Torvex Kit
FDA Label NDC 84460-801

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 [see Warnings and Precautions (5.1)].
• Diclofenac sodium topical solution is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4)and Warnings and Precautions (5.1)].

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 [see Warnings and Precautions (5.2)].

Diclofenac sodium topical solution is indicated for the treatment of signs and symptoms of osteoarthritis of the knee(s).

Diclofenac sodium topical solution: 1.5% w/w

Diclofenac sodium topical solution is contraindicated in the following patients:

• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [see Warnings and Precautions (5.7,5.9)].
• 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 [see Warnings and Precautions (5.7,5.8)].
• In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)].

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1)]
• GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2)]
• Hepatotoxicity [see Warnings and Precautions (5.3)]
• Hypertension [see Warnings and Precautions (5.4)]
• Heart Failure and Edema [see Warnings and Precautions (5.5)]
• Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6)]
• Anaphylactic Reactions [see Warnings and Precautions (5.7)]
• Serious Skin Reactions [see Warnings and Precautions (5.9)]
• Hematologic Toxicity [see Warnings and Precautions (5.12)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to diclofenac sodium topical solution of 911 patients treated between 4 and 12 weeks (mean duration of 49 days) in seven Phase 3 controlled trials, as well as exposure of 793 patients treated in an open-label study, including 463 patients treated for at least 6 months, and 144 patients treated for at least 12 months. The population mean age was approximately 60 years, 89% of patients were Caucasians, 64% were females, and all patients had primary osteoarthritis. The most common adverse events with diclofenac sodium topical solution were application site skin reactions. These events were the most common reason for withdrawing from the studies.

Application Site Reactions

In controlled trials, the most common treatment-related adverse events in patients receiving diclofenac sodium topical solution were application site skin reactions. Application site reactions were characterized by one or more of the following: dryness, erythema, induration, vesicles, paresthesia, pruritus, vasodilation, acne, and urticaria. The most frequent of these reactions were dry skin (32%), contact dermatitis characterized by skin erythema and induration (9%), contact dermatitis with vesicles (2%) and pruritus (4%). In one controlled trial, a higher rate of contact dermatitis with vesicles (4%) was observed after treatment of 152 subjects with the combination of diclofenac sodium topical solution and oral diclofenac. In the open label uncontrolled long-term safety study, contact dermatitis occurred in 13% and contact dermatitis with vesicles in 10% of patients, generally within the first 6 months of exposure, leading to a withdrawal rate for an application site event of 14%.

Adverse Events Common to the NSAID Class

In controlled trials, subjects treated with diclofenac sodium topical solution experienced some adverse events associated with the NSAID class more frequently than subjects using placebo (constipation, diarrhea, dyspepsia, nausea, flatulence, abdominal pain, edema; see Table 1). The combination of diclofenac sodium topical solution and oral diclofenac, compared to oral diclofenac alone, resulted in a higher rate of rectal hemorrhage (3% vs. less than 1%), and more frequent abnormal creatinine (12% vs. 7%), urea (20% vs. 12%), and hemoglobin (13% vs. 9%), but no difference in elevation of liver transaminases.

Table 1 lists all adverse reactions occurring in ≥ 1% of patients receiving diclofenac sodium topical solution, where the rate in the diclofenac sodium topical solution group exceeded placebo, from seven controlled studies conducted in patients with osteoarthritis. Since these trials were of different durations, these percentages do not capture cumulative rates of occurrence.

Table 1: Adverse Reactions occurring in ≥ 1% of patients treated with diclofenac sodium topical solution in placebo and oral diclofenac-controlled trials.

