Clinical UM Guideline


Subject: Drug Dosage, Frequency, and Route of Administration
Guideline #:  CG-DRUG-53 Publish Date:    06/06/2018
Status: Reviewed Last Review Date:    05/03/2018


This document addresses the clinical criteria for review of the medical necessity of dosage, frequency, and route of administration of a drug or biosimilar product (collectively referred to as drugs within this document).

Note: The medical necessity of the drug may be determined separately when located under any of the following applicable documents:

Clinical Indications

Medically Necessary:

Drug Dosage, Frequency, and Route of Administration

The dosage, frequency, and route of administration of a drug is considered medically necessary when either criteria (A) or (B) is met:

  1. The drug dosage, frequency, and route of administration is supported by one or more of the following for the treatment indication:
    1. U.S. Food and Drug Administration (FDA) prescribing information; or
    2. American Hospital Formulary Service Drug Information® (AHFS) Drug Information®; or
    3. DRUGDEX® System; Truven Health Analytics; or
    4. National Comprehensive Cancer Network® (NCCN®) Drug & Biologics Compendium®;
  2. In the absence of drug dosage, frequency, and route of administration prescribing information listed in criteria (A) for the treatment indication:

Not Medically Necessary:

The drug dosage, frequency, and route of administration of a drug is considered not medically necessary when the above conditions are not met.


Specific coding does not apply to this document.

Discussion/General Information

Prior to being allowed to be marketed in the U.S., the FDA Center for Drug Evaluation and Research (CDER) evaluates safety and efficacy of a new drug. The FDA may approve those drugs for which the sponsor has provided sufficient evidence from clinical trials supporting that a drug is safe and effective. The drug label, approved by the FDA, is meant to be a valuable tool to convey information about a drug’s indication, dosage, pharmacology and adverse effects. Post marketing surveillance continues after approval and this monitoring frequently results in label changes. Approximately 400-500 product label changes are done every year (Kircik, 2016). This process supports that health care providers utilizing the drug label information are receiving the most current information available on a pharmaceutical product.  

The FDA requires that labeling include known and relevant information regarding safe and effective dosing and administration for each drug indication. This information includes, but is not limited to:

American Hospital Formulary Service Drug Information (AHFS, Greenwood Village, CO) includes both FDA and off-label indications. In addition to providing information on drug usage for specific indications, AHFS includes dosage and administration information and descriptions of the available preparations for each drug.

DRUGDEX (Truven Health Analytics, Ann Arbor, MI) includes DrugPoints, a summary document of DRUGDEX. Therapeutic drug indications in the two documents may vary. DRUGDEX is the comprehensive document which includes all FDA approved indications, off-label indications and dosing and administration information. DrugPoints includes limited information in a summary format.

The National Comprehensive Cancer Network (NCCN) Drug & Biologics Compendium is a listing of appropriate uses of agents as defined in and derived from the NCCN Clinical Guidelines in Oncology®. The compendium lists both FDA-approved uses and NCCN designated off-label indications. The Compendium, which is updated in conjunction with NCCN guidelines, includes information on route of administration as well as recommended uses in specific diseases.

The Company takes into account credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community. Peer-reviewed medical literature does not include publications or supplements to publications that are sponsored to a significant extent by a pharmaceutical manufacturing company or health carrier.


Drug (as defined by the FDA):

Off-label: Utilization of an FDA approved drug for uses other than those listed in the FDA approved label.

Route of Administration: The way a drug is administered to an individual.


Peer Reviewed Publications:

  1. Kircik L, Sung JC, Stein-Gold L, Goldenberg G. United States Food and Drug Administration Product Label Changes. J Clin Aesthet Dermatol. 2016; 9(1):39-48.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Hospital Formulary Service® (AHFS). AHFS Drug Information 2017®. Bethesda, MD: American Society of Health-System Pharmacists®; 2017.
  2. DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: Accessed on April 11, 2018.
  3. Frattarelli DA, Galinkin JL, Green TP, et al; American Academy of Pediatrics Committee on Drugs. Off-label use of drugs in children. Pediatrics. 2014; 133(3):563-567.
  4. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium™ (electronic version). For additional information visit the NCCN website: Accessed on April 11, 2018.
  5. U.S. Food and Drug Administration (FDA). Dosage Forms. Last updated on March 2018. Available at: Accessed on May 22, 2018.
  6. U.S. Food and Drug Administration (FDA). Drugs@ FDA Glossary of Terms. Drugs. Available at: Accessed on April 11, 2018.
  7. U.S. Food and Drug Information (FDA). Guidance for Industry: Dosage and Administration Section of Labeling for Human Prescription Drug and Biological Products- Content and Format. March 2010. Available at: Accessed on April 11, 2018.
Websites for Additional Information
  1. U.S. Food and Drug Administration. Drug Information for Consumers. Last updated on December 28, 2017. Available at: Accessed on April 11, 2018.
  2. U.S. National Library of Medicine MedlinePlus. Drugs, Herbs and Supplements. Last updated on April 28, 2015. Available at: Accessed on April 11, 2018.






Medical Policy & Technology Assessment Committee (MPTAC) review.



Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date. Updated References section.



MPTAC review.



Hematology/Oncology Subcommittee review. Updated Description and References sections.



MPTAC review.



Hematology/Oncology Subcommittee review. Initial document development.