Nonprescription Drug Screening
Loperamide Hydrochloride by Lydia M. Daugherty, PharmD
Introduction operamide hydrochloride is a piperidine derivative used in the management of diarrhea. 1 Loperamide is available on a nonprescription basis in selected dosage forms and has an advantage over prescription-only antidiarrheals because of its apparent lack of opiate-like side effects and abuse potential. This monograph reviews the pharmacology of loperamide and compares it to other agents currently available.
Trade Name: Imodium A-D
Dosage Forms: 1 mg/5 ml liquid 2 mg caplet (also available as 2-mg capsule by prescription order)
Indications and Actions Loperamide has been approved for nonprescription use in the treatment of acute, nonspecific diarrhea. In general, diarrhea that does not improve within 48 hours (24 hours in children) should be evaluated by a physician. As a prescription drug, loperamide may also be prescribed for the control and symptomatic relief of chronic diarrhea associated with inflammatory or functional bowel diseases. Loperamide also may be used to decrease the volume of discharge after ileostomies. 2,3 Loperamide locally inhibits peristaltic activity through direct action on the circulatory and longitudinal muscles located primarily in the jejunum. 1 Loperamide interacts with peripheral opiate receptors in a manner similar to codeine. 4 It may interact like morphine and diphenoxylate by enhancing contractions of circular muscles, which slows peristaltic activity.5 Loperamide increases gut capacitance allowing gastric contents to remain within
American Pharmacy, Vol. NS30, No. 12 December 19901745
the gut longer. 4 ,6 Unlike codeine and other opiate drugs, loperamide binds to calmodulin, a protein thought to be an important regulator of intestinal ion transport. 4 Tolerance to the antidiarrheal effects of loperamide has not been observed.
Side Effects Unlike centrally acting antidiarrheal agents, loperamide is generally well tolerated and adverse effects are usually minor. Physical dependence has not been reported with chronic use. 2 Adverse effects related to its antidiarrheal properties include constipation, abdominal pain, and distention or discomfort. 1 ,6 Other side effects noted include drowsiness or dizziness and hypersensitivity reactions such as skin rash. 1 ,2,5-8 In comparison trials, loperamide caused significantly more constipation than bismuth subsalicylate. 8 However, in trials with opiate derivatives and codeine, loperamide was associated with fewer side effects. 7 ,9 Toxic megacolon has been reported with the use of loperamide. 10 As with many agents, an overdose can cause severe side effects including constipation (toxic megacolon! ileus), central nervous system (CNS) depression, and gastrointestinal irritation. Children experience greater CNS depression than do adults if an overdose occurs. 2
Drug Interactions Loperamide has been shown to interfere with the absorption of 45
The(}-24, a sustained-release theophylline product. 6 Loperamide decreased the rate of theophylline absorption by 25%; however, it did not alter completeness of absorption of the product. The clinical significance of this interaction needs further investigation. Use of the drug with opiate analgesics may potentiate the development of constipation. Therefore, concurrent use of these agents should be carefully monitored.
Llperamide is not indicated for use in children less than two years old. This is due to the lack of data in this age group. Additionally, loperamide is not indicated in patients with a known hypersensitivity to the drug or in patients who must avoid constipation. The agent currently is not recommended for the treatment of diarrhea caused by enterotoxigenic bacteria (Esherichea coli, Salmonella, Shigella) or for antibioticinduced diarrhea. 2,11
Dosage and Administration Acute Diarrhea For treating acute diarrhea in adults, the initial dose of loperamide is 4 mg followed by 2 mg after each unformed stool. For self-medication, the over-the-counter preparation recommends a maximum dosage of 8 mg per day. 2,5 For children six to eight years old, the dose is 2 mg followed by 1 mg after each loose bowel movement, not
Use During Pregnancy Llperamide is classified as Category B (of moderate therapeutic value) by the Food and Drug Administration since the safety of loperamide in pregnancy has not been established. Animal studies have not shown teratogenicity or impairment of fertility.2,11 However, there are no well-controlled and adequate trials in humans. Therefore, loperamide should be used only when the potential benefit to the mother exceeds potential risk to the fetus.
