Horizon Inflammation Care Horizon Inflammation Care
For U.S. Healthcare Professionals

DESIGNED TO DELIVER RELIEF WHEN YOUR PATIENTS NEED IT MOST

The only delayed-release prednisone for the treatment of RA and other inflammatory conditions. A bedtime dose of RAYOS (~10 PM) delivers prednisone at an optimal time to coincide with the rise of inflammation (~2 AM).1,2

FOR PATIENTS WITH RA, MORNINGS CAN BE MISERY

Inflammatory symptoms of RA, such as joint pain, swelling, and stiffness, are commonly most severe for patients upon waking.2*

Key cytokines associated with RA inflammation peak in the early morning hours2,3

Chronotherapy—timing the dose of medication to coincide with the nocturnal rise in inflammatory mediators—may be appropriate for patients with certain inflammatory conditions2

GLUCOCORTICOIDS CAN BE TIMED WITH THE OVERNIGHT RISE OF INFLAMMATION3

A study by Arvidson et al. set out to uncover whether chronotherapy could help provide relief from RA inflammation and symptoms.

STUDY OBJECTIVE4:

To test the hypothesis that the timing of prednisolone administration is important in determining its effect on the diurnal inflammatory process in patients with active RA.

ASSESSMENTS (conducted at 7:30 AM)4:

  • Duration of morning stiffness (minutes)
  • Joint pain at rest
  • Joint inflammation severity
  • IL-6 serum levels (pg/L)

STUDY DESIGN:

Study compared baseline with values obtained after 5 days of therapy for the 7:30 AM and 2 AM groups, not between dose groups4

This study did not include treatment with RAYOS delayed-release tablets

IR=immediate release

OVERNIGHT (2 AM) ADMINISTRATION SIGNIFICANTLY REDUCED INFLAMMATION4

STUDY RESULTS4:

2 AM dosing of prednisolone (active prednisone metabolite) resulted in significant decreases in key inflammatory measures4*

*The relative efficacy of delayed-release prednisone compared with immediate-release prednisone has not been established.1

Study compared baseline with values obtained after 5 days of therapy for the 7:30 AM (n=13) and 2 AM (n=13) groups, not between dose groups. P values reflect statistical significance in difference of values between Days 1 and 5 within each dose group.

Although symptom control is improved with 2 AM dosing, it may be inconvenient for patients to wake up to take IR prednisone at that hour3,4

Digital Clock Created with Sketch.

RAYOS IS DESIGNED TO DELIVER PREDNISONE WHEN KEY PROINFLAMMATORY CYTOKINES ARE PEAKING1-3

RAYOS has a unique delayed-release shell that allows for 2 AM prednisone release when taken at bedtime1

REPLAY

Tablets shown are not actual size. For illustration purposes only.

Individualize dosing based on disease severity and patient response. The timing of administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated.

RAYOS can be taken at bedtime to achieve peak plasma concentrations that match the peak in proinflammatory cytokine cycles1

The release of RAYOS coincides with maximal adrenal cortex activity (2 AM–8 AM), thereby minimizing adrenal suppression1,3,5,6

SELECT IMPORTANT SAFETY INFORMATION

  • Corticosteroids can cause hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome and hyperglycemia. Monitor patients for these conditions with chronic use. Taper doses gradually for withdrawal after chronic use

ADDING RAYOS TO STABLE DMARD THERAPY SIGNIFICANTLY IMPROVED CLINICAL RESPONSE1,2

RAYOS significantly improved ACR20 and ACR50 response in only 12 weeks1,2§

CAPRA-2 was a multicenter, double-blind, placebo-controlled, randomized, 12-week study of 350 adult patients with active RA receiving DMARD therapy given either RAYOS or placebo. Primary endpoint was ACR20.

