Iroko Summarizes Low-Dose SoluMatrix® NSAID Efficacy and Safety Data at American Association of Nurse Practitioners National Conference

Low-Dose NSAIDs Can Help Healthcare Practitioners Align with FDA Recommendations to Prescribe NSAIDs at Lowest Effective Dosage for Shortest Duration

Philadelphia, June 23, 2016 — To support the efforts of nurse practitioners who are on the front lines of treating the hundreds of millions of people living in pain1 in the United States, Iroko Pharmaceuticals, LLC, a global specialty pharmaceutical company dedicated to advancing the science of analgesia, today summarizes efficacy and safety data supporting the use of low-dose SoluMatrix® non-steroidal anti-inflammatory drugs (NSAIDs) for the management of mild to moderate acute pain or osteoarthritis (OA) pain at the American Association of Nurse Practitioners 2016 National Conference in San Antonio, Texas.

Pain affects many Americans1 and NSAIDs are among the most commonly used medications to treat pain. In 2015, 127 million prescriptions were filled for NSAIDs in the United States2 and it is reported that one-third of the general population have used over-the-counter (OTC) NSAIDs3. Although NSAIDs are effective for treating pain, as a class, they are associated with dose-related gastrointestinal (GI bleeds, ulcers and perforations), cardiovascular (myocardial infarction and stroke) and renal (acute renal failure) serious adverse events (SAEs). FDA recommends the use of NSAIDs at the lowest effective dosage for the shortest duration to minimize potential risk of SAEs4,5.

With the understanding that patients need pain treatment options that align with FDA NSAID dosing recommendations, Iroko has developed and markets three low-dose SoluMatrix® NSAIDs: ZORVOLEX®, TIVORBEX® and VIVLODEX®. The parent molecules of these low–dose NSAIDs are diclofenac, indomethacin and meloxicam, respectively, and are among the most frequently prescribed NSAID pain medications in the United States6. ZORVOLEX (diclofenac) is approved for the management of mild to moderate acute pain and OA pain7. TIVORBEX (indomethacin) is approved for the treatment of mild to moderate acute pain in adults8. VIVLODEX (meloxicam) is approved for the management of OA pain9.  ZORVOLEX, TIVORBEX and VIVLODEX were developed using SoluMatrix Fine Particle Technology™, which enables rapid absorption with low overall systemic exposure.

“Nurse practitioners see a large number of patients in pain and play a vital role in making sure patients and their caregivers are aware of the risks and benefits of all available pain medication options,” said Brett Snodgrass, FNP-C, CPE, FACPP, Director of Clinical Operations, LifeLinc Pain Centers. “Low-dose SoluMatrix® NSAIDs should be included in discussions with patients about their treatment plans because these medications have been shown to provide effective pain relief while also aligning with FDA NSAID dosing recommendations.”

“Iroko has developed a franchise of re-engineered low-dose SoluMatrix® NSAIDs that offer effective pain management options for healthcare professionals, including nurse practitioners, and their patients in light of FDA recommendations to use the lowest effective NSAID dosage for the shortest duration,” said Dr. Clarence Young, Chief Medical Officer of Iroko.

ZORVOLEX and TIVORBEX were evaluated in separate phase 3 studies in patients experiencing acute pain. In both studies, patients treated with either ZORVOLEX or TIVORBEX experienced significantly greater overall reductions in pain intensity over 48 hours compared to placebo.

ZORVOLEX and VIVLODEX were evaluated in separate phase 3 studies to evaluate their efficacy for management of OA pain. In the ZORVOLEX OA study, patients were administered ZORVOLEX 35 mg TID or BID or placebo. Patients treated with ZORVOLEX 35 mg TID experienced significantly greater reductions in OA pain compared to placebo. In the VIVLODEX OA study, patients received VIVLODEX 5 mg or 10 mg once daily or placebo. Patients treated with VIVLODEX experienced significantly greater reductions in OA pain compared to placebo.

IMPORTANT SAFETY INFORMATION

Cardiovascular Thrombotic Events

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal.  This risk may occur early in treatment and may increase with duration of use.

ZORVOLEX, TIVORBEX, and VIVLODEX are 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.

ZORVOLEX, TIVORBEX, and VIVLODEX are contraindicated in patients with:  a known hypersensitivity to the respective active ingredient (diclofenac, indomethacin or meloxicam) or their inactive ingredients; a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.

ZORVOLEX, TIVORBEX, or VIVLODEX should be used at the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.

Elevation of one or more liver tests may occur during therapy with NSAIDs.  Rare, sometimes fatal, cases of severe hepatic injury have been reported.  Physicians should measure transaminases before starting and periodically during long-term treatment with ZORVOLEX.  ZORVOLEX, TIVORBEX, or VIVLODEX should be discontinued immediately if clinical signs and symptoms of liver disease develop.

NSAIDs, including ZORVOLEX, TIVORBEX, and VIVLODEX, can lead to the new onset of hypertension or worsening of preexisting hypertension, which may contribute to the increased incidence of CV events.  Blood pressure should be monitored during treatment with ZORVOLEX, TIVORBEX, or VIVLODEX.  NSAIDs may diminish the antihypertensive activity of loop and thiazide diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers.

NSAID use has been associated with an increase in the risk of MI, hospitalizations due to heart failure, and death.  Also, fluid retention and edema have been observed in patients taking NSAIDs.  Avoid the use of ZORVOLEX, TIVORBEX, or VIVLODEX in patients with severe heart failure.

