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Medicines Overview

At Horizon Pharma plc, our focus is to improve patients’ lives by identifying, acquiring and commercializing differentiated medicines that address unmet medical needs. The company markets a portfolio of medicines through its orphan, rheumatology and primary care business units.

Orphan

Actimmune(R)


Buphenyl(R)


PROCYSBI


Ravicti(R)

Rheumatology

Rayos(R)


KRYSTEXXA

Primary Care

Duexis(R)


MIGERGOT


PENNSAID(R)


vimovoLogo290

ACTIMMUNE Important Safety Information

ACTIMMUNE is contraindicated in patients who develop or have known hypersensitivity to interferon-gamma, E. coli-derived products, or any component of the product.

The most common adverse experiences occurring with ACTIMMUNE therapy are “flu like”, or constitutional symptoms such as fever, headache, chills, myalgia, or fatigue, which may decrease in severity as treatment continues. Some of the “flu-like” symptoms may be minimized by bedtime administration of ACTIMMUNE. Acetaminophen may be used to prevent or partially alleviate the fever and headache.

Reversible neutropenia and thrombocytopenia have been observed during ACTIMMUNE therapy. Caution should be exercised when administering ACTIMMUNE in patients with myelosuppression or in combination with other potentially myelosuppressive agents. ACTIMMUNE may also depress hepatic metabolism of certain drugs that are metabolized by the hepatic cytochrome P-450 system. ACTIMMUNE has not been tested for carcinogenic potential. ACTIMMUNE is pregnancy Category C and it is unknown if ACTIMMUNE is excreted in human milk.

Reversible elevations of AST and/or ALT have been observed during ACTIMMUNE therapy. Patients begun on ACTIMMUNE therapy before one year of age should receive monthly assessments of liver function. If severe hepatic enzyme elevations develop, ACTIMMUNE dosage should be modified.

At doses 10 times greater than the weekly recommended dose, ACTIMMUNE may exacerbate pre-existing cardiac conditions or may cause reversible neurological effects such as decreased mental status, gait disturbance and dizziness. Therefore, caution is advised when ACTIMMUNE is administered to patients with seizure disorders or compromised CNS function or when administered to patients with cardiac conditions such as ischemia, heart failure or arrhythmia.

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

For more information on ACTIMMUNE, please see the Full Prescribing Information.

BUPHENYL Important Safety Information

CONTRAINDICATIONS:

  • BUPHENYL should not be used to manage acute hyperammonemia, which is a medical emergency.

WARNINGS AND PRECAUTIONS:

  • Use with great care, if at all, in patients with congestive heart failure or severe renal insufficiency, and in clinical states in which there is sodium retention with edema.
  • Use caution when administering BUPHENYL to patients with hepatic or renal insufficiency or inborn errors of beta oxidation.
  • Probenecid may affect renal excretion of the conjugated product of BUPHENYL as well as its metabolite.
  • Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels.
  • BUPHENYL should not be administered to patients with known hypersensitivity to sodium phenylbutyrate or any component of this preparation.
  • There have been published reports of hyperammonemia being induced by haloperidol and by valproic acid.

ADVERSE REACTIONS:

The assessment of clinical adverse events came from 206 patients treated with sodium phenylbutyrate. Adverse events (both clinical and laboratory) were not collected systematically in these patients, but were obtained from patient-visit reports by the 65 co-investigators.

