Prepopik - Product Information
|Form:||Liquid solution, Powder|
|Ingredients:||sodium picosulfate, magnesium oxide, anhydrous citric acid, otassium hydrogen carbonate, saccharin sodium, orange flavor which contains acacia gum, lactose, ascorbic acid and butylated hydroxyanisole or the cranberry flavor which contains maltodextrin, glyceryl triacetate (triacetin) and sodium octenyl succinated starch|
Indications and Usage
Prepopik (sodium picosulfate, magnesium oxide and anhydrous citric acid) for oral solution is indicated for cleansing of the colon as a preparation for colonoscopy in adults.
Dosage and Administration
Prepopik, supplied as a powder, must be reconstituted with cold water right before its use [see Dosage and Administration]. There are two dosing regimens, each requires two separate dosing times:
- The preferred method is the "Split-Dose" method and consists of two separate doses: the first dose during the evening before the colonoscopy and the second dose the next day, during the morning prior to the colonoscopy [see Dosage and Administration]
- The alternative method is the "DayBefore" method and consists of two separate doses: the first dose during the afternoon or early evening before the colonoscopy and the second dose 6 hours later during the evening before the colonoscopy [see Dosage and Administration].
Additional fluids must be consumed after every dose in both dosing regimens [see Dosage and Administration]. Instruct patients to consume only clear liquids (no solid food or milk) on the day before the colonoscopy up until 2 hours before the time of the colonoscopy. Instruct patients that if they experience severe bloating, distention, or abdominal pain following the first dose, delay the second dose until their symptoms resolve.
Reconstitution of the Prepopik Powder
- Reconstitute the Prepopik powder right before each administration. Do not prepare the solution in advance.
- Fill the supplied dosing cup with cold water up to the lower (5-ounce) line on the cup and pour in the contents of one packet of Prepopik powder.
- Stir for 2 to 3 minutes. The reconstituted Prepopik solution may become slightly warm as the powder dissolves.
Split-Dose Dosing Regimen (Preferred Method)
The Split-Dose regimen is the preferred dosing method. Instruct patients to take two separate doses in conjunction with fluids, as follows:
- Take the first dose during the evening before the colonoscopy (e.g., 5:00 to 9:00 PM) followed by five 8-ounce drinks (upper line on the dosing cup) of clear liquids before bed. Consume clear liquids within 5 hours.
- Take second dose the next day approximately 5 hours before the colonoscopy followed by at least three 8-ounce drinks of clear liquids before the colonoscopy. Consume clear liquids within 5 hours up until 2 hours before the time of the colonoscopy.
Day-Before Dosing Regimen (Alternative Method)
The Day-Before regimen is the alternative dosing method for patients for whom the Split-Dosing is inappropriate. Instruct patients to take two separate doses in conjunction with fluids, as follows:
- Take the first dose in the afternoon or early evening (e.g., 4:00 to 6:00 PM) before the colonoscopy followed by five 8-ounce drinks (upper line on the dosing cup) of clear liquids before the next dose. Consume clear liquids within 5 hours.
- Take the second dose approximately 6 hours later in the late evening (e.g., 10:00 PM to 12:00 AM), the night before the colonoscopy followed by three 8-ounce drinks of clear liquids before bed. Consume clear liquids within 5 hours.
Dosage Forms and Strengths
For oral solution: Each of the two packets contains 10 mg of sodium picosulfate, 3.5 grams of magnesium oxide, and 12.0 grams of anhydrous citric acid in 16.1grams of powder for orange flavor or 16.2 grams of powder for cranberry flavor.
Prepopik is contraindicated in the following conditions:
- Patients with severely reduced renal function (creatinine clearance less than 30 mL/minute ) which may result in accumulation of magnesium [see Warnings and Precautions]
- Gastrointestinal obstruction or ileus [see Warnings and Precautions]
- Bowel perforation
- Toxic colitis or toxic megacolon
- Gastric retention
- An allergy to any of the ingredients in Prepopik
Warnings and Precautions
Serious Fluid and Serum Chemistry Abnormalities
Advise patients to hydrate adequately before, during, and after the use of Prepopik. Use caution in patients with congestive heart failure when replacing fluids. If a patient develops significant vomiting or signs of dehydration including signs of orthostatic hypotension after taking Prepopik, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN) and treat accordingly. Approximately 20% of patients in both arms (Prepopik, 2L of PEG + E plus two × 5-mg bisacodyl tablets) of clinical trials of Prepopik had orthostatic changes (changes in blood pressure and/or heart rate) on the day of colonoscopy. In clinical trials orthostatic changes were documented out to seven days post colonoscopy. [see Adverse Reactions]
Fluid and electrolyte disturbances can lead to serious adverse events including cardiac arrhythmias or seizures and renal impairment. Fluid and electrolyte abnormalities should be corrected before treatment with Prepopik. In addition, use caution when prescribing Prepopik for patients who have conditions or who are using medications that increase the risk for fluid and electrolyte disturbances or that may increase the risk of adverse events of seizure, arrhythmia, and renal impairment.
