Demographics of the study population

Among anticancer agents that cause pDDIs, alkylating agent + corticosteroids [32 (21.05%)] were found to be the most common interacting group in cancer patients followed by corticosteroids + mitotic inhibitors [31 (20.3%)], alkylating + mitotic inhibitors [26 (17.1%)] and the other interacting groups are summarized in [Table 2]. Similarly, in supportive care agents, corticosteroids + aprepitant [34 (22.3%)] were found to be the common interacting pair in cancer patients followed by histamine H2 antagonist + analgesics, 19 (12.5%), and the other interacting groups are described in [Table 3].

Frequency of potential drug-drug interactions involving anticancer drugs (n=152)

Frequency of potential drug-drug interactions involving supportive care drugs («=152)_

Out of 152 patients, 659 pDDIs were observed in the study. The most common interacting drug pair in the study population was found to be dexamethasone + aprepitant [41 (26.9%)] followed by cisplatin + dexamethasone [32 (21.05%)] the other interacting pairs are summarized in [Table 4] and [5]. QT interval prolongation [62 (40.1%)] was found to be the most common pDDI outcome in cancer patients.

Interacting pair of anticancer drugs with outcome and severity (n=152)

Interacting pair of supportive care drugs with outcome and severity (n=152)

According to the severity of drug interactions, 416 (63.1%) of pDDIs were moderate followed by major [172 (26.1%)] and minor [67 (10.1%)]. Among the 659 interactions, 563 (85.4%) of pDDIs did not specify their onset [23 (3.4%)] were delayed onset, and 73 (11%) were rapid onset. The documentation levels of significance of pDDIs were fair [556 (84.3%)] followed by good [66 (10%)] and rapid [37 (5.6%)].

Discussion

Drug–drug interactions (DDIs) occur when one drug increases or decreases the efficacy of another drug, when both are administered together. When the interaction causes an increase in the effect of one or both of the drugs, that interaction is called synergistic effect. The opposite effect to synergetic effect is termed antagonism.[8]

The current study analyzed the pattern of pDDIs and their assessment among cancer patients. In this study, it was noticed that male (64.4%) patients constituted a major proportion of the study population than females (35.6%). Similar result was shown in the study conducted by Leeuwen et al.[9] where it was reported that males (55%) were higher than females (45%). However, contradictory results were shown in the study conducted by Ussai et al.,[10] in which female (69%) patients constituted the major proportion of the study population than male patients (31%).

Majority of the pDDIs were seen in patients in the age group of 50–59 years (33.5%) in our study. The study conducted by Riechelmann et al.[11] showed the similar results, where the drug interactions were common in the age group of 58 years. Our study results are in contrast to the study conducted by Ko et al.,[12] in which the maximum number of drug interactions in the age group was >65 years. This may be because organ dysfunction and comorbid conditions are more likely to be associated with older age. This further increases their risk for developing pDDIs.

In the present study, the most common tumor was found to be breast cancer (14.4%). A comparable result was shown in the study conducted by van Leeuwen et al.,[13] where it was found to be 17.2%. However, Mouzon et al.[14] concluded that higher incidence was observed with gastrointestinal cancer (27.9%). These findings were contradictory to the current study results.

The median number of medications received per patient in the present study was found to be 8 (range 1–21). A comparable result of median value of 9 in the range of 2–22 drugs was observed in the study conducted by van Leeuwen et al.[13] However, comparatively lesser median value of 5 was reported by Riechelmann et al.,[11] making it not comparable with the present study results.

In this study, the most frequently prescribed anticancer agents were cisplatin (14.5%) and docetaxel (1.9%). The study results were comparable to the conducted by Mouzon et al.,[14] where it was found to be cisplatin (22.1%) and docetaxel (13%).

In the current study, cisplatin [49 (32.2%)] was the most frequently drug involved in pDDIs. A comparable result was found in the study conducted by Mouzon et al.,[14] where it was found that cisplatin (22.1%) was the most frequently involved anticancer drug in pDDIs.

Another important finding in the study was the incidence of pDDIs that may result in adverse events which include QT interval prolongation (40.1%) and GI toxicity (9.2%). A comparable result was found in the study conducted by Leeuwen et al.,[9] where it was found to be QT interval prolongation (16.1%) and GI toxicity (11.2%).

In the present study, pain related to the cancer was treated with nonsteroidal anti-inflammatory drugs and opioids. These findings were consistent with the study conducted by Espinosa et al.[15] and van Leeuwen et al.[13]

The incidence of pDDIs in our hospital during the study period was 84.4%. Contradictory results were shown in the study conducted by Riechelmann et al.,[11] where it was reported to be 31.34%. This is due to that the patients involved in the study had more comorbidities; therefore, a large number of drugs were administered.

According to the severity of pDDIs, the study showed that 63.1% were moderate followed by major (26.1%) and minor interactions (10.1%). These findings were comparable to the study conducted by Leeuwen et al.,[9] where it was reported that most of the interactions were major (33%) followed by moderate (60.3%) and minor (6%).

Conclusion

The present study shows that cancer patients are at a high risk of pDDIs. The incidence of pDDIs among cancer patients was 84.44%. The most common interacting drug pair in the study population was found to be dexamethasone + aprepitant [41 (26.9%)] followed by cisplatin + dexamethasone [32 (21.05)] and other interacting pairs. According to the severity of classification of pDDIs, majority of them were moderate (63.1%) followed by major (26.1%) and minor (10.1%) interactions. QT interval prolongation (40.1%) and irregular heartbeat (24.3%) were the most common outcomes of the pDDIs in cancer patients. To avoid harmful effects, screening of pDDIs should take place before administering the therapy. The physician and pharmacist must collaborate for the early detection and prevention of DDIs and their related harmful effects. Screening of pDDIs should take place before starting the therapy to avoid potential drug interactions. Clinical pharmacist in health-care team has a certain role in detecting interactions and making recommendations, to reduce medication-related problem and effective drug therapy to improve the quality of life in these patients.

Conflict of Interest

There are no conflicts of interest.

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Publication History

Article published online:
17 June 2021

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