SELECT IMPORTANT SAFETY INFORMATION

  • Corticosteroids can cause elevated blood pressure, salt and water retention and hypokalemia. Monitor blood pressure and sodium, potassium serum levels. RAYOS should be used with caution in patients with a history of recent myocardial infarction, congestive heart failure, hypertension or renal insufficiency

§ACR20 was defined as a 20% improvement in tender or swollen joint count and a 20% improvement in 3 out of 5 of the following: patient’s global assessment, physician’s global assessment, patient’s assessment of pain, degree of disability, and level of acute-phase reactant. ACR50 was defined as a 50% improvement in these criteria.7

WITH RAYOS, MORNINGS CAN BE MEMORABLE AGAIN

Taking RAYOS at ~10 PM shortened the duration of morning stiffness1,2

From a baseline of ~2 hours, patients taking RAYOS + a DMARD had a median relative reduction of 55% in the duration of morning stiffness vs 33% with placebo + a DMARD (P<0.002).1,2

SELECT IMPORTANT SAFETY INFORMATION

  • RAYOS may increase susceptibility to new infection and increase risk of exacerbation, dissemination or reactivation of latent infection. RAYOS may mask signs and symptoms of infection. The rate of infectious complications increases with increasing doses of corticosteroids
55%

reduction in duration
of morning stiffness1,2

When considering low-dose prednisone for your patients with RA, USE AS MUCH AS NECESSARY—BUT AS LITTLE AS POSSIBLE8

Multiple dosing strengths enable small titration increments to reach the lowest dose that will maintain an effective clinical response.

When transitioning your patients with RA from immediate-release prednisone1:

  • Switch to RAYOS at an equivalent milligram dosage
  • Use the lowest dose to maintain clinical response and monitor patients regularly

Reduce gradually if discontinuing long-term or high-dose therapy

DOSING GUIDELINES

RAYOS should be taken once daily, for example, at bedtime1
  • In clinical trials, RAYOS was taken at ~10 PM1
  • Available in 5-, 2- and 1-mg doses1
  • Use the lowest dosage that will maintain an adequate clinical response1
  • Patients already taking a corticosteroid can be switched to the equivalent dose of RAYOS1
RAYOS should be taken
with food1,2
  • In clinical trials, RAYOS was taken with a light meal or snack if more than 2 to 3 hours had passed since the evening meal2
  • RAYOS plasma levels were similar when taken 2.5 hours after a light meal or immediately after dinner1

Important considerations

  • RAYOS tablets should not be broken, divided, or chewed because the delayed release of prednisone is dependent on an intact coating1
  • For missed doses, patients should be told to take the missed dose as soon as they remember. If it is almost time for the next dose, the missed dose should be skipped, and the medicine taken at the next regularly scheduled time. Patients should not take an extra dose to make up for the missed dose1

THE ONLY DELAYED-RELEASE PREDNISONE FOR THE TREATMENT OF RA

Bedtime dosing (~10 PM) delivers prednisone at an optimal time to coincide with the rise of inflammation (~2 AM)1-3

Reduced RA symptoms, including duration of morning stiffness, when added to stable DMARD therapy1,2

Multiple dosage strengths for small titration increments1

Once-a-day, bedtime dosing1

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FOR YOUR OA OR RA PATIENTS

Powerful relief + built-in gastroprotection

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FOR YOUR OA KNEE PAIN PATIENTS

Targeted pain relief + reduced systemic exposure of a topical

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INDICATIONS AND IMPORTANT SAFETY INFORMATION


RAYOS® (PREDNISONE) DELAYED-RELEASE TABLETS INDICATIONS AND USAGE

RAYOS is a corticosteroid indicated:

  • As an anti-inflammatory or immunosuppressive agent for certain allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, specific infectious diseases or conditions and organ transplantation
  • For the treatment of certain endocrine conditions
  • For palliation of certain neoplastic conditions

RAYOS® (PREDNISONE) DELAYED-RELEASE TABLETS IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • Known hypersensitivity to prednisone or any excipients in the formulation

