What Is Trulance Used For

What is TRULANCE and how is it used?

TRULANCE is a prescription medicine used in adults to treat:

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

It is not known if TRULANCE is safe and constructive in children less than eighteen years of historic period.

What are the possible side effects of TRULANCE?

TRULANCE can cause serious side furnishings, including:

Come across "What is the most important information I should know about TRULANCE?"
Diarrhea is the about common side consequence of TRULANCE, and it can sometimes be severe.
- Diarrhea often begins within the first iv weeks of TRULANCE treatment.

Stop taking TRULANCE and call your doctor if you develop severe diarrhea.

These are not all the possible side effects of TRULANCE. Call your doctor for medical advice about side effects. Y'all may study side furnishings to FDA at 1-800-FDA-1088.

Alarm

RISK OF SERIOUS Dehydration IN PEDIATRIC PATIENTS

TRULANCE is contraindicated in patients less than six years of historic period; in nonclinical studies in immature juvenile mice administration of a single oral dose of plecanatide caused deaths due to dehydration [see CONTRAINDICATIONS, Utilize In Specific Populations].
Avert use of TRULANCE in patients half dozen years to less than 18 years of age [see WARNINGS AND PRECAUTIONS, Use In Specific Populations].
The safety and effectiveness of TRULANCE have not been established in patients less than xviii years of age [see Use In Specific Populations].

Description

TRULANCE (plecanatide) is a guanylate cyclase-C (GC-C) agonist. Plecanatide is a 16 amino acid peptide with the post-obit chemical proper noun: L-Leucine, L-asparaginyl-Fifty-α-aspartyl-L-α-glutamyl-L-cysteinyl-L-αglutamyl-50-leucyl-L-cysteinyl-L-valyl-L-asparaginyl-L-valyl-50-alanyl-50-cysteinyl-50-threonylglycyl-Lcysteinyl-, circadian (4→12),(vii→15)-bis(disulfide).

The molecular formula of plecanatide is C₆₅H₁₀₄N₁₈O₂₆S_four and the molecular weight is 1682 Daltons. The amino acid sequence for plecanatide is shown below:

TRULANCE (plecanatide) Structural Formula Illustration

The solid lines linking cysteines illustrate disulfide bridges.

Plecanatide is an amorphous, white to fair pulverisation. Information technology is soluble in water. TRULANCE tablets are supplied every bit iii mg tablets for oral administration. The inactive ingredients are magnesium stearate and microcrystalline cellulose.

INDICATIONS

TRULANCE is indicated in adults for the treatment of:

chronic idiopathic constipation (CIC).
irritable bowel syndrome with constipation (IBS-C).

DOSAGE AND Assistants

Recommended Dosage

The recommended dosage of TRULANCE for the treatment of CIC and IBS-C is iii mg taken orally once daily.

Grooming And Administration Instructions

Take TRULANCE with or without nutrient [see CLINICAL PHARMACOLOGY].
If a dose is missed, skip the missed dose and have the next dose at the regular time. Do not take two doses at the same time.
Eat a tablet whole for each dose.
For adult patients with swallowing difficulties, TRULANCE tablets can exist crushed and administered orally either in absurdity or with h2o 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 shop the mixture for after use.

Oral Administration In Water

Place the TRULANCE tablet in a clean cup.
Pour approximately 30 mL of room temperature water into the loving cup.
Mix by gently swirling the tablet and water mixture for at least 10 seconds. The TRULANCE tablet will fall apart in the h2o.
Swallow the entire contents of the tablet-water mixture immediately.
If whatsoever portion of the tablet is left in the loving cup, add another 30 mL of water to the cup, swirl for at least x seconds, and swallow immediately.
Do not store the tablet-h2o mixture for later apply.