Use by Lactating Mothers It is not known whether loperamide is excreted in breast milk. 2 The drug's safety in lactating women has not been established although loperamide has not been shown to have adverse effects in nursing infants. 11
Other Precautions and Special Considerations Diarrhea is frequently a symptom of another problem. In acute diarrhea, if clinical improvement is not observed within 48 hours, if fever occurs, or if there is a bloody discharge, the patient should discontinue use and consult a physician immediately. Since acute diarrhea can cause dehydration, especially in young children and the elderly, rehydration fluids should be started immediately. 2,11 Patients with chronic liver disease should use loperamide with caution, since it undergoes extensive firstpass metabolism. Chronic liver disease may predispose the patient to CNS toxicity, therefore referral of these patients to a physician may be appropriate. 2 46
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It is important to determine if a patient's condition warrants referral to a physician or if it can be safely and effectively treated with loperamide. The following questions as noted in the Handbook of Nonprescription Drugs, Eighth Edition, may assist the pharmacist in this decision. 13 • Is the diarrhea associated with other symptoms such as fever, vomiting, or pain? • How long have you had diarrhea? Was it sudden in onset? When was your last bowel movement? • Are the stools foul smelling, light in color, or greasy? Have you noted blood or mucus in the stool? • What is the age of the patient? Have other members of the family experienced similar symptoms? • Can you relate the onset of diarrhea to a specific cause such as a particular food (milk products), change in diet, or to travel to a foreign country? • Are you currently taking or have you recently stopped taking any antibiotics or other prescription or nonprescription drugs? • Do you have diabetes, liver disease, or other chronic diseases of the gastrointestinal tract? • Have you tried any other antidiarrheal products? Have any of them been of benefit?
American Pharmacy, Vol. NS30, No. 12 December 19901746
to exceed 4 mg per day. For children nine to 11 years old, the regimen is the same except the maximum recommended dose is 6 mg. Use for more that two days without medical supervision is not recommended.
Chronic Diarrhea When loperamide is prescribed for treating chronic diarrhea in adults, the initial dose is 4 mg, followed by 2 mg after each loose stool until diarrhea is controlled. Individual dosage requirements range from 4 to 8 mg per day in single or divided doses. Loperamide is unlikely to be effective if diarrhea has not been controlled in 10 days at the maximum recommended daily dosages of 16 mg. 5 It is not indicated in treating chronic diarrhea in children. 2 ,5
Comparison with Other Nonprescription Drugs The Food and Drug Administration (FDA) Advisory Review Panel on Over-the-Counter Laxative, Antidiarrheal, Emetic, and Antiemetic Drug Products has classified opiate combinations and polycarbophil as the only agents both safe and effective for nonprescription management of diarrhea. The FDA considered these recommendations, along with new evidence, and published its tentative final monograph in 1986. 12 The monograph listed polycarbophil and its calcium salt, and activated attapulgite as category I (safe and effective), placing opiate combination products in category ill (insufficient data). Since publication of the
Patient Information The patient should be advised to read the consumer information accompanying loperamide products. The pharmacist should emphasize the following points: • Consult your physician if any of the following symptoms are present: bloody stools, high fever, abdominal tenderness, dehydration, weight loss of greater than 5% of body weight, or diarrhea lasting for more than two days. • Loperamide is not indicated for self-medication in children less than six years old. For treatment of diarrhea in this age group, a physician should be consulted. • Caution should be taken if you are concurrently taking a narcotic pain reliever that may increase side effects of loperamide. • Oral rehydration fluids should be started as soon as possible to prevent the development of dehydration, especially in children and the elderly.
