FROM THE CANADIAN PAEDIATRIC SOCIETY
SOCIETE CANADIENNE DE PEDIATRIE COMMUNIQUE
Initial therapy for bacterial meningitis Infectious Diseases and Immunization Committee,* Canadian Paediatric Society
In a previous statement our committee recommended the use of cefuroxime for invasive disease caused by Haemophilus influenzae type b (Hib), including meningitis.' Because recent studies have revealed a significant delay in the sterilization of cerebrospinal fluid (CSF) in children with bacterial meningitis receiving cefuroxime, as compared with those receiving ceftriaxone,2'3 we recommend that cefuroxime should not be used for initial treatment of bacterial meningitis in children. Instead, therapy should be started with ampicillin plus chloramphenicol, cefotaxime or ceftriaxone. As soon as the pathogen is identified the therapy should be changed to penicillin for pneumococcal or meningococcal meningitis and to ampicillin for Hib infection with ampicillin-susceptible organisms because of the expense of cephalosporins. Cephalosporin therapy should be continued if there is an ampicillin-resistant Hib strain or purulent meningitis with negative culture results. There has always been some concern about cefuroxime's activity against Hib. Although the drug has been found to be significantly less active than ampicillin, chloramphenicol, cefotaxime and ceftriaxone, the initial results of clinical trials have not detected any significant differences in outcome between cefuroxime and other antibiotics.4-6 However, in one study 4 of 39 children given cefuroxime had positive CSF culture results 24 hours or more after
the start of therapy, as compared with none of those given ampicillin and chloramphenicol.7 In the Dallas studies there was no difference in mortality rates between children receiving cefuroxime and those receiving ceftriaxone.1 However, CSF cultures were positive for Hib between 18 and 36 hours after the start of the therapy for 15% of the children in the cefuroxime group, as compared with 7% of those in the ceftriaxone group. Children with delayed sterilization were more severely ill on presentation, younger (mean age 7.1 v. 13.8 months) and more likely to have had seizures before admission (41% v. 13%) and had significantly lower CSF glucose concentrations before treatment (11 v. 29 mg/dl [0.6 v. 1.6 mmol/L]). Delayed sterilization occurred in 17 of 238 children with Hib meningitis but in only 1 of 31 with pneumococcal meningitis and none of 27 with meningococcal meningitis. Among children with delayed sterilization the clinical course and outcome were less favourable and neurologic complications during the hospital stay and at discharge more common; 6 weeks after discharge significantly more of the delayed-sterilization group than of the negative-culture group (40.0% v. 13.6%) had at least one neurologic abnormality. As long-term follow-up is not yet complete, differences in the ultimate outcome are not known. The results in Dallas have been confirmed in a prospective comparison of cefuroxime and ceftriax-
*Members: Drs. Ann Hawkins (director responsible), Izaak Walton Killam Hospitalfor Children, Halifax; Ronald Gold (chairman and principal author), Department of Pediatrics, Hospitalfor Sick Children, Toronto; Scott A. Halperin, Department of Pediatrics, Izaak Walton Killam Hospitalfor Children, Halifax; Normand Lapointe, Department of Pediatrics, hopital Sainte-Justine, Montreal; Barbara J. Law, Department of Pediatric Infectious Disease, Health Sciences Centre, Winnipeg; Noni E. MacDonald, head, Infectious Disease Service, Children's Hospital of Eastern Ontario, Ottawa; and Elaine L. Mills, Infectious Disease Service, Montreal Children's Hospital. Consultants: Drs. Jaqueline A.K Carlson, Disease Control and Epidemiology Service, Ontario Ministry of Health, Toronto; Pierre Dery, Department of Pediatrics, Centre hospitalier de l'universite Laval, Ste-Foy, PQ; Victor Marchessault, executive vice-president, Canadian Paediatric Society, Ottawa; David W. Scheifele, Research Center, British Columbia's Children's Hospital, Vancouver; and John R. Waters, director, Communicable Disease Control and Epidemiology, Alberta Department of Social Services and Community Health, Edmonton. American Academy of Pediatrics liaison: Dr. Stanley Plotkin, Division of Infectious Diseases, Children's Hospital of Philadelphia. Reprint requests to: Infectious Diseases and Immunization Committee, Canadian Paediatric Society, Children's Hospital of Eastern Ontario, 401 Smyth Rd., Ottawa, Ont. KIH 8LI CAN MED ASSOC J 1990; 142 (4)
305
one in Switzerland.3 Delayed sterilization occurred in 12% of children treated with cefuroxime, as compared with 2% of those who received ceftriaxone. At 6 to 8 weeks after discharge hearing impairment was detected in 17% of those treated with cefuroxime and in 3.8% of those treated with ceftriaxone (p < 0.05). No other differences in neurologic sequelae were present. A review of the experience since 1979 at the Hospital for Sick Children, Toronto, has shown no change in the incidence of deafness or neurologic sequelae since the introduction in July 1983 of cefuroxime for the initial treatment of meningitis (R.G.: unpublished data, 1989). However, the rate of severe deafness in Toronto is only 2% to 3% (R.G.: unpublished data, 1989), as compared with 12% to 14% in Dallas;4 thus, it would be very difficult to detect a difference in outcome in Toronto. Although cefuroxime is no longer recommended for the treatment of bacterial meningitis, it remains an excellent choice for the initial treatment of other invasive bacterial infections such as pneumonia, osteomyelitis, septic arthritis, epiglottitis and cellulitis caused by Hib, Streptococcus pneumoniae, Neisseria meningitidis or Staphylococcus aureus - as long as meningitis has been excluded.
