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

ZORVOLEX is a nonsteroidal anti-inflammatory drug (NSAID) indicated for management of mild to moderate acute pain or OA pain.1

  • ZORVOLEX is indicated for the management of mild to moderate acute pain at low dosages (18 mg TID and 35 mg TID)1
    • ZORVOLEX 54 mg per day (18 mg TID) is the lowest effective daily dosage for diclofenac1,2
  • ZORVOLEX is indicated for management of OA pain at a dosage of 35 mg TID1

ZORVOLEX was developed to align with US Food and Drug Administration (FDA) recommendations on NSAID dosing: ZORVOLEX should be used at the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.3,4

ZORVOLEX® offers a unique pharmacokinetic profile1,5*

Diclofenac plasma concentrations during the first 12 hours5

This chart shows that ZORVOLEX, a low dose diclofenac demonstrated early plasma levels.
  • ZORVOLEX delivers low systemic exposure1,5,6
  • ZORVOLEX provides early (within 1 hour) plasma levels, which ensures the drug is available for distribution to tissues1,5
  • ZORVOLEX 18 mg and 35 mg achieve comparable times to peak plasma levels as diclofenac potassium IR 50 mg1,5

The clinical relevance of the differences in pharmacokinetic measurements is unknown.

*Based on phase 1 study in healthy subjects.Although the 18-mg dose was not directly compared with diclofenac potassium IR 50 mg, based on dose-proportional kinetics for ZORVOLEX, the overall systemic exposure is 62% lower.

ZORVOLEX® delivers low systemic exposure1,5,6*

The clinical relevance of differences in pharmacokinetic measurements is unknown.

LS mean=least squares mean.*Based on a phase 1 study in healthy subjects.Although the 18-mg dose was not directly compared with diclofenac potassium IR 50 mg, based on dose-proportional kinetics for ZORVOLEX, the overall systemic exposure is estimated to be 62% lower.The LS mean for diclofenac potassium IR 50 mg was 1288.

ZORVOLEX® delivered impressive efficacy at low doses in patients with mild to moderate acute pain1,7

Study design: Multicenter, randomized, double-blind, placebo-controlled, parallel-arm study comparing ZORVOLEX 18 mg or 35 mg TID to placebo in 428 patients with pain following bunionectomy.1

Primary end point: Sum of pain intensity differences over 48 hours1,7

n based on ITT population.LS mean=least squares mean; VAS SPID=visual analog scale sum of pain intensity difference (the sum of pain measurement differences from baseline at all measurement points).

ZORVOLEX®: Average pain intensity over 48 hours1

ZORVOLEX demonstrated higher level of pain relief in a Placebo control clinical test
VAS PI=visual analog scale pain intensity (average pain intensity scores at all measurement points; lower VAS PI scores indicate greater pain relief).

ZORVOLEX® delivered impressive efficacy at low doses in patients with mild to moderate acute pain1,7

The baseline mean pain intensity was 74 (VAS 0-100) for the overall study population1

  • ZORVOLEX 18 mg TID and 35 mg TID reduced pain by ~50% at 12 hours, ~70% at 24 hours, and ~85% at 48 hours6
  • The corresponding reductions in the placebo arm were 23% at 12 hours, 51% at 24 hours, and 73% at 48 hours6

Reductions in pain intensity at 12, 24 and 48 hours6

Post-hoc analysis based on secondary end point assessment of pain intensity differences (PID) measured by visual analog scale (VAS).VAS PID=visual analog scale pain intensity difference (average pain intensity difference at all measurement points).

ZORVOLEX® was generally well tolerated in patients with mild to moderate acute pain1

In a postoperative acute pain clinical trial, these adverse reactions occurred in ≥2% of patients treated with ZORVOLEX and more frequently than with placebo1

Adverse reactionsZORVOLEX®
18 mg and 35 mg TID
(n=216)
Placebo
(n=106)
Postprocedural edema33%32%
Constipation8%4%
Pruritus7%6%
Flatulence3%2%
Pain in extremity3%1%
Dyspepsia2%1%
Abdominal pain2%1%
Procedural pain2%0%

ZORVOLEX® delivered impressive efficacy at low doses in patients with OA pain1,8

Study design: Random, double-blind, double-dummy, placebo-controlled study in 305 men and women with clinically and radiographically confirmed hip and/or knee OA.1,6

ZORVOLEX significantly reduced OA pain compared with placebo over 12 weeks, as measured by the WOMAC Pain Subscale (the primary end point).1,8

Change from baseline in WOMAC pain subscale scores at weeks 2, 6, and 121,6,8*

LS mean=least squares mean.WOMAC=Western Ontario and McMaster Universities Arthritis Index.*Measurements at weeks 2 and 6 were secondary end points.