• If symptoms have not improved in 48 hours or if fever develops, discontinue use and consult a physician.
monograph, the FDA has also approved loperamide as a single ingredient product. 12 The FDA panel has classified adsorbents such as kaolin, pectin, and bismuth subsalicylate as safe for treating diarrhea. However, there is a lack of clinical evidence for efficacy. Adsorbents may actually bind drugs and cause drug interactions, a feature not observed with loperamide. 13 For the treatment of diarrhea, efficacy studies have shown loperamide superior when compared to kaolin. The time needed for 50% of patients to become symptom free was less than 12 hours with loperamide and approximately 80 hours with kaolin. 14 Loperamide has been compared to bismuth subsalicylate for the treatment of acute traveler's diarrhea. 8 Although not indicated for this purpose, loperamide was found to significantly reduce the number of unformed stools in the first 48 hours. Loperamide's mechanism of action is similar to that of paregoric, an opium derivative available, in combination with other agents, on a nonprescription basis (Schedule V). Both are effective for treating acute and chronic diarrhea; however, loperamide lacks the opiate side effects. Loperamide, as compared to anticholinergic and paregoric-containing products available on a nonprescription basis, exerts primarily local effects. These other agents can cause CNS toxicities not seen with loperamide. Polycarbophil is a hydrophilic resin promoted as a laxative and antidiarrheal agent. It has the capacity for binding many times its weight in water. Since it is nonabsorbed, there are no system toxicities. Loperamide may work quicker than polycarbophil in acute diarrhea. However, both agents are effecti ve in treating acute and chronic diarrhea. Loperamide and polycarbophil share the nuisance side effects, including bloating and epigastric pain. 13
Conclusions • Loperamide should not be taken for traveler's diarrhea unless authorized by your physician.
American Pharmacy, Vol. NS30, No. 12 December 19901747
The availability of loperamide as an over-the-counter antidiarrheal agent represents a significant addition to the pharmacist in terms 47
of product recommendation considerations for management of acute diarrhea. No nonprescription antidiarrheal product should be used for more than 48 hours if improvement is not seen.
This Nonprescription Drug Screening Monograph was prepared under the auspices of the APhA Academy of Pharmacy Practice and Management Section on Clinical Pharmacotherapeutic Practice. Lydia M. Daugherty, PharmD, is a clinical pharmacist, Duke University Medical Center, and Adjunct Instructor, University of North Carolina School of Pharmacy. Jerry Snidow, PharmD , associate director of drug information at Glaxo Inc.; Gina Upchurch, BS, resident in geriatrics, Program on Aging, University of North Carolina at Chapel Hill; and Daniel A. Hussar, PhD, Remington professor ofpharmacy, School ofPharmacy, Philadelphia College of Pharmacy
and Science, Philadelphia, PA, served on the review panel for this monograph. 8.
References 1. Galambos JT, Hersh T, et al. Loperamide: a new antidiarrheal agent in the treatment of chronic diarrhea. Gastroenterology. 1976;70(6): 1026-9. 2. Kastrup EK, Olin BR, eds. Facts and Comparisons. St. Louis, Mo: JB Lippincott Co, 1987, p. 324b-c. 3. Mainquet P, Fiasse R. Double-blind placebo-controlled study of loperamide (Imodium) in chronic diarrhea caused by ileocolic disease or resection. Gut. 1977;18(7):575- 9. 4. Schiller LR, Santa Ana CA, Morawski SG, et al. Mechanism of the antidiarrheal effect of loperamide. Gastroenterology. 1984;86:1475-80. 5. McEvoy GK, ed. AHFS Drug Information 90. Bethesda, Md: American Society of Hospital Pharmacists, 1990. 6. Bryson JC , Dukes GE, Kirby MG, et al. Effect of altering small bowel transit time on su stained release theophylline absorption. J Clin Pharmacol. 1989;29:733-8. 7. Pelemans W, Vantrappen G. A double
Now faster healing is a fact with
Aquaphor® AqiKfpoor. I\S5iSls !he skKI'snatural heoIIngplOcess. forveryClly
sldn.rmor cuts ondblms.
9.
10. 11.
12.
13.
