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Medications to Prevent or Control CINV, RINV and PONV

Until recently, nausea and vomiting were thought to be unavoidable side effects of cancer treatment and surgery.

Not anymore!

Medicines that are easy to take and that can provide full 24-hour prevention of nausea and vomiting can make your life much easier. These medicines are less likely to interact with other medicines you may be taking for other conditions. Some of these medicines can be taken even if you have heart, liver or kidney problems - so don't forget to tell your doctor about any other conditions you might have.

While not all chemotherapy drugs and radiation treatments cause nausea and vomiting, and not all people undergoing surgery will suffer from PONV, there are medicines that can help you control and even prevent your CINV, RINV and PONV.

If you experience CINV, your doctor will prescribe a specific antiemetic medicine based on the type of CINV you have (acute, delayed, or anticipatory) and the chemotherapy you are receiving.

If you experience RINV, your doctor will prescribe a specific antiemetic medicine based on the dose of radiation you are being given and the area of your body being treated.

If you are having surgery, your doctor will prescribe a specific antiemetic medicine based on the type of surgery being performed.

Antiemetic medicines typically work by blocking the effects of certain chemicals in the body that activate the brain's vomiting center. For this reason, antiemetic medicines are best given immediately before chemotherapy or radiation therapy.

The chemicals that are blocked by these medications are also involved in other bodily functions. So, some of these drugs can be used to treat other conditions too.

Like most medicines, antiemetics are all slightly different and may work better for some patients than others. For instance:

• certain medicines must be taken more often than others to maintain control over the symptoms of nausea and vomiting.



• certain medicines may interact with other medication you're taking, lessening their impact or making you ill.



• each medicine may be broken down by the body in different ways. Therefore, patients with liver conditions should ask their doctor about which medication will be less likely to cause potential bad effects.

Like most medicines, antiemetic medicines have both good and bad side effects. It's very important to keep your doctor, nurse or pharmacist informed about any effects you experience - and always make sure you tell your doctor, nurse and pharmacist about other medicines you are taking.

Antiemetic drugs can be given by mouth, by injection, or by suppository. Sometimes, if vomiting is severe, these drugs cannot be taken by mouth. In these cases an injection or suppository may be used. If an antiemetic drug comes in more than one form, you should discuss the dosing for each different medicine with your doctor and choose the one that works best for you.

Schedule and dosage depends on the type and amount of chemotherapy or radiation you are receiving. Doses also may be based on your weight. Talk to your doctor about which dose is right for you.

Combination therapy, the combination of two or more antiemetic medications, may be more effective for some people.

Drugs Used to Treat CINV and RINV

Several classes are used to treat and possibly prevent CINV and RINV^*:

• Antihistamines
  
  
• Benzamides
  
  
• Benzodiazepines
  
  
• Butyrophenones
  
  
• Cannabinoids
  
  
• Corticosteroids
  
  
• Neurokinin-1-receptor Antagonists
  
  
• Phenothiazines
  
  
• Serotonin Antagonists
  

Antihistamines

Benadryl^® (diphenhydramine) and Atarax^® (hydroxyzine) are commonly used antihistamines to control nausea and vomiting. Antihistamines work by blocking the effects of the chemical histamine in the body, but they aren't very effective in stopping nausea and vomiting in people undergoing cancer treatment. Antihistamines are frequently used in combination with other groups of antiemetic drugs, such as benzamides, butyrophenones, and phenothiazines, because they can decrease some of the side effects of these medications. Benadryl^® - the most commonly used drug - is also available over-the-counter and can be given by mouth or injection. Mild relaxation, or drowsiness, is the most common side effect of antihistamines. Dry mouth and constipation also may occur.

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Benzamides

Reglan^® (metoclopramide) is part of the benzamide class of drugs, which work by blocking the effects of the chemical dopamine in the part of the brain that contains the vomiting center. At high doses, benzamides can also affect the chemical serotonin in the stomach. What's more, these drugs help move material out of the stomach more quickly, reducing nausea. Reglan^® can be taken by mouth or by injection, but injections are considered most effective, especially when high doses of the medication are given.

