PRESCRIBING INFORMATION LAX-A-DAY

Transcription

1 PRESCRIBING INFORMATION LAX-A-DAY Polyethylene Glycol 3350 Powder for Oral Solution Laxative Pendopharm, Division of Pharmascience Inc Royalmount Ave., Suite 100 Montreal, Quebec H4P 2T4 Date of Preparation: July 24, 2008 Date of revision: March 25, 2014 LAX-A-DAY is a registered trademark of Pharmascience Inc. Page 1 of 13

2 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION...3 SUMMARY PRODUCT INFORMATION...3 INDICATIONS AND CLINICAL USE...3 CONTRAINDICATIONS...3 WARNINGS AND PRECAUTIONS...4 ADVERSE REACTIONS...5 DRUG INTERACTIONS...5 DOSAGE AND ADMINISTRATION...6 OVERDOSAGE...6 ACTION AND CLINICAL PHARMACOLOGY...7 STORAGE AND STABILITY...8 SPECIAL HANDLING INSTRUCTIONS...8 DOSAGE FORMS, COMPOSITION AND PACKAGING...8 PART II: SCIENTIFIC INFORMATION...9 PHARMACEUTICAL INFORMATION...9 CLINICAL TRIALS...9 TOXICOLOGY...10 REFERENCES...11 PART III: CONSUMER INFORMATION...12 Page 2 of 13

3 LAX-A-DAY Polyethylene Glycol 3350 Powder for Oral Solution THERAPEUTIC CLASSIFICATION Laxative PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY PRODUCT INFORMATION Route of Administration Oral Dosage Form / Strength Powder for oral solution Clinically Relevant Nonmedicinal Ingredients None. For a complete listing see Dosage Forms, Composition and Packaging section. INDICATIONS AND CLINICAL USE Adults LAX-A-DAY (Polyethylene Glycol 3350 Powder for Oral Solution) is indicated for: Constipation LAX-A-DAY is indicated as a laxative for the treatment of occasional constipation. (See DOSAGE AND ADMINISTRATION). CONTRAINDICATIONS LAX-A-DAY is contraindicated in patients with: known or suspected bowel obstruction, and known allergies to polyethylene glycol. Page 3 of 13

4 WARNINGS AND PRECAUTIONS General Patients with symptoms suggestive of bowel obstruction, appendicitis or inflamed bowels (fever, nausea, vomiting, abdominal pain or distention) should consult a doctor to rule out these conditions before initiating LAX-A-DAY therapy. Overuse or extended use of any laxative may cause dependence for bowel function. Do not take any type of laxative for more than one (1) week, unless recommended by a physician. A laxative should not be taken within two (2) hours of another medicine because the desired effect of the other medicine may be reduced. Patients presenting with complaints of constipation should have a thorough medical history and physical examination to detect associated metabolic, endocrine and neurogenic conditions, and medications. A diagnostic evaluation should include a structural examination of the colon. Patients should be educated about good defecatory and eating habits (such as high fiber diets) and lifestyle changes (adequate dietary fiber and fluid intake, regular exercise) which may produce more regular bowel habits. LAX-A-DAY should be administered after being dissolved in approximately 250 ml of water, juice, soda, coffee, or tea. Special Populations Pregnant Women: Animal reproductive studies have not been performed with Polyethylene Glycol It is also not known whether Polyethylene Glycol 3350 can cause fetal harm when administered to a pregnant woman, or can affect reproductive capacity. The use of LAX-A- DAY should be avoided in women who are pregnant unless clearly needed and directed by a physician. Nursing Women: It is unknown if LAX-A-DAY is excreted in human milk. Because many drugs are excreted in human milk, precaution should be exercised. The use of LAX-A-DAY should be avoided in nursing women unless clearly needed and directed by a physician. Pediatrics (<18 years of age): Safety and effectiveness of LAX-A-DAY in pediatric patients has not been established. Geriatrics (> 65 years of age): There is no evidence for special considerations when LAX-A- DAY is administered to elderly patients. If diarrhea occurs, LAX-A-DAY should be discontinued. Page 4 of 13

