VELTASSA

VELTASSA- patiromer powder, for suspension
Vifor Pharma, Inc.

1 INDICATIONS AND USAGE

Veltassa is indicated for the treatment of hyperkalemia.

Limitation of Use: Veltassa should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2)].

2 DOSAGE AND ADMINISTRATION

2.1 General Information

Administer Veltassa at least 3 hours before or 3 hours after other oral medications except those shown to not have a clinically important interaction [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

Do not heat Veltassa (e.g., microwave) or add to heated foods or liquids. Do not take Veltassa in its dry form.

2.2 Recommended Dosing and Titration

The recommended starting dose of Veltassa is 8.4 grams patiromer once daily. Monitor serum potassium and adjust the dose of Veltassa based on the serum potassium level and the desired target range. The dose may be increased or decreased, as necessary, to reach the desired serum potassium concentration, up to a maximum dose of 25.2 grams once daily. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 grams.

2.3 Preparation of Veltassa

Prepare each dose immediately prior to administration.

Measure 1/3 cup of water. Pour half of the water into a glass, then add Veltassa and stir. Add the remaining half of the water and stir thoroughly. The powder will not dissolve and the mixture will look cloudy. Add more water to the mixture as needed for desired consistency.

Drink the mixture immediately. If powder remains in the glass after drinking, add more water, stir and drink immediately. Repeat as needed to ensure the entire dose is administered.

Other beverages, or soft foods (e.g., apple sauce, yogurt, pudding) can be used instead of water to prepare the mixture by following the same steps as described above.

The potassium content of liquids or soft foods used to prepare the mixture should be considered as part of the dietary recommendations on potassium intake for each individual patient.

3 DOSAGE FORMS AND STRENGTHS

Veltassa is an off-white to light-brown powder for oral suspension packaged in single-use packets containing 8.4 grams, 16.8 grams or 25.2 grams patiromer.

4 CONTRAINDICATIONS

Veltassa is contraindicated in patients with a history of a hypersensitivity reaction to Veltassa or any of its components [see Adverse Reactions (6.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Worsening of Gastrointestinal Motility

Avoid use of Veltassa in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because Veltassa may be ineffective and may worsen gastrointestinal conditions.

Patients with a history of bowel obstruction or major gastrointestinal surgery, severe gastrointestinal disorders, or swallowing disorders were not included in the clinical studies.

5.2 Hypomagnesemia

Veltassa binds to magnesium in the colon, which can lead to hypomagnesemia. In clinical studies, hypomagnesemia was reported as an adverse reaction in 5.3% of patients treated with Veltassa [see Adverse Reactions (6.1)]. Monitor serum magnesium. Consider magnesium supplementation in patients who develop low serum magnesium levels on Veltassa.

6 ADVERSE REACTIONS

The following adverse reaction is discussed in greater detail elsewhere in the label:

• Hypomagnesemia [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Veltassa cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.

In the safety and efficacy clinical trials, 666 adult patients received at least one dose of Veltassa, including 219 exposed for at least 6 months and 149 exposed for at least one year.

Table 1 provides a summary of the most common adverse reactions (occurring in ≥ 2% of patients) in patients treated with Veltassa in these clinical trials. Most adverse reactions were mild to moderate. Constipation generally resolved during the course of treatment.

Table 1: Adverse Reactions Reported in ≥ 2% of Patients

Adverse Reactions	Patients treated with Veltassa(N=666)
Constipation	7.2%
Hypomagnesemia	5.3%
Diarrhea	4.8%
Nausea	2.3%
Abdominal discomfort	2.0%
Flatulence	2.0%

During the clinical studies, the most commonly reported adverse reactions leading to discontinuation of Veltassa were gastrointestinal adverse reactions (2.7%), including vomiting (0.8%), diarrhea (0.6%), constipation (0.5%) and flatulence (0.5%).

Mild to moderate hypersensitivity reactions were reported in 0.3% of patients treated with Veltassa in clinical trials. Reactions have included edema of the lips.

Laboratory Abnormalities

Approximately 4.7% of patients in clinical trials developed hypokalemia with a serum potassium value < 3.5 mEq/L.

Approximately 9% of patients in clinical trials developed hypomagnesemia with a serum magnesium value < 1.4 mg/dL.

7 DRUG INTERACTIONS

Veltassa has the potential to bind some oral co-administered medications, which could decrease their gastrointestinal absorption. Binding of Veltassa to other oral medications not listed in Table 3 below could cause decreased gastrointestinal absorption and loss of efficacy when taken close to the time Veltassa is administered. Administer other oral medications at least 3 hours before or 3 hours after Veltassa [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

7.1 Clinically Important Interaction of Veltassa With Other Drugs

The in-vitro binding of the following drugs to patiromer was evaluated and potentially clinically significant binding was observed. Some drugs were subsequently tested in-vivo and significant reduction in systemic exposure was observed [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

Table 2. Clinically important drug interactions of Veltassa

Angiotensin II receptor blockers (ARB) Telmisartan
Clinical Impact	Binding by Veltassa may reduce the systemic exposure and decrease the clinical efficacy resulting in inadequate control of hypertension.
Intervention	Separate administration by at least 3 hours from Veltassa.
β-adrenoceptor blockers (β-blocker) Bisoprolol, carvedilol, nebivolol
Clinical Impact	Binding by Veltassa may reduce the systemic exposure and decrease the clinical efficacy resulting in inadequate control of hypertension.
Intervention	Separate administration by at least 3 hours from Veltassa.
Antibiotics Ciprofloxacin
Clinical Impact	When co-administered, binding by Veltassa reduced the systemic exposure which may result in reduction in antibiotic efficacy. Systemic exposure was not affected when separated by 3 hours.
Intervention	Separate administration by at least 3 hours from Veltassa.
Anti-Parathyroid Agents and Thyroid Preparations Levothyroxine
Clinical Impact	When co-administered, binding by Veltassa reduced the systemic exposure which may result in reduction in efficacy. Systemic exposure was not affected when separated by 3 hours.
Intervention	Separate administration by at least 3 hours from Veltassa.
Blood Glucose Lowering Drugs Metformin
Clinical Impact	When co-administered, binding by Veltassa reduced the systemic exposure which may result in reduction in glycemic control. Systemic exposure was not affected when separated by 3 hours.
Intervention	Separate administration by at least 3 hours from Veltassa.
Immunosuppressants Mycophenolate mofetil
Clinical Impact	Binding by Veltassa may reduce the systemic exposure and decrease the clinical efficacy.
Intervention	Separate administration by at least 3 hours from Veltassa.
Others Quinidine, thiamine
Clinical Impact	Binding by Veltassa may reduce the systemic exposure and decrease the clinical efficacy.
Intervention	Separate administration by at least 3 hours from Veltassa.