  • In female patients, the most common clinical adverse event reported was amenorrhea/menstrual dysfunction (occurring in 23% of the menstruating patients).
  • Decreased appetite, body odor (probably caused by the metabolite PAA), and bad taste or taste aversion were each reported in 4%, 3%, and 3% of patients, respectively.
  • Neurotoxicity was reported in cancer patients receiving intravenous phenylacetate. Manifestations were predominately somnolence, fatigue, and lightheadedness; with less frequent headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of a pre-existing neuropathy.
  • Laboratory adverse events occurring in >2% of UCD patients by body system were:
    • Metabolic: acidosis, alkalosis, hyperchloremia, and hypophosphatemia
    • Nutritional: hypoalbuminemia and decreased total protein
    • Hepatic: increased alkaline phosphatase and increased liver transaminases
    • Hematologic: anemia, leukopenia, leukocytosis, and thrombocytopenia

USE IN SPECIAL POPULATIONS:

  • Pregnancy Category C: It is not known whether BUPHENYL can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. BUPHENYL should be given to a pregnant woman only if clearly needed. A voluntary patient registry will include evaluation of pregnancy outcomes in patients with UCDs. For more information regarding the registry program, visit www.ucdregistry.com or call 1-855-823-2595.
  • Nursing mothers: It is not known whether BUPHENYL is excreted in human milk. Caution should be exercised when BUPHENYL is administered to a nursing woman.
  • Pediatric use: The use of tablets for neonates, infants, and children to the weight of 20 kg is not recommended.

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

Please review Full Prescribing Information and Patient Package Insert.

PROSCYBI Important Safety Information

CONTRAINDICATIONS:

  • Hypersensitivity to penicillamine or cysteamine.

WARNINGS AND PRECAUTIONS:

  • Ehlers-Danlos-like Syndrome: Skin and bone lesions that resemble clinical findings for Ehlers-Danlos-like syndrome have been reported in patients treated with high doses of immediate-release cysteamine bitartrate or other cysteamine salts.
    • These include molluscoid pseudotumors (purplish hemorrhagic lesions), skin striae, bone lesions (including osteopenia, compression fractures, scoliosis and genu valgum), leg pain, and joint hyperextension.
    • One patient on immediate-release cysteamine bitartrate with serious skin lesions subsequently died of acute cerebral ischemia with marked vasculopathy.
    • Monitor patients for development of skin or bone lesions and interrupt PROCYSBI dosing if patients develop these lesions. PROCYSBI may be restarted at a lower dose under close supervision, then slowly increase to the appropriate therapeutic dose.
  • Skin Rash: Severe skin rashes such as erythema multiforme bullosa or toxic epidermal necrolysis have been reported in patients receiving immediate-release cysteamine bitartrate. If severe skin rashes develop, permanently discontinue use of PROCYSBI.
  • Gastrointestinal Ulcers and Bleeding: Gastrointestinal (GI) ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate.
    • GI tract symptoms including nausea, vomiting, anorexia and abdominal pain, sometimes severe, have been associated with cysteamine. If severe GI tract symptoms develop, consider decreasing the dose of PROCYSBI.
  • Central Nervous System Symptoms: Central Nervous System (CNS) symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with immediate-release cysteamine.
    • Neurological complications have also been described in some patients with cystinosis who have not been treated with cysteamine.
    • Carefully evaluate and monitor patients who develop CNS symptoms. Interrupt medication or adjust the dose as necessary for patients with severe symptoms or with symptoms that persist or progress.
    • Inform patients that PROCYSBI may impair their ability to perform tasks such as driving or operating machinery.
  • Leukopenia and/or Elevated Alkaline Phosphatase Levels: Cysteamine has been associated with reversible leukopenia and elevated alkaline phosphatase levels. Monitor white blood cell counts and alkaline phosphatase levels. If tests values remain elevated, consider decreasing the dose or discontinuing the drug until values revert to normal.
  • Benign Intracranial Hypertension: Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema has been reported in patients receiving immediate- release cysteamine bitartrate treatment.
    • Monitor patients for signs and symptoms of PTC, including headache, tinnitus, dizziness, nausea, diplopia, blurry vision, loss of vision, pain behind the eye or pain with eye movement. If signs/symptoms persist, interrupt dosing or decrease the dose and refer the patient to an ophthalmologist. If the diagnosis is confirmed, permanently discontinue use of PROCYSBI.

