Common Adverse Drug-Drug Interactions in Dermatology: Oral Therapies
Main Article Content
Keywords
drug-drug interactions, oral therapies, methotrexate, acitretin, bexarotene, macrolides, cyclosporine, epinephrine, isotretinoin, spirinolactone, allopurinol, oral contraceptives
Abstract
Drug-drug interactions between systemic oral therapies in dermatology can result in preventable iatrogenic causes of patient morbidity and mortality. Most of these interactions are due to cytochrome P450 or renal excretion interactions. We review here a number of drugs and drug-drug interactions seen in general dermatology, including methotrexate, bexarotene, macrolides, cyclosporine, epinephrine, isotretinoin, spirinolactone, allopurinol, and oral contraceptives.
References
1. Egger SS, Drewe J, Schlienger RG. Potential drug-drug interactions in the medication of medical patients at hospital discharge. Eur J Clin Pharmacol. 2003;58(11):773-8.
2. Jankel CA, Fitterman LK. Epidemiology of drug-drug interactions as a cause of hospital admissions. Drug Saf. 1993;9(1):51-9.
3. Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J. Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin Pharmacokinet. 1996;30(3):194-210.
4. Toivo TM, Mikkola JA, Laine K, Airaksinen M. Identifying high risk medications causing potential drug-drug interactions in outpatients: A prescription database study based on an online surveillance system. Res Social Adm Pharm. 2016;12(4):559-68.
5. Bourre-Tessier J, Haraoui B. Methotrexate drug interactions in the treatment of rheumatoid arthritis: a systematic review. J Rheumatol. 2010;37(7):1416-21.
6. Chan AJ, Rajakumar I. High-dose methotrexate in adult oncology patients: A case-control study assessing the risk association between drug interactions and methotrexate toxicity. J Oncol Pharm Pract. 2014;20(2):93-9.
7. Hall JJ, Bolina M, Chatterley T, Jamali F. Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors. Ann Pharmacother. 2017;51(2):163-78.
8. Colebatch AN, Marks JL, Edwards CJ. Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). Cochrane Database Syst Rev. 2011(11):Cd008872.
9. Rollman O, Vahlquist A. Retinoid concentrations in skin, serum and adipose tissue of patients treated with etretinate. Br J Dermatol 1983;109(4):439-47.
10. Larsen FG, Jakobsen P, Eriksen H, Gronhoj J, Kragballe K, Nielsen-Kudsk F. The pharmacokinetics of acitretin and its 13-cis-metabolite in psoriatic patients. J Clin Pharmacol. 1991;31(5):477-83.
11. Larsen FG, Jakobsen P, Knudsen J, Weismann K, Kragballe K, Nielsen-Kudsk F. Conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol. J Invest Dermatol. 1993;100(5):623-7.
12. Gronhoj Larsen F, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff PB, Nielsen-Kudsk F. Acitretin is converted to etretinate only during concomitant alcohol intake. Br J Dermatol. 2000;143(6):1164-9.
13. Talpur R, Ward S, Apisarnthanarax N, Breuer-Mcham J, Duvic M. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2002;47(5):672-84.
14. von Rosensteil NA, Adam D. Macrolide antibacterials. Drug interactions of clinical significance. Drug Saf. 1995;13(2):105-22.
15. Patel AM, Shariff S, Bailey DG, Juurlink DN, Gandhi S, Mamdani M, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158(12):869-76.
16. Westphal JF. Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. Br J Clin Pharmacol. 2000;50(4):285-95.
17. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351(11):1089-96.
18. Svanstrom H, Pasternak B, Hviid A. Use of azithromycin and death from cardiovascular causes. N Engl J Med. 2013;368(18):1704-12.
19. Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366(20):1881-90.
20. Bramow S, Ott P, Thomsen Nielsen F, Bangert K, Tygstrup N, Dalhoff K. Cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine A and sirolimus (Rapamycin). Pharmacol Toxicol. 2001;89(3):133-9.
21. Shitara Y, Itoh T, Sato H, Li AP, Sugiyama Y. Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. J Pharmacol Exp Ther. 2003;304(2):610-6.
22. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19(1):117-25.
23. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH. Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000;21(9):353-64.
24. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80(6):565-81.
25. Asberg A, Hartmann A, Fjeldsa E, Bergan S, Holdaas H. Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Am J Transplant. 2001;1(4):382-6.
26. Foster CA, Aston SJ. Propranolol-epinephrine interaction: a potential disaster. Plast Reconstr Surg. 1983;72(1):74-8.
27. Mito RS, Yagiela JA. Hypertensive response to levonordefrin in a patient receiving propranolol: report of case. J Am Dent Assoc. 1988;116(1):55-7.
28. Hjemdahl P, Akerstedt T, Pollare T, Gillberg M. Influence of beta-adrenoceptor blockade by metoprolol and propranolol on plasma concentrations and effects of noradrenaline and adrenaline during i.v. infusion. Acta Physiol Suppl. 1983;515:45-53.
29. Rehling M, Svendsen TL, Maltbaek N, Tango M, Trap-Jensen J. Haemodynamic effects of atenolol, pindolol and propranolol during adrenaline infusion in man. Eur J Clin Pharmacol. 1986;30(6):659-63.
30. Houben H, Thien T, van 't Laar A. Effect of low-dose epinephrine infusion on hemodynamics after selective and nonselective beta-blockade in hypertension. Clin Pharmacol Ther. 1982;31(6):685-90.
31. Dzubow LM. The interaction between propranolol and epinephrine as observed in patients undergoing Mohs' surgery. J Am Acad Dermatol. 1986;15(1):71-5.
32. Lester RS, Schachter GD, Light MJ. Isotretinoin and tetracycline in the management of severe nodulocystic acne. International journal of dermatology. Int J Dermatol. 1985;24(1):252-7.
33. Friedman DI. Medication-induced intracranial hypertension in dermatology. Am J Clin Dermatol. 2005;6(1):29-37.
34. Chiu AM, Chuenkongkaew WL, Cornblath WT, Trobe JD, Digre KB, Dotan SA, Musson KH, Eggenberger ER. Minocycline treatment and pseudotumor cerebri syndrome. Am J Ophthalmol. 1998;126(1):116-21.
35. Lee AG. Pseudotumor cerebri after treatment with tetracycline and isotretinoin for acne. Cutis. 1995;55(3):165-8.
36. Nagler AR, Milam EC, Orlow SJ. The use of oral antibiotics before isotretinoin therapy in patients with acne. J Am Acad Dermatol. 2016;74(2):273-9.
37. Bettoli V, Borghi A, Mantovani L, Scorrano R, Minghetti S, Toni G, Sarno O, Zauli S, Virgili A. Safe use of oral isotretinoin after pseudo-tumor cerebri due to minocycline. Eur J Dermatol. 2012;21(6):1024-5.
38. Saint-Jean M, Ballanger F, Nguyen JM, Khammari A, Dréno B. Importance of spironolactone in the treatment of acne in adult women. J Eur Acad Dermatol Venereol. 2011;25(12):1480-1.
39. Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, Weir MA, Juurlink DN. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. BMJ. 2011;343:d5228.
40. Antoniou T, Hollands S, Macdonald EM, Gomes T, Mamdani MM, Juurlink DN. Trimethoprim–sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ. 2015;187(4):E138-43.
41. Abbas S, Ihle P, Harder S, Schubert I. Risk of hyperkalemia and combined use of spironolactone and long‐term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real‐life data: a population‐and insurance‐based cohort. Pharmacoepidemiol Drug Saf. 2015;24(4):406-13.
42. Plovanich M, Weng QY, Mostaghimi A. Low usefulness of potassium monitoring among healthy young women taking spironolactone for acne. JAMA Dermatol. 2015;151(9):941-4.
43. Gearry RB, Day AS, Barclay ML, Leong RW, Sparrow MP. Azathioprine and allopurinol: A two-edged interaction. J Gastroenterol Hepatol. 2010;25(4):653-5.
44. Leung Y, Sparrow MP, Schwartz M, Hanauer SB. Long term efficacy and safety of allopurinol and azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease. J Crohns Colitis. 2009;3(3):162-7.
