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Drug of last resort
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<h2 id="purposes">Purposes</h2> <p>The use of a drug of last resort may be based on agreement among members of a patient's care network, including physicians and healthcare professionals across multiple specialties, or on a patient's desire to pursue a particular course of treatment and a practitioner's willingness to administer that course. Certain situations such as severe bacterial related <a href="/facts/Sepsis/n52bkffJ">sepsis</a> or <a href="/facts/Septic_shock/yc9mgmrz">septic shock</a> can more commonly lead to last resorts. </p><p>Therapies considered to be drugs of last resort may at times be used earlier in the event that an agent would likely show the most immediate <a href="/facts/Dose-response_relationship/DLcuLdHc">dose-response</a> related efficacy in time-critical situations such as high mortality circumstances. Many of the drugs considered last resorts fall into one or more of the categories of <a href="/facts/Antibiotics/sF1kIfxg">antibiotics</a>, <a href="/facts/Antiviral_drug/Xgbd2eI2">antivirals</a>, and <a href="/facts/Chemotherapy/fWTLbaUT">chemotherapy</a> agents. These agents often exhibit what are considered to be among the most efficient dose-response related effects, or are drugs for which few or no resistant strains are known. </p><p>With regard to antibiotics, antivirals, and other agents indicated for treatment of infectious pathological disease, drugs of last resort are commonly withheld from administration until after the trial and failure of more commonly used treatment options to prevent the development of drug resistance. One of the most commonly known examples of both antimicrobial resistance and the relationship to the classification of a drug of last resort is the emergence of <a href="/facts/Methicillin-resistant_Staphylococcus_aureus/4DGUo2co"><i>Staphylococcus aureus</i></a> (MRSA) (sometimes also referred to as multiple-drug resistant <i>S. aureus</i> due to resistance to non-penicillin antibiotics that some strains of <i>S. aureus</i> have shown to exhibit). In cases presenting with suspected <i>S. aureus</i>, it is suggested by many public health institutions (including the <a href="/facts/World_Health_Organization/YNN3bgug">World Health Organization</a> (WHO) and the <a href="/facts/Centers_for_Disease_Control_and_Prevention/NmoJNDV5">Centers for Disease Control and Prevention</a> (CDC) in the United States) to treat first with empirical therapies for <i>S. aureus</i>, with an emphasis on evaluating the response to initial treatment and laboratory diagnostic techniques to isolate cases of drug resistance. </p><p>Due to the possibility of potential severe or fatal consequences of resistant strains, initial treatment often includes concomitant administration of multiple antimicrobial agents that are not known to show cross-resistance, so as to reduce the possibility of a resistant strain remaining inadequately treated by a single agent during the evaluation of drug response. Once a specific resistance profile has been isolated via clinical laboratory findings, treatment is often modified as indicated. </p><p><a href="/facts/Vancomycin/enHvz4uP">Vancomycin</a> has long been considered a drug of last resort, due to its efficiency in treating multiple drug-resistant infectious agents and the requirement for <a href="/facts/Intravenous/AwwuD3Nu">intravenous</a> administration. Recently, resistance to even vancomycin has been shown in some strains of <i>S. aureus</i> (sometimes referred to as <a href="/facts/Vancomycin-resistant_Staphylococcus_aureus/wJ0sGIVK">vancomycin resistant <i>S. aureus</i></a> (VRSA) or vancomycin intermediate-resistance <i>S. aureus</i> (VISA)) often coinciding with methicillin/penicillin resistance, prompting the inclusion of newer antibiotics (such as <a href="/facts/Linezolid/c6kpn1Yr">linezolid</a>) that have shown efficacy in highly drug-resistant strains. There are also strains of enterococci that have developed resistance to vancomycin referred to as <a href="/facts/Vancomycin_resistant_enterococcus/PoYxRTLJ">vancomycin resistant enterococcus</a> (VRE). </p><p>Agents classified as fourth-line (or