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Travel Medicine and Infectious Disease (2014) xx, 1e6
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
Potential drug interactions in travelers with chronic illnesses: A large retrospective cohort study* Q7
Shmuel Stienlauf a,b,c,*, Eyal Meltzer a,b,c, Daniel Kurnik b,c, Eyal Leshem a,b,c, Eran Kopel a,b, Bianca Streltsin c,d, Eli Schwartz a,b,c a
Q2
The Center of Geographic Medicine, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel Department of Internal Medicine, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel c The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel d The Arrow Project, The Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel b
Received 28 February 2014; received in revised form 9 April 2014; accepted 24 April 2014
KEYWORDS
Q4
Travelers; Chronic disease; Chronic use of prescription drugs; Israel; Developing countries; Drug interactions; Retrospective cohort study
Summary Background: Data regarding the prevalence of potential interactions between travel-related medications (TRM) and chronic medications in use, or medical conditions of travelers to developing countries are limited. Methods: A retrospective cohort study of travelers to low income countries. We extracted data on demographics, travel destinations, use of chronic medications, drug allergies, and relevant medical conditions. The following TRM were evaluated: mefloquine, primaquine, doxycycline, atovaquone/proguanil, fluoroquinolone antibiotics, rifaximin, azithromycin, and acetazolamide. Results: A total of 16,263 travelers were included in the analysis, of whom 3299(20%) suffered from chronic illnesses and 2316(14%) reported chronic medication use. A potential drugedrug interaction with TRM was identified in 1047(45%) of travelers using chronic medication. Fluoroquinolones and azithromycin were the most commonly implicated TRMs. A potential medical condition interaction with TRM was identified in 717(22%) of travelers having chronic illnesses. acetazolamide, primaquine and mefloquine, were the most commonly TRMs implicated.
* Parts of the work were presented at the: (a.) Annual Meeting of the Israel Society for Parasitology, Protozoology and Tropical Diseases, Ramat Gan, Israel, December 12, 2012. (b.) 13th Conference of the International Society of Travel Medicine, May 19e23, 2013, Maastricht, The Netherlands. Q3 * Corresponding author. The Department of Internal Medicine “C”, Sheba Medical Center, Tel Hashomer 52621, Israel. Tel.: þ972 52 6666131; fax: þ972 3 5535953. E-mail addresses: [email protected], [email protected] (S. Stienlauf), [email protected] (E. Meltzer), d_ [email protected] (D. Kurnik), [email protected] (E. Leshem), [email protected] (E. Kopel), [email protected] (B. Streltsin), [email protected] (E. Schwartz).
http://dx.doi.org/10.1016/j.tmaid.2014.04.008 1477-8939/ª 2014 Published by Elsevier Ltd.
Please cite this article in press as: Stienlauf S, et al., Potential drug interactions in travelers with chronic illnesses: A large retrospective cohort study, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.04.008
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S. Stienlauf et al. Drug allergies, which can pose a relative contraindication for use of acetazolamide, were reported by 1323(8.1%) of all travelers. Conclusions: Potential drugedrug and drug-disease interactions involving TRM might occur in a significant proportion of travelers with chronic medical conditions. Education of health practitioners regarding such potential drug interactions and caution when in prescribing travelrelated medications is warranted. ª 2014 Published by Elsevier Ltd.
Q5
Introduction Travelers to developing countries who consult a travel clinic prior to their departure are commonly prescribed travel related medications (TRM) for malaria prophylaxis, standby therapy for traveler’s diarrhea, or for prevention/ treatment of high altitude sickness. Between 11 and 59% of travelers to developing countries, who consulted a pretravel clinic, report having at least 1 chronic medical condition, most of whom were regularly taking prescription medications [1e4]. There are potential drugedrug interactions between TRM and many other medications, and caution is advised for their concomitant use [5]. Furthermore, medical conditions and drug allergies may pose a risk for the use of several travel related medications [6,7]. Data regarding the prevalence of possible interactions between travel-related medications and chronic medical conditions and medications used by travelers to developing countries are lacking. Our objective was to assess the prevalence and types of potential drugedrug and drugedisease interactions among a cohort of travelers to developing countries attending our pre-travel clinic.
