Exceptions & Appeals Process Information

Exceptions & Appeals Process Information

Each payer follows a different process when filing exceptions and appeals.

This brochure has been developed to help healthcare providers understand how to work with payers for coverage of medically necessary drug therapies.
Supporting Appropriate Payer Coverage Decisions

Uniform Prescription Drug Prior Authorization Request Forms & Notification Requirements for Health Plans

Some health plans in select states must use their state's Uniform Prior Authorization request form. Please contact Janssen CarePath at 877-CarePath (877-227-3728) for assistance in obtaining prior authorization forms.

Click here to see if your state is included:

Uniform Prior Authorization Information for Select States

The information below provides a summary of each payer's general exceptions and appeals process, which may pertain to services as well as to drugs and products. Some payers provide additional and specific exceptions and appeals information in the individual drug formularies. For this information, refer to the payer's specific drug formulary.

The information provided is not a guarantee of coverage or payment (partial or full). Actual benefits are determined by each plan administrator in accordance with its respective policy and procedures. This information is presented for informational purposes only and is not intended to provide reimbursement or legal advice, nor does it promise or guarantee coverage, levels of reimbursement, payment, or charge. It is not intended to increase or maximize reimbursement by any payer. Laws, regulations, and policies concerning reimbursement are complex and are updated frequently. While we have made an effort to be current as of the issue date of this document, the information may not be as current or comprehensive when you view it. Please refer to the applicable plan's Web site, or contact the plan for more information about coverage or any restrictions or prerequisites that may apply. We strongly recommend you consult the payer organization for its reimbursement policies.

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Exceptions and Appeals Process Information

Click on the payer link to be taken to detailed exceptions and appeals process information.

Aetna has a multilevel Dispute and Appeals process that depends in part on which type of plan the patient has, and in which state the patient resides. The Aetna Web site has instructions with contact information for providers and providers may use a provider area for online submissions. The form for medical exception of drugs is accessible by selecting Rx Medical Exception/Precertification Request Form.

For Medicare, Aetna has a formal Precertification or Exceptions Process in place for requesting a coverage determination which is submitted by either the patient or the provider. Drug clinical policies are available on the Web site so that the provider may be aware of any limitations or restrictions on coverage by reviewing the available policy materials. If the coverage determination/precertification is not approved, then either the patient or the provider may proceed through an appeals or redetermination process.

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Anthem Blue Cross Blue Shield has a provider area linked from the home page of their Web site. Providers can then select the applicable state from the pulldown menu. Medical Policies and Clinical Guidelines are available from the navigation links which detail medical necessity criteria for specific drugs. An online submission form to request a formulary addition is available. Prior Authorization is handled electronically via a secure provider area after login. The Provider Appeals and Billing Disputes and the Member Grievances, Appeals, and Exceptions Information page details the multilevel exceptions and appeals process. The member, his/her representative, or a provider may use this process once an adverse determination review such as a precertification/preauthorization has been made. The provider may submit appeals orally, in writing, or electronically with supporting documentation.

For Medicare, the provider may submit a Medicare Provider Coverage Determination Form to request drug coverage and then, if appropriate when following an adverse determination, may file an appeal. Appeal processing information and forms are located on the Medicare Appeals and Grievances page.

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For Blue Cross and Blue Shield of Alabama commercial plans, call 1-800-216-9920 for general provider pharmacy inquiries. For pharmacy reviews, providers may call the pharmacy review representative at 1-800-206-1048.

For Medicare plans, Blue Cross and Blue Shield of Alabama has posted forms and instructions on its Web site detailing its Medicare Complaints and Appeals process. Drug pharmacy policies are available on the Web site for review. The patient or his/her representative, such as a provider, may apply for a coverage determination on the basis of requesting coverage for a drug not on the formulary, changing a restriction to a drug's coverage, changing coverage for a drug's cost basis, or appealing a previously denied process.

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The Blue Cross and Blue Shield of Florida Web site has posted formularies under Medication Guide for both commercial and Medicare plans. For commercial plans, available prior authorization/exception forms are based on the type of authorization being requested as detailed on the Prescription Drug Forms page. Pharmacy Medical Policies are also available.

