Voltaren Rapide 50 mg

Interactions with herbal products have not been established.

Patients experiencing visual disturbances, dizziness, vertigo, somnolence or other central nervous system disturbances while taking VOLTAREN RAPIDE should refrain from driving or using machines.

Interactions with food have not been established.

Diclofenac increases platelet aggregation time but does not affect bleeding time, plasma thrombin clotting time, plasma fibrinogen, or factors V and VII to XII. Statistically significant changes in prothrombin and partial thromboplastin times have been reported in normal volunteers. The mean changes were observed to be less than 1 second in both instances, and are unlikely to be clinically important.

Persistently abnormal or worsening renal, hepatic or hematological test values should be followed up carefully since they may be related to therapy.

Lower doses of VOLTAREN RAPIDE should be considered in patients with impaired hepatic function (see Warnings and Precautions, Hepatic/Biliary/Pancreatic).

In the elderly, frail and debilitated, the dosage should be reduced to the lowest level providing control of symptoms, and adjusted when necessary (see Warnings and Precautions, Special Populations, Geriatrics).

VOLTAREN RAPIDE (diclofenac potassium) 50 mg sugar-coated tablets:

VOLTAREN RAPIDE is indicated for short-term treatment only, i.e., for a maximum of a few weeks only.

VOLTAREN RAPIDE should be taken with food.

The recommended daily dose for VOLTAREN RAPIDE is one 50 mg tablet, every 6-8 hours as required for a total daily maximum amount of 150 mg. For primary dysmenorrhea, treatment may be initiated with a loading dose of 100 mg, followed by 50 mg every six to eight hours, when required. When a loading dose is necessary, the first day maximum total amount is 200 mg.

Patients should be maintained on the lowest effective dose.

Lower doses of VOLTAREN RAPIDE should be considered in patients with impaired renal function (see Warnings and Precautions, Renal).

Patients who miss one or more doses of VOLTAREN RAPIDE (diclofenac potassium) should not increase the dose of VOLTAREN RAPIDE to compensate for the missed dose or doses, but should continue with their therapy as soon as possible.

hepatic necrosis, hepatic failure.

Evidence from clinical studies and post-market experience suggests that use in the geriatric population is associated with differences in safety (see Warnings and Precautions).

Safety and efficacy have not been established in the pediatric population.

There is no typical clinical picture resulting from diclofenac overdosage. Overdosage can cause symptoms such as vomiting, gastrointestinal haemorrhage, diarrhoea, dizziness, tinnitus or convulsions. In the event of significant poisoning, acute renal failure and liver damage are possible.

Management of acute poisoning with NSAIDs, including VOLTAREN RAPIDE essentially consists of supportive measures and symptomatic treatment. Supportive measures and symptomatic treatment should be given for complications such as hypotension, renal failure, convulsions, gastrointestinal disorder, and respiratory depression. Special measures such as forced diuresis, dialysis or haemoperfusion are probably of no help in eliminating NSAIDs, including VOLTAREN RAPIDE due to the high protein binding and extensive metabolism. Activated charcoal may be considered after ingestion of a potentially toxic overdose, and gastric decontamination (e.g. vomiting, gastric lavage) after ingestion of a potentially life threatening overdose.

Patients with pre-existing renal insufficiency (GFR <60 mL/min or 1 mL/s), dehydrated patients, patients on salt restricted diets, those with congestive heart failure, cirrhosis, liver dysfunction, taking angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, cyclosporin, diuretics, and the elderly should have their renal function monitored (e.g. urine output, serum creatinine, creatinine clearance and serum urea) during therapy with VOLTAREN RAPIDE.

Electrolytes, including serum potassium, should be monitored periodically, especially in patients with diabetes mellitus, renal failure, increased age, or those receiving concomitant therapy with adrenergic blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, cyclosporin, or some diuretics.

(See Contraindications, Coronary Artery Bypass Graft Surgery.)

Numerous studies have shown that the concomitant use of NSAIDs and anti-coagulants increases the risk of bleeding. Concurrent therapy of VOLTAREN RAPIDE with warfarin requires close monitoring of the international normalized ratio (INR).

Even with therapeutic INR monitoring, increased bleeding may occur.

In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary diseases or chronic infections of the respiratory tract (especially if linked to allergic rhinitis-like symptoms), reactions on NSAIDs like asthma exacerbations (so-called intolerance to analgesics/analgesics-asthma), Quincke’s oedema or urticaria are more frequent than in other patients. Therefore, special precaution is recommended in such patients (readiness for emergency). This is applicable as well for patients who are allergic to other substances, e.g. with skin reactions, pruritus or urticaria.

