK, however, did readily admit that using Zofran for nausea and vomiting in pregnant women has not been tested. Yet, that didn’t stop them from promoting off-label use of the drug.

“The safety of for use in human pregnancy has not been established… (The company) monitors and reports all adverse event reports,” a representative for GSK stated.

Zofran Complaints Reported in Canada

The safety of Zofran during pregnancy is an issue in Canada as well. A myriad of women have come forward after experiencing adverse effects after taking the medication. In fact, along with the risks of birth defects in their infants, other side effects that directly affect the mother include:

  • Rashes, hives, and itching
  • Shortness of breath
  • Body swelling
  • Constipation
  • Irregular heartbeat
  • Dizziness
  • Fainting
  • Difficulties in breathing and swallowing

At least 20 Canadian women experienced these severe side effects. One infant also died according to FDA records. Four infants that were born to mothers who used Zofran weighed around four pounds at birth. Six infants were said to have “fetal growth restriction.”

“Here is a drug not meant for pregnancy, given in pregnancy, with no data. So how do you know it’s safe for a baby? It’s an extrapolation that doctors do,” director of Motherrisk, Dr. Gideon Koren said.

Additional Studies Needed

Zofran is not approved for use during pregnancy by the FDA, but continues to be prescribed during pregnancy for morning sickness. GSK has received dozens of reports of adverse reactions to the drug since its approval in 1992. Additional research indicates conflicts in research regarding the safety of Zofran as compared to other similar medications. Questions regarding the safety of the medication have also resulted in serious inquiry into the ethics and marketing of GSK.

More studies are needed to substantiate the data from previous studies. Until then, always speak with your doctor regarding whether you should take Zofran while pregnant. Your physician has a legal obligation to inform you of any risks associated with medications prescribed to you.

Zofran for morning sickness: The risks are minimal

Last week, I had a patient who was really worked up during her ultrasound. At the end of the test, she asked me, “Does everything look OK?” I reassured her that everything looked as normal as it possibly could. But she seemed more anxious than usual.

When I asked her why, she said she’d seen a law firm’s commercial about birth defects and ondansetron (also known as Zofran®). She was upset because she had taken the medication for morning sickness – nausea and vomiting during pregnancy – and she was afraid the drug had harmed her baby.

Morning sickness can usually be managed with simple dietary changes. Sometimes, though, symptoms don’t go away with dietary changes alone. Doctors prescribe medications like ondansetron so you won’t get dehydrated or lose weight because of persistent morning sickness symptoms – which could cause a whole host of problems for you and your baby.

Is ondansetron safe?

Ondansetron was originally used to treat nausea associated with chemotherapy or surgery. In the United States, it rapidly became the most frequently prescribed drug for morning sickness. Estimates suggest one out of every four pregnant women receive a prescription for ondansetron.

Definitive studies evaluating the safety of medications, especially during pregnancy, are difficult to find. For ondansetron, physicians have relied on two imperfect methods of study. One method involves looking at registries of children born with birth defects and asking their mothers what medications they remember taking during their pregnancy. The other involves comparing outcomes in children whose mothers received prescriptions for ondansetron to those who received a prescription for another nausea medication. Clearly, neither method is sufficient to give us all the answers we need.

Original work suggested no increase in birth defects in women who took ondansetron early in pregnancy. However, more recent studies have raised concern over the possibility of a doubling in risk of cleft palate and heart defects in newborns exposed to ondansetron during pregnancy.

It’s important to note that another study using similar information did not show the same increased risk for birth defects. Until we have better information about the true risks, ondansetron should be tried only after other therapies have failed.

What are alternative nausea remedies?

I always advise women suffering from morning sickness to start with dietary changes and eliminate “triggers” that cause or worsen symptoms. Ninety percent of pregnant women with morning sickness symptoms see improvement just by altering their diets.

