TRULANCE

1 Dosing Considerations • No dose adjustments are required for patients with hepatic or renal impairment. In some patients, TRULANCE taken with food led to looser stools and/or increased abdominal cramping. Patients experiencing gastrointestinal adverse events should avoid high-fat, high-calorie meals near the time of dosing.

Some patients had an improvement in the number of bowel movements starting as early as 24 hours after taking TRULANCE. 2 Recommended Dose and Dosage Adjustment The recommended dosage of TRULANCE for the treatment of IBS-C and CIC is 3 mg taken orally once daily with or without food.

1 INDICATIONS, Pediatrics). 4. 4 Administration TRULANCE can be taken with or without food. The tablet should be swallowed whole. 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 1. In a clean container, crush the TRULANCE tablet to a powder and mix with 1 teaspoonful of room temperature applesauce.

2. Consume the entire tablet-applesauce mixture immediately. Do not store the mixture for later use. Oral Administration in Water 1. Place the TRULANCE tablet in a clean cup. 2. Pour approximately 30 mL of room temperature water into the cup.

3. Mix by gently swirling the tablet and water mixture for at least 10 seconds. The TRULANCE tablet will fall apart in the water. 4. Swallow the entire contents of the tablet water mixture immediately. 5. 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.

6. Do not store the tablet-water mixture for later use. Administration via a Nasogastric or Gastric Feeding Tube (with water) Serious Warnings and Precautions • TRULANCE is contraindicated in patients less than 6 years of age. • Avoid use of TRULANCE in patients between 6 years and 18 years of age.

(see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, Special Populations, NON-CLINCIAL TOXICOLOGY, Reproductive and Developmental Toxicity) PrTRULANCETM Product Monograph Page 6 of 31 1. Place the TRULANCE tablet in a clean cup with 30 mL of room temperature water.

1 Adverse Reaction Overview Irritable Bowel Syndrome with Constipation (IBS-C) The safety of TRULANCE in IBS-C was evaluated in two placebo-controlled studies involving a total of 1879 patients (ITT-S, 1255 patients treated with TRULANCE and 624 treated with placebo).

7%) arms of the study. 1% for combined TRULANCE; 0% for placebo). 1% in the combined TRULANCE group. No SAE in the placebo-controlled studies was considered related to study drug. There was no obvious pattern in the types of serious adverse events experienced in either the placebo or TRULANCE group.

0%). Other AEs reported in at least 1% of either active treatment group included headache, nausea, influenza, nasopharyngitis, urinary tract infection, upper respiratory tract infection and dizziness. There were two deaths reported in the IBS-C clinical study, neither were related to TRULANCE.

One patient did not receive TRULANCE and the second patient died of drowning. TRULANCE was generally well-tolerated with most AEs being mild to moderate in intensity. Chronic Idiopathic Constipation (CIC) The safety of TRULANCE in CIC was evaluated in two placebo-controlled studies involving a total of 2345 patients (ITT-S, 1557 patients treated with TRULANCE and 786 treated with placebo).

9%) arms of the study. 1% each). All other SAE were reported in 1 plecanatide patient each. Two SAEs were considered related to study drug, which were acute diverticulitis of the sigmoid colon in a patient in the placebo group and liver function test abnormal in a patient in the 6 mg plecanatide group.

3%). 2%). There was one death reported in the CIC clinical study. Patient in the 6 mg plecanatide treatment group of long-term safety study died due to the SAE of myocardial infarction. Consequently, it was not related to study drug. 2 Clinical Trial Adverse Reactions Irritable Bowel Syndrome with Constipation (IBS-C) Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

, 10 CLINICAL PHARMACOLOGY, Special Populations). 8%) were 65 years of age 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.

Chronic Idiopathic Constipation (CIC) Of 2,601 subjects in placebo-controlled clinical trials of TRULANCE, 273 (10%) were 65 years of age 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.

2 CONTRAINDICATIONS TRULANCE (plecanatide) is contraindicated in: • Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.

• Patients less than 6 years of age due to the risk of serious dehydration (see 7 WARNINGS AND PRECAUTIONS, Special Populations). • Patients with known or suspected mechanical gastrointestinal obstruction. 1 Dosing Considerations • No dose adjustments are required for patients with hepatic or renal impairment.

In some patients, TRULANCE taken with food led to looser stools and/or increased abdominal cramping. Patients experiencing gastrointestinal adverse events should avoid high-fat, high-calorie meals near the time of dosing. Some patients had an improvement in the number of bowel movements starting as early as 24 hours after taking TRULANCE.

2 Recommended Dose and Dosage Adjustment The recommended dosage of TRULANCE for the treatment of IBS-C and CIC is 3 mg taken orally once daily with or without food. 1 INDICATIONS, Pediatrics). 4. 4 Administration TRULANCE can be taken with or without food.

The tablet should be swallowed whole. 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.

, 7 WARNINGS AND PRECAUTIONS, 10 CLINICAL PHARMACOLOGY, Special Populations). 8%) were 65 years of age 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.

Chronic Idiopathic Constipation (CIC) Of 2,601 subjects in placebo-controlled clinical trials of TRULANCE, 273 (10%) were 65 years of age 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.

2 CONTRAINDICATIONS TRULANCE (plecanatide) is contraindicated in: • Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.

• Patients less than 6 years of age due to the risk of serious dehydration (see 7 WARNINGS AND PRECAUTIONS, Special Populations). • Patients with known or suspected mechanical gastrointestinal obstruction.