to warrant professional care affects. 2% to 4% of the general popula- tion. Cassem1 has observed that. "92% of all persons suffering from it are either treated by ...
applicants each year, the ratio of acceptable candidates to places available in medicine would not be quite so unfavourable to would-be physicians. As it is, enrolment cuts would likely increase the number of repeat applicants and reduce the opportunities for young Canadians to study medicine. EVA RYTEN, B SOC sc
Research division Association of Canadian Medical Colleges Ottawa, Ont.
Duricef cefadroxil monohydrate
THERAPEUTIC CLASSIFICATION: Antibiotic INDICATIONS: DURICEF may be indicated for the treatment of the following infections when caused by susceptible strains of the organisms indicated * Acute uncomplicated urinary tract infections when caused by E. coli, Klebsiella species and some strains of Proteus mirabilis. * Integumentary infections when caused by Staphylococcus aureus and group A betahemolytic streptococci. * Acute pharyngitis when caused by group A betahemolytic streptococci. Appropriate bacteriological studies should be performed prior to and during therapy in order to identify and determine the susceptibility of the causative organismlsl. CONTRAINDICATIONS: DURICEF is contraindicated in patients with a known hypersensitivity to the cephalosporin group of antibiotics.
Symptoms of withdrawal from tricyclic antidepressants To the editor: Depression sufficient to warrant professional care affects 2% to 4% of the general population. Cassem1 has observed that "92% of all persons suffering from it are either treated by nonpsychiatric personnel or are not treated at all". Tricyclic antidepressants constitute the major form of treatment of depression.2 They are also used to treat various other conditions, such as phobias, obsessive-compulsive disorders, enuresis, sleep disorders (e.g., narcolepsy) and depressive equivalents (e.g., chronic pain). Their quinidine-like properties may soon prompt the use of these drugs as antiarrhythmic agents. Side effects of tricyclic antidepres.ants are well known; these include dry mouth, blurred vision, constipation, reduced sweating, urinary retention, tachycardia, prostatism, raised intraocular tension in narrow-angle glaucoma, and toxic atropine-like effects on the central nervous system (e.g., delirium).2 Mentioned less often are the withdrawal symptoms, including nausea, vomiting, diaphoresis. restlessness, insomnia, headaches, dizziness, coryza, chills, gooseflesh, weakness, fatigue, musculoskeletal pain, abdominal cramps, malaise, anxiety, irritability, electrocardiogram changes, an akathisia-like syndrome and delirium.24 Similar symptoms are also reported when antipsychotic agents with potent an420
WARNINGS: There is clinical and laboratory evidence of cross-allergenicity between the penicillin and cephalosporin groups of antibiotics. There are instances of patients who have had reactions to both classes of antibiotics lincluding fatal anaphylactoid reactions after parenteral administrationl. In patients with known hypersensitivity to the penicillins, cephalosporin antibiotics lincluding DURICEFI should be administered with great caution. Antibiotics, including DURICEF, should be administered with caution and then only when absolutely necessary to any patient who has a history of some form of allergy, particularly to drugs. PRECAUTIONS: Patients should be carefully monitored to detect the development of any adverse effect or other manifestations of drug idiosyncrasy. If an allergic reaction to DURICEF occurs, its administration should be discontinued and the patient treated symptomatically. Prolonged use of DURICEF can result in the overgrowth of non-susceptible organisms. If superinfe6tion occurs during therapy, the administration of DURICEF should be discontinued and appropriate measures taken. If an organism becomes resistant during treatment with DURICEF alternate therapy should be instituted. DURICEF should be used with caution in the presence of markedly impaired renal function I i.e. a creatinine clearance rate of less than 50 mL/min/1.73m2-See DOSAGE AND ADMINISTRATION). In patients with known or suspected renal impairment careful clinical evaluation and appropriate laboratory studies should be performed prior to and during therapy, since DURICEF can accumulate in serum and tissues. DURICEF has been shown to inhibit platelet function in vitro. The clinical importance of this finding snot known. If DURICEF is to be used for long-term therapy, hematologic, renal and hepatic functions should be monitored periodically. Positive direct Coombs tests have been reported during treatment with the cephalosporin antibiotics. In hematologic studies or in transfusion cross-matching procedures, when antiglobulin tests are performed on the minor side or in Coombs testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs test may be due to the drug. During treatment with DURICEF a false positive reaction for glucose in the urine may occur with Benedict's or Fehlings solution or with Clinitest tablets, but not with enzyme-based tests such as Clinistix or Tes-Tape. The safety of DURICEF in the treatment of infections during pregnancy has not been established. The administration of DURICEF is not recommended during pregnancy. If, in the opinion of the attending physician, the administration of DURICEF is considered to be necessary, its use requires that the anticipated benefits be weighed against the possible hazards to the fetus. Cephalosporin antibiotics are excreted in human breast milk, and therefore, would be ingested by the neonate during breast feeding. Nursing mothers receiving DURICEF should, therefore, discontinue breast feeding.
