Trulance Immediate release Plecanatide 3 mg Tablet, 30-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Guanylate Cyclase-C Agonist class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Plecanatide is used in adults to treat chronic idiopathic constipation (CIC; difficult or infrequent passage of stools that lasts for 3 months or longer and is not caused by a disease or a medication) and irritable bowel syndrome with constipation (IBS-C; a condition that causes stomach pain or cramps, bloating, and constipation.) Plecanatide is in a class of medications called guanylate cyclase-C agonists. It works by increasing the movement of food and waste through the stomach and intestines.
Read the full MedlinePlus article ↗- Trulance is designed to relieve constipation — whether you have chronic idiopathic constipation (ongoing constipation with no clear cause) or irritable bowel syndrome with constipa...
- What is Trulance actually supposed to do for me?
- Trulance can be taken with or without food — that's flexible. Just be aware that taking it with a meal, especially a high-fat one, may lead to looser stools than taking it fasted....
- Does it matter if I take Trulance with food or on an empty stomach?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Plecanatide — tap one for details:
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
2 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $17.836 | $535.08 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $18.16 | $544.90 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $21.06 | $631.80 / 30 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Trulance Immediate release 3 mgthis 65649-0003-30 | Salix | 30 tablets | $17.836 | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 9919024 ↗ | Method of use | U-2230 | Sep 15, 2031 |
| US 9610321 ↗ | Method of use | U-1999 | Sep 15, 2031 |
| US 9610321 ↗ | Method of use | U-2230 | Sep 15, 2031 |
| US 9919024 ↗ | Method of use | U-1999 | Sep 15, 2031 |
| US 12146003 ↗ | Drug product | — | Jun 5, 2034 |
| US 7041786 ↗ | Drug substance | — | Jan 30, 2028 |
| US 9925231 ↗ | Drug product | — | Sep 15, 2031 |
| US 9616097 ↗ | Drug product | — | Aug 20, 2032 |
| US 10011637 ↗ | Drug substance | — | Jun 5, 2034 |
| US 11142549 ↗ | Drug product | — | Jun 5, 2034 |
| US 11834521 ↗ | Drug product | — | Jun 5, 2034 |
| US 11319346 ↗ | Drug product | — | Mar 1, 2032 |
Is there a generic version of TRULANCE 3 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 65649-0003-01 | 1 BOTTLE in 1 CARTON (65649-003-01) / 1 TABLET in 1 BOTTLE | — | — | 2017-02-21 | Active |
| 65649-0003-03 | 1 BOTTLE in 1 CARTON (65649-003-03) / 3 TABLET in 1 BOTTLE | — | — | 2017-02-21 | Active |
| 65649-0003-07 | 1 BOTTLE in 1 CARTON (65649-003-07) / 7 TABLET in 1 BOTTLE | — | — | 2017-02-21 | Active |
| 65649-0003-30 You're viewing this | 30 TABLET in 1 BOTTLE (65649-003-30) | $17.84 / ea | $535.08 | 2017-02-21 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 65649-0003-30?
What is the difference between NDC 65649-0003-30 and NDC 65649-0003-01?
What NDC number is used to bill for this package of Trulance Immediate release Plecanatide 3 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS TRULANCE is contraindicated in patients less than 6 years of age; in nonclinical studies in young juvenile mice, administration of a single oral dose of plecanatide caused deaths due to dehydration [see Contraindications (4) , Use in Specific Populations (8.4) ] . Avoid use of TRULANCE in patients 6 years to less than 18 years of age [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ] . The safety and effectiveness of TRULANCE have not been established in patients less than 18 years of age [see Use in Specific Populations (8.4) ] .
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS See full prescribing information for complete boxed warning. TRULANCE is contraindicated in patients less than 6 years of age; in young juvenile mice, plecanatide caused death due to dehydration. ( 4 , 8.4 ) Avoid use of TRULANCE in patients 6 years to less than 18 years of age.
( 5.1 , 8.4 ) The safety and effectiveness of TRULANCE have not been established in patients less than 18 years of age. ( 8.4 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE TRULANCE is indicated in adults for the treatment of: chronic idiopathic constipation (CIC). irritable bowel syndrome with constipation (IBS-C). TRULANCE is a guanylate cyclase-C agonist indicated in adults for treatment of: chronic idiopathic constipation (CIC). ( 1 ) irritable bowel syndrome with constipation (IBS-C). ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended adult dosage of TRULANCE is CIC: 3 mg taken orally once daily. ( 2.1 ) IBS-C: 3 mg taken orally once daily. ( 2.1 ) Administration Instructions ( 2.2 ): Take with or without food.