45. Jick H, Slone D, Shapiro S. Excess of ampicillin rashes associated with allopurinol or hyperuricemia. N Engl J Med. 1972;286:505-7.
46. Jick H, Porter JB. Potentiation of ampicillin skin reactions by allopurinol or hyperuricemia. J Clin Pharmacol. 1981;21(10):456-8.
47. Ben Fredj N, Aouam K, Chaabane A, Toumi A, Ben Rhomdhane F, Boughattas N, Chakroun M. Hypersensitivity to amoxicillin after drug rash with eosinophilia and systemic symptoms (DRESS) to carbamazepine and allopurinol: a possible co-sensitization. Br J Clin Pharmacol. 2010;70(2):273-6.
48. Jones J, Mosher W, Daniels K. Current contraceptive use in the United States, 2006–2010, and changes in patterns of use since 1995. Natl Health Stat Report. 2012;60:1-25.
49. Dickinson BD, Altman RD, Nielsen NH, Sterling ML. Drug interactions between oral contraceptives and antibiotics. Ostet Gynecol. 2001;98(5):853-60.
50. Helms SE, Bredle DL, Zajic J, Jatjoura D, Brodell RT, Krishnarao I. Oral contraceptive failure rates and oral antibiotics. J Am Acad Dermatol. 1997;36(5):705-10.
51. Archer JS, Archer DF. Oral contraceptive efficacy and antibiotic interaction: a myth debunked. J Am Acad Dermatol. 2002;46(6):917-23.
52. Toh S, Mitchell AA, Anderka M, Hernández-Díaz S, Study NB. Antibiotics and oral contraceptive failure—a case-crossover study. Contraception. 2011;83(5):418-25.
2. Jankel CA, Fitterman LK. Epidemiology of drug-drug interactions as a cause of hospital admissions. Drug Saf. 1993;9(1):51-9.
3. Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J. Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin Pharmacokinet. 1996;30(3):194-210.
4. Toivo TM, Mikkola JA, Laine K, Airaksinen M. Identifying high risk medications causing potential drug-drug interactions in outpatients: A prescription database study based on an online surveillance system. Res Social Adm Pharm. 2016;12(4):559-68.
5. Bourre-Tessier J, Haraoui B. Methotrexate drug interactions in the treatment of rheumatoid arthritis: a systematic review. J Rheumatol. 2010;37(7):1416-21.
6. Chan AJ, Rajakumar I. High-dose methotrexate in adult oncology patients: A case-control study assessing the risk association between drug interactions and methotrexate toxicity. J Oncol Pharm Pract. 2014;20(2):93-9.
7. Hall JJ, Bolina M, Chatterley T, Jamali F. Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors. Ann Pharmacother. 2017;51(2):163-78.
8. Colebatch AN, Marks JL, Edwards CJ. Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). Cochrane Database Syst Rev. 2011(11):Cd008872.
9. Rollman O, Vahlquist A. Retinoid concentrations in skin, serum and adipose tissue of patients treated with etretinate. Br J Dermatol 1983;109(4):439-47.
10. Larsen FG, Jakobsen P, Eriksen H, Gronhoj J, Kragballe K, Nielsen-Kudsk F. The pharmacokinetics of acitretin and its 13-cis-metabolite in psoriatic patients. J Clin Pharmacol. 1991;31(5):477-83.
11. Larsen FG, Jakobsen P, Knudsen J, Weismann K, Kragballe K, Nielsen-Kudsk F. Conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol. J Invest Dermatol. 1993;100(5):623-7.
12. Gronhoj Larsen F, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff PB, Nielsen-Kudsk F. Acitretin is converted to etretinate only during concomitant alcohol intake. Br J Dermatol. 2000;143(6):1164-9.
13. Talpur R, Ward S, Apisarnthanarax N, Breuer-Mcham J, Duvic M. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2002;47(5):672-84.
14. von Rosensteil NA, Adam D. Macrolide antibacterials. Drug interactions of clinical significance. Drug Saf. 1995;13(2):105-22.
