Tenapanor (Phosphate-removing Agent) (Monograph)

Brand name: Xphozah
Drug class: Phosphate-reducing Agents

Introduction

Tenapanor hydrochloride is a locally acting inhibitor of sodium hydrogen exchanger 3 (NHE3).

Uses for Tenapanor (Phosphate-removing Agent)

Tenapanor hydrochloride has the following uses:

Tenapanor hydrochloride (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.

For use of tenapanor in the treatment of irritable bowel syndrome (IBS), see tenapanor 56:92.

Tenapanor (Phosphate-removing Agent) Dosage and Administration

General

Tenapanor is available in the following dosage form(s) and strength(s):

Tablets: 10 mg, 20 mg, and 30 mg

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Recommended dosage: 30 mg orally twice daily before the morning and evening meals. Monitor serum phosphorus and adjust the dosage as needed to manage GI tolerability.

• Take just prior to the first and last meals of the day.

• Instruct patients not to take right before a hemodialysis session, and instead take right before the next meal following dialysis.

Related/similar drugs

MiraLAX, sucralfate, Linzess, polyethylene glycol 3350, Carafate, sevelamer, lubiprostone

Cautions for Tenapanor (Phosphate-removing Agent)

Contraindications

Pediatric patients under 6 years of age.

Patients with known or suspected mechanical GI obstruction.

Warnings/Precautions

Diarrhea

Diarrhea was the 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 associated with dehydration and hyponatremia in less than 1% of patients. Treatment with tenapanor should be discontinued in patients who develop severe diarrhea.

Specific Populations

Pregnancy

Tenapanor is essentially non-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 tenapanor 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).

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.

Lactation

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 essentially non-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 tenapanor and any potential adverse effects on the breastfed infant from tenapanor or from the underlying maternal condition.

Pediatric Use

Tenapanor is contraindicated in patients less than 6 years of age. In nonclinical studies, deaths occurred in young juvenile rats (less than 1-week old rats; approximate human age-equivalent of less than 2 years of age) and in older juvenile rats (approximate human age-equivalent of 2 years of age) following oral administration of tenapanor, as described below in Juvenile Animal Toxicity Data.

The safety and effectiveness of tenapanor in pediatric patients have not been established.

Juvenile Animal Toxicity Data

In a 21-day oral dose range finding toxicity study in juvenile rats, tenapanor was administered to neonatal rats (post-natal day (PND) 5) at doses of 5 and 10 mg/kg/day. Tenapanor was not tolerated in male and female pups and the study was terminated on PND 16 due to mortalities and decreased body weight (24% to 29% reduction in females at the respective dose groups and 33% reduction in males in the 10 mg/kg/day group, compared to control).

In a second dose range finding study, tenapanor doses of 0.1, 0.5, 2.5, or 5 mg/kg/day were administered to neonatal rats from PND 5 through PND 24. Treatment-related mortalities were observed at 0.5, 2.5, and 5 mg/kg/day doses. These premature deaths were observed as early as PND 8, with majority of deaths occurring between PND 15 and 25. In the 5 mg/kg/day group, mean body weights were 47% lower for males on PND 23 and 35% lower for females on PND 22 when compared to the controls. Slightly lower mean tibial lengths (5% to 11%) were noted in males and females in the 0.5, 2.5, and 5 mg/kg/day dose groups on PND 25 and correlated with the decrements in body weight noted in these groups. Lower spleen, thymus, and/or ovarian weights were noted at the 0.5, 2.5, and 5 mg/kg/day doses. Tenapanor-related GI distension and microscopic bone findings of increased osteoclasts, eroded bone, and/or decreased bone in sternum and/or femorotibial joint were noted in males and females in the 0.5, 2.5, and 5 mg/kg/day dose groups.

In juvenile rats administered tenapanor at 0.03, 0.1, or 0.3 mg/kg/day on PND 5 through PND 61, treatment-related mortalities were observed at 0.3 mg/kg/day. Lower mean body weight gains were noted in the 0.3 mg/kg/day group males and females compared to the control group primarily during PND 12–24 but continuing sporadically during the remainder of the dosing period; corresponding lower mean food consumption was noted in this group during PND 21–33. As a result, mean body weights were up to 15.8% and 16.8% lower in males and females, respectively, compared to the control group; the greatest difference was on PND 24 for males and PND 21 for females. Mean body weight in the 0.3 mg/kg/day group males was only 3.9% lower than the control group on PND 61. There were no tenapanor-related effects on mean body weights, body weight gains, or food consumption in the 0.03 and 0.1 mg/kg/day group males and females. A dosage level of 0.1 mg/kg/day was considered to be the no-observed-adverse-effect level (NOAEL) for juvenile toxicity of tenapanor.

In a 21-day oral dose range finding study in older (weaned) juvenile rats administered tenapanor at 0.1, 1, or 5 mg/kg/day on PND 21 through PND 41 (approximate human age-equivalent of 2 to 12 years of age), treatment-related mortalities or moribundities were observed during the first two days of the study in the 1 mg/kg/day males and the 5 mg/kg/day males and females. Watery feces, decreased food consumption, and lower mean body weight were also observed in the 1 and 5 mg/kg/day groups.

In weaned juvenile rats administered tenapanor at 0.1, 0.3, and 0.7 (males) or 1 (females) mg/kg/day on PND 21 through PND 80, no mortalities were observed. Significant decreases in mean body weights were observed in the 0.3 and 0.7 mg/kg/day males throughout the dosing period (up to 20.3% lower than control) and in the 1 mg/kg/day females between PND 23 to 35 (up to 16.7% lower than control), with food consumption notably decreased on PND 21 to 29. There were also reductions in tibia length between PND 76 and 80 in the 0.3 and 0.7 mg/kg/day males, and between PND 36 and 64 in the 0.7 mg/kg/day males, which were not observed during the 14-day recovery period. The NOAEL was considered to be 0.1 mg/kg/day for juvenile toxicity of tenapanor.

Geriatric Use

Of 1010 adult patients with CKD on dialysis randomized and treated in two randomized, double-blind, placebo-controlled randomized withdrawal clinical trials for tenapanor (TEN-02-201 and TEN-02-301) as well as a third randomized, double-blind, placebo-controlled trial (TEN-02-202) for tenapanor in combination with phosphate binders, 282 (28%) were 65 years of age and older. Clinical studies of tenapanor did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently than younger patients.

Common Adverse Effects

Most common adverse reaction in the combined clinical trials was diarrhea, reported by 43-53% of patients.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• 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.

• Sodium Polystyrene Sulfonate (SPS): Separate administration by at least 3 hours.

Actions

Mechanism of Action

Tenapanor is a locally acting inhibitor that targets the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the epithelium of the small intestine and colon. Inhibition of NHE3 by tenapanor results in reduced sodium absorption and decreased phosphate absorption by reducing phosphate permeability through the paracellular pathway.

Advice to Patients

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

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

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

• Patients should be counseled 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 take the dose just before the next meal; do not take 2 doses at the same time.

• Advise patients to keep tenapanor in a dry place. Protect from moisture and keep in the original bottle. Do not remove desiccant from the bottle. Keep bottles tightly closed

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.

Reload page with references included

Medical Disclaimer