Swallow tablets whole. For patients who have difficulty swallowing tablets whole or those with a nasogastric or gastric feeding tube, see full prescribing information with instructions for crushing the tablet and administering with applesauce or water.
2.1Recommended Dosage The recommended dosage of TRULANCE for the treatment of CIC and IBS-C is 3 mg taken orally once daily.
2.2Preparation and Administration Instructions Take TRULANCE with or without food [see Clinical Pharmacology (12.3) ] . If a dose is missed, skip the missed dose and take the next dose at the regular time. Do not take two doses at the same time.
Swallow a tablet whole for each dose. For adult patients with swallowing difficulties, TRULANCE tablets can be crushed and administered orally either in applesauce or with water or administered with water via a nasogastric or gastric feeding tube. Mixing TRULANCE crushed tablets in other soft foods or in other liquids has not been tested.
Oral Administration in Applesauce: In a clean container, crush the TRULANCE tablet to a powder and mix with 1 teaspoonful of room temperature applesauce. Consume the entire tablet-applesauce mixture immediately. Do not store the mixture for later use.
Oral Administration in Water: Place the TRULANCE tablet in a clean cup. Pour approximately 30 mL of room temperature water into the cup. Mix by gently swirling the tablet and water mixture for at least 10 seconds.
The TRULANCE tablet will fall apart in the water. Swallow the entire contents of the tablet-water mixture immediately. If any portion of the tablet is left in the cup, add another 30 mL of water to the cup, swirl for at least 10 seconds, and swallow immediately.
Do not store the tablet-water mixture for later use. Administration with Water via a Nasogastric or Gastric Feeding Tube: Place the TRULANCE tablet in a clean cup with 30 mL of room temperature water. Mix by gently swirling the tablet and water mixture for at least 15 seconds.
The TRULANCE tablet will fall apart in the water. Flush the nasogastric or gastric feeding tube with 30 mL of water using a catheter tip syringe. Draw up the mixture using the syringe and immediately administer via the nasogastric or gastric feeding tube.
Do not reserve for future use. If any portion of the tablet is left in the cup, add another 30 mL of water to the cup, swirl for at least 15 seconds, and using the same syringe, administer via the nasogastric or gastric feeding tube. Using the same or a fresh syringe, flush the nasogastric or gastric feeding tube with at least 10 mL of water.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 3 mg ( 3 ) TRULANCE Tablets: 3 mg: white to off-white, plain, round tablet debossed with “SP” on one side and “3” for 3 mg on the other side.
⛔ Contraindications ▾
4 CONTRAINDICATIONS TRULANCE is contraindicated in: Patients less than 6 years of age due to the risk of serious dehydration [see Warnings and Precautions (5.1) , Use in Specific Populations (8.4) ] . Patients with known or suspected mechanical gastrointestinal obstruction. Patients less than 6 years of age due to the risk of serious dehydration. ( 4 , 5.1 , 8.4 ) Patients with known or suspected mechanical gastrointestinal obstruction. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Diarrhea: Patients may experience severe diarrhea. If severe diarrhea occurs, suspend dosing and rehydrate the patient. ( 5.2 )
5.1Risk of Serious Dehydration in Pediatric Patients 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. In young juvenile mice (human age equivalent of approximately 1 month to less than 2 years), plecanatide increased fluid-secretion into the intestines as a consequence of stimulation of guanylate cyclase-C (GC-C), resulting in mortality in some mice within the first 24 hours, apparently due to dehydration.
Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences. Avoid the use of TRULANCE in patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in younger mice and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of TRULANCE in patients 6 years to less than 18 years of age [see Contraindications (4) , Warnings and Precautions (5.2) , Use in Specific Populations (8.4) ] .
5.2Diarrhea 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. Severe diarrhea was reported in 0.6% of patients in two trials in patients with CIC and in 0.6% of patients in the two trials in patients with IBS-C [see Adverse Reactions (6.1) ] . If severe diarrhea occurs, suspend dosing and rehydrate the patient.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reaction (≥2%) is diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Demographic characteristics were comparable between the TRULANCE and placebo groups in all studies [see Clinical Studies (14) ] . Chronic Idiopathic Constipation (CIC) The safety data described below reflect data from 1,733 adult patients with CIC randomized in two double-blind, placebo-controlled clinical trials (Study 1 and Study 2) to receive placebo or 3 mg of TRULANCE once daily for 12 weeks.
