ZORVOLEX® (diclofenac) is the first low-dose SoluMatrix® diclofenac for patients with mild to moderate acute pain or osteoarthritis (OA) pain

Zorvolex introduction

ZORVOLEX is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the management of mild to moderate acute pain or OA pain.

  • ZORVOLEX is approved for management of mild to moderate acute pain at low dosages (18 mg TID and 35 mg TID).
    • ZORVOLEX 54 mg per day (18 mg TID) is the lowest effective daily dosage for diclofenac.1
  • ZORVOLEX is approved for management of OA pain at a dosage of 35 mg TID.
  • Although the 18-mg dose was not directly compared to diclofenac potassium IR 50 mg, based on dose-proportional kinetics for ZORVOLEX, the overall systemic exposure is 62% lower. (LS mean = 487)
  • LS mean = least square mean.
    Based on phase 1 study in healthy subjects.

The Science of Less: Low-Dose SoluMatrix® NSAIDs

The US Food and Drug Administration (FDA) issued a Public Health Advisory recommending that NSAIDs be used at “lowest effective dose for the shortest duration consistent with individual patient treatment goals.”2
The Science of Less: Low-Dose SoluMatrix<sup>®</sup>  NSAIDs

NSAID dosing and potential adverse events

The risk of serious cardiovascular, gastrointestinal, and renal adverse events (AEs) associated with NSAID use has been shown to be dose-related.3-8 Even short-term NSAID therapy places patients at risk: Serious AEs can occur in as little as 1 week following initial dosing.5,9,10

Research has shown that NSAID doses:

Increased the risk of cardiovascular events

Increased the risk of cardiovascular events

Increased the risk of upper GI complications

Increased the risk of upper GI complications

Increased the risk of acute renal failure

Increased the risk of acute renal failure

Smaller Particles11

SoluMatrix® Fine Particle Technology®

  • Creates diclofenac particles approximately 10 to 20 times smaller than original size.
  • Reduction in particle size increases surface area, which promotes dissolution.
Original drug particles
Solumatrix drug particles

See SoluMatrix® Fine Particle Technology® in action

Watch a video that illustrates how SoluMatrix® Fine Particle Technology® works.

ZORVOLEX: The first low-dose SoluMatrix® diclofenac for patients with mild to moderate acute pain or OA pain

ZORVOLEX is an NSAID indicated for the management of mild to moderate acute pain or OA pain.

  • ZORVOLEX is approved for management of mild to moderate acute pain at low dosages (18 mg TID and 35 mg TID).
    • ZORVOLEX 54 mg per day (18 mg TID) is the lowest effective daily dosage for diclofenac.1
  • ZORVOLEX is approved for management of OA pain at a dosage of 35 mg TID.
Zorvolex 18-mg and 35-mg capsules

ZORVOLEX:

  • Delivers low systemic exposure.
  • Delivered impressive efficacy at low doses.
  • Most common adverse reactions (incidence ≥2%) 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.

Copay for Commercially Eligible Patients (Non-Government)

Indication
ZORVOLEX is indicated for:
  • Management of mild to moderate acute pain
  • Management of osteoarthritis pain
Important Safety Information About Zorvolex

Cardiovascular Thrombotic EventsNonsteroidal 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 is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and PerforationNSAIDs 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
ZORVOLEX is contraindicated in the following patients:
  • a known hypersensitivity to diclofenac or any components of the drug
  • a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients
  • in the setting of coronary artery bypass graft (CABG) surgery

Warnings and Precautions
Post-MI Patients: Avoid the use of ZORVOLEX in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. Monitor these patients for signs of cardiac ischemia.

Hepatotoxicity: Elevation of one or more liver tests may occur during therapy with NSAIDs including ZORVOLEX. Rare, sometimes fatal, cases of severe hepatic injury have been reported. Inform patients of the warning signs and symptoms of hepatotoxicity. Discontinue immediately if clinical signs and symptoms of liver disease develop.