Administration With Water Via A Nasogastric Or Gastric Feeding Tube

Place the TRULANCE tablet in a clean cup with xxx mL of room temperature water.
Mix past gently swirling the tablet and h2o mixture for at to the lowest degree 15 seconds. The TRULANCE tablet will fall apart in the water.
Flush the nasogastric or gastric feeding tube with 30 mL of h2o using a catheter tip syringe.
Draw upward the mixture using the syringe and immediately administer via the nasogastric or gastric feeding tube. Do not reserve for future utilize.
If any portion of the tablet is left in the cup, add another 30 mL of h2o 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 x mL of water.

HOW SUPPLIED

Dosage Forms And Strengths

TRULANCE Tablets:

3 mg: white to fair, plain, round tablet debossed with "SP" on 1 side and "three" for 3 mg on the other side.

Storage And Handling

TRULANCE tablets are packaged in an aluminum foil unit of measurement dose blister pack of 30 in a kid-resistant pack or in a white, opaque, high-density polyethylene round bottle with a screw-superlative polypropylene child-resistant cap and heat-activated induction seal. Each canteen container-closure system also contains a desiccant and a polyester coil.

TRULANCE iii mg tablets are white to fair, plain and round, debossed with "SP" on one side and "3" for 3 mg on the other side and supplied every bit:

NDC Number	Size
65649-003-thirty	Bottle of xxx
70194-003-30	Aluminum foil unit dose blister pack of thirty in a child-resistant pack

Store at room temperature, 20 to 25°C (68 to 77°F); excursions permitted to 15 to 30°C (59 to 86°F) [come across USP Controlled Room Temperature].

Keep TRULANCE in a dry place. Protect from moisture. For bottles, go on TRULANCE in the original bottle. Do not remove desiccant from the canteen. Do not subdivide or repackage.

Distributed by: Salix Pharmaceuticals, a sectionalization of Bausch Health US, LLC, Bridgewater, NJ 08807 USA. Revised: April 2021

QUESTION

You are constipated if you don't have a bowel motion every day. See Answer

Side Effects & Drug Interactions

SIDE EFFECTS

Clinical Trials Experience

Because clinical studies are conducted under widely varying weather condition, agin reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of some other drug and may not reflect the rates observed in practise.

Demographic characteristics were comparable between the TRULANCE and placebo groups in all studies [run into Clinical Studies].

Chronic Idiopathic Constipation (CIC)

The rubber data described below reflect information from 1,733 developed patients with CIC randomized in two double-blind, placebo-controlled clinical trials (Study 1 and Study two) to receive placebo or 3 mg of TRULANCE once daily for 12 weeks.

Most Mutual Adverse Reactions

Table i provides the incidence of agin 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 one: Most Common Agin Reactions^a in Two Placebo-Controlled Trials of TRULANCE [Study i and Study two] in Patients with CIC

Adverse Reaction	TRULANCE, iii mg (N = 863) %	Placebo (N = 870) %
Diarrhea^b	5	1
^a: Reported in at least ii% 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.

Diarrhea

The majority of reported cases of diarrhea occurred within 4 weeks of treatment initiation. Severe diarrhea was reported in 0.half-dozen% of TRULANCE-treated patients compared to 0.iii% of placebo-treated patients. Severe diarrhea was reported to occur inside the first iii days of treatment [run across WARNINGS AND PRECAUTIONS].

Agin Reactions Leading to Discontinuation

Discontinuations due to adverse reactions occurred in iv% of TRULANCE-treated patients and 2% of placebo-treated patients. The most common agin reaction leading to discontinuation was diarrhea: ii% of TRULANCE-treated patients and 0.5% of placebo-treated patients withdrew due to diarrhea.

Less Common Adverse Reactions

Agin 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 (ii patients with alanine aminotransferase (ALT) greater than five to 15 times the upper limit of normal and three 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 beneath reflect information from ane,449 adults patients with IBS-C randomized in 2 double-bullheaded, placebo-controlled clinical trials (Written report 3 and Study iv) to receive placebo or 3 mg TRULANCE once daily for 12 weeks.

Most Common Adverse Reactions

Table two provides the incidence of adverse reactions reported in at to the lowest degree two% of IBS-C patients treated with TRULANCE and at an incidence that was greater than in the placebo group.

