EPIFENAC suppositories relief pain and reduce inflammatory swelling and oedema( fluid retention in the body. The build-up of fluid causes affected tissue to become swollen).

EPIFENAC is capable of relieving the pain and reducing the extent of bleeding during your menstruation. EPIFENAC also has beneficial effects on the symptoms of migraine attacks.

Facts about EPIFENAC suppositories

1. 1. The active substance is ( diclofenac sodium). One suppository contains 12.5 mg, 25 mg, 50 mg, or 100 mg of diclofenac sodium. Certain dosage strengths may not be available in all countries. 
   2. EPIFENAC (Diclofenac) is a nonsteroidal compound with pronounced antirheumatic, anti-inflammatory, analgesic. and antipyretic properties. It inhibits prostaglandin biosynthesis which plays a major role in causing inflammation,  pain and fever. Diclofenac sodium belongs to a group of medicines known as “Non-steroidal anti-inflammatory drugs” (NSAIDs)
   3. After the administration of EPIFENAC suppositories, maximum effect is attained on average within 1 hour. 
   4. EPIFENAC suppositories should not be taken during the last three months of pregnancy( Diclofenac is contraindicated in the third trimester of pregnancy).
   5. 150 mg Diclofenac sodium is the maximum adult daily dose, as a general recommendation, the dose should be individually adjusted and the lowest effective dose given for the shortest possible duration.
   6. children  dosage: in children aged 1 year or over and adolescents below 14 years of age., the dose should be adjusted depending on the body weight. 0.5 to 2 mg diclofenac sodium/kg body weight daily in 2 to 3 divided doses
   7. The suppositories should not be cut apart, as this may lead to uneven distribution of the active substance.
   8. The suppositories should be inserted well into the rectum. It is recommended to take the suppositories after passing stools. Do not use EPIFENAC suppositories if you suffer from Proctitis ( inflammation of the lining of the rectum). 
   9. EPIFENAC suppositories should be kept out of the reach and sight of children.

EPIFENAC suppositories should not be used after the date marked “EXP” on the pack.

EPIFENAC

EPIFENAC suppositories most common side effects are:

Nausea.

Vomiting.

Diarrhoea.

Dyspepsia( Indigestion, also known as dyspepsia. It can happen when your body has trouble digesting food. It occurs in your gastrointestinal (GI) tract. The GI tract is a sequence of organs that play a part in digestion)

abdominal pain

Flatulence( an accumulation of gas in the gastrointestinal tract)

anorexia( loss of appetite). 

Headache

dizziness( a range of sensations, such as feeling faint, woozy, weak or unsteady).

Vertigo( false sense that you or your surroundings are spinning or moving).

Transaminases increased(disorder in liver function).

rash.

Non-steroidal anti-inflammatory drugs (NSAIDs) WARNING

Cardiovascular Risk : 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 cardiovas-cular disease may be at greater risk.  EPIFENAC is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) Surgery.

Gastrointestinal Risk : 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. 

COMPOSITION AND PHARMACEUTICAL FORM

The active substance is ( diclofenac sodium). One suppository contains 12.5 mg, 25 mg, 50 mg, or 100 mg of diclofenac sodium. Certain dosage strengths may not be available in all countries. 

INDICATIONS 

Treatment of: 

Inflammatory and degenerative forms of rheumatism: rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and spondyloarthritis, painful syndromes of the vertebral.

non-articular rheumatism.

Acute attacks of gout.

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

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

Migraine attacks.

As an adjuvant in severe painful inflammatory.

Infections of the ear, nose or throat, e.g. pharyngo-tonsillitis, otitis. In keeping with general therapeutic principles, the underlying disease should be treated with basic therapy. as appropriate. N.B. :Fever alone is not an indication. 

EPIFENAC is simillar (alternative) to Diclogesic

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 suppositories should be inserted well into the rectum. It is recommended to take the suppositories after passing stools. Not to be taken by mouth, as per rectal use only. 

Adults : The recommended initial daily dose is 100 to 150 mg. In milder cases, as well as for long-term therapy, 75 to 100 mg daily is usually sufficient. The total daily pose should generally be divided into 2 to 3 doses.

To suppress nocturnal pain and morning stiffness, treatment with tablets during the day can be supplemented by the administration of a suppository at bedtime (up to a total maximum daily dose of 150 mg).

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

Treatment of migraine attacks with EPIFENAC suppositories should be started with a dose of 100 mg at the first signs of an impending attack. Additional suppositories up to 100 mg may be taken on the same day if required. Should the patient require further therapy on the following days, the maximum daily dose should be limited to 150 mg in divided doses.

