Voltaren/Voltaren SR Special Precautions

General: The concomitant use of Voltaren with systemic NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided due to the absence of any evidence demonstrating synergistic benefits and the potential for additive undesirable effects (see Interactions).
Caution is required in the elderly on basic medical grounds. In particular, it is recommended that the lowest effective dose be used in frail elderly patients or those with a low body weight.
Respiratory effects (pre-existing asthma): 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 to NSAIDs such as asthma exacerbations (analgesic intolerance or analgesic-induced 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 (e.g. rash, pruritus or urticaria) to other substances.
Gastrointestinal effects: As with all NSAIDs, including diclofenac, close medical surveillance is required and particular caution should be exercised when prescribing Voltaren in patients with symptoms indicative of gastrointestinal (GI) disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see Adverse Reactions). The risk of GI bleeding is greater with higher NSAID doses and in patients with a history of ulcers (particularly if complicated with bleeding or perforation) and in the elderly.
Treatment should be initiated and maintained at the lowest effective dose to reduce the risk of GI toxicity in patients with a history of ulcers (particularly if complicated with bleeding or perforation) and in the elderly.
Combination therapy with protective agents (e.g. proton pump inhibitors or misoprostol) should be considered for these patients, and also for patients requiring concomitant use of medicinal products containing low-dose acetylsalicylic acid (ASA)/aspirin or other medicinal products likely to increase gastrointestinal risk.
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding). Caution is required in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, antiplatelet agents or selective serotonin reuptake inhibitors (see Interactions).
Hepatic effects: Close medical surveillance is required when prescribing Voltaren to patients with impaired hepatic function, as their condition may be exacerbated (see Adverse Reactions).
As with other NSAIDs, including diclofenac, values of one or more liver enzymes may increase. During prolonged treatment with Voltaren (e.g. in the form of tablets or suppositories), regular monitoring of hepatic function is indicated as a precautionary measure. If abnormal liver function tests persist or worsen, if clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (e.g. eosinophilia, rash), Voltaren should be discontinued. Hepatitis may occur with use of diclofenac without prodromal symptoms.
Caution is required when using Voltaren in patients with hepatic porphyria, since it may trigger an attack.
Renal effects: As fluid retention and oedema have been reported in association with NSAID therapy, including diclofenac, particular caution is required in patients with impaired cardiac or renal function, in patients with a history of hypertension, in the elderly, in patients receiving concomitant treatment with diuretics or medicinal products that can significantly impact renal function, and in patients with substantial extracellular volume depletion from any cause, e.g. before or after major surgery (see Contraindications). Monitoring of renal function is recommended as a precautionary measure when using Voltaren in such cases. Patients usually recover to their pre-treatment state following discontinuation of therapy.
Haematological effects: As with other NSAIDs, complete blood counts are recommended during long-term treatment with Voltaren.
Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with coagulation disorders should be carefully monitored.
Effects on ability to drive and use machines: Patients experiencing visual disturbances, light-headedness, dizziness, drowsiness, vertigo, somnolence, or other central nervous system disturbances while taking Voltaren should refrain from driving or using machines.
Voltaren EC tablet: General: Voltaren gastro-resistant tablets contain lactose and therefore are not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
Gastrointestinal effects: Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn's disease, as their condition may be exacerbated (see Adverse Reactions).
Voltaren SR-FC tablet: General: Voltaren prolonged-release coated tablets contain sucrose and are therefore not recommended in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency.
This medicine contains less than 1 mmol (23 mg) of sodium per dosage unit (coated tablet and prolonged-release coated tablet), making it practically "sodium-free".
Gastrointestinal effects: NSAIDs, including diclofenac, can be associated with an increased risk of a gastrointestinal anastomosis leak. Caution is required with the use of Voltaren after gastrointestinal surgery and close medical monitoring is recommended.
NSAIDs cause an increased risk of serious gastrointestinal 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 are at greater risk for serious gastrointestinal events.