Table 2: Most Mutual Agin Reactions^a in Two Placebo-Controlled Trials of TRULANCE [Study iii and Study 4] in Patients with IBS-C

Adverse Reaction	TRULANCE, three mg (N = 723) %	Placebo (Due north = 726) %
Diarrhea^b	4.three	1
^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

The bulk of reported cases of diarrhea occurred within iv weeks of treatment initiation. Severe diarrhea was reported in 1% of TRULANCE-treated patients compared to 0.1% of placebo-treated patients [encounter WARNINGS AND PRECAUTIONS]. Severe diarrhea was reported to occur within the first day of handling.

Adverse Reactions Leading to Discontinuation

Discontinuations due to agin reactions occurred in 2.5% of TRULANCE-treated patients and 0.4% of placebo-treated patients. The almost mutual adverse reaction leading to discontinuation was diarrhea: one.2% of TRULANCE-treated patients and 0% of placebo-treated patients withdrew due to diarrhea.

Less Mutual Agin Reactions

Agin reactions reported in 1% or more but less than 2% of TRULANCE-treated patients and at an incidence greater than placebo were: nausea, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and dizziness. 2 patients reported increased liver biochemical tests (alanine aminotransferase (ALT) greater than five to 15 times the upper limit of normal).

Postmarketing Experience

The following adverse reactions have been identified during postal service-approval use of TRULANCE. Because these reactions are reported voluntarily from a population of uncertain size, information technology is not always possible to reliably estimate their frequency or establish a causal relationship to TRULANCE exposure.

Hypersensitivity Reactions: peel itching, hives, rash

Airsickness

DRUG INTERACTIONS

No Data Provided

WARNINGS

Included as role of the "PRECAUTIONS" Section

PRECAUTIONS

Risk Of Serious Dehydration In Pediatric Patients

TRULANCE is contraindicated in patients less than half dozen years of age. The prophylactic 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 bloodshed in some mice within the offset 24 hours, apparently due to aridity. Due to increased intestinal expression of GC-C, patients less than vi years of historic period may be more than likely than patients 6 years of age and older to develop astringent diarrhea and its potentially serious consequences.

Avoid the utilise of TRULANCE in patients 6 years to less than xviii 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 information in pediatric patients, avoid the use of TRULANCE in patients 6 years to less than eighteen years of age [see CONTRAINDICATIONS, Diarrhea, Use In Specific Populations].

Diarrhea

Diarrhea was the well-nigh mutual adverse reaction in iv placebo-controlled clinical trials, two in patients with CIC and ii in patients with IBS-C. Severe diarrhea was reported in 0.half-dozen% of patients in two trials in patients with CIC and in 0.six% of patients in the two trials in patients with IBS-C [meet Adverse REACTIONS]. If astringent diarrhea occurs, append dosing and rehydrate the patient.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT Information).

Suggest Patients:

Diarrhea

To stop TRULANCE and contact their healthcare provider if they feel severe diarrhea [run across WARNINGS AND PRECAUTIONS].

Accidental Ingestion

Accidental ingestion of TRULANCE in children, especially in children less than 6 years of historic period, may result in severe diarrhea and aridity. Instruct patients to accept steps to store TRULANCE securely and out of attain of children and to dispose of unused TRULANCE [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS].

Assistants And Handling Instructions

To have TRULANCE once daily with or without food [see DOSAGE AND ADMINISTRATION].
If a dose is missed, skip the missed dose and accept the side by side dose at the regular time. Do not have 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 h2o, or administered with water via a nasogastric or gastric feeding tube, as described in the Medication Guide.
To go along TRULANCE in a dry place. Protect from moisture. For bottles, keep TRULANCE in the original bottle. Practice not remove desiccant from the bottle. Do not subdivide or repackage. Remove and discard polyester whorl after opening. Keep bottles closed tightly [run into HOW SUPPLIED].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Damage Of Fertility

Carcinogenesis

The carcinogenic potential of plecanatide was assessed in ii-year carcinogenicity studies in mice and rats. Plecanatide was not tumorigenic in mice at oral doses up to 90 mg/kg/mean solar day or in rats at oral doses up to 100 mg/kg/mean solar day. Limited systemic exposure to plecanatide was achieved at the tested dose levels in animals, whereas no detectable exposure occurred in humans. Therefore, animal and human doses should not exist compared directly for evaluating relative exposure.

