Fosaprepitant

What is Fosaprepitant?

• Fosaprepitant (Emend) for injection is a substance P/neurokinin-1 (NK1) receptor antagonist used with other medicines that treat nausea and vomiting in patients 18 years of age and older to prevent nausea and vomiting caused by certain anti-cancer (chemotherapy) medicines.

Fosaprepitant

Fosaprepitant-3D-spacefill

Fosaprepitant-3D-balls

What are the uses of this medicine?

Fosaprepitant (Emend) for injection used in adults, in combination with other antiemetic agents, for the prevention of:

• acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin.
• delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

Limitations of use:

• Fosaprepitant for injection is not used to treat nausea and vomiting that you already have.
• It is not known if fosaprepitant for injection is safe and effective in children less than 6 months of age.

How does this medicine work?

• Fosaprepitant is a prodrug of aprepitant and accordingly, its antiemetic effects are attributable to aprepitant.
• 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:

• who are hypersensitive to any component of the product.
• taking pimozide.

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Be sure to mention any of the following:

• pimozide (Orap)
• anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); certain antifungals such as itraconazole (Onmel, Sporanox) and ketoconazole
• benzodiazepines such as alprazolam (Xanax), midazolam, and triazolam (Halcion)
• certain cancer chemotherapy medications such as ifosfamide (Ifex), vinblastine (Velban), and vincristine (Marqibo)
• carbamazepine (Tegretol, Teril, others)
• clarithromycin (Biaxin, in Prevpac)
• diltiazem (Cardizem, Cartia, Diltzac, others)
• certain HIV protease inhibitors such as nelfinavir (Viracept) and ritonavir (Norvir, in Kaletra, Technivie, Viekira Pak)
• nefazodone
• steroids such as dexamethasone and methylprednisolone (Depo-medrol, Medrol, Solu-medrol)
• phenytoin] (Dilantin, Phenytek)
• rifampin (Rifadin, Rimactane, in Rifamate, Rifater)

Is this medicine FDA approved?

• Fosaprepitant was developed by Merck & Co. and was approved for medical use in the United States, and in the European Union in January 2008.

How should this medicine be used?

Recommended dosage:

• Administer fosaprepitant for injection as an intravenous infusion; complete the infusion approximately 30 minutes prior to chemotherapy.

1-Day Dosing Regimen:

• Adults: 150 mg on Day 1.

3-Day Dosing Regimen:

• Fosaprepitant for injection (115 mg) is administered on Day 1 as an infusion over 15 minutes initiated approximately 30 minutes prior to chemotherapy.
• Aprepitant capsules (80 mg) are given orally on Days 2 and 3.
• Fosaprepitant for injection and aprepitant capsules are part of a regimen to prevent nausea and vomiting induced by HEC or MEC that includes a corticosteroid and a 5-HT3 antagonist.

Administration: In Adults 18 years of age and older:

• Fosaprepitant for injection will be given on Day 1 of chemotherapy treatment.
• It will be given to you by intravenous (IV) infusion in your vein about 50 to 60 minutes before you start your chemotherapy treatment.

or

Fosaprepitant for injection 115 mg given along with capsules of aprepitant.

• Day 1 (Day of chemotherapy): Fosaprepitant for injection 115 mg will be given to you by intravenous (IV) infusion in your vein about 30 minutes before you start your chemotherapy treatment.
• You will get a prescription for two capsules of aprepitant
• Day 2 and Day 3 (the two days after chemotherapy): Take one 80 mg capsule of aprepitant (white) by mouth, each morning for the 2 days after your chemotherapy treatment.

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

This medicine is available in fallowing doasage form:

• As Fosaprepitant for Injection: 115 mg and 150 mg fosaprepitant, lyophilized powder in single-dose vials for reconstitution.

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:

• tiredness
• diarrhea
• low white blood cell and red blood cell counts
• weakness
• feeling weak or numb in your arms and legs
• painful, difficult, or changes in your digestion (dyspepsia)
• urinary tract infection
• pain in your arms and legs

Fosaprepitant for injection may cause serious side effects, including:

• Serious allergic reactions
• Severe skin reactions, which may include rash, skin peeling, or sores, may occur
• Infusion site reactions

What special precautions should I follow?

• Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, during or soon after infusion of fosaprepitant have occurred. Monitor patients during and after infusion. If hypersensitivity reactions occur, discontinue the infusion and administer appropriate medical therapy. Do not reinitiate fosaprepitant for injection in patients who experience these symptoms with previous use.
• Infusion site reactions (ISRs) have been reported with the use of fosaprepitant for injection. Avoid infusion of fosaprepitant for injection into small veins or through a butterfly catheter. If a severe ISR develops during infusion, discontinue the infusion and administer appropriate medical treatment.
• Co-administration of fosaprepitant for injection with warfarin, may result in a clinically significant decrease in the International Normalized Ratio (INR) of prothrombin time. Monitor the INR in patients on chronic warfarin therapy in the 2-week period, particularly at 7 to 10 days, following initiation of fosaprepitant for injection with each chemotherapy cycle.
• Upon co-administration with fosaprepitant for injection, the efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of fosaprepitant for injection. Advise patients to use effective alternative or back-up methods of contraception during treatment with fosaprepitant for injection and for 1 month following administration of fosaprepitant for injection.
• It is not known if fosaprepitant for injection passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you receive fosaprepitant for injection.

What to do in case of emergency/overdose?

In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• In the event of overdose, fosaprepitant for injection should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of fosaprepitant for injection, drug-induced emesis may not be effective in cases of fosaprepitant overdosage.
• Aprepitant is not removed by hemodialysis.

Can this medicine be used in pregnancy?

• There are insufficient data on use of fosaprepitant for injection in pregnant women to inform a drug associated risk.
• It is not known if fosaprepitant for injection 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 backup method of birth control that does not contain hormones, such as condoms and spermicides, during treatment with fosaprepitant for injection and for 1 month after receiving fosaprepitant for injection.

Can this medicine be used in children?

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

What are the active and inactive ingredients in this medicine?

• Active ingredient: fosaprepitant dimeglumine
• Inactive ingredients: edetate disodium, polysorbate 80, lactose anhydrous, sodium hydroxide and/or hydrochloric acid (for pH adjustment)

Who manufactures and distributes this medicine?

Manufactured for:

• Mylan Institutional LLC
• Rockford, IL U.S.A.

Manufactured by:

• Mylan Laboratories Limited
• Bangalore, India

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

• Fosaprepitant for Injection vials must be refrigerated, store at 2° to 8°C (36° to 46°F).
• The reconstituted final drug solution is stable for 24 hours at ambient room temperature [at or below 25°C (77°F)].

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

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