Aprepitant

What is Aprepitant?

• Aprepitant (Emend) is a substance P/neurokinin 1 (NK1) receptor antagonist used with other drugs to prevent nausea and vomiting caused by chemotherapy. It is also used to prevent nausea and vomiting after surgery.

What are the uses of this medicine?

Aprepitant (Emend) is a prescription medicine used:

• with other medicines that treat nausea and vomiting in patients 12 years of age and older to prevent nausea and vomiting caused by certain anti-cancer (chemotherapy) medicines
• In adults to prevent nausea and vomiting after surgery

Limitations of use:

• Aprepitant capsules are not used to treat nausea and vomiting that you already have.
• Aprepitant capsules should not be used continuously for a long time (chronic use).

How does this medicine work?

• Aprepitant (a pre’ pi tant) is a complex molecule with a central morpholine core and two ring carbons and fluorinated phenyl groups.
• Aprepitant acts as a substance P antagonist blocking the neurokinin 1 (NK1) receptor, which is found in the central nervous system and induces the vomiting reflex when activated by substance P.
• Aprepitant has been shown to inhibit both acute and delayed nausea and vomiting associated with cancer chemotherapy and surgical procedures.
• It appears to act synergistically with serotonin type 3 (5-HT3) receptor blockers.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• are allergic to aprepitant or any of the ingredients in aprepitant capsules.
• are taking pimozide

What drug interactions can this medicine cause?

• Aprepitant capsules may affect the way other medicines work, and other medicines may affect how aprepitant capsules work causing serious side effects.
• Efficacy of contraceptives may be reduced during administration of and for 28 days following the last dose of aprepitant. Use effective alternative or back-up methods of contraception.
• Aprepitant is contraindicated with Pimozide.

Is this medicine FDA approved?

• Aprepitant was approved for use in the United States in 2003 and current indications include prevention of postoperative and chemotherapy associated nausea and vomiting.

How should this medicine be used?

Recommended dosage: For Prevention of Chemotherapy Induced Nausea and Vomiting (CINV):

• Aprepitant capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3.
• Administer aprepitant 1 hour prior to chemotherapy on Days 1, 2, and 3.
• If no chemotherapy is given on Days 2 and 3, administer aprepitant in morning.

For postoperative nausea and vomiting (PONV):

• Adults: 40 mg aprepitant capsules within 3 hours prior to induction of anesthesia.

Administration:

• Swallow aprepitant capsules whole.
• Aprepitant capsules may be taken with or without food.
• If you take too much aprepitant, call your healthcare provider, or go to the nearest hospital emergency room.
• Aprepitant capsules are taken as 3 doses over 3 days - starting on the day you have chemotherapy, and for the following 2 days.

In adults, your healthcare provider may prescribe aprepitant capsules for you:

• Capsules of aprepitant by mouth for all 3 doses:
• You should get a package that has 3 capsules of aprepitant.
• Day 1 (Day of chemotherapy): Take one 125 mg capsule of aprepitant (white and pink) by mouth 1 hour before you start your chemotherapy treatment.
• Day 2 and Day 3: Take one 80 mg capsule of aprepitant (white) by mouth 1 hour before you start your chemotherapy treatment. If no chemotherapy treatment is given on Days 2 and 3, aprepitant capsules should be taken in the morning.

In children 12 years of age and older who can swallow capsules by mouth, aprepitant is prescribed as capsules of aprepitant by mouth for all 3 doses:

• You should get a package that has 3 capsules of aprepitant capsules.
• Day 1 (Day of chemotherapy): Take one 125 mg capsule of aprepitant capsules (white and pink) by mouth 1 hour before you start your chemotherapy treatment.
• Day 2 and Day 3: Take one 80 mg capsule of aprepitant (white) by mouth 1 hour before you start your chemotherapy treatment. If no chemotherapy treatment is given on Days 2 and 3, aprepitant should be taken in the morning.

If you are an adult and are having surgery:

• Your doctor will prescribe a 40 mg capsule of aprepitant for you before surgery. Take aprepitant within 3 hours before surgery.
• Follow your healthcare provider’s instructions about restrictions on eating and drinking before surgery.
• If you take the blood thinner medicine warfarin sodium (COUMADIN®, JANTOVEN®), your healthcare provider may do blood tests after you take aprepitant capsules to check your blood clotting.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Aprepitant Capsules, USP: 40 mg; 80 mg; 125 mg

This medicine is available in fallowing brand namesː

• Emend

What side effects can this medication cause?

