Drugs and Biologicals, Intended and Off-label Coverage (L33394) (2023)

Document information

numer LCD
L33394

LCD title
Coverage of pharmaceuticals and biologics, intended and off-label uses

Proposed LCD display during commenting period
not applicable

Recommended LCD source
DL33394

original effective date
For services performed from October 1, 2015

Effective date of the change
For services performed on or after January 1, 2022

review completion date
not applicable

retirement date
not applicable

The start date of the notification period
September 15, 2022

End date of the notification period
October 31, 2022

AMA CPT / ADA CDT / AHA NUBC Copyright Notice

Course schedules, relative value units, conversion factors, and/or associated components are not assigned by the AMA, are not part of the CPT, and are not recommended by the AMA. The AMA does not practice medicine or provide medical services, directly or indirectly. AMA is not responsible for the data contained or not contained in this document.

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ask

description of the problem

Off-label/off-label use is defined as use in a non-FDA-approved indication, i.e. an indication that is not listed on the drug's official labeling/prescription information. An indication is defined as a diagnosis, disease, injury, syndrome, condition or other clinical parameter for which a drug can be administered. Off-label use is further defined as administration that deviates significantly from label information for a specific indication. This includes, but is not limited to, the dose, route of administration, duration and frequency of administration, and the population to which the drug will be administered. Off-label drugs may be covered by Medicare if the drug's use is determined to be medically acceptable based on a major drug compendium, authoritative medical literature, and/or accepted standards of practice. Decisions about whether drug therapy is reasonable and necessary for a given patient are made on appeal on the same basis as all other decisions (i.e., supported by peer-reviewed literature, with advice from a medical advisor, against recognized standard medical standards) . practices, taking into account individual medical conditions).

According to Pub 100-02, Chapter 15, Section 50.4.5 D and Pub 100-02, Chapter 15, Section 50.4.5 B, the entries of nivolumab and filgrastim representing 100% of anti-cancer drugs will be removed from this LCD. In addition, the Rituximab and IVIG entries will be removed and become the new LCD. In addition, references and articles related to these four drugs will be removed from the LCD display.

Question - Explanation of the differences between the proposed LCD and the final LCD

not applicable

CMS national coverage policy

Language quoted from the terms and conditions of the Centers for Medicare & Medicaid Services (CMS), National Coverage Determination (NCD), and Interpretive Manuals is italicized throughout the policy. Scope provisions in the NCD and Interpretation Manual are not subject to the LCD review process (42 CFR 405.860[b] and 42 CFR 426 [Part D]). In addition, administrative law judges cannot review the TCD. see art. 1869(f)(1)(A)(i) of the Social Security Act.

Unless stated otherwise,italicsText indicates quotes from one or more of the following CMS sources:

Article XVIII of the Social Security Act (USS):

Section 1862(a)(1)(A) excludes expenses for items or services that are not necessary and reasonable to diagnose or treat a disease or injury or to improve the function of a deformed body member.

Section 1833(e) prohibits Medicare from paying claims that do not contain the information necessary to process the claim.

CMS publications

CMS Publication 100-02,Medicare benefits policy booklet,Chapter 15:

50 - Medicines and biological products

50.4.5 - Off-label use of drugs and biologics in cancer chemotherapy regimens

CMS Publication 100-04,Medicare Claims Handbook,Chapter 17:

10 - Payment Policy for Pharmaceutical and Biological Products

coverage guide

Indications, limitations and/or medical needs

Abstract:

In the case of drugs used in anticancer chemotherapy regimens, off-label use was includedMedicare benefits policy booklet(CMS Publication 100-2, Chapter 15, Section 50.4.5).

In order to meet the necessary requirements for rational drug use and treatment of disease, drugs must be safe and effective. Drugs approved by the Food and Drug Administration (FDA) are considered safe and effective when used for the indications stated on the label. Therefore, Medicare will pay for the use of FDA-approved drugs if:

Was injected on or after the FDA approval date;
it is reasonable and necessary for the individual patient; AND
Meet all other applicable coverage requirements.

Indications:

A medically acceptable indication covered by a national government service is one of the following:

FDA approvals, labeled indications or uses supported by American Hospital Formulary Service (AHFS-DI), NCCN Compendium of Drugs and Biologics, Truven Health Analytics Micromedex DrugDex®, Elsevier/Gold Standard Clinical Pharmacology and Wolters Kluwer Lexi-Drugs® as acceptable pharmacopoeia based on CMS 6191 revision request (the pharmacopoeia serves as the authoritative source for determining the "medically acceptable indication" of drugs and off-label biologic drugs). cancer chemotherapy); or
Articles published by national government services or local coverage findings (LCD).

