ALPHA DICLOFENAC Tablet

Indications

Treatment of:

- inflammation and degenerative forms of rheumatism: rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and spondylarthritis, painful syndromes of the vertebral column, non-articular rheumatism.

- Acute attacks of gout.

- Post-traumatic and post-operative pain, inflammation and swelling e.g. following dental or orthopedic surgery.

- Painful and/or inflammatory conditions in gynaecology, e.g. primary dysmenorrhea or adnexitis

- As an adjuvant in severe painful inflammatory infections of the ear, nose or throat, e.g. pharyngotonsillitis, otitis. In keeping with general therapeutic principles, the underlying disease should be treated with basic therapy, as appropriated. Fever alone is not an indication.

Dosage and administration

As a general recommendation, the dose should be individually adjusted and the lowest effective dose given for the shortest possible duration.

The total daily dose should be swallowed whole with liquid, preferably before meals, and must not be divided or chewed.

Adults

The recommended initial daily dose is 100 to 150mg. In milder cases, as well as for long-term therapy, 75 to 100 mg daily is usually sufficient.

The total daily dose should generally be divided into 2 to 3 doses.

In primary dysmenorrhea, the daily dose should be individually adjusted and is generally 50 to 150mg. a dose of 50 to 100mg should be given initially and if necessary, increased over the course of several menstrual cycles up to a maximum of 200mg/day. Treatment should be started on appearance of the first symptoms and, depending on the symptomatology, continued for a few days.

Children and adolescents

Children aged 1 year or over and adolescents should be given 0.5 to 2mg/kg body weight daily in 2 to 3 divided doses, depending on the severity of the disorder. For treatment of juvenile rheumatoid arthritis, the daily dose can be raised up to a maximum of 3mg/kg daily, given in divided doses.

The maximum daily dose of 150mg should not be exceeded.

Because of their dosage strength, Alpha DICLOFENAC Sod. Tab. 50mg, are not recommended for use in children and adolescents below 14 years of age, Alpha DICLOFENAC Sod. Tab. 50mg could be used in these patients.

・Known hypersensitivity to the active substance or to any of the excipients.

・Active gastric or intestinal ulcer, bleeding or perforation.

・Last trimester of pregnancy.

・Severe hepatic, renal or cardiac failure.

・Like other non-steroidal anti-inflammatory drugs (NSAIDs) Alpha DICLOFENAC Sod. Tab. 50mg is also contraindicated in patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs.

Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: common (≥ 1/100, ≥ 1/10), uncommon (≥ 1/1,000, ≥ 1/100) rare (≥ 1/10,000, < 1/1,000), Very rare (≥ 1/10,000), including isolated reports.

The following adverse effects include those reported with Alpha DICLOFENAC Sod. Tab. 50mg gastro-resistant tablets and/or other pharmaceutical forms of diclofenac, with either short-term or long-term use.

- Blood and lymphatic system disorders:

Very rare: Thrombocytopenia, leukopenia, anaemia (including haemolytic and aplastic anaemia), agranulocytosis.

-Immune system disorders:

Rare: Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock).

Very rare: Angioneurotic oedema (including face oedema).

- Psychiatric disorders:

Very rare: Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder.

- Nervous system disorders:

Common: Headache, dizziness.

Rare: Somnolence.

Very rare: Paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident.

The following interactions include those observed with Alpha DICLOFENAC Sod. Tab. 50mg gastro-resistant tablets and/or other pharmaceutical forms of diclofenac.

Lithium: if used concomitantly, diclofenac may raise plasma concentrations of lithium. Monitoring of the serum lithium level is recommended.

Digoxin: if used concomitantly, diclofenac may raise plasma concentrations of digoxin. Monitoring of the serum digoxin level is recommended.

Diuretics and antihypertensive agents: Like other NSAIDs, concomitant use of diclofenac or antihypertensive agents (e.g. beta-blockers, angiotensin converting enzyme (ACE) inhibitor) may cause a decrease in their antihypertensive effect. Therefore, the combination should be administered with caution and patients, especially the elderly, should have their blood pressure periodically monitored. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE inhibitors due to the increased risk of nephrotoxicity. Concomitant treatment with potassium-sparing drugs may be associated with increased serum potassium levels, which should therefore be monitored frequently.

Other NSAIDs and corticosteroids: concomitant administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the frequency of gastrointestinal adverse effects.

Anticoagulants and anti-platelet agents: Caution is recommended since concomitant administration could increase the risk of bleeding. Although clinical investigations do not appear to indicate that diclofenac affect the action of anticoagulants, there are isolated reports of an increased risk of haemorrhage in patients receiving diclofenac and anticoagulant concomitantly. Close monitoring of such patients is therefore recommended.

Selective serotonin reuptake inhibitors (SSRIs): concomitant administration of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.

Antidiabetics: clinical studies have shown that diclofenac can be given together with oral antidiabetic agents without influencing their clinical effect. However, there have been isolated reports of both hypoglycaemic and hyperglycaemic effects necessitating changes in the dosage of the antidiabetic agents during treatment with diclofenac. For this reason, monitoring of the blood glucose level is recommended as a precautionary measure during concomitant therapy.

Methotrexate: caution is recommended when NSAIDs are administered less than 24 hours before or after treatment with methotrexate, since blood concentrations of methotrexate may rise and the toxicity of this substance be increased.

Cyclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporin due to the effect on renal. Therefore, it should be given at doses lower than those that would be used in patient not receiving cyclosporin.

Quinolone antibacterial: There have been isolated reports of convulsions which may have been due to concomitant use of quinolone and NSAIDs.

Warnings

Gastrointestinal bleeding, ulceration or perforation, which can be fatal, have been reported with all NSAIDs and may occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. They generally have more serious consequences in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving Alpha DICLOFENAC Sod. Tab. 50mg, the medicinal product should be withdrawn.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including Alpha DICLOFENAC Sod. Tab. 50 mg. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Alpha DICLOFENAC Sod. Tab. 50mg should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur in rare cases without earlier exposure to diclofenac.

Like other NSAIDs, Alpha DICLOFENAC Sod. Tab. 50mg may mask the signs and symptoms of infection due to its pharmacodynamic properties.

Precautions

General

The concomitant use of Alpha DICLOFENAC Sod. Tab. 50mg 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 adverse effects.

Caution is indicated 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.

Alpha DICLOFENAC Sod. Tab. 50mg 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.

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 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.

Gastrointestinal effects

As with all NSAIDs, close medical surveillance is imperative and particular caution should be exercised when prescribing Alpha DICLOFENAC Sod. Tab. 50mg in patients with symptoms indicative of gastrointestinal (GI) disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see adverse effects). The risk of GI bleeding is higher with increasing NSAID does and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation and in the elderly.

To reduce the risk of GI toxicity in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly, the treatment should be initiated and maintained at the lowest effective dose. 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 recommended in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants, anti-platelet agents or selective serotonin0reuptake inhibitors.

Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn’s disease, as their condition may be exacerbated.

Hepatic effects

Close medical surveillance is required when prescribing Alpha DICLOFENAC Sod. Tab. 50mg to patients with impaired hepatic function, as their condition may be exacerbated.

As with other NSAIDs, values of one or more liver enzymes may increase. During prolonged treatment with Alpha DICLOFENAC Sod. Tab. 50mg, 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), Alpha DICLOFENAC Sod. Tab. 50mg should be discontinued. Hepatitis may occur without prodromal symptoms.

Caution is called for when using Alpha DICLOFENAC Sod. Tab. 50mg in patients with hepatic porphyria, since it may trigger an attack.