Benzamides can cause spasms, which make the whole body or individual parts of the body move uncontrollably. These extrapyramidal side effects may be more common in people under 30, but can happen at any age. In addition, this side effect is more common when the drugs are given at high doses and taken orally. Benadryl^® can help ease some of these unwanted effects. Diarrhea, drowsiness, anxiety, and depression are other effects of the benzamides.

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Benzodiazepines

Ativan^® (lorazepam) and Xanax^® (alprazolam) are two popular benzodiazepines that have been used as antiemetics. Benzodiazepines are a group of drugs that are used as tranquilizers, , usually to treat problems with anxiety. They work by calming the brain, but, like antihistamines, benzodiazepines are not very effective for CINV and RINV when used alone. They are often combined with other antiemetic medicines like serotonin antagonists and corticosteroids to increase their effectiveness.

The benzodiazepines are effective when given by mouth or injection and generally do not cause any problems when used for short amounts of time. Drowsiness is the most common side effect.

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Butyrophenones

Haldol^® (haloperidol) and Inapsine^® (droperidol) are members of the butyrophenone class of antiemetics that can used to treat CINV and RINV. Haldol^® is normally used as an antipsychotic drug, and Inapsine^® helps produce anesthesia. They work by blocking the effects of the chemical dopamine in the body, but are only somewhat effective as antiemetic drugs. The butyrophenones work best when given by injection; in fact, Inapsine^® is only available in liquid form for injection.

Like the benzamides, butyrophenones may cause troublesome spasms (extrapyramidal side effects), but this problem is not as common in the butyrophenones. Other side effects include drowsiness, reduced blood pressure, and an increase in heart rate.

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Cannabinoids

Marinol^® (dronabinol), from the cannabinoid class of antiemetic drugs, can be used for CINV. The cannabinoids do not work by blocking the effects of any chemicals in the body. Rather, they work in an area of the brain that is thought to be partly responsible for causing nausea and vomiting.

Cannabinoids are effective when taken by mouth. They give relief to people whose chemotherapy drug causes minimal nausea and vomiting. Mild drowsiness, dizziness, and euphoria (a state of cheerfulness and well-being) are the common side effects of cannabinoids.

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Corticosteroids

Decadron^® (dexamethasone) and Medrol^® (methylprednisolone) are two of the most commonly used corticosteroids, or steroids, used to treat CINV and RINV. Steroids are antiemetic drugs; they can also improve the antiemetic characteristics of other medications. Because of this, steroids are frequently used alone or with other antiemetic drugs to treat CINV and RINV. Steroids are most often used with serotonin antagonists or Reglan^®.

Even though it is not known exactly how steroids work to control nausea and vomiting, it is clear that they reduce the effects of prostaglandins, chemicals that help control blood pressure and other functions. Steroids are also used to treat asthma, allergic reactions, and other conditions.

Steroids are effective when given by mouth or injection; they are often injected before chemotherapy. The most common effects of steroids are upset stomach, anxiety, or trouble sleeping. Increased blood sugar (hyperglycemia) also may be a problem when a steroid is used for several days. This may be a concern for people with diabetes.

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Neurokinin-1-receptor Antagonists (NK₁-receptor Antagonists)

Emend^® (aprepitant) is the first NK₁-receptor Antagonist to be introduced for the treatment of CINV. This type of drug should be used in combination with other antiemetic drugs – namely a serotonin antagonist and a corticosteroid – in order to provide antiemetic protection from chemotherapy that causes nausea and vomiting.

NK₁-receptor antagonists work by blocking the actions of a chemical, substance P, which is thought to activate a specific pathway in the brain that causes nausea and vomiting.

