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ph-91212

Combination NSAID Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-91212

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
07-01-2025	01-01-2024

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Duexis® (ibuprofen/ famotidine) Tablet*	Relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers, which in the clinical trials was defined as a gastric and/or duodenal ulcer, in patients who are taking ibuprofen for those indications	* Generic available	4
Vimovo® (naproxen/ esomeprazole) Tablet*	Indicated in adult and adolescent patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of arthritis and esomeprazole magnesium to decrease the risk of developing naproxen associated gastric ulcers. The naproxen component of Vimovo is indicated for relief of signs and symptoms of: osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults juvenile idiopathic arthritis (JIA) in adolescent patients The esomeprazole magnesium component of Vimovo is indicated to decrease the risk of developing naproxen-associated gastric ulcers.	* Generic available	1
Yosprala® (aspirin/omeprazole) Tablet	Indicated for patients who require aspirin for secondary prevention of cardiovascular and cerebrovascular events and who are at risk of developing aspirin associated gastric ulcers. The aspirin component of Yosprala is indicated for: Reducing the combined risk of death and nonfatal stroke in patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli Reducing the combined risk of death and nonfatal myocardial infarction (MI) in patients with previous MI or unstable angina pectoris Reducing the combined risk of MI and sudden death in patients with chronic stable angina pectoris Use in patients who have undergone revascularization procedures [coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA)] when there is a pre-existing condition for which aspirin is already indicated The omeprazole component of Yosprala is indicated for decreasing the risk of developing aspirin associated gastric ulcers in patients at risk for developing aspirin-associated gastric ulcers due to age (greater than or equal to 55) or documented history of gastric ulcers.		5

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Clinical Rationale

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, cause considerable morbidity and mortality related to gastric and duodenal mucosal injury. Thus, prevention of NSAID-induced gastrointestinal (GI) toxicity is an important issue. Strategies for gastroprotection during NSAID therapy include supplementation with a synthetic prostaglandin analog (misoprostol), gastric acid suppression (proton pump inhibitors), or the selective use of those NSAIDs least likely to inhibit gastric prostaglandins.(2,3) Per the American College of Gastroenterology (ACG) 2009 practice guidelines on prevention of NSAID-related ulcers, the following are risk factors for developing an NSAID-induced GI ulcer(3):

Age greater than or equal to 65 years
Prior history of peptic, gastric, or duodenal ulcer
History of NSAID-related ulcer
History of clinically significant GI bleeding
Untreated or active H. pylori gastritis
Concurrent use of oral corticosteroids
Concurrent use of anticoagulants
Concurrent use of antiplatelets

Efficacy

Although Vimovo, Duexis, and Yosprala showed statistically significant efficacy over placebo or single NSAID agents, no clinical trials were conducted comparing these combination agents against taking both active ingredients separately but at the same time.(1,4,5)

Safety

Duexis is contraindicated in the following:(4)

History of asthma, urticaria, or allergic reactions after taking aspirin or other NSAIDs
In the setting of coronary artery bypass graft (CABG) surgery
Known hypersensitivity to ibuprofen or famotidine or any components of Duexis
Known hypersensitivity to other H2-receptor antagonists

Duexis carries the following boxed warnings:(4)

Ibuprofen, a component of Duexis, may increase the risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction, and stroke, which can be fatal. The risk may occur early and may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Duexis is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
NSAIDs, including ibuprofen, a component of Duexis, increase the risk of serious gastrointestinal (GI) adverse reactions including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. Reactions can occur at any time without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk.

Vimovo is contraindicated in the following:(1)

Known hypersensitivity to naproxen, esompraole, magnesium, substituted benzimidazoles or to any components of the drug product including omeprazole
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
In the setting of coronary artery bypass graft (CABG) surgery
Patients receiving rilpivirine-containing products

Vimovo carries the following boxed warning:(1)

Naproxen, a component of Vimovo, may cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Vimovo is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
NSAIDs, including naproxen, a component of Vimovo, cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patient with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious gastrointestinal (GI) events.