ADVERSE REACTIONS:

The most common adverse reactions (≥5%) in patients treated in clinical trials are vomiting, nausea, abdominal pain, breath odor, diarrhea, skin odor, fatigue, rash, and headache.

DRUG INTERACTIONS:

  • PROCYSBI should be administered at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate.
  • Consumption of alcohol with PROCYSBI may increase the rate of cysteamine release and/or adversely alter the pharmacokinetic properties, as well as the effectiveness and safety of PROCYSBI.
  • PROCYSBI can be administered with electrolyte (except bicarbonate) and mineral replacements necessary for management of Fanconi Syndrome as well as vitamin D and thyroid hormone.

USE IN SPECIFIC POPULATIONS:

Lactation: Breastfeeding is not recommended while taking PROCYSBI

Please see the Full Prescribing Information at www.PROCYSBI.com.

To report SUSPECTED ADVERSE REACTIONS, contact Raptor Pharmaceuticals Inc. at 1-855-888-4004 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

RAVICTI Important Safety Information

LIMITATIONS OF USE:

  • RAVICTI is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels
  • The safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established

CONTRAINDICATIONS:

  • In patients less than 2 months of age
  • In patients who develop or have known hypersensitivity to phenylbutyrate

WARNINGS AND PRECAUTIONS:

  • Phenylacetate (PAA), the major metabolite of RAVICTI, may be toxic at levels ≥500 µg/mL. Reduce RAVICTI dosage if symptoms of neurotoxicity, including vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or other intercurrent illnesses.
  • Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion of RAVICTI and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely.
  • RAVICTI should be used with caution in patients who are pregnant or planning to become pregnant. Based on animal data RAVICTI may cause fetal harm. A voluntary patient registry will include evaluation of pregnancy outcomes in patients with UCDs. For more information regarding the registry program, visit www.ucdregistry.com or call 1-855-823-2592
  • Caution should be exercised when administering RAVICTI to nursing mothers, as breastfeeding is not recommended with maternal use of RAVICTI. It is not known whether RAVICTI or its metabolites are present in breast milk

ADVERSE EVENTS:

  • Adverse reactions occurring in ≥10% of adult patients during short-term treatment (4 weeks) with RAVICTI were diarrhea, flatulence, and headache (n=44). Adverse reactions occurring in ≥10% of adult patients during long-term treatment (12 months) with RAVICTI were nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, dizziness, headache, and fatigue (n=51).
  • Adverse events occurring in ≥10% of pediatric patients during long-term treatment (12 months) with RAVICTI were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, and headache (n=26)

DRUG INTERACTIONS:

  • Corticosteroids, valproic acid, or haloperidol: May increase plasma ammonia level. Monitor ammonia levels closely.
  • Probenecid: May affect renal excretion of metabolites of RAVICTI, including PAGN and PAA.

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

For more information on RAVICTI, please see the Full Prescribing Information.

RAYOS Important Safety Information

Do not use RAYOS if you are allergic to prednisone.

Long-term use of RAYOS can affect your hormones and one of the ways your body responds to stress. Symptoms, among others, can include weight gain, changes in body appearance (particularly the face), severe fatigue, weak muscles, and high blood sugar. Tell your doctor if you develop any of these symptoms after taking RAYOS.

RAYOS can weaken your immune system, making it easier for you to get an infection or worsening an infection you already have or have recently had. Signs and symptoms of infection may be hidden. Tell your doctor if you have had a recent or ongoing infection or if you have been exposed to chickenpox or measles.

RAYOS can cause high blood pressure, salt and water retention, and low blood potassium. Your doctor should monitor these levels.

There is an increased risk of developing perforations in the stomach or intestines if you have certain stomach and intestinal disorders. Signs and symptoms may be hidden.

Behavior and mood changes can occur, including intense excitement or happiness, sleeplessness, mood swings, personality changes, severe depression, and psychosis. Existing conditions may become worse.