Mutagenesis

Plecanatide was non genotoxic in the in vitro bacterial contrary mutation (Ames) assay, in vitro mouse lymphoma mutation analysis, or the in vivo mouse bone marrow micronucleus assay.

Harm Of Fertility

Plecanatide had no event on fertility or reproductive function in male or female person mice at oral doses of upwards to 600 mg/kg/day.

Use In Specific Populations

Pregnancy

Chance Summary

Plecanatide and its agile metabolite are negligibly absorbed systemically following oral administration [run across CLINICAL PHARMACOLOGY] and maternal use is not expected to result in fetal exposure to the drug. The bachelor data on TRULANCE employ in pregnant women are not sufficient to inform any drug-associated risks for major birth defects and miscarriage. In animate being 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 groundwork adventure of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a groundwork chance of nascency defect, loss, or other adverse outcomes. In the Usa general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and xv% to xx%, respectively.

Data

Animal data

Pregnant mice and rabbits were administered plecanatide during the period of organogenesis. At that place 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/mean solar day in mice during organogenesis through lactation produced no developmental abnormalities or effects on growth, learning and retentiveness, or fertility in the offspring through maturation.

The maximum recommended man dose is approximately 0.05 mg/kg/24-hour interval, based on a 60-kg torso weight. Limited systemic exposure to plecanatide was achieved in animals during organogenesis (area under the plasma concentration-time curve (AUCt) = 449 ng•h/mL in rabbits given 250 mg/kg/day). Plecanatide and its active metabolite are not measurable in man plasma post-obit assistants of the recommended clinical dosage. Therefore, animal and human being doses should not be compared straight for evaluating relative exposure.

Lactation

Chance 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, six 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 one time daily for up to 12 weeks [see CLINICAL PHARMACOLOGY].

Maternal utilise of TRULANCE is non expected to effect in clinically relevant exposure to plecanatide or its active metabolite in breastfed infants. The developmental and wellness benefits of breastfeeding should be considered along with the mother's clinical demand for TRULANCE and any potential adverse effects on the breastfed baby from TRULANCE or from the underlying maternal condition.

Pediatric 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 [meet CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]. The safe and effectiveness of TRULANCE in patients less than 18 years of historic period 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 two years) following oral administration of plecanatide, as described beneath in Juvenile Animal Toxicity Information. Because of increased abdominal expression of GC-C, patients less than 6 years of historic period may exist more likely than patients half-dozen years of age and older to develop diarrhea and its potentially serious consequences. TRULANCE is contraindicated in patients less than half dozen 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 xviii years of age.

Juvenile Animal Toxicity Data

Single oral doses of plecanatide at 0.v mg/kg and 10 mg/kg caused mortality in young juvenile mice on postnatal days 7 and fourteen, respectively (human being age equivalent of approximately i calendar 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 xiv (human age equivalent of approximately less than 2 years), consistent with increased fluid in the intestinal lumen. Although the recommended homo dose is approximately 0.05 mg/kg/day, based on a sixty-kg torso weight, plecanatide and its active metabolite are not measurable in developed man plasma, whereas systemic assimilation was demonstrated in the juvenile animal toxicity studies. Brute and human doses should not exist compared directly for evaluating relative exposure.

Geriatric Use

Chronic Idiopathic Constipation (CIC)

Of 2,601 subjects in placebo-controlled clinical trials of TRULANCE, 273 (ten%) 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 anile 65 and over to determine whether they answer differently from patients eighteen 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 (eight.three%) were 65 years of age and over, and 25 (ane.5%) were 75 years and over. Clinical studies of TRULANCE did non include sufficient numbers of patients aged 65 and over to make up one's mind whether they respond differently from patients 18 years to less than 65 years of age.