(RANnIIDINE HCI)
PRESCRIBING INFORMATION ZANTAC TABLETS (ranitidine hydrochloride)
Pharmaological Classification Histamine H2 - receptor antagonist Indications and Clinical use Zantac Tablets are indicated for the treatment of all conditions where a controlled reduction of gastric secretion is required for the rapid relief of pain and/or ulcer healing. These include duodenal ulcer, Xgojgagastric ulcer and reflux oesopbgitis ContaIndIcations - Zantac is contraindicated for patients known to have hypersensitivity to the drug. Warnings - Gastric ulcer - Treatment with a histamine H2 - antagonist may mask symptoms associated with carcinoma of the stomach and therefore may delay diagnosis of the condition. Accordingly, where gastric ulcer is suspected the possibility of malignancy should be excluded before therapy with Zantac is instituted. Precautions - Use in pregnancy and nursing mothers - The safety of Zantac in the treatment of conditions where a controlled reduction of gastric secretion is required during pregnancy has not been established. Reproduction studies performed in rats and rabbits have revealed no evidence of impaired fertility or harm to the foetus due to Zantac. If the administration of Zantac is considered to be necessary, its use requires that the potential benefits be weighed against possible hazards to the patient and to the foetus. Ranitidine is secreted in breast milk in lactating mothers but the clinical significance of this has not been fully evaluated. Use In impaired renal function - Ranitidine is excreted via the kidney and in the presence of severe renal impairment plasma levels of ranitidine are increased and prolonged. Accordingly, in the presence of severe renal impairment clinicians may wish to reduce the dose by one half. Children - Experience with Zantac Tablets in children is limited and such use has not been fully evaluated in clinical studies. It has however been used successfully in children aged 8-18 years in doses up to 150 mg twice daily without adverse effect. Interactions with other drugs - Although ranitidine has been reported to bind weakly to cytochrome P450 in vitro, recommended doses to the drug do not inhibit the action of the cytochrome P450-linked oxygenase in the liver. There are conflicting reports in the literature about possible interactions between ranitidine and several drugs, the clinical significance of these reports has not been substantiated. Amongst the drugs studied were warfarin, diazepam, metoprolol and nifedipine. If high doses (2g) of sucralfate are co-administered with ranitidine the absorption of the latter may be reduced. This effect is not seen if sucralfate is taken after an interval of 2 hours. Adverse Reactions - Headache, sometimes severe, rash, dizziness, constipation, diarrhoea and nausea have been reported in a very small proportion of drug-treated patients but these also occurred in patients receiving placebo. A few patients on re-challenge with Zantac have had a recurrence of skin rash, headache or dizziness. Rare reports of bradycardia have occurred. Rare cases of reversible mental confusion and hallucinations have been reported, predominantly in severely ill and elderly patients. There have been a few reports of reversible blurred vision suggestive of a change in accommodation. Some increases in serum transaminases and gamma-glutamyl transpeptidase have been reported which have returned to normal either on continued treatment or on stopping Zantac. In placebo controlled studies involving nearly 2,500 patients, there was no difference between the incidence of elevations of SGOT and/or SGPT values in the Zantac treated or placebo treated groups. There have been occasional reports of reversible hepatitis (hepatocellular, hepatocanicular or mixed) with or without jaundice. Hypersensitivity reactions (urticaria, angioneurotic oedema, bronchospasm, hypotension) have been seen rarely following the parenteral and oral administration of Zantacl These reactions have occasionally occurred after a single dose. Reversible blood count changes (leucopaenia, thrombocytopaenia) have occurred in a few patients. Rare cases of agranulocytosis or of pancytopaenia sometimes with marrow hypoplasia have been reported. Other haematological and renal laboratory tests have not revealed any drug related abnormalities. No clinically significant interference with endocrine or gonadal function has been reported. There have