15. Patel AM, Shariff S, Bailey DG, Juurlink DN, Gandhi S, Mamdani M, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158(12):869-76.
16. Westphal JF. Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. Br J Clin Pharmacol. 2000;50(4):285-95.
17. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351(11):1089-96.
18. Svanstrom H, Pasternak B, Hviid A. Use of azithromycin and death from cardiovascular causes. N Engl J Med. 2013;368(18):1704-12.
19. Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366(20):1881-90.
20. Bramow S, Ott P, Thomsen Nielsen F, Bangert K, Tygstrup N, Dalhoff K. Cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine A and sirolimus (Rapamycin). Pharmacol Toxicol. 2001;89(3):133-9.
21. Shitara Y, Itoh T, Sato H, Li AP, Sugiyama Y. Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. J Pharmacol Exp Ther. 2003;304(2):610-6.
22. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19(1):117-25.
23. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH. Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000;21(9):353-64.
24. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80(6):565-81.
25. Asberg A, Hartmann A, Fjeldsa E, Bergan S, Holdaas H. Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Am J Transplant. 2001;1(4):382-6.
26. Foster CA, Aston SJ. Propranolol-epinephrine interaction: a potential disaster. Plast Reconstr Surg. 1983;72(1):74-8.
27. Mito RS, Yagiela JA. Hypertensive response to levonordefrin in a patient receiving propranolol: report of case. J Am Dent Assoc. 1988;116(1):55-7.
28. Hjemdahl P, Akerstedt T, Pollare T, Gillberg M. Influence of beta-adrenoceptor blockade by metoprolol and propranolol on plasma concentrations and effects of noradrenaline and adrenaline during i.v. infusion. Acta Physiol Suppl. 1983;515:45-53.
29. Rehling M, Svendsen TL, Maltbaek N, Tango M, Trap-Jensen J. Haemodynamic effects of atenolol, pindolol and propranolol during adrenaline infusion in man. Eur J Clin Pharmacol. 1986;30(6):659-63.
30. Houben H, Thien T, van 't Laar A. Effect of low-dose epinephrine infusion on hemodynamics after selective and nonselective beta-blockade in hypertension. Clin Pharmacol Ther. 1982;31(6):685-90.
31. Dzubow LM. The interaction between propranolol and epinephrine as observed in patients undergoing Mohs' surgery. J Am Acad Dermatol. 1986;15(1):71-5.
32. Lester RS, Schachter GD, Light MJ. Isotretinoin and tetracycline in the management of severe nodulocystic acne. International journal of dermatology. Int J Dermatol. 1985;24(1):252-7.
33. Friedman DI. Medication-induced intracranial hypertension in dermatology. Am J Clin Dermatol. 2005;6(1):29-37.
34. Chiu AM, Chuenkongkaew WL, Cornblath WT, Trobe JD, Digre KB, Dotan SA, Musson KH, Eggenberger ER. Minocycline treatment and pseudotumor cerebri syndrome. Am J Ophthalmol. 1998;126(1):116-21.
35. Lee AG. Pseudotumor cerebri after treatment with tetracycline and isotretinoin for acne. Cutis. 1995;55(3):165-8.
36. Nagler AR, Milam EC, Orlow SJ. The use of oral antibiotics before isotretinoin therapy in patients with acne. J Am Acad Dermatol. 2016;74(2):273-9.
37. Bettoli V, Borghi A, Mantovani L, Scorrano R, Minghetti S, Toni G, Sarno O, Zauli S, Virgili A. Safe use of oral isotretinoin after pseudo-tumor cerebri due to minocycline. Eur J Dermatol. 2012;21(6):1024-5.
38. Saint-Jean M, Ballanger F, Nguyen JM, Khammari A, Dréno B. Importance of spironolactone in the treatment of acne in adult women. J Eur Acad Dermatol Venereol. 2011;25(12):1480-1.
39. Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, Weir MA, Juurlink DN. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. BMJ. 2011;343:d5228.
40. Antoniou T, Hollands S, Macdonald EM, Gomes T, Mamdani MM, Juurlink DN. Trimethoprim–sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ. 2015;187(4):E138-43.