Overdosage & Contraindications

OVERDOSE

No Information Provided

CONTRAINDICATIONS

TRULANCE is contraindicated in:

Patients less than half-dozen years of historic period due to the adventure of serious dehydration [see WARNINGS AND PRECAUTIONS, Use In Specific Populations].
Patients with known or suspected mechanical gastrointestinal obstruction.

CLINICAL PHARMACOLOGY

Mechanism Of Activeness

Plecanatide is a structural analog of homo uroguanylin, and similarly to uroguanylin, plecanatide functions equally a guanylate cyclase-C (GC-C) agonist. Both plecanatide and its agile 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 subtract in the activity of hurting-sensing nerves in animate being models of visceral pain. Peak 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 abdominal transit, and cause changes in stool consistency.

In an creature model of visceral pain, plecanatide reduced intestinal musculus contractions, a measure of intestinal pain.

Pharmacodynamics

Food Effect

Subjects who received either a low-fat, low calorie (LF-LC) meal or a high fatty, loftier calorie (HF-HC) meal reported looser stools than fasted subjects upwards to 24 hours after a single dose of TRULANCE nine mg (3 times the recommended dose). In clinical studies, TRULANCE was administered with or without food [see DOSAGE AND Administration].

Pharmacokinetics

Absorption

Plecanatide was minimally captivated with negligible systemic availability post-obit oral administration. Concentrations of plecanatide and its active metabolite in plasma were beneath the limit of quantitation in the majority of analyzed plasma samples after an oral TRULANCE dose of 3 mg. Therefore, standard pharmacokinetic parameters such every bit AUC, maximum concentration (Cmax), and one-half-life (t_½) could not exist calculated.

Food Effect

In a crossover study, 24 healthy subjects were given a unmarried dose of TRULANCE 9 mg (iii times the recommended dose) in 3 unlike states: fasted; following a low-fat, low-calorie repast (LF-LC; approximately 350 calories: 17% from fatty, 66% from carbohydrate, and 17% from protein); and following a high-fatty, high-calorie meal (HF-HC; approximately 1,000 calories: 60% from fat, 25% from carbohydrate, and xv% from protein). Plecanatide was detected in 1 subject (fasted state) at 0.5 and ane 60 minutes post dose. Plecanatide concentrations were below the limit of quantitation for all other time points and for all other subjects. The active metabolite was non detected in whatever 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 information technology exerted its effects as a GC-C agonist with negligible systemic exposure. Plecanatide exhibited lilliputian to no bounden to human serum albumin or human α-ane-acid glycoprotein.

Elimination

Metabolism

Plecanatide was metabolized in the GI tract to an active metabolite past loss of the last 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 accept been conducted in humans. Plecanatide and its active metabolite were not measurable in plasma post-obit 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 non 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.

Clinical Studies

Chronic Idiopathic Constipation (CIC)

The efficacy of TRULANCE for the direction of symptoms of CIC was established in two 12-week, double-blind, placebo-controlled, randomized, multicenter clinical studies in adult patients (Report 1 and Written report 2). In the Intention-to-Care for (ITT) population, a total of 905 patients (Study ane) and 870 patients (Study 2) were randomized ane:one to either placebo or TRULANCE iii mg, once daily. In clinical studies, study medication was administered without respect to nutrient intake. Demographics for these studies included an overall mean historic period of 45 years (range 18 to 80 years), 80% female, 72% white, and 24% black.