306
CAN MED ASSOC J 1990; 142 (4)
References 1. Infectious Diseases and Immunization Committee, Canadian Paediatric Society: Initial antibiotic treatment of bacterial meningitis in children. Can MedAssoc J 1986; 135: 1085-1086 2. Lebel MH, McCracken GH: Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children. Pediatrics 1989; 83: 161-167 3. Schaad UB, Wedgwood J, Suter S et al: Prospective comparison of ceftriaxone (CRO) and cefuroxime (CXM) for therapy of bacterial meningitis in 106 infants and children [abstr 11 15]. In Abstracts of the 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Washington, 1989: 291
4. Lebel MH, Freij BJ, Syriogiannopolous GA: Dexamethasone therapy for bacterial meningitis: results of two double-blind, placebo-controlled trials. N Engl J Med 1988; 319: 964-971 5. Swedish Study Group: Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis. Lancet 1982; 1: 295-298
6. Schaad UB, Krucko J, Pfenninger J: An extended experience with cefuroxime therapy of childhood bacterial meningitis. Pediatr In fect Dis 1984; 2: 410-416 7. Marks WA, Stutman HR, Marks MI et al: Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial. J Pediatr 1986; 109: 123-130
been a few reports of breast symptoms (swelling and/or discomfort) in men taking ranitidine; some cases have resolved on continued treatment. Symptoms and Tleatment of Overdosage - No particular problems are expected following overdosage with Zantac. Symptomatic and supportive therapy should be given as appropriate. If need be, the drug may be removed from the plasma by haemodialysis. Dosage and Administration - Adults Duodenal ulceration, benign gastric ulceration, or ref lux oesophagitis: 300mg once daily at bedtime. It is not necessary to time the dose in relation to meals. In most cases of duodenal ulcer and benign gastrc ulcer, healing will occur in four weeks. In the small number of patients whose ulcers may not have fully healed, these are likely to respond to a further course of treatment. Patients who have responded to this short term therapy, particularIl those with a historv of recurrent ulcer. may usefully have extended maintenance treatment at a reduced dosag f n 1 mg tablet at bedtime. To help in the management of reflux oesophagitis, the recommended course uf treatment is one 300 mg tablet once daily at bedtime or one 150 mg tablet twice daily for up to 8 weeks. Children: Experience with Zantac in children is limited and it has not been fully evaluated in clinical studies - see Precautions. Availability - Zantac Tablets are available as white film-coated tablets engraved ZANTAC 150 on one face and GLAXO on the other, containing 150 mg ranitidine (as the hydrochloride), in packs of 30 and 60 tablets. Zantac Tablets are also available as white, capsule shaped, film-coated tablets engraved ZANTAC 300 on one face and GLAXO on the other, containing 300 mg ranitidine (as the hydrochloride), in packs of 30 tablets. Zantac Injection is available as 2 mL ampoules each containing 50 mg ranitidine (as the hydrochloride) in 2 mL solution for intravenous or intramuscular administration. Packages of 10 ampoules. Product Monograph available on request. References 1. Ireland etal: The Lancet, August 4, 1984; 274-275. 2. Barbara etal: International J. of Clinical Pharmacology, Therapy and Toxicology 1986; 24 (2): 104-107. 3. Product Monograph. 4. Silvis etal: J. of Clinical Gastroenterology 1985; 7 (6): 482-487. 5. Gough et aI: The Lancet, September 22, 1984; 659-662. 6. Simon etal: J. of Clinical Gastroenterology 1986; 8 (3): 482-487. 7. Jensen etal: New England Journal of Medicine 1983; 308: 883-887. 8. Data on File. 9. Smith etal: Br. J. of Clin Pharmacology 1987; (23): 311-315. 10. Powell eta/: Arch Internal Med 1984; (144): 484-486. 11. Sutherland et al: Eur J Clin Pharmacology 1987; 32: 159-164. 12. Siepler et al: Clin Pharmacy 1986; 5: 129-142. 13& Wormsley: Postgrad Med J 1988; 64 (Suppl 1): 47-53.
Glaxo Glaxo Canada Inc.