Most Common Adverse Reactions Table 1 provides the incidence of adverse reactions reported in at least 2% of CIC patients in the TRULANCE-treated group and at an incidence that was greater than in the placebo group. Table 1: Most Common Adverse Reactions a in Two Placebo-Controlled Trials of TRULANCE [Study 1 and Study 2] in Patients with CIC Adverse Reaction TRULANCE, 3 mg (N = 863) % Placebo (N = 870) % a: Reported in at least 2% of TRULANCE-treated patients with CIC and at an incidence greater than placebo. b: Verbatim reports of diarrhea were recorded as adverse reactions; reports of loose stools and increase in stool frequency were recorded as adverse reactions if they were also reported to be bothersome to the patient.
Diarrheaᵇ 5 1 Diarrhea The majority of reported cases of diarrhea occurred within 4 weeks of treatment initiation. Severe diarrhea was reported in 0.6% of TRULANCE-treated patients compared to 0.3% of placebo-treated patients. Severe diarrhea was reported to occur within the first 3 days of treatment [see Warnings and Precautions (5.2) ] .
Adverse Reactions Leading to Discontinuation Discontinuations due to adverse reactions occurred in 4% of TRULANCE-treated patients and 2% of placebo-treated patients. The most common adverse reaction leading to discontinuation was diarrhea: 2% of TRULANCE-treated patients and 0.5% of placebo-treated patients withdrew due to diarrhea . Less Common Adverse Reactions Adverse reactions reported in less than 2% of TRULANCE-treated patients and at an incidence greater than placebo were: sinusitis, upper respiratory tract infection, abdominal distension, flatulence, abdominal tenderness, and increased liver biochemical tests (2 patients with alanine aminotransferase (ALT) greater than 5 to 15 times the upper limit of normal and 3 patients with aspartate aminotransferase (AST) greater than 5 times the upper limit of normal).
Irritable Bowel Syndrome with Constipation (IBS-C) The safety data described below reflect data from 1,449 adults patients with IBS-C randomized in two double-blind, placebo-controlled clinical trials (Study 3 and Study 4) to receive placebo or 3 mg TRULANCE once daily for 12 weeks. Most Common Adverse Reactions Table 2 provides the incidence of adverse reactions reported in at least 2% of IBS-C patients treated with TRULANCE and at an incidence that was greater than in the placebo group. Table 2: Most Common Adverse Reactions a in Two Placebo-Controlled Trials of TRULANCE [Study 3 and Study 4] in Patients with IBS-C Adverse Reaction TRULANCE, 3 mg (N = 723) % Placebo (N = 726) % a: Reported in at least 2% of TRULANCE-treated patients with IBS-C and at an incidence greater than placebo. b: Verbatim reports of diarrhea were recorded as adverse reactions; reports of loose stools and increase in stool frequency were recorded as adverse reactions if they were also reported to be bothersome to the patient.
Diarrhea b 4.3 1 Diarrhea The majority of reported cases of diarrhea occurred within 4 weeks of treatment initiation. Severe diarrhea was reported in 1% of TRULANCE-…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Plecanatide and its active metabolite are negligibly absorbed systemically following oral administration [see Clinical Pharmacology (12.3) ] and maternal use is not expected to result in fetal exposure to the drug. The available data on TRULANCE use in pregnant women are not sufficient to inform any drug-associated risks for major birth defects and miscarriage. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of plecanatide in mice and rabbits during organogenesis at doses much higher than the recommended human dosage.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Pregnant mice and rabbits were administered plecanatide during the period of organogenesis. There was no evidence of harm to embryo-fetal development at oral doses up to 800 mg/kg/day in mice and 250 mg/kg/day in rabbits. Oral administration of up to 600 mg/kg/day in mice during organogenesis through lactation produced no developmental abnormalities or effects on growth, learning and memory, or fertility in the offspring through maturation.
The maximum recommended human dose is approximately 0.05 mg/kg/day, based on a 60-kg body weight. Limited systemic exposure to plecanatide was achieved in animals during organogenesis (area under the plasma concentration-time curve (AUC t ) = 449 ng ● h/mL in rabbits given 250 mg/kg/day). Plecanatide and its active metabolite are not measurable in human plasma following administration of the recommended clinical dosage.