For Medicare, select the Medicare drug plan from the Prescription Drug Coverage Determination Criteria and Forms page and click through the approval page to exit the payer's Web site and enter the pharmacy benefit manager's Web site. Drug coverage requests and limitation variances are discussed. Coverage determination and redetermination (appeals) process, contact information and forms are available and may be submitted by the provider.

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Blue Cross and Blue Shield of Illinois commercial plans have separate Claim Review and Appeal processes depending on the type of claim issue to be resolved. The appeals process is used to request a reconsideration review after a denial by the payer's medical management. A provider may then initiate the appeals process by phone or in writing and follow the request with supporting documentation. The member or authorized representative, such as a provider or facility, may request a specific member appeal such as clinical appeal made by a physician, a nonclinical appeal by a nonmedical appeals committee, or an urgent/expedited appeal based on the circumstances of the appeal. The Prior Authorization and Step Therapy Programs page has links to an online prior authorization form and drug criteria.

For Medicare, the appeal process is outlined on the Medicare Coverage Determination and Redetermination page. The provider may submit a Medicare Provider Coverage Determination Form for coverage or submit a request for a Formulary Exception for coverage of a not-on-formulary (not covered) drug or submit a request for a drug to be covered at a lower tier, if available for the member's benefit plan. Then, if appropriate when following an adverse determination, the provider may file an Appeal/Redetermination Form by following the Appeal Instructions that are also provided on a separate page.

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Blue Cross Blue Shield of Massachusetts has a provider page where pharmacy information and forms can be found. The pharmacy page has a medication lookup tool as well as information about requirements for medications administered. There is a forms library where review and appeals assistance is also available.

For Medicare, the Pharmacy Benefits area has links to the current formulary, coverage requirements such as prior authorization and step therapy, and appeals. More information about appeals is available by calling Member Services at 1-800-200-4255.

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Blue Cross Blue Shield of Michigan has a Pharmacy Services page that has the formularies, prior authorization, and Resolving Problems area for commercial plans that addresses benefit inquiries and, if needed, the grievance and appeals process following an adverse benefit decision. The member or provider may initiate an inquiry using the contact information located on the member's ID card, Explanation of Benefits documents, or information provided on the Contact Us page. For an appeals process, information is provided on internal and external review processes and depends on the type of member coverage.

For Medicare, the Appeals, Complaints and Coverage Decisions page states that initially a coverage determination is submitted by either the patient or the provider to request a coverage benefit. If denied, then an appeal or coverage redetermination may be filed according to the process on the Decision Appeals page using the detailed instructions.

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Formulary exceptions are handled by completing the online Request for Prescription Drug Coverage Exception, which is linked from the pharmacy benefit administrator, Prime Therapeutics, in the Prescription Drugs and Pharmacy section of the Forms page on the Blue Cross and Blue Shield of Minnesota Web site.

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Blue Cross and Blue Shield of Montana commercial plans have pharmacy policies, prior authorization criteria, and online prior authorization requests on the Provider Forms And Documents page. In the event of a denial, the provider may follow the instructions on the Claim Review And Appeal page.

The Blue Cross and Blue Shield of Montana Medicare Part D prescription drug plan is linked on the Medicare Plans page under the Compare Plans area. Use the MedicareBlue Rx link to access the payer's Medicare Part D regional Web site, MedicareBlue Solutions, for Medicare Part D coverage information for both group and individual plans. Select the Documents link below to access the formularies, prior authorization criteria, and forms for formulary exceptions, coverage determinations and redeterminations (appeals).

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For Blue Cross and Blue Shield of New Mexico's commercial plans, providers may refer to the Pharmacy Program and the Medical Review Drugs and Criteria pages available online that detail medical necessity, formulary criteria, and prior authorization for specific drugs. An Appeal Request Form is available for providers.

For Medicare, Blue Cross and Blue Shield of New Mexico members may submit a Drug Coverage Determination Form to the contact provided on the Coverage Determination and Redetermination page. Determinations for drug coverage may be based on payment or provisions made by the payer such as requesting a formulary exception or removing a limitation regarding the drug. The Medicare Formulary or Tier Exception Form is available online. Instructions for filing the determination or subsequent appeal form are discussed in the Request for Redetermination of Medicare Prescription Drug Denial document.