5 Monitoring and Laboratory Tests No clinically significant effects (1,2,3,5,6) on laboratory tests have been demonstrated. In one study (1), CBC, blood chemistry, and urinalysis were performed after the 14-day treatment period. Laboratory data were compared by repeated measures of analysis of variance. A value p < 0.05 was considered statistically significant. No statistically or clinically significant differences between placebo and laxative groups were detected for laboratory measurements. In another study (2), CBC, blood chemistry, and urinalysis were performed before and after each10-day treatment period. No clinically significant changes in laboratory measurements were seen. ADVERSE REACTIONS Adverse Drug Reaction Overview Occasionally, LAX-A-DAY may cause nausea, abdominal bloating, cramping, diarrhea and/or gas. High doses may produce diarrhea and excessive stool frequency, particularly in elderly nursing home patients. On rare occasions, hives and skin rashes have been reported which are suggestive of an allergic reaction. Patients taking other medications containing polyethylene glycol have occasionally developed urticaria suggestive of an allergic reaction. DRUG INTERACTIONS No specific drug interactions have been demonstrated. A laxative should not be taken within two (2) hours of taking another medicine because the desired effect of the other medicine may be reduced. Page 5 of 13

6 DOSAGE AND ADMINISTRATION Recommended Dose and Dosage Adjustment ADULTS: The usual dose is 17 grams (about 1 heaping tablespoon or one single-dose sachet) of LAX-A- DAY powder per day (or as directed by physician) to be stirred in a cup (250 ml) of water, juice, soda, coffee, or tea until completely dissolved. This product should be used for one week or less or as directed by a physician. Treatment for two to four days (48 to 96 hours) may be required to produce a bowel movement. Each bottle of LAX-A-DAY is supplied with a dosing cap marked to contain 17 grams of laxative powder when filled to the indicated line. LAX-A-DAY is also available in single-dose sachets of 17 grams each. Two to 4 days (48 to 96 hours) may be required to produce a bowel movement. Special Patient Populations: Treatment of Pregnant or Nursing Women LAX-A-DAY should only be administered to a pregnant or nursing woman on the advice of a physician. (See WARNINGS AND PRECAUTIONS). Elderly Patients No dose adjustment is recommended for elderly patients solely on the basis of their age (see WARNINGS AND PRECAUTIONS). Pediatrics LAX-A-DAY is not indicated for use in children under 18 years of age unless recommended by a physician (See WARNINGS AND PRECAUTIONS). OVERDOSAGE There have been no reports of accidental overdosage. In the event of overdosage, diarrhea would be the expected major event. If an overdose of drug occurred without concomitant ingestion of fluid, dehydration due to diarrhea may result. In the event of overdose, medication should be terminated and free water administered. Page 6 of 13

7 ACTION AND CLINICAL PHARMACOLOGY Mechanism of Action Pharmacology: Polyethylene Glycol 3350 is an osmotic agent which causes water to be retained with the stool. Essentially, complete recovery of Polyethylene Glycol 3350 was shown in normal subjects without constipation. Attempts at recovery of Polyethylene Glycol 3350 in constipated patients resulted in incomplete and highly variable recovery. An in vitro study showed indirectly that Polyethylene Glycol 3350 was not fermented into hydrogen or methane by the colonic microflora in human feces Polyethylene Glycol 3350 appears to have no effect on the active absorption or secretion of glucose or electrolytes. There is no evidence of tachyphylaxis. Special Populations and Conditions Pediatrics: The safety and efficacy of LAX-A-DAY for use in children under 18 years of age have not been established. LAX-A-DAY is not indicated for use in children under 18 years of age. Geriatrics: There is no evidence for special considerations when LAX-A-DAY is administered to elderly patients. In geriatric nursing home patients a higher incidence of diarrhea occurred at the recommended 17 gram dose. Page 7 of 13

8 STORAGE AND STABILITY Store at room temperature (15 C to 30 C). SPECIAL HANDLING INSTRUCTIONS None. DOSAGE FORMS, COMPOSITION AND PACKAGING LAX-A-DAY is available in powdered form, for oral administration after complete dissolution in water, juice, soda, coffee, or tea. LAX-A-DAY is available in the following formats: bottles (119 g, 238 g, or 510 g) and single-dose sachets of 17 g (available in packs of 10 sachets). The dosing cap provided with each bottle is marked with a measuring line and should be used to measure a single daily dose of LAX-A-DAY (17 grams, or about 1 heaping tablespoon). Composition of Product Polyethylene Glycol 3350 Page 8 of 13

