Ondansetron (Zofran) vs. promethazine (Phenergan): What's the difference?

What are ondansetron and promethazine?

Ondansetron is an anti-nausea medication used to prevent nausea and vomiting caused by cancer chemotherapy. It is also used to prevent vomiting and nausea after surgery. Chemotherapy drugs increase secretion of serotonin, which stimulates serotonin (5-HT3) receptors in the brain, causing nausea and vomiting. Ondansetron works by selectively blocking serotonin (5-HT3) receptors, reducing the effect of increased serotonin due to chemotherapy.

Promethazine is a phenothiazine in the same drug class as chlorpromazine (Thorazine) and trifluoperazine (Stelazine). Unlike other phenothiazines, promethazine is not used as an anti-psychotic. It is used as an antihistamine, sedative, and antiemetic (anti-nausea). The body releases histamine during several types of allergic reactions. When histamine binds to its receptors on cells, it stimulates changes within the cells that lead to sneezing, itching, and increased mucus production. Antihistamines such as promethazine compete with histamine for one of the receptors for histamine (the H1 receptor) on cells. However, when the antihistamines bind to the receptors they do not stimulate the cells. Instead, they prevent histamine from binding and stimulating the cells. Promethazine also blocks the action of acetylcholine (anticholinergic effect), and this may explain its benefit in reducing the nausea of motion sickness. It is used as a sedative because it causes drowsiness as a side effect.

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What are the side effects of ondansetron and promethazine?

Ondansetron

Side effects of ondansetron are

Some individuals may develop abnormal heart rate and rhythm.

Promethazine

Promethazine causes sedation, confusion, and disorientation. In children less than 2 years old, it can depress respiration and lead to death. Therefore, it should not be used in children less than 2 years old. Dizziness may also occur. Ironically, promethazine sometimes stimulates patients, particularly children. Such stimulation may be manifest by restlessness, inability to sleep, heart palpitations or even seizures.

Other side effects include anticholinergic side effects such as:

Extrapyramidal symptoms (EPS) may occur. EPS are categorized as dystonic reactions (alterations in muscle tone), sharp, involuntary muscle movements (often limited to one muscle or muscle group), akathisia (subjective restlessness), and Parkinsonism. Parkinsonian symptoms are more common in older persons, whereas children more often develop involuntary muscle movement reactions. Dystonic reactions are most commonly seen during the first week of treatment. Restlessness and Parkinsonian symptoms usually develop days to weeks after starting therapy.

A serious complex called neuroleptic malignant syndrome (NMS) can occur in patients receiving phenothiazines. NMS consists of high body temperature, severe EPS, changes in consciousness and mental status, and increased heart rate with low or high blood pressure. NMS occurs more frequently in young men and in persons who are dehydrated.

Rarely, blood cell disorders can occur; low white cell counts can lead to infections.

Phenothiazines such as promethazine can cause skin hyperpigmentation (darkening) but usually only after prolonged use. The effect usually is restricted to areas of the body exposed to sunlight. Thus, people who need long-term treatment with promethazine should either keep out of the sun or use effective sunscreens.

Phenothiazines can cause blurred vision, difficulty with nighttime vision, or changes in color vision.

Liver damage has been reported rarely with phenothiazines. Jaundice is possible. Jaundice also may occur in newborns of mothers who receive phenothiazines during pregnancy.

Phenothiazines such as promethazine block dopamine receptors. This effect can lead to increases in blood levels of prolactin, a hormone involved in lactation (formation of breast milk). As a result, phenothiazines can cause the breast to produce fluid ("milk") even when a woman is not pregnant.

Additionally, phenothiazines can cause:

  • missed menstrual periods,
  • breast enlargement or tenderness,
  • loss of sexual drive,
  • impotence,
  • inability to ejaculate, and
  • priapism, and
  • weight gain.

What is the dosage of ondansetron vs. promethazine?

Ondansetron

Dosage for adults:

  • Highly nauseating chemotherapy: 24 mg orally dissolved on tongue 30 minutes prior to start of a single-day chemotherapy.
  • Moderately nauseating chemotherapy: Take 8 mg tablet 30 minutes prior to chemotherapy and repeat in 8 hours, then 8 mg every 12 hours for 1 to 2 days after chemotherapy.
  • Radiation-induced nausea and vomiting: Take 8 mg orally 1 to 2 hours prior to radiation and every 8 hours after first dose, as needed.
  • Post-surgery nausea and vomiting: 16 mg orally 1 hour before anesthesia.

Dosage for children:

  • Moderately nauseating chemotherapy (12 years and older): 8 mg orally prior to chemotherapy and repeat in 8 hours, then 8 mg every 12 hours for 1 to 2 days after chemotherapy.
  • Moderately nauseating chemotherapy (4 to 11 years): 4 mg orally 30 minutes prior to chemotherapy and repeat in 4 and 8 hours after the first dose, then every 8 hours for 1 to 2 days after chemotherapy.
  • Not recommended for children under 4 years old.

Promethazine

  • Allergic reactions are treated with 6.25-25 mg orally 3 times daily. A single 25 mg dose administered at bedtime also may suffice. A 25 mg injection is also used.
  • Nausea and vomiting may be managed with 12.5-25 mg administered orally by injection every 4-6 hours as needed.
  • Doses of 25-50 mg by injection are used for sedation before or after surgery.
  • For prevention of motion sickness, 25 mg is used 30 to 60 minutes before the motion begins and then every 8 to 12 hours as needed. Oral, rectal and injectable doses are similar.
  • Promethazine injections are used when the oral route is not possible (for example, with severe vomiting).
  • Tablets may be taken with or without food.
  • Suppositories are unwrapped and moistened with water before insertion into the rectum. If the suppository is too soft from being stored in a warm place, it may be chilled in the refrigerator for 20 to 30 minutes or placed in cold water before the wrapper is removed.

What drugs interact with ondansetron and promethazine?

Ondansetron

Ondansetron and apomorphine should not be used together due to sudden lowering in blood pressure and loss of consciousness.

Phenytoin, carbamazepine, and rifampin can increase ondansetron elimination and decrease blood levels, possibly lowering the effects of ondansetron.

Dronedarone can increase blood levels of ondansetron by reducing its breakdown in the liver. This may increase side effects of ondansetron. This combination may also increase the risk of abnormal heartbeats.

Promethazine

CNS Depressants

Promethazine may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as:

These agents should be avoided or administered in reduced dosage to patients receiving promethazine. When given concomitantly with promethazine, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of promethazine relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.

Epinephrine

Because of the potential for promethazine to reverse epinephrine’s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine overdose.

Anticholinergics

Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

Monoamine Oxidase Inhibitors (MAOIs)

Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly.

Inform your doctor and pharmacist of all the medications you take, including prescription and over-the-counter drugs and herbal supplements.

Are ondansetron and promethazine safe to use while pregnant or breastfeeding?

Ondansetron

There are no adequate studies of ondansetron in pregnant women to determine its safe and effective use during pregnancy.

It is not known whether ondansetron enters breast milk; therefore, it is best for nursing mothers to be cautious before using it.

Promethazine

There are no adequate studies of promethazine in pregnant women. Administration of promethazine within two weeks of delivery may affect platelet function in the newborn.

It is not known whether promethazine is excreted in breast milk.

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Summary

Ondansetron, an anti-nausea medication, and promethazine, a phenothiazine, are used to prevent nausea and vomiting. Promethazine is also used as an antihistamine and sedative. Side effects of both medications include drowsiness and sedation, constipation, and dizziness.

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Medically Reviewed on 7/29/2019
References
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