The choice of which serotonin antagonist and corticosteroid to combine with Emend^® is important, as certain medications may interact and produce unwanted effects ( drug–drug interactions). Careful consideration is needed to determine the most appropriate combination of antiemetic drugs. For instance, the recommended doses of the corticosteroids Decadron^® and Medrol^® should be decreased when they are combined with Emend^®. The most appropriate serotonin antagonist for combination with Emend^® is the one with the least risk for producing a drug–drug interaction. However, some of the serotonin antagonists may interact with Emend^® or other drugs – either through known drug–drug interactions or due to the drug remaining in the body for a long time. Presently, the only serotonin antagonists that have been studied in combination with Emend^® are Kytril^®, Zofran^® and Aloxi ™.

Emend^® is given by mouth. Fatigue is the most common side effect reported with this drug.

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Phenothiazines

Compazine^® (prochlorperazine) is the most commonly used medication from the phenothiazine class of antiemetics. Phenothiazines block the chemical dopamine from entering the brain's vomiting center. But these drugs are not very effective for CINV. Phenothiazines work better at higher doses, which increase the risk of side effects. People taking phenothiazines may experience spasms, tremors, and other side effects. The drugs may also cause drowsiness and reduced blood pressure. Compazine^® can be given by mouth, by injection or as a suppository. The drug is usually given three or four times a day.

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Serotonin Antagonists

The introduction of the Serotonin Antagonists was a major development in the treatment of CINV, RINV and PONV, and they are the most commonly prescribed drugs for CINV and RINV. Kytril^® (granisetron), Zofran^® (ondansetron), Anzemet^® (dolasetron), Navoban^® (tropisetron) and Aloxi ™ (palonosetron) are five medications available in this class of antiemetic drugs.

These medications work by blocking the actions of a chemical, serotonin, in the vomiting center of the brain and in the intestine. They are very effective in treating CINV, RINV and PONV.

Unlike many of the other antiemetic drugs, serotonin antagonists do not cause spasms or similar movement problems because they do not affect the chemical dopamine. Serotonin antagonists are well tolerated. The most common side effects associated with their use are mild headache, fever, and constipation or diarrhea. However, some serotonin antagonists have been associated with changes in certain heart functions. In patients with compromised heart function, it may be advisable to consider using a serotonin antagonist that does not have a heart warning/precaution in its product information (e.g. Kytril^®). If you are concerned about this, talk to your doctor about which serotonin antagonist is best for you.

Certain serotonin antagonists are known to be involved in drug–drug interactions. If you are receiving a number of medications at the same time, then it may be advisable to use a serotonin antagonist that has not been associated with any drug–drug interactions (e.g. Kytril^®).

The serotonin antagonists can be taken by mouth or by injection (except Aloxi ™, which can only be administered by injection). The oral forms work as well, or even better, than the injections, and are more convenient.

The different serotonin antagonists remain in the body for different amounts of time. The most convenient agent is the one that will produce a long lasting antiemetic effect from a single dose. However, an overly long duration in the body (for example Aloxi ™has been measured in the body up to 128 hours following administration) may increase the potential for drug–drug interactions with other agents that are being taken, which may include other antiemetic agents and chemotherapy drugs. Alternatively, an antiemetic that only remains in the body for a short amount of time (for example the effects of Zofran^® have only been measured to last for approximately 9 hours) may need to be given multiple times in order to provide antiemetic action over the entire course of treatment

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Ask your doctor the following questions about medicines to control your nausea and vomiting:

• Can I have a medicine that is easy for me to take (especially if I am already taking other medicines)?



• Can I have a medicine that is least likely to interact with other medicines I am taking?



• Is my medicine OK to take if I have other conditions (such as a heart, liver or kidney condition)?



• How many times a day do I need to take my medicine?



• What happens if I forget to take it on time?



• Will I be free of symptoms day and night?



• Who should I tell if my medicine doesn't work?



• Are there any side effects from the medicine?



• What if it begins to wear off and I feel sick? Can I take more?



• What alternative medicines are there if my medicine does not provide full 24-hour control or relief of my nausea and vomiting (for example, if I wake up at night feeling sick, or feel sick before it's time to take my next dose of medicine).

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