The most common side effects of this medicine include: For Prevention of Chemotherapy Induced Nausea and Vomiting (CINV): In adults:

• tiredness, diarrhea, weakness, indigestion, stomach (abdominal) pain, hiccups, decrease in white blood cell count, dehydration, and changes in liver function tests.

For postoperative nausea and vomiting (PONV): In adults:

• constipation and low blood pressure (hypotension)

In children 6 months to 17 years of age:

• decrease in white blood cell count, headache, diarrhea, decreased appetite, cough, tiredness, decrease in red blood cell count, dizziness, and hiccups

What special precautions should I follow?

• Instruct patients on chronic warfarin therapy to follow instructions from their healthcare provider regarding blood draws to monitor their INR during the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day regimen of aprepitant with each chemotherapy cycle, or following administration of a single 40-mg dose of aprepitant for the prevention of postoperative nausea and vomiting.
• Advise patients that administration of aprepitant may reduce the efficacy of hormonal contraceptives. Instruct patients to use effective alternative or back-up methods of contraception (such as condoms and spermicides) during treatment with aprepitant and for 1 month following the last dose of aprepitant.
• Hypersensitivity reactions, including anaphylaxis, have been reported in patients taking aprepitant. Advise patients to stop taking aprepitant and seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction, such as hives, rash and itching, skin peeling or sores, or difficulty in breathing or swallowing.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• Drowsiness and headache

Management of overdosage:

• In the event of overdose, aprepitant should be discontinued and general supportive treatment and monitoring should be provided.
• Because of the antiemetic activity of aprepitant, drug-induced emesis may not be effective in cases of aprepitant overdosage.
• Aprepitant is not removed by hemodialysis.

Can this medicine be used in pregnancy?

• It is not known if aprepitant capsules can harm your unborn baby.
• Women who use birth control medicines containing hormones to prevent pregnancy (birth control pills, skin patches, implants, and certain IUDs) should also use a back-up method of birth control that does not contain hormones, such as condoms and spermicides, during treatment with aprepitant capsules and for 1 month after your last dose of aprepitant capsules.

Can this medicine be used in children?

• The safety and effectiveness of aprepitant for the prevention of nausea and vomiting associated with HEC or MEC have not been established in patients less than 6 months.
• The safety and effectiveness of aprepitant have not been established for the prevention of postoperative nausea and vomiting in pediatric patients.

What are the active and inactive ingredients in this medicine?

• Active ingredient: aprepitant
• Inactive ingredients: colloidal silicon dioxide, hydroxyethyl cellulose, microcrystalline cellulose, mannitol, poloxamer, povidone, sodium stearyl fumarate, vitamin E polyethylene glycol succinate, and purified water. The capsule shell excipients are gelatin, sodium lauryl sulphate and titanium dioxide. The 40-mg capsule shell also contains iron oxide yellow, and the 125-mg capsule also contains FD&C Red #3. Non-volatile solvents in the imprinting ink are shellac, iron oxide black and potassium hydroxide.

Who manufactures and distributes this medicine?

Manufactured by:

• Glenmark Pharmaceuticals Limited
• Plot No. 2, Phase-2, Pharma Zone SEZ
• Pithampur, Dist.-Dhar
• Madhya Pradesh, India

Manufactured for:

• Glenmark Pharmaceuticals Inc., USA
• Mahwah, NJ

What should I know about storage and disposal of this medication?

• Store at room temperature, between 68°F to 77°F (20°C to 25°C).

• Dailymed label info on Aprepitant
• FDA Aprepitant

Aprepitant Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

The following are antidepressant subclasses and drugs

MAO Inhibitors Isocarboxazid, Phenelzine, Tranylcypromine

SNRIs Duloxetine, Levomilnacipran, Venlafaxine

SSRIs Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Vilazodone, Vortioxetine

Tricyclics Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine

Miscellaneous Bupropion, Flibanserin, Mirtazapine, Nefazodone, Trazodone

Antidiarrheal agents

Antidiarrheal agents include bulk forming agents, hydroscopic agents, bile acid resins, bismuth, inhibitors of intestinal motility, non-absorbed antibiotics and hormones. Bulk forming agents include methylcellulose; hydroscopic agents include pectin and kaolin; bile acid resins are cholestyramine, colestipol and colesevalam; inhibitors of intestinal motility include opioids such as diphenoxylate and loperamide. Antibiotics include rifamycin and rifaximin which are non-absorbed and are used for travelers' diarrhea. Hormones with antidiarrheal activity include octretide and somatostatin. Most antidiarrheal agents are active locally in the small intestine and colon and are largely not absorbed. Some, however, have been implicated in rare causes of liver injury (senna, cascara, cholestyramine). Telotristat is a relatively new agent that inhibits the synthesis of serotonin and is used specifically for the diarrhea of carcinoid syndrome.