greater) treatments or experimental therapies could be considered by default to be drugs of last resort due to their low placement in the treatment hierarchy. Such placement may result from a multitude of considerations, including greater efficacy of other agents, socioeconomic considerations, availability issues, <a href="/facts/Adverse_drug_reaction/Ea0ktF6J">unpleasant side effects</a> or similar issues relating to patient tolerance. Some experimental therapies might also be called drugs of last resort when administered following the failure of all other currently accepted treatments. </p><p>Although most of the notable drugs of last resort are antibiotics or antivirals, other drugs are sometimes considered drugs of last resort, such as <a href="/facts/Cisapride/9JMdgmW8">cisapride</a>.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> </p> <h2 id="examples">Examples</h2> <h3>Antimicrobials</h3> <ul><li><a href="/facts/Aminoglycoside/eNQrtDg0">Aminoglycosides</a> — their use is extremely restricted due to risk of hearing loss and kidney damage.</li> <li><a href="/facts/Amphotericin_B/c2H3NmRQ">Amphotericin B</a> — used for life-threatening <a href="/facts/Fungal_infections/YVK551qC">fungal infections</a> and <a href="/facts/Naegleriasis/Qdc1sc7T">primary amoebic meningoencephalitis</a>;<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> <a href="/facts/Amphotericin_B/c2H3NmRQ">its side effects</a> are often severe or potentially fatal.</li> <li><a href="/facts/Carbapenem/ydKuuwfQ">Carbapenems</a> (such as <a href="/facts/Imipenem%2fcilastatin/Ejg1LCjU">imipenem/cilastatin</a>) — used as a drug of last resort for a variety of different bacterial infections.</li> <li><a href="/facts/Ceftobiprole/kDVb7BrT">Ceftobiprole</a> and <a href="/facts/Ceftaroline/vX1P6uyB">ceftaroline</a> — fifth-generation <a href="/facts/Cephalosporin/WeB7I75T">cephalosporins</a> active against methicillin-resistant <i>Staphylococcus aureus</i> (<a href="/facts/MRSA/4DGUo2co">MRSA</a>); use is limited to prevent development of <a href="/facts/Antimicrobial_resistance/jsbAywgx">drug resistance</a>.</li> <li><a href="/facts/Cefiderocol/WJ8EpJT1">Cefiderocol</a> — a cephalosporin used to treat complicated <a href="/facts/Urinary_tract_infection/4NwY9tL0">urinary tract infections</a> (cUTI) caused by multi-drug resistant <a href="/facts/Gram-negative_bacteria/S1PbVtp4">Gram-negative bacteria</a> in patients with limited or no alternative options.</li> <li><a href="/facts/Chloramphenicol/4KQxQKvs">Chloramphenicol</a> — formerly first-line therapy for <a href="/facts/Rocky_Mountain_spotted_fever/YvVk1Mtl">Rocky Mountain spotted fever</a> (until <a href="/facts/Doxycycline/A8DBTzNh">doxycycline</a> became available).<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> Also first-line therapy (used topically) for <a href="/facts/Bacterial_conjunctivitis/u1NJfh3A">bacterial conjunctivitis</a>, and systemically for <a href="/facts/Meningitis/4m4STzJB">meningitis</a> when allergies to <a href="/facts/Penicillin/Abo8VQ3p">penicillin</a> or <a href="/facts/Cephalosporin/WeB7I75T">cephalosporin</a> exist. Unacceptably high risk of irreversible, fatal <a href="/facts/Aplastic_anemia/8VMHLI6J">aplastic anemia</a> and <a href="/facts/Gray_baby_syndrome/q1vCGDFk">gray baby syndrome</a> causes intravenous chloramphenicol to be a drug of last resort.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a></li> <li><a href="/facts/Colistin/pyjhChRz">Colistin</a> — used against certain life-threatening infections, such as those caused by <i><a href="/facts/Pseudomonas/FKEX7p7K">Pseudomonas</a></i>; carries risk of kidney and nerve damage.</li> <li><a href="/facts/Fostemsavir/Sfedd9VL">Fostemsavir</a> (an <a href="/facts/Entry_inhibitor/WaA9HqHH">HIV attachment inhibitor</a>) and <a href="/facts/Lenacapavir/n1qNfzTI">lenacapavir</a> (an <a href="/facts/HIV_capsid_inhibition/UAoltuDr">HIV capsid inhibitor</a>) are indicated in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></li> <li><a href="/facts/Melarsoprol/FK7XqP17">Melarsoprol</a> — a highly toxic antiprotozoal typically reserved for use only in late stages of the <i><a href="/facts/Trypanosoma_brucei/nNTY1A0A">T. b. rhodesiense</a></i> type of <a href="/facts/African_trypanosomiasis/zuvUoRKC">African trypanosomiasis</a>, wherein it remains the only treatment. Its toxicity often results in <a href="/facts/Polyneuropathy/CnbsnY0J">polyneuropathy</a> and <a href="/facts/Encephalopathy/mbArdl2s">reactive encephalopathy</a>, resulting in death in around 5% of patients.