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Blue Cross and Blue Shield of North Carolina has an appeals process described on its Provider Appeals pages for Level I appeal. Level I appeals may be used to appeal denials of medical necessity or preauthorization requests. There is an Appeals: Frequently Asked Questions page with answers for members and providers about the levels. The Level I Appeal form is accessible from Forms and Documentation.

Blue Cross and Blue Shield of North Carolina Medicare providers may review the drug formularies, prior authorization, and limitations to determine if a drug determination is required. For redeterminations, the payer has Level I and II Medicare appeals processes that the provider may subsequently submit on the basis of medical necessity. The provider may submit supporting documentation along with the Medicare forms appropriate for each level of appeal.

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For commercial plans, Blue Cross and Blue Shield of Oklahoma has common prescription coverage topics on the Frequently Asked Questions page. For appeals, a Review Request Form is also available from the Health Care Provider Forms page.

For Medicare, Blue Cross and Blue Shield of Oklahoma formularies include information on prior authorization, dispensing limitations or step therapy. Quantity limit or step therapy exception forms are located on the Utilization Management page. Drug Coverage Determination information and forms are available on the payer's site. Determinations for drug coverage may be based on payment or provisions made by the payer such as requesting a formulary exception or removing a limitation regarding the drug.

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For commercial plans, Blue Cross Blue Shield Of Tennessee's Pharmacy Resources and Forms page has links to covered medication, including a physician-administered specialty drug product list and drug prior authorization forms. The prior authorization forms include both a Formulary Exception Request form and the Pharmacy Medication Review Request Form that is submitted with an appeal or along with an exception request.

For Medicare, the payer has a Pharmacy Forms and Documents page that is plan-specific and includes links to the formulary, and the criteria documents for prior authorization, step therapy, and quantity limits. In addition, the payer links to a Request for Medicare Prescription Drug Coverage Determination Form and, if an appeal is needed after a denial, a Request for Redetermination Form is available as well.

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For commercial plans, BlueCross BlueShield of Texas has a Pharmacy Program page that has links to an electronic prior authorization request form, drug lists, step therapy, and prior authorization criteria and specialty drug programs. Contact the payer directly for questions regarding a coverage denial.

For Medicare, BlueCross BlueShield of Texas has an exceptions process in place for requesting a Coverage Determination which can be used to request coverage for a drug not on its formulary or, in limited cases, lower the cost-sharing tier for a drug. The physician must support the request with additional supporting documentation. If the coverage determination is not approved, then the patient or his/her representative, such as the provider, may proceed through an Appeals or Redetermination process.

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CareFirst BlueCross BlueShield has contact information for provider inquiries regarding patient coverage in its Provider Quick Reference Guides. The Pharmacy Prior Authorization page has a drug list also that provides a link to drug prescribing criteria as well. The Formulary Exception Form is available on the Pharmacy Forms page for both brand drugs and limitation exceptions. The Provider Inquiry Resolution Form, linked from the Inquiries & Appeals page, may be used to submit inquiries regarding coverage review rejections and to submit additional supporting materials for medical necessity. There is also a plan-specific Frequently Asked Questions which has pharmacy and appeals information.

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Cigna has an Appeals Policy & Procedures for Health Care Professionals page that has information on a single-level appeal process for a denied authorization. Forms are provided on the Claim Adjust & Appeal Guidelines page for a benefit limitation or exclusion. Benefit inquiries or appeals information is located on the Healthcare Appeals & Grievances page.

For Medicare, Cigna has an appeals process for both standard and expedited appeals which may be submitted by the patient, an appointed representative, or the provider following an adverse coverage decision. A Coverage Determination Request Form is available and may be used to request coverage for a drug that is not covered or to alter a limitation relating the drug's coverage. If a Notice of Denial has not been received, the Coverage Determination Request Form should be submitted first. The Appeals Form, a request for a redetermination of coverage, is submitted by mail or fax to the contact information on the form following an adverse coverage decision.

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For the CVS Caremark commercial formulary, contact the payer using the information on the Pharmacy Help Desk page for exceptions and appeals information. Prescription drug prior authorization information and forms are available online.