In non-U.S. postmarketing surveillance, the following adverse reactions have been reported during post-approval use of diclofenac sodium topical solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: abdominal pain, accidental injury, allergic reaction, asthenia, back pain, body odor, chest pain, edema, face edema, halitosis, headache, lack of drug effect, neck rigidity, pain

Cardiovascular: palpitation, cardiovascular disorder

Digestive: diarrhea, dry mouth, dyspepsia, gastroenteritis, decreased appetite, mouth ulceration, nausea, rectal hemorrhage, ulcerative stomatitis

Metabolic and Nutritional: creatinine increased

Musculoskeletal: leg cramps, myalgia

Nervous: depression, dizziness, drowsiness, lethargy, paresthesia, paresthesia at application site

Respiratory: asthma, dyspnea, laryngismus, laryngitis, pharyngitis

Skin and Appendages: At the Application Site: Adverse Reactions: contact dermatitis, contact dermatitis with vesicles, dry skin, pruritus, rash; Other Skin and Appendages: eczema, rash, pruritus, skin discoloration, urticaria

Special Senses: abnormal vision, blurred vision, cataract, ear pain, eye disorder, eye pain, taste perversion

See Table 2 for clinically significant drug interactions with diclofenac.

Table 2: Clinically Significant Drug Interactions with Diclofenac

Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions (5.1,5.2,5.4,5.6)].

Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Emesis is not recommended due to a possibility of aspiration and subsequent respiratory irritation by DMSO contained in diclofenac sodium topical solution. Consider activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. For additional information about overdose treatment, contact a poison control center (1-800-222-1222).

Diclofenac sodium topical solution 1.5% is a nonsteroidal anti-inflammatory drug, available as a clear, colorless to faintly pink-orange solution for topical application.

Diclofenac sodium topical solution contains 1.5% w/w diclofenac sodium, USP, a benzeneacetic acid derivative that is a nonsteroidal anti-inflammatory drug (NSAID), designated chemically as 2-[(2,6-dichlorophenyl)amino]-benzeneacetic acid, monosodium salt. It is a white to off-white crystalline powder, hygroscopic, and odorless that is freely soluble in methanol, soluble in alcohol, and sparingly soluble in water. The molecular weight is 318.13. Its molecular formula is C₁₄H₁₀Cl₂NNaO₂ and it has the following structural formula.

Structural Formula (Torvex Kit 1)

Each 1 mL of solution contains 16.05 mg of diclofenac sodium, USP. The inactive ingredients in diclofenac sodium topical solution include: alcohol, dimethyl sulfoxide USP (DMSO, 45.5% w/w), glycerin, propylene glycol, and purified water.

Diclofenac sodium topical solution 1.5% w/w is supplied as a clear, colorless to faintly pink-orange solution containing 16.05 mg of diclofenac sodium per 1 mL of solution, in a white high density polyethylene bottle with a white low-density dropper cap. It is available as follows:

150 mL bottle NDC 65162-911-74

Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Advise the patient to read the FDA-approved patient labeling (Medication Guide) and Instructions for Use that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with diclofenac sodium topical solution and periodically during the course of ongoing therapy.

Cardiovascular Thrombotic Events

Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [see Warnings and Precautions (5.1)].

Gastrointestinal Bleeding, Ulceration, and Perforation

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding [see Warnings and Precautions (5.2)].

Hepatotoxicity

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, instruct patients to stop diclofenac sodium topical solution and seek immediate medical therapy [see Warnings and Precautions (5.3)].

Heart Failure and Edema

Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see Warnings and Precautions (5.5)].

Anaphylactic Reactions

Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [see Contraindications (4)and Warnings and Precautions (5.7)].

Serious Skin Reactions, including DRESS

Advise patients to stop taking diclofenac sodium topical solution immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [see Warnings and Precautions (5.9, 5.10)].

Female Fertility

Advise females of reproductive potential who desire pregnancy that NSAIDs, including diclofenac sodium topical solution, may be associated with a reversible delay in ovulation [see Use in Specific Populations (8.3)]

Fetal Toxicity

Inform pregnant women to avoid use of diclofenac sodium topical solution and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with diclofenac sodium topical solution is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours [see Warnings and Precautions (5.11) and Use in Specific Populations (8.1)].

Avoid Concomitant Use of NSAIDs

Inform patients that the concomitant use of diclofenac sodium topical solution with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy [see Warnings and Precautions (5.2)and Drug Interactions (7)]. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.

Use of NSAIDS and Low-Dose Aspirin

Inform patients not to use low-dose aspirin concomitantly with diclofenac sodium topical solution until they talk to their healthcare provider [see Drug Interactions (7)].