To be eligible for the studies, patients were required to meet modified Rome Iii criteria for at to the lowest degree 3 months prior to the screening visit, with symptom onset for at least 6 months prior to diagnosis. Rome 3 criteria were modified to require that patients report less than three defecations per week, rarely have a loose stool without the use of laxatives, not apply manual maneuvers to facilitate defecations, and not come across criteria for IBS-C. In addition, patients were required to report at least two of the following symptoms:

Straining during at least 25% of defections
Lumpy or hard stool in at least 25% of defecations
Sensation of incomplete evacuations for at to the lowest degree 25% of defecations
Sensation of anorectal obstacle/blockage for at to the lowest degree 25% of defecations

Patients who met these criteria were also required to demonstrate the following during the concluding 2 weeks of the screening flow:

Less than 3 complete spontaneous bowel movements (CSBMs) (a CSBM is an SBM that is associated with a sense of complete evacuation) in each of the two weeks
Bristol Stool Form Scale (BSFS) of 6 or 7 in less than 25% of spontaneous bowel movements (SBMs) (an SBM is a bowel movement occurring in the absenteeism of laxative apply)
One out of the following three:
- BSFS of 1 or 2 in at least 25% of defecations
- A straining value recorded on at least 25% of days when a BM was reported
- At least 25% of BMs result in a sense of incomplete evacuation

The efficacy of TRULANCE was assessed using a responder assay and modify-from-baseline in CSBM and SBM endpoints. Efficacy was assessed using information provided by patients on a daily ground in an electronic diary.

A responder was divers as a patient who had at to the lowest degree 3 CSBMs in a given week and an increase of at least 1 CSBM from baseline in the same week for at least ix weeks out of the 12-week treatment period and at to the lowest degree 3 of the last 4 weeks of the study. The responder rates are shown in Table 3.

Tabular array 3: Efficacy Responder Rates in the Two Placebo-controlled Studies of CIC: at least ix of 12 weeks and at least iii of the last iv weeks (ITT Population)

Study 1
	TRULANCE iii mg N = 453	Placebo Due north = 452	Treatment Difference^a [95% CI^b]
Responder^c	21%	10%	eleven% [six.1%, fifteen.4%]
Report two
	TRULANCE 3 mg N = 430	Placebo N = 440	Treatment Difference^a [95% CI^b]
Responder^c	21%	13%	8% [two.half-dozen%, 12.4%]
^a: p-value <0.005 ^b: CI = confidence interval ^c: Primary endpoint defined as a patient who had a least 3 CSBMs in a given calendar week and an increase of at least 1 CSBM from baseline in the same week for at to the lowest degree 9 weeks out of the 12-week treatment period and at least 3 of the last iv weeks of the study.

In both studies, improvements in the frequency of CSBMs/week were seen as early as calendar week 1 with improvement maintained through week 12. The difference between the TRULANCE group and the placebo grouping in the mean change of CSBMs/calendar week frequency from baseline to week 12 was approximately 1.1 CSBMs/calendar week.

Over the 12-week treatment menstruum, improvements were observed in stool frequency (number of CSBMs/week and SBMs/calendar week) and/or stool consistency (as measured by the BSFS), and/or in the amount of straining with bowel movements (corporeality of time pushing or physical endeavour to pass stool) in the TRULANCE group as compared to placebo.

Following completion of the study drug handling period, patients continued to record data in the daily diary for a 2-calendar week Postal service-Treatment Menstruum. During this fourth dimension, TRULANCE-treated patients more often than not returned to baseline for these report endpoints.

In Studies 1 and 2, a 3rd randomized treatment arm of TRULANCE 6 mg once daily did not demonstrate additional treatment benefit and had a greater incidence of adverse reactions than TRULANCE three mg one time daily. Therefore, TRULANCE six mg in one case daily is not recommended [come across DOSAGE AND Assistants].

Irritable Bowel Syndrome With Constipation (IBS-C)

The efficacy of TRULANCE for the direction of symptoms of IBS-C was established in two 12-calendar week, double-bullheaded, placebo-controlled, randomized, multicenter clinical studies in adult patients (Study 3 and Study four). In the Intention-to- Treat (ITT) population, a total of 699 patients (Study three) and 754 patients (Study 4) received treatment with placebo or TRULANCE three mg once daily. In clinical studies, study medication was administered without respect to food intake. Demographics for these studies included an overall mean historic period of 44 years (range 18 to 83 years), 74% female, 73% white, and 22% black.