The above curriculum will be accepted at the following levels;

American Hospital Formulary Service - Drug Information (AHFS-DI) - Guidance is helpful
NCCN Compendium of Drugs and Biologics: Indications are Class 1 or Class 2A
Micromedex DrugDex®: Indications are Class I, IIa or IIb or
CLINICAL PHARMACOLOGY – INDICATIONS ARE SUPPORTIVE
Lexi-Drugs - 'Level A' Rated Indication

When new off-label uses of a drug are published in these pharmacopoeias at recommended acceptable levels, the effective date for coverage by national government services of these off-label uses is the date of publication of our revised information article. , not the date of inclusion in the compendium.

In order to reduce the number of articles related to LCD displays or off-label drug use indications, national government services will publish articles on off-label drugs that require education or concern about their use. These articles will include links to FDA and pharmacopoeia approvals listed in the American Hospital Formulary Service (AHFS), Elsevier/Gold Standard Clinical Pharmacology, NCCN Drug and Biologics Compendium, Truven Health Analytics Micromedex DrugDex® Compendium, and/or Wolters Kluwer Drugs for approval. uses Lexi-Drugs®. Only off-label uses requested by the supplier in accordance with the criteria below will be considered for inclusion.

A supplier may request off-label approval of a medicine by submitting a written request with data to support its use. The data must include:

Clinically supported uses that have emerged from at least two phase III clinical trials that have clearly demonstrated safety and efficacy; or,
If evidence from Phase III trials is not available, at least two Phase II trials are conducted within a reasonable timeframe with large patient samples showing consistent safety and efficacy results, e.g. for rare diseases where Phase II trials may be needed difficult after completion of Phase II trials or when overwhelming evidence of safety and efficacy is observed in Phase II trials.
Applying an accepted standard of medical practice. “Are there any published recommendations from professional associations or other authoritative evidence-based guidelines?” (e.g. recent review articles published in recognized textbooks or reputable journals) It should be noted that even limited HCP acceptance does not generally mean general HCP acceptance in the medical community. Evidence for this limited acceptance, together with limited case studies disseminated by sponsors with potential financial conflicts of interest in the results, is insufficient to demonstrate general acceptance by the medical community. Before drawing any conclusions, the wide range of available evidence should be considered and its quality assessed.

Phase III or II studies must come from different centers and be published in peer-reviewed national or international journals (medical editorial board). Peer-reviewed medical literature includes scientific and medical publications. Does not include abstracts or internal publications of pharmaceutical companies (including conference abstracts).

Basically, the classification of research designs is based on the ability of each category of research designs to minimize bias. Below is a representative list of research designs (some of which have alternative names) ranked methodologically from most to least rigorous, according to their potential ability to minimize bias:

randomized controlled trial
non-randomized controlled trial
prospective cohort study
retrospective case-control study
cross-sectional study
Monitor research (for example, using records or surveys)
ongoing case series and
single case description

Designing, conducting and analyzing the study are also important factors. For example, a well-designed, well-conducted, large-sample observational study is likely to provide stronger evidence than a poorly-designed, poorly-conducted, small-sample randomized controlled trial.

The quality of published evidence should be considered when determining whether there is clinical evidence to support a particular use of a drug. This note includes an evaluation of the following characteristics of the study:

If the number of items is enough;
Response rate;
Impact on key status and survival indicators. That is, effects on patient health and other responses to treatment indicated to be effective (for example, reduction in mortality, morbidity, signs and symptoms);
Adequacy of study design, that is, whether the design of the experiment is appropriate to answer the research question, given the drug and condition being studied. (For example, in some clinical trials, the use of randomized, double-blind, placebo, or crossover may not be necessary or feasible); AND
Disease prevalence and life history by evaluating the adequacy of patient numbers and response rates.

Upon receipt of such evidence, the national government department, with the appropriate assistance of the designated professional advisor, will determine the scope for the non-FDA approved indication (off-label use) of the drug or biologics.

If it is based on existing or provided evidence, if the drug has been shown to be safe and effective and does not violate national or local health insurance decisions and regulations. The approval will include, but is not limited to, diagnosis, dosage and route of administration, duration and frequency, and appropriate patient population.

limit:

Unless specified by the CMS or FDA, or if not specified by the American Hospital Formulary Service (AHFS), Elsevier/Gold Standard Clinical Pharmacology, NCCN Compendium of Drugs and Biologics, Truven Health Analytics Micromedex DrugDex®, and/or Wolters Kluwer Lexi -Drugs ® Compendium, off-label use not allowed, drug not covered.