For CVS Caremark SilverScript, the Prescription Drug Coverage Determination page discusses the coverage request and approval process. A Medicare coverage determination for a drug can be requested for several reasons including to ask that a drug not on the drug list be covered, to waive a restriction regarding the drug's coverage, to request that a drug's cost-sharing tier be lowered, or to request a prior approval of a drug that has limitations for coverage. A patient or his/her physician or representative may submit a coverage determination request. An appeals process is also in place if a negative coverage determination results.

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EmblemHealth has a provider Pharmacy Services page that contains a link to a Pharmacy Services chapter of the provider manual. The vertical navigation has links to documentation for obtaining specialty or nonpreferred drugs. The Pharmacy Services chapter has information on prior authorization as well as dispute resolution if an appeal is requested following a denial. Medical policies for drugs are available online.

For Medicare, there is a Dispute Resolution process for providers and members to follow once a written adverse determination is made. The initial adverse determination includes instructions for the member or the member's representative, such as a provider, to file an appeal or grievance for both regular and expedited appeals. A reconsideration may be made later by the provider if the original appeal did not include the provider's input. The member or his/her representative, such as a provider, may request a Medicare Coverage Determination to handle drug coverage requests due to medical necessity, formulary exception requests, exception requests from a tier structure, amounts of cost sharing, prior authorization, or utilization management. After a denial, redetermination may be requested in writing with supporting documentation provided by the physician. Both regular and expedited processes are detailed.

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Harvard Pilgrim Health Care has commercial plan appeal information for both members and providers linked on the Appeal page in its Web site. There is a downloadable Provider Appeals Form online, and instructions are in the Provider Appeals Overview document. The Provider Manual has documentation requirements and the specified timeframe for the appeals process. A multi-level appeals process is available for providers and may be made for several specified reasons including denial of preauthorization request. Providers may appeal a denial decision by following the downloadable instructions on the Provider Appeals Overview and submitting a Provider Appeal Form to the contact information provided in the instructions. An Injectable/Infusible Drug Exception Request Form is available for a formulary exception request.

For Medicare Part D, there is a Provider Portal for Medicare Part D plan resources. The Part D Coverage Decisions, Exceptions, Grievances and Appeal Processes page has information on formulary exceptions that may be filed for several reasons, such as to request a drug that is not covered, to reduce the co-pay on a drug that is nonpreferred, or to remove a limitation on a drug such as a quantity limit. An appeal may be filed by the patient or an appointed representative, such as a physician, in case of an adverse coverage determination.

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For Medicare, Health Net has appeals information under its state-based Appeals and Grievances pages. Appeals may be filed once a benefit determination or decision has been made by Health Net. The appeal may be initiated by letter or submitted with a Request for Reconsideration Form linked from the Appeals and Grievances page which may be submitted by using the contact information on the Appeals and Grievances page. For plan-specific information, refer to the particular state Web site that has plan information for the patient's state.

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For commercial Highmark Blue Cross Blue Shield plans, an appeal may be filed on the patient's behalf following an adverse drug coverage determination. Provider-initiated appeals information may be found in the provider manual: Procedural Guide for Providers. Benefit appeals may be filed by phone or in writing. Contact information is provided in the manual. The Formulary Information page has links to payer formularies. There is also a Pharmacy Authorization Submission Process for Physicians document available which describes the electronic drug approval process.

For Medicare, Highmark Blue Cross Blue Shield has a document called Summary of the Highmark's Grievance and Coverage Determination (Exceptions) Process that details the initial coverage determination requests and redeterminations/appeals process. An appeal may follow an initial adverse determination decision.

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Horizon Blue Cross Blue Shield of New Jersey has a provider page where Pharmacy Programs such as Pharmacy Guidelines and Specialty Pharmaceuticals for Office Administration are linked. Pharmacy Guidelines discusses medical necessity determinations, formulary tier exceptions, and prior authorization details. In addition, there is a link to the Medical Injectables Program page that details the medical necessity determination process for specialty injectable drugs and includes a link to prescription drug medical policies.