Therefore, animal and human doses should not be compared directly for evaluating relative exposure.
8.2Lactation Risk Summary After administration of multiple doses of TRULANCE 3 mg once daily for 2 weeks to nursing mothers, plecanatide and its active metabolite were not measurable in breast milk collected at 2 hours, 6 hours, and 12 hours post-dosing. In adults, concentrations of plecanatide and its active metabolite were mostly unmeasurable in plasma following multiple doses of TRULANCE 3 mg once daily for up to 12 weeks [see Clinical Pharmacology ( 12.3 )] . Maternal use of TRULANCE is not expected to result in clinically relevant exposure to plecanatide or its active metabolite in breastfed infants.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TRULANCE and any potential adverse effects on the breastfed infant from TRULANCE or from the underlying maternal condition.
8.4Pediatric Use 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 [see Contraindications (4) , Warnings and Precautions (5.1) ]. The safety and effectiveness of TRULANCE in patients less than 18 years of age have not been established.
In nonclinical studies, deaths occurred within 24 hours in young juvenile mice (human age equivalent of approximately 1 month to less than 2 years) following oral administration of plecanatide, as described below in Juvenile Animal Toxicity Data. Because of increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop diarrhea and its potentially serious consequences. TRULANCE is contraindicated in patients less than 6 years of age.
Given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of TRULANCE in patients 6 years to less than 18 years of age. Juvenile Animal Toxicity Data Single oral doses of plecanatide at 0.5 mg/kg and 10 m…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Plecanatide and its active metabolite are negligibly absorbed systemically following oral administration [see Clinical Pharmacology (12.3) ] and maternal use is not expected to result in fetal exposure to the drug. The available data on TRULANCE use in pregnant women are not sufficient to inform any drug-associated risks for major birth defects and miscarriage. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of plecanatide in mice and rabbits during organogenesis at doses much higher than the recommended human dosage.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Pregnant mice and rabbits were administered plecanatide during the period of organogenesis. There was no evidence of harm to embryo-fetal development at oral doses up to 800 mg/kg/day in mice and 250 mg/kg/day in rabbits. Oral administration of up to 600 mg/kg/day in mice during organogenesis through lactation produced no developmental abnormalities or effects on growth, learning and memory, or fertility in the offspring through maturation.
The maximum recommended human dose is approximately 0.05 mg/kg/day, based on a 60-kg body weight. Limited systemic exposure to plecanatide was achieved in animals during organogenesis (area under the plasma concentration-time curve (AUC t ) = 449 ng ● h/mL in rabbits given 250 mg/kg/day). Plecanatide and its active metabolite are not measurable in human plasma following administration of the recommended clinical dosage.
Therefore, animal and human doses should not be compared directly for evaluating relative exposure.
🧒 Pediatric Use ▾
8.4Pediatric Use 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 [see Contraindications (4) , Warnings and Precautions (5.1) ]. The safety and effectiveness of TRULANCE in patients less than 18 years of age have not been established.
In nonclinical studies, deaths occurred within 24 hours in young juvenile mice (human age equivalent of approximately 1 month to less than 2 years) following oral administration of plecanatide, as described below in Juvenile Animal Toxicity Data. Because of increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop diarrhea and its potentially serious consequences. TRULANCE is contraindicated in patients less than 6 years of age.
Given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of TRULANCE in patients 6 years to less than 18 years of age. Juvenile Animal Toxicity Data Single oral doses of plecanatide at 0.5 mg/kg and 10 mg/kg caused mortality in young juvenile mice on postnatal days 7 and 14, respectively (human age equivalent of approximately 1 month to less than 2 years). Treatment-related increases in the weight of intestinal contents were observed in juvenile mice following single doses of plecanatide on postnatal day 14 (human age equivalent of approximately less than 2 years), consistent with increased fluid in the intestinal lumen.
Although the recommended human dose is approximately 0.05 mg/kg/day, based on a 60-kg body weight, plecanatide and its active metabolite are not measurable in adult human plasma, whereas systemic absorption was demonstrated in the juvenile animal toxicity studies. Animal and human doses should not be compared directly for evaluating relative exposure.