WARNINGS AND PRECAUTIONS

  • Corticosteroids can cause hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome and hyperglycemia. Monitor patients for these conditions with chronic use. Taper doses gradually for withdrawal after chronic use
  • RAYOS may increase susceptibility to new infection and increase risk of exacerbation, dissemination or reactivation of latent infection. RAYOS may mask signs and symptoms of infection. The rate of infectious complications increases with increasing doses of corticosteroids
  • Corticosteroids can cause elevated blood pressure, salt and water retention and hypokalemia. Monitor blood pressure and sodium, potassium serum levels. RAYOS should be used with caution in patients with a history of recent myocardial infarction, congestive heart failure, hypertension or renal insufficiency
  • There is an increased risk of gastrointestinal (GI) perforation in patients with certain GI disorders. RAYOS may mask signs and symptoms of GI perforation
  • Corticosteroid use may be associated with behavioral and mood disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression and psychosis. Existing conditions may be aggravated
  • Corticosteroid use may lead to inhibition of bone growth in children and adolescents and the development of osteoporosis at any age. Give special consideration to patients at increased risk of osteoporosis (eg, postmenopausal women) before initiating corticosteroid therapy, and bone density should be monitored in patients on long-term corticosteroid therapy
  • Prolonged use of corticosteroids may result in cataracts, infections and glaucoma. Monitor intraocular pressure if corticosteroid therapy is continued for more than 6 weeks
  • Do not administer live or attenuated vaccines to patients receiving immunosuppressive doses of corticosteroids
  • Long‐term use of corticosteroids can have negative effects on growth and development in children. Monitor pediatric patients on long‐term corticosteroid therapy
  • Corticosteroids can cause fetal harm, including a small but inconsistent risk of orofacial clefts during the first trimester. Advise pregnant women of potential harm to the fetus
  • Prednisolone has been found in human milk following administration to lactating women; use the lowest dose in lactating women to achieve desired clinical effect

ADVERSE REACTIONS

  • Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain

Please see full Prescribing Information.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.

DUEXIS® (IBUPROFEN AND FAMOTIDINE) SELECT IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 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.
  • DUEXIS® (ibuprofen and famotidine) is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

  • NSAIDs cause an increased risk of serious gastrointestinal (GI) 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 patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

DUEXIS® (IBUPROFEN AND FAMOTIDINE) INDICATIONS AND USAGE

DUEXIS® (ibuprofen and famotidine), a combination of the NSAID ibuprofen and the histamine H2-receptor antagonist famotidine, is indicated for the 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. The clinical trials primarily enrolled patients less than 65 years of age without a prior history of gastrointestinal ulcer. Controlled trials do not extend beyond 6 months.

DUEXIS® (IBUPROFEN AND FAMOTIDINE) IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • DUEXIS is contraindicated in patients:
    • With a known hypersensitivity to ibuprofen or famotidine or any components of the drug product or known hypersensitivity to other H2-receptor antagonists
    • Who have a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Fatal anaphylactic reactions to NSAIDs have been reported in such patients
    • In the setting of coronary artery bypass graft (CABG) surgery

WARNINGS AND PRECAUTIONS

  • Use ibuprofen at the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
  • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as DUEXIS, increases the risk of serious GI events.
  • Elevation of one or more liver tests may occur during therapy with NSAIDs. DUEXIS should be discontinued immediately if clinical signs and symptoms consistent with liver disease develop.
  • Hypertension can occur with NSAID treatment. Monitor blood pressure closely with DUEXIS treatment.
  • Avoid use of DUEXIS in patients with severe heart failure unless benefits are expected to outweigh the risk.
  • Discontinue DUEXIS if active and clinically significant bleeding from any source occurs.
  • Long-term administration of NSAIDs can result in renal papillary necrosis, other renal injury, and renal toxicity. Use DUEXIS with caution in patients at greatest risk of this reaction.
  • DUEXIS is not recommended in patients with creatinine clearance <50 mL/min.
  • Anaphylactic reactions may occur in patients with or without known hypersensitivity to DUEXIS and in patients with aspirin-sensitive asthma.
  • DUEXIS can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Discontinue use at first appearance of skin rash or any other sign of hypersensitivity.
  • Anemia has occurred in NSAID-treated patients. Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.
  • Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen, which is a component of DUEXIS.
  • See full Prescribing Information for a list of clinically important drug interactions.

