ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Oct. 1975, p. 453-456 Copyright i 1975 American Society for Microbiology
Vol. 8, No. 4 Printed in U.S.A.
Vestibular Reactions Associated with Minocycline JAY A. JACOBSON* AND BRENDA DANIEL Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgia 30333,* and Doctors Hospital, Tucker, Georgia 30084 Received for publication 10 June 1975
Several recent reports have indicated that minocycline, a drug effective for meningococcal disease prophylaxis, is associated with a high incidence of vestibular side effects. In January 1975, a questionnaire on adverse reactions was completed by all 29 staff members of a North Georgia hospital who had taken minocycline at the recommended dosage after exposure to a suspected meningococcal meningitis case and by 25 age-, sex-, and occupation-matched nontreated controls. In the treated group 86% experienced moderate to severe vestibular symptoms; 84% of the symptomatic persons experienced their onset after one or two doses of 100 mg. Fifty-two per-cent of the treated staff members stopped taking the medication because of these effects. The symptoms resolved within 48 h after affected persons discontinued the medication. Until the safety of minocycline can be reestablished, rifampin is recommended for meningococcal disease prophylaxis, and alternative drugs are encouraged for other indications.
Because of the isolation of sulfonamide-resistant meningococci in 1963 (11) and their continued prevalence (10), many other drugs have been tested for efficacy in eliminating the meningococcal carrier state. Whereas two drugs, minocycline and rifampin, have been efficacious, neither has been a perfect substitute for sulfonamides. Rifampin, a relatively expensive product, has been associated with the emergence of resistant strains (5, 7), and minocycline, a semisynthetic derivative of tetracycline, can stain developing teeth if it is administered during pregnancy or early childhood (15). During the first several years of its use, the reported incidence of all side effects associated with minocycline varied; it was 0% in a study done in a military population in 1970 (4), 7% in a larger military study in 1971 (6), and 18% in a civilian population in Brazil in 1972 (12). In 1974, a study from Boston (16) indicated that 89% of all persons who had received minocycline at recommended dosages experienced adverse reactions, principally vertigo, nausea, and vomiting. A similar experience was documented in New Jersey in November 1974 (1). The disparity between these recent reports and the earlier ones suggested that some recent alteration in the product might have accounted for the increased incidence of vestibular symptoms. All minocycline is manufactured by one company, Lederle Laboratories, but it is also distributed in the United States by Parke-Davis and by the manufacturer's affiliates abroad.
The manufacturer (17) questioned the validity of the above-mentioned recent studies and declared that the drug tested in the Boston study (16) had shown no alterations in purity or stability. This study was undertaken to document the frequency and character of adverse reactions associated with minocycline. MATERIALS AND METHODS Between 9 and 14 January 1975, in Tucker, Georgia, minocycline, 100 mg twice a day for 5 days, was prescribed from the hospital pharmacy for 29 hospital employees who had been exposed to a suspected case of meningococcal meningitis. A nontreated control group of 26 persons was selected from hospital personnel and matched with the treated group for age, sex, and occupation. One individual for whom the drug was prescribed chose not to take any of the medication and was included as a control. Another person for whom minocycline was not originally prescribed secured the drug outside the hospital. Thus, the drugtreated group included 29 persons, and the control group contained 26 persons. A questionnaire about side effects was distributed to all members of the treated and nontreated groups. Subsequently, an investigator interviewed five persons who had experienced vestibular symptoms to characterize them and assess their severity. Investigators also telephoned or interviewed in person each of the 29 drug recipients to determine how long symptoms persisted after they stopped taking the drug.
453
RESULTS All persons queried completed the questionnaires. The mean age of the treated group was
454
ANTIMICROB. AGENTS CHEMOTHER.
JACOBSON AND DANIEL
29 years, and the control group's mean age was 34 years. The age, sex, and occupation of the treated and nontreated groups are shown in Table 1. The incidence of all symptoms (Table 2) in the treated group was 86% (25/29), compared with 15% (4/26) in the controls. Eighty-six percent (25/29) of the treated group experienced at least one vestibular symptom-defined as vertigo, nausea, vomiting, or ataxia-compared with 12% (3/26) of the controls. The incidence of vestibular symptoms was significantly different from that in the control group (P < 10-7). All of the symptomatic individuals experienced their onset after three or fewer 100-mg doses, and 56% (14/25) experienced onset after a single dose. The five persons interviewed, who had experienced vestibular symptoms, said that the reactions interfered with their daily activities but did not prevent them from working. Fiftytwo percent (15/29) of the treated group discontinued the drug because of intolerance. Ten percent (3/29) sought medical advice about their symptoms. In all cases the symptoms resolved within 48 h after minocycline was discontinued. The minocycline administered was distributed by Parke-Davis and Lederle Laboratories and came from several different lots.
TABLE 2. Adverse reactions in personnel who received minocycline and in nontreated controls in a Tucker,
Ga., hospital, January t975a No. (%)
Reaction
-Treated group
Symptomaticc Vestibular symptoms Nausea Vomiting Vertigo or dizziness Difficulty walking Change in hearing Diarrhea Rash Somnolence Other
25 (86) 25 (86) 19 (66) 3 (10) 22 (76) 6 (21) 2 (7) 1 (3) 0 (0) 4 (14) 6 (21)
Control group
P value,
4 (15) 3 (12)
Vol. 8, No. 4 Printed in U.S.A.