There have been reports of generalized tonic-clonic seizures with the use of bowel preparation products in patients with no prior history of seizures. The seizure cases were associated with electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia) and low serum osmolality. The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities.
Use caution when prescribing Prepopik for patients with a history of seizures and in patients at risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, patients with known or suspected hyponatremia. [see Adverse Reactions]
Use in Patients with Renal Impairment
As in other magnesium containing bowel preparations, use caution when prescribing Prepopik for patients with impaired renal function or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs). These patients may be at increased risk for renal injury. Advise these patients of the importance of adequate hydration before, during and after the use of Prepopik. Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients. In patients with severely reduced renal function (creatinine clearance < 30 mL/min), accumulation of magnesium in plasma may occur.
There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Use caution when prescribing Prepopik for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged QT, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy). Pre-dose and post-colonoscopy ECGs should be considered in patients at increased risk of serious cardiac arrhythmias.
Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis
Osmotic laxatives may produce colonic mucosal aphthous ulcerations and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of additional stimulant laxatives with Prepopik may increase this risk. The potential for mucosal ulcerations should be considered when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease. [see Adverse Reactions]
Use in Patients with Significant Gastrointestinal Disease
If gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering Prepopik. Use with caution in patients with severe active ulcerative colitis.
Patients with impaired gag reflex and patients prone to regurgitation or aspiration should be observed during the administration of Prepopik. Use with caution in these patients.
Not for Direct Ingestion
Each packet must be dissolved in 5 ounces of cold water and administered at separate times according to the dosing regimen. Ingestion of additional water is important to patient tolerance. Direct ingestion of the undissolved powder may increase the risk of nausea, vomiting, dehydration, and electrolyte disturbances.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
In randomized, multicenter, controlled clinical trials, nausea, headache, and vomiting were the most common adverse reactions (>1%) following Prepopik administration. The patients were not blinded to the study drug. Since abdominal bloating, distension, pain/cramping, and watery diarrhea are known to occur in response to colon cleansing preparations, these effects were documented as adverse events in the clinical trials only if they required medical intervention (such as a change in study drug or led to study discontinuation, therapeutic or diagnostic procedures, met the criteria for a serious adverse event), or showed clinically significant worsening during the study that was not in the frame of the usual clinical course, as determined by the investigator.
Prepopik was compared for colon cleansing effectiveness with a preparation containing two liters (2L) of polyethylene glycol plus electrolytes solution (PEG + E) and two 5-mg bisacodyl tablets, all administered the day before the procedure. Table 1 displays the most common adverse reactions in Study 1 and Study 2 for the Prepopik Split-Dose and Day-Before dosing regimens, respectively, each as compared to the comparator preparation.
|Adverse Reaction||Study 1: Split-Dose Regimen||Study 2: Day-Before Regimen|
n (% = n/N)
|2L PEG+E† with 2 × 5-mg bisacodyl tablets|
n (% = n/N)
n (% = n/N)
|2L PEG+E† with 2 × 5-mg bisacodyl tablets |
n (% = n/N)
|Nausea||8 (2.6)||11 (3.7)||9 (3.0)||13 (4.3)|
|Headache||5 (1.6)||5 (1.7)||8 (2.7)||5 (1.7)|
|Vomiting||3 (1.0)||10 (3.4)||4 (1.4)||6 (2.0)|
* abdominal bloating, distension, pain/cramping, and watery diarrhea not requiring an intervention were not collected
†2L PEG + E = two liters polyethylene glycol plus electrolytes solution.
In general, Prepopik was associated with numerically higher rates of abnormal electrolyte shifts on the day of colonoscopy compared to the preparation containing 2L of PEG + E plus two × 5-mg bisacodyl tablets (Table 2). These shifts were transient in nature and numerically similar between treatment arms at the Day 30 visit.