CMA JOURNAL/SEPTEMBER 1. 1981/VOL. 125
Pseudomembranous colitis has been reported as a complication of antibiotic therapy, including therapy with the cephalosporins.
ADVERSE REACTIONS: Adverse reactions observed during the use of DURICEF include: Gastrointestinal: The most frequently observed have been nausea and vomiting. The incidence and severity are dose dependent and the latter has been severe enough to warrant cessation of therapy, but infrequently. Other reactions reported were abdominal cramps. gastric upset, heartburn, gas and diarrhea. Hypersensitivity: Rash, swollen and running eyes. urticaria, eosinophilia, angioedema and positive direct Coombs test. CNS: Dizziness, weakness, drowsiness, vertigo, nervousness and headaches. Miscellaneous: Vaginitis, monilial vaginitis, vaginal itching, cramps in side and legs, transient neutropenia and elevations in BUN, alkaline phosphatase and SGOT. These adverse reactions were seen during clinical trials with DURICEF in 43 out of a total of 737 patients 5.8%).
DOSAGE AND ADMINISTRATION: DURICEF is administered orally and may be taken without regard to meals.
ADULTS: Normal Renal Function: The recommended dose is 1 to 2 grams per day. Urinary Tract Infections: The recommended daily dose is 2 grams. This may be given as a single dose (four 500 mg capsules) at bedtime or divided into two 1 gram doses for twice-a-day administration levery 12 hours). The usual duration of therapy is 10 days. While shorter or longer courses may be appropriate for some patients, DURICEF should be administered for a sufficient period of time to render the urine sterile. The sterility of the urine should be re-evaluated 2 to 4 weeks after cessation of therapy. NB.: The incidence and severity of gastrointestinal complaints is dose dependent. Administration with food may be helpful to diminish potential intestinal complaints sometimes associated with oral cephalosporin therapy. Infegumentary Infections and Acute Pharyngitis: The recommended dose is 500 mg lone capsule) two times per day (every 12 hours). Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained.
A MINIMUM OF 10 DAYS TREATMENT IS RECOMMENDED FOR INFECTIONS CAUSED BY GROUP A BETA-HEMOLYTIC STREPTOCOCCI. Impaired Renal Function: The dosage of DURICEF should be adjusted according to creatinine clearance rates to prevent drug accumulation. The initial dose is equal to that for a patient with normal renal function (see above) and the maintenance dose (based on the creatinine clearance rate) is 500 mg (1 capsule) at the time intervals listed below. Creatinine Clearance Dose Interval (mL/min/1.73m2) (hours) 0-10 36 10-25 24 25-50 12 CHILDREN: There is clinical experience only for the treatment of integumentary infections and acute pharyngitis in children 7 years of age and over. For these infections the recommended dose is 500 mg (one capsule) every 12 hours. DOSAGE FORMS: DURICEF (cefadroxil capsules U.S.P.) is available in maroon and white hard gelatin capsules containing 500 mg of cefadroxil as cefadroxil monohydrate in bottles of 50 capsules.
PRODUCT MONOGRAPH AVAILABLE ON REQUEST
PA A H BRISTOL LABORATORIES of Canada isiol-Myers Canada Inc. Candiac. Believille,Ouebec Oniario
BRISTOL uni of Br .T.M Authorized user
DF1203
timuscarinic effects are suddenly discontinued.6 These symptoms are probably due to cholinergic rebound.7 Antipsychotic agents inhibit the metabolism of tricyclic antidepressants, so that the plasma levels of the drugs rise.8 Hence, withdrawal symptoms are more likely when combinations of these drugs are abruptly discontinued. These symptoms have been reported with the most common tricyclic antidepressants in use imipramine, amitriptyline and doxepin.3'4 They can occur with cessation of low doses, as in the case of a 29-year-old woman whose dose of amitriptyline was being tapered after 1 year of treatment; she had insomnia, anxiety, excessive sweating and abdominal cramps for 2 nights. They can also occur after a single dose is missed during active treatment.9 A 28-year-old woman who was depressed had been taking doxepin (25 mg three times a day) for about 28 days; nausea, restlessness and insomnia developed when she missed a single night's dose. These symptoms can also occur following withdrawal from an overdose. A 29-year-old woman who had received treatment for an amitriptyline overdose complained of insomnia, restlessness, nausea, vomiting, excessive sweating, abdominal cramps and tension in the back of her head, all lasting for 2 days. These withdrawal symptoms usually last about 48 hours and then, if the tricyclic antidepressant is not reinstated, will spontaneously remit. Physicians need to be on the lookout not only for the adverse effects of tricyclic antidepressants but also for withdrawal symptoms, and they should always taper the dosage when discontinuing their use. Some of these symptoms (e.g., insomnia, fatigue, restlessness, malaise, anxiety and irritability) can also be presenting complaints in depression.