Regardless of evidence of coverage for a specific off-label use, payment will only be made if the use is reasonable and necessary to treat the specific disease or injury of the patient receiving the drug.

Services related to uninsured services or drugs are also not covered (administrative services, for example).

Once reviewed, if a drug use is not in line with FDA recommendations, it will not appear in the American Hospital Formulary Service (AHFS), Elsevier/Gold Standard Clinical Pharmacology, NCCN Compendium of Drugs and Biologics, Truven Health Analytics Micromedex DrugDex ® and/or Wolters If the compendium Kluwer Lexi-Drugs® or the National Government Service has not published the LCD or off-label article listed below, the drug is not approved and may be refused use. However, a decision on whether drug therapy is reasonable and necessary for an individual patient can be made on appeal on the same basis as all other decisions (i.e., supported by peer-reviewed literature, with the advice of a medical advisor). accepted standards of medical procedure, taking into account the individual medical conditions of the case).

The route of administration must be as rational and necessary as the drug. (Publication 100-02,Medicare benefits policy booklet,Chapter 15, Section 50.2 - Determination of self-administration of drugs or biologics (Rev. 91; Issued: 6/20/08; Effective/Implementation Date: 7/21/08). National government services will use evidence-based clinical guidelines to determine the medical necessity of the route of administration.

Specific drugs and biological coverage

FDA and Pharmacopoeia approved uses

The following drugs include FDA approved uses and compendium approved uses.

Bevacizumab and biosimilars

bortezomib

Denosumab (Prolia™, Xgeva™)

Intra-articular injection of hyaluronic acid

Omalizumab

ranibizumab i aflibercept

FDA, pharmacopoeia and off-label approved

In addition to FDA-approved uses and Pharmacopoeia-approved uses, off-label uses of the following drugs will also be included.

Eculizumab - NGS has approved eculizumab for the treatment of biopsy-proven dense deposit disease.

Sodium Ibandronate - NGS Ibandronate is approved for the treatment of senile osteoporosis in men.

Hideburi Mukashi Sury biosimilars- NGS has approved infliximab in the following cases:

Behcet's disease (BD), also known as Behcet's syndrome, is used in patients who do not respond adequately to initial treatment for clinical symptoms of BD, such as severe eye involvement, major organ involvement, stomach involvement, or nervous system involvement. and resistant cases. joint or mucosal involvement (i.e. painful mouth and genital ulcers).
Pyoderma gangrenosum with concomitant inflammatory bowel disease.
Steroids and other standard treatments for refractory sarcomas.
Severe immune-related colitis that does not respond immediately (within 1 week) to high-dose steroid therapy. A single dose of infliximab is sufficient to resolve immune-related colitis in most patients.

Luteinizing Hormone Releasing Hormone (LHRH) Analogues: Leuprolide Acetate has been approved by the NG for the following uses:

Breast cancer, breast cancer (treatment): palliative care for advanced breast cancer in premenopausal and perimenopausal women
Chronic pelvic pain (6 months or more) due to suspected endometriosis after appropriate pre-treatment assessment (excluding other causes) and failure of initial OC and NSAID treatment; not exceed 3 months
Head and neck cancers - cancers of the salivary glands

Goserelin Acetate: NGS has approved Goserelin Acetate for the following applications:

Treatment of leiomyoma: 3.6 mg per month for the short term (3-6 months).

Paclitaxel (e.g. Taxol®/Abraxane™): Paclitaxel is approved by the NGS for the following uses:

hormone-resistant prostate cancer
Cancer of the renal pelvis and ureter
Rabdomiosarcoma
leiomyosarcoma

Summary of evidence

not applicable

Analysis of the evidence (reasons for the judgment)

not applicable

FAQs

What does it mean when a drug is off-label? ›

Off-label drug use refers to the practice of prescribing a drug for a different purpose than what the FDA approved. This practice is called “off-label” because the drug is being used in a way not described on its package insert.

Learn More ›

What are some examples of off-label drug use? ›

TABLE

Category and drug	Off-label use(s)^a
Isoflurane	Seizure, status epilepticus
Donepezil	Frontotemporal dementia²³
Gabapentin	Bipolar disorder, diabetes, fibromyalgia, neuropathic pain symptoms, headache, hiccups, hot flashes, restless leg syndrome²⁴
Lidocaine	Postherpetic neuralgia²⁴

53 more rows

Show Me More ›

Does Medicare pay for off-label drugs? ›

Drugs used for indications other than those in the approved labeling may be covered under Medicare if it is determined that the use is medically accepted, taking into consideration the major drug compendia, authoritative medical literatures and/or accepted standards of medical practice.

