Effect of rifampicin on anticoagulation of warfarin: A case report

Table 1 Summary of outpatient anticoagulation management by pharmacist

Date	Warfarin dosage in mg/d	INR,	Pharmacist intervention node	Pharmacist medication intervention	Warfarin dosage changes
		1.5-2.5
2019-05-19	3	0.97		Taking rifampicin, doxycycline and other drugs at the same time	None
2019-05-24	3	0.97		Taking rifampicin, doxycycline and other drugs at the same time	None
2019-05-30	3.75	0.97	(1)	Taking rifampicin, doxycycline and other drugs at the same time	Increased to 3.75 mg/d (+ 25%)
2019-06-10	3.75	0.97		Taking rifampicin, doxycycline and other drugs at the same time	None
2019-06-10	5	1.01	(2)	Taking rifampicin, doxycycline and other drugs at the same time. Considering there was no significant change in INR value when warfarin dosage was 3.75 mg/d, warfarin dosage increased and changed to imported warfarin	Increased to 5.00 mg/d (+ 33%)
2019-06-18	6	1.06	(2)	Taking rifampicin, doxycycline and other drugs at the same time. Considering there was no significant change in INR value when warfarin dosage was 5.00 mg/d, warfarin dosage increased and changed to imported warfarin	Increase to 6.00 mg/d (+ 20%)
2019-06-20	6.75	1.2	(3)	Taking rifampicin, doxycycline and other drugs at the same time. The INR value increased, and the warfarin dose continued to increase slightly	Increased to 6.75 mg/d (+ 12%)
2019-07-09	7.5	1.26	(4)	Taking rifampicin, doxycycline and other drugs at the same time. The INR value increased, and the warfarin dose continued to increase slightly	Increased to 7.50 mg/d (+ 11%)
2019-07-23	8.25	1.49	(4)	Taking rifampicin, doxycycline and other drugs at the same time. The INR value increased, and the warfarin dose continued to increase slightly	Increased to 8.25 mg/d (+ 10%)
2019-07-30	9.75	1.57		Taking rifampicin and doxycycline at the same time. The lower limit of the INR value guideline was reached, but the increase was limited, so continued to increase warfarin dosage significantly	Increased to 9.75 mg/d (+ 18%)
2019-08-12	10.5	1.63		Taking rifampicin and doxycycline at the same time. Reaching the INR value therapeutic range. Continued to increase slightly	Increased to 10.5 mg/d (+ 8%)
2019-08-19	10.5	1.6	(5)	Taking rifampicin and doxycycline at the same time	None
2019-08-22	8.25	1.58	(5)	Stopped taking rifampicin and doxycycline. There is no more rifampicin interaction. Taking into account that 10.5 mg/d was the highest dose we used and stopping rifampicin could have a great impact, we greatly reduced the warfarin dose	Reduced to 8.25 mg/d (-21%)
2019-08-24	7.5	1.65	(6)	Considering the long half-life of warfarin, we continued to reduce the warfarin dose	Reduced to 7.50 mg/d (-9%)
2019-09-03	6	1.9	(6)	7.50 mg/d is already a large dose for Asians. INR value was increased after the 9% dosage reduction. Continued to reduce the dosage	Reduced to 6.00 mg/d (-20%)
2019-09-10	6	1.78	(7)	In the therapeutic range. No change	None
2019-09-17	7.5	1.63	(7)	INR value decreased, so increased warfarin dose	Increased to 7.50 mg/d (+ 25%)
2019-09-25	8.25	1.72	(7)	Limited rise in INR, so increased warfarin dose	Increased to 8.25 mg/d (+ 10%)
2019-10-22	8.25	2.64	(8)	Occasionally higher INR value observed	None
2019-11-22	8.25	2.68	(8)	INR was still high. Occasional bleeding gums	None
2019-12-09	7.5	2.38	(9)	INR was in the range of 1.5-2.5	Reduced to 7.50 mg/d (-9%)
2020-02-14	7.5	1.78	(10)	INR was in the range of 1.5-2.5	None
2019-03-09	7.5	1.98		INR was in the range of 1.5-2.5	None

(1)-(10): Pharmacist intervention notes. INR: International normalized ratio.