Yosprala is contraindicated in the following:(5)

History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
In pediatric patients with suspected viral infections, with or without fever, because of the risk of Reye's Syndrome
Known hypersensitivity to aspirin, omeprazole, substituted benzimidazoles, or to any of the excipients of Yosprala
Patients receiving rilpivirine-containing products

REFERENCES

Number	Reference
1	Vimovo prescribing information. Horizon Medicines, LLC. November 2024.
2	Bhatt DL, Scheiman JM, Abraham NS, et al. ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use. J Am Coll Cardiol. 2008;52(18):1502-1519.
3	Lanza FL, Chan FKL, Quigley EMM, et al. American College of Gastroenterology (ACG) Practice Guidelines: Guidelines for Prevention of NSAID-Related Ulcer Complications. Am J Gastroenterol. 2009;104:728–738.
4	Duexis prescribing information. Horizon Medicines, LLC. November 2024.
5	Yosprala prescribing information. Pharmaceutika LTD. November 2024.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

Aspirin/omeprazole er ; Yosprala	aspirin-omeprazole tab delayed release	325-40 MG ; 81-40 MG	M ; N ; O ; Y	M ; N
Duexis	ibuprofen-famotidine tab	800-26.6 MG	M ; N ; O ; Y	O ; Y
Vimovo	naproxen-esomeprazole magnesium tab dr	375-20 MG ; 500-20 MG	M ; N ; O ; Y	O ; Y

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

Aspirin/omeprazole er ; Yosprala	aspirin-omeprazole tab delayed release	325-40 MG ; 81-40 MG	30	Tablets	30	DAYS
Duexis	ibuprofen-famotidine tab	800-26.6 MG	90	Tablets	30	DAYS
Vimovo	naproxen-esomeprazole magnesium tab dr	375-20 MG ; 500-20 MG	60	Tablets	30	DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Aspirin/omeprazole er ; Yosprala	aspirin-omeprazole tab delayed release	325-40 MG ; 81-40 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Duexis	ibuprofen-famotidine tab	800-26.6 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Vimovo	naproxen-esomeprazole magnesium tab dr	375-20 MG ; 500-20 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Aspirin/omeprazole er ; Yosprala	aspirin-omeprazole tab delayed release	325-40 MG ; 81-40 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Duexis	ibuprofen-famotidine tab	800-26.6 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Vimovo	naproxen-esomeprazole magnesium tab dr	375-20 MG ; 500-20 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Target Agent(s) will be approved when ALL of the following are met: ONE of the following: BOTH of the following: ONE of the following: For Duexis or ibuprofen/famotidine requests, the patient has a diagnosis of at least ONE of the following: Rheumatoid arthritis OR Osteoarthritis OR For Vimovo or naproxen/esomeprazole requests, the patient has a diagnosis of at least ONE of the following: Osteoarthritis in adults OR Rheumatoid arthritis in adults OR Ankylosing spondylitis in adults OR Juvenile idiopathic arthritis (JIA) in adolescents weighing greater than or equal to 38 kg AND The patient has at least ONE of the following risk factors for developing NSAID-induced gastrointestinal (GI) ulcers: Age greater than or equal to 65 years Prior history of peptic, gastric, or duodenal ulcer History of NSAID-related ulcer History of clinically significant GI bleeding Untreated or active H. pylori gastritis Concurrent use of oral corticosteroids Concurrent use of anticoagulants Concurrent use of antiplatelets OR For Yosprala or aspirin/omeprazole requests, BOTH of the following: The patient has an indication of use of at least ONE of the following: Reducing the combined risk of death and nonfatal stroke in patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli OR Reducing the combined risk of death and nonfatal myocardial infarction (MI) in patients with previous MI or unstable angina pectoris OR Reducing the combined risk of MI and sudden death in patients with chronic stable angina pectoris OR Use in patients who have undergone revascularization procedures (coronary artery bypass graft [CABG] or percutaneous transluminal coronary angioplasty [PTCA]) when there is a pre-existing condition for which aspirin is already indicated AND The patient has at least ONE of the following risk factors for developing NSAID-induced gastrointestinal (GI) ulcers: Age greater than or equal to 55 years Prior history of peptic, gastric, or duodenal ulcer History of NSAID–related ulcer History of clinically significant GI bleeding Untreated or active H. pylori gastritis Concurrent use of oral corticosteroids Concurrent use of anticoagulants Concurrent use of antiplatelets AND If the patient has an FDA labeled indication, then ONE of the following: The patient’s age is within FDA labeling for the requested indication for the requested agent OR There is support for using the requested agent for the patient’s age for the requested indication AND There is support for why the use of the individual ingredients within the target combination agent, as separate dosage forms, is not clinically appropriate for the patient AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Module

