INDICATIONS & USAGE SECTION

Highlight: 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)

1 INDICATIONS AND USAGE

TRULANCE is indicated in adults for the treatment of:

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

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CONTRAINDICATIONS SECTION

Highlight: * 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)

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.

BOXED WARNING SECTION

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)

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USE IN SPECIFIC POPULATIONS SECTION

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

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.

8.2 Lactation

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.

8.4 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 [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.

8.5 Geriatric 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.

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SPL MEDGUIDE SECTION

This Medication Guide is approved by the U.S. Food and Drug Administration.

Revised: 03/2024
9705704

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SPL UNCLASSIFIED SECTION

Distributed by:
Salix Pharmaceuticals, a division of
Bausch Health US, LLC
Bridgewater, NJ 08807 USA

Patented. See https://patents.salix.com for US patent information.

TRULANCE is a trademark of Salix Pharmaceuticals, Inc. or its affiliates.

© 2024 Salix Pharmaceuticals, Inc. or its affiliates

9705704

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