41. Abbas S, Ihle P, Harder S, Schubert I. Risk of hyperkalemia and combined use of spironolactone and long‐term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real‐life data: a population‐and insurance‐based cohort. Pharmacoepidemiol Drug Saf. 2015;24(4):406-13.
42. Plovanich M, Weng QY, Mostaghimi A. Low usefulness of potassium monitoring among healthy young women taking spironolactone for acne. JAMA Dermatol. 2015;151(9):941-4.
43. Gearry RB, Day AS, Barclay ML, Leong RW, Sparrow MP. Azathioprine and allopurinol: A two-edged interaction. J Gastroenterol Hepatol. 2010;25(4):653-5.
44. Leung Y, Sparrow MP, Schwartz M, Hanauer SB. Long term efficacy and safety of allopurinol and azathioprine or 6-mercaptopurine in patients with inflammatory bowel disease. J Crohns Colitis. 2009;3(3):162-7.
45. Jick H, Slone D, Shapiro S. Excess of ampicillin rashes associated with allopurinol or hyperuricemia. N Engl J Med. 1972;286:505-7.
46. Jick H, Porter JB. Potentiation of ampicillin skin reactions by allopurinol or hyperuricemia. J Clin Pharmacol. 1981;21(10):456-8.
47. Ben Fredj N, Aouam K, Chaabane A, Toumi A, Ben Rhomdhane F, Boughattas N, Chakroun M. Hypersensitivity to amoxicillin after drug rash with eosinophilia and systemic symptoms (DRESS) to carbamazepine and allopurinol: a possible co-sensitization. Br J Clin Pharmacol. 2010;70(2):273-6.
48. Jones J, Mosher W, Daniels K. Current contraceptive use in the United States, 2006–2010, and changes in patterns of use since 1995. Natl Health Stat Report. 2012;60:1-25.
49. Dickinson BD, Altman RD, Nielsen NH, Sterling ML. Drug interactions between oral contraceptives and antibiotics. Ostet Gynecol. 2001;98(5):853-60.
50. Helms SE, Bredle DL, Zajic J, Jatjoura D, Brodell RT, Krishnarao I. Oral contraceptive failure rates and oral antibiotics. J Am Acad Dermatol. 1997;36(5):705-10.
51. Archer JS, Archer DF. Oral contraceptive efficacy and antibiotic interaction: a myth debunked. J Am Acad Dermatol. 2002;46(6):917-23.
52. Toh S, Mitchell AA, Anderka M, Hernández-Díaz S, Study NB. Antibiotics and oral contraceptive failure—a case-crossover study. Contraception. 2011;83(5):418-25.
Article Sidebar
Published
Aug 31, 2017
Article Details
How to Cite
Dong, J., Bonomo, L., & Lebwohl, M. (2017). Common Adverse Drug-Drug Interactions in Dermatology: Oral Therapies. SKIN The Journal of Cutaneous Medicine, 1(2), 74–82. https://doi.org/10.25251/skin.1.2.3
Issue
Section
In-Depth Reviews
This work is licensed under a Creative Commons Attribution 4.0 International License.
All authors retain copyright in their articles. All articles published open access allowing for immediate free access to the work and permitting any user to read, download, copy, distribute, print, search, or link to the full texts of articles, crawl them for indexing, pass them as data to software or use them for any other lawful purpose. Permitted reuse is defined by the following user license:
Creative Commons Attribution (CC BY): lets others distribute and copy the article, to create extracts, abstracts, and other revised versions, adaptations or derivative works of or from an article (such as a translation), to include in a collective work (such as an anthology), to text or data mine the article, even for commercial purposes, as long as they credit the author(s), do not represent the author as endorsing their adaptation of the article, and do not modify the article in such a way as to damage the author's honor or reputation.
Authors retain copyright in their work and license the publisher to publish the content. The publisher is the National Society for Cutaneous Medicine, with production and publishing support provided by OJS, Open Journal Systems,see https://pkp.sfu.
Prior to January 2022, authors transferred copyright to the National Society for Cutaneous Medicine. However, all articles are freely available to anyone in the world. There are no subscription fees, page charges, or article processing charges.
Author Biographies