VOLTAREN RAPIDE (diclofenac potassium) is not a substitute for corticosteroids. It does not treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids (see Drug Interactions, Drug-Drug Interactions, Glucocorticoids).

ASA-induced asthma is an uncommon but very important indication of ASA and NSAID sensitivity. It occurs more frequently in patients with asthma who have nasal polyps.

Patients on long-term treatment with VOLTAREN RAPIDE should have an ophthalmologic examination performed periodically, and if they experience blurred and/or diminished vision.

VOLTAREN RAPIDE is contraindicated for use during the third trimester of pregnancy because of risk of premature closure of the ductus arteriosus and the potential to prolong parturition.

Caution should be exercised in prescribing VOLTAREN RAPIDE during the first and second trimesters of pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryofoetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation after use of a prostaglandin synthesis inhibitor in early pregnancy.

In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. Diclofenac potassium readily crosses the placental barrier.

As with other NSAIDs, borderline elevations of one or more liver enzyme tests (AST, ALT, alkaline phosphatase) may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction, while on therapy with VOLTAREN RAPIDE. Severe hepatic reactions including jaundice and cases of fatal hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes, have been reported with VOLTAREN RAPIDE.

Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop (e.g. jaundice), or if systemic manifestations occur (e.g. eosinophilia, associated with rash, etc.), this drug should be discontinued.

If there is a need to prescribe this drug in the presence of impaired liver function, it must be done under strict observation.

Caution is advised when using VOLTAREN RAPIDE in patients with hepatic porphyria, since VOLTAREN RAPIDE may trigger an attack.

Some NSAIDs are associated with persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy with an NSAID. Should urinary symptoms occur, in the absence of an alternate explanation, treatment with VOLTAREN RAPIDE should be stopped to ascertain if symptoms disappear. This should be done before urological investigations or treatments are carried out.

Some patients may experience drowsiness, dizziness, blurred vision, vertigo, tinnitus, hearing loss, insomnia or depression with the use of NSAIDs, such as VOLTAREN RAPIDE. If patients experience such adverse reaction(s) they should exercise caution in carrying out activities that require alertness.

Frail or debilitated patients may tolerate side effects less well and therefore special care should be taken in treating this population. To minimize the potential risk for an adverse event, the lowest effective dose should be used for the shortest possible duration. As with other NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, hepatic or cardiac function. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

VOLTAREN RAPIDE is not recommended for use with other NSAIDs, with the exception of low-dose ASA for cardiovascular prophylaxis, because of the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions. (See Drug Interactions, Drug-Drug Interactions, Acetylsalicylic acid (ASA) or other NSAIDs.)

Diclofenac potassium should not be used concomitantly with diclofenac sodium (e.g. VOLTAREN or VOLTAREN SR) since both exist in plasma as the same active organic anion.

Serious GI toxicity (sometimes fatal), such as peptic/duodenal ulceration, inflammation, perforation, obstruction and gastrointestinal bleeding, can occur at any time, with or without warning symptoms, in patients treated with NSAIDs, such as VOLTAREN RAPIDE. Minor upper GI problems, such as dyspepsia, commonly occur at any time. Health care providers should remain alert for ulceration and bleeding in patients treated with VOLTAREN RAPIDE, even in the absence of previous GI tract symptoms. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore special care should be taken in treating this population. To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. For high risk patients, alternate therapies that do not involve NSAIDs should be considered (see Warnings and Precautions, Special Populations, Geriatrics).

Patients should be informed about the signs and/or symptoms of serious GI toxicity and instructed to discontinue using VOLTAREN RAPIDEand seek emergency medical attention if they experience any such symptoms. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Most patients who develop a serious upper GI adverse event on NSAID therapy have no symptoms. Upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue, thus increasing the likelihood of developing a serious GI event at some time during the course of therapy. Even a short-term therapy has its risks.

Caution should be taken if prescribing VOLTAREN RAPIDE to patients with a prior history of peptic/duodenal ulcer disease or gastrointestinal bleeding as these individuals have a greater than 10-fold higher risk for developing a GI bleed when taking a NSAID than patients with neither of these risk factors. Other risk factors for GI ulceration and bleeding include the following: H. pylori infection, increased age, prolonged use of NSAID therapy, excess alcohol intake, smoking, poor general health status or concomitant therapy with any of the following: anti-coagulants (e.g. warfarin); anti-platelet agents (e.g. ASA, clopidogrel); oral corticosteroids (e.g. prednisone); Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g. citalopram, fluotexine, paroxetine, sertraline).