Table 2 Summary of studies reporting interaction of rifampin and warfarin

Ref.	Country	Race	Age in yr	Sex	Therapeutic INR range	Disease	Warfarin dose range in mg/d	Warfarin dose adjustment
Romankiewicz et al[8], 1975	United States	Black	48	Male	Prothrombin time	Tuberculosis, pulmonary embolism	7.5-20	Starting dose of 7.5 mg/d, increased to 20 mg/d within 8 d, and warfarin dose decreased by 50% 7 d after rifampicin was discontinued
Self et al[25], 1975	United States	Unknown	72	Male	Prothrombin time	Pulmonary tuberculosis, pulmonary embolism	5-20	Initially 5 mg/d, increased to 20 mg/d, decreased to 15 mg/d after 8 d of rifampicin discontinuation, and gradually decreased to 10 mg/d
Almog et al[26], 1988	Israel	White	30	Female	Prothrombin time	Chronic obstructive lung disease, pulmonary tuberculosis, deep vein thrombosis, pulmonary embolism	8.7-15.3	Average 15.3 mg/d to attain therapeutic INR and decreased by 50% to average 8.7 mg/d after rifampicin discontinued
Casner et al[27], 1996	United States	Black	36	Male	2.0-3.0	Staphylococcus aureus infection, pulmonary embolism	5-20	10 mg/d, increased to 20 mg/d in 20 d, decreased to 5 mg/d immediately after rifampin is stopped
Lee et al[22], 2001	United States	Unknown	58	Female	2.0-3.0	Pulmonary tuberculosis, left ventricular dysfunction	5-25	Starting at 5 mg/d, increased by 233% over 4 mo and unable to attain therapeutic INR during rifampicin combination. A gradual 70% reduction in warfarin dose over 4-5 wk after rifampicin discontinued
Baciewicz et al[9], 2013	United States	Unknown	79	Male	2.0-3.0	Deep vein thrombosis, pulmonary embolism, osteomyelitis	5-25	Taking long-term warfarin at 5 mg/d, the dose increased by 10%-25% weekly to 25 mg/d after combined use. The dose was reduced by 70% within 4-5 wk to 5 mg/d after rifampicin discontinued
Unal et al[28], 2007	Turkey	Unknown	16	Female	2.0-3.0	Drug abuse	—	Acute event, not comparable
Krajewski et al[18], 2010	United States	White	71	Male	2.0-3.0	Deep vein thrombosis, prosthetic knee infection due to methicillin-resistant Staphylococcus aureus	5-25	Starting at 5 mg/d, increased to 25 mg/d in 2 mo, and the 5-fold increase did not reach the therapeutic INR. After stopping rifampicin, it was reduced by 30% to 17.5 mg/d, and after 3 d it was reduced by 20% to 12.5 mg/d, reduced to 10 mg/d after 1 wk, then gradually reduced to 5-5.5 mg/d in the next 2-3 mo
Martins et al[19], 2013	Brazil	Non-white	59	Female	2.0-3.0	Atrial fibrillation, pleural TB	5.3-11	Long-term use of 7.5 mg/d, increased to 11 mg/d within 3 mo after combined use, hematuria occurred after rifampicin was discontinued, the drug was stopped twice, the dose decreased by 33% to 7.5 mg/d, and then adjusted to 5.3 mg/d
Fahmi et al[20], 2016	Sri Lanka	White	34	Female	2.5-3.5	Mitral valve replacement, infective endocarditis	7.5-30	7.5 mg/d, conservatively increased to 15 mg/d in 1 mo, 22 mg/d in 2 wk, and then increased to 30 mg/d. Continuous monitoring of INR value after antibiotics discontinued without dose adjustment. At 11 d of discontinuation, the INR value increased to 10.2, then dose reduced to 7.5 mg/d
Raru et al[29], 2019	United States	White	67	Male	2.0-3.0	Pulmonary vein thrombosis, tuberculosis	-	10 mg/d

INR: International normalized ratio; TB: Tuberculosis.