• Cholestyramine
• Colesevelam
• Colestipol
• Crofelemer
• Difenoxin
• Diphenoxylate
• Kaolin
• Loperamide
• Methylcellulose
• Octreotide
• Pectin
• Rifamycin
• Rifaximin
• Somatostatin
• Telotristat

Antiemetics are a diverse group of medications that act at different points in the pathways that regulate nausea and vomiting. These include antihistamines, anticholinergic agents, phenothiazines, serotonin type 3 receptor blockers, centrally acting benzamides, cannabinoid receptor agonists, substance P antagonists and miscellaneous.

Anticholinergic Agents

• Hyoscyamine, Methscopolamine, Scopolamine

Antihistamines

• Cyclizine, Dimenhydrinate, Hydroxyzine, Meclizine, and Promethazine

Cannabinoid Receptor Agonists

• Dronabinol, Nabilone, Tetrahydrocannabinol
• Phenothiazines [See Antipsychotic Agents]
• Chlorpromazine, Prochlorperazine

Serotonin 5-HT3 Receptor Antagonists

• Alosetron, Dolasetron, Granisetron, Ondansetron, Palonosetron

Substance P/Neurokinin 1 Receptor Antagonists

• Aprepitant, Fosaprepitant, Rolapitant

Miscellaneous

• Dexamethasone, Metoclopramide, Trimethobenzamide

Acid peptic disease/antiulcer agents that include antacids, the histamine type 2 receptor blockers (H2 blockers), and the proton pump inhibitors (PPIs). These agents are some of the most commonly taken medications and are very well tolerated, most being available both by prescription and over-the-counter. While many of these drugs are approved for use in duodenal and gastric ulcer disease, their major use is for acid reflux and indigestion.

Histamine H2 Receptor Antagonists (H2 Blockers) Cimetidine, Famotidine, Nizatidine, Ranitidine

Proton Pump Inhibitors

• Dexlansoprazole, Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole

Cathartics, laxatives or agents for constipation include bulk forming agents, osmotic agents, stool wetting agents, nonspecific stimulants, prokinetic agents and agents that increase fluid secretion. Many of these therapies are not systemically absorbed and none are considered particularly hepatotoxic. Naldemedine and naloxegol are opioid antagonists and are used to treat the constipation associated with opioid use.

• Bisacodyl
• Cascara Sagrada
• Castor Oil
• Docusate
• Fiber, Bran
• Lactulose
• Magnesium Sulfate
• Methylcellulose
• Naldemedine (Opioid Antagonist)
• Naloxegol (Opioid Antagonist)
• Plecanatide (for Chronic Idiopathic Constipation)
• Prucalopride (for Chronic Idiopathic Constipation)
• Senna

Inflammatory bowel disease encompasses several disorders, most commonly ulcerative colitis and Crohn colitis. Agents can be classified as 5-aminosalicyclic acid (5-ASA) based agents, immunosuppressive drugs, antitumor necrosis factor agents, corticosteroids, antibiotics and miscellaneous.

5-Aminosalicyclic Acid (5-ASA) Derivatives

• Balsalazide, Mesalamine, Olsalazine, Sulfasalazine

Immunosuppressive Agents

• Azathioprine, Mercaptopurine, Methotrexate

Tumor Necrosis Factor Antagonists

• Adalimumab, Certolizumab, Golimumab, Infliximab

Miscellaneous

• Metronidazole, Natalizumab, Vedolizumab

Irritable Bowel Syndrome Agents Antimuscarinics/Antispasmodics [See Anticholinergic agents

• Dicyclomine, Glycopyrrolate, Hyoscyamine, Methscopolamine

Prokinetic Agents - See Serotonin 5-ht4 receptor agonists Alosetron, Cisapride, Domperidone, Linaclotide, Lubiprostone, Metoclopramide, Plecanatide, Prucalopride, Tegaserod

Other

• Eluxadoline