ICP
SOCIETE CANADIENNE DE PEDIATRIE COMMUNIQUE
Initial therapy for bacterial meningitis Infectious Diseases and Immunization Committee,* Canadian Paediatric Society
In a previous statement our committee recommended the use of cefuroxime for invasive disease caused by Haemophilus influenzae type b (Hib), including meningitis.' Because recent studies have revealed a significant delay in the sterilization of cerebrospinal fluid (CSF) in children with bacterial meningitis receiving cefuroxime, as compared with those receiving ceftriaxone,2'3 we recommend that cefuroxime should not be used for initial treatment of bacterial meningitis in children. Instead, therapy should be started with ampicillin plus chloramphenicol, cefotaxime or ceftriaxone. As soon as the pathogen is identified the therapy should be changed to penicillin for pneumococcal or meningococcal meningitis and to ampicillin for Hib infection with ampicillin-susceptible organisms because of the expense of cephalosporins. Cephalosporin therapy should be continued if there is an ampicillin-resistant Hib strain or purulent meningitis with negative culture results. There has always been some concern about cefuroxime's activity against Hib. Although the drug has been found to be significantly less active than ampicillin, chloramphenicol, cefotaxime and ceftriaxone, the initial results of clinical trials have not detected any significant differences in outcome between cefuroxime and other antibiotics.4-6 However, in one study 4 of 39 children given cefuroxime had positive CSF culture results 24 hours or more after
the start of therapy, as compared with none of those given ampicillin and chloramphenicol.7 In the Dallas studies there was no difference in mortality rates between children receiving cefuroxime and those receiving ceftriaxone.1 However, CSF cultures were positive for Hib between 18 and 36 hours after the start of the therapy for 15% of the children in the cefuroxime group, as compared with 7% of those in the ceftriaxone group. Children with delayed sterilization were more severely ill on presentation, younger (mean age 7.1 v. 13.8 months) and more likely to have had seizures before admission (41% v. 13%) and had significantly lower CSF glucose concentrations before treatment (11 v. 29 mg/dl [0.6 v. 1.6 mmol/L]). Delayed sterilization occurred in 17 of 238 children with Hib meningitis but in only 1 of 31 with pneumococcal meningitis and none of 27 with meningococcal meningitis. Among children with delayed sterilization the clinical course and outcome were less favourable and neurologic complications during the hospital stay and at discharge more common; 6 weeks after discharge significantly more of the delayed-sterilization group than of the negative-culture group (40.0% v. 13.6%) had at least one neurologic abnormality. As long-term follow-up is not yet complete, differences in the ultimate outcome are not known. The results in Dallas have been confirmed in a prospective comparison of cefuroxime and ceftriax-
*Members: Drs. Ann Hawkins (director responsible), Izaak Walton Killam Hospitalfor Children, Halifax; Ronald Gold (chairman and principal author), Department of Pediatrics, Hospitalfor Sick Children, Toronto; Scott A. Halperin, Department of Pediatrics, Izaak Walton Killam Hospitalfor Children, Halifax; Normand Lapointe, Department of Pediatrics, hopital Sainte-Justine, Montreal; Barbara J. Law, Department of Pediatric Infectious Disease, Health Sciences Centre, Winnipeg; Noni E. MacDonald, head, Infectious Disease Service, Children's Hospital of Eastern Ontario, Ottawa; and Elaine L. Mills, Infectious Disease Service, Montreal Children's Hospital. Consultants: Drs. Jaqueline A.K Carlson, Disease Control and Epidemiology Service, Ontario Ministry of Health, Toronto; Pierre Dery, Department of Pediatrics, Centre hospitalier de l'universite Laval, Ste-Foy, PQ; Victor Marchessault, executive vice-president, Canadian Paediatric Society, Ottawa; David W. Scheifele, Research Center, British Columbia's Children's Hospital, Vancouver; and John R. Waters, director, Communicable Disease Control and Epidemiology, Alberta Department of Social Services and Community Health, Edmonton. American Academy of Pediatrics liaison: Dr. Stanley Plotkin, Division of Infectious Diseases, Children's Hospital of Philadelphia. Reprint requests to: Infectious Diseases and Immunization Committee, Canadian Paediatric Society, Children's Hospital of Eastern Ontario, 401 Smyth Rd., Ottawa, Ont. KIH 8LI CAN MED ASSOC J 1990; 142 (4)
305
one in Switzerland.3 Delayed sterilization occurred in 12% of children treated with cefuroxime, as compared with 2% of those who received ceftriaxone. At 6 to 8 weeks after discharge hearing impairment was detected in 17% of those treated with cefuroxime and in 3.8% of those treated with ceftriaxone (p < 0.05). No other differences in neurologic sequelae were present. A review of the experience since 1979 at the Hospital for Sick Children, Toronto, has shown no change in the incidence of deafness or neurologic sequelae since the introduction in July 1983 of cefuroxime for the initial treatment of meningitis (R.G.: unpublished data, 1989). However, the rate of severe deafness in Toronto is only 2% to 3% (R.G.: unpublished data, 1989), as compared with 12% to 14% in Dallas;4 thus, it would be very difficult to detect a difference in outcome in Toronto. Although cefuroxime is no longer recommended for the treatment of bacterial meningitis, it remains an excellent choice for the initial treatment of other invasive bacterial infections such as pneumonia, osteomyelitis, septic arthritis, epiglottitis and cellulitis caused by Hib, Streptococcus pneumoniae, Neisseria meningitidis or Staphylococcus aureus - as long as meningitis has been excluded.