If that doesn’t work for you, there are two other methods I frequently suggest before prescribing ondansetron:

  • Ginger: Formulations that contain ginger can help reduce symptoms.
  • Vitamin B6 and doxylamine: A safe medication, made from these two ingredients, is approved to treat morning sickness symptoms.

However, if you have severe nausea and vomiting that does not improve with these methods or other nausea medication, your doctor may prescribe ondansetron. The medication can keep you from losing weight or becoming dehydrated, which can harm you and your baby.

If you are pregnant and have taken ondansetron or Zofran® during pregnancy, I want to reassure you that it likely has not affected your baby. Even if the increased risk for cleft palate or heart defects turns out to be true, the risk to your baby is still very, very small.

As always, I encourage you to ask questions. Talk to your doctor if you have concerns about taking ondansetron or Zofran®.

Ondansetron

Before taking ondansetron,

  • tell your doctor and pharmacist if you are allergic to ondansetron, alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), palonosetron (Aloxi, in Akynzeo), any other medications, or any of the ingredients in ondansetron products. Ask your pharmacist for a list of the ingredients.
  • tell your doctor if you are receiving apomorphine (Apokyn). Your doctor will probably tell you not to take ondansetron if you are receiving this medication.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol) or phenytoin (Dilantin); clarithromycin (Biaxin, in Prevpac); erythromycin (E.E.S., Erythrocin, others); fentanyl (Abstral, Actiq, Duragesic, Fentora, Lazanda, Onsolis, Subsys); lithium (Lithobid); medications for irregular heart beat; medications for mental illness; medications to treat migraines such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig); methylene blue; mirtazapine (Remeron); monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), linezolid (Zyvox), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); moxifloxacin (Avelox); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); and tramadol (Conzip, Ultram, in Ultracet). Your doctor may need to change the doses of your medications or monitor you more carefully for side effects. Many other medications may also interact with ondansetron, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
  • 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), or another type of irregular heart beat or heart rhythm problem, or if you have or have ever had low blood levels of magnesium or potassium in your blood, heart failure (HF; condition in which the heart cannot pump enough blood to other parts of the body), or liver disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking ondansetron, call your doctor.
  • if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that the orally disintegrating tablets contain aspartame that forms phenylalanine.

A brand-name drug maker such as GlaxoSmithKline (GSK) which makes Zofran has the exclusive right to sell and market that drug so long as it enjoys patent protection. Zofran enjoyed this privilege in the United States between January 4, 1991 and mid-2007. By that time the relevant patents had expired and the 180 day grace period following patent expiration had also lapsed.

There were several generic drug manufacturers who were ready and willing to make generic Zofran right away. It is important to remember that Zofran is just a brand name for the drug substance is chemically known as ondansetron. GSK copyrighted the name Zofran, and no other drug company–generic or otherwise–can use the name Zofran without its permission. That is why all the generic companies making this drug use the name ondansetron.

Compared with getting FDA approval for a brand new drug, the process for getting generic drug approval from the FDA a is relatively easy. The generic maker files what is called an Abbreviated New Drug Application (ANDA). To receive the FDA permission to sell a generic drug, that company’s ANDA must establish that the generic drug is identical to the brand name drug (also called the reference listed drug or RLD) with respect to: (1) route of administration, (2) active ingredients, (3) strength, (4) dosage form, and (5) conditions of use recommended in the labeling.

The FDA approves an ANDA application only if the generic drug is the “same as” the brand name drug. The FDA has defined “same as” to mean “identical.” Generic drugs’ labeling must also remain the “same as” the brand name drug at all times after the ANDA approval.

Since 2007, there have been nearly 50 approved ANDAs to sell generic Zofran (ondansetron). Sadly, and due to the FDA regulation requiring generic Zofran labeling to be the “same as” brand name Zofran, there is no difference in the generic drug information that is provided about expectant mothers taking Zofran during pregnancy. It is identical to the brand name label.

The FDA has recommended a change in the labeling rules that would give generic drug makers the latitude to change their labels whenever they think it is prudent to do so. A final decision on that rule will be made later this year.

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