Children and adolescents:  Children aged 1 year or over and adolescents should be given 0.5 to 2 mg/kg body weight daily in 2 to 3 divided doses, depending on the severity of the disorder. For treatment of juvenile rheumatoid arthritis, the dose can be raised up to a maximum of 3 mg/ kg daily, given in divided doses. The maximum daily dose of 150 mg should not be exceeded. 

EPIFENAC 12.5 mg or 25 mg suppositories are recommended for use in children and adolescents below 14 years of age.

Because of their dosage strength, EPIFENAC 50 mg suppositories are not recommended for children and adolescents below 14 years of age. EPIFENAC 100 mg suppositories are not suitable for children and adolescents. 

CONTRAINDICATIONS

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 and cardiac failure.

Like other non-steroidal anti-inflammatory drugs (NSAIDs), EPIFENAC is also contraindicated in patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs. 

Proctitis ( inflammation of the lining of the rectum). 

SPECIAL WARNINGS 

Gastrointestinal warning: 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 occur in patients receiving EPIFENAC, the medicinal product should be withdrawn. 

Skin disorders warning: Serious skin reactions, some of them fatal, including:

exfoliative dermatitis.

Stevens-Johnson syndrome.

toxic epidermal necrolysis.

These skin disorders have been reported very rarely in association with the use of NSAIDs, including EPIFENAC. 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. EPIFENAC 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, EPIFENAC may mask the signs and symptoms of infection due to its pharmacodynamic properties.

EPIFENAC is simillar(Alternative) to Rofenac

 

PRECAUTIONS FOR USE

The concomitant use of EPIFENAC 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.

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. 

Pre-existing asthma: in patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa,  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), Ouincke’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, dose medical surveillance is imperative and particular caution should be exercised when prescribing EPIFENAC in patients with symptoms indicative of gastrointestinal (GI) disorders or with a history suggestive of gastric or intestinal ulceration, bleeding or perforation. The risk of GI bleeding is higher with increasing NSAID doses 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, antiplatelet agents or selective serotonin- reuptake 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 EPIFENAC to patients with impaired hepatic function, their condition may be exacerbated. As with other NSAID , values of one or more liver enzymes may increase. During prolonged treatment with EPIFENAC, 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), EPIFENAC should be discontinued. Hepatitis may occur without prodromal symptoms. Caution is called for when using EPIFENAC 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, particular caution is called for in patients with impaired cardiac or renal function, history of hypertension, the elderly, patients receiving concomitant treatment with diuretics or medicinal products that can significantly impact renal function, and in those patients with substantial extracellular volume depletion from any cause, e.g. before or after major surgery. Monitoring of renal function is recommended as a precautionary measure when using EPIFENAC in such cases. Discontinuation of therapy is usually followed by recovery to the pre-treatment state. 

Haematological effects: During prolonged treatment with EPIFENAC, as with other NSAIDs, monitoring of the blood count is recommended. Like other NSAIDs, EPIFENAC may temporarily inhibit platelet aggregation. Patients with defects of haemostasis should be carefully monitored. 

EPIFENAC

INTERACTIONS

The following interactions include those observed with EPIFENAC suppositories 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 with diuretics or antihypertensive agents (e.g. beta-blockers, angiotensin converting enzyme (ACE) inhibitors) 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 undesirable effects.

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

Selective serotonin reuptake inhibitors (SSRIs): Concomitant administration of systemic NSAIDs and SSRIs could 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. 

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

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

PREGNANCY, LACTATION AND FERTILITY

Pregnancy: The use of diclofenac in pregnant women has not been studied. Therefore, EPIFENAC should not be used during the first two trimesters of pregnancy unless the potential benefit to the mother outweighs the risk to the foetus. As with other NSAIDs, use during the third trimester of pregnancy is contraindicated owing to the possibility of uterine inertia and/or premature closure of the ductus arteriosus. Animal studies have not shown any directly or indirectly harmful effects on pregnancy, embryonal/fetal development, parturition or postnatal development .

Lactation:  Like other NSAIDs, diclofenac passes into the breast milk in small amounts. Therefore, EPIFENAC should not be administered during breast feeding in order to avoid undesirable effects in the infant. 

Fertility: As with other NSAIDs, the use of EPIFENAC may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of EPIFENAC should be considered. 

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES 

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

UNDESIRABLE EFFECTS

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 accidents.

Ear and labyrinth disorders 

(Common): Vertigo.

(Very rare): Tinnitus, hearing impaired.

Gastrointestinal disorders 

(Common): Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia. 

(Rare): Gastritis, gastrointestinal haemorrhage, haematemesis. melaena, diarrhoea haemorrhagic, gastrointestinal ulcer (with or without bleeding or perforation), proctitis.