ADVERSE REACTIONS

  • The most common adverse reactions in the pivotal trials (≥1% and greater than ibuprofen alone) were nausea, diarrhea, constipation, upper abdominal pain, and headache.

USE IN SPECIFIC POPULATIONS

  • DUEXIS should not be used in pregnant or lactating women. Consider withdrawal of NSAIDs, including DUEXIS, in women who have difficulties conceiving or who are undergoing investigation of infertility.
  • Safety and efficacy of DUEXIS in pediatric patients has not been established.

For further information on DUEXIS, please see full Prescribing Information, including Boxed Warning and the Medication Guide.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.

PENNSAID® (DICLOFENAC SODIUM TOPICAL SOLUTION) 2% W/W (PENNSAID 2%) SELECT IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 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.
  • PENNSAID® (diclofenac sodium topical solution) 2% w/w (PENNSAID 2%) is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

  • NSAIDs cause an increased risk of serious gastrointestinal (GI) 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 patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

PENNSAID® (DICLOFENAC SODIUM TOPICAL SOLUTION) 2% W/W (PENNSAID 2%) INDICATIONS AND USAGE

PENNSAID® (diclofenac sodium topical solution) 2% w/w (PENNSAID 2%) is a nonsteroidal anti-inflammatory drug indicated for the treatment of the pain of osteoarthritis of the knee(s).

PENNSAID® (DICLOFENAC SODIUM TOPICAL SOLUTION) 2% W/W (PENNSAID 2%) IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • PENNSAID is contraindicated in patients:
    • With a known hypersensitivity to diclofenac or any components of the drug product
    • Who have a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Fatal anaphylactic reactions to NSAIDs have been reported in such patients
    • In the setting of coronary artery bypass graft (CABG) surgery

WARNINGS AND PRECAUTIONS

  • Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
  • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as PENNSAID, increases the risk of serious GI events.
  • Elevation of one or more liver tests may occur during therapy with NSAIDs. Measure transaminases at baseline and periodically in patients receiving long-term therapy with PENNSAID. PENNSAID should be discontinued immediately if abnormal liver tests persist or worsen or if clinical signs and/or symptoms consistent with liver disease develop.
  • Hypertension can occur with NSAID treatment. Monitor blood pressure closely with PENNSAID treatment.
  • Avoid use of PENNSAID in patients with severe heart failure unless benefits are expected to outweigh the risk.
  • Long-term administration of NSAIDs can result in renal papillary necrosis, other renal injury, and renal toxicity. Use PENNSAID with caution in patients at greatest risk of this reaction.
  • Anaphylactic reactions may occur in patients with or without known hypersensitivity to PENNSAID and in patients with aspirin-sensitive asthma.
  • PENNSAID can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Discontinue use at first appearance of skin rash or any other sign of hypersensitivity.
  • Anemia has occurred in NSAID-treated patients. Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.
  • Do not:
    • Apply PENNSAID to open wounds
    • Shower for at least 30 minutes after applying PENNSAID
    • Wear clothing over the PENNSAID treated knee(s) until the treated knee(s) is dry
  • Do:
    • Wash and dry hands before and after use. Avoid contact of PENNSAID with the eyes and mucous membranes
    • Protect treated knee(s) from natural or artificial sunlight
    • Wait until the treated knee(s) is completely dry before applying sunscreen, insect repellent, lotion, moisturizer, cosmetics, or other topical medication
  • Concurrent use with oral NSAIDs should be avoided unless benefit outweighs risk and periodic laboratory evaluations are conducted.
  • See full Prescribing Information for a list of clinically important drug interactions.

