Solaraze Description

Solaraze® (diclofenac sodium) Gel, 3%, contains the active ingredient, diclofenac sodium, in a clear, transparent, colorless to slightly yellow gel base. Diclofenac sodium is a white to slightly yellow crystalline powder. It is freely soluble in methanol, soluble in ethanol, sparingly soluble in water, slightly soluble in acetone, and partially insoluble in ether. The chemical name for diclofenac sodium is:

Sodium [o-(2,6-dichloranilino) phenyl] acetate

Diclofenac sodium has a molecular weight of 318.13.

The CAS number is CAS-15307-79-6. The structural formula is represented below:

Solaraze® Gel also contains benzyl alcohol, hyaluronate sodium, polyethylene glycol monomethyl ether, and purified water.

1 g of Solaraze® (diclofenac sodium) Gel contains 30 mg of the active substance, diclofenac sodium.

Solaraze - Clinical Pharmacology

The mechanism of action of diclofenac sodium in the treatment of actinic keratoses (AK) is unknown. The contribution to efficacy of individual components of the vehicle has not been established.

Indications and Usage for Solaraze

Solaraze® (diclofenac sodium) Gel is indicated for the topical treatment of actinic keratoses (AK). Sun avoidance is indicated during therapy.

Clinical Studies

Clinical trials were conducted involving a total of 427 patients (213 treated with Solaraze® and 214 with a gel vehicle). Each patient had no fewer than five AK lesions in a major body area, which was defined as one of five 5 cm x 5 cm regions: scalp, forehead, face, forearm and hand. Up to three major body areas were studied in any patient. All patients were 18 years of age or older (male and female) with no clinically significant medical problems outside of the AK lesions and had undergone a 60-day washout period from disallowed medications (masoprocol, 5-fluorouracil, cyclosporine, retinoids, trichloroacetic acid/lactic acid/peel, 50% glycolic acid peel) and hyaluronan-containing cosmetics. Patients were excluded from participation for reasons of known or suspected hypersensitivity to any Solaraze® ingredient, pregnancy, allergies to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), or other dermatological conditions which might affect the absorption of the study medication. Application of dermatologic products such as sunscreens, cosmetics, and other drug products was not permitted. Patients were instructed to apply a small amount of Solaraze® Gel (approximately 0.5 g) onto the affected skin, using their fingers, and gently smoothing the gel over the lesion. In addition, all patients were instructed to avoid sun exposure. Complete clearing of the AK lesions 30 days after completion of treatment was the primary efficacy variable. No long-term patient follow-ups, after the 30-day assessments, were performed for the detection of recurrence.

Contraindications

Solaraze® (diclofenac sodium) Gel is contraindicated in patients with a known hypersensitivity to diclofenac, benzyl alcohol, polyethylene glycol monomethyl ether 350 and/or hyaluronate sodium.

Solaraze® (diclofenac sodium) Gel is contraindicated in the following patients:
- In the setting of coronary artery bypass graft (CABG) surgery.

Warnings

Fetal Toxicity

Premature Closure of Fetal Ductus Arteriosus:

Avoid use of NSAIDs, including Solaraze® Gel, in pregnant women at about 30 weeks gestation and later. NSAIDs including Solaraze® Gel, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment:

Use of NSAIDs, including Solaraze® Gel, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit Solaraze® Gel use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if Solaraze® Gel treatment extends beyond 48 hours. Discontinue Solaraze® Gel if oligohydramnios occurs and follow up according to clinical practice [see PRECAUTIONS; Pregnancy].

As with other NSAIDs, anaphylactoid reactions may occur in patients without prior exposure to diclofenac. Diclofenac sodium should be given with caution to patients with the aspirin triad. The triad typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Serious Skin Reactions, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

Drug Rash with Eosinophiliaand Systemic Symptoms (DRESS)

Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in patients taking NSAIDs such as Solaraze® Gel. Some of these events have been fatal or life-threatening. DRESS typically although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue Solaraze® Gel and evaluate the patient immediately.

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

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 diclofenac, increases the risk of serious gastrointestinal (GI) events.

Status Post Coronary Artery Bypass Graft (CABG) Surgery

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG.

Post-MI Patients

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.

Avoid the use of Solaraze® Gel in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Solaraze® Gel is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Heart Failure and Edema

The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of diclofenac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)].

Avoid the use of Solaraze® Gel in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Solaraze® Gel is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Precautions

Adverse Reactions/Side Effects

Of the 423 patients evaluable for safety in adequate and well-controlled trials, 211 were treated with Solaraze® drug product and 212 were treated with a vehicle gel. Eighty-seven percent (87%) of the Solaraze®-treated patients (183 patients) and 84% of the vehicle-treated patients (178 patients) experienced one or more adverse events (AEs) during the studies. The majority of these reactions were mild to moderate in severity and resolved upon discontinuation of therapy.