|Laboratory Parameter (direction of change)||Visit||Study 1: Split-Dose Regimen||Study 2: Day-Before Regimen|
|PREPOPIK||2L PEG+E with 2× 5 mg bisacodyl tablets||PREPOPIK||2L PEG+E with 2× 5 mg bisacodyl tablets|
|n/N (%)||n/N (%)|
|Potassium (low)||Day of Colonoscopy||19/260 (7.3)||11/268 ( 4.1 )||13/274 (4.7)||13/271 (4.8)|
|24-48 hours||3/302 (1.0)||2/294 (0.7)||3/287 (1.0)||5/292 (1.7)|
|Day 7||11/285 (3.9)||8/279 (2.9)||6/276 (2.2)||14/278 (5.0)|
|Day 30||11/284 (3.9)||8/278 (2.9)||7/275 (2.5)||8/284 (2.8)|
|Sodium (low)||Day of Colonoscopy||11/298 (3.7)||3/295 (1.0)||3/286 (1.0)||3/295 (1.0)|
|24-48 hours||1/303 (0.3)||1/295 (0.3)||1/288 (0.3)||1/293 (0.3)|
|Day 7||2/300 (0.7)||1/292 (0.3)||1/285 (0.4)||1/291 (0.3)|
|Day 30||2/299( 0.7)||3/291 (1.0)||1/284( 0.4)||1/296 (0.3)|
|Chloride (low)||Day of Colonoscopy||11/301 (3.7)||1/298 (0.3)||3/287 (1.0)||0/297 (0.0)|
|24-48 hours||1/303 (0.3)||0/295 (0.0)||2/288 (0.7)||0/293 (0.0)|
|Day 7||1/303 (0.3)||3/295 (1.0)||0/285 (0.0)||0/293 (0.0)|
|Day 30||2/302 (0.7)||3/294 (1.0)||0/285 (0.0)||0/298 (0.0)|
|Magnesium (high)||Day of Colonoscopy||34/294 (11.6)||0/294 (0.0)||25/288 (8.7)||1/289 (0.3)|
|24-48 hours||0/303 (0.0)||0/295 (0.0)||0/288 (0.0)||0/293 (0.0)|
|Day 7||0/297 (0.0)||1/291 (0.3)||1/286 (0.3)||1/285 (0.4)|
|Day 30||1/296 (0.3)||2/290 (0.7)||0/286 (0.0)||0/290 (0.0)|
|Calcium (low)||Day of Colonoscopy||2/292 (0.7)||1/286 (0.3)||0/276 (0.0)||2/282 (0.7)|
|24-48 hours||0/303 (0.0)||0/295 (0.0)||0/288 (0.0)||0/293 (0.0)|
|Day 7||0/293 (0.0)||1/283 (0.4)||0/274 (0.0)||0/278 (0.0)|
|Day 30||0/292 (0.0)||1/282 (0.4)||0/274 (0.0)||1/283 (0.4)|
|Creatinine (high)||Day of Colonoscopy||5/260 (1.9)||13/268 (4.9)||12/266 (4.5)||16/270 (5.9)|
|24-48 hours||1/303 (0.3)||0/295 (0.0)||0/288 (0.0)||0/293 (0.0)|
|Day 7||10/264 (0.4)||13/267 (4.8)||10/264 (3.8)||10/265 (3.8)|
|Day 30||11/264 (4.2)||14/265(5.3)||18/264 (6.8)||10/272 (3.7)|
|eGFR (low)||Day of Colonoscopy||22/221 (10.0)||17/214 (7.9)||26/199 (13.1)||25/224 (11.2)|
|24-48 hours||76/303 (25.1)||72/295 (24.4)||82/288 (28.5)||62/293 (21.2)|
|Day 7||22/223 (10.0)||17/213 (8.0)||11/198 (5.6)||28/219 (12.8)|
|Day 30||24/223(10.8)||21/211 (10.0)||21/199 (10.6)||24/224 (10.7)|
The following foreign spontaneous reports have been identified during use of formulations similar to Prepopik. Because these events 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.
Cases of hypersensitivity reactions including rash, urticaria, and purpura have been reported.
There have been reports of hypokalemia, hyponatremia and hypermagnesemia with the use of Prepopik for colon preparation prior to colonoscopy.
Abdominal pain, diarrhea, fecal incontinence, and proctalgia have been reported with the use of Prepopik for colon preparation prior to colonoscopy. There have been isolated reports of reversible aphthoid ileal ulcers. Ischemic colitis has been reported with the use of Prepopik for colon preparation prior to colonoscopy. However, a causal relationship between these ischemic colitis cases and the use of Prepopik has not been established.
There have been reports of generalized tonic-clonic seizures associated with and without hyponatremia in epileptic patients.