ADVERSE REACTIONS

  • The most common adverse reactions to PENNSAID 1.5% or PENNSAID 2% in clinical trials were: application site reactions such as dryness, exfoliation, erythema, pruritus, pain, induration, rash, scabbing, contact dermatitis characterized by skin erythema and induration, contact dermatitis with vesicles; urinary tract infection; contusion; sinus congestion; nausea; dyspepsia; abdominal pain; flatulence; diarrhea; constipation; edema.

USE IN SPECIFIC POPULATIONS

  • PENNSAID should not be used in pregnant or lactating women. Consider withdrawal of NSAIDs, including PENNSAID, in women who have difficulties conceiving or who are undergoing investigation of infertility.
  • Safety and efficacy of PENNSAID in pediatric patients has not been established.

For further information on PENNSAID, please see full Prescribing Information, including Boxed Warning and the Medication Guide.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.

REFERENCES

  1. RAYOS (prednisone) delayed-release tablets [prescribing information] Horizon.
  2. Buttgereit F, Mehta D, Kirwan J, et al. Low dose prednisone chronotherapy for rheumatoid arthritis: a randomized clinical trial (CAPRA-2). Ann Rheum Dis. 2013;72(2):204-210.
  3. Cutolo M, Masi AT. Circadian rhythms and arthritis. Rheum Dis Clin North Am. 2005;31(1):115-129.
  4. Arvidson NG, Gudbjörnsson B, Larsson A, Hällgren R. The timing of glucocorticoid administration in rheumatoid arthritis. Ann Rheum Dis. 1997;56(1):27-31.
  5. Cutolo M. Chronobiology and the treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2012;24(3):312-318.
  6. Ohdo S. Chronotherapeutic strategy: Rhythm monitoring, manipulation and disruption. Adv Drug Deliv Rev. 2010;62(9-10):859-875.
  7. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002;46(2):328-346.
  8. Buttgereit F, Burmester GR, Lipworth BJ. Optimised glucocorticoid therapy: the sharpening of an old spear. Lancet. 2005;365(9461):801-803.

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INDICATIONS AND IMPORTANT SAFETY INFORMATION


RAYOS® (PREDNISONE) DELAYED-RELEASE TABLETS INDICATIONS AND USAGE

RAYOS is a corticosteroid indicated:

  • As an anti-inflammatory or immunosuppressive agent for certain allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, specific infectious diseases or conditions and organ transplantation
  • For the treatment of certain endocrine conditions
  • For palliation of certain neoplastic conditions

RAYOS® (PREDNISONE) DELAYED-RELEASE TABLETS IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • Known hypersensitivity to prednisone or any excipients in the formulation

WARNINGS AND PRECAUTIONS

  • Corticosteroids can cause hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome and hyperglycemia. Monitor patients for these conditions with chronic use. Taper doses gradually for withdrawal after chronic use
  • RAYOS may increase susceptibility to new infection and increase risk of exacerbation, dissemination or reactivation of latent infection. RAYOS may mask signs and symptoms of infection. The rate of infectious complications increases with increasing doses of corticosteroids
  • Corticosteroids can cause elevated blood pressure, salt and water retention and hypokalemia. Monitor blood pressure and sodium, potassium serum levels. RAYOS should be used with caution in patients with a history of recent myocardial infarction, congestive heart failure, hypertension or renal insufficiency
  • There is an increased risk of gastrointestinal (GI) perforation in patients with certain GI disorders. RAYOS may mask signs and symptoms of GI perforation
  • Corticosteroid use may be associated with behavioral and mood disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression and psychosis. Existing conditions may be aggravated
  • Corticosteroid use may lead to inhibition of bone growth in children and adolescents and the development of osteoporosis at any age. Give special consideration to patients at increased risk of osteoporosis (eg, postmenopausal women) before initiating corticosteroid therapy, and bone density should be monitored in patients on long-term corticosteroid therapy
  • Prolonged use of corticosteroids may result in cataracts, infections and glaucoma. Monitor intraocular pressure if corticosteroid therapy is continued for more than 6 weeks
  • Do not administer live or attenuated vaccines to patients receiving immunosuppressive doses of corticosteroids
  • Long‐term use of corticosteroids can have negative effects on growth and development in children. Monitor pediatric patients on long‐term corticosteroid therapy
  • Corticosteroids can cause fetal harm, including a small but inconsistent risk of orofacial clefts during the first trimester. Advise pregnant women of potential harm to the fetus
  • Prednisolone has been found in human milk following administration to lactating women; use the lowest dose in lactating women to achieve desired clinical effect