(RANnIIDINE HCI)
PRESCRIBING INFORMATION ZANTAC TABLETS (ranitidine hydrochloride)
Pharmaological Classification Histamine H2 - receptor antagonist Indications and Clinical use Zantac Tablets are indicated for the treatment of all conditions where a controlled reduction of gastric secretion is required for the rapid relief of pain and/or ulcer healing. These include duodenal ulcer, Xgojgagastric ulcer and reflux oesopbgitis ContaIndIcations - Zantac is contraindicated for patients known to have hypersensitivity to the drug. Warnings - Gastric ulcer - Treatment with a histamine H2 - antagonist may mask symptoms associated with carcinoma of the stomach and therefore may delay diagnosis of the condition. Accordingly, where gastric ulcer is suspected the possibility of malignancy should be excluded before therapy with Zantac is instituted. Precautions - Use in pregnancy and nursing mothers - The safety of Zantac in the treatment of conditions where a controlled reduction of gastric secretion is required during pregnancy has not been established. Reproduction studies performed in rats and rabbits have revealed no evidence of impaired fertility or harm to the foetus due to Zantac. If the administration of Zantac is considered to be necessary, its use requires that the potential benefits be weighed against possible hazards to the patient and to the foetus. Ranitidine is secreted in breast milk in lactating mothers but the clinical significance of this has not been fully evaluated. Use In impaired renal function - Ranitidine is excreted via the kidney and in the presence of severe renal impairment plasma levels of ranitidine are increased and prolonged. Accordingly, in the presence of severe renal impairment clinicians may wish to reduce the dose by one half. Children - Experience with Zantac Tablets in children is limited and such use has not been fully evaluated in clinical studies. It has however been used successfully in children aged 8-18 years in doses up to 150 mg twice daily without adverse effect. Interactions with other drugs - Although ranitidine has been reported to bind weakly to cytochrome P450 in vitro, recommended doses to the drug do not inhibit the action of the cytochrome P450-linked oxygenase in the liver. There are conflicting reports in the literature about possible interactions between ranitidine and several drugs, the clinical significance of these reports has not been substantiated. Amongst the drugs studied were warfarin, diazepam, metoprolol and nifedipine. If high doses (2g) of sucralfate are co-administered with ranitidine the absorption of the latter may be reduced. This effect is not seen if sucralfate is taken after an interval of 2 hours. Adverse Reactions - Headache, sometimes severe, rash, dizziness, constipation, diarrhoea and nausea have been reported in a very small proportion of drug-treated patients but these also occurred in patients receiving placebo. A few patients on re-challenge with Zantac have had a recurrence of skin rash, headache or dizziness. Rare reports of bradycardia have occurred. Rare cases of reversible mental confusion and hallucinations have been reported, predominantly in severely ill and elderly patients. There have been a few reports of reversible blurred vision suggestive of a change in accommodation. Some increases in serum transaminases and gamma-glutamyl transpeptidase have been reported which have returned to normal either on continued treatment or on stopping Zantac. In placebo controlled studies involving nearly 2,500 patients, there was no difference between the incidence of elevations of SGOT and/or SGPT values in the Zantac treated or placebo treated groups. There have been occasional reports of reversible hepatitis (hepatocellular, hepatocanicular or mixed) with or without jaundice. Hypersensitivity reactions (urticaria, angioneurotic oedema, bronchospasm, hypotension) have been seen rarely following the parenteral and oral administration of Zantacl These reactions have occasionally occurred after a single dose. Reversible blood count changes (leucopaenia, thrombocytopaenia) have occurred in a few patients. Rare cases of agranulocytosis or of pancytopaenia sometimes with marrow hypoplasia have been reported. Other haematological and renal laboratory tests have not revealed any drug related abnormalities. No clinically significant interference with endocrine or gonadal function has been reported. There have