What is off-label use of FDA approved drugs? ›

Off-label prescribing is when a physician gives you a drug that the U.S. Food and Drug Administration (FDA) has approved to treat a condition different than your condition. This practice is legal and common. In fact, one in five prescriptions written today are for off-label use.

Read On ›

Why can doctors prescribe off-label? ›

Off-label prescribing is a common and legal practice in medicine. This practice is justified when scientific evidence suggests the efficacy and safety of a medication for an indication for which it does not have FDA approval and when the practice is supported by expert consensus or practice guidelines.

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What is the difference between off-label and FDA approved? ›

“Off-label” use occurs when an FDA-approved drug or biologic is utilized outside of its approved labeling. IRB oversight is only required when the drug or biologic is being used in a clinical investigation. The FDA has defined “clinical investigation” to be synonymous with “research.”

Do insurance companies cover off-label use? ›

Many insurance companies will not pay for an expensive drug that's used to treat a condition that is not on the approved drug label. When an insurance company denies a medication, an appeal has to be filed. The appeal process is common among all insurance plans: First Appeal.

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Does insurance cover off-label use? ›

Coverage depends on the drug—and what condition your physician prescribes it to treat. Reimbursement for medications prescribed off-label can sometimes be difficult, as insurance companies may be wary of paying out for fraudulent reasons.

Get More Info ›

What are off brand drugs called? ›

What are generic drugs? A generic drug is a medication with the exact same active ingredient as the brand-name drug, is taken the same way and offers the same effect. They do not need to contain the same inactive ingredients as the name-brand product and they can only be sold after the brand-name drug's patent expires.

Read The Full Story ›

What drugs does Medicare not cover? ›

Medicare does not cover:

Drugs used to treat anorexia, weight loss, or weight gain. ...
Fertility drugs.
Drugs used for cosmetic purposes or hair growth. ...
Drugs that are only for the relief of cold or cough symptoms.
Drugs used to treat erectile dysfunction.

More items...

Explore More ›

Why can't Medicare patients get discounts on drugs? ›

Within the pharmaceutical industry, the Anti-Kickback Statute made it a crime for pharmaceutical manufacturers to offer drug coupons to Medicare beneficiaries. This is because it became illegal to influence the purchase of any prescription drugs that Medicare could later reimburse.

Keep Reading ›

Can pharmacists prescribe off-label? ›

Off-label use of drugs will continue to be an integral part of medicine, and pharmacists can continue to dispense drugs for purposes not officially approved by the FDA but based on sound scientific evidence and published literature.

Tell Me More ›

What is the FDA final rule for off-label use? ›

Most significantly, the final rule clarifies that a firm will not be regarded as intending an unapproved new, or off-label, use for a drug or device based solely on that firm's knowledge that the product was prescribed or used by health care providers for the use.

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How many drugs are prescribed off-label? ›

Surveys have shown that approximately 1 in 5 prescriptions in the US are for off-label use. In certain populations of patients, off-label drug use is even higher.

Discover More Details ›

What is the FDA final rule for Labelling? ›

The final rule applies to symbols in the labeling for a device, including its label. Labeling is defined in section 201(m) of the FD&C Act to include "all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying any such article."

Explore More ›

Can all drugs be prescribed off-label? ›

The practice, called "off-label" prescribing, is entirely legal and very common. More than one in five outpatient prescriptions written in the U.S. are for off-label therapies. "Off-label" means the medication is being used in a manner not specified in the FDA's approved packaging label, or insert.

Explore More ›

What is the difference between off-label and on label drugs? ›

A physician prescribing a drug exactly as approved by FDA is doing so on-label. When a physician veers from that path, he or she is prescribing a drug off-label.

Read On ›

What are the FDA rules for off-label promotion? ›

LEGAL STATUS OF OFF-LABEL PROMOTION

Although marketing materials are not permitted to promote additional uses, physicians are free to prescribe any approved drug for any purpose, even a use that the FDA has not approved.

How do you explain off-label use? ›

Off-label means that the person prescribing the medicine wants to use it in a different way than that stated in its licence. This could mean using the medicine for a different condition or a different group of patients, or it could mean a change in the dose or that the medicine is taken in a different way.

See Details ›

Does off-label mean generic? ›

This off-label prescribing is most commonly done with older, generic medications that have found new uses but have not had the formal (and often costly) applications and studies required by the FDA to formally approve the drug for these new indications.

What is off-label or unlicensed use of medicines? ›

An off-label use of a medicine is when a medicine is being used in a way that is different to that described in the product licence. Some examples of off-label uses are: using a medicine for a health condition different to that stated in the licence.

