Table 1 Drug Interaction Probability Scale (DIPS)
From: Probable tacrolimus toxicity from tibolone co-administration in a woman: a case report
DIPS Questions | Answer | Score | Comments |
|---|---|---|---|
   1. Are there previous credible reports of this interaction in humans? | N/A | 0 | No other case reports exist. |
   2. Is the observed interaction consistent with the known interactive properties of precipitant drug? | Yes/Unknown | 1/0 | Given the evidence of tibolone's interaction with warfarin, and the individual variation seen with that interaction, it is reasonable to suggest that in some individuals, there are known interactive properties of the precipitant drug. However, it could also be argued that there is not enough information regarding the mechanism of the interaction between tibolone and warfarin to make this inference. |
   3. Is the observed interaction consistent with the known interactive properties of the object drug? | Yes | 1 | Tacrolimus is certainly known to interact with inhibitors of the CYP450 system, of which tibolone is known to be one. |
   4. Is the event consistent with the known or reasonable time course of the interaction? | Yes | 1 | Tibolone was started 10 days prior to presentation. As our case report had been stable for some time on tacrolimus, there was no baseline blood test. However, the development of the symptoms consistent with acute tacrolimus toxicity occurred within a reasonable time course of the start of tibolone use. |
   5. Did the interaction remit upon dechallenge of the precipitant drug with no change in the object drug? | N/A | 0 | Tibolone was ceased immediately, but due to the effects of the tacrolimus toxicity (acute kidney injury in a transplant patient) the dose of tacrolimus was also altered. |
   6. Did the interaction reappear when the precipitant drug was readministered in the presence of continued use of the object drug? | N/A | 0 | She was reluctant to re-challenge with tibolone. |
   7. Are there reasonable alternative causes for the event? | No | 1 | As discussed above, alternative causes were looked for and none were found. |
   8. Was the object drug detected in the blood or other fluids in concentrations consistent with the proposed interaction? | Yes | 1 | See Figure 1 for tacrolimus concentrations. |
   9. Was the drug interaction confirmed by any objective evidence consistent with the effects on the object drug (other than drug concentrations)? | Yes | 1 | She was hyperglycemic and hypertensive, both known effects of tacrolimus toxicity. She also displayed a tremor, and had symptoms of anxiety. |
   10. Was the interaction greater when the precipitant drug dose was increased or less when the precipitant drug dose was decreased? | N/A | 0 | The tibolone was ceased at presentation and alternate doses were not used. |