2. BERNSTEIN JG: Chemotherapy in psychiatry. ibid: 451-482 3. KRAMER JC,
KLEIN
DF,
FINK
M:
With-
drawal symptoms following discontinuation of imipramine therapy. Am J Psychiatry 1961; 118: 549-550 4. SANTOS AR JR, McCuRoY L: Delirium after
abrupt withdrawal from doxepin: case report. Am J Psychiatry 1980; 137: 239-240 5. SHATAN C: Withdrawal symptoms after abrupt termination of imipramine. Can Psychiatr Assoc J 1966; 11 (suppl): S150-S158
6. MELNYK
WT,
WORTHINGTON
AG, LAVERTY
SG: Abrupt withdrawal of chlorpromazine and thioridazine from schizophrenic in-patients. Ibid: 410-413 7. LucHINs DJ, FREED WJ, WYATr RJ: The role of cholinergic supersensitivity in the medical symptoms associated with withdrawal of antipsychotic drugs. Am J Psychiatry 1980; 137: 1395-1398 8. GRAM LF, 0vER. KF: Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. Br Med 1 1972; 1: 463-465 9. STERN SL, MENOELs J: Withdrawal symptoms during the course of imipramine therapy. J Clin Psychiatry 1980; 41: 66-67
Birthweight and handicaps
could start by reminding ourselves that the keys to the prevention of handicaps are: (a) regular prenatal care for all mothers; (b) education on nutrition, smoking, and the use of alcohol and other drugs; (c) the early identification of pregnant women at high risk and appropriate perinatal care; and (d) quality care in the delivery room and nursery. W.J. ROBERTSON, MD, FRCP[C] 955 Queen St. E, Ste. 215 Sault Ste. Marie, Ont.
References I. BROWN JC: Prevention of Handicap: a Case for improved Prenatal and Perinatal Care. A Background Paper, Canadian Institute of Child Health, Ottawa, 1978 2. WYNN M, WYNN A: Prevention of Handicap of Perinatal Origin: an Introduction to French Policy and Legislation, Foundation for Education and Research in Childbearing, London, EngI, 1976 3. FITZHARDINGE PM, STEVEN EN: The smallfor-date infant. II. Neurological and intellectual sequelae. Pediatrics 1972; 50: 50-57 4. CHANCE 0: Perinatal medicine and the prevention of cerebral palsy. Presented at the Ontario Crippled Children's Centre, Toronto, Nov 9, 1977 5. McM.Nus F, RANG M, CHANCE 0, WssrrTAKER J: Is cerebral palsy a preventable disease? Obstet Gynecol 1977; 50: 71-77 6. Ontario Advisory Committee on Reproductive Medical Care: A Regionalized System for Reproductive Medical Care for Ontario: Report of the Advisory Committee on Reproductive Care to the Minister of Health for Ontario, Ontario Ministry of Health, Toronto, 1979
To the editor: As we proceed through 1981 - the International Year of Disabled Persons - let us remember the role we physicians have in the prevention of much disability. The background paper published by the Canadian Institute of Child Health in 1978 states that of approximately 330 000 infants born in Canada annually 25 000 will be of low birthweight and many will be at risk of handicap.1 In 1976 Wynn and Wynn2 Bacteroides fragilis cited studies from France, the United Kingdom and the United septicemia during States. In the French study 14.1% cefamandole therapy of the handicaps resulted from difficulties during delivery, includ- To the editor: Cephalosporins have ing asphyxia; 33.7% from prema- been used as alternatives to penicilturity, low birthweight, postmaturity lin in treating nonclostridial anand related socioeconomic prob- aerobic infections,"2 but they are lems; 2.1 % from isoimmunization; not recommended for the treatment 14.6% from obstetric complications of BaCteroides fragilis infections. I report two cases of B. fragilis and illnesses of the mother, including diabetes and virus infections septicemia that occurred after 4 such as rubella; and 35.0% from days of cefamandole therapy. B. fraanomalies of the fetus, including gilis was identified with anaerobic genetic and chromosomal anomalies API strips (Analytab Products, Plainview, New York). Sensitivity and defects in early development. Canadian studies have pointed to tests were performed by the KirbyM. OLUWAFEMI AGBAYEWA, MB, BS, the efforts needed to minimize han- Bauer method on blood agar inDIP PSYCH, MRC PSYCH dicaps of perinatal origin.3. The cubated anaerobically. Psychiatric Centre Weyburn, Sask. jurisdictions with the best organized Case reports perinatal care have the lowest inCase 1: A 44-year-old man unof perinatal death and, cidence References presumably, disability.6 Canadian derwent abdominoperineal resecdoctors can probably make the best tion for adenocarcinoma of the recI. cASSEM NH: Depression. In HACKETF TP, CASSEM NH (eds): MGH Handbook ci contribution by redoubling their tum. Therapy with cefamandole, St Mosby, General Hospital Psychiatry, Louis, 1978: 209-225 efforts to prevent disability. We 8 g/d, was begun preoperatively. On 422
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