Long-term use of RAYOS can cause decreases in bone density. You should talk with your doctor about this risk before you initiate therapy, particularly if you are postmenopausal. Your doctor should monitor bone density with long-term therapy.

RAYOS can cause cataracts, eye infections, and glaucoma. Your doctor should monitor eye pressure if you use RAYOS for more than 6 weeks.

Do not receive a “live” vaccine while taking RAYOS. The vaccine may not work as well during this time, and may not fully protect you from disease. Tell your doctor if you have recently received a vaccine.

Taking RAYOS during the first trimester of pregnancy can harm an unborn baby.

Long-term use of RAYOS can slow growth and development in children. Children on long-term therapy should be monitored for this.

The most common side effects with RAYOS are water retention, high blood sugar, high blood pressure, unusual behavior and mood changes, increased appetite, and weight gain.

Talk to your doctor before you stop taking RAYOS. You may need to gradually reduce the amount of RAYOS you are taking. Stopping RAYOS suddenly may cause unwanted side effects.

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

For more information on RAYOS, please see the Full Prescribing Information.

*Outside the United States, RAYOS is approved under the brand name LODOTRA in 16 European countries, Australia and Israel for the treatment of moderate-to-severe active RA when accompanied by morning stiffness. Horizon has granted commercialization rights for LODOTRA in Europe, Asia and Latin America to its distribution partner Mundipharma International Corporation Limited.

KRYSTEXXA Important Safety Information

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS

  • Anaphylaxis and infusion reactions have been reported to occur during and after administration of Krystexxa.
  • Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion.
  • However, delayed-type hypersensitivity reactions have also been reported.
  • Krystexxa should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.
  • Patients should be premedicated with antihistamines and corticosteroids.
  • Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of Krystexxa.
  • Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.

CONTRAINDICATIONS

  • Glucose-6-phosphate dehydrogenase (G6PD) Deficiency: Before starting Krystexxa, patients at higher risk for G6PD deficiency (e.g., those of African and Mediterranean ancestry) should be screened due to the risk of hemolysis and methemoglobinemia.

WARNINGS AND PRECAUTIONS

  • Anaphylaxis: Anaphylaxis occurred in patients treated with Krystexxa. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported. Krystexxa should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis. Patients should be premedicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of Krystexxa.
  • Infusion Reactions: Infusion reactions occurred in patients treated with Krystexxa. Krystexxa should be administered in a healthcare setting and by healthcare providers prepared to manage infusion reactions. Patients should be premedicated with antihistamines and corticosteroids. Monitor patients closely for signs and symptoms of infusion reactions. In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate. If a severe infusion reaction occurs, discontinue infusion and institute treatment as needed. The risk of an infusion reaction is higher in patients who have lost therapeutic response.
    • Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.
    • Concomitant use of Krystexxa and oral urate-lowering agents may blunt the rise of serum uric acid levels. It is recommended that patients discontinue oral urate-lowering agents and not institute therapy with oral urate-lowering agents while taking Krystexxa.
  • Gout Flares: An increase in gout flares is frequently observed upon initiation of antihyperuricemic therapy, including treatment with Krystexxa. If a gout flare occurs during treatment, Krystexxa need not be discontinued. Gout flare prophylaxis with a nonsteroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of Krystexxa therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.
  • Congestive Heart Failure: Krystexxa has not been formally studied in patients with congestive heart failure, but some patients in clinical trials experienced exacerbation. Exercise caution when using Krystexxa in patients who have congestive heart failure, and monitor patients closely following infusion.
  • Re-treatment: No controlled clinical data is available on the safety and efficacy of re-treatment with Krystexxa after stopping treatment for longer than 4 weeks. Patients receiving re-treatment may be at increased risk for anaphylaxis and infusion reactions and should be monitored carefully.