🧓 Geriatric Use ▾
8.5Geriatric Use Chronic Idiopathic Constipation (CIC) Of 2,601 subjects in placebo-controlled clinical trials of TRULANCE, 273 (10%) were 65 years of age and over, and 47 (2%) were 75 years and over. Clinical studies of TRULANCE did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from patients 18 years to less than 65 years of age. Irritable Bowel Syndrome with Constipation (IBS-C) Of 1,621 subjects in the placebo-controlled clinical studies of TRULANCE, 134 (8.3%) were 65 years of age and over, and 25 (1.5%) were 75 years and over.
Clinical studies of TRULANCE did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from patients 18 years to less than 65 years of age.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Plecanatide is a structural analog of human uroguanylin, and similarly to uroguanylin, plecanatide functions as a guanylate cyclase-C (GC-C) agonist. Both plecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP).
Elevation of extracellular cGMP has been associated with a decrease in the activity of pain-sensing nerves in animal models of visceral pain. Elevation of intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, plecanatide has been shown to increase fluid secretion into the gastrointestinal (GI) tract, accelerate intestinal transit, and cause changes in stool consistency.
In an animal model of visceral pain, plecanatide reduced abdominal muscle contractions, a measure of intestinal pain.
12.2Pharmacodynamics Food Effect Subjects who received either a low-fat, low calorie (LF-LC) meal or a high fat, high calorie (HF-HC) meal reported looser stools than fasted subjects up to 24 hours after a single dose of TRULANCE 9 mg (3 times the recommended dose). In clinical studies, TRULANCE was administered with or without food [see Dosage and Administration (2.2) ] .
12.3Pharmacokinetics Absorption Plecanatide was minimally absorbed with negligible systemic availability following oral administration. Concentrations of plecanatide and its active metabolite in plasma were below the limit of quantitation in the majority of analyzed plasma samples after an oral TRULANCE dose of 3 mg. Therefore, standard pharmacokinetic parameters such as AUC, maximum concentration (C max ), and half-life (t ½ ) could not be calculated.
Food Effect In a crossover study, 24 healthy subjects were given a single dose of TRULANCE 9 mg (3 times the recommended dose) in 3 different states: fasted; following a low-fat, low-calorie meal (LF-LC; approximately 350 calories: 17% from fat, 66% from carbohydrate, and 17% from protein); and following a high-fat, high-calorie meal (HF-HC; approximately 1,000 calories: 60% from fat, 25% from carbohydrate, and 15% from protein). Plecanatide was detected in 1 subject (fasted state) at 0.5 and 1 hour post dose. Plecanatide concentrations were below the limit of quantitation for all other time points and for all other subjects.
The active metabolite was not detected in any subject. Distribution Given that plecanatide concentrations following clinically relevant oral doses were not measurable, plecanatide is expected to be minimally distributed in tissues. Oral plecanatide was localized to the GI tract where it exerted its effects as a GC-C agonist with negligible systemic exposure.
Plecanatide exhibited little to no binding to human serum albumin or human α-1-acid glycoprotein. Elimination Metabolism Plecanatide was metabolized in the GI tract to an active metabolite by loss of the terminal leucine moiety. Both plecanatide and the metabolite were proteolytically degraded within the intestinal lumen to smaller peptides and naturally occurring amino acids.
Excretion No excretion studies have been conducted in humans. Plecanatide and its active metabolite were not measurable in plasma following administration of the recommended clinical doses. Drug Interaction Studies Neither plecanatide nor its active metabolite inhibited the cytochrome P450 (CYP) enzymes 2C9 and 3A4, and they did not induce CYP3A4 in vitro.
Plecanatide and its active metabolite were neither substrates nor inhibitors of the transporters P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) in vitro .
🧬 Mechanism of Action ▾
12.1Mechanism of Action Plecanatide is a structural analog of human uroguanylin, and similarly to uroguanylin, plecanatide functions as a guanylate cyclase-C (GC-C) agonist. Both plecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of the intestinal epithelium. Activation of GC-C results in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP).
Elevation of extracellular cGMP has been associated with a decrease in the activity of pain-sensing nerves in animal models of visceral pain. Elevation of intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid and accelerated transit. In animal models, plecanatide has been shown to increase fluid secretion into the gastrointestinal (GI) tract, accelerate intestinal transit, and cause changes in stool consistency.