Hypertension: NSAIDs, including ZORVOLEX, can lead to the new onset or worsening of existing hypertension, either of which may contribute to the increased incidence of CV events. Monitor blood pressure during treatment with ZORVOLEX.

Heart Failure and Edema: Avoid use of ZORVOLEX in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure. If ZORVOLEX is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Renal Toxicity and Hyperkalemia: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Avoid the use of ZORVOLEX in patients with advanced renal disease unless the benefits are expected to outweigh the risk. Monitor for signs of worsening renal function.

Anaphylactic Reactions: Anaphylactic reactions may occur in patients taking diclofenac or those with or without a known hypersensitivity to ZORVOLEX and in patients with aspirin-sensitive asthma. Seek emergency help if an anaphylactic reaction occurs.

Serious Skin Reactions: NSAIDs can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Discontinue ZORVOLEX if rash or other signs of local skin reaction occur.

Premature Closure of Fetal Ductus Arteriosus: Starting at 30 weeks of gestation, ZORVOLEX and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur.

Hematologic Toxicity: Anemia has occurred in patients treated with NSAIDs. Monitor hemoglobin or hematocrit in patients showing symptoms of anemia. ZORVOLEX may increase the risk of bleeding.

Adverse Reactions
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.

Drug Interactions
Drugs that Interfere with Hemostasis (e.g. warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking ZORVOLEX with drugs that interfere with hemostasis. Concomitant use of ZORVOLEX and analgesic dose of aspirin is not generally recommended.

ACE Inhibitors, Angiotensin Receptor Blockers (ARB), or Beta Blockers: Concomitant use with ZORVOLEX may diminish the antihypertensive effect of these drugs. Monitor blood pressure.

ACE Inhibitors and ARBs: Concomitant use with ZORVOLEX in the elderly, volume depleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function.

Diuretics: NSAIDs can reduce the natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects.

Digoxin: Concomitant use with ZORVOLEX can increase serum concentration and prolong half-life of digoxin levels.

Use in Specific Populations
Pregnancy: Use of NSAIDs during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs in pregnant women starting at 30 weeks of gestation.

Infertility: NSAIDs are associated with reversible infertility. Consider withdrawal of ZORVOLEX in women who have difficulties conceiving.

Please see full Prescribing Information including Boxed Warning and Medication Guide.

To report SUSPECTED ADVERSE REACTIONS, contact Zyla Life Sciences at 1-800-518-1084 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. U.S. Food and Drug Administration. Orange book: Approved drug products with therapeutic equivalence evaluations. 39th Edition. https://www.fda.gov/media/71474/download. Accessed August 27, 2019.
  2. U.S. 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). Published April 2005. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/cox-2-selective-includes-bextra-celebrex-and-vioxx-and-non-selective-non-steroidal-anti-inflammatory. Accessed August 27, 2019.
  3. Castellsague J, Riera-Guardia N, Calingaert B, et al; Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127-1146.
  4. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLOS Med. 2011;8(9):e1001098.
  5. Huerta C, Castellsague J, Varas-Lorenzo C, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis. 2005;45(3):531-539.
  6. Garcia-Rodriguez LA, Hernandez-Diaz S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology. 2001;2(5):570-576.
  7. Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769-779.
  8. García Rodríguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol. 2008;52(20):1628-1636.
  9. Helin-Salmivaara A, Virtanen A, Vesalainen R, et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J. 2006;27(14):1657-1663.
  10. Helin-Salmivaara A, Saarelainen S, Gronroos JM, Vesalainen R, Klaukka T, Huupponen R. Risk of upper gastrointestinal events with the use of various NSAIDs: a case-control study in a general population. Scand J Gastroenterol. 2007;42(8):923-93.
  11. Desjardins PJ, Olugemo K, Solorio D, Young CL. Pharmacokinetic properties and tolerability of low-dose SoluMatrix diclofenac. Clin Ther. 2015;37(2):448-461.