Can doctors prescribe non FDA approved drugs? ›

Although the FDA approves all prescription drugs sold in the United States, the agency can't limit how doctors prescribe drugs after they're on the market. Doctors often direct patients to take medications for conditions that have not been approved by the FDA. This is called off-label drug use.

Know More ›

What things are not covered by insurance? ›

What Healthcare Services Often Aren't Covered?

Adult Dental Services. ...
Vision Services. ...
Hearing Aids. ...
Uncovered Prescription Drugs. ...
Acupuncture and Other Alternative Therapies. ...
Weight Loss Programs and Weight Loss Surgery. ...
Cosmetic Surgery. ...
Infertility Treatment.

More items...

Feb 22, 2023

See Details ›

Does insurance cover non FDA approved treatments? ›

If the drug is not a medication approved for sale and use in the U.S. in humans by the FDA then coverage will not be provided. 5.

Know More ›

What is off-label use of medical products? ›

What is off-label use? A. "Off-label" or physician directed use for prescription drugs, biologics, and approved medical devices means any use that is not specified in the labeling approved by the U.S. Food and Drug Administration (FDA).

Find Out More ›

Does off-label mean unlicensed? ›

Off-label' use means that the medicine has a license for treating some conditions, but that the manufacturer of the medicine has not applied for a license for it to be used to treat your condition.

Discover More Details ›

What are off-label uses for Adderall? ›

Some medical providers prescribe Adderall for unapproved, off-label uses, including anxiety, depression, bipolar depression and weight loss.

Find Out More ›

What are the 4 types of drug names? ›

Chemical, approved and proprietary names. The three main types of name for pharmaceutical substances are the chemical name, the approved (official or generic) name and the proprietary (brand, trade or invented) name (see Table 1).

Learn More Now ›

What are the 3 different names for drugs? ›

A marketed drug has three names: a chemical name, a generic name, and a brand name.

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What are the 4 types of medicine? ›

Types of medicines

Liquid. The active part of the medicine is combined with a liquid to make it easier to take or better absorbed. ...
Tablet. The active ingredient is combined with another substance and pressed into a round or oval solid shape. ...
Capsules. ...
Topical medicines. ...
Suppositories. ...
Drops. ...
Inhalers. ...
Injections.

More items...

Find Out More ›

What is the difference between on label and off-label? ›

A physician prescribing a drug exactly as approved by FDA is doing so on-label. When a physician veers from that path, he or she is prescribing a drug off-label.

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Is off-label drug use ethical? ›

ETHICS OF OFF-LABEL DRUG USE

Drugs used off-label for conditions in which little or no approved treatment indications exist in particular patient populations (such as children, pregnant women or older adults) are highly understudied. Drug safety is a concern in off-label use and continued monitoring is recommended.

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Is off-label drug use common? ›

Surveys have shown that approximately 1 in 5 prescriptions in the US are for off-label use. In certain populations of patients, off-label drug use is even higher. One study found that almost 8 out of 10 children discharged from pediatric hospitals are on at least one off-label drug.

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What is an example of off label marketing? ›

Off-label Marketing

For example, nifedipine was approved to treat blood pressure, but the sales representatives of some companies kept telling doctors that the same drug is also effective at treating migraines.

Learn More ›

What is Adderall off-label called? ›

Generic Adderall

The generic name for the drug in both the tablet and the capsule is amphetamine/dextroamphetamine salts. Generic drugs usually cost less than the brand-name version.

View Details ›

What medications are used off-label for ADHD? ›

6 Nonstimulant ADHD Medications for Children and Adults

Usage.
Nonstimulants for ADHD.
Atomoxetine.
Viloxazine.
Clonidine.
Guanfacine.
Amantadine.
Antidepressants.

More items...

Mar 30, 2022

Read On ›

What type of drug is Adderall that keeps you focused and alert? ›

Adderall is a combination of amphetamine and dextroamphetamine, two central nervous stimulants that improve focus and reduce impulsivity by increasing dopamine and norepinephrine levels in the brain.

Keep Reading ›

Are off-label drugs bad? ›

Off-label prescribing isn't necessarily bad. It can be beneficial, especially when patients have exhausted all other approved options, as may be the case with rare diseases or cancer.

Get More Info Here ›

What percentage of drugs are prescribed off-label? ›

A review of commonly used medications in general office-based practice showed that 21 percent of prescriptions were prescribed for an off-label indication.

Is off-label use intentional or unintentional? ›

Off-label use* Situations where a medicinal product is intentionally used for a medical purpose not in accordance with the authorised product information.

Keep Reading ›