9 PART II: SCIENTIFIC INFORMATION PHARMACEUTICAL INFORMATION Drug Substance Proper name: Polyethylene Glycol 3350 Chemical name: Molecular formula: Poly(oxy-1,2-ethanediyl), -hydro-τ-hydroxy- HO(C2H4O)nH (n represents the average number of oxyethylene groups) Molecular mass: average molecular weight of 3350 (The actual molecular weight is not less than 90.0 percent and not greater than percent of the nominal value) Structural formula: Physical Form: A white powder for reconstitution Solubility: Below 55 C it is a free flowing white powder freely soluble in water. CLINICAL TRIALS In two separate studies (1,3), 151 and 23 patients with less than 3 bowel movements per week were randomized to Polyethylene Glycol 3350, 17 grams, or placebo for 14 days. An increase in bowel movement frequency was observed for both treatment groups during the first week of treatment. Polyethylene Glycol 3350 was statistically superior to placebo during the first and second week of treatment. No clinically significant changes in blood chemistry, CBC, or urinalysis were observed. PEG laxative is safe and effective in the short term for the treatment of constipation. Page 9 of 13

10 In a second study (2), 50 patients with 3 bowel movements or less per week and/or less than 300 grams of stool per week were randomized to 2 dose levels of Polyethylene Glycol 3350 or placebo for 10 days each. Success was defined by an increase in both bowel movement frequency and daily stool weight. For both parameters, superiority of the 17gram dose of Polyethylene Glycol 3350 over placebo was demonstrated. There were no significant differences in laboratory changes or adverse experiences recorded between groups. PEG laxative is safe and effective in the short term treatment of constipation for ambulatory outpatients and is safe for long-term care patients. In a fourth study (5), 304 patients with 3 bowel movements or less per week were randomized to 17 grams of Polyethylene Glycol 3350 or placebo for 6 months. Successful treatment according to the primary efficacy variable was seen in 52.0% of PEG and 11% of placebo subjects (p < 0.001). Similar efficacy was seen in a subgroup of 75 elderly subjects. According to the primary efficacy definition (based on individual treatment weeks), 61% of PEG treatment weeks versus 22% of the placebo weeks were successful (p < 0.001). There were no significant differences in laboratory findings of adverse events, except for the gastrointestinal category where diarrhea, flatulence, and nausea were the most frequent with PEG although they were not individually statistically significant compared to placebo. Similar results were observed when analyzed for differences due to gender, race or age. PEG laxative is safe and effective for use in patients with chronic constipation for 6 months. In a fifth study (6), 24 adult patients aged > 19 years with a history of constipation were randomized to 3 dose levels of Polyethylene Glycol 3350 (51, 68 and 85 g) or placebo for a 24 hour period. Over a 72 hr period, subjects rated bowel movements, completeness of evacuation and satisfaction. There were no significant differences in laboratory changes or adverse experiences recorded between groups. A 68 g dose of PEG laxative seems to provide safe and effective relief in constipated adults within a 24 hour period. TOXICOLOGY Acute Toxicity: The oral LD50 is >50 gm/kg in mice, rats and rabbits. Carcinogenesis, Mutagenesis, Impairment of Fertility: Long term carcinogenicity studies, genetic toxicity studies and reproductive toxicity studies in animals have not been performed with Polyethylene Glycol Page 10 of 13