(Very rare): Colitis (including haemorrhagic and exacerbration of ulcerative colitis or Crohn’s disease), constipation, stomatitis, glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis, haemorrhoids aggravated. 

Hepatobiliary disorders 

Common: Transaminases increased.

Rare: Hepatitis, jaundice, liver disorder. 

Very rare: Fulminant hepatitis.

Skin and subcutaneous tissue disorders

Common : Rash.

Rare:  Urticaria. 

Very rare: Bullous eruptions, eczema, erythema, erythema multiforme. Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), dermatitis exfoliative, loss of hair, photosensitivity reaction, purpura, allergic purpura, pruritus.

General disorders and administration site conditions 

Common: Application site irritation.

Rare: Oedema. 

RARE AND VERY RARE DISORDERS

Blood and lymphatic system disorders (Very rare): Thrombocytopenia, leukopenia, anaemia (including haemolytic and aplastic anaemia), agranulocytosis.

Eye disorders (Very rare): Visual disturbance,vision blurred, diplopia.

Cardiac disorders (Very rare): Palpitations, chest pain, cardiac failure, myocardial infarction. 

Vascular disorders (Very rare): Hypertension, vasculitis.

Respiratory, thoracic and mediastinal disorders (Rare): Asthma (induding dyspnoea). (Very rare): Pneumonitis.

Renal and urinary disorders ( Very rare): Acute renal failure acute, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis. 

OVERDOSE 

Symptoms: There is no typical clinical picture resulting from diclofenac overdose. 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. 

Therapeutic measures:  Management of acute poisoning with NSAIDs 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 hemoperfusion are probably of no help in eliminating NSAIDs due to the high protein binding and extensive metabolism. 

PHARMACODYNAMICS 

Mechanism of action: EPIFENAC contains diclofenac sodium, a non-steroidal compound with pronounced antirheumatic, anti-inflammatory, analgesic, and antipyretic properties. Inhibition of prostaglandin biosynthesis, which has been demonstrated in experiments, is considered fundamental to its mechanism of action. Prostaglandins play a major role in causing inflammation, pain, and fever. Diclofenac sodium in vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to those reached in humans 

Pharmacodynamic effects

In rheumatic diseases, the anti-inflammatory and analgesic properties of EPIFENAC elicit a clinical response characterised by marked relief from signs and symptoms such as :pain at rest, pain on movement, morning stiffness, and swelling of the joints, as well as by an improvement in function.

In post-traumatic and post-operative inflammatory conditions, EPIFENAC rapidly relieves both spontaneous pain and pain on movement and reduces inflammatory swelling and wound oedema.

In clinical trials EPIFENAC has also been found to exert a pronounced analgesic effect in moderate and severe pain of non-rheumatic origin. 

Clinical studies have also revealed that, in primary dysmenorrhoea, EPIFENAC is capable of relieving the pain and reducing the extent of bleeding. 

EPIFENAC also has beneficial effects on the symptoms of migraine attacks 

PHARMACOKINETICS

Diclofenac shows a rapid onset of absorption from suppositories, although the rate of absorption is slower than from gastro-resistant tablets administered orally. After the administration of 50 mg suppositories, peak plasma concentrations are attained on average within 1 hour, but maximum concentrations per dose unit are about two thirds of those reached after administration of gastro-resistant tablets. 

The amount absorbed is linearly related to the size of the dose. Since about half of diclofenac is metabolised during its first passage through the liver (“first pass” effect), the area under the concentration curve (AUC) following oral or rectal administration is about half that following an equivalent parenteral dose. 

Pharmacokinetic behaviour does not change after repeated administration. No accumulation occurs provided the recommended dosage intervals are observed. 

The plasma concentrations attained in children given equivalent doses (mg/kg body weight) are similar to those obtained in adults. 

There was no evidence that diclofenac had a teratogenic potential in mice, rats or rabbits. 

Diclofenac had no influence on the fertility of parent animals in rats. 

The prenatal, perinatal and postnatal development of the offspring was not affected. 

EPIFENAC suppositories should not be used after the date marked “EXP” on the pack. 

INSTRUCTIONS FOR USE AND HANDLING 

A medicament is a product which affects your health and consumption contrary to instructions is dangerous for you. 

Follow strictly the doctor’s prescription, the method of use and the instructions of the pharmacist who sold the medicament.

The doctor and the pharmacist are experts in medicine, its benefits and risks. 

Do not by yourself interrupt the period of treatment prescribed for you. 

Do not repeal the same prescription without consulting your doctor.

Patient Information Leaflet

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