14.
blind crossover comparison of loperamide with diphenoxylate in the symptomatic treatment of chronic diarrhea. Gastroenterology. 1976;70(6): 1030-4. Johnson PC , Ericsson CD, DuPont HL, et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute traveler's diarrhea. JAMA. 1986;255(6 ):757-60. Multicenter general practice comparison of loperamide and diphenoxylate with atropine in the treatment of acute diarrhea in adults. Br J Clin Pract. 1979;33(3):77-9. Brown JW. Toxic megacolon associated with loperamide therapy. JAMA . 1979;241(5):501-2. Drug Information for the Health Care Provider, 10th ed. Rockville, Md: United States Pharmacopeial Convention, Inc, 1990. Dukes GE. Over-the-counter antidiarrheal medications used for the self-treatment of acute nonspecific diarrhea. Am J Med . 1990;88:6a/24s26s. Handbook of Nonprescription Drugs, 8th ed. Washington, DC: American Pharmaceutical Association, 1986. John GI. Symptomatic treatment of acute self-limiting diarrhea in adults . . Practitioner. 1977 ;219 :396.
Aclinical confirms it: Aquaphor®,a pharmacists' favorite compounding agent, helps heal wounds significantly faster. Thars right. The compounding agent you've trusted for years has been proven to speed healing when applied singularly to wounds. Aquaphor provides a unique protective environment. Unlike other petrolatum-based products, Aquaphor allows the natural passage of fluids and air, while retaining vital moisture. Irs this ideal combination that helps severely dry or damaged skin and minor burns heal faster Aquaphor contains no fragrances, preservatives or known irritants to interfere with healing. So alone or as a compound, Aquaphor helps enhance the healing process.
Aquaphor Healing Ointment: the clinicallyproven way to heal wounds faster. Irs about time.
Aquaphor treated experimental wound on day 10 (final day) of clinical resuHs.
Untreated experimental wound on day 10 (final day) of clinical resuHs.
Aquaphor is a registered trademark of Beiersdorf AG
1Data
on file, Beiersdorf, Inc.
Beiersdorf Inc Norwalk, CT 06856-5529 © 1990
48
American Pharmacy, Vol. NS30, No. 12 December 19901748
Loperamide Hydrochloride by Lydia M. Daugherty, PharmD
Introduction operamide hydrochloride is a piperidine derivative used in the management of diarrhea. 1 Loperamide is available on a nonprescription basis in selected dosage forms and has an advantage over prescription-only antidiarrheals because of its apparent lack of opiate-like side effects and abuse potential. This monograph reviews the pharmacology of loperamide and compares it to other agents currently available.
Trade Name: Imodium A-D
Dosage Forms: 1 mg/5 ml liquid 2 mg caplet (also available as 2-mg capsule by prescription order)
Indications and Actions Loperamide has been approved for nonprescription use in the treatment of acute, nonspecific diarrhea. In general, diarrhea that does not improve within 48 hours (24 hours in children) should be evaluated by a physician. As a prescription drug, loperamide may also be prescribed for the control and symptomatic relief of chronic diarrhea associated with inflammatory or functional bowel diseases. Loperamide also may be used to decrease the volume of discharge after ileostomies. 2,3 Loperamide locally inhibits peristaltic activity through direct action on the circulatory and longitudinal muscles located primarily in the jejunum. 1 Loperamide interacts with peripheral opiate receptors in a manner similar to codeine. 4 It may interact like morphine and diphenoxylate by enhancing contractions of circular muscles, which slows peristaltic activity.5 Loperamide increases gut capacitance allowing gastric contents to remain within
American Pharmacy, Vol. NS30, No. 12 December 19901745
the gut longer. 4 ,6 Unlike codeine and other opiate drugs, loperamide binds to calmodulin, a protein thought to be an important regulator of intestinal ion transport. 4 Tolerance to the antidiarrheal effects of loperamide has not been observed.
