1 INDICATIONS AND USAGE MoviPrep is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. MoviPrep is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years or older. (1)
3 DOSAGE FORMS AND STRENGTHS Powder for Oral Solution: MoviPrep is available in a carton that contains 2 pouches labeled Pouch A and 2 pouches labeled Pouch B. Each pouch A contains 100 grams of polyethylene glycol (PEG) 3350, NF, 7.5 grams of sodium sulfate, USP, 2.691 grams of sodium chloride, USP, and 1.015 grams of potassium chloride, USP, plus the following excipients: aspartame, NF (sweetener), acesulfame potassium, NF (sweetener), and lemon flavoring. Each pouch B contains 4.7 grams of ascorbic acid, USP and 5.9 grams of sodium ascorbate, USP. Powder for Oral Solution: 2 pouches labeled Pouch A and 2 pouches labeled Pouch B. Each pouch A contains 100 grams of polyethylene glycol (PEG) 3350, NF, 7.5 grams of sodium sulfate, USP, 2.691 grams of sodium chloride, USP, and 1.015 grams of potassium chloride, USP, plus the following excipients: aspartame, NF (sweetener), acesulfame potassium, NF (sweetener), and lemon flavoring (3) Each pouch B contains 4.7 grams of ascorbic acid, USP and 5.9 grams of sodium ascorbate, USP. (3)
4 CONTRAINDICATIONS MoviPrep is contraindicated in the following conditions: Gastrointestinal (GI) obstruction Bowel perforation Gastric retention Ileus Toxic colitis or toxic megacolon Hypersensitivity to any components of MoviPrep [see DESCRIPTION (11)] Gastrointestinal (GI) obstruction (4) Bowel perforation (4) Gastric retention (4) Ileus (4) Toxic colitis or toxic megacolon (4) Hypersensitivity to any components of MoviPrep (4)
5 WARNINGS AND PRECAUTIONS Risk of fluid and electrolyte abnormalities, arrhythmias, seizures and renal impairment – encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after use (5.1, 5.2, 5.3) Patients with impaired renal function or patients taking concomitant medications that affect renal function – use caution, ensure adequate hydration and consider testing (5.4) Suspected GI obstruction or perforation – rule out the diagnosis before administration (5.6) Patients at risk for aspiration —observe during administration (5.7) Glucose-6-phosphate dehydrogenase deficiency (G-6-PD) – use with caution (5.8) Contains phenylalanine (5.9) 5.1 Serious Fluid and Electrolyte Abnormalities Advise patients to hydrate adequately before, during, and after the use of MoviPrep. If a patient develops significant vomiting or signs of dehydration after taking MoviPrep consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN). Fluid and electrolyte disturbances can lead to serious adverse events including cardiac arrhythmias, seizures and renal impairment. Patients with electrolyte abnormalities should have them corrected before treatment with MoviPrep. MoviPrep should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities [such as diuretics, angiotensin converting enzyme (ACE)-inhibitors or angiotensin receptor blockers (ARBs)] or in patients with known or suspected hyponatremia. Consider performing pre-dose and post-colonoscopy laboratory tests (sodium, potassium, calcium, creatinine, and BUN) in these patients. [ See DRUG INTERACTIONS (7.1)] 5.2 Cardiac Arrhythmias There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Use caution when prescribing MoviPrep 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. 5.3 Seizures There have been rare reports of generalized tonic-clonic seizures and/or loss of consciousness associated with 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 MoviPrep for patients with a history of seizures and in patients at increased risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, or patients with known or suspected hyponatremia. 5.4 Renal Impairment Use with caution in patients with impaired renal function or patients taking concomitant medications that affect renal function (such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs). Advise these patients of the importance of adequate hydration, and consider performing pre-dose and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients. 5.5 (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 stimulant laxatives and MoviPrep may increase the risk and is not recommended. The potential for mucosal ulcerations resulting from the bowel preparation should be considered when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease. 5.6 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 MoviPrep. If a patient experiences severe bloating, abdominal distension, or abdominal pain, administration should be slowed or temporarily discontinued until symptoms abate. Use with caution in patients with severe ulcerative colitis. 5.7 Aspiration Patients with impaired gag reflex and patients prone to regurgitation or aspiration should be observed during the administration of MoviPrep. Use with caution in these patients. 5.8 Glucose-6-phosphate dehydrogenase (G-6-PD) Deficiency Since MoviPrep contains sodium ascorbate and ascorbic acid, MoviPrep should be used with caution in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, especially G-6-PD deficiency patients with an active infection, with a history of hemolysis, or taking concomitant medications known to precipitate hemolytic reactions. 5.9 Contains Phenylalanine Phenylketonurics: Contains aspartame 233 mg per treatment which corresponds to 131 mg of phenylalanine per treatment (after hydrolysis of the aspartame molecule in-vivo to aspartic acid and phenylalanine).