Vestibular Reactions Associated with Minocycline JAY A. JACOBSON* AND BRENDA DANIEL Bureau of Epidemiology, Center for Disease Control, Atlanta, Georgia 30333,* and Doctors Hospital, Tucker, Georgia 30084 Received for publication 10 June 1975
Several recent reports have indicated that minocycline, a drug effective for meningococcal disease prophylaxis, is associated with a high incidence of vestibular side effects. In January 1975, a questionnaire on adverse reactions was completed by all 29 staff members of a North Georgia hospital who had taken minocycline at the recommended dosage after exposure to a suspected meningococcal meningitis case and by 25 age-, sex-, and occupation-matched nontreated controls. In the treated group 86% experienced moderate to severe vestibular symptoms; 84% of the symptomatic persons experienced their onset after one or two doses of 100 mg. Fifty-two per-cent of the treated staff members stopped taking the medication because of these effects. The symptoms resolved within 48 h after affected persons discontinued the medication. Until the safety of minocycline can be reestablished, rifampin is recommended for meningococcal disease prophylaxis, and alternative drugs are encouraged for other indications.
Because of the isolation of sulfonamide-resistant meningococci in 1963 (11) and their continued prevalence (10), many other drugs have been tested for efficacy in eliminating the meningococcal carrier state. Whereas two drugs, minocycline and rifampin, have been efficacious, neither has been a perfect substitute for sulfonamides. Rifampin, a relatively expensive product, has been associated with the emergence of resistant strains (5, 7), and minocycline, a semisynthetic derivative of tetracycline, can stain developing teeth if it is administered during pregnancy or early childhood (15). During the first several years of its use, the reported incidence of all side effects associated with minocycline varied; it was 0% in a study done in a military population in 1970 (4), 7% in a larger military study in 1971 (6), and 18% in a civilian population in Brazil in 1972 (12). In 1974, a study from Boston (16) indicated that 89% of all persons who had received minocycline at recommended dosages experienced adverse reactions, principally vertigo, nausea, and vomiting. A similar experience was documented in New Jersey in November 1974 (1). The disparity between these recent reports and the earlier ones suggested that some recent alteration in the product might have accounted for the increased incidence of vestibular symptoms. All minocycline is manufactured by one company, Lederle Laboratories, but it is also distributed in the United States by Parke-Davis and by the manufacturer's affiliates abroad.
The manufacturer (17) questioned the validity of the above-mentioned recent studies and declared that the drug tested in the Boston study (16) had shown no alterations in purity or stability. This study was undertaken to document the frequency and character of adverse reactions associated with minocycline. MATERIALS AND METHODS Between 9 and 14 January 1975, in Tucker, Georgia, minocycline, 100 mg twice a day for 5 days, was prescribed from the hospital pharmacy for 29 hospital employees who had been exposed to a suspected case of meningococcal meningitis. A nontreated control group of 26 persons was selected from hospital personnel and matched with the treated group for age, sex, and occupation. One individual for whom the drug was prescribed chose not to take any of the medication and was included as a control. Another person for whom minocycline was not originally prescribed secured the drug outside the hospital. Thus, the drugtreated group included 29 persons, and the control group contained 26 persons. A questionnaire about side effects was distributed to all members of the treated and nontreated groups. Subsequently, an investigator interviewed five persons who had experienced vestibular symptoms to characterize them and assess their severity. Investigators also telephoned or interviewed in person each of the 29 drug recipients to determine how long symptoms persisted after they stopped taking the drug.
453
RESULTS All persons queried completed the questionnaires. The mean age of the treated group was
454
ANTIMICROB. AGENTS CHEMOTHER.
JACOBSON AND DANIEL
29 years, and the control group's mean age was 34 years. The age, sex, and occupation of the treated and nontreated groups are shown in Table 1. The incidence of all symptoms (Table 2) in the treated group was 86% (25/29), compared with 15% (4/26) in the controls. Eighty-six percent (25/29) of the treated group experienced at least one vestibular symptom-defined as vertigo, nausea, vomiting, or ataxia-compared with 12% (3/26) of the controls. The incidence of vestibular symptoms was significantly different from that in the control group (P < 10-7). All of the symptomatic individuals experienced their onset after three or fewer 100-mg doses, and 56% (14/25) experienced onset after a single dose. The five persons interviewed, who had experienced vestibular symptoms, said that the reactions interfered with their daily activities but did not prevent them from working. Fiftytwo percent (15/29) of the treated group discontinued the drug because of intolerance. Ten percent (3/29) sought medical advice about their symptoms. In all cases the symptoms resolved within 48 h after minocycline was discontinued. The minocycline administered was distributed by Parke-Davis and Lederle Laboratories and came from several different lots.
TABLE 2. Adverse reactions in personnel who received minocycline and in nontreated controls in a Tucker,
Ga., hospital, January t975a No. (%)
Reaction
-Treated group
Symptomaticc Vestibular symptoms Nausea Vomiting Vertigo or dizziness Difficulty walking Change in hearing Diarrhea Rash Somnolence Other
25 (86) 25 (86) 19 (66) 3 (10) 22 (76) 6 (21) 2 (7) 1 (3) 0 (0) 4 (14) 6 (21)
Control group
P value,
4 (15) 3 (12)