Side Effects Unlike centrally acting antidiarrheal agents, loperamide is generally well tolerated and adverse effects are usually minor. Physical dependence has not been reported with chronic use. 2 Adverse effects related to its antidiarrheal properties include constipation, abdominal pain, and distention or discomfort. 1 ,6 Other side effects noted include drowsiness or dizziness and hypersensitivity reactions such as skin rash. 1 ,2,5-8 In comparison trials, loperamide caused significantly more constipation than bismuth subsalicylate. 8 However, in trials with opiate derivatives and codeine, loperamide was associated with fewer side effects. 7 ,9 Toxic megacolon has been reported with the use of loperamide. 10 As with many agents, an overdose can cause severe side effects including constipation (toxic megacolon! ileus), central nervous system (CNS) depression, and gastrointestinal irritation. Children experience greater CNS depression than do adults if an overdose occurs. 2
Drug Interactions Loperamide has been shown to interfere with the absorption of 45
The(}-24, a sustained-release theophylline product. 6 Loperamide decreased the rate of theophylline absorption by 25%; however, it did not alter completeness of absorption of the product. The clinical significance of this interaction needs further investigation. Use of the drug with opiate analgesics may potentiate the development of constipation. Therefore, concurrent use of these agents should be carefully monitored.
Llperamide is not indicated for use in children less than two years old. This is due to the lack of data in this age group. Additionally, loperamide is not indicated in patients with a known hypersensitivity to the drug or in patients who must avoid constipation. The agent currently is not recommended for the treatment of diarrhea caused by enterotoxigenic bacteria (Esherichea coli, Salmonella, Shigella) or for antibioticinduced diarrhea. 2,11
Dosage and Administration Acute Diarrhea For treating acute diarrhea in adults, the initial dose of loperamide is 4 mg followed by 2 mg after each unformed stool. For self-medication, the over-the-counter preparation recommends a maximum dosage of 8 mg per day. 2,5 For children six to eight years old, the dose is 2 mg followed by 1 mg after each loose bowel movement, not
Use During Pregnancy Llperamide is classified as Category B (of moderate therapeutic value) by the Food and Drug Administration since the safety of loperamide in pregnancy has not been established. Animal studies have not shown teratogenicity or impairment of fertility.2,11 However, there are no well-controlled and adequate trials in humans. Therefore, loperamide should be used only when the potential benefit to the mother exceeds potential risk to the fetus.
Use by Lactating Mothers It is not known whether loperamide is excreted in breast milk. 2 The drug's safety in lactating women has not been established although loperamide has not been shown to have adverse effects in nursing infants. 11
Other Precautions and Special Considerations Diarrhea is frequently a symptom of another problem. In acute diarrhea, if clinical improvement is not observed within 48 hours, if fever occurs, or if there is a bloody discharge, the patient should discontinue use and consult a physician immediately. Since acute diarrhea can cause dehydration, especially in young children and the elderly, rehydration fluids should be started immediately. 2,11 Patients with chronic liver disease should use loperamide with caution, since it undergoes extensive firstpass metabolism. Chronic liver disease may predispose the patient to CNS toxicity, therefore referral of these patients to a physician may be appropriate. 2 46
,
i,..
~
~
Questions to Ask tile,Ratient '~«
"j ..
~:":d
~:J,.~:;>,~it~:f;
~ ~~ ~"');~"" ,,'...
". . . ., >~~ ~
':... ...
~
...
~.,'
...
It is important to determine if a patient's condition warrants referral to a physician or if it can be safely and effectively treated with loperamide. The following questions as noted in the Handbook of Nonprescription Drugs, Eighth Edition, may assist the pharmacist in this decision. 13 • Is the diarrhea associated with other symptoms such as fever, vomiting, or pain? • How long have you had diarrhea? Was it sudden in onset? When was your last bowel movement? • Are the stools foul smelling, light in color, or greasy? Have you noted blood or mucus in the stool? • What is the age of the patient? Have other members of the family experienced similar symptoms? • Can you relate the onset of diarrhea to a specific cause such as a particular food (milk products), change in diet, or to travel to a foreign country? • Are you currently taking or have you recently stopped taking any antibiotics or other prescription or nonprescription drugs? • Do you have diabetes, liver disease, or other chronic diseases of the gastrointestinal tract? • Have you tried any other antidiarrheal products? Have any of them been of benefit?
American Pharmacy, Vol. NS30, No. 12 December 19901746
to exceed 4 mg per day. For children nine to 11 years old, the regimen is the same except the maximum recommended dose is 6 mg. Use for more that two days without medical supervision is not recommended.
