Jamp-Electropeg Product Monograph

SUMMARY PRODUCT INFORMATION

INDICATIONS AND CLINICAL USE

Adults

JAMP-ElectroPEG, a polyethylene glycol (PEG)/electrolytes-based product, is indicated for:

• Bowel cleansing prior to colonoscopy or barium enema x-ray examination or surgical procedures requiring a clean colon.

CONTRAINDICATIONS

JAMP-ElectroPEG is contraindicated in patients with:

• Ileus
• Gastric retention
• Bowel perforation
• Gastrointestinal obstruction
• Toxic colitis
• Toxic megacolon
• Hypersensitivity to this drug or to any ingredient in the formulation or component of the container.

For a complete listing, see the Dosage Forms, Composition and Packaging section of this prescribing information.

WARNINGS AND PRECAUTIONS

General

• Use of JAMP-ElectroPEG is not recommended when abdominal pain, nausea, or vomiting are present.
• Unconscious or semiconscious patient should be observed during the administration of JAMP- ElectroPEG via nasogastric tube.
• A laxative should not be taken within 2 hours of another medicine because the desired effect of the other medicine may be reduced.

No additional flavorings or ingredients may be added to the solution.

Advise all patients to hydrate adequately before, during, and after the use of JAMP-ElectroPEG.

Cardiovascular

Cardiac Arrhythmias

There have been rare reports of serious cardiac arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Use caution when prescribing JAMP-ElectroPEG 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.

Gastrointestinal

JAMP-ElectroPEG should be used with caution in patients with ulcerative colitis (UC). Patients suffering from UC or from an acute exacerbation of inflammatory bowel disease have not been studied.

Patients with impaired gag reflex and patients prone to regurgitation or aspiration should be observed during the administration of JAMP-ElectroPEG, especially if it is administered via nasogastric tube. If gastrointestinal obstruction or perforation is suspected, appropriate studies should be performed to rule out those conditions before administration of JAMP-ElectroPEG.

If a patient experiences severe bloating, distension, or abdominal pain, administration of the solution should be slowed or temporarily discontinued until the symptoms abate.

There is a potential risk of Ischemic Colitis with co-exposure to osmotic laxatives (PEG 3550/Macrogol) such as JAMP-ElectroPEG, and stimulant laxatives (e.g., bisacodyl). If patients develop severe abdominal pain and/or rectal bleeding, immediate evaluation and close medical attention should be provided.

Immune

Cases of urticaria, rhinorrhea, dermatitis, and anaphylactic reactions have been reported with PEG/electrolytes-based lavage products that have the same medicinal ingredients as JAMP- ElectroPEG but with different brand names. This may represent allergic reactions.

Neurologic

PEG/electrolytes-based gastrointestinal lavage products have resulted in reports of generalized tonic-clonic seizures in patients with no prior history of seizures. Electrolyte abnormalities, such as hyponatremia and hypokalemia, as well as severe vomiting and excessive beverage consumption have been associated with these cases. A correction of fluid and electrolyte abnormalities resolved the neurologic irregularity. Therefore, in patients with known or suspected hyponatremia, or in patients using concomitant medications that increase the risk of electrolyte abnormalities (such as diuretics), JAMP-ElectroPEG should be used with caution. In these patients, baseline and post-colonoscopy laboratory tests (sodium, potassium, calcium, creatinine, and BUN) should be monitored.

Renal

The close monitoring of patients with impaired renal function should be performed, especially if severe vomiting occurs. Measurement of electrolytes (sodium, potassium, calcium), BUN, and creatinine is desirable.

Special Populations

Pregnant Women: Animal reproduction studies have not been conducted with PEG/electrolytes-based gastrointestinal lavage products, like JAMP-ElectroPEG, and it is also not known whether JAMP-ElectroPEG can affect reproductive capacity or harm the fetus when administered to a pregnant patient. JAMP-ElectroPEG should be given to a pregnant patient only if clearly needed.

Breastfeeding Women: 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 JAMP-ElectroPEG is administered to a breastfeeding woman.

Pediatrics: Safety and effectiveness of JAMP-ElectroPEG in children have not been established.

Geriatrics (> 60 years of age): There are isolated reports of serious post-marketing events following the administration of PEG/electrolytes-based colon preparation products in patients over 60 years of age (acute pulmonary edema after vomiting and aspirating the PEG-based solution, asystole, esophageal perforation, and upper GI bleeding from a Mallory-Weiss tear).

Caution is required in patients with renal and cardiac dysfunction in whom fluid and electrolyte shifts are of extra risk.