ADVERSE REACTIONS

  • Common adverse reactions for corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain

Please see full Prescribing Information.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.

DUEXIS® (IBUPROFEN AND FAMOTIDINE) SELECT IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 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.
  • DUEXIS® (ibuprofen and famotidine) is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

  • NSAIDs cause an increased risk of serious gastrointestinal (GI) 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 patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

DUEXIS® (IBUPROFEN AND FAMOTIDINE) INDICATIONS AND USAGE

DUEXIS® (ibuprofen and famotidine), a combination of the NSAID ibuprofen and the histamine H2-receptor antagonist famotidine, is indicated for the 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. The clinical trials primarily enrolled patients less than 65 years of age without a prior history of gastrointestinal ulcer. Controlled trials do not extend beyond 6 months.

DUEXIS® (IBUPROFEN AND FAMOTIDINE) IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • DUEXIS is contraindicated in patients:
    • With a known hypersensitivity to ibuprofen or famotidine or any components of the drug product or known hypersensitivity to other H2-receptor antagonists
    • Who have a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Fatal anaphylactic reactions to NSAIDs have been reported in such patients
    • In the setting of coronary artery bypass graft (CABG) surgery

WARNINGS AND PRECAUTIONS

  • Use ibuprofen at the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
  • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as DUEXIS, increases the risk of serious GI events.
  • Elevation of one or more liver tests may occur during therapy with NSAIDs. DUEXIS should be discontinued immediately if clinical signs and symptoms consistent with liver disease develop.
  • Hypertension can occur with NSAID treatment. Monitor blood pressure closely with DUEXIS treatment.
  • Avoid use of DUEXIS in patients with severe heart failure unless benefits are expected to outweigh the risk.
  • Discontinue DUEXIS if active and clinically significant bleeding from any source occurs.
  • Long-term administration of NSAIDs can result in renal papillary necrosis, other renal injury, and renal toxicity. Use DUEXIS with caution in patients at greatest risk of this reaction.
  • DUEXIS is not recommended in patients with creatinine clearance <50 mL/min.
  • Anaphylactic reactions may occur in patients with or without known hypersensitivity to DUEXIS and in patients with aspirin-sensitive asthma.
  • DUEXIS can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Discontinue use at first appearance of skin rash or any other sign of hypersensitivity.
  • Anemia has occurred in NSAID-treated patients. Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.
  • Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen, which is a component of DUEXIS.
  • See full Prescribing Information for a list of clinically important drug interactions.

ADVERSE REACTIONS

  • The most common adverse reactions in the pivotal trials (≥1% and greater than ibuprofen alone) were nausea, diarrhea, constipation, upper abdominal pain, and headache.

USE IN SPECIFIC POPULATIONS

  • DUEXIS should not be used in pregnant or lactating women. Consider withdrawal of NSAIDs, including DUEXIS, in women who have difficulties conceiving or who are undergoing investigation of infertility.
  • Safety and efficacy of DUEXIS in pediatric patients has not been established.

For further information on DUEXIS, please see full Prescribing Information, including Boxed Warning and the Medication Guide.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.