11 REFERENCES 1. DiPalma JA, DeRidder PH, Orlando RC, Kolts BE, and Cleveland MB. A Randomized, Placebo-Controlled, Multicenter Study of the Safety and Efficacy of a New Polyethylene Glycol Laxative. Am. J of Gastroenterol 2000; Vol. 95; No. 2, p DiPalma JA, MacRae DH, Reichelderfer M, Hamilton JW, and Cleveland MB. Braintree Polyethylene Glycol (PEG) laxative for Ambulatory and Long-Term Care Facility Constipation Patients: Report of Randomized, Cross-Over Trials. Online J of Digestive Health; Vol. 1, No. 2 (March), Mark Cleveland, David P. Flavin, Robert A. Ruben, Roger M. Epstein, and Geoffery E. Clark. New Polyethylene Glycol Laxative for Treatment of Constipation in Adults: A Randomized, Double-Blind, Placebo-Controlled Study. Southern Medical Journal, May 2001; Vol. 94; No. 5, p Davendra Ramkumar and Satish S.C. Rao. Efficacy and Safety of Traditional Medical Therapies for Chronic Constipation: Systemic Review. Am. J. of Gastroenterol. 2005, 100, p Jack A. DiPalma, Mark B. Cleveland, John McGowan, and Jorge L. Herrera. A Randomized, Multicenter, Placebo-Controlled Trial of Polyethylene Glycol Laxative for Chronic Treatment of Chronic Constipation. Am J Gastroenterol 2007; 102, p Jack A. DiPalma, Julie R. Smith, and Mark B. Cleveland. Overnight Efficacy of Polyethylene Glycol Laxative. Am J Gastroenterol 2002; 97, p Patient Information, Paddock Laboratories Inc., (04-06) Page 11 of 13

12 IMPORTANT: PLEASE READ PART III: CONSUMER INFORMATION LAX-A-DAY Polyethylene Glycol 3350 Powder for Oral Solution This leaflet is part III of a three-part Prescribing Information published when LAX-A-DAY was approved for sale in Canada and is designed specifically for Consumers. This leaflet is a summary and will not tell you everything about LAX-A- DAY. Contact your doctor or pharmacist if you have any questions about the drug. Please read this information carefully before you start to take your medicine, even if you have taken this drug before. Do not throw away this leaflet until you have finished your medicine as you may need to read it again. For further information or advice, please see your doctor or pharmacist. ABOUT THIS MEDICATION What the medication is used for: LAX-A-DAY is a laxative used to treat occasional constipation. What it does: LAX-A-DAY softens the stool and increases the frequency of bowel movements by retaining water in the stool. Your first bowel movement will usually happen in two to four days, although results may vary for individual patients. When it should not be used: If you are allergic to polyethylene glycol, do not use this drug product. Stop taking the drug and contact your doctor immediately if you experience an allergic reaction or any severe or unusual side effects. Do not use LAX-A-DAY if you have a known or suspected bowel obstruction. LAX-A-DAY should not be used by children under 18 years of age unless recommended by a physician. Although there is no evidence for special considerations when LAX-A-DAY is administered to elderly patients, if diarrhea occurs, LAX-A-DAY should be discontinued. If pregnant or breast-feeding, ask a health care professional before use. What the medicinal ingredient is: Polyethylene Glycol 3350 What the non-medicinal ingredients are: There are no non-medicinal ingredients in LAX-A-DAY. What dosage forms it comes in: LAX-A-DAY is available in powdered form, for oral administration after dissolution in water, juice, soda, coffee, or tea. LAX-A-DAY is available in the following formats: bottles (119 g, 238 g, or 510 g) and single-dose sachets of 17 g (available in packs of 10 sachets). The bottle formats include a dosing cap marked with a measuring line which should be used to measure a single LAX-A-DAY dose of 17 g (about 1 heaping tablespoon). WARNINGS AND PRECAUTIONS Patients with symptoms suggestive of bowel obstruction, appendicitis, or inflamed bowel (fever, nausea, vomiting, abdominal pain or bloating) should consult a doctor to rule out these conditions before initiating LAX-A-DAY therapy. Taking more than the recommended dose of LAX-A- DAY may cause loss of fluid or dehydration due to severe diarrhea. Should unusual cramps, bloating, or diarrhea occur, consult your physician. This product should be used for one (1) week or less or as directed by a physician. Prolonged, frequent or excessive use of LAX-A-DAY may result in electrolyte imbalance and dependence on laxatives. Before taking LAX-A-DAY, tell your doctor or pharmacist: if you have ever had any allergic reaction to medications, food, etc; about your medical conditions and medications; if you are pregnant or thinking about becoming pregnant, or if you are breast feeding. INTERACTIONS WITH THIS MEDICATION No specific drug interactions have been demonstrated. However, the desired effect of other medications may be reduced if taken with laxatives. Avoid taking LAX-A-DAY within two (2) hours of taking another medication. PROPER USE OF THIS MEDICATION Usual dose: A single dose is 17 grams and should be taken once a day or as directed by your physician or a health care professional. Directions: Note (bottles): The bottle formats are supplied with a dosing cup marked to contain 17 grams of powder when filled to the indicated line. 1. Bottles: Pour 17 grams (about 1 heaping tablespoon) of powder into the dosing cap provided. Sachets: Open one sachet (17 g). 2. Stir the powder in a cup (250 ml) of water, juice, soda, coffee, or tea until completely dissolved. 3. Drink the solution. 4. Treatment for 2 to 4 days may be required to produce a bowel movement. LAX-A-DAY should be used for one week or less or as directed by a physician. Treatment for two to four days (48 to 96 hours) may be required to produce a bowel movement. You may discontinue taking the drug after you have had several satisfactory bowel movements. Should unusual cramps, bloating, or diarrhea occur, consult your physician. LAX-A-DAY is intended for up to a one week course of therapy. You should not use for a longer time unless directed by your physician. Page 12 of 13

