Feminax Ultra

Feminax Ultra 250mg Gastro-resistant Tablets

Each tablet contains 250 mg of naproxen. For excipients, see 6.1.

Gastro-Resistant Tablet

White, round, biconvex enteric coated tablets, overprinted in black 3N3.

Indicated for the treatment of primary dysmenorrhoea in women aged 15 to 50 years.

For oral administration.

To be taken preferably with or after food swallowed whole with water. Not to be broken or crushed.

Adolescents (post puberty) and adult females between the ages of 15 and 50:

On the first day 2 tablets (500 mg) should be taken initially and then one tablet (250 mg) after 6 to 8 hours if needed.

On the second and third day, if needed, one tablet (250mg) should be taken every 6 to 8 hours. Not more than 3 tablets to be taken per day. The maximum duration of continuous treatment in any one cycle (period) is 3 days.

Naproxen is contra-indicated for patients with known hypersensitivity to naproxen, naproxen sodium formulations or any of the excipients.

Naproxen is contra-indicated in patients with a history of, or active, peptic ulceration and active gastrointestinal bleeding (two or more distinct episodes of proven ulceration or bleeding).

Naproxen is contra-indicated in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Naproxen should not be given to patients in whom aspirin or other non-steroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis, nasal polyps, angioedema or urticaria, as the potential exists for cross-sensitivity reactions.- Pregnancy and lactation).

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see warnings on GI and cardiovascular risks below). Patients treated with NSAIDs long-term should undergo regular medical supervision to monitor for adverse events.

The anti-inflammatory and antipyretic activities of Naproxen may reduce inflammation and fever, thereby diminishing their utility as diagnostic signs.

As with other non-steroidal anti-inflammatory drugs, elevations of one or more liver function tests may occur. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. Severe hepatic reactions, including jaundice and hepatitis (some cases of hepatitis have been fatal) have been reported with this drug as with other nonsteroidal anti-inflammatory drugs. Cross reactivity has been reported.

Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined.

Although sodium retention has not been reported in metabolic studies, it is possible that patients with questionable or compromised cardiac function may be at a greater risk when taking Naproxen.

Combination with other NSAIDs

The combination of naproxen-containing products and other NSAIDs including ibuprofen, cyclooxygenase-2 selective inhibitors or aspirin is not recommended, because of the cumulative risks of inducing serious NSAID-related adverse events.

Elderly:

The elderly and/or debilitated patients have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal. Prolonged use of NSAIDs in these patients is not recommended. Where prolonged therapy is required, patients should be reviewed regularly.

Respiratory disorders

Caution is required if administered to patients suffering from, or with a history of, bronchial asthma or allergic disease, since administration of naproxen or other NSAIDs may elicit bronchospasm.

Cardiovascular, Hepatic Impairment and Renal failure linked to reduced prostaglandin production:

The administration of an NSAID may cause a dose dependant reduction in prostaglandin formation and precipitate renal failure.).

Cardiovascular and cerebrovascular effects

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or mild to moderate heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infaction or stroke).).

Patients with a history of GI toxicity should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.

If GI bleeding or ulceration occurs in patients receiving the product, the treatment should be withdrawn.

Serious gastro-intestinal adverse reactions may occur at any time in patients on therapy with non-steroidal anti-inflammatory drugs. The duration of therapy does not seem to change the risk of occurrence. Studies to date have not identified any subset of patients not at risk of developing peptic ulcer and bleeding. However, elderly and debilitated patients tolerate gastro-intestinal ulceration or bleeding less well than others. Most of the serious gastro-intestinal events associated with non-steroidal anti-inflammatory drugs occurred in this patient population.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated.

Haematological

Patients who have coagulation disorders or patients who are receiving drug therapy that interferes with haemostasis should be carefully observed if naproxen-containing products are administered.

Patients at high risk of bleeding or those on full anti-coagulation therapy (e.g. dicoumarol derivatives) can be at increased risk of bleeding if given naproxen-containing products concurrently.

Anaphylactic (anaphylactoid) reactions

In susceptible individuals hypersensitivity reactions may occur. Anaphylactic (anaphylactoid) reactions may occur both in patients with and without a history of hypersensitivity or exposure to aspirin, other non-steroidal anti-inflammatory drugs or naproxen-containing products. They may also occur in individuals with a history of angioedema, bronchospastic reactivity (e.g. asthma), rhinitis and nasal polyps.

Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.

Steroids

Patients taking steroids should not take naproxen except under the supervision of their doctor. If steroid dosage is eliminated or reduced during therapy, the steroid dosage should be reduced slowly and the patients must be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

Ocular effects

Studies have not shown any changes in the eye attributable to naproxen administration. Rarely, adverse ocular disorders including papillitis, retrobulbar optic neuritis and papilledema, have been reported in users of NSAIDs including naproxen, although a cause-and-effect relationship cannot be established; accordingly, patients who develop visual disturbances during treatment with naproxen-containing products should have an ophthalmological examination.

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.

Dermatological

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. Patients appear to be at highest risk for these reactions early in the course of the therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. The product should be discontinued at the first appearance of skin rash, mucosal lesion, or any other sign of hypersensitivity.

Precautions related to female fertility:

The use of naproxen, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, 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 fertility, withdrawal of naproxen should be considered.

This product should not be taken, except on the advice of a doctor, by women who first experience period pain more than a year after starting menstruation.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The label will include:

Dizziness, drowsiness, vertigo, insomnia, fatigue, depression or visual disturbances are possible undesirable effects after taking NSAIDs. If affected, patients should not drive or operate machinery.

The following adverse events have been reported with NSAIDs and naproxen.