There is no definitive evidence that the concomitant administration of histamine H₂-receptor antagonists and/or antacids will either prevent or reduce the occurrence of gastrointestinal adverse events associated with the use of VOLTAREN RAPIDE.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike acetylsalicylic acid (ASA), their effect on platelet function is quantitatively less, or of shorter duration, and is reversible.

VOLTAREN RAPIDE and other NSAIDs have no proven efficacy as anti-platelet agents and should not be used as a substitute for ASA or other anti-platelet agents for prophylaxis of cardiovascular thromboembolic diseases. Anti-platelet therapies (e.g. ASA) should not be discontinued. There is some evidence that use of NSAIDs with ASA can markedly attenuate the cardioprotective effects of ASA (see Drug Interactions, Drug-Drug Interactions, Acetylsalicylic Acid (ASA) or other NSAIDs).

Concomitant administration of VOLTAREN RAPIDE with low dose ASA increases the risk of GI ulceration and associated complications.

VOLTAREN RAPIDE should not be given to patients with complete or partial syndrome of ASA-intolerance (rhinosinusitis, urticaria/angioedema, nasal polyps, asthma) in whom asthma, anaphylaxis, urticaria/angioedema, rhinitis or other allergic manifestations are precipitated by ASA or other NSAIDs. Fatal anaphylactoid reactions have occurred in such individuals. As well, individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse reaction (see Contraindications).

Patients sensitive to any one of the NSAIDs may be sensitive to any of the other NSAIDs as well.

The use of VOLTAREN RAPIDE, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of VOLTAREN RAPIDE should be considered.

Use of NSAIDs, such as VOLTAREN RAPIDE, can promote sodium retention in a dose-dependant manner, which can lead to fluid retention and edema, and consequences of increased blood pressure and exacerbation of congestive heart failure. Thus, caution should be exercised in prescribing VOLTAREN RAPIDE in patients with a history of congestive heart failure, compromised cardiac function, hypertension, increased age or other conditions predisposing to fluid retention (see Warnings and Precautions, Cardiovascular).

Use of NSAIDs, such as VOLTAREN RAPIDE, can increase the risk of hyperkalemia, especially in patients with diabetes mellitus, renal failure, increased age, or those receiving concomitant therapy with adrenergic blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, cyclosporin, or some diuretics. Electrolytes should be monitored periodically (see Contraindications).

VOLTAREN RAPIDE, in common with other NSAIDs, may mask signs and symptoms of an underlying infectious disease.

(See Contraindications.)

(See Warnings and Precautions, Neurologic.)

Patients older than 65 years (referred to in this document as older or elderly) and frail or debilitated patients are most susceptible to a variety of adverse reactions from NSAIDs. The incidence of these adverse reactions increases with dose and duration of treatment. In addition, these patients are less tolerant to ulceration and bleeding. Most reports of fatal GI events are in this population. Older patients are also at risk of lower esophageal injury including ulceration and bleeding.

For such patients, the dosage should be given to a starting dose lower than the one usually recommended, with individual adjustment when necessary and under close supervision.

As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known prior exposure to VOLTAREN RAPIDE. In post-marketing experience, rare cases of anaphylactic/anaphylactoid reactions and angioedema have been reported in patients receiving VOLTAREN RAPIDE. VOLTAREN RAPIDE should not be given to patients with the ASA-triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking ASA or other NSAIDs (see Contraindications).

Patients on long-term treatment with VOLTAREN RAPIDE should have their hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), and platelets checked if they exhibit any signs or symptoms of anemia or blood loss or blood dyscrasia.

(See Contraindications.)

(See Warnings and Precautions, Skin.)

Blood dyscrasias (such as neutropenia, leukopenia, thrombocytopenia, aplastic anemia and agranulocytosis) associated with the use of NSAIDs are rare, but could occur with severe consequences.

Anemia is sometimes seen in patients receiving NSAIDs, including VOLTAREN RAPIDE. This may be due to fluid retention, GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including VOLTAREN RAPIDE, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia or blood loss.

(See Warnings and Precautions, Infection, Aseptic Meningitis.)

Rarely, with some NSAIDs, the symptoms of aseptic meningitis (stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissue diseases, etc.) seem to be pre-disposed. Therefore, in such patients, the health care provider must be vigilant to the development of this complication.

In rare cases, serious skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and erythema multiforme have been associated with the use of some NSAIDs. Because the rate of these reactions is low, they have usually been noted during post-marketing surveillance in patients taking other medications also associated with the potential development of these serious skin reactions. Thus, causality is not clear. These reactions are potentially life threatening but may be reversible if the causative agent is discontinued and appropriate treatment instituted. Patients should be advised that if they experience a skin rash they should discontinue their NSAID and contact their physician for assessment and advice, including which additional therapies to discontinue.