Clinical Criteria for Approval

Target Agent(s) will be approved when ALL of the following are met:

ONE of the following:
1. BOTH of the following:
  1. ONE of the following:
    1. For Duexis or ibuprofen/famotidine requests, the patient has a diagnosis of at least ONE of the following:
      1. Rheumatoid arthritis OR
      2. Osteoarthritis OR
    2. For Vimovo or naproxen/esomeprazole requests, the patient has a diagnosis of at least ONE of the following:
      1. Osteoarthritis in adults OR
      2. Rheumatoid arthritis in adults OR
      3. Ankylosing spondylitis in adults OR
      4. Juvenile idiopathic arthritis (JIA) in adolescents weighing greater than or equal to 38 kg AND
  2. The patient has at least ONE of the following risk factors for developing NSAID-induced gastrointestinal (GI) ulcers:
    1. Age greater than or equal to 65 years
    2. Prior history of peptic, gastric, or duodenal ulcer
    3. History of NSAID-related ulcer
    4. History of clinically significant GI bleeding
    5. Untreated or active H. pylori gastritis
    6. Concurrent use of oral corticosteroids
    7. Concurrent use of anticoagulants
    8. Concurrent use of antiplatelets OR
2. For Yosprala or aspirin/omeprazole requests, BOTH of the following:
  1. The patient has an indication of use of at least ONE of the following:
    1. Reducing the combined risk of death and nonfatal stroke in patients who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli OR
    2. Reducing the combined risk of death and nonfatal myocardial infarction (MI) in patients with previous MI or unstable angina pectoris OR
    3. Reducing the combined risk of MI and sudden death in patients with chronic stable angina pectoris OR
    4. Use in patients who have undergone revascularization procedures (coronary artery bypass graft [CABG] or percutaneous transluminal coronary angioplasty [PTCA]) when there is a pre-existing condition for which aspirin is already indicated AND
  2. The patient has at least ONE of the following risk factors for developing NSAID-induced gastrointestinal (GI) ulcers:
    1. Age greater than or equal to 55 years
    2. Prior history of peptic, gastric, or duodenal ulcer
    3. History of NSAID–related ulcer
    4. History of clinically significant GI bleeding
    5. Untreated or active H. pylori gastritis
    6. Concurrent use of oral corticosteroids
    7. Concurrent use of anticoagulants
    8. Concurrent use of antiplatelets AND
If the patient has an FDA labeled indication, then ONE of the following:
1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
2. There is support for using the requested agent for the patient’s age for the requested indication AND
There is support for why the use of the individual ingredients within the target combination agent, as separate dosage forms, is not clinically appropriate for the patient AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Quantity limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) does NOT exceed the program quantity limit OR The requested quantity (dose) exceeds the program quantity limit AND ONE of the following: BOTH of the following: The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND There is support for therapy with a higher dose for the requested indication OR BOTH of the following: The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR BOTH of the following: The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months

Module

Clinical Criteria for Approval

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

The requested quantity (dose) does NOT exceed the program quantity limit OR
The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
1. BOTH of the following:
  1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
  2. There is support for therapy with a higher dose for the requested indication OR
2. BOTH of the following:
  1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
  2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
3. BOTH of the following:
  1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
  2. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

Commercial _ PS _ Combination_NSAID_PAQL _ProgSum_