Monitoring and Laboratory Tests

Monitoring of serum electrolytes is advised.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

The most frequent adverse reactions, occurring in up to 50% of patients who have undergone PEG/electrolytes-based gastrointestinal lavage products, are nausea, abdominal fullness, and bloating. Abdominal cramps, vomiting and anal irritation occur less frequently. These adverse effects are transient.

Post-Market Adverse Drug Reactions

The following rare adverse events have been reported following administration of a PEG/electrolytes-based gastrointestinal lavage:

Cardiovascular: bradycardia, acute pulmonary edema, hypotension

Eye: sensitivity to light, painful irritated eyes

Gastrointestinal: rectal bleeding (occult blood in stool), sores in mouth, Ischemic Colitis (when used in conjunction with a stimulant laxative)

General and Administration Site Conditions: chills, loss of appetite

Hematologic: anemia

Metabolism and Nutrition: fluid imbalance, hypoglycaemia

Musculoskeletal and Connective Tissue: muscle pain

Nervous System: headaches, unconscious, coma, seizures, shakes

Psychiatric: confused feeling, disorientation

Respiratory, Thoracic and Mediastinal: aspiration

Skin and Subcutaneous Tissue: oily hair and skin, facial swelling, leg swelling

Isolated cases of urticaria, rhinorrhea, and dermatitis have been reported, which may represent allergic reactions.

PEG/electrolytes-based colon preparation has resulted in reports of generalized tonic-clonic seizures (see Warnings and Precautions).

DRUG INTERACTIONS

Drug-Drug Interactions

JAMP-ElectroPEG, as any other laxatives, should not be taken within 2 hours of another medicine because the desired effect of the other medicine may be reduced.

There is a potential risk of Ischemic Colitis with co-exposure to osmotic laxatives (PEG 3550/Macrogol) such as JAMP-ElectroPEG and stimulant laxatives (e.g., bisacodyl). If patients develop severe abdominal pain and/or rectal bleeding, immediate evaluation and close medical attention should be provided.

Drug-Food Interactions

When JAMP-ElectroPEG is used for a bowel preparation, no food, except clear liquids, should be taken at least 3 hours prior to administration.

Patients should adequately hydrate before, during, and after the use of JAMP-ElectroPEG.

DOSAGE AND ADMINISTRATION

General considerations

No additional ingredients, e.g. flavouring, should be added to the solution. Refrigerate the solution as chilling improves the taste.

Recommended Dose and Dosage Adjustment

Prior to gastrointestinal examination or procedure:

Patients should fast at least 3 hours prior to administration. No foods except clear liquids should be permitted prior to examination after JAMP-ElectroPEG administration. JAMP-ElectroPEG can be administered orally or by nasogastric tube.

Oral: Dissolve the entire contents of 4 L bottle by filling up to the bottle fill line and stir rapidly to dissolve. No additional ingredients, eg. flavouring should be added to the solution. Refrigerate the solution as chilling improves the taste. For further directions and warnings, see the Consumer

Information in the folded pages.

Nasogastric Tube: JAMP-ElectroPEG is administered at a rate of 20 to 30 mL/minute (1.2 to 1.8 L/hour).

The first bowel movement should occur approximately 1 hour after the start of JAMP-ElectroPEG administration. Administration of JAMP-ElectroPEG should be continued until the fecal discharge is clear. Lavage is usually complete after the ingestion of 3 to 4 L of JAMP-ElectroPEG solution. The unused portion should be discarded. A 1-hour waiting period after the appearance of clear liquid stools should be allowed prior to examination to complete bowel evacuation.

Reconstitution of the solution

JAMP-ElectroPEG powder: Fill water to the top of the line on bottle.

OVERDOSAGE

There are no specific antidotes that are required to be administered in the event of overdose; however, supportive care may be required in order to prevent dehydration and/or electrolyte imbalance.

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Polyethylene glycol 3350 (PEG 3350) is an osmotic lavage which causes water to be retained with the stool leading to decrease stool consistency, soften the stools, increase fecal bulk, and facilitate bowel movements.

JAMP-ElectroPEG cleanses the bowel by induction of diarrhea.

The osmotic activity of PEG 3350, in combination with the electrolyte concentration, results in virtually no net absorption or secretion of ions, such as sodium or potassium, and water. Accordingly, large volumes may be administered over a short period of time without significant changes in fluid and electrolyte balance.

Pharmacokinetics

PEG 3350 is poorly absorbed through the gastrointestinal track, and is not metabolized by the colonic bacteria.

