Scot. med. J., 1975, 20: 55
RIFAMPICIN OVERDOSAGE-'THE RED MAN SYNDROME' R. W. Newton and A. R. W. Forrest Regional Poisoning Treatment Centre, Royal Infirmary, Edinburgh
Summary. A patient is described who was admitted to hospital 5 hours after a
massive overdose of rifampicin. The unusual clinical features and the lack of severe hepatotoxicity following self-poisoning by this drug do not seem to have been reported previously.
Rifamycins are complex macrocyclic antibiotics produced by Streptomyces T mediterranei and were first isolated in 1959 HE
(Goodman & Gillman, 1973). Rifampicin is a semi-synthetic derivative widely used in Britain in the chemotherapy of tuberculosis. Toxic reactions to rifampicin are not common although allergic reactions, gastrointestinal effects (Bergmani et al., 1970) an influenza-like syndrome, thrombocytopenia and rarely blood dyscrasias have been reported (Blajchman et al., 1970). A substantial proportion of patients on the drug develop abnormal liver function tests (Lal et al., 1972) and the clinical picture together with liver biopsy appearances of 'rifampicin hepatitis' have recently been described (Scheuer et al., 1974). Rifampicin and its metabolites are highly coloured and in therapeutic doses may cause transient orange discolouration of skin and mucous membranes and reddish urine (Bergmani et al., 1970).
metabolites (measured by microbiological assay) in plasma and urine during the 3 day period after ingestion are shown in Tables I and II. Serial blood counts, electrocardiograms and estimations of plasma glucose, urea, electrolytes, serum amylase and prothrombin time were within normal limits on 4 consecutive days. However the plasma bilirubin, alkaline phosphatase and SGOT rose to 3.7 mg. per 100 ml., 24 K.A. units per 1. and 61 i.u, per 1. respectively 48 hours after ingestion (Table III) but these values returned to normal over the next 2 days. The patient remained symptomatically well and the red pigmentation of his skin, the orange discolouration of his sweat and the deep red colour of his plasma and urine gradually faded. He was discharged 4 days after admission and continued to take rifampicin in therapeutic doses.
Discussion
Overdosage of rifampicin is an unusual form of self-poisoning. The striking red colour of the skin and the urine is expected since the urine is often red in patients taking therapeutic doses (Bergmani et al., 1970). A single oral dose of 450 mg. of rifampicin produces plasma concentrations of 6 to 9 ug. per ml. at 2 to 4 hours with a half-life of l!- to 5 hours (Reiss, 1972). The concentration at 12 hours of 400 ug. per ml. in our patient is consistent Case report with absorption of at least the stated dose. The patient was a 55-year-old labourer who had Despite the very high plasma levels, there taken drugs in overdosage on 2 previous occasions. He was subject to fits of depression when he drank was biochemical evidence of only mild liver heavily. For the previous year up until the time of damage and it is possible moreover that the admission he was receiving rifampicin, ethambutol bright red colour of the plasma may have and isoniazid for pulmonary tuberculosis. Five hours prior to admission at 03.00 hr. on ~.1.74. ~ claimed caused falsely high estimations of the bilirubin to have ingested about 40 300 mg. rifampicin tablets. levels. One hour after taking the drug he felt flushed, The striking generalised vivid red colour of sweated profusely and vomited on 4 occasions bringing up orange liquid and red tablet material. the skin in this patient initially caused some On admission he was fully conscious but presented an alarming picture with bright red skin resembling concern to the supporting medical staff. However despite his remarkable presentation the colour of a boiled lobster. The pulse was regular at 100 per min. and the blood pressure was 160/110 recovery was uneventful. mm, Hg but physical examination was otherwise
normal. The stomach was washed out using a 30 English gauge Jacques tube and 20 litres of warm water. The return was initially bright orange in colour. The concentrations of rifampicin and its active
A C K NOW LED GEM E N T s. We are grateful for the advice and encouragement of Dr L. F. Prescott in preparation of this report. We are indebted to Dr A. T. Wallace of the Bacteriology Laboratory, City Hospital, Edinburgh, for technical assistance.