Chronic Diarrhea When loperamide is prescribed for treating chronic diarrhea in adults, the initial dose is 4 mg, followed by 2 mg after each loose stool until diarrhea is controlled. Individual dosage requirements range from 4 to 8 mg per day in single or divided doses. Loperamide is unlikely to be effective if diarrhea has not been controlled in 10 days at the maximum recommended daily dosages of 16 mg. 5 It is not indicated in treating chronic diarrhea in children. 2 ,5
Comparison with Other Nonprescription Drugs The Food and Drug Administration (FDA) Advisory Review Panel on Over-the-Counter Laxative, Antidiarrheal, Emetic, and Antiemetic Drug Products has classified opiate combinations and polycarbophil as the only agents both safe and effective for nonprescription management of diarrhea. The FDA considered these recommendations, along with new evidence, and published its tentative final monograph in 1986. 12 The monograph listed polycarbophil and its calcium salt, and activated attapulgite as category I (safe and effective), placing opiate combination products in category ill (insufficient data). Since publication of the
Patient Information The patient should be advised to read the consumer information accompanying loperamide products. The pharmacist should emphasize the following points: • Consult your physician if any of the following symptoms are present: bloody stools, high fever, abdominal tenderness, dehydration, weight loss of greater than 5% of body weight, or diarrhea lasting for more than two days. • Loperamide is not indicated for self-medication in children less than six years old. For treatment of diarrhea in this age group, a physician should be consulted. • Caution should be taken if you are concurrently taking a narcotic pain reliever that may increase side effects of loperamide. • Oral rehydration fluids should be started as soon as possible to prevent the development of dehydration, especially in children and the elderly.
• If symptoms have not improved in 48 hours or if fever develops, discontinue use and consult a physician.
monograph, the FDA has also approved loperamide as a single ingredient product. 12 The FDA panel has classified adsorbents such as kaolin, pectin, and bismuth subsalicylate as safe for treating diarrhea. However, there is a lack of clinical evidence for efficacy. Adsorbents may actually bind drugs and cause drug interactions, a feature not observed with loperamide. 13 For the treatment of diarrhea, efficacy studies have shown loperamide superior when compared to kaolin. The time needed for 50% of patients to become symptom free was less than 12 hours with loperamide and approximately 80 hours with kaolin. 14 Loperamide has been compared to bismuth subsalicylate for the treatment of acute traveler's diarrhea. 8 Although not indicated for this purpose, loperamide was found to significantly reduce the number of unformed stools in the first 48 hours. Loperamide's mechanism of action is similar to that of paregoric, an opium derivative available, in combination with other agents, on a nonprescription basis (Schedule V). Both are effective for treating acute and chronic diarrhea; however, loperamide lacks the opiate side effects. Loperamide, as compared to anticholinergic and paregoric-containing products available on a nonprescription basis, exerts primarily local effects. These other agents can cause CNS toxicities not seen with loperamide. Polycarbophil is a hydrophilic resin promoted as a laxative and antidiarrheal agent. It has the capacity for binding many times its weight in water. Since it is nonabsorbed, there are no system toxicities. Loperamide may work quicker than polycarbophil in acute diarrhea. However, both agents are effecti ve in treating acute and chronic diarrhea. Loperamide and polycarbophil share the nuisance side effects, including bloating and epigastric pain. 13
Conclusions • Loperamide should not be taken for traveler's diarrhea unless authorized by your physician.
American Pharmacy, Vol. NS30, No. 12 December 19901747
The availability of loperamide as an over-the-counter antidiarrheal agent represents a significant addition to the pharmacist in terms 47
of product recommendation considerations for management of acute diarrhea. No nonprescription antidiarrheal product should be used for more than 48 hours if improvement is not seen.