Materials and methods We performed a cohort study based on the medical records of all travelers attending the pre-travel clinic at the Chaim Sheba Medical Center between January 1st, 2005 and December 31st, 2007. Travelers to developed countries [8] or those with missing data about travel destination were excluded. The study was approved by the Sheba Medical Center Institutional Review Board. The Sheba Medical Center pre-travel clinic provides medical advice to approximately 6000e7000 travelers annually. At the clinic visit, every traveler completes a structured questionnaire. The data collected includes age and gender, travel destinations, planned duration of travel, expected date of travel, and purpose of travel. Travelers are asked to select one of the following purposes for their trip: leisure/tourism, business, governmental/nongovernmental organization worker, research/education, returning to region of origin of self or family to visit friends and relatives (VFR). Travelers are also asked to record chronic medical conditions, chronic use of medication, and drug allergies. All data are stored in a computerized database using Microsoft Access 2010 (Microsoft, Redmond, WA, USA), which served as the source for the present study. Chronic use of medications was based on self-reporting. We analyzed separately, travelers who used medications
for chronic medical conditions, and healthy women who used oral contraceptives. Drug interactions with travel related medications: We defined the following medications as travel related medications (TRM): Drugs used for malaria prophylaxis (mefloquine, primaquine, doxycycline and atovaquone/proguanil [Malaroneª]), medications prescribed as stand-by therapy for traveler’s diarrhea (fluoroquinolone antibiotics [ciprofloxacin, ofloxacin], rifaximin and azithromycin), and the carbonic anhydrase inhibitor acetazolamide, used for the prophylaxis and therapy of high altitude sickness. We used Micromedex Healthcare Series database [5] to extract all medications considered to have interactions with TRM, including the effect of each interaction, its severity (mild, moderate, major, Contraindicated), and the quality of documentation in the medical literature (Excellent: Controlled studies have clearly established the existence of the interaction; Good: Documentation strongly suggests the interaction exists, but well-controlled studies are lacking; Fair: Available documentation is poor, but pharmacologic considerations lead clinicians to suspect the interaction exists; or, documentation is good for a pharmacologically similar drug). The Micromedex database classifies the severity of the drugedrug interaction as follows [5]: Contraindicated: The drugs are contraindicated for concurrent use; Major e The interaction may be life-threatening and/or require medical intervention to minimize or prevent serious adverse effects; Moderate e The interaction may result in exacerbation of the patient’s condition and/or require an alteration in therapy; Minor e The interaction would have limited clinical effects, e.g. increase the frequency or severity of the side effects, but generally would not require a major alteration in therapy. Chronic illness and TRM interactions: We used Micromedex Healthcare Series database [5] to extract all medical conditions considered to have interactions with TRM and its severity (Precaution needed, Contraindicated). Statistical analysis: Continuous data were described as mean standard deviation, or median with interquartile range (IQR). Proportions and 95% confidence intervals were calculated for categorical variables using the Wilson method [9]. Funding: No funding source was provided for the design conduct and reporting of the study.
Results During the study period, 16,263 travelers to developing countries sought pre-travel advice and were included in the
Please cite this article in press as: Stienlauf S, et al., Potential drug interactions in travelers with chronic illnesses: A large retrospective cohort study, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.04.008
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MODEL
A large retrospective cohort study in travelers with chronic illnesses Table 1
Demographics and travel destinations.