Downloaded from scm.sagepub.com at UNIVERSITY OF WINDSOR on October 5, 2015
Newton and Forrest
Table I. Plasma rifampicin concentrations (microbiological assay) on consecutive days after admission.
Table II. Urinary rifampicin concentrations.
Date
Time
Cone. ug./mI.
Date
Time
6.1.74 7.1.74 8.1.74
11.10
08.10 07.30
400 64 0.1
7.1.74
06.30 12.00 16.00 23.00 04.30 17.30 06.00
8.1.74
REFERENCES
Bergmani, N., Bachini, V., Ferrario, A., Innocenti, G., Fowst, G. (1970). Rifampicin-s-a clinical survey. Arzneimmittel-Forseh, 20, 1546 Blajchman, M. A., Lowry, R. C., Pettit, J. E., Stradling, P. (1970). Rifampicin induced immune thrombocytopenia. British Medical Journal, 3, 24 Goodman L. S., Gillman, A. The Pharmacological basis of Therapeutics, 4th Edition, p, 1333, New York: The MacMillan Coy. Lal, S., Singhal, S. N., Burley, D. M., Crossley G. (1972). Effect of rifampicin and isoniazid on liver function. British Medical Journal, I, 148 Reiss, W. (1972). Symposium on Rimactane CIBA 36 Scheuer, P .•r; Summerfield, J. A., Lal, S., Sherlock, S. (1974). Rifampicin hepatitis. Lancet, 1, 421
9.1.74
Cone. ug./ml. 313 625 78.1 78.1 6.3 0.4 0.1
Table m. Serial liver function tests following rifampicin overdosage.
Date 6.1.74 7.1.74 8.1.74 9.1.74
Plasma Alkaline SGPT bilirubin phosphatase (mg./l00) (K.A. units/l.) (i.u.jl.) 2.4 3.7 0.7 0.5
S6 Downloaded from scm.sagepub.com at UNIVERSITY OF WINDSOR on October 5, 2015
21 24 20 18
9 14 37 34
SGOT (i.u.jl.) 14 61 51 33
RIFAMPICIN OVERDOSAGE-'THE RED MAN SYNDROME' R. W. Newton and A. R. W. Forrest Regional Poisoning Treatment Centre, Royal Infirmary, Edinburgh
Summary. A patient is described who was admitted to hospital 5 hours after a
massive overdose of rifampicin. The unusual clinical features and the lack of severe hepatotoxicity following self-poisoning by this drug do not seem to have been reported previously.
Rifamycins are complex macrocyclic antibiotics produced by Streptomyces T mediterranei and were first isolated in 1959 HE
(Goodman & Gillman, 1973). Rifampicin is a semi-synthetic derivative widely used in Britain in the chemotherapy of tuberculosis. Toxic reactions to rifampicin are not common although allergic reactions, gastrointestinal effects (Bergmani et al., 1970) an influenza-like syndrome, thrombocytopenia and rarely blood dyscrasias have been reported (Blajchman et al., 1970). A substantial proportion of patients on the drug develop abnormal liver function tests (Lal et al., 1972) and the clinical picture together with liver biopsy appearances of 'rifampicin hepatitis' have recently been described (Scheuer et al., 1974). Rifampicin and its metabolites are highly coloured and in therapeutic doses may cause transient orange discolouration of skin and mucous membranes and reddish urine (Bergmani et al., 1970).
metabolites (measured by microbiological assay) in plasma and urine during the 3 day period after ingestion are shown in Tables I and II. Serial blood counts, electrocardiograms and estimations of plasma glucose, urea, electrolytes, serum amylase and prothrombin time were within normal limits on 4 consecutive days. However the plasma bilirubin, alkaline phosphatase and SGOT rose to 3.7 mg. per 100 ml., 24 K.A. units per 1. and 61 i.u, per 1. respectively 48 hours after ingestion (Table III) but these values returned to normal over the next 2 days. The patient remained symptomatically well and the red pigmentation of his skin, the orange discolouration of his sweat and the deep red colour of his plasma and urine gradually faded. He was discharged 4 days after admission and continued to take rifampicin in therapeutic doses.