6 ADVERSE REACTIONS Most common adverse reactions for split dosing (incidence ³ 5%) are malaise, nausea, abdominal pain, vomiting, and upper abdominal pain (6). The most common adverse reactions for evening only dosing (incidence ³ 5%) are abdominal distension, anal discomfort, thirst, nausea, abdominal pain, sleep disorder, rigors, hunger, malaise, vomiting, and dizziness (6). To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals, Inc. at 1-800-508-0024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies 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 the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the MoviPrep trials, abdominal distension, anal discomfort, thirst, nausea, and abdominal pain were some of the most common adverse reactions to MoviPrep administration. Since diarrhea was considered as a part of the efficacy of MoviPrep, diarrhea was not defined as an adverse reaction in the clinical studies. Tables 1 and 2 display the most common drug-related adverse reactions of MoviPrep and its comparator in the controlled MoviPrep trials. Table 1: The Most Common Drug-Related Adverse Reactions1 (≥ 2%) in the Study of MoviPrep vs. 4 Liter Polyethylene Glycol plus Electrolytes Solution MoviPrep® (split dose) N=180 4L PEG + E2 N=179 n (% = n/N) n (% = n/N) Malaise 35 (19.4) 32 (17.9) Nausea 26 (14.4) 36 (20.1) Abdominal pain 24 (13.3) 27 (15.1) Vomiting 14 (7.8) 23 (12.8) Upper abdominal pain 10 (5.6) 11 (6.1) Dyspepsia 5 (2.8) 2 (1.1) 1 Drug-related adverse reactions were adverse events that were possibly, probably, or definitely related to the study drug. 2 4L PEG + E is 4 liter Polyethylene Glycol plus Electrolytes Solution Table 2: The Most Common Drug-Related Adverse Reactions1 (≥ 5%) in the Study of MoviPrep vs. 90 mL Oral Sodium Phosphate Solution MoviPrep® (evening-only) (full dose) N=169 90 mL OSPS2 N=171 n (% = n/N) n (% = n/N) Abdominal distension 101 (59.8) 70 (40.9) Anal discomfort 87 (51.5) 89 (52.0) Thirst 80 (47.3) 112 (65.5) Nausea 80 (47.3) 80 (46.8) Abdominal pain 66 (39.1) 55 (32.2) Sleep disorder 59 (34.9) 49 (28.7) Rigors 57 (33.7) 51 (29.8) Hunger 51 (30.2) 121 (70.8) Malaise 45 (26.6) 90 (52.6) Vomiting 12 (7.1) 14 (8.2) Dizziness 11 (6.5) 31 (18.1) Headache 3 (1.8) 9 (5.3) Hypokalemia 0 (0) 10 (5.8) Hyperphosphatemia 0 (0) 10 (5.8) 1 Drug-related adverse reactions were adverse events that were possibly, probably, or definitely related to the study drug. In addition to the recording of spontaneous adverse events, patients were also specifically asked about the occurrence of the following symptoms: shivering, anal irritations, abdominal bloating or fullness, sleep loss, nausea, vomiting, weakness, hunger sensation, abdominal cramps or pain, thirst sensation, and dizziness. 2 OSPS is Oral Sodium Phosphate Solution Isolated cases of urticaria, rhinorrhea, dermatitis, and anaphylactic reaction have been reported with PEG-based products and may represent allergic reactions. Published literature contains isolated reports of serious adverse events following the administration of PEG-based products in patients over 60 years of age. These adverse events included upper gastrointestinal bleeding from a Mallory-Weiss tear, esophageal perforation, asystole, and acute pulmonary edema after aspirating PEG-based preparation. 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse events have been identified during post-approval use of MoviPrep. Because they 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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting or causal connection to MoviPrep, or a combination of these factors. Cardiovascular: Tachycardia, palpitations, hypertension, arrhythmia, atrial fibrillation, peripheral edema. General: Hypersensitivity reactions including anaphylaxis (some of which were severe, including shock), rash, urticaria, pruritus, lip, tongue and facial swelling, dyspnea, chest tightness and throat tightness. Fever, chills and dehydration. Nervous system: Syncope, tremor, seizure. Renal: Renal impairment and/or failure.
7 DRUG INTERACTIONS Oral medications may not be absorbed when administered while taking MoviPrep (7). 7.1 Drugs That May Increase Risks Due to Fluid and Electrolyte Abnormalities Use caution when prescribing MoviPrep for patients with conditions, or who are using medications that increase the risk for fluid and electrolyte disturbances or may increase the risk of adverse events of seizure, arrhythmias, and prolonged QT in the setting of fluid and electrolyte abnormalities. Consider additional patient evaluations as appropriate. [See WARNINGS (5)] 7.2 Potential for Altered Drug Absorption Oral medication administered within 1 hour of the start of administration of MoviPrep may be flushed from the gastrointestinal tract and the medication may not be absorbed.
8 USE IN SPECIFIC POPULATIONS Pregnancy: No human or animal data. Use only if clearly needed. (8.1) 8.1 Pregnancy Pregnancy Category C. Animal reproduction studies have not been performed with MoviPrep. It is also not known if MoviPrep can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. MoviPrep should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers 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 MoviPrep is administered to a nursing woman. 8.4 Pediatric Use The safety and effectiveness of MoviPrep in pediatric patients has not been established. 8.5 Geriatric Use Of the 413 patients in clinical studies receiving MoviPrep, 91 (22%) patients were aged 65 or older, while 25 (6%) patients were over 75 years of age. No overall differences in safety or effectiveness were observed between geriatric patients and younger patients, and other reported clinical experience has not identified differences in responses between geriatric patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.