Of the 211 patients treated with Solaraze®, 172 (82%) experienced AEs involving skin and the application site compared to 160 (75%) vehicle-treated patients. Application site reactions (ASRs) were the most frequent AEs in both Solaraze®-and vehicle-treated groups. Of note, four reactions, contact dermatitis, rash, dry skin and exfoliation (scaling) were significantly more prevalent in the Solaraze® group than in the vehicle-treated patients.

Eighteen percent of Solaraze®-treated patients and 4% of vehicle-treated patients discontinued from the clinical trials due to adverse events (whether considered related to treatment or not). These discontinuations were mainly due to skin irritation or related cutaneous adverse reactions.

Table 1 below presents the AEs reported at an incidence of >1% for patients treated with either Solaraze® Gel or vehicle (60- and 90-day treatment groups) during the phase 3 studies.

Skin and Appendages Adverse Events Reported for Solaraze® at Less Than 1% Incidence in the Phase 3 Studies: skin hypertrophy, paresthesia, seborrhea, urticaria, application site reactions (skin carcinoma, hypertonia, skin hypertrophy lacrimation disorder, maculopapular rash, purpuric rash, vasodilation).

Adverse Reactions Reported for Oral Diclofenac Dosage Form (not topical Solaraze® Gel): *Incidence Greater than 1% marked with asterisk.

Body as a Whole: abdominal pain or cramps*, headache*, fluid retention*, abdominal distention*, malaise, swelling of lips and tongue, photosensitivity, anaphylaxis, anaphylactoid reactions, chest pain.

Cardiovascular: hypertension, congestive heart failure, palpitations, flushing, tachycardia, premature ventricular contractions, myocardial infarction, hypotension.

Digestive: diarrhea*, indigestion*, nausea*, constipation*, flatulence*, liver test abnormalities*, PUB*, i.e., peptic ulcer, with or without bleeding and/or perforation, or bleeding without ulcer, vomiting, jaundice, melena, esophageal lesions, aphthous stomatitis, dry mouth and mucous membranes, bloody diarrhea, hepatitis, hepatic necrosis, cirrhosis, hepatorenal syndrome, appetite change, pancreatitis with or without concomitant hepatitis, colitis, intestinal perforation.

Hemic and Lymphatic: hemoglobin decrease, leukopenia, thrombocytopenia, eosinophilia, hemolytic anemia, aplastic anemia, agranulocytosis, purpura, allergic purpura, bruising.

Metabolic and Nutritional Disorders: azotemia, hypoglycemia, weight loss.

Nervous System: dizziness*, insomnia, drowsiness, depression, diplopia, anxiety, irritability, aseptic meningitis, convulsions, paresthesia, memory disturbance, nightmares, tremor, tic, abnormal coordination, disorientation, psychotic reaction.

Respiratory: epistaxis, asthma, laryngeal edema, dyspnea, hyperventilation, edema of pharynx.

Skin and Appendages: rash*, pruritus*, alopecia, urticaria, eczema, dermatitis, bullous eruption, erythema multiforme major, angioedema, Stevens-Johnson syndrome, excess perspiration, exfoliative dermatitis.

Special Senses: tinnitus*, blurred vision, taste disorder, reversible and irreversible hearing loss, scotoma, vitreous floaters, night blindness, amblyopia.

Urogenital: nephrotic syndrome, proteinuria, oliguria, interstitial nephritis, papillary necrosis, acute renal failure, urinary frequency, nocturia, hematuria, impotence, vaginal bleeding.

Overdosage

Due to the low systemic absorption of topically-applied Solaraze® Gel, overdosage is unlikely. There have been no reports of ingestion of Solaraze®. In the event of oral ingestion, resulting in significant systemic side effects, it is recommended that the stomach be emptied by vomiting or lavage. Forced diuresis may theoretically be beneficial because the drug is excreted in the urine. The effect of dialysis or hemoperfusion in the elimination of diclofenac (99% protein-bound) remains unproven. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption of diclofenac. Supportive and symptomatic treatment should be given for complications such as renal failure, convulsions, gastrointestinal irritation and respiratory depression.

Solaraze Dosage and Administration

Solaraze® Gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Solaraze® Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. The recommended duration of therapy is from 60 days to 90 days. Complete healing of the lesion(s) or optimal therapeutic effect may not be evident for up to 30 days following cessation of therapy. Lesions that do not respond to therapy should be carefully re-evaluated and management reconsidered.

How is Solaraze supplied

Available in tubes of 100 g (NDC 10337-844-01). Each gram of gel contains 30 mg of diclofenac sodium.

Medication Guide
Solaraze (sol-ar-aze)
(diclofenac sodium) Gel, 3%

What is the most important information I should know about Solaraze Gel and medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

Solaraze Gel is an NSAID medicine that is used on the skin only (topical). Do not use Solaraze Gel in or on the eyes.
NSAIDs can cause serious side effects, including:
• Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:
o with increasing doses of NSAIDs
o with longer use of NSAIDs

Do not take or use NSAIDs right before or after a heart surgery called a “coronary artery bypass graft (CABG)”. Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take or use NSAIDs after a recent heart attack.

• Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:
o anytime during use
o without warning symptoms
o that may cause death

The risk of getting an ulcer or bleeding increases with:
o past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs
o taking medicines called “corticosteroids”, “anticoagulants”, “SSRIs”, or “SNRIs”
o increasing doses of NSAIDs
o longer use of NSAIDs
o smoking
o drinking alcohol
o older age
o poor health
o advanced liver disease
o bleeding problems

NSAIDs should only be used:
• exactly as prescribed
• at the lowest dose possible for your treatment
• for the shortest time needed

What is Solaraze Gel?
Solaraze Gel is an NSAID that is used on the skin (topical) to treat a skin condition called actinic keratosis.
Solaraze Gel is not for use in children.

Who should not use Solaraze Gel?
Do not use Solaraze Gel:
• if you have had an allergic reaction to any of the ingredients in Solaraze Gel. See the end of this Medication Guide for a complete list of ingredients in Solaraze Gel.
• right before or after heart bypass surgery.

Before using Solaraze Gel, tell your healthcare provider about all of your medical conditions, including if you:
• have liver or kidney problems
• have high blood pressure
• have asthma
• are pregnant or plan to become pregnant. Taking NSAIDS at about 20 weeks of pregnancy or later may harm your unborn baby. If you need to take NSAIDs for more than 2 days when you are between 20 and 30 weeks of pregnancy, your healthcare provider may need to monitor the amount of fluid in your womb around your baby. You should not take NSAIDs after about 30 weeks of pregnancy.

• are breastfeeding or plan to breastfeed. You and your healthcare provider should decide if you will use Solaraze Gel or breastfeed. You should not do both.

Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins, or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.

How should I use Solaraze Gel?
• Use Solaraze Gel exactly as your healthcare provider tells you to use it.
• Apply Solaraze Gel 2 times a day.
• Apply enough Solaraze Gel to cover each skin lesion and gently rub in.
• Solaraze Gel may be used for 60 to 90 days. You may not see improvement of skin lesions for up to 30 days after stopping treatment. See your healthcare provider if lesions do not respond to treatment.
• Wash your hands after applying Solaraze Gel.

What should I avoid while using Solaraze Gel?
• Avoid spending time in sunlight or artificial light, such as tanning beds or sunlamps. Solaraze Gel can make your skin sensitive to sunlight and the light from tanning beds and sunlamps.
• You should avoid applying Solaraze Gel to open skin wounds, skin infections, or peeling skin.

What are the possible side effects of Solaraze Gel?

Solaraze and other NSAIDs can cause serious side effects, including:
See “What is the most important information I should know about Solaraze Gel and medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?
• new or worse high blood pressure
• heart failure
• liver problems including liver failure
• kidney problems including kidney failure
• low red blood cells (anemia)
• life-threatening skin reactions
• life threatening allergic reactions

Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

Get emergency help right away if you get any of the following symptoms:
• shortness of breath or trouble breathing
• chest pain
• weakness in one part or side of your body
• slurred speech
• swelling of the face or throat

Stop using Solaraze Gel and call your healthcare provider right away if you get any of the following symptoms:
• nausea
• more tired or weaker than usual
• diarrhea
• itching
• your skin or eyes look yellow
• indigestion or stomach pain
• flu-like symptoms
• vomit blood
• there is blood in your bowel movement or it is black and sticky like tar
• unusual weight gain
• skin rash or blisters with fever
• swelling of the arms, legs, hands and feet

Application site skin reactions are common with Solaraze Gel and include: skin redness, itching, rash, dry skin, scaling, and peeling.

If Solaraze Gel is accidentally taken by mouth, call your healthcare provider or get medical help right away.
These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other information about NSAIDs
Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.

Some NSAIDs are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

How should I store Solaraze Gel?
• Store Solaraze Gel at room temperature 68°F to 77°F (20°C to 25°C).
• Keep Solaraze Gel away from heat. Avoid freezing Solaraze Gel.

Keep Solaraze Gel and all medicines out of the reach of children.

General information about the safe and effective use of Solaraze Gel
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Solaraze Gel for a condition for which it was not prescribed. Do not give Solaraze Gel to other people, even if they have the same symptoms that you have. It may harm them.

If you would like more information about Solaraze Gel, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Solaraze Gel that is written for health professionals.

What are the ingredients in Solaraze Gel?
Active ingredient: diclofenac sodium
Inactive ingredient: benzyl alcohol, hyaluronate sodium, polyethylene glycol monomethyl ether, and purified water.

Manufactured by:
PharmDerm®, A division of Fougera Pharmaceuticals Inc.,
Melville, New York 11747
For more information, go to www.pharmaderm.com or call 1-800-645-9833.

This Medication Guide has been approved by the U.S. Food and Drug Administration.
Issued: 02/2016

46185066B
R04/2021
#330

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 100G CONTAINER

NDC 10337-844-01
Net Wt. 100 g
Rx Only
SOLARAZE ® GEL
Diclofenac Sodium-3%

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 100 G CARTON

NDC 10337-844-01
Rx Only
SOLARAZE ® GEL
Diclofenac Sodium-3%
Net Wt. 100 g
PharmaDerm ®