Discussion
Overdosage of rifampicin is an unusual form of self-poisoning. The striking red colour of the skin and the urine is expected since the urine is often red in patients taking therapeutic doses (Bergmani et al., 1970). A single oral dose of 450 mg. of rifampicin produces plasma concentrations of 6 to 9 ug. per ml. at 2 to 4 hours with a half-life of l!- to 5 hours (Reiss, 1972). The concentration at 12 hours of 400 ug. per ml. in our patient is consistent Case report with absorption of at least the stated dose. The patient was a 55-year-old labourer who had Despite the very high plasma levels, there taken drugs in overdosage on 2 previous occasions. He was subject to fits of depression when he drank was biochemical evidence of only mild liver heavily. For the previous year up until the time of damage and it is possible moreover that the admission he was receiving rifampicin, ethambutol bright red colour of the plasma may have and isoniazid for pulmonary tuberculosis. Five hours prior to admission at 03.00 hr. on ~.1.74. ~ claimed caused falsely high estimations of the bilirubin to have ingested about 40 300 mg. rifampicin tablets. levels. One hour after taking the drug he felt flushed, The striking generalised vivid red colour of sweated profusely and vomited on 4 occasions bringing up orange liquid and red tablet material. the skin in this patient initially caused some On admission he was fully conscious but presented an alarming picture with bright red skin resembling concern to the supporting medical staff. However despite his remarkable presentation the colour of a boiled lobster. The pulse was regular at 100 per min. and the blood pressure was 160/110 recovery was uneventful. mm, Hg but physical examination was otherwise
normal. The stomach was washed out using a 30 English gauge Jacques tube and 20 litres of warm water. The return was initially bright orange in colour. The concentrations of rifampicin and its active
A C K NOW LED GEM E N T s. We are grateful for the advice and encouragement of Dr L. F. Prescott in preparation of this report. We are indebted to Dr A. T. Wallace of the Bacteriology Laboratory, City Hospital, Edinburgh, for technical assistance.
Downloaded from scm.sagepub.com at UNIVERSITY OF WINDSOR on October 5, 2015
Newton and Forrest
Table I. Plasma rifampicin concentrations (microbiological assay) on consecutive days after admission.
Table II. Urinary rifampicin concentrations.
Date
Time
Cone. ug./mI.
Date
Time
6.1.74 7.1.74 8.1.74
11.10
08.10 07.30
400 64 0.1
7.1.74
06.30 12.00 16.00 23.00 04.30 17.30 06.00
8.1.74
REFERENCES
Bergmani, N., Bachini, V., Ferrario, A., Innocenti, G., Fowst, G. (1970). Rifampicin-s-a clinical survey. Arzneimmittel-Forseh, 20, 1546 Blajchman, M. A., Lowry, R. C., Pettit, J. E., Stradling, P. (1970). Rifampicin induced immune thrombocytopenia. British Medical Journal, 3, 24 Goodman L. S., Gillman, A. The Pharmacological basis of Therapeutics, 4th Edition, p, 1333, New York: The MacMillan Coy. Lal, S., Singhal, S. N., Burley, D. M., Crossley G. (1972). Effect of rifampicin and isoniazid on liver function. British Medical Journal, I, 148 Reiss, W. (1972). Symposium on Rimactane CIBA 36 Scheuer, P .•r; Summerfield, J. A., Lal, S., Sherlock, S. (1974). Rifampicin hepatitis. Lancet, 1, 421
9.1.74
Cone. ug./ml. 313 625 78.1 78.1 6.3 0.4 0.1
Table m. Serial liver function tests following rifampicin overdosage.
Date 6.1.74 7.1.74 8.1.74 9.1.74
Plasma Alkaline SGPT bilirubin phosphatase (mg./l00) (K.A. units/l.) (i.u.jl.) 2.4 3.7 0.7 0.5
S6 Downloaded from scm.sagepub.com at UNIVERSITY OF WINDSOR on October 5, 2015
21 24 20 18
9 14 37 34
SGOT (i.u.jl.) 14 61 51 33