Long-term administration of NSAIDs can result in renal papillary necrosis and other renal injury.  ZORVOLEX, TIVORBEX, or VIVLODEX should be used with caution in patients at greatest risk of this reaction, including the elderly, those with impaired renal function, heart failure, liver dysfunction, dehydration, hypovolemia, and those taking diuretics, ACE inhibitors, or ARBs.  Avoid the use of NSAIDs in patients with advanced renal disease.  Increases in serum potassium levels, including hyperkalemia, have been reported with NSAID use.

Anaphylactic reactions may occur in patients with the aspirin triad or in patients without prior exposure to ZORVOLEX, TIVORBEX, or VIVLODEX. These NSAIDs should be discontinued immediately if an anaphylactic reaction occurs.

NSAIDs can cause serious skin adverse events such as exfoliative dermatitis, Stevens – Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.  ZORVOLEX, TIVORBEX, or VIVLODEX should be discontinued if rash or other signs of local skin reaction occur.

Indomethacin may aggravate depression, and other psychiatric disturbances, epilepsy, or parkinsonism, and should be used with caution in patients with these conditions.  Indomethacin may cause drowsiness; therefore patients should be cautioned about engaging in activities requiring mental alertness and motor coordination.  Discontinue TIVORBEX if severe central nervous system (CNS) adverse reactions develop.

Corneal deposits and retinal disturbances have been observed after prolonged therapy with indomethacin.  Periodic ophthalmologic examinations are advisable in patients receiving prolonged therapy.  TIVORBEX is not indicated for long-term treatment.

Starting at 30 weeks of gestation, NSAIDs, including ZORVOLEX, TIVORBEX and VIVLODEX, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur.

Concomitant administration of anticoagulants, antiplatelet agents (e.g., aspirin), SSRIs, SNRIs, salicylates, or other NSAIDs with ZORVOLEX, TIVORBEX, or VIVLODEX may increase the risk of bleeding.

The anti-inflammatory and anti-pyretic activity of ZORVOLEX, TIVORBEX, or VIVLODEX may mask the signs of infection.

Since serious GI, hepatic, and renal events have been reported with NSAID use, consider monitoring CBC and chemistry profile in patients on long-term NSAID therapy.

Most common adverse reactions (incidence ≥2%) in clinical trials with ZORVOLEX include:  edema, nausea, headache, dizziness, vomiting, constipation, pruritus, diarrhea, flatulence, pain in extremity, abdominal pain, sinusitis, alanine aminotransferase increased, blood creatinine increased, hypertension, and dyspepsia.

Most common adverse reactions (incidence ≥2%) in clinical trials with TIVORBEX include:   nausea, post procedural edema, headache, dizziness, vomiting, post procedural hemorrhage, constipation, pruritus, diarrhea, dyspepsia, post procedural swelling, presyncope, rash, upper abdominal pain, somnolence, generalized pruritus, hyperhidrosis, decreased appetite, hot flush, and syncope.

Most common adverse reactions (incidence ≥2%) in clinical trials with VIVLODEX include:  diarrhea, nausea, and abdominal discomfort.

ZORVOLEX, TIVORBEX, or VIVLODEX capsules do not result in an equivalent systemic exposure to other formulations of oral diclofenac, indomethacin, or meloxicam, respectively.  Therefore, do not substitute similar dose strengths of other:  diclofenac products for ZORVOLEX; indomethacin products for TIVORBEX; or meloxicam products for VIVLODEX.

Please see full prescribing information for ZORVOLEX, TIVORBEX and VIVLODEX for additional important safety and dosing information.

About Iroko Pharmaceuticals, LLC

Iroko is a global specialty pharmaceutical company, based in Philadelphia, dedicated to advancing the science of analgesia. The company develops and globally commercializes pharmaceutical products. Iroko is at the forefront of the development of SoluMatrix® NSAIDs – new low dose drug products based on existing NSAIDs – using iCeutica Inc.’s proprietary SoluMatrix Fine Particle Technology™ exclusively licensed to Iroko for NSAIDs.  For more information, visit www.iroko.com.

Contacts:

Caitlin Finnegan for Iroko Pharmaceuticals, LLC, 212-303-2321

Meg Kramer, Iroko Pharmaceuticals, LLC, 267-546-1656

 

SoluMatrix Fine Particle Technology™ is a trademark of iCeutica Inc., and the technology is licensed to Iroko for exclusive use in NSAIDs.

SoluMatrix® is a trademark of iCeutica Pty Ltd and is licensed to Iroko.

ZORVOLEX®, TIVORBEX® and VIVLODEX® are trademarks of Iroko Pharmaceuticals, LLC.

 

 


1. Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US); 2011.
2. Data on file, Iroko Pharmaceuticals.
3. Koffeman A, et al. High-risk use of over-the-counter non-steroidal anti-inflammatory drugs: a population-based cross-sectional study. Br J Gen Pract. 2014 Apr; 64(621): e191–e198.
4. US Food and Drug Administration. Public health advisory – FDA announces important changes and additional warnings for COX-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/
ucm150314.htm. Published April 7, 2005. Accessed June 14, 2016.
5. US Food and Drug Administration. Drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm Published July 9, 2015. Accessed June 14, 2016.
6. Data on file, Iroko Pharmaceuticals.
7. Full Prescribing Information for ZORVOLEX. 2016. Iroko Pharmaceuticals, LLC.
8. Full Prescribing Information for TIVORBEX. 2016. Iroko Pharmaceuticals, LLC.
9. Full Prescribing Information for VIVLODEX. 2015. Iroko Pharmaceuticals, LLC.

FRN-0082 6/2016