Drug of last resort

A drug of last resort (DoLR), also known as a heroic dose, is a pharmaceutical drug which is tried after all other drug options have failed to produce an adequate response in the patient. Drug resistance, such as antimicrobial resistance or antineoplastic resistance, may make the first-line drug ineffective, especially with multidrug-resistant pathogens or tumors. Such an alternative may be outside of extant regulatory requirements or medical best practices, in which case it may be viewed as salvage therapy.

Purposes

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 sepsis or septic shock can more commonly lead to last resorts.

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 dose-response 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 antibiotics, antivirals, and chemotherapy 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.

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 Staphylococcus aureus (MRSA) (sometimes also referred to as multiple-drug resistant S. aureus due to resistance to non-penicillin antibiotics that some strains of S. aureus have shown to exhibit). In cases presenting with suspected S. aureus, it is suggested by many public health institutions (including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) in the United States) to treat first with empirical therapies for S. aureus, with an emphasis on evaluating the response to initial treatment and laboratory diagnostic techniques to isolate cases of drug resistance.

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.

Vancomycin has long been considered a drug of last resort, due to its efficiency in treating multiple drug-resistant infectious agents and the requirement for intravenous administration. Recently, resistance to even vancomycin has been shown in some strains of S. aureus (sometimes referred to as vancomycin resistant S. aureus (VRSA) or vancomycin intermediate-resistance S. aureus (VISA)) often coinciding with methicillin/penicillin resistance, prompting the inclusion of newer antibiotics (such as linezolid) that have shown efficacy in highly drug-resistant strains. There are also strains of enterococci that have developed resistance to vancomycin referred to as vancomycin resistant enterococcus (VRE).

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, unpleasant side effects 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.

Although most of the notable drugs of last resort are antibiotics or antivirals, other drugs are sometimes considered drugs of last resort, such as cisapride.[1]

Examples

Antimicrobials

Other drugs

References

  1. 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.
  2. 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.
  3. "Rocky Mountain Spotted Fever (RMSF) - Symptoms, Diagnosis, and Treatment". US Centers for Disease Control. Retrieved 12 March 2014.
  4. RMSF
  5. "Lotronex (alosetron hydrochloride) Tablets. Full Prescribing Information" (PDF). Prometheus Laboratories Inc., 9410 Carroll Park Drive, San Diego, CA 92121.
  6. 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.
  7. "Felbamate". MedlinePlus : U.S. National Library of Medicine. Retrieved 19 May 2013.
  8. 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.
  9. "An Americal View of Minoxidil — a Powerful 'Last Resort' Antihypertensive". InPharma. 229 (1): 2. March 1, 1980. doi:10.1007/BF03292651. S2CID 198213029.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. "Marplan (isocarboxazid) Tablets. Full Prescribing Information" (PDF). Validus Pharmaceuticals. pp. 2, 5. Retrieved 22 May 2017.
  15. "Sabril (vigabatrin) Tablets for Oral Use, Powder for Oral Solution. Full Prescribing Information" (PDF). Lundbeck.
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.