13 IMPORTANT: PLEASE READ Patients presenting with complaints of constipation should have a thorough medical history and physical examination to detect associated metabolic, endocrine and neurogenic conditions, and medications. A diagnostic evaluation should include a structural examination of the colon. Patients should be educated about good defecatory and eating habits (such as high fiber diets) and lifestyle changes (adequate dietary fiber and fluid intake, regular exercise) which may produce more regular bowel movements. Overdose: There have been no reports of accidental overdosage. In the event of an overdosage, dehydration due to diarrhea may result. Stop taking LAX-A-DAY and drink plenty of water. SIDE EFFECTS AND WHAT TO DO ABOUT THEM Like all medications, LAX-A-DAY can cause some side effects. You may not experience any of them. For most patients these side effects are likely to be minor and temporary. If you experience an allergic reaction (including red skin, hives, itching, swelling of the lips, face, tongue, throat, trouble breathing, wheezing, shortness of breath, skin rashes, blisters of the skin, sores or pain in the mouth or eyes) or any severe or unusual side effects, stop taking the drug and contact your doctor immediately. Some side effects of LAX-A-DAY are: Nausea, abdominal bloating, cramping and flatulence Diarrhea and excessive stool frequency, particularly in elderly nursing home patients Urticaria suggestive of an allergic reaction SERIOUS SIDE EFFECTS, HOW OFTEN THEY HAPPEN AND WHAT TO DO ABOUT THEM Symptom/effect Talk with your doctor or pharmacist right away Seek urgent medical attention Common Uncommon Rare Nausea, abdominal bloating, cramping and flatulence Diarrhea Allergic reactions [red skin, hives, itching, swelling of the lips, face, tongue, throat, trouble breathing, wheezing, shortness of breath, skin rashes, blisters of the skin, sores or pain in the mouth or eyes] Only if severe In all cases HOW TO STORE IT Store LAX-A-DAY at room temperature (15 C -30 C), in a dry place. Keep container tightly closed. Keep all medicines out of the reach of children. REPORTING SUSPECTED SIDE EFFECTS You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways: Report online at Call toll-free at Complete a Canada Vigilance Reporting Form and: - Fax toll-free to , or - Mail to: Canada Vigilance Program Health Canada Postal Locator 0701E Ottawa, Ontario K1A 0K9 Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect Canada Web site at NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice. MORE INFORMATION This document plus the full prescribing information, prepared for health professionals can be obtained by contacting the sponsor, Pendopharm, division of Pharmascience Inc., at: This leaflet was prepared by Pendopharm, division of Pharmascience Inc. Last revised: March 25, 2014 LAX-A-DAY is a registered trademark of Pharmascience Inc. This is not a complete list of side effects. For any unexpected effects while taking LAX-A-DAY, contact your doctor or pharmacist. Page 13 of 13