PENNSAID® (DICLOFENAC SODIUM TOPICAL SOLUTION) 2% W/W (PENNSAID 2%) SELECT IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) 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.
  • PENNSAID® (diclofenac sodium topical solution) 2% w/w (PENNSAID 2%) is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

  • NSAIDs cause an increased risk of serious gastrointestinal (GI) 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 patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

PENNSAID® (DICLOFENAC SODIUM TOPICAL SOLUTION) 2% W/W (PENNSAID 2%) INDICATIONS AND USAGE

PENNSAID® (diclofenac sodium topical solution) 2% w/w (PENNSAID 2%) is a nonsteroidal anti-inflammatory drug indicated for the treatment of the pain of osteoarthritis of the knee(s).

PENNSAID® (DICLOFENAC SODIUM TOPICAL SOLUTION) 2% W/W (PENNSAID 2%) IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • PENNSAID is contraindicated in patients:
    • With a known hypersensitivity to diclofenac or any components of the drug product
    • Who have a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Fatal anaphylactic reactions to NSAIDs have been reported in such patients
    • In the setting of coronary artery bypass graft (CABG) surgery

WARNINGS AND PRECAUTIONS

  • Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
  • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as PENNSAID, increases the risk of serious GI events.
  • Elevation of one or more liver tests may occur during therapy with NSAIDs. Measure transaminases at baseline and periodically in patients receiving long-term therapy with PENNSAID. PENNSAID should be discontinued immediately if abnormal liver tests persist or worsen or if clinical signs and/or symptoms consistent with liver disease develop.
  • Hypertension can occur with NSAID treatment. Monitor blood pressure closely with PENNSAID treatment.
  • Avoid use of PENNSAID in patients with severe heart failure unless benefits are expected to outweigh the risk.
  • Long-term administration of NSAIDs can result in renal papillary necrosis, other renal injury, and renal toxicity. Use PENNSAID with caution in patients at greatest risk of this reaction.
  • Anaphylactic reactions may occur in patients with or without known hypersensitivity to PENNSAID and in patients with aspirin-sensitive asthma.
  • PENNSAID can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Discontinue use at first appearance of skin rash or any other sign of hypersensitivity.
  • Anemia has occurred in NSAID-treated patients. Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.
  • Do not:
    • Apply PENNSAID to open wounds
    • Shower for at least 30 minutes after applying PENNSAID
    • Wear clothing over the PENNSAID treated knee(s) until the treated knee(s) is dry
  • Do:
    • Wash and dry hands before and after use. Avoid contact of PENNSAID with the eyes and mucous membranes
    • Protect treated knee(s) from natural or artificial sunlight
    • Wait until the treated knee(s) is completely dry before applying sunscreen, insect repellent, lotion, moisturizer, cosmetics, or other topical medication
  • Concurrent use with oral NSAIDs should be avoided unless benefit outweighs risk and periodic laboratory evaluations are conducted.
  • See full Prescribing Information for a list of clinically important drug interactions.

ADVERSE REACTIONS

  • The most common adverse reactions to PENNSAID 1.5% or PENNSAID 2% in clinical trials were: application site reactions such as dryness, exfoliation, erythema, pruritus, pain, induration, rash, scabbing, contact dermatitis characterized by skin erythema and induration, contact dermatitis with vesicles; urinary tract infection; contusion; sinus congestion; nausea; dyspepsia; abdominal pain; flatulence; diarrhea; constipation; edema.

USE IN SPECIFIC POPULATIONS

  • PENNSAID should not be used in pregnant or lactating women. Consider withdrawal of NSAIDs, including PENNSAID, in women who have difficulties conceiving or who are undergoing investigation of infertility.
  • Safety and efficacy of PENNSAID in pediatric patients has not been established.

For further information on PENNSAID, please see full Prescribing Information, including Boxed Warning and the Medication Guide.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.