This Nonprescription Drug Screening Monograph was prepared under the auspices of the APhA Academy of Pharmacy Practice and Management Section on Clinical Pharmacotherapeutic Practice. Lydia M. Daugherty, PharmD, is a clinical pharmacist, Duke University Medical Center, and Adjunct Instructor, University of North Carolina School of Pharmacy. Jerry Snidow, PharmD , associate director of drug information at Glaxo Inc.; Gina Upchurch, BS, resident in geriatrics, Program on Aging, University of North Carolina at Chapel Hill; and Daniel A. Hussar, PhD, Remington professor ofpharmacy, School ofPharmacy, Philadelphia College of Pharmacy
and Science, Philadelphia, PA, served on the review panel for this monograph. 8.
References 1. Galambos JT, Hersh T, et al. Loperamide: a new antidiarrheal agent in the treatment of chronic diarrhea. Gastroenterology. 1976;70(6): 1026-9. 2. Kastrup EK, Olin BR, eds. Facts and Comparisons. St. Louis, Mo: JB Lippincott Co, 1987, p. 324b-c. 3. Mainquet P, Fiasse R. Double-blind placebo-controlled study of loperamide (Imodium) in chronic diarrhea caused by ileocolic disease or resection. Gut. 1977;18(7):575- 9. 4. Schiller LR, Santa Ana CA, Morawski SG, et al. Mechanism of the antidiarrheal effect of loperamide. Gastroenterology. 1984;86:1475-80. 5. McEvoy GK, ed. AHFS Drug Information 90. Bethesda, Md: American Society of Hospital Pharmacists, 1990. 6. Bryson JC , Dukes GE, Kirby MG, et al. Effect of altering small bowel transit time on su stained release theophylline absorption. J Clin Pharmacol. 1989;29:733-8. 7. Pelemans W, Vantrappen G. A double
Now faster healing is a fact with
Aquaphor® AqiKfpoor. I\S5iSls !he skKI'snatural heoIIngplOcess. forveryClly
sldn.rmor cuts ondblms.
9.
10. 11.
12.
13.
14.
blind crossover comparison of loperamide with diphenoxylate in the symptomatic treatment of chronic diarrhea. Gastroenterology. 1976;70(6): 1030-4. Johnson PC , Ericsson CD, DuPont HL, et al. Comparison of loperamide with bismuth subsalicylate for the treatment of acute traveler's diarrhea. JAMA. 1986;255(6 ):757-60. Multicenter general practice comparison of loperamide and diphenoxylate with atropine in the treatment of acute diarrhea in adults. Br J Clin Pract. 1979;33(3):77-9. Brown JW. Toxic megacolon associated with loperamide therapy. JAMA . 1979;241(5):501-2. Drug Information for the Health Care Provider, 10th ed. Rockville, Md: United States Pharmacopeial Convention, Inc, 1990. Dukes GE. Over-the-counter antidiarrheal medications used for the self-treatment of acute nonspecific diarrhea. Am J Med . 1990;88:6a/24s26s. Handbook of Nonprescription Drugs, 8th ed. Washington, DC: American Pharmaceutical Association, 1986. John GI. Symptomatic treatment of acute self-limiting diarrhea in adults . . Practitioner. 1977 ;219 :396.
Aclinical confirms it: Aquaphor®,a pharmacists' favorite compounding agent, helps heal wounds significantly faster. Thars right. The compounding agent you've trusted for years has been proven to speed healing when applied singularly to wounds. Aquaphor provides a unique protective environment. Unlike other petrolatum-based products, Aquaphor allows the natural passage of fluids and air, while retaining vital moisture. Irs this ideal combination that helps severely dry or damaged skin and minor burns heal faster Aquaphor contains no fragrances, preservatives or known irritants to interfere with healing. So alone or as a compound, Aquaphor helps enhance the healing process.
Aquaphor Healing Ointment: the clinicallyproven way to heal wounds faster. Irs about time.
Aquaphor treated experimental wound on day 10 (final day) of clinical resuHs.
Untreated experimental wound on day 10 (final day) of clinical resuHs.
Aquaphor is a registered trademark of Beiersdorf AG
1Data
on file, Beiersdorf, Inc.
Beiersdorf Inc Norwalk, CT 06856-5529 © 1990
48
American Pharmacy, Vol. NS30, No. 12 December 19901748