In an animal model of visceral pain, plecanatide reduced abdominal muscle contractions, a measure of intestinal pain.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING TRULANCE tablets are packaged in a white, opaque, high-density polyethylene round bottle with a screw-top polypropylene child-resistant cap and heat-activated induction seal. Each bottle container-closure system also contains a desiccant and a polyester coil. TRULANCE 3 mg tablets are white to off-white, plain and round, debossed with “SP” on one side and “3” for 3 mg on the other side and supplied as: NDC Number Size 65649-003-30 Bottle of 30 Store at room temperature, 20 to 25°C (68 to 77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].
Keep TRULANCE in a dry place. Protect from moisture. Keep TRULANCE in the original bottle.
Do not remove desiccant from the bottle. Do not subdivide or repackage.
📦 Storage and Handling ▾
Store at room temperature, 20 to 25°C (68 to 77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Keep TRULANCE in a dry place. Protect from moisture. Keep TRULANCE in the original bottle. Do not remove desiccant from the bottle. Do not subdivide or repackage.
📋 Description ▾
11 DESCRIPTION TRULANCE (plecanatide) is a guanylate cyclase-C (GC-C) agonist. Plecanatide is a 16 amino acid peptide with the following chemical name: L-Leucine, L-asparaginyl-L-α-aspartyl-L-α-glutamyl-L-cysteinyl-L-α-glutamyl-L-leucyl-L-cysteinyl-L-valyl-L-asparaginyl-L-valyl-L-alanyl-L-cysteinyl-L-threonylglycyl-L-cysteinyl-, cyclic (4→12),(7→15)-bis(disulfide). The molecular formula of plecanatide is C 65 H 104 N 18 O 26 S 4 and the molecular weight is 1682 Daltons.
The amino acid sequence for plecanatide is shown below: The solid lines linking cysteines illustrate disulfide bridges. Plecanatide is an amorphous, white to off-white powder. It is soluble in water.
TRULANCE tablets are supplied as 3 mg tablets for oral administration. The inactive ingredients are magnesium stearate and microcrystalline cellulose. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Advise patients: Diarrhea To stop TRULANCE and contact their healthcare provider if they experience severe diarrhea [see Warnings and Precautions (5.2) ] . Accidental Ingestion 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 [see Contraindications (4) , Warnings and Precautions (5.2) ] . Administration and Handling Instructions To take TRULANCE once daily with or without food [see Dosage and Administration (2.2) ] . If a dose is missed, skip the missed dose and take the next dose at the regular time.
Do not take two doses at the same time. To swallow TRULANCE tablets whole. If adult patients have swallowing difficulties, TRULANCE tablets can be crushed and administered orally in either applesauce or with water, or administered with water via a nasogastric or gastric feeding tube, as described in the Medication Guide.
To keep TRULANCE in a dry place. Protect from moisture. Keep TRULANCE in the original bottle.
Do not remove desiccant from the bottle. Do not subdivide or repackage. Remove and discard polyester coil after opening.
Keep bottles closed tightly [see How Supplied/Storage and Handling (16) ] .
💬 Medication Guide ▾
Medication Guide TRULANCE ® (TROO lans) (plecanatide) tablets, for oral use What is the most important information I should know about TRULANCE? Do not give TRULANCE to children who are less than 6 years of age. It may harm them.
You should not give TRULANCE to children 6 years to less than 18 years of age. It may harm them. See “What are the possible side effects of TRULANCE?” for more information about side effects.
What is TRULANCE? 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).
It is not known if TRULANCE is safe and effective in children less than 18 years of age. Who should not take TRULANCE? Do not give TRULANCE to children who are less than 6 years of age.
Do not take TRULANCE if a doctor has told you that you have a bowel blockage (intestinal obstruction). Before taking TRULANCE, tell your doctor about all of your medical conditions, including if you: are pregnant or plan to become pregnant. It is not known if TRULANCE will harm your unborn baby. are breastfeeding or plan to breastfeed.
Talk with your doctor about the best way to feed your baby if you take TRULANCE. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should I take TRULANCE?
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.
Place the TRULANCE tablet in a clean cup with 1 ounce (30 mL) of room temperature water. Gently swirl the TRULANCE tablet and water for at least 15 seconds. The TRULANCE tablet will fall apart in the water.
Flush the nasogastric or gastric feeding tube with 1 ounce (30 mL) of water. Draw up the TRULANCE tablet and water mixture into a catheter tip syringe and give right away through the nasogastric or gastric feeding tube. 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 15 seconds and use the same catheter tip syringe to give the mixture through the nasogastric or gastric feeding tube. Using the same or another catheter tip syringe, flush the nasogastric or gastric feeding tu…