Hepatic effects: As with all NSAIDs, including diclofenac, levels of one or more liver enzymes may rise during treatment with Voltaren. This has been observed very frequently with diclofenac in clinical studies (in approximately 15% of patients), but is very rarely accompanied by clinical symptoms. Most of these cases involve borderline increases. Frequently (in 2.5% of cases) the increases observed were moderate (≥3 to <8 times the upper limit of normal), while the incidence of marked increases (≥8 times the upper limit of normal) remained around 1%. Elevated liver enzyme levels were accompanied by clinically manifest liver damage in 0.5% of cases in the previously mentioned clinical studies. Elevated enzyme levels were generally reversible after discontinuation of the drug.
In addition to elevated liver enzymes, there have been rare reports of severe hepatic reactions, including jaundice and fulminant hepatitis, hepatic necrosis and hepatic failure which, in isolated cases, had a fatal outcome.
In rare cases, diclofenac has been associated with serious liver injury.
Renal effects: Owing to the importance of prostaglandins in maintaining renal blood flow, prolonged treatment with high doses of NSAIDs, including diclofenac, frequently (1-10%) results in oedema and hypertension.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of Voltaren in patients with advanced renal disease. Therefore, treatment with Voltaren is not recommended in these patients with advanced renal disease. If therapy must be initiated, close monitoring of the patient's renal function is advisable.
Cardiovascular effects: Treatment with NSAIDs including diclofenac, particularly at high doses and for prolonged periods, may be associated with a slightly increased risk of serious cardiovascular thrombotic events (including myocardial infarction and stroke).
Treatment with Voltaren is generally not recommended in patients with established cardiovascular disease (heart failure, established ischaemic heart disease, peripheral arterial disease) or uncontrolled hypertension. If needed, patients with established cardiovascular disease, uncontrolled hypertension or significant risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus and smoking) should be treated with Voltaren only after careful consideration and only at doses of up to 100 mg daily if treated for more than 4 weeks.
As the cardiovascular risks of diclofenac may increase with dose and duration of exposure, the lowest effective daily dose should be used for the shortest duration possible. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially when treatment continues for more than 4 weeks.
Patients should remain alert for the signs and symptoms of serious arterial thromboembolic events (e.g. chest pain, shortness of breath, weakness, slurring of speech), which can occur without warning. Patients should be instructed to see a physician immediately in case of such an event.
NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Use in Pregnancy: Voltaren is contraindicated for use during the third trimester of pregnancy because of risks of premature closure of the ductus arteriosus and the potential to prolong parturition. Caution is recommended in prescribing Voltaren during the first and second trimesters of pregnancy, particularly from the middle to end of the second trimester of pregnancy (onset at approximately 20 weeks) due to possible fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment or failure.
Voltaren should not be used during the first two trimesters of pregnancy unless the expected benefits to the mother outweigh the risks to the fetus.
Published studies and post-marketing reports describe maternal Non-Steroidal Anti-Inflammatory Drug (NSAID) use at approximately 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment or failure. NSAIDs were shown to cause significant reduction in fetal urine production prior to reduction of amniotic fluid volume. There have also been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction and renal impairment without oligohydramnios, some of which were irreversible, even after treatment discontinuation.
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.
Complications of prolonged oligohydramnios may for example, include limb contractures and delayed lung maturation. In some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If after careful consideration of the benefit-risk, NSAID treatment is considered necessary to be administered anywhere from the middle (onset at approximately 20 weeks) to the end of the second trimester of pregnancy, the use should be limited to the lowest effective dose and shortest duration possible. It is also recommended that ultrasound monitoring of amniotic fluid be considered if Voltaren treatment extends beyond 48 hours and that NSAIDs treatment be discontinued if oligohydramnios occurs, followed by appropriate medical follow up.
Voltaren suppository: Gastrointestinal effects: Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn's disease, as their condition may be exacerbated (see Adverse Reactions).