Pizensy

PIZENSY is indicated for chronic idiopathic constipation (CIC) in adults.

Recommended Dosage

• The recommended adult dosage of PIZENSY is 20 grams orally once daily, preferably with meals .
• Reduce the dosage to 10 grams once daily for persistent loose stools.
• Administer oral medications at least 2 hours before or 2 hours after PIZENSY .

Preparation And Administration Instructions

PIZENSY Multi-Dose Bottle

NOTE: The bottle top is a measuring cap marked to contain 10 grams of powder when filled to the top of white section in the cap marked by the arrow.

1. Using the measuring cap, measure the prescribed dose.
   • 20-gram dose: Fill the measuring cap twice to the top of the white section in cap marked by the arrow.
   • 10-gram dose: Fill the measuring cap once to the top of the white section in cap marked by the arrow.
2. Pour the measured dose into an empty 8-ounce glass.
3. Add 4 ounces to 8 ounces of water, juice or other common beverages (coffee, tea, soda) and stir to dissolve.
4. Drink the entire contents of the glass.

PIZENSY Unit-Dose Packets

1. Pour the contents of one or two unit-dose packets, as prescribed, into an empty 8-ounce glass.
2. Add 4 ounces to 8 ounces of water, juice or other common beverages (coffee, tea, soda) to the glass containing the powder and stir thoroughly to dissolve.
3. Drink the entire contents of the glass.

PIZENSY is contraindicated in patients with:

• known or suspected mechanical gastrointestinal obstruction
• galactosemia

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a 26-week carcinogenicity study in Tg.rasH2 mice at daily oral doses of lactitol up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area), there were no drug-related neoplasms.

Published studies indicated that lactitol was negative in the Ames test, chromosome aberration test with cultured mammalian cells, and in vivo mouse micronucleus test.

Published studies indicated that lactitol did not cause any adverse effect on fertility and early embryonic development in rats at doses up to 10 g/kg/day (about 4.6 times the recommended daily human dose based on body surface area).

Use In Specific Populations

Pregnancy

Risk Summary

Lactitol is minimally absorbed systemically following oral administration , and it is unknown whether maternal use will result in fetal exposure to the drug. Available data from case reports on lactitol use in pregnant women are insufficient to evaluate for any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of lactitol to rats and rabbits during organogenesis at doses much higher than the maximum recommended human dosage.

The estimated background risk of major birth defects and miscarriage for the indicated population 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.

Data

Animal Data

Reproduction studies have been performed in pregnant rats at oral doses of lactitol up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area) and in pregnant rabbits at oral doses up to 1 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area) administered during the period of organogenesis. These studies did not reveal any evidence of harm to the fetus due to lactitol.

In a pre-and postnatal development study in rats, lactitol, administered from gestation day 6 to lactation day 20, did not cause any adverse effect on pre and postnatal development up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area).

Lactation

Risk Summary

There are no data on the presence of lactitol in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Lactitol is minimally absorbed systemically following oral administration . It is unknown whether the minimal systemic absorption of lactitol by adults will 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 PIZENSY and any potential adverse effects on the breastfed infant from PIZENSY or from the underlying maternal condition.

Pediatric Use

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

Geriatric Use

Of the 807 patients who received PIZENSY in clinical trials, 202 (25%) were 65 years of age or older, and 59 (7%) were 75 years of age or older. No overall differences in safety or effectiveness of PIZENSY were observed between geriatric patients and younger patients.

Reduced Absorption Of Other Oral Medications

PIZENSY may reduce the absorption of concomitantly administered oral medications. Administer oral medications at least 2 hours before or 2 hours after PIZENSY .

Clinical Trials Experience

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

The data described below reflect exposure to PIZENSY in 807 patients with CIC in a six-month placebo-controlled trial (Study 1), a three-month active-controlled trial (Study 2) , and a one-year uncontrolled safety study (NCT02819310). Of the 298 patients in the one-year uncontrolled study, 55 patients were enrolled from Study 1 or Study 2.

Most Common Adverse Reactions

Table 1 provides the incidence of adverse reactions in Study 1 reported in at least 3% of patients in the PIZENSY treatment group and at higher incidence than placebo.

Table 1: Common Adverse Reactions¹ Reported in Adult Patients with CIC in Study 1

In Study 2, the safety profile of PIZENSY was similar to Study 1.

In the 1-year uncontrolled safety study, adverse reactions reported in patients receiving PIZENSY (N=298) with an incidence of at least 3% that are not represented in Table 1 include urinary tract infection (5%) and abdominal pain (3%).

Adverse Reaction Of Special Interest - Severe Diarrhea

In Study 1, severe diarrhea was reported in 2 (1%) PIZENSY-treated patients compared to no patients in the placebo group.

Adverse Reactions Leading To Discontinuation

In Study 1, 11/291 (4%) PIZENSY-treated patients discontinued due to adverse reactions, compared to 10/302 (3%) of patients in the placebo group. The most common adverse reactions leading to discontinuation in PIZENSY-treated patients (1% each) were elevated creatinine kinase, flatulence, diarrhea and increased blood pressure.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of lactitol outside of the United States. 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, including rash and pruritus

No Information provided

Dosage Forms And Strengths

PIZENSY is a white to off-white crystalline powder for oral solution supplied as:

• 280 grams of lactitol in multi-dose bottles
• 560 grams of lactitol in multi-dose bottles
• 10 grams of lactitol in unit-dose packets

Storage And Handling

PIZENSY is supplied in a white to off-white crystalline powder form, for oral administration following reconstitution. PIZENSY is available in three sizes:

280 grams of lactitol in multi-dose bottles (NDC 52268-600-01)

560 grams of lactitol in multi-dose bottles (NDC 52268-600-02)

carton of 28 unit-dose packets each containing 10 grams of lactitol (NDC 52268-600-03)

The measuring cap on each multi-dose bottle is marked to contain 10 grams of powder when filled to the top of white section in cap and may be used to measure the appropriate PIZENSY dose.

Each bottle contains a white desiccant packet printed “Do Not Eat.”

Storage

Store at 20°C to 25°C (68° to 77°F). Excursions permitted between 15° to 30°C (59° to 86°F).

Distributed by : Braintree Laboratories, Inc. Braintree, MA 02185. Revised: Feb 2020