Plecanatide

What is Plecanatide?

• Plecanatide (Trulance) is a guanylate cyclase-C agonist, used for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation.

Plecanatide sequence

What are the uses of this medicine?

Plecanatide (Trulance) is a prescription medicine used in adults to treat:

• a type of constipation called chronic idiopathic constipation (CIC). Idiopathic means the cause of the constipation is unknown.
• irritable bowel syndrome with constipation (IBS-C).

How does this medicine work?

• Plecanatide (ple kan’ a tide) is synthetic analogue of uroguanylin, the endogenous guanylate cyclase-C receptor agonist which acts by increasing intracellular concentrations of cyclic guanosine monophosphate (cGMP) which activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel.
• The CFTR ion channel stimulates secretion of chloride and bicarbonate into the lumen of the intestine which increases intraluminal fluid and speeds intestinal transit.
• In several prelicensure clinical trials, plecanatide therapy was associated with increases in the number of spontaneous bowel movements, improved stool consistency and alleviation of symptoms of chronic constipation.

Who Should Not Use this medicine ?

This medicine cannot be used in:

• Patients less than 6 years of age due to the risk of serious dehydration.
• Patients with known or suspected mechanical gastrointestinal obstruction.

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.

Is this medicine FDA approved?

• Plecanatide was approved for therapy of chronic idiopathic constipation in adults in 2017, the second guanylate cyclase agonist approved for this indication in the United States, the first being linaclotide.
• Plecanatide is available in tablets of 3 mg under the brand name Trulance.

How should this medicine be used?

Recommended dosage: The recommended adult dosage of Trulance is:

• CIC: 3 mg taken orally once daily.
• IBS-C: 3 mg taken orally once daily.

Administration:

• Plecanatide comes as a tablet to take by mouth.
• Take Trulance exactly as your doctor tells you to take it.
• Take Trulance by mouth, 1 time each day with or without food.
• If you miss a dose, skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.
• Trulance tablets should be swallowed whole.
• Adults who cannot swallow Trulance tablets whole may crush the Trulance tablet and mix with applesauce or dissolve Trulance in water before swallowing.
• Trulance tablets may also be taken with water by adults through a nasogastric or gastric feeding tube.
• It is not known if Trulance is safe and effective when crushed and mixed with other foods or dissolved in other liquids.

Taking Trulance in applesauce:

• Crush the Trulance tablet in a clean container until it is a powder and mix with 1 teaspoon of room temperature applesauce.
• Swallow all of the Trulance and applesauce mixture right away.
• Do not keep the Trulance and applesauce mixture for future use.

Taking Trulance in water:

• Place the Trulance tablet in a clean cup and pour 1 ounce (30 mL) of room temperature water into the cup.
• Gently swirl the Trulance tablet and water for at least 10 seconds.
• The Trulance tablet will fall apart in the water.
• Swallow all of the Trulance tablet and water mixture right away.
• Do not keep the mixture for future use.
• If you see any part of the tablet left in the cup, add another 1 ounce (30 mL) of water to the cup, swirl for at least 10 seconds, and swallow right away.

Taking Trulance through a nasogastric or gastric feeding tube:

• Gather the supplies you will need to take your Trulance dose.
• Your doctor should tell you what size catheter tip syringe you will need for your dose.
• Ask your doctor if you have any questions about how to give Trulance the right way.

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

This medicine is available in fallowing doasage form:

• As Tablets: 3 mg

This medicine is available in fallowing brand namesː

• Trulance

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea

• Other adverse events include abdominal pain, bloating, flatulence and headache.

Less common side effects may include:

• nausea, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and dizziness.

What special precautions should I follow?

• Trulance is contraindicated in patients less than 6 years of age. The safety and effectiveness of Trulance in patients less than 18 years of age have not been established. Avoid the use of Trulance in patients 6 years to less than 18 years of age.
• Diarrhea was the most common adverse reaction in four placebo-controlled clinical trials, two in patients with CIC and two in patients with IBS-C. If severe diarrhea occurs, suspend dosing and rehydrate the patient.
• Accidental ingestion of Trulance in children, especially in children less than 6 years of age, may result in severe diarrhea and dehydration. Instruct patients to take steps to store Trulance securely and out of reach of children and to dispose of unused Trulance.
• Tell your doctor if you may have or have a blockage in your stomach or intestines. Your doctor will probably tell you not to take plecanatide.
• It is not known if Trulance passes into your breast milk. Talk with your doctor about the best way to feed your baby if you take Trulance.
• Plecanatide has not been linked to serum enzyme elevations during treatment or to episodes of clinically apparent liver injury.

What to do in case of emergency/overdose?

Symptoms of overdose may include:

• diarrhea
• dehydration

Management of overdosage:

• 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.

Can this medicine be used in pregnancy?

• The available data on Trulance use in pregnant women are not sufficient to inform any drug-associated risks for major birth defects and miscarriage.
• It is not known if Trulance will harm your unborn baby.

Can this medicine be used in children?

• Trulance is contraindicated in pediatric patients less than 6 years of age. Avoid use of Trulance in patients 6 years to less than 18 years of age.
• The safety and effectiveness of Trulance in patients less than 18 years of age have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: plecanatide
• Inactive ingredients: magnesium stearate and microcrystalline cellulose

Who manufactures and distributes this medicine?

Manufactured for:

• Synergy Pharmaceuticals Inc. 420 Lexington Avenue, Suite 2012 New York, New York

• Trulance® is a registered trademark of Synergy Pharmaceuticals Inc.

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

• Store Trulance at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Trulance in a secure place and in the bottle or blister pack that it comes in.
• The Trulance bottle contains a desiccant packet to help keep your medicine dry (protect it from moisture). Do not remove the desiccant packet from the bottle.
• The Trulance bottle contains a polyester coil to help protect the tablets during shipping. Remove the polyester coil from the bottle and throw it away after opening the bottle.
• Keep the container of Trulance tightly closed and in a dry place.
• Safely throw away Trulance that is out of date or no longer needed.

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

• Dailymed label info on Plecanatide
• FDA Plecanatide

Plecanatide Resources
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