27/19. Tenapanor- (IBSRELA)- @-(Sept 19)- Irritable bowel syndrome
Drug Name:27/19. Tenapanor- (IBSRELA)- @-(Sept 19)- Irritable bowel syndrome
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:
Covered under Pharmacology/Pharmaokinetics
Indication:
BRIEF SUMMARY
TENAPANOR-(Sept 2019)
Indn- To treat irritable bowel syndrome with constipation in adults
Comp- Tablets: 50 mg tenapanor. is a sodium/hydrogen exchanger 3 (NHE3) inhibitor indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.
ADR- Most common adverse reactions (=2%) are diarrhea, abdominal distension, flatulence and dizziness
CI- • Pediatric patients less than 6 years of age.
• Patients with known or suspected mechanical gastrointestinal obstruction.
WARNINGS-
Diarrhea: Patients may experience severe diarrhea. If severe diarrhea occurs, suspend dosing and rehydrate patient.
Pat Inform-
Diarrhea
Instruct patients to stop and contact their healthcare provider if they experience severe diarrhea
Accidental Ingestion
Accidental ingestion in children, especially children less than 6 years of age, may result in severe diarrhea and dehydration. Instruct patients to store securely and out of reach of children
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U.S. FDA APPROVED DRUGS DURING 2019
Sr.No.27
Name of the Drug- IBSRELA
Active Ingredient - Tenapanor
Pharmacological Classification-
To treat irritable bowel syndrome with constipation in adults
Date of Approval - 9/12/2019
(Ref- FDA approved List 2019
.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
IBSRELA® safely and effectively. See full prescribing information for IBSRELA. IBSRELA (tenapanor) tablets, for oral use
Initial U.S. Approval: 2019
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS
See full prescribing information for complete boxed warning.
• IBSRELA is contraindicated in patients less than 6 years of age; in young juvenile rats, tenapanor caused death presumed to be due to dehydration.
• Avoid use of IBSRELA in patients 6 years to less than 12 years of age.
• The safety and effectiveness of IBSRELA have not been established in pediatric patients less than 18 years of age.
INDICATIONS AND USAGE
IBSRELA is a sodium/hydrogen exchanger 3 (NHE3) inhibitor indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (=2%) are diarrhea, abdominal distension, flatulence and dizziness.
Contra-Indications:
CONTRAINDICATIONS
• Pediatric patients less than 6 years of age.
• Patients with known or suspected mechanical gastrointestinal obstruction.
WARNINGS AND PRECAUTIONS
Diarrhea: Patients may experience severe diarrhea. If severe diarrhea occurs, suspend dosing and rehydrate patient.
Dosages/ Overdosage Etc:
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS
See full prescribing information for complete boxed warning.
• IBSRELA is contraindicated in patients less than 6 years of age; in young juvenile rats, tenapanor caused death presumed to be due to dehydration.
• Avoid use of IBSRELA in patients 6 years to less than 12 years of age.
• The safety and effectiveness of IBSRELA have not been established in pediatric patients less than 18 years of age.
INDICATIONS AND USAGE
IBSRELA is a sodium/hydrogen exchanger 3 (NHE3) inhibitor indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.
DOSAGE AND ADMINISTRATION
The recommended dosage in adults is 50 mg, orally twice daily.
• Take immediately prior to breakfast or the first meal of the day and immediately prior to dinner.
DOSAGE FORMS AND STRENGTHS
Tablets: 50 mg tenapanor.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patients to read the FDA-approved patient labeling (Medication Guide).
Diarrhea
Instruct patients to stop IBSRELA and contact their healthcare provider if they experience severe diarrhea
Accidental Ingestion
Accidental ingestion of IBSRELA in children, especially children less than 6 years of age, may result in severe diarrhea and dehydration. Instruct patients to store IBSRELA securely and out of reach of children
Administration and Handling Instructions
Instruct Patients:
• To take IBSRELA immediately prior to breakfast or the first meal of the day and
immediately before dinner.
• If a dose is missed, skip the missed dose and take the next dose at the regular time.
Do not take 2 doses at the same time.
• To keep IBSRELA in a dry place. Protect from moisture. Keep in the original bottle. Do not remove desiccant from the bottle. Do not subdivide or repackage. Keep bottles tightly closed
Marketed by Ardelyx, Inc. 34175 Ardenwood Blvd., Suite 100 Fremont, CA 94555
IBSRELA® is a registered trademark of Ardelyx, Inc.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Tenapanor is a locally acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium.
2. Pharmacodynamics
Cardiac Electrophysiology
At 3 times the mean maximum exposure of M1 at the recommended dosage, there were no clinically relevant effects on the QTc interval.