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a></li> <li><a href="/facts/Linezolid/c6kpn1Yr">Linezolid</a> — use is limited due to high cost and risk of vision loss or myopathy (due to mitochondrial damage).</li> <li><a href="/facts/Tigecycline/03JBAmzM">Tigecycline</a> — used to kill <i><a href="/facts/Acinetobacter/AQaLIf6T">Acinetobacter</a></i> and <i><a href="/facts/Legionella/98PA98kj">Legionella</a></i> species; this drug is limited by high cost and risk of liver injury.</li></ul> <h3>Other drugs</h3> <ul><li><a href="/facts/Alosetron/lbJntJdD">Alosetron</a> — used in the management of severe chronic diarrhea-predominant <a href="/facts/Irritable_bowel_syndrome/FW24EYbP">irritable bowel syndrome</a> (IBS-D) in females not responsive to conventional therapy. Its use is restricted due to serious gastrointestinal adverse reactions, e.g. <a href="/facts/Ischemic_colitis/CCYNFDCt">ischemic colitis</a> and complications of constipation.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a></li> <li><a href="/facts/Cisapride/9JMdgmW8">Cisapride</a> — used for severe <a href="/facts/Gastroesophageal_reflux_disease/8YhncnDz">gastroesophageal reflux disease</a> (GERD); carries risk of <a href="/facts/Heart_arrhythmia/ooEpr46Q">heart arrhythmias</a>.</li> <li><a href="/facts/Clomethiazole/NJ4zM4U1">Clomethiazole</a> — a <a href="/facts/Sedative/JWzvq66P">sedative</a>/hypnotic agent used in the treatment of <a href="/facts/Alcohol_withdrawal/FRX036Vk">alcohol withdrawal</a> when <a href="/facts/Benzodiazepines/IgbJr4jy">benzodiazepines</a> are not effective.</li> <li><a href="/facts/Clozapine/N0Lqztg1">Clozapine</a> — used in treatment-resistant schizophrenia not responsive to at least two different antipsychotics; the main reason for such restriction is <a href="/facts/Agranulocytosis/3AP5MDpD">agranulocytosis</a> and other severe side effects including <a href="/facts/Seizures/zuIrQyze">seizures</a> and <a href="/facts/Myocarditis/ypoBJ4Pp">myocarditis</a>.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></li> <li><a href="/facts/Felbamate/LxFRqrFr">Felbamate</a> — an <a href="/facts/Anticonvulsant/uR8cxJbj">anticonvulsant</a> used in refractory <a href="/facts/Epilepsy/wawyp56a">epilepsy</a>. Its use is associated with an increased risk of <a href="/facts/Aplastic_anemia/8VMHLI6J">aplastic anemia</a> and <a href="/facts/Liver_failure/AB5ocI30">liver failure</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></li> <li><a href="/facts/Isotretinoin/XBKv4fQJ">Isotretinoin</a> — when all topical treatments or antibiotics against <a href="/facts/Acne/TKJxhHSd">acne</a> have failed, many dermatologists resort to isotretinoin, which is an oral treatment that permanently dries out the <a href="/facts/Sebaceous_gland/HKMXmv1Y">sebum</a> production of the skin and is often a permanent solution against acne. It can cause severe <a href="/facts/Nosebleed/QXEqRDmw">nosebleeds</a>, causes <a href="/facts/Birth_defect/ESfzQhTx">birth defects</a> when taken while pregnant, is said to cause <a href="/facts/Major_depressive_disorder/l2lQeWqr">depression</a>, <a href="/facts/Hair_loss/uEPKUafl">hair loss</a> and can permanently dry out the skin all over the body and is therefore not the first treatment.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a></li> <li><a href="/facts/Levosimendan/mrw6ACG8">Levosimendan</a> — used in <a href="/facts/Acute_decompensated_heart_failure/QDnk289N">acutely decompensated</a> severe chronic <a href="/facts/Heart_failure/7fckX3Jm">heart failure</a> in situations where conventional therapy is not sufficient.</li> <li><i>Oral</i> <a href="/facts/Minoxidil/H20coNLM">minoxidil</a> for <a href="/facts/Hypertension/wlAvBfcf">hypertension</a>,<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> however <i>topical</i> minoxidil is a first-line drug for hair loss.