Horizon's Medicare Prescription (Part D) member page has links to their Medicare Part D drug plan details accessible via the View Plan link. Scroll through the list of plans and select the View Plan Details of the patient's plan, and then the subsequent page's View Additional Plan Documentation link to access the Formulary, Coverage Determination and Redetermination forms, and Appeals and Grievances pages of the payer's Web site. Coverage determinations may be submitted for formulary and tier exceptions.

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For commercial plans, physicians may request a prior authorization or a medical exception for drug coverage using the contact information and Humana forms on the Provider Prior Authorization for Pharmacy Drugs page.

For Medicare, members or his/her representatives, such as a provider, may submit a Medicare Coverage Determination Request Form to handle drug coverage requests online or by phone or fax. Physicians are requested to use the contact information, and forms are available on the Medicare Drug Coverage Determination page. If the coverage determination request results in a denial, a Request for Redetermination of Medicare Prescription Drug Denial may be filed using the form provided with supporting documentation.

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Independence Blue Cross has a Policies & Guidelines area of its Web site that has links to pharmacy information such as formulary, prior authorization, drug and medical policies. Under the Tools and Resources navigation menu is a link to a Forms page that has the Nonformulary Exception Request Form that may be used to request drug coverage. If a denial results, a provider may file an appeal on the patient's behalf by faxing additional supporting documentation according to the For Providers: Frequently Asked Questions page information.

For Medicare, there is a Prior Authorization page that discusses the process for requesting formulary exceptions due to non-coverage of a drug, changing a quantity limit, or requesting a cost-sharing tier change, as well as a Medicare Prescription Drugs page that has links to formularies. The payer also has an Organization Determination, Appeals, and Grievances page that describes requirements for prior authorization, coverage determination, and appeals. There are also downloadable forms to submit these requests.

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For commercial and Medicare Part D coverage, Kaiser Permanente has formulary drugs accessible by first selecting the Health and Wellness link from the home page and then the Drugs and Natural Medicines link. The Formulary link requires that a state or region be selected to access its corresponding formulary. Both Commercial and Medicare formularies can be accessed from the formulary link. A patient can request an exception to the formulary by sending a secure email to his or her provider. An online form can also be submitted to Member Services.

Kaiser Permanente (WA) has appeals process information and forms on the Coverage and Claim Appeals page. There is a formal internal appeals process for review of member coverage and disputes that includes both first-level appeals process and an optional second-level review. There is a downloadable appeals form that a member can mail or fax and an online submission form available as well.

Kaiser Permanente (WA) Medicare formulary exception requests may be made to cover a nonformulary drug or waive a drug's coverage restrictions. The exception may be filed by the member or the member's representative, such as a provider. Information and contact information is located on the Exceptions, Appeals, and Grievances page. The Medicare Prescription Drug Coverage Determination Form is available online. If a coverage determination request is denied, an appeal or redetermination may be submitted using the Request for Redetermination of Medicare Prescription Drug Denial Form.

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Premera Blue Cross has information on prior authorizations, medical policies, and the formulary exceptions process on the Drugs Requiring Approval page. Appeals may be submitted by either the physician or the member patient. Plan-specific drug coverage is located on the Rx Search page. Contact information for the payer regarding drug coverage is located under Pharmacy Services on the Provider Contacts page.

For Medicare, the Part D Pharmacy Resources page has links to the formulary and a discussion on the types of formulary exceptions that may be filed. Exceptions forms and frequently asked questions may be found on the Appeals & Grievances pages under the Part D Coverage Determinations, Exceptions, Appeals and Grievances section.

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Wellmark Blue Cross and Blue Shield has a Provider Drug Information area that has the Wellmark drug list and formulary exception process. Information about the provider Appeals Process is also available. The provider area of its Web site also states that physicians may request an initial medical necessity determination using a Provider Prior Authorization Form for medications. For nonformulary drugs or formulary exception requests, the provider may call Wellmark’s Clinical Call Center at 800-600-8065 or use the CVS/Caremark (benefit administrator) Global Prior Authorization Form. The Formulary Exception Process page details the instructions. Provider Appeals and Inquiries are located in a secured provider area of the site accessible by clicking on the Appeals and Inquiries link under the Provider Claim Review Forms section on the Forms page.

