Tenapanor Hydrochloride (Phosphate-Removing Agent) (Monograph)

Brand name: Xphozah
Drug class: Phosphate-reducing Agents

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Locally acting sodium hydrogen exchanger 3 (NHE3) inhibitor.

Uses for Tenapanor Hydrochloride (Phosphate-Removing Agent)

Hyperphosphatemia

Used 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.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend limiting dietary phosphate intake either alone or in combination with other treatments in patients with CKD and hyperphosphatemia; phosphate-lowering therapies should be implemented in patients with progressively or persistently elevated serum phosphate in addition to increased dialytic phosphate removal.

Tenapanor Hydrochloride (Phosphate-Removing Agent) Dosage and Administration

General

Patient Monitoring

• Monitor serum phosphorus and adjust dosage as needed.

• Monitor GI tolerability and adjust dosage accordingly. Treatment with tenapanor should be discontinued in patients who develop severe diarrhea.

Administration

Administer orally twice daily.

Should be taken just prior to first and last meals of the day.

Should not be taken right before a hemodialysis session; instead take right before the next meal following dialysis, as patients may experience diarrhea after taking tenapanor.

If a dose is missed, skip missed dose and take next dose at regular time.

Dosage

Available as tenapanor hydrochloride; dosage expressed in terms of tenapanor.

Adults

Hyperphosphatemia

Oral

30 mg twice daily before morning and evening meals.

Monitor serum phosphorus and adjust dosage as needed to manage GI tolerability.

Special Populations

Hepatic Impairment

No specific population dosage recommendations at this time.

Renal Impairment

No specific population dosage recommendations at this time.

Geriatric Patients

No specific population dosage recommendations at this time.

Cautions for Tenapanor Hydrochloride (Phosphate-Removing Agent)

Contraindications

• Age <6 years due to risk of diarrhea and severe dehydration.

• Known or suspected mechanical GI obstruction.

Warnings/Precautions

Diarrhea

Diarrhea was most common adverse reaction in tenapanor-treated patients with CKD on dialysis. In clinical trials, diarrhea was reported in up to 53% of patients, reported as severe in 5%, and was associated with dehydration and hyponatremia in <1% of patients.

Discontinue treatment in patients who develop severe diarrhea.

Specific Populations

Pregnancy

Tenapanor is essentially non-absorbed systemically, with plasma concentrations below limit of quantification (<0.5 ng/mL) following oral administration. Therefore, maternal use is not expected to result in fetal exposure to the drug. Available data 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.

Lactation

There are no data on the presence of tenapanor in human milk, the effects on the breast-fed child, or the effects on milk production. The minimal systemic absorption will not result in a clinically relevant exposure to breast-fed infants.

Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for tenapanor or any potential adverse effects on the breast-fed infant from tenapanor or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients not established. Tenapanor is contraindicated in patients <6 years of age.

Geriatric Use

Clinical studies with tenapanor did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently than younger subjects.

Hepatic Impairment

Compared to patients with normal hepatic function, geometric mean peak plasma concentration of the M1 metabolite was lower in patients with moderate (Child-Pugh class B) hepatic impairment.

Renal Impairment

Steady state plasma concentration of M1 metabolite in patients with CKD on dialysis was not notably different from healthy patients given similar tenapanor dosages.

Common Adverse Effects

Most common adverse effect (43—53% of patients): diarrhea.

Drug Interactions

Tenapanor and its primary metabolite, M1, do not inhibit cytochrome P-450 (CYP) 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6. Tenapanor and M1 do not induce CYP1A2 and 2B6.

Not a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 2B1, and OATP1B3. M1 is a substrate of P-gp.

Not an inhibitor of P-gp, BCRP, OATP1B1, OATP1B3, and peptide transporter (PEPT) 1. M1 does not inhibit P-gp, BCRP, OATP1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, multidrug and toxin extrusion (MATE) 1, and MATE2-K.

Inhibitor of OATP2B1.

Drugs Affecting or Affected by Transport Systems

Drugs which are substrates of OATP2B1 may have reduced exposures when concomitantly taken with tenapanor. Monitor for signs related to loss of efficacy and adjust dosage of concomitantly administered drug as needed.

Specific Drugs

Tenapanor Hydrochloride (Phosphate-Removing Agent) Pharmacokinetics

Plasma concentrations below the limit of quantification (<0.5 ng/mL) following single and repeated oral administration of tenapanor 30 mg twice daily. Therefore, standard pharmacokinetic parameters such as AUC, peak plasma concentrations (C_max), and half-life cannot be determined.

Absorption

Bioavailability

Minimally absorbed following repeated twice daily oral administration.

Effect of Food

Administration 5 to 10 minutes before meal increases 24-hour stool phosphorus excretion compared to fed or fasting condition.

Distribution

Plasma Protein Binding

Tenapanor: 99% (in vitro).

M1 (major metabolite): 97% (in vitro).

Elimination

Metabolism

Primarily by CYP3A4/5.

Elimination Route

70% excreted in feces through 120 hours post-dose (79% through 240 hours post-dose), mostly as parent drug accounting for 65% of dose within 144 hours post-dose.

Approximately 9% of administered dose recovered in urine, primarily as metabolites; M1 excreted in urine unchanged, accounting for 1.5% of dose within 144 hours post-dose.

Stability

Storage

Oral

Tablets, film-coated

Store at 20—25ºC; excursions permitted between 15-30ºC.

Dispense and store in original bottle with the desiccant to protect from moisture. Keep bottle tightly closed.

Actions

• Locally acting inhibitor that targets the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of epithelium of small intestine and colon.

• Inhibition of NHE3 results in reduced sodium absorption and decreased phosphate absorption by reducing phosphate permeability through paracellular pathway.

Advice to Patients

• Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide).

• Advise patients to contact their healthcare provider if they experience severe diarrhea.

• Advise patients not to use stool softeners or laxatives with tenapanor.

• Advise patients to take tenapanor just prior to the first and last meals of the day.

• Advise patients not to take tenapanor right before a hemodialysis session, and to take tenapanor right before the next meal, as some patients may experience diarrhea after taking tenapanor.

• If a dose is missed, advise patients to skip the missed dose and take the next dose at the regular time. Advise patients not to take 2 doses at the same time.

• Advise patients to keep tenapanor in a dry place to protect from moisture. Tenapanor should be kept in the original bottle. Advise patients not to remove the desiccant from the bottle and to keep bottles tightly closed.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tenapanor is obtained through designated specialty pharmacies and distributors. Contact manufacturer or consult the tenapanor website ([Web]) for specific availability information.

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