STORAGE AND STABILITY

JAMP-ElectroPEG Powder for oral solution

Store the bottle at room temperature, 15 to 30^oC.

Once reconstituted, the solution should be used within 48 hours after mixing if stored at room temperature.

DOSAGE FORMS, COMPOSITION AND PACKAGING

Each bottle of JAMP-ElectroPEG powder, to be dissolved in 4 L of water, contains the following medicinal ingredients:

Polyethylene Glycol 3350................................................. 236 g

Sodium sulphate ............................................................ 22.74 g

Sodium bicarbonate ......................................................... 6.74 g

Sodium chloride .............................................................. 5.86 g

Potassium chloride........................................................... 2.97 g

and the non medicinal ingredients: Maltodextrin, Sodium saccharin, Natural lemon flavour.

Once reconstituted with the appropriate volume of water, the solution contains:

The osmolarity of a prepared JAMP-ElectroPEG solution ranges from 235-304 mOsmol /L.

PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Drug Substance

TOXICOLOGY

Acute Toxicity:

The oral LD₅₀ is >50 g/kg in mice, rats, and rabbits.

Rats

Chronic oral toxicity studies were conducted in rats (up to 6 g/kg/day) up to six months duration. The major target organ of toxicity in the rat appeared to be the kidney (focal or multi focal cytoplasmic vacuolation in cortical tubular epithelial cells in males at 6 g/kg/day).

Dogs

Chronic oral toxicity studies were conducted in dogs (up to 3 g/kg/day) up to nine months duration.

Following oral administration of PEG 3350 for 28-days, the target organs of toxicity appeared to be the lungs (minimal to moderate interstitial fibrosis characterized by thickening of alveolar septa with associated pneumocyte hypertrophy/hyperplasia and the presence of a small number of mononuclear inflammatory cells and alveolar histiocytes; foamy or vacuolated histiocytes in perivascular or peribronchiolar regions characterized as perivascular mononuclear infiltrates), gastrointestinal tract (minimal subacute inflammation or crypt abscesses, hemorrhage and lymphoid hyperplasia in cecum, colon, ileum and/or rectum; lymphoid hyperplasia of the gut- associated lymphoid tissue in females at 3, 6, and 9.3 g/kg/day), testes (hypospermia in the epididymides and seminiferous tubule degeneration or multiucleated spermatids of the testes), and salivary gland (atrophy).

Following 9-month oral administration of PEG 3350 in dogs (up to 3 g/kg/day), the target organs of toxicity appeared to be testes (retarded development) and prostate (lymphocyte infiltrate) in the

males, and mammary gland (glandular hyperplasia), liver (vacuolation), and gallbladder (lymphocyte infiltrate and epithelial hyperplasia) in females.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenesis

No tumorigenic effect was seen in mice and rats up to 6 g/kg/day. The carcinogenic potential of PEG 3350 has also been examined in CD-J mice (l04 weeks) and Sprague Dawley rats (l04 weeks).

Mutagenesis

PEG 3350 was negative in the Ames test. No clastogenic potential was shown in the chromosome aberration test with human peripheral blood lymphocytes. It was also negative in in vivo oral rat micronucleus test.

Development and reproductive toxicity

Reproduction studies with PEG 3350 have been performed in pregnant rats (oral doses up to

2 g/kg/day) and in pregnant rabbits (oral doses up to 2 g/kg/day) and have revealed no adverse effects on fertility or harm to the fetus.

In pre- and post-natal developmental study in rats up to 2 g/kg/day dose, PEG 3350 did not show any adverse effect on F_l postnatal survival, body weight, developmental landmarks, startle response, motor activity, learning and memory and reproductive performance, intrauterine growth and survival of F₂ fetuses and external and developmental parameters of F₂ fetuses.

REFERENCES

1. 1. Barkun A, Chiba N, Enns R, et al. Commonly used preparations for colonoscopy: efficacy, tolerability and safety - A Canadian Association of Gastroenterology position paper. Can J Gastroenterol. 2006 Nov;20(110:699-710.
2. 2. Hammer HF, Santa Ana CA, Schiller LR, Fordtran JS. Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. J Clin Invest. 1989 Oct;84(4):1056-62.
3. 3. Pelham RW, Nix LC, Chavira RE, Cleveland MV and Stetson P. Clinical trial: single- and multi-dose pharmacokinetics of polyethylene glycol (PEG-3350) in healthy young and elderly subjects. Aliment Pharmacol Ther. 2008;28:256-265