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R3

Indication

DARZALEX® is a CD38-directed cytolytic antibody indicated:

  • in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant
  • in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy
  • in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
  • as monotherapy, for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.
Important Safety Information

CONTRAINDICATIONS

DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion Reactions – DARZALEX® can cause severe and/or serious infusion reactions, including anaphylactic reactions. In clinical trials, approximately half of all patients experienced an infusion reaction. Most infusion reactions occurred during the first infusion and were grade 1-2. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing an infusion. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, laryngeal edema and pulmonary edema. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently discontinue therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Interference with Serological Testing – Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.

Neutropenia – DARZALEX® may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. DARZALEX® dose delay may be required to allow recovery of neutrophils. No dose reduction of DARZALEX® is recommended. Consider supportive care with growth factors.

Thrombocytopenia – DARZALEX® may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. DARZALEX® dose delay may be required to allow recovery of platelets. No dose reduction of DARZALEX® is recommended. Consider supportive care with transfusions.

Interference with Determination of Complete Response – Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Adverse Reactions – The most frequently reported adverse reactions (incidence ≥20%) in clinical trials were: infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy and upper respiratory tract infection.

In patients who received DARZALEX® in combination with bortezomib, melphalan, and prednisone (DVMP), the most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory tract infection (48%), infusion reactions (28%), and peripheral edema (21%). Serious adverse reactions (≥2% compared to the VMP arm) were pneumonia (11%), upper respiratory tract infection (5%), and pulmonary edema (2%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities ≥20% were lymphopenia (58%), neutropenia (44%), and thrombocytopenia (38%).

In patients who received DARZALEX® in combination with lenalidomide and dexamethasone, the most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory tract infection (65%), infusion reactions (48%), diarrhea (43%), fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea (21%) and pyrexia (20%). The overall incidence of serious adverse reactions was 49%. Serious adverse reactions (≥2% compared to Rd) were pneumonia (12%), upper respiratory tract infection (7%), influenza (3%), and pyrexia (3%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities ≥20% were neutropenia (53%) and lymphopenia (52%).

In patients who received DARZALEX® in combination with bortezomib and dexamethasone, the most frequently reported adverse reactions (incidence ≥20%) were: peripheral sensory neuropathy (47%), infusion reactions (45%), upper respiratory tract infection (44%), diarrhea (32%), cough (27%), peripheral edema (22%), and dyspnea (21%). The overall incidence of serious adverse reactions was 42%. Serious adverse reactions (≥2% compared to Vd) were upper respiratory tract infection (5%), diarrhea (2%) and atrial fibrillation (2%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities ≥20% were lymphopenia (48%) and thrombocytopenia (47%).

In patients who received DARZALEX® in combination with pomalidomide and dexamethasone, the most frequent adverse reactions (>20%) were fatigue (50%), infusion reactions (50%), upper respiratory tract infection (50%), cough (43%), diarrhea (38%), constipation (33%), dyspnea (33%), nausea (30%), muscle spasms (26%), back pain (25%), pyrexia (25%), insomnia (23%), arthralgia (22%), dizziness (21%), and vomiting (21%). The overall incidence of serious adverse reactions was 49%. Serious adverse reactions reported in ≥5% patients included pneumonia (7%). Treatment-emergent hematology Grade 3-4 laboratory abnormalities ≥20% were anemia (30%), neutropenia (82%), and lymphopenia (71%).

In patients who received DARZALEX® as monotherapy, the most frequently reported adverse reactions (incidence ≥20%) were: infusion reactions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%), cough (21%), and upper respiratory tract infection (20%). The overall incidence of serious adverse reactions was 33%. The most frequent serious adverse reactions were pneumonia (6%), general physical health deterioration (3%), and pyrexia (3%). Treatment-emergent Grade 3-4 hematology laboratory abnormalities ≥20% were lymphopenia (40%) and neutropenia (20%).

DRUG INTERACTIONS
Effect of Other Drugs on Daratumumab: The coadministration of lenalidomide, pomalidomide or bortezomib with DARZALEX® did not affect the pharmacokinetics of daratumumab.

Effect of Daratumumab on Other Drugs: The coadministration of DARZALEX® with bortezomib or pomalidomide did not affect the pharmacokinetics of bortezomib or pomalidomide.

Please see full Prescribing Information.

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