ADVERSE REACTIONS

The most commonly reported serious adverse reactions in the pivotal trial with the approved regimen of 8 mg Krystexxa administered every 2 weeks were gout flares, infusion reactions, and anaphylaxis. Most common adverse reactions: gout flares (77%), infusion reactions (26%), nausea (12%), contusion or ecchymosis (11%), nasopharyngitis (7%), constipation (6%), chest pain (6%), anaphylaxis (5%), and vomiting (5%). In addition to events occurring in greater than 5%, exacerbation of pre-existing congestive heart failure occurred in 2%.

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

Please see the Full Prescribing Information, including Boxed Warning and Medication Guide at www.KRYSTEXXA.com.

DUEXIS 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 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 is not right for everyone. People who have had asthma, hives, or an allergic reaction to aspirin or other NSAIDs should not take DUEXIS. Women in the late stages of pregnancy should not take DUEXIS. People who have had allergic reactions to medications like famotidine (histamine H2‐receptor antagonists) should not take DUEXIS.

Tell your health care provider right away if you have signs of active bleeding (persistent and unexplained) while you are taking DUEXIS.

NSAID‐containing medications like DUEXIS can cause high blood pressure or make existing high blood pressure worse, either of which can increase the chance of a heart attack or stroke. Your health care provider should check your blood pressure while you are taking DUEXIS.

Before you start taking DUEXIS, tell your health care provider if you have heart problems, kidney problems, or liver problems, or if you are taking medications for high blood pressure. DUEXIS can increase the chance of potentially significant liver injury and/or kidney injury, which may be fatal. Stop taking DUEXIS immediately and contact your health care provider if you experience any signs and/or symptoms of liver or kidney injury.

Serious allergic reactions, including skin reactions, can happen without warning and can be life threatening. Stop taking DUEXIS and consult your doctor immediately if you get a skin rash or if you start to have problems breathing or swallowing, or if you develop swelling of your face or throat.

The most common side effects of DUEXIS include nausea, diarrhea, constipation, upper abdominal pain, and headache.

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

For more information on DUEXIS, please see the Medication Guide and Full Prescribing Information.

MIGERGOT Important Safety Information

WARNING

Serious and/or life-threatening peripheral ischemia has been associated with the co-administration of ergotamine tartrate and caffeine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of ergotamine tartrate and caffeine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.

CONTRAINDICATIONS

  • Do not administer MIGERGOT with potent CYP 3A4 inhibitors such as protease inhibitors or macrolide antibiotics as this has been associated with acute ergot toxicity (ergotism) characterized by vasospasm and ischemia of the extremities, with some cases resulting in amputation. There have been rare reports of cerebral ischemia in patients on protease inhibitor therapy when ergotamine tartrate and caffeine was coadministered, at least one resulting in death.
  • Do not use MIGERGOT in women who are, or may become, pregnant, or who are nursing, as it may cause harm to the fetus or nursing infant.
  • Do not use MIGERGOT in patients with peripheral vascular disease, coronary heart disease, hypertension, impaired hepatic or renal function, or sepsis.
  • Do not use MIGERGOT in patients with known hypersensitivity to any of its components.

WARNINGS AND PRECAUTIONS

  • Coadministration of ergotamine with potent CYP 3A4 inhibitors such as protease inhibitors or macrolide antibiotics has been associated with serious adverse events; for this reason, these drugs should not be given concomitantly with ergotamine. While these reactions have not been reported with less potent CYP 3A4 inhibitors, there is a potential risk for serious toxicity including vasospasm when these drugs are used with ergotamine.
  • There have been reports of patients on ergotamine tartrate and caffeine therapy developing retroperitoneal and/or pleuropulmonary fibrosis. There have also been rare reports of fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with long-term continuous use of ergotamine tartrate and caffeine. Ergotamine tartrate suppositories should not be used for chronic daily administration.
  • Ergotamine tartrate and caffeine should not be administered with other vasoconstrictors. Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.
  • While most cases of ergotism results from frank overdosage, some have involved apparent hypersensitivity. Care should be exercised so that the patient remains within the limits of the recommended dosage.
  • In rare instances, patients may display withdrawal symptoms consisting of rebound headaches upon discontinuation of the drug.
  • Rare cases of solitary rectal or anal ulcer have occurred from product abuse. Spontaneous healing occurs within usually 4-8 weeks after drug withdrawal.
  • No more than 2 suppositories should be taken for any single migraine attack. No more than 5 suppositories should be taken during any 7-day period.