Parameter
All travelers
Travelers on chronic medications
Travelers not using chronic medications
Number, n (%) Females, n (%) Age Mean (SD) Median (IQR) Destination: Asia Latin America Sub-Saharan Africa
16,263 7859 (48)
2316 (14) 1168 (50)
13,947 (86) 6691 (48)
32.2 14.5 26 (22e40) 10,620 (65)
47.6 17 53 (29e53) 1467 (63)
29.7 12.3 25 (22e32) 9153 (66)
4023 (25) 1896 (12)
533 (23) 393 (17)
3490 (25) 1503 (11)
study. Demographics and travel destinations are reported in Table 1. Oral contraceptive usage was reported by 817 (14% of female travelers
TMAID736_proof ■ 8 May 2014 ■ 1/6
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MODEL
Travel Medicine and Infectious Disease (2014) xx, 1e6
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
Potential drug interactions in travelers with chronic illnesses: A large retrospective cohort study* Q7
Shmuel Stienlauf a,b,c,*, Eyal Meltzer a,b,c, Daniel Kurnik b,c, Eyal Leshem a,b,c, Eran Kopel a,b, Bianca Streltsin c,d, Eli Schwartz a,b,c a
Q2
The Center of Geographic Medicine, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel Department of Internal Medicine, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel c The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel d The Arrow Project, The Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel b
Received 28 February 2014; received in revised form 9 April 2014; accepted 24 April 2014
KEYWORDS
Q4
Travelers; Chronic disease; Chronic use of prescription drugs; Israel; Developing countries; Drug interactions; Retrospective cohort study
Summary Background: Data regarding the prevalence of potential interactions between travel-related medications (TRM) and chronic medications in use, or medical conditions of travelers to developing countries are limited. Methods: A retrospective cohort study of travelers to low income countries. We extracted data on demographics, travel destinations, use of chronic medications, drug allergies, and relevant medical conditions. The following TRM were evaluated: mefloquine, primaquine, doxycycline, atovaquone/proguanil, fluoroquinolone antibiotics, rifaximin, azithromycin, and acetazolamide. Results: A total of 16,263 travelers were included in the analysis, of whom 3299(20%) suffered from chronic illnesses and 2316(14%) reported chronic medication use. A potential drugedrug interaction with TRM was identified in 1047(45%) of travelers using chronic medication. Fluoroquinolones and azithromycin were the most commonly implicated TRMs. A potential medical condition interaction with TRM was identified in 717(22%) of travelers having chronic illnesses. acetazolamide, primaquine and mefloquine, were the most commonly TRMs implicated.
* Parts of the work were presented at the: (a.) Annual Meeting of the Israel Society for Parasitology, Protozoology and Tropical Diseases, Ramat Gan, Israel, December 12, 2012. (b.) 13th Conference of the International Society of Travel Medicine, May 19e23, 2013, Maastricht, The Netherlands. Q3 * Corresponding author. The Department of Internal Medicine “C”, Sheba Medical Center, Tel Hashomer 52621, Israel. Tel.: þ972 52 6666131; fax: þ972 3 5535953. E-mail addresses: [email protected], [email protected] (S. Stienlauf), [email protected] (E. Meltzer), d_ [email protected] (D. Kurnik), [email protected] (E. Leshem), [email protected] (E. Kopel), [email protected] (B. Streltsin), [email protected] (E. Schwartz).
http://dx.doi.org/10.1016/j.tmaid.2014.04.008 1477-8939/ª 2014 Published by Elsevier Ltd.
Please cite this article in press as: Stienlauf S, et al., Potential drug interactions in travelers with chronic illnesses: A large retrospective cohort study, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.04.008
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122
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S. Stienlauf et al. Drug allergies, which can pose a relative contraindication for use of acetazolamide, were reported by 1323(8.1%) of all travelers. Conclusions: Potential drugedrug and drug-disease interactions involving TRM might occur in a significant proportion of travelers with chronic medical conditions. Education of health practitioners regarding such potential drug interactions and caution when in prescribing travelrelated medications is warranted. ª 2014 Published by Elsevier Ltd.
Q5
Introduction Travelers to developing countries who consult a travel clinic prior to their departure are commonly prescribed travel related medications (TRM) for malaria prophylaxis, standby therapy for traveler’s diarrhea, or for prevention/ treatment of high altitude sickness. Between 11 and 59% of travelers to developing countries, who consulted a pretravel clinic, report having at least 1 chronic medical condition, most of whom were regularly taking prescription medications [1e4]. There are potential drugedrug interactions between TRM and many other medications, and caution is advised for their concomitant use [5]. Furthermore, medical conditions and drug allergies may pose a risk for the use of several travel related medications [6,7]. Data regarding the prevalence of possible interactions between travel-related medications and chronic medical conditions and medications used by travelers to developing countries are lacking. Our objective was to assess the prevalence and types of potential drugedrug and drugedisease interactions among a cohort of travelers to developing countries attending our pre-travel clinic.
