Dosage & Administration
The recommended adult dosage of TRULANCE is
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Trulance Prescribing Information
- 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.,
4 CONTRAINDICATIONSTRULANCE 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.
- Patients with known or suspected mechanical gastrointestinal obstruction.
]8.4 Pediatric UseTRULANCE 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 DataSingle 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.
- Patients less than 6 years of age due to the risk of serious dehydration
- Avoid use of TRULANCE in patients 6 years to less than 18 years of age[see.,
5.1 Risk of Serious Dehydration in Pediatric PatientsTRULANCE 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)].]8.4 Pediatric UseTRULANCE 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 DataSingle 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.
- The safety and effectiveness of TRULANCE have not been established in patients less than 18 years of age[see.]
8.4 Pediatric UseTRULANCE 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 DataSingle 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.
TRULANCE is indicated in adults for the treatment of:
- chronic idiopathic constipation (CIC).
- irritable bowel syndrome with constipation (IBS-C).
The recommended adult dosage of TRULANCE is
- CIC: 3 mg taken orally once daily. ()
2.1 Recommended DosageThe recommended dosage of TRULANCE for the treatment of CIC and IBS-C is 3 mg taken orally once daily.
- IBS-C: 3 mg taken orally once daily. ()
2.1 Recommended DosageThe recommended dosage of TRULANCE for the treatment of CIC and IBS-C is 3 mg taken orally once daily.
- 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.
- 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.
- 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.
- 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.
- 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.
Tablets: 3 mg (
Tablets: 3 mg
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.
Plecanatide and its active metabolite are negligibly absorbed systemically following oral administration
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 (Cmax), and half-life (t½) could not be calculated.
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.
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.
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.
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.
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
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.
TRULANCE is contraindicated in:
- Patients less than 6 years of age due to the risk of serious dehydration[see.,
5.1 Risk of Serious Dehydration in Pediatric PatientsTRULANCE 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)].]8.4 Pediatric UseTRULANCE 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 DataSingle 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.
- Patients with known or suspected mechanical gastrointestinal obstruction.