</li> <li><a href="/facts/Monoamine_oxidase_inhibitor/obewT56a">Monoamine oxidase inhibitors</a> — due to potentially lethal dietary and <a href="/facts/Drug_interaction/T5VcSVGd">drug interactions</a> which may trigger <a href="/facts/Hypertensive_crisis/dDPo1RB3">hypertensive crisis</a> and/or <a href="/facts/Serotonin_syndrome/PqLvx901">serotonin syndrome</a>,<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> they are generally used only when other classes of antidepressants (e.g., <a href="/facts/Selective_serotonin_reuptake_inhibitor/L6jjcmEH">SSRIs</a> or <a href="/facts/Serotonin%25E2%2580%2593norepinephrine_reuptake_inhibitor/PSr56Vxh">SNRIs</a>) don't work.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a><a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a></li> <li><a href="/facts/Thalidomide/FWQGuD2A">Thalidomide</a> — withdrawn in 1961 owing to widespread incidence of severe birth defects (<a href="/facts/Phocomelia/JtNfNEnN">phocomelia</a> or <a href="/facts/Tetraamelia/6C4Jfphh">tetraamelia</a>) after prenatal use by pregnant women, US <a href="/facts/Food_and_Drug_Administration/rCEnh9WB">Food and Drug Administration</a> approved thalidomide for <a href="/facts/Erythema_nodosum_leprosum/bwAR5QYs">erythema nodosum leprosum</a> (ENL) in 1998, and 2008 for new cases of <a href="/facts/Multiple_myeloma/Pp9Tt33l">multiple myeloma</a> (administered with <a href="/facts/Dexamethasone/rwAhDqls">dexamethasone</a>). A large "off-label" business in thalidomide began for rare cancers even while it was only FDA-approved for erythema nodosum leprosum.</li> <li><a href="/facts/Tolcapone/sm2NBopp">Tolcapone</a> — used in patients with <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a> who are not appropriate candidates for other adjunctive therapies. Use is restricted due to <a href="/facts/Hepatotoxicity/xbLcKPNG">hepatotoxicity</a>.</li> <li><a href="/facts/Vigabatrin/b0JuB1XC">Vigabatrin</a> — used only in extreme treatment-resistant <a href="/facts/Epilepsy/wawyp56a">epilepsy</a> due to the risk of permanent <a href="/facts/Vision_loss/sFuqKj3n">vision loss</a>.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a></li></ul> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Heroic_measure/v00j854E">Heroic measure</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>The American Heritage Stedman's Medical Dictionary. Houghton Mifflin Company. 2004. ISBN 9780618428991. <a href="9780618428991" target="_blank">9780618428991</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Ciment, J. (5 February 2000). "FDA tells doctors to use heartburn drug as last resort". BMJ. 320 (7231): 336. doi:10.1136/bmj.320.7231.336. PMC 1173548. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1173548" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1173548</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Grace, Eddie; Asbill, Scott; Virga, Kris (November 2015). "Naegleria fowleri: Pathogenesis, Diagnosis, and Treatment Options". Antimicrobial Agents and Chemotherapy. 59 (11): 6677–6681. doi:10.1128/AAC.01293-15. PMC 4604384. PMID 26259797. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604384" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604384</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Rocky Mountain Spotted Fever (RMSF) - Symptoms, Diagnosis, and Treatment". US Centers for Disease Control. Retrieved 12 March 2014. <a href="https://www.cdc.gov/rmsf/symptoms/index.html" target="_blank">https://www.cdc.gov/rmsf/symptoms/index.html</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>RMSF <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>"Rukobia (fostemsavir) Extended-Release Tablets, for Oral Use. Full Prescribing Information" (PDF). U.S. Food and Drug Administration. June 2020. <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf" target="_blank">https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>"Sunlenca (lenacapavir) Tablets, for Oral Use; Sunlenca (lenacapavir) Injection, for Subcutaneous Use. Full Prescribing Information" (PDF). U.S. Food and Drug Administration. December 2022. <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf" target="_blank">https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215973s000lbl.pdf</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Pepin, J (2014). "Infectious Disease & Antimicrobial Agents - Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense (African Trypanosomiasis)". antimicrobe.org. Archived from the original on 7 February 2024. Retrieved 27 July 2024. <a href="http://www.antimicrobe.org/b54.asp" target="_blank">http://www.antimicrobe.org/b54.asp</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>"Lotronex (alosetron hydrochloride) Tablets. Full Prescribing Information" (PDF). Prometheus Laboratories Inc., 9410 Carroll Park Drive, San Diego, CA 92121. Archived from the original (PDF) on 2016-02-22. Retrieved 2019-12-21. <a href="https://web.archive.org/web/20160222142743/https://www.lotronex.com/hcp/_docs/Lotronex_PI.pdf" target="_blank">https://web.archive.org/web/20160222142743/https://www.lotronex.com/hcp/_docs/Lotronex_PI.pdf</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Schulte, P. (2003). "What is an adequate trial with clozapine?: therapeutic drug monitoring and time to response in treatment-refractory schizophrenia". Clinical Pharmacokinetics. 42 (7): 607–618. doi:10.2165/00003088-200342070-00001. PMID 12844323. S2CID 25525638. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>"Felbamate". MedlinePlus : U.S. National Library of Medicine. Retrieved 19 May 2013. <a href="https://www.nlm.nih.gov/medlineplus/druginfo/meds/a606011.html" target="_blank">https://www.nlm.nih.gov/medlineplus/druginfo/meds/a606011.html</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Costa, Caroline S; Bagatin, Ediléia; Martimbianco, Ana Luiza C; da Silva, Edina MK; Lúcio, Marília M; Magin, Parker; Riera, Rachel (2018-11-24). "Oral isotretinoin for acne". The Cochrane Database of Systematic Reviews. 2018 (11): CD009435. doi:10.1002/14651858.CD009435.pub2. ISSN 1469-493X. PMC 6383843. PMID 30484286. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383843" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383843</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>"An Americal View of Minoxidil — a Powerful 'Last Resort' Antihypertensive". InPharma. 229 (1): 2. March 1, 1980. doi:10.1007/BF03292651. S2CID 198213029. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Mann, Samuel J. (2012). Hypertension and you : old drugs, new drugs, and the right drugs for your high blood pressure. Lanham, Md.: Rowman & Littlefield Publishers. p. 90. ISBN 978-1-4422-1517-7. <a href="978-1-4422-1517-7" target="_blank">978-1-4422-1517-7</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Grady, MM; Stahl, SM (26 April 2012). "Practical Guide for Prescribing MAOIs: Debunking Myths and Removing Barriers". CNS Spectrums. 17 (1): 2–10. doi:10.1017/S109285291200003X. PMID 22790112. S2CID 206312008. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Turkington, C; Harris, JR (2009). The Encyclopedia of the Brain and Brain Disorders (3rd ed.). New York: Facts On File. p. 238. ISBN 978-0816063956. <a href="978-0816063956" target="_blank">978-0816063956</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Krings-Ernst, Ilana; Ulrich, Sven; Adli, Mazda (1 October 2013). "Antidepressant Treatment with MAO-Inhibitors During General and Regional Anesthesia: a Review and Case Report of Spinal Anesthesia for Lower Extremity Surgery Without Discontinuation of Tranylcypromine". International Journal of Clinical Pharmacology and Therapeutics. 51 (10): 763–70. doi:10.5414/CP201898. PMID 23993253. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>"Marplan (isocarboxazid) Tablets. Full Prescribing Information" (PDF). Validus Pharmaceuticals. pp. 2, 5. Archived from the original (PDF) on 18 August 2017. Retrieved 22 May 2017. <a href="https://web.archive.org/web/20170818214332/http://marplan.com/wp-content/uploads/sites/6/2014/06/marplan-prescribing-info.pdf" target="_blank">https://web.archive.org/web/20170818214332/http://marplan.com/wp-content/uploads/sites/6/2014/06/marplan-prescribing-info.pdf</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>"Sabril (vigabatrin) Tablets for Oral Use, Powder for Oral Solution. Full Prescribing Information" (PDF). Lundbeck. <a href="http://www.lundbeck.com/upload/us/files/pdf/Products/Sabril_PI_US_EN.pdf" target="_blank">http://www.lundbeck.com/upload/us/files/pdf/Products/Sabril_PI_US_EN.pdf</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> </ol>