ZORVOLEX® reduced the impact of OA pain1,8

78% of patients treated with ZORVOLEX 35 mg reported 30% improvement in the WOMAC Pain Subscale.
  • 63% of patients treated with ZORVOLEX 35 mg TID reported ≥50% improvement in the WOMAC Pain Subscale8*
  • 60% of patients taking placebo reported ≥30% improvement and 46% of patients taking placebo reported a ≥50% improvement8
*Secondary end point.

ZORVOLEX® was generally well tolerated in patients with OA pain1

In a 12-week clinical trial in patients with OA, these adverse reactions occurred in ≥2% of patients treated with ZORVOLEX and more frequently than with placebo1

Adverse reactionsZORVOLEX® 35 mg*
(n=202)
Placebo
(n=103)
Nausea7%2%
Diarrhea6%3%
Headache4%3%
Upper abdominal pain3%1%
Sinusitis3%1%
Vomiting3%1%
Alanine aminotransferase increased2%0%
Blood creatinine increased2%0%
Dyspepsia2%1%
Flatulence2%0%
Hypertension2%1%
*Combined ZORVOLEX 35 mg BID and TID treatment regimens.

Summary of adverse reactions (≥2%) in a 52-week, open-label study of patients with OA pain1

Adverse reactionsZORVOLEX® 35 mg
(n=216)
Upper respiratory tract infection8%
Headache8%
Urinary tract infection7%
Diarrhea6%
Nasopharyngitis6%
Nausea6%
Constipation5%
Sinusitis5%
Osteoarthritis5%
Cough4%
Alanine aminotransferase increased4%
Back pain3%
Dyspepsia3%
Procedural pain3%

In a 52-week, open-label safety trial in patients with OA pain of the knee or hip1,9:

  • All patients started on 35 mg BID, with the option to increase to TID after 3 days
  • 50% of patients remained on BID (ie, did not increase to TID)

Dosing and administration for ZORVOLEX®

Available in low 18-mg and 35-mg doses1

  • ZORVOLEX is indicated for management of mild to moderate acute pain at low dosages (18 mg TID and 35 mg TID)1
    • ZORVOLEX 54 mg per day (18 mg TID) is the lowest effective daily dosage available for diclofenac1,2
  • ZORVOLEX is indicated for management of OA pain at a dosage of 35 mg TID1
  • ZORVOLEX has no therapeutic equivalent1
ZORVOLEX diclofenac capsules for OA pain treatment

FDA recommends that NSAIDs be used at the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.3,4

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References

  1. Full Prescribing Information for ZORVOLEX (diclofenac) capsules. Iroko Pharmaceuticals, LLC; 2016.
  2. US Food and Drug Administration. Orange book: approved drug products with therapeutic equivalence evaluations. http://www.accessdata.fda.gov/scripts/cder/ob/docs/tempai.cfm. Accessed August 1, 2016.
  3. 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 August 1, 2016.
  4. 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 August 1, 2016.
  5. Desjardins PJ, Olugemo K, Solorio D, Young CL. Pharmacokinetic properties and tolerability of low-dose SoluMatrix diclofenac. Clin Ther. 2015;37(2):448-461.
  6. Data on file, Iroko Pharmaceuticals, LLC.
  7. Gibofsky A, Silberstein S, Argoff C, Daniels S, Jensen S, Young C. Lower-dose diclofenac submicron particle capsules provide early and sustained acute patient pain relief in a phase 3 study. Postgrad Med. 2013;125(5):130-138.
  8. Gibofsky A, Hochberg MC, Jaros MJ, Young CL. Efficacy and safety of low-dose submicron diclofenac for the treatment of osteoarthritis pain: a 12 week, phase 3 study. Curr Med Res Opin. 2014;30(9):1883-1893.
  9. Altman RD, Strand V, Hochberg MC, Gibofsky A. et al. Low-dose SoluMatrix diclofenac in the treatment of osteoarthritis: A 1-year, open-label, Phase III safety study. Postgrad Med. 2015;127(5):517-528.