Use of VOLTAREN RAPIDE may cause photosensitivity upon exposure to sunlight or UV light causing symptoms such as sunburn, skin rash, skin blisters, pruritus, erythema and discolouration.

(See Contraindications.)

Hepatic function (e.g. serum transaminases, bilirubine) should be monitored regularly during therapy with VOLTAREN RAPIDE.

(Hypertension): Blood pressure should be monitored regularly during therapy with VOLTAREN RAPIDE.

In a study of ten patients with impaired hepatic function (chronic hepatitis and non-decompensated cirrhosis) receiving a single 100 mg oral dose of diclofenac sodium, the kinetics and metabolism of diclofenac were similar to patients without liver disease.

No relevant age-dependant differences in the absorption, metabolism, or excretion of diclofenac have been observed.

Diclofenac sodium is extensively bound (99%) to serum albumin. The apparent volume of distribution is 0.12 to 0.17 L/kg. Single-dose (P.O. or I.M.) studies in rheumatoid patients with joint effusions have shown that diclofenac is distributed to the synovial fluid, where T_max occurs 2 to 4 hours after plasma T_max. Synovial fluid concentrations exceed plasma levels within 4 to 6 hours of administration. This elevation above plasma concentrations can be maintained for up to 12 hours. The synovial fluid elimination half-life is at least 3 times greater than that for plasma.

In humans, diclofenac can be detected in the plasma within 10 minutes of oral administration of diclofenac potassium tablets. Absorption is virtually complete. The area under the plasma curve (AUC) is dose proportional. A 50 mg tablet produces a mean peak plasma concentration of 3.8 μmol/L, 20-60 min post dose. The amount of diclofenac absorbed from VOLTAREN RAPIDE is the same as that obtained from an equivalent VOLTAREN enteric-coated tablet dose. Since diclofenac undergoes extensive first pass metabolism, only half of an orally administered dose is systemically available. The rate and extent of absorption of diclofenac are insignificantly affected (slightly delayed) when diclofenac potassium tablets are taken with food. When given in a regimen of 50 mg TID for 8 days, diclofenac potassium did not produce plasma accumulation of diclofenac.

Diclofenac, the active substance of VOLTAREN RAPIDE (diclofenac potassium), is a non-steroidal anti-inflammatory (NSAID) drug with analgesic properties. Diclofenac inhibits prostaglandin synthesis by interfering with the action of prostaglandin synthetase. This inhibitory effect may partially explain its actions. It is considered to be a peripherally acting analgesic.

Diclofenac potassium tablets have a rapid onset of action, making them particularly suitable for the treatment of acute painful inflammatory conditions.

Plasma clearance of diclofenac is 263±56 mL/min. The mean terminal drug half-life in plasma is 1.8 hr after oral doses. In humans about 60% of the drug and its metabolites are eliminated in the urine and the balance through the bile in the feces. About 1% of an oral dose is excreted unchanged in urine.

In patients suffering from renal impairment, no accumulation of the unchanged active substance can be inferred from the single-dose kinetics when applying the usual dosage schedule. At a creatinine clearance of <10 mL/min, the calculated steady-state plasma levels of the hydroxy metabolites are about 4 times higher than in normal subjects. However, the metabolites are ultimately cleared through the bile. Although no accumulation of pharmacologically active substance seems to occur, caution is advised while administering VOLTAREN RAPIDE to patients with impaired kidney function (i.e. GFR <60 mL/min or 1 mL/sec) (see Warnings and Precautions, Renal). VOLTAREN RAPIDE is contraindicated in patients with severely impaired or deteriorating renal function (creatinine clearance <30 mL/min (0.5 mL/s) (see Contraindications).

The potassium salt of diclofenac in VOLTAREN RAPIDE yields the same active organic anion produced by the sodium salt found in VOLTAREN enteric coated tablets. Therefore, the fate of the systemically available anion is the same for both formulations.

Diclofenac undergoes single and multiple hydroxylation and methoxylation, producing 3'-, 4'-, 5-hydroxy, 4'- 5-hydroxy and 3'-hydroxy-4'-methoxy derivatives of diclofenac. These phenolic metabolites are largely inactive, and (along with the parent compound) are mostly converted to glucuronide conjugates.

The effects of VOLTAREN RAPIDE are largely mediated by inhibition of cyclooxygenases (COXs, COX-1, COX-2). These enzymes are found throughout the body and produce prostaglandins, which are important mediators of pain, fever, and adaptive and protective reactions in many organs and (inflamed) tissues.

VOLTAREN RAPIDE is contraindicated in children and adolescents less than 16 years of age (see Contraindications).