1/17. Plecanatide- (TRULANCE)-@- (Jan 2017) to treat idiopathic Constipation (CIC) in adult patientsiopathic Constipation
Drug Name:1/17. Plecanatide- (TRULANCE)-@- (Jan 2017) to treat idiopathic Constipation (CIC) in adult patientsiopathic Constipation
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
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 are neither substrates nor inhibitors
of the transporters P-glycoprotein (P-gp) or breast cancer resistance
protein (BCRP) in vitro.
Indication:
BRIEF SUMMARY
PLECANATIDE -(Jan 2017)
Indn- To treat Chronic Idiopathic Constipation (CIC) in adult patients
Comp- Tablets: 3 mg The recommended adult dosage of TRULANCE is 3 mg taken orally once daily.
ADR- 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.
CI- Patients less than 6 years of age due to the risk of serious dehydratio
[see Warnings and Precautions
Patients with known or suspected mechanical gastrointestinal obstruction.
WARNINGS-
1. Risk 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.
Pat Infn-
Advise Patients:
Diarrhea
To stop TRULANCE and contact their healthcare provider if they experience
severe diarrhea.
Accidental Ingestion
Accidental ingestion 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 securely and out of reach
of children and to dispose of unused drug
===============================================================
U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 1
Name of the Drug- TRULANCE
Active Ingredient- Plecanatide Pharmacological Classification-
To treat Chronic Idiopathic Constipation (CIC) in adult patients
Date of Approval- 01-19-2017
(Ref- FDA approved List 2017) HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
TRULANCE safely and effectively. See full prescribing information for TRULANCE.
TRULANCE (plecanatide) tablets, for oral use Initial U.S. Approval: 2017
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.
Avoid use of TRULANCE in patients 6 years to less than 18 years of age.
The safety and effectiveness of TRULANCE have not been established in patients
less than 18 years of age.
Adverse Reaction:
ADVERSE REACTIONS
1. Clinical 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.
The safety data described below reflect data from 1733 adult patients
with CIC randomized in two double-blind, placebo-controlled
clinical trials (Study 1 and Study 2) to receive placebo or 3 mg o
TRULANCE once daily for 12 weeks. Demographic characteristics
were comparable between the TRULANCE and placebo groups..
Contra-Indications:
CONTRAINDICATIONS-
TRULANCE is contraindicated in:
Patients less than 6 years of age due to the risk of serious dehydratio
[see Warnings and Precautions
Patients with known or suspected mechanical gastrointestinal obstruction.
WARNINGS AND PRECAUTIONS
1. Risk 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 olde
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..
2. Diarrhea
Diarrhea was the most common adverse reaction in the two placebo-controlled
clinical trials. Severe diarrhea was reported in 0.6% of patients
If severe diarrhea occurs, suspend dosing and rehydrate the patient.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
TRULANCE is a guanylate cyclase-C agonist indicated in adults for treatment
of chronic idiopathic constipation (CIC).
DOSAGE AND ADMINISTRATION
The recommended adult dosage of TRULANCE is 3 mg taken orally once daily.
Administration Instructions
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.
DOSAGE FORMS AND STRENGTHS
Tablets: 3 mg
Patient Information:
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.
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
Administration and Handling Instructions
1.To take TRULANCE once daily with or without food
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.
3.To swallow TRULANCE tablets whole.
4.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.
5.To keep TRULANCE in a dry place. Protect from moisture.
6. For bottles, 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
TRULANCE is a trademark of Synergy Pharmaceuticals Inc.
Manufactured for:
Synergy Pharmaceuticals Inc.
420 Lexington Avenue, Suite 2012
New York, New York 10170
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Plecanatide is structurally related to human uroguanylin, and similar 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 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.
2. Pharmacodynamics
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 ..
3. Pharmacokinetics
Absorption
Plecanatide is minimally absorbed with negligible systemic availability following
oral administration. Concentrations of plecanatide and its active metabolite
in plasma are below the limit of quantitation after an oral TRULANCE dose of 3 mg.
Therefore, standard pharmacokinetic parameters such as AUC, maximum
concentration (Cmax), and half-life (t½) cannot be calculated.
Distribution
Given that plecanatide concentrations following clinically relevant oral doses
are not measurable, plecanatide is expected to be minimally distributed in tissues.
Oral plecanatide is localized to the GI tract where it exerts its effects as a GC-C
agonist with negligible systemic exposure.
Plecanatide exhibits little to no binding to human serum albumin or human á-1-acid glycoprotein.
Elimination
Metabolism
Plecanatide is metabolized in the GI tract to an active metabolite by loss of
the terminal leucine moiety. Both plecanatide and the metabolite are
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 are 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 are neither substrates nor inhibitors
of the transporters P-glycoprotein (P-gp) or breast cancer resistance
protein (BCRP) in vitro.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Risk Summary
Plecanatide and its active metabolite are negligibly absorbed systemically
following oral administration 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.
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.
2. Lactation
Risk Summary
There is no information regarding the presence of plecanatide in human milk,
or its effects on milk production or the breastfed infant.
No lactation studies in animals have been conducted.
It is unknown whether the negligible systemic absorption of plecanatide
by adults will result in a clinically relevant exposure to breastfed infants
Exposure to plecanatide in breastfed infants has the potential for serious
adverse effects.
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.
3.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.
The safety and effectiveness of TRULANCE in patients less than 18 years
of age have not been established.
4. Geriatric Use
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.
Of 2601 subjects in clinical trials of TRULANCE, 273 (10%) were 65 years
of age and over, and 47 (2%) were 75 years and over.
In general, dose selection for an elderly patient should be cautious,
reflecting the greater frequency of decreased hepatic, renal, or cardiac function
and of concomitant disease or other drug therapy.