Drugs That May Increase Risks of Fluid and Electrolyte Abnormalities
Use caution when prescribing Prepopik for patients with conditions or who are using medications that increase the risk for fluid and electrolyte disturbances or may increase the risk of seizure, arrhythmias, and prolonged QT in the setting of fluid and electrolyte abnormalities. This includes patients receiving drugs which may be associated with hypokalemia (such as diuretics or corticosteroids, or drugs where hypokalemia is a particular risk, such as cardiac glycosides) or hyponatremia. Use caution when Prepopik is used in patients on nonsteroidal anti-inflammatory drugs (NSAIDS) or drugs known to induce Antidiuretic Hormone Secretion (SIADH), such as tricyclic antidepressants, selective serotonin re-uptake inhibitors, antipsychotic drugs and carbamazepine, as these drugs may increase the risk of water retention and/or electrolyte imbalance. Consider additional patient evaluations as appropriate. [see Adverse Reactions (6.1, 6.2)]
Potential for Altered Drug Absorption
Oral medication administered within one hour of the start of administration of Prepopik solution may be flushed from the GI tract and the medication may not be absorbed.
Tetracycline and fluoroquinolone antibiotics, iron, digoxin, chlorpromazine and penicillamine, should be taken at least 2 hours before and not less than 6 hours after administration of Prepopik to avoid chelation with magnesium.
Prior or concomitant use of antibiotics with Prepopik may reduce efficacy of Prepopik as conversion of sodium picosulfate to its active metabolite BHPM is mediated by colonic bacteria.
Use in Specific Populations
Pregnancy Category B
Reproduction studies with Prepopik have been performed in pregnant rats at oral doses up to 2000 mg/kg/day (about 1.2 times the recommended human dose based on the body surface area), and did not reveal any evidence of impaired fertility or harm to the fetus due to Prepopik. The reproduction study in rabbits was not adequate, as treatment-related mortalities were observed at all doses. A pre and postnatal development study in rats showed no evidence of any adverse effect on pre and postnatal development at oral doses up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on the body surface area). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Prepopik should be used during pregnancy only if clearly needed.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Prepopik is administered to a nursing woman.
The safety and effectiveness of Prepopik in pediatric patients has not been established.
In controlled clinical trials of Prepopik, 215 of 1201 (18%) patients were 65 years of age or older. The overall incidence of treatment-emergent adverse events was similar among patients ≥65 years of age (73%) and patients <65 years of age (71%). Among all patients ≥65 years of age, the proportion of patients with successful colon cleansing was greater in the Prepopik group (81.1%) than in the comparator group (70.9%).
Patients with impaired renal function or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs) may be at increased risk for further renal injury. Advise these patients of the importance of adequate hydration before, during and after the use of Prepopik. Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients. In patients with severely reduced renal function (creatinine clearance < 30 mL/min), accumulation of magnesium in plasma may occur. The signs and symptoms of hypermagnesemia may include, but are not limited to, diminished or absent deep tendon reflexes, somnolence, hypocalcemia, hypotension, bradycardia, muscle, respiratory paralysis, complete heart block, and cardiac arrest.
The patient who has taken an overdose should be monitored carefully, and treated symptomatically for complications.
How Supplied/Storage and Handling
Prepopik is supplied in a carton containing 2 packets, each holding 16.1 grams of powder in orange flavor or 16.2 grams of powder in cranberry flavor for oral solution, along with a pre-marked dosing cup. Each packet for both flavors contains 10 mg sodium picosulfate, 3.5 g magnesium oxide and 12 g anhydrous citric acid. The excipients for both flavors include potassium hydrogen carbonate, sodium saccharin, orange or cranberry flavor. The orange flavor contains acacia gum, lactose, ascorbic acid, and butylated hydroxyanisole, and the cranberry flavor contains maltodextrin, glyceryl triacetate (triacetin) and sodium octenyl succinated starch.
Store at 25°C (77°F). Excursions permitted at 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
NDC# 55566-9300-2 Kit, 2 packets and cup
NDC# 55566-9700-1- Kit, 2 packets and cup
Patient Counseling Information
See FDA-approved patient labeling (Consumer Medicine Information).
- Ask patients to let you know if they have trouble swallowing or are prone to regurgitation or aspiration.
- Tell patients not to take other laxatives while they are taking Prepopik.
- Tell patients that if they experience severe bloating, distention or abdominal pain following the first packet of Prepopik, delay the second administration until the symptoms resolve.
- Instruct patients to contact their healthcare provider if they develop signs and symptoms of dehydration.
- Not for Direct Ingestion: Each packet must be dissolved in 5 ounces of cold water and administered at separate times according to the dosing regimen. Ingestion of additional water is important to patient tolerance. Direct ingestion of the undissolved powder may increase the risk of nausea, vomiting, dehydration, and electrolyte disturbances. Inform patients that oral medication administered within one hour of the start of administration of Prepopik solution may not be absorbed completely.
Ferring Pharmaceuticals (China) Co., Ltd.
No. 6 HuiLing Lu (Ferring Road)
National Health Technology Park
Zhongshan City, Guangdong Province, CHINA
Ferring Pharmaceuticals Inc.
Parsippany, N.J. 07054