Materials and methods We performed a cohort study based on the medical records of all travelers attending the pre-travel clinic at the Chaim Sheba Medical Center between January 1st, 2005 and December 31st, 2007. Travelers to developed countries [8] or those with missing data about travel destination were excluded. The study was approved by the Sheba Medical Center Institutional Review Board. The Sheba Medical Center pre-travel clinic provides medical advice to approximately 6000e7000 travelers annually. At the clinic visit, every traveler completes a structured questionnaire. The data collected includes age and gender, travel destinations, planned duration of travel, expected date of travel, and purpose of travel. Travelers are asked to select one of the following purposes for their trip: leisure/tourism, business, governmental/nongovernmental organization worker, research/education, returning to region of origin of self or family to visit friends and relatives (VFR). Travelers are also asked to record chronic medical conditions, chronic use of medication, and drug allergies. All data are stored in a computerized database using Microsoft Access 2010 (Microsoft, Redmond, WA, USA), which served as the source for the present study. Chronic use of medications was based on self-reporting. We analyzed separately, travelers who used medications
for chronic medical conditions, and healthy women who used oral contraceptives. Drug interactions with travel related medications: We defined the following medications as travel related medications (TRM): Drugs used for malaria prophylaxis (mefloquine, primaquine, doxycycline and atovaquone/proguanil [Malaroneª]), medications prescribed as stand-by therapy for traveler’s diarrhea (fluoroquinolone antibiotics [ciprofloxacin, ofloxacin], rifaximin and azithromycin), and the carbonic anhydrase inhibitor acetazolamide, used for the prophylaxis and therapy of high altitude sickness. We used Micromedex Healthcare Series database [5] to extract all medications considered to have interactions with TRM, including the effect of each interaction, its severity (mild, moderate, major, Contraindicated), and the quality of documentation in the medical literature (Excellent: Controlled studies have clearly established the existence of the interaction; Good: Documentation strongly suggests the interaction exists, but well-controlled studies are lacking; Fair: Available documentation is poor, but pharmacologic considerations lead clinicians to suspect the interaction exists; or, documentation is good for a pharmacologically similar drug). The Micromedex database classifies the severity of the drugedrug interaction as follows [5]: Contraindicated: The drugs are contraindicated for concurrent use; Major e The interaction may be life-threatening and/or require medical intervention to minimize or prevent serious adverse effects; Moderate e The interaction may result in exacerbation of the patient’s condition and/or require an alteration in therapy; Minor e The interaction would have limited clinical effects, e.g. increase the frequency or severity of the side effects, but generally would not require a major alteration in therapy. Chronic illness and TRM interactions: We used Micromedex Healthcare Series database [5] to extract all medical conditions considered to have interactions with TRM and its severity (Precaution needed, Contraindicated). Statistical analysis: Continuous data were described as mean standard deviation, or median with interquartile range (IQR). Proportions and 95% confidence intervals were calculated for categorical variables using the Wilson method [9]. Funding: No funding source was provided for the design conduct and reporting of the study.
Results During the study period, 16,263 travelers to developing countries sought pre-travel advice and were included in the
Please cite this article in press as: Stienlauf S, et al., Potential drug interactions in travelers with chronic illnesses: A large retrospective cohort study, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.04.008
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
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+ Q1
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MODEL
A large retrospective cohort study in travelers with chronic illnesses Table 1
Demographics and travel destinations.
Parameter
All travelers
Travelers on chronic medications
Travelers not using chronic medications
Number, n (%) Females, n (%) Age Mean (SD) Median (IQR) Destination: Asia Latin America Sub-Saharan Africa
16,263 7859 (48)
2316 (14) 1168 (50)
13,947 (86) 6691 (48)
32.2 14.5 26 (22e40) 10,620 (65)
47.6 17 53 (29e53) 1467 (63)
29.7 12.3 25 (22e32) 9153 (66)
4023 (25) 1896 (12)
533 (23) 393 (17)
3490 (25) 1503 (11)
study. Demographics and travel destinations are reported in Table 1. Oral contraceptive usage was reported by 817 (14% of female travelers
