The apparent volume of distribution (V/F) of Diclo sodium is 1.4 L/kg.
Diclo is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15-105 mcg/mL) achieved with recommended doses.
Diclo diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of Diclo.
In clinical trials of Diclo- containing products, meaningful elevations (i.e., more than 3 times the ULN) of AST (SGOT) were observed in about 2% of approximately 5,700 patients at some time during Diclo treatment (ALT was not measured in all studies).
In a large, open-label, controlled trial of 3,700 patients treated with oral Diclo sodium for 2-6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of patients and included marked elevations (greater than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3-8 times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in patients receiving Diclo when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.
Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with Diclo in 42 of the 51 patients in all trials who developed marked transaminase elevations.
In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with Diclo. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.
In a European retrospective population-based, case-controlled study, 10 cases of Diclo associated drug-induced liver injury with current use compared with non-use of Diclo were associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this particular study, based on an overall number of 10 cases of liver injury associated with Diclo, the adjusted odds ratio increased further with female gender, doses of 150 mg or more, and duration of use for more than 90 days.
Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with Diclo, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with Diclo. However, severe hepatic reactions can occur at any time during treatment with Diclo.
If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), VOLTAREN should be discontinued immediately.
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue VOLTAREN immediately, and perform a clinical evaluation of the patient.
To minimize the potential risk for an adverse liver related event in patients treated with VOLTAREN, use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing VOLTAREN with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, anti-epileptics).
Diclo and Alcohol
You should not drink alcohol while taking Diclo. It can increase the risk of stomach bleeding and may cause damage to your kidneys.
What are the uses for Diclo?
Diclo is used to relieve the signs and symptoms of:
People who take nonsteroidal anti-inflammatory drugs (NSAIDs) (other than aspirin) such as Diclo may have a higher risk of having a heart attack or a stroke than people who do not take these medications. These events may happen without warning and may cause death. This risk may be higher for people who take NSAIDs for a long time. Do not take an NSAID such as Diclo if you have recently had a heart attack, unless directed to do so by your doctor. Tell your doctor if you or anyone in your family has or has ever had heart disease, a heart attack, or a stroke, if you smoke, and if you have or have ever had high cholesterol, high blood pressure, or diabetes. Get emergency medical help right away if you experience any of the following symptoms: chest pain, shortness of breath, weakness in one part or side of the body, or slurred speech.
If you will be undergoing a coronary artery bypass graft (CABG; a type of heart surgery), you should not take Diclo right before or right after the surgery.
NSAIDs such as Diclo may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may develop at any time during treatment, may happen without warning symptoms, and may cause death. The risk may be higher for people who take NSAIDs for a long time, are older in age, have poor health, or drink large amounts of alcohol while taking Diclo. Tell your doctor if you take any of the following medications: anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); aspirin; other NSAIDs such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, Sarafem, Selfemra, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); or serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), and venlafaxine (Effexor XR). Also tell your doctor if you have or have ever had ulcers, bleeding in your stomach or intestines, or other bleeding disorders. If you experience any of the following symptoms, stop taking Diclo and call your doctor: stomach pain, heartburn, vomiting a substance that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools.
Keep all appointments with your doctor and the laboratory. Your doctor will monitor your symptoms carefully and will probably order certain tests to check your body's response to Diclo. Be sure to tell your doctor how you are feeling so that your doctor can prescribe the right amount of medication to treat your condition with the lowest risk of serious side effects.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with Diclo and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) to obtain the Medication Guide.
Mechanism Of Action
Diclo has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action of VOLTAREN, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).
Diclo is a potent inhibitor of prostaglandin synthesis in vitro. Diclo concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because Diclo is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.
Common side effects
Common side effects of Diclo tablets, capsules and suppositories happen in more than 1 in 100 people.
Talk to your doctor or pharmacist if these side effects bother you or don't go away:
- feeling dizzy or vertigo
- stomach ache, wind or loss of appetite
- feeling sick (nausea)
- being sick (vomiting) or diarrhoea
- mild rash
You're less likely to have side effects with Diclo gel or plasters. This is because not as much of the medicine gets into your body. But you may still get the same side effects, especially if you use a lot on a large area of skin.
In addition, using Diclo gel or plasters can affect your skin. It can make your skin:
- more sensitive to sunlight than normal
- develop a rash where the gel or plaster has been applied
- dry or irritated (eczema)
- itchy or inflamed (dermatitis)
What Other Drugs Interact with Diclo?
If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.
Severe interactions of Diclo include:
Serious Interactions of Diclo include:
Diclo has moderate interactions with at least 247 different drugs.
Diclo has mild interactions with at least 109 different drugs.
This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.