To be eligible, patients were required to run into the Rome Three criteria for IBS for at least 3 months prior to the screening visit, with symptom onset for at least 6 months prior to diagnosis. Diagnosis required recurrent abdominal pain or discomfort at least 3 days/month in the last iii months associated with 2 or more of 1) improvement with defecation, ii) onset associated with a alter in frequency of stool, and three) onset associated with a change in form (appearance) of stool. Patients also met the IBS-C differentiation criteria for constipation, characterized past a stool pattern such that at least 25% of defecations are difficult or lumpy stools and no more than than 25% of defecations are loose or watery stool.

Patients who met these criteria were excluded if they demonstrated the following during the last two weeks of the screening period:

Worst intestinal pain intensity (WAPI) score of 0 on an 11-point scale for more than 2 days during each week
An average WAPI of less than 3 for either week
More than 3 consummate spontaneous bowel movements (CSBMs) or more than 6 spontaneous bowel movements (SBMs) per calendar week in either week
Bristol Stool Course Calibration (BSFS) of 7 for any SBM recorded
More than 1 day in either week with a BSFS of 6 for whatsoever SBM recorded
No use of rescue laxative (bisacodyl) inside 72 hours before randomization

The efficacy of TRULANCE was assessed using a responder analysis based on abdominal pain intensity and a stool frequency responder (CSBM) endpoint. Efficacy was assessed using information provided by patients on a daily ground through an electronic phone diary system.

A responder was divers as a patient who met both the intestinal pain intensity and stool frequency responder criteria in the aforementioned week for at to the lowest degree 6 of the 12 treatment weeks. The abdominal pain intensity and stool frequency responder criteria assessed each week were divers as:

Abdominal hurting intensity responder: a patient who experienced a subtract in the weekly average of worst abdominal hurting in the past 24 hours score (measured daily) of at to the lowest degree 30% compared with baseline weekly average.
Stool frequency responder: a patient who experienced an increase of at least 1 CSBM per week from baseline.

The responder rates are shown in Table 4.

Table four: Efficacy Responder Rates in the Two Placebo-controlled Studies of IBS-C:Overall Responder for at least 6 of the 12 Handling Weeks (ITT Population)

Study iii
	Placebo N = 350	TRULANCE iii mg N = 349	Handling Difference [95% CI^a]
Responder^b	18%	30%	12% [vi%, 18%]
Components of Responder Endpoint
Abdominal Pain Responder^c	32%	41%
CSBM Responder^d	35%	48%
Study 4
	Placebo N = 379	TRULANCE three mg N = 375	Handling Deviation [95% CI^a]
Responder^b	xiv%	21%	7% [2%, 13%]
Components of Responder Endpoint
Abdominal Pain Responder^c	23%	33%
CSBM Responder^d	28%	34%
^a: CI = confidence interval ^b: A responder for these trials was defined as a patient who met both the abdominal hurting and CSBM weekly responder criteria for at least 6 of the 12 weeks. ^c: An intestinal pain responder was defined equally a patient who met the criteria of at least 30% reduction from baseline in weekly average of the worst daily abdominal hurting, for at to the lowest degree 6 of the 12 weeks. ^d: A CSBM responder was defined as a patient who achieved an increment in at least 1 CSBM per week, from baseline, for at least 6 of 12 weeks.

In both studies, the proportion of responders who were also weekly responders for at least 2 of the 4 treatment weeks in month 3, the terminal month of handling was greater in the TRULANCE groups compared to placebo.

Over the 12-week treatment period, improvements were observed in both stool consistency (as measured by the BSFS) and in the corporeality of straining with bowel movements (amount of time pushing or physical effort to pass stool) in the 3 mg TRULANCE group every bit compared to placebo.

Following completion of the written report drug treatment flow, patients continued to record data in the daily diary for a 2-week Post-Treatment Period. During this time, TRULANCE-treated patients generally returned to baseline for these report endpoints.