306
CAN MED ASSOC J 1990; 142 (4)
References 1. Infectious Diseases and Immunization Committee, Canadian Paediatric Society: Initial antibiotic treatment of bacterial meningitis in children. Can MedAssoc J 1986; 135: 1085-1086 2. Lebel MH, McCracken GH: Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children. Pediatrics 1989; 83: 161-167 3. Schaad UB, Wedgwood J, Suter S et al: Prospective comparison of ceftriaxone (CRO) and cefuroxime (CXM) for therapy of bacterial meningitis in 106 infants and children [abstr 11 15]. In Abstracts of the 29th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Washington, 1989: 291
4. Lebel MH, Freij BJ, Syriogiannopolous GA: Dexamethasone therapy for bacterial meningitis: results of two double-blind, placebo-controlled trials. N Engl J Med 1988; 319: 964-971 5. Swedish Study Group: Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis. Lancet 1982; 1: 295-298
6. Schaad UB, Krucko J, Pfenninger J: An extended experience with cefuroxime therapy of childhood bacterial meningitis. Pediatr In fect Dis 1984; 2: 410-416 7. Marks WA, Stutman HR, Marks MI et al: Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial. J Pediatr 1986; 109: 123-130
been a few reports of breast symptoms (swelling and/or discomfort) in men taking ranitidine; some cases have resolved on continued treatment. Symptoms and Tleatment of Overdosage - No particular problems are expected following overdosage with Zantac. Symptomatic and supportive therapy should be given as appropriate. If need be, the drug may be removed from the plasma by haemodialysis. Dosage and Administration - Adults Duodenal ulceration, benign gastric ulceration, or ref lux oesophagitis: 300mg once daily at bedtime. It is not necessary to time the dose in relation to meals. In most cases of duodenal ulcer and benign gastrc ulcer, healing will occur in four weeks. In the small number of patients whose ulcers may not have fully healed, these are likely to respond to a further course of treatment. Patients who have responded to this short term therapy, particularIl those with a historv of recurrent ulcer. may usefully have extended maintenance treatment at a reduced dosag f n 1 mg tablet at bedtime. To help in the management of reflux oesophagitis, the recommended course uf treatment is one 300 mg tablet once daily at bedtime or one 150 mg tablet twice daily for up to 8 weeks. Children: Experience with Zantac in children is limited and it has not been fully evaluated in clinical studies - see Precautions. Availability - Zantac Tablets are available as white film-coated tablets engraved ZANTAC 150 on one face and GLAXO on the other, containing 150 mg ranitidine (as the hydrochloride), in packs of 30 and 60 tablets. Zantac Tablets are also available as white, capsule shaped, film-coated tablets engraved ZANTAC 300 on one face and GLAXO on the other, containing 300 mg ranitidine (as the hydrochloride), in packs of 30 tablets. Zantac Injection is available as 2 mL ampoules each containing 50 mg ranitidine (as the hydrochloride) in 2 mL solution for intravenous or intramuscular administration. Packages of 10 ampoules. Product Monograph available on request. References 1. Ireland etal: The Lancet, August 4, 1984; 274-275. 2. Barbara etal: International J. of Clinical Pharmacology, Therapy and Toxicology 1986; 24 (2): 104-107. 3. Product Monograph. 4. Silvis etal: J. of Clinical Gastroenterology 1985; 7 (6): 482-487. 5. Gough et aI: The Lancet, September 22, 1984; 659-662. 6. Simon etal: J. of Clinical Gastroenterology 1986; 8 (3): 482-487. 7. Jensen etal: New England Journal of Medicine 1983; 308: 883-887. 8. Data on File. 9. Smith etal: Br. J. of Clin Pharmacology 1987; (23): 311-315. 10. Powell eta/: Arch Internal Med 1984; (144): 484-486. 11. Sutherland et al: Eur J Clin Pharmacology 1987; 32: 159-164. 12. Siepler et al: Clin Pharmacy 1986; 5: 129-142. 13& Wormsley: Postgrad Med J 1988; 64 (Suppl 1): 47-53.
Glaxo Glaxo Canada Inc.
ICP
