Tenapanor
FDA Drug Information • Also known as: Xphozah 10 Mg, Xphozah 20 Mg, Xphozah 30 Mg
- Brand Names
- Xphozah 10 Mg, Xphozah 20 Mg, Xphozah 30 Mg
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION XPHOZAH (tenapanor) tablets contain tenapanor hydrochloride as an active ingredient. Tenapanor hydrochloride is a sodium/hydrogen exchanger 3 (NHE3) inhibitor for oral use. The chemical name for tenapanor hydrochloride is 12,15-Dioxa-2,7,9-triazaheptadecanamide, 17-[[[3-[(4S)-6,8-dichloro-1,2,3,4-tetrahydro-2-methyl-4-isoquinolinyl]phenyl]sulphonyl]amino]-N-[2-[2-[2-[[[3-[(4S)-6,8-dichloro-1,2,3,4-tetrahydro-2-methyl-4-isoquinolinyl]phenyl]sulphonyl]amino]ethoxy]ethoxy]ethyl]-8-oxo-, hydrochloride (1:2). Tenapanor hydrochloride has the molecular formula of C 50 H 68 Cl 6 N 8 O 10 S 2 , the molecular weight of 1218 Daltons, and the chemical structure below: Tenapanor hydrochloride is a white to off-white to light brown hygroscopic amorphous solid. It is practically insoluble in water. XPHOZAH tablets contain the equivalent of 10, 20, or 30 mg of tenapanor (provided as 10.6, 21.3, and 31.9 mg of tenapanor hydrochloride, respectively). Inactive ingredients in the tablet are colloidal silicon dioxide, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, propyl gallate, stearic acid, tartaric acid, and the coating agent OPADRY ® , which consists of hypromellose, titanium dioxide and triacetin, as well as iron oxide yellow as colorant [10 mg and 20 mg tablets], iron oxide red as colorant [20 mg and 30 mg tablets] and iron oxide black as colorant [30 mg tablet]. Chemical Structure
What Is Tenapanor Used For?
1 INDICATIONS AND USAGE XPHOZAH is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. XPHOZAH is a sodium hydrogen exchanger 3 (NHE3) inhibitor indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Recommended dosage: 30 mg orally twice daily before the morning and evening meals ( 2.1 ). Manage serum phosphorus levels and tolerability with dosage adjustments ( 2.1 ). Take just prior to the first and last meals of the day ( 2.2 ). Instruct patients not to take right before a hemodialysis session, and instead take right before the next meal following dialysis ( 2.2 ). 2.1 Recommended Dosage The recommended dosage is 30 mg orally twice daily before the morning and evening meals. Monitor serum phosphorus and adjust the dosage as needed to manage gastrointestinal tolerability. 2.2 Administration Instructions Instruct patients to take XPHOZAH just prior to the first and last meals of the day [see Clinical Pharmacology (12.2) ] . Instruct patients not to take XPHOZAH right before a hemodialysis session, and instead take right before the next meal following dialysis, as patients may experience diarrhea after taking XPHOZAH [see Warnings and Precautions (5.1) ] . Instruct patients who miss a dose to skip the missed dose and take the next dose at the regular time.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Most common adverse reaction in the combined clinical trials was diarrhea, reported by 43-53% of patients ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Ardelyx at 1-844-974-6924 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials 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 754 adults with CKD on dialysis taking XPHOZAH in clinical trials as monotherapy and in combination with phosphate binders. Among the 754 patients, 258 patients were exposed to tenapanor for at least 26 weeks and 75 were exposed to tenapanor for at least one year. [see Clinical Studies (14) ] . Most Common Adverse Reaction Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials [see Warnings and Precautions (5.1) ] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of XPHOZAH. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity reactions: pruritis, rash, and urticaria
Drug Interactions