ADVERSE REACTIONS

Cardiovascular: Vasoconstrictive complications of a serious nature may occur at times. These include ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, EKG changes and muscle pains. Although these effects occur most commonly with long-term therapy at relatively high doses, they have also been reported with short-term or normal doses. Other cardiovascular adverse effects include transient tachycardia or bradycardia and hypertension.

Gastrointestinal: Nausea and vomiting; rectal or anal ulcer (from overuse of suppositories).

Neurological: Paresthesias, numbness, weakness, and vertigo.

Allergic: Localized edema and itching.

Fibrotic Complications: (See WARNINGS AND PRECAUTIONS).

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

Please see the Full Prescribing Information, including Boxed Warning at www.MIGERGOT.com.

PENNSAID Important Safety Information

WARNING: CARDIOVASCULAR AND GASTROINTESTINAL RISK

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 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.


CONTRAINDICATIONS

  • DO NOT USE PENNSAID if you:
    • are in the hospital for certain heart surgeries
    • know you are allergic to diclofenac sodium or any other ingredient of PENNSAID.
    • have experienced asthma, hives, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, allergic reactions, that will rarely kill you, to NSAIDs have been reported in such patients

WARNINGS AND PRECAUTIONS

  • To minimize the potential for increased risk of serious heart events while being treated with an NSAID, use the lowest effective dose for the shortest duration possible
  • Elevation of one or more liver tests may occur during therapy with NSAIDs. PENNSAID should be discontinued immediately if abnormal liver tests persist or worsen
  • Use with caution in patients with fluid retention or heart failure
  • Hypertension can occur with NSAID treatment. Monitor blood pressure closely with PENNSAID treatment
  • Long-term use of NSAIDs can result in severe kidney injury. Use PENNSAID with caution in patients at greatest risk of this reaction, including the elderly, those with impaired kidney function, heart failure, liver dysfunction and those taking diuretics and ACE-inhibitors (certain blood pressure medicines)
  • Severe allergic reactions may occur without prior use of PENNSAID. NSAIDs can cause serious skin reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), which can kill you
  • Wash and dry hands before and after use. Avoid contact of PENNSAID with the eyes, nose and mouth
  • PENNSAID was not studied under the conditions of heat application, complete covering bandages or exercise; therefore, concurrent use of PENNSAID under these conditions is not recommended
  • Do not:
    • Apply PENNSAID to open wounds
    • Shower for at least 30 minutes after applying PENNSAID
    • Wear clothing over the PENNSAID treated knee until the treated knee is dry
  • Protect treated knee(s) from natural or artificial sunlight
  • Protect treated knee(s) from sunlight (real and tanning booths)
  • Topicals, such as sunscreen and bug repellent, should not be used until after PENNSAID treated knee(s) are completely dry
  • Do not use with oral NSAIDs unless your doctor says it is OK and you have lab tests to check your progress
  • There is no consistent evidence that regular use of aspirin lessens the increased risk of serious heart events, such as heart clotting, heart attack and stroke associated with NSAID use. As with all NSAIDs, regular administration of PENNSAID and aspirin is not generally recommended because of the potential of increased risks