In Studies 3 and 4, a third randomized handling arm of TRULANCE six mg once daily did non demonstrate additional treatment benefit over the iii mg dose. Therefore, TRULANCE 6 mg once daily is not recommended [come across DOSAGE AND ADMINISTRATION].

PATIENT INFORMATION

TRULANCE^®
(TROO lans)
(plecanatide) tablets, for oral use

What is the most important information I should know virtually TRULANCE?

Exercise not give TRULANCE to children who are less than vi years of age. It may harm them.
You should not give TRULANCE to children half-dozen years to less than 18 years of age. It may harm them.

See "What are the possible side furnishings of TRULANCE?" for more data nearly side furnishings.

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 eighteen years of age.

Who should not take TRULANCE?

Practice not give TRULANCE to children who are less than 6 years of historic period.
Do non 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 weather condition, including if you lot:

are pregnant or program to become pregnant. It is non 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 infant if you lot take TRULANCE.

Tell your doctor about all the medicines y'all 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 oral fissure, 1 fourth dimension each twenty-four hours with or without food.
If yous miss a dose, skip the missed dose. Take the adjacent dose at your regular fourth dimension. Practise not accept 2 doses at the same fourth dimension.
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 besides be taken with h2o by adults through a nasogastric or gastric feeding tube.

It is not known if TRULANCE is rubber and constructive 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 correct abroad. Do not keep the TRULANCE and applesauce mixture for futurity use.

Taking TRULANCE in water:

Place the TRULANCE tablet in a make clean cup and pour i ounce (30 mL) of room temperature water into the cup.
Gently swirl the TRULANCE tablet and water for at to the lowest degree 10 seconds. The TRULANCE tablet will autumn 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 meet any part of the tablet left in the loving cup, add another 1 ounce (30 mL) of h2o to the cup, swirl for at to the lowest degree 10 seconds, and consume right away.

Taking TRULANCE through a nasogastric or gastric feeding tube:

Gather the supplies you lot will demand 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 whatsoever questions nearly 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 autonomously in the water.
Flush the nasogastric or gastric feeding tube with 1 ounce (30 mL) of water.
Depict upwardly the TRULANCE tablet and water mixture into a catheter tip syringe and give right abroad through the nasogastric or gastric feeding tube. Practise not proceed the mixture for hereafter utilize.
If you see any function of the tablet left in the cup, add some other 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 tube with at least x mL of water.

What are the possible side effects of TRULANCE?

TRULANCE tin cause serious side furnishings, including:

See "What is the nigh of import information I should know about TRULANCE?"
Diarrhea is the most common side effect of TRULANCE, and information technology can sometimes be astringent.
- Diarrhea often begins within the first 4 weeks of TRULANCE treatment.

Stop taking TRULANCE and phone call your doctor if you develop severe diarrhea.

These are not all the possible side effects of TRULANCE.

Call your dr. for medical advice almost side effects. Yous may report side effects to FDA at 1-800-FDA-1088.

How should I shop TRULANCE?

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 cicatrice pack that information technology comes in.
The TRULANCE bottle contains a desiccant packet to help keep your medicine dry out (protect information technology from moisture). Do not remove the desiccant packet from the bottle.
The TRULANCE bottle contains a polyester coil to aid protect the tablets during shipping. Remove the polyester whorl from the canteen and throw it away later on opening the bottle.
Keep the container of TRULANCE tightly closed and in a dry place.
Safely throw away TRULANCE that is out of appointment or no longer needed.

Go along TRULANCE and all medicines out of the achieve of children.

General information about the safe and constructive use of TRULANCE.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not utilize TRULANCE for a condition for which information technology was not prescribed. Do not give TRULANCE to other people, even if they take the same symptoms that you have. It may impairment them.

Y'all can enquire your doctor or pharmacist for information about TRULANCE that is written for health professionals.

What are the ingredients in TRULANCE?

Active ingredient: plecanatide

Inactive ingredients: magnesium stearate and microcrystalline cellulose

This Medication Guide is approved past the U.S. Food and Drug Assistants.

From

FDA Logo

Report Bug to the Food and Drug Administration

You lot are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.