7 DRUG INTERACTIONS OATP2B1 Substrates: Potential for reduced exposure of the concomitant drug (e.g., enalapril). Monitor for signs related to loss of efficacy and adjust the dosage of the concomitantly administered drug as needed ( 7.1 ). Sodium Polystyrene Sulfonate (SPS): Separate administration by at least three hours ( 7.2 ). 7.1 OATP2B1 Substrates Tenapanor is an inhibitor of intestinal uptake transporter, OATP2B1 [see Clinical Pharmacology (12.3) ] . Drugs which are substrates of OATP2B1 may have reduced exposures when concomitantly taken with XPHOZAH. Monitor for signs related to loss of efficacy and adjust the dose of concomitantly administered drug as needed. Enalapril is a substrate of OATP2B1. When enalapril was coadministered with XPHOZAH (30 mg twice daily for five days), the peak exposure (C max ) of enalapril and its active metabolite, enalaprilat, decreased by approximately 70% and total systemic exposures (AUC) decreased by 50 to 65% compared to when enalapril was administered alone [see Clinical Pharmacology (12.3) ] . However, the decrease in enalaprilat's exposure with XPHOZAH may be offset by the inherently higher exposures observed in patients with CKD on dialysis due to its reduced renal clearance. Therefore, a lower starting dose of enalapril, which is otherwise recommended in patients with CKD on dialysis is not required when enalapril is coadministered with XPHOZAH. 7.2 Sodium Polystyrene Sulfonate Separate administration of XPHOZAH and sodium polystyrene sulfonate (SPS) by at least 3 hours. SPS binds to many commonly prescribed oral medicines.
Contraindications
4 CONTRAINDICATIONS XPHOZAH is contraindicated in patients under 6 years of age because of the risk of diarrhea and serious dehydration [see Warnings and Precautions (5.1) , Use in Specific Populations (8.5) ]. XPHOZAH is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Pediatric patients under 6 years of age ( 4 ). Patients with known or suspected mechanical gastrointestinal obstruction ( 4 ).
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Tenapanor is essentially non-absorbed systemically, with plasma concentrations below the limit of quantification (less than 0.5 ng/mL) following oral administration [see Clinical Pharmacology (12.3) ]. Therefore, maternal use is not expected to result in fetal exposure to the drug. The available data on XPHOZAH 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. In reproduction studies with tenapanor in pregnant rats and rabbits, no adverse fetal effects were observed in rats at 0.2 times the maximum recommended human dose and in rabbits at doses up to 15 times the maximum recommended human dose (based on body surface area) [see Nonclinical Toxicology (13.1) ] . The estimated background risk of major birth defects and miscarriage for women with CKD on dialysis with hyperphosphatemia 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. Animal Data In an embryofetal development study in rats, tenapanor was administered orally to pregnant rats during the period of organogenesis at dose levels of 1, 10 and 30 mg/kg/day. Tenapanor doses of 10 and 30 mg/kg/day were not tolerated by the pregnant rats and was associated with mortality and moribundity with body weight loss. The 10 and 30 mg/kg dose group animals were sacrificed early, and the fetuses were not examined for intrauterine parameters and fetal morphology. No adverse fetal effects were observed in rats at 1 mg/kg/day (approximately 0.2 times the maximum recommended human dose) and in rabbits at doses up to 45 mg/kg/day (approximately 15 times the maximum recommended human dose, based on body surface area). In a pre- and post-natal...
Overdosage
10 OVERDOSAGE No data are available regarding overdosage of XPHOZAH in patients. Based on nonclinical data, overdose of XPHOZAH 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 [see Warnings and Precautions (5.1) ] .
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING XPHOZAH is supplied as 10-, 20-, or 30-mg oval, biconvex, film-coated tablets supplied in white, opaque, high-density polyethylene bottles containing 60 or 14 tablets with a silica gel canister (as the desiccant) and screw-top polypropylene child-resistant cap lined with an induction-activated aluminum foil liner: Strength Color Deboss NDC Bottle/14 Bottle/60 10 mg Yellow /T10 73154-110-14 73154-110-60 20 mg Brown /T20 73154-120-14 73154-120-60 30 mg Red /T30 73154-130-14 73154-130-60 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Keep bottle tightly closed to protect from moisture. Store and dispense in original bottle with the desiccant. Image Image Image
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.