THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 10, NO.1, 1997

Short Reports11

Drug interaction: Rifampicin andglibenclamide

SUREKHA Y., 1. Y. PETER, L. JEYASEELAN,A. M. CHERIAN

ABSTRACTBackground. Rifampicin is a potent inducer of the hepatic

microsomal enzyme system. However, the drug has beenshown to cause clinically important interactions with manydrugs. This study was designed to test the interaction ofrifampicin with the oral hypoglycaemic agent glibenclamide.

Methods. Twenty-nine well-controlled diabetic patients ona combination therapy of diet and glibenclamide, and willing toparticipate in the trial, received a daily dose of 450 mg (bodyweight <50 kg) or 600 mg (body-weight >50 kg) of rifampicin for10 days.

Results. There was a significant (p<o.ool) worsening offasting and post-prandial blood sugar after administration ofrifampicin. Dose modification of glibenclamide was required in15 of the 17 patients in whom the diabetes became uncon-trolled. Blood sugar nonnalized by day 6 after stopping rifampicinin all patients.

Conclusion. Rifampicin and glibenclamide interact. There-fore, necessary dose modifications should be made in order toachieve euglycaemia if these two drugs are given together.Natl Mad J India 1997;10:11-12

INTRODUCTIONThere are few studies on drug interaction in the literature. Thesubject is, however, important because (i) the use of several drugsis often essential to obtain a desired therapeutic objective or totreat co-existing diseases; (ii) the concurrent use of drugs caneither enhance or diminish the effect of one or both drugs or leadtoa new effect not seen with either; (iii) estimates of the incidenceof clinical drug interactions range from 3% to 5% in patientstaking a few drugs to 20% in patients taking 10 to 20 drugs. I

Rifampicin is a potent inducer of the hepatic microsomalenzyme system.' It has been shown to cause clinically importantinteractions when combined with other drugs including oralanticoagulants.v' oral contraceptives." glucocorticoids.' digoxin.tnifedipine,?verapamil, 10quinidine, IImethadone, 12barbiturates,"theophylline, 14.1'cyclosporine, 16ketoconazole'? and phenytoin. IIInteraction between oral hypoglycaemics and rifampicin has beenstudied in diabetics who present with tuberculosis. 19.20The pres-ence of tuberculosis itself, however, could have altered glucose

Christian Medical College and Hospital. Vellore 632004. Tamil Nadu,India

SUREKHA V .• 1. V. PETER. A. M. CHERIAN Department ofMedicine

L. JEY ASEELAN Department of Biostatistics

Correspondence to A. M. CHERIAN

Q The National Medical Journal of India 1997

metaboiism and may be a confounder. Zilly et at. 13found evidenceof an interaction between intravenous tolbutamide and rifampicinin healthy volunteers. We therefore designed this study to evalu-ate the interaction between gJibenclamide and rifampicin inotherwise healthy diabetic volunteers.

PATIENTS AND METHODSDiabetics presenting to the medical outpatient clinic of ourhospital were included in the study. Patients had to have adequatecontrol of diabetes (fasting plasma sugar <140 mg/dl and 2-hourpost-prandial plasma sugar <200 mg/dl) on a combination of dietand gJibenclamide. Patients were excluded if they were onbiguanides, if their blood sugar was poorly controlled or if theywere on other drugs known to be hepatic enzyme inhibitors orinducers. Those with a past history of allergy to rifampicin orraised serum liver enzyme levels were also excluded.

Twenty-nine patients who fulfilled the inclusion criteria andgave informed consent formed the study population. The inter-vention was the administration of rifampicin (450 mg once dailyfor patients <50 kg body weight and 600 mg once daily for those>50 kg) on an empty stomach for 10 days. This duration waschosen as the interaction of rifampicin with other drugs such asoral anticoagulants is said to occur between 5 and 8 days. I

Patients were advised not to change their dietary habits duringthe study period and also to report any adverse effects.

Blood sugar measurement was repeated after 10 days ofadministration of rifampicin and subsequently every third day andthe dose of gJibenclamide was adjusted to obtain euglycaemiclevels.

Statistical methodWilcoxon sign-rank test was used to analyse the change in bloodsugar between pre- and post-rifampicin administration and thechange in the dose of glibenclamide.

RESULTSThere were 13males (45%) and 16 females (55%). The mean ageof the study population was 50.4 years (26-71 years). A majorityof the patients (76%) were using 10 mg or less of glibenclamideper day for diabetic control.

The mean pre-intervention fasting blood sugar level was 114mg/dl and the mean post-prandial blood sugar was 170 mg/dl.There was a significant change (p<O.oo1)in the mean fasting (129mg/dl) and post-prandial blood sugar (209 mg/dl) on day 10(Table I). The blood sugar increased in 17out of29 (59%) patients(fasting blood sugar >140 mgldl; post-prandial sugar >200 mgldl). Dose modification of oral hypoglycaemic agents was requiredin 15 out of 17 patients to achieve euglycaemia. Dose modifica-tion was not required in 2 patients whose fasting blood sugarlevels were only mildly raised (145 mg/dl and 147 mg/dl). Bloodsugar levels returned to normal in 11 of these patients by day 13,and in the remaining by day 16 after starting rifampicin. The meandose changes of gJibenclamide are shown in Table II.

DISCUSSIONThere are few reports on drug interaction between oralhypoglycaemic agents and rifampicin.IJ.19.2oThese reportsI9.20were on patients who had co-existing diabetes and tuberculosis.

12

TABLEI. Changes in blood sugar levels after rifampicin therapy

Mean (SO) blood sugar (mgldl) p value *

Baseline (n=29)Fasting 114 (20)Post-prandial 170 (28)Day 10 (n=29)Fasting 129 (31) 0.001Post-prandial 209 (31) 0.001Day 13 (n=15Jt.Fasting 134 (34) nsPost-prandial 194 (46) nsDay 16 (n=4)+Fasting 127 (10) nsPost-prandial 199 (20) ns

• p values--<:omparison of blood sugar with baseline values ns not significantt Blood sugar estimations on the 15 patients who required dose modificarion+ Blood sugar estimations on the 4 patients who were not conrrolled on day 13

Our study was undertaken in otherwise healthy diabetic volun-teers.

We found that glibenclamide and rifampicin interact as evi-denced by a rise in the blood sugar levels in 17 of 29 patients(59%). To achieve euglycaemia a change in the dose schedule oforal hypoglycaemic agents was required in 15 of 17 patients. Byday 16 of the study, the blood sugar values showed a decline,indicating that enzyme induction had ended. There were noadverse effects.

We conclude that blood sugar levels should be carefullymonitored and the dose of oral hypoglycaemic agents adjusted inall diabetics who are put on rifampicin therapy.

ACKNOWLEDGEMENTThis study was funded by the 'Fluid research grant' of the ChristianMedical College and Hospital, Vellore, Tamil Nadu.

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THE NATIONAL MEDICAL JOURNAL OF INDIA VOL. 10, NO. I, 1997

TABLEII. Mean dose of gJibencIamide for 29 patients

Mean (SO) glibenc1amide dose (mg)

Pre-studyDay 10Day 13Day 16

8.1 (5.9)9.7 (6.3)*9.9 (6.3)t9.9 (6.3)

• Two patients also required metforrnin for controlt Three parients required metforrnin for control

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