Food Effect
Administration of IBSRELA 5 to 10 minutes before a meal increased the 24-hour stool sodium excretion compared to taking IBSRELA in the fed or fasting condition
In clinical trials, IBSRELA was administered immediately prior to the first meal of the day and immediately prior to dinner.
3. Pharmacokinetics
Absorption
Tenapanor is minimally absorbed following repeated twice daily oral administration. Plasma concentrations of tenapanor were below the limit of quantitation (less than 0.5 ng/mL) in the majority of samples from healthy subjects following single and repeated oral administration of IBSRELA 50 mg twice daily.
Therefore, standard pharmacokinetic parameters such as area under the curve (AUC), maximum concentration (Cmax), and half-life (t1/2) could not be determined.
Distribution
Plasma protein binding of tenapanor and its major metabolite, M1, is approximately 99% and 97%, respectively, in vitro.
Elimination
Metabolism
Tenapanor is metabolized primarily by CYP3A4/5 and low levels of its major metabolite, M1, are detected in plasma. The Cmax of M1 is approximately 13 ng/mL after single dose of IBSRELA 50 mg and 15 ng/mL at steady state following repeated dosing of IBSRELA 50 mg twice daily in healthy subjects.
Excretion
Following administration of a single 15 mg radiolabeled 14C-tenapanor dose to healthy subjects, approximately 70% of the radioactivity was excreted in feces within 120 hours post-dose and 79% within 240 hours post-dose, mostly as the parent drug accounting for 65% of dose within 144 hours post-dose.
Approximately 9% of the administered dose was recovered in urine, primarily as metabolites. M1 is excreted in urine unchanged accounting for 1.5% of dose within 144 hours post-dose.
Specific Populations
Patients with Renal Impairment
Based on a cross-study comparison, plasma concentrations of M1 in end-stage renal disease patients on hemodialysis (eGFR less than 15 mL/min/1.73m2) was not notably different from those of healthy subjects given comparable doses of IBSRELA.
Drug Interaction Studies
CYP Metabolism Mediated Drug Interactions
Tenapanor and M1 did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6 in vitro.
Tenapanor and M1 did not induce CYP1A2 and CYP2B6 in vitro.
No significant inhibition or induction of CYP3A4 enzyme using midazolam as a substrate was observed when IBSRELA 50 mg was administered twice a day for 13 days in healthy subjects.
Following co-administration of a single dose of IBSRELA 50 mg with repeated doses of itraconazole 200 mg, a CYP3A4 inhibitor, the mean AUC and Cmax of M1 was decreased 50% in healthy subjects.
Plasma concentrations of tenapanor were mostly below the limit of quantitation (less than 0.5 ng/mL) after co-administration of itraconazole.
Membrane Transporter Mediated Drug Interactions
Tenapanor and M1 did not inhibit P-gp, BCRP, OATP1B1, and OATP1B3. M1 did not inhibit OAT1, OAT3, OCT2, MATE1, and MATE2-K.
M1 is a substrate of P-gp. Tenapanor is not a substrate of P-gp, BCRP, OATP1B1, and OATP1B3. M1 is not a substrate of BCRP, OAT1, OAT3, OCT2, MATE1 and MATE2-K.
No significant effect on PepT1 activity using cefadroxil as a substrate was observed when IBSRELA 50 mg was administered twice a day for 12 days in healthy subjects.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration
Therefore, maternal use is not expected to result in fetal exposure to the drug.
The available data on IBSRELA exposure from a small number of pregnant women have not identified any drug associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes.
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary
Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration
[
Therefore, maternal use is not expected to result in fetal exposure to the drug.
The available data on IBSRELA exposure from a small number of pregnant women have not identified any drug associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes.
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 are no data available on the presence of tenapanor in either human or animal milk, its effects on milk production or its effects on the breastfed infant.
Tenapanor is minimally absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration
The minimal systemic absorption of tenapanor will not result in a clinically relevant exposure to breastfed infants.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for IBSRELA and any potential adverse effects on the breastfed infant from IBSRELA or from the underlying maternal condition.
3.Pediatric Use
IBSRELA is contraindicated in patients less than 6 years of age. Avoid IBSRELA in patients 6 years to less than 12 years of age
The safety and effectiveness of IBSRELA in patients less than 18 years of age have not been established.
4.Geriatric Use-
.Of the 1203 patients in placebo-controlled clinical trials of IBSRELA, 100 (8%) were 65 years of age and older.
No overall differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
OVERDOSAGE
Based on nonclinical data, overdose of IBSRELA may result in gastrointestinal adverse effects such as diarrhea as a result of exaggerated pharmacology with a risk for dehydration if diarrhea is severe or prolonged
