DRUG INTERACTIONS-(summary)

 • Take other orally adminisdetailstered drugs at least 6 hours before or 6 hours after Veltassa. 

DRUG INTERACTIONS-(details)

No formal drug interaction studies have been conducted in humans. In in vitro binding studies, Veltassa was shown to bind about half of the oral medications that were tested.

Binding of Veltassa to other oral medications could cause decreased gastrointestinal absorption and loss of efficacy when taken close to the time Veltassa is administered. Administer other oral medications at least 6 hours before or 6 hours after Veltassa.

Monitor for clinical response and/or blood levels where possible.

30/15 PRODUCT DETAILS 

Name of the drug-      VELTASSA

Active ingriendents-   Patiromer for Oral Suspension

FDA approved use-    To treat hyperkalemia, a serious condition in which the amount                                        of potassium in the blood is too high                                                                                 

 Date of Approval         10/21/2015

HIGHLIGHTS OF PRESCRIBING INFORMATION-

 These highlights do not include all the information needed to use VELTASSA™ safely and effectively. See full prescribing information for VELTASSA.

VELTASSA (patiromer) for oral suspension

Initial U.S. Approval: 2015

WARNING:                                                                                                                 BINDING TO OTHER ORAL MEDICATIONS Veltassa binds to many orally administered medications, which could decrease their absorption and reduce their effectiveness.

Administer other oral medications at least 6 hours before or 6 hours after Veltassa. Choose Veltassa or the other oral medication if adequate dosing separation is not possible.

INDICATIONS AND USAGE -

 Veltassa is a potassium binder indicated for the treatment of hyperkalemia.

(1) Limitation of Use Veltassa should not be used as an emergency treatment for life threatening hyperkalemia because of its delayed onset of action.

ADVERSE REACTIONS-

 • Most common adverse reactions (incidence = 2%) are constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort and flatulence.

CONTRAINDICATIONS -

 • Known hypersensitivity to Veltassa or any of its components.

WARNINGS AND PRECAUTIONS-

 • Worsening of Gastrointestinal Motility

 • Hypomagnesemia 

DOSAGE AND ADMINISTRATION -

 • The recommended starting dose of Veltassa is 8.4 grams administered orally once daily with food. (

 • Adjust dose by 8.4 grams daily as needed at one week intervals to obtain desired serum potassium target range. 

DOSAGE FORMS AND STRENGTHS-

 • Powder: 8.4, 16.8 and 25.2 grams patiromer packets.

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Drug Interactions Advise patients who are taking other oral medication to separate the dosing of Veltassa by at least 6 hours (before or after) [see Drug Interactions (7)].

Dosing Recommendations Inform patients to take Veltassa as directed with food and adhere to their prescribed diets.

Instruct patients to prepare each dose separately using the preparation instructions provided in the FDA-approved patient labeling (Medication Guide).

Inform patients that Veltassa should not be heated (e.g., microwaved) or added to heated foods or liquids and should not be taken in its dry form.

Manufactured for: Relypsa, Inc. Redwood City, CA 94063 Version 01; October 2015

CLINICAL PHARMACOLOGY-

1. Mechanism of Action-

Veltassa is a non-absorbed, cation exchange polymer that contains a calcium-sorbitol counterion.

Veltassa increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, resulting in a reduction of serum potassium levels.

2. Pharmacodynamics-                                                                                                     In a Phase 1 study in healthy adult subjects (6 to 8 subjects per group), Veltassa (0 grams to 50.4 grams per day) administered three times a day for 8 days caused a dose-dependent increase in fecal potassium excretion.

A corresponding dose-dependent decrease in urinary potassium excretion with no change in serum potassium were also observed. Compared to placebo,

Veltassa doses of 25.2 and 50.4 grams per day significantly decreased mean daily urinary potassium excretion. In a Phase 1, open-label, multiple-dose crossover study in 12 healthy subjects, 25.2 grams of patiromer per day was administered orally as a once daily, twice daily or thrice daily regimen for 6 days in a randomly assigned order.

A significant increase in mean daily fecal potassium excretion and concomitant decrease in mean daily urinary potassium excretion were observed during the treatment periods for all three dosing regimens.

The mean increase in fecal potassium excretion ranged from 1283 to 1550 mg/day, and the mean decrease in urinary potassium excretion ranged from 1438 to 1534 mg/day across the three dosing regimens. No significant differences were observed among the dosing regimens with respect to mean daily fecal potassium and urinary potassium excretion.

This was true for the overall comparison among the three dosing regimens, as well as for the pairwise comparisons. Reference ID: 3836559 In an open-label, uncontrolled study, 25 patients with hyperkalemia (mean baseline serum potassium of 5.9 mEq/L) and chronic kidney disease were given a controlled potassium diet for 3 days, followed by 16.8 grams patiromer daily (as divided doses) for 2 days while the controlled diet was continued.

A statistically significant reduction in serum potassium (-0.2 mEq/L) was observed at 7 hours after the first dose. Serum potassium levels continued to decline during the 48-hour treatment period (-0.8 mEq/L at 48 hours after the first dose). Potassium levels remained stable for 24 hours after the last dose, then rose during the 4-day observation period following discontinuation of Veltassa.

3. Pharmacokinetics In radiolabeled ADME studies in rats and dogs, patiromer was not systemically absorbed and was excreted in the feces. Quantitative whole-body autoradiography analysis in rats demonstrated that radioactivity was limited to the gastrointestinal tract, with no detectable level of radioactivity in any other tissues or organs.

Drug Interactions-                                                                                                       Veltassa binds many other orally administered medications in the gastrointestinal tract, which could lead to a decrease in absorption of other medications.

1. USE IN SPECIFIC POPULATIONS-

Pregnancy Risk Summary-

 Veltassa is not absorbed systemically following oral administration and maternal use is not expected to result in fetal risk.

2. Lactation Risk Summary Veltassa is not absorbed systemically by the mother, so breastfeeding is not expected to result in risk to the infant. Reference ID: 3836559

3. Pediatric Use-                                                                                                          Safety and efficacy in pediatric patients have not been established.

4. Geriatric Use-                                                                                                               Of the 666 patients treated with Veltassa in clinical studies, 59.8% were age 65 and over, and 19.8% were age 75 and over.

No overall differences in effectiveness were observed between these patients and younger patients.

Patients age 65 and older reported more gastrointestinal adverse reactions than younger patients.

5. Renal Impairment-                                                                                                       Of the 666 patients treated with Veltassa in clinical studies, 93% had chronic kidney disease (CKD). No special dosing adjustments are needed for patients with renal impairment.

 OVERDOSAGE -

Doses of Veltassa in excess of 50.4 grams per day have not been tested. Excessive doses of Veltassa may result in hypokalemia.

Restore serum potassium if hypokalemia occurs.