ADVERSE REACTIONS

  • The most common adverse events in a phase 2 clinical trial of PENNSAID 2% were application site reactions, such as dryness (22%), peeling (7%), redness (4%), itching (2%), pain (2%), skin hardening (2%), rash (2%) and scabbing (<1%). Other adverse reactions occurring in >1% of patients receiving PENNSAID 2% included bladder infection (3%), bruising (2%), sinus congestion (2%) and nausea (2%)
  • The most common treatment-related adverse events in patients receiving PENNSAID 1.5% were application site skin reactions including dry skin (32%), skin reaction characterized by redness and hardening (9%), skin reaction with blisters (2%) and itching (4%). In a long term safety study, skin reactions occurred in 13% and skin reactions with blisters in 10% of patients, generally within the first 6 months of exposure, leading to a withdrawal rate for an application site event of 14%. Other common adverse events greater than placebo include: stomach upset (9%), stomach pain (6%), gas (4%), diarrhea (4%) and nausea (4%)

USE IN SPECIFIC POPULATIONS

  • PENNSAID should not be used in pregnant woman or in women who are breastfeeding and is not approved for use in children

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

For more information on PENNSAID, please see the Medication Guide and Full Prescribing Information, available at www.PENNSAID.com.

VIMOVO Indications and Usage

VIMOVO (naproxen and esomeprazole magnesium) is a combination product that contains naproxen and esomeprazole. It is indicated for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis and to decrease the risk of developing gastric ulcers in patients at risk of developing NSAID‐associated gastric ulcers. VIMOVO is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products. Controlled studies do not extend beyond 6 months.

LIMITATIONS OF USE
VIMOVO is not interchangeable with the individual components of naproxen and esomeprazole magnesium.

Important Safety Information

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs), a component of VIMOVO, 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.
  • VIMOVO is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

  • NSAIDs, a component of VIMOVO, 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.


CONTRAINDICATIONS

  • VIMOVO is contraindicated in patients:
    • With known hypersensitivity to naproxen, esomeprazole magnesium, substituted benzimidazoles, or any component of the drug product, including omeprazole.
    • 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. VIMOVO can be administered with low‐dose aspirin (≤325 mg/day) therapy. The concurrent use of aspirin and an NSAID, such as VIMOVO, increases the risk of serious GI events. As with all NSAIDs, concurrent administration of naproxen and aspirin is not generally recommended because of the increased risk of bleeding.
  • Elevation of one or more liver tests may occur during therapy with NSAIDs. VIMOVO should be discontinued immediately if clinical signs and symptoms consistent with liver disease develop. VIMOVO is not recommended in patients with severe hepatic insufficiency.
  • Hypertension can occur with NSAID treatment. Monitor blood pressure closely with VIMOVO treatment
  • Avoid use of VIMOVO 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 VIMOVO with caution in patients at greatest risk of this reaction.
  • Anaphylactic reactions may occur in patients with or without known hypersensitivity to VIMOVO and in patients with aspirin-sensitive asthma.
  • VIMOVO 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.
  • Discontinue VIMOVO if active and clinically significant bleeding from any source occurs.
  • In adults, symptomatic response to esomeprazole, a component of VIMOVO, does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing.
  • PPI use has been associated with acute interstitial nephritis, new onset or exacerbation of cutaneous or systemic lupus erythematosus, malabsorption of cyanocobalamin, hypomagnesemia, increased risk of diarrhea associated with Clostridium difficile infection, and increased risk for osteoporosis‐related fractures of the hip, wrist, or spine.
  • Avoid concomitant use of VIMOVO with:
    • Other naproxen-containing products or other non-aspirin NSAIDs.
    • Clopidogrel due to a reduction in plasma concentrations of the active metabolite of clopidogrel. When using esomeprazole consider alternative anti‐platelet therapy.
    • St. John’s Wort or rifampin due to the potential reduction in esomeprazole levels.
    • Methotrexate which may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity.

Note: see full Prescribing Information for a list of clinically important drug interactions.

ADVERSE REACTIONS

The most commonly observed adverse events in clinical trials (experienced by >5% patients in the VIMOVO group) were gastritis and diarrhea.

USE IN SPECIFIC POPULATIONS

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

For further information on VIMOVO, please see the Medication Guide and full Prescribing Information, including boxed warning, at www.VIMOVO.com.

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.

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