Eye Exposure

Instruct patients to avoid contact of diclofenac sodium topical solution with the eyes and mucosa. Advise patients that if eye contact occurs, immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.

Prevention of Secondary Exposure

Instruct patients to avoid skin-to-skin contact between other people and the knee(s) to which diclofenac sodium topical solution was applied until the knee(s) is completely dry.

Application Site Reactions

Diclofenac sodium topical solution can cause a localized skin reaction at the application site. Advise patients to contact their physicians as soon as possible if they develop any type of localized application site rash.

Special Application Instructions

• Instruct patients not to apply diclofenac sodium topical solution to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and reduce tolerability of the drug.
• Instruct patients to wait until the area treated with diclofenac sodium topical solution is completely dry before applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medication.
• Instruct patients to minimize or avoid exposure of treated knee(s) to natural or artificial sunlight.

Distributed by:
Amneal Pharmaceuticals
Bridgewater, NJ 08807

Rev. 05-2021-03

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised 11-2020-02

Diclofenac (dye-KLOE-fen-ak) Sodium Topical Solution 1.5%

Read the Medication Guide that comes with diclofenac sodium topical solution first. Be sure that you read, understand and follow these Instructions for Use before you use diclofenac sodium topical solution for the first time.

Important: For use on the skin only (topical). Do not get diclofenac sodium topical solution in your eyes, nose or mouth.

Before you use diclofenac sodium topical solution:

• Apply diclofenac sodium topical solution exactly as your healthcare provider tells you. Talk with your healthcare provider or pharmacist if you are not sure.
• Only use diclofenac sodium topical solution to treat pain from osteoarthritis in your knee or knees.
• Apply diclofenac sodium topical solution on clean, dry skin that does not have any cuts, infections or rashes.
• Use diclofenac sodium topical solution 4 times each day on your knee or knees as prescribed.
• Your total dose for each knee is 40 drops of diclofenac sodium topical solution, each time you use it.
• If you get diclofenac sodium topical solution in your eyes, rinse your eyes right away with water or saline. Call your healthcare provider if your eyes are irritated for more than one hour.

Steps for using diclofenac sodium topical solution:

Step 1. Wash your hands with soap and water before applying diclofenac sodium topical solution.

Step 2. Put 10 drops of diclofenac sodium topical solution either on your hand or directly on your knee (see Figure A).

Figure A



Figure A1 (Torvex Kit 2)

or



Figure A2 (Torvex Kit 3)

Step 3. Spread diclofenac sodium topical solution evenly on the front, back and sides of your knee (see Figures B and C). Repeat steps 2 and 3, three times so that your knee is completely covered with a total of 40 drops of diclofenac sodium topical solution.

Figure B



Figure B (Torvex Kit 4)

Figure C



Figure C (Torvex Kit 5)

Step 4. If your healthcare provider has prescribed diclofenac sodium topical solution for both knees, repeat steps 2 and 3 for the other knee.

After you use diclofenac sodium topical solution:

• Wash your hands with soap and water right away after applying diclofenac sodium topical solution.

Do not:

• touch the treated knee or allow another person to touch the knee treated with diclofenac sodium topical solution until your knee is completely dry.
• cover your knee with clothing until your knee is completely dry.
• put sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medicines on your knee until it is completely dry.
• take a shower or a bath for at least 30 minutes after you put diclofenac sodium topical solution on your knee.
• use heating pads or cover the treated area with bandages where you have applied diclofenac sodium topical solution.
• use sunlamps and tanning beds. Protect your treated knee from sunlight. Wear clothes that cover your skin if you have to be in sunlight.

How should I store diclofenac sodium topical solution?

• Store diclofenac sodium topical solution at room temperature between 68°F to 77°F (20°C to 25°C).

Keep diclofenac sodium topical solution and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

*Trademarks are the property of their respective owners.

Distributed by:
Amneal PharmaceuticalsBridgewater, NJ 08807

Rev. 11-2016-01

Menthol
Methyl Salicylate

The packaging for Torvex is shown below:

Pdp (Torvex Kit 9)