Gastro-intestinal: the most commonly-observed adverse events are gastrointestinal in nature.- Special warnings and precautions for use) and oesophagitis have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs in patients with, or without, a history of previous hypersensitivity reaction to NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis, erythema multiforme and Stevens-Johnson Syndrome).

Metabolic and nutrition disorders: hyperkalaemia.

Psychiatric disorders: Insomnia, dream abnormalities, depression, confusion and hallucinations.

Cardiac disorders: Oedema, palpitations, hypertension, and cardiac failure, and congestive heart failure have been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

Eosinophilic pneumonitis has also been reported.

Vascular disorders: Hypertension, vasculitis.

Renal and urinary disorders: Nephrotoxicity in various forms, including glomerular nephritis, interstitial nephritis, nephrotic syndrome, haematuria, raised serum creatinine, renal papillary necrosis and renal failure.

Hepatobiliary disorders: Abnormal liver function, fatal hepatitis and jaundice.

Nervous system disorders: Convulsions, dizziness, retrobulbar, optic neuritis, headaches, lightheadednesss, drowsiness, paraesthesia, inability to concentrate and cognitive dysfunction have been reported. Reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation.

Eye disorders: Visual disturbances, corneal opacity, papillitis and papilloedema.

Ear and Labyrinth disorders: Tinnitus, hearing disturbances including impairment and vertigo.

Respiratory, thoracic and mediastinal disorders: Dyspnoea, asthma, eosinophilic pneumonitis and pulmonary oedema.

Blood and lymphatic system disorders: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia, hyperkalaemia and haemolytic anaemia.

Skin and subcutaneous tissue disorders:

Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare). Skin rashes including fixed drug eruption, itching (puritus), urticaria, ecchymoses, purpura, sweating. Also alopecia, erythema multiforme, erythema nodosum, lichen planus, pustular reaction, SLE, epidermal necrolysis, photosensitivity reactions (including cases in which skin resembles porphyria cutanea tarda “pseudoporphyria”) or epidermolysis bullosa-like reactions which may occur rarely.

If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored.

Musculoskeletal and connective tissue disorders: Myalgia and muscle weakness.

Reproductive system and breast disorders: Female infertility.

General disorders and administration site conditions: Thirst, pyrexia, fatigue and malaise.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Symptoms

Human experiences of overdosage with naproxen may result in drowsiness, heartburn, indigestion, headache, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, dizziness, tinnitus, fainting, nausea or vomiting. In cases of significant poisoning acute renal failure and liver damage are possible.

Respiratory depression and coma may occur after the ingestion of NSAIDs but are rare.

In one case of naproxen overdose, transient prolongation of the prothrombin time due to hypothrombinaemia may have been due to selective inhibition of the synthesis of vitamin-K dependent clotting factors.

A few patients have experienced seizures, but it is not known whether these were naproxen-related or not. It is not known what dose of the drug would be life-threatening.

Therapeutic measures

Patients should be treated symptomatically as required.

The stomach may be emptied by inducing emesis or aspiration and lavage.). Further treatment is symptomatic.

Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.

Good urine output should be closely monitored.

Renal and liver functions should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequently or prolonged convulsions should be treated with intravenous diazepam.

Other measures may be indicated by the patient's clinical condition.

Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding. However, haemodialysis may still be appropriate for a patient with renal failure who has taken naproxen.

Correction of severe electrolyte abnormalities should be considered.

Naproxen is a propionic acid derivative. It acts as an anti-inflammatory agent, analgesic and has anti-pyretic activity in man. By its action on cyclo-oxygenase, naproxen inhibits prostaglandin synthesis (as do other NSAIDs). Naproxen exhibits its anti-inflammatory effect even in adrenalectomised animals, indicating that its action is not mediated through the pituitary-adrenal axis. As with other NSAIDs, however, the exact mechanism of its anti-inflammatory action is not known.

ATC Code: M01A E02 (anti-inflammatory and antirheumatic products, non-steroids, propionic acid derivatives).

Animal studies suggest that prompt administration of activated charcoal would reduce the absorption of naproxen.

Following oral administration, naproxen is fully absorbed from the gastro-intestinal tract. Depending on food in-take, peak plasma concentrations are reached 2 to 4 hours after ingestion. Naproxen is present in the blood mainly as unchanged drug, extensively bound to plasma proteins. More than 99% is bound to plasma proteins. The plasma half-life is between 12 and 15 hours, enabling a steady state to be achieved within 3 days of initiation of therapy on a twice daily dose regimen. The degree of absorption is not significantly affected by either foods or most antacids. Excretion in urine accounts for approximately 95% of the dose. Naproxen crosses the placental barrier and is excreted in breast milk.

Metabolism in children is similar to that in adults. Chronic alcoholic liver disease reduces the total plasma concentration of naproxen but the concentration of unbound naproxen increases. In the elderly, the unbound plasma concentration of naproxen is increased although total plasma concentration is unchanged.

When naproxen is administered in the enteric-coated form, the peak plasma levels are delayed when compared with the standard tablets. However, the mean areas under the plasma concentration time curves, and hence bioavailability, are equivalent. The tablets do not disintegrate until they reach the small intestine, where dissolution is rapid and complete. This delay in absorption makes Naproxen EC of value for patients in whom gastric dissolution is undesirable.

Carcinogenicity

Naproxen was administered with food to Sprague-Dawley rats for 24 months at doses of 8, 16 and 24mg/kg/day. Naproxen was not carcinogenic in rats.

Mutagenicity

Mutagenicity was not seet in Salmonella typhimurium (5 cell lines), Sachharomyces cerevisisae (1 cell line), and mouse lymphoma tests.

Fertility

Naproxen did not affect the fertility of rats when administered orally at doses of 30mg/kg/day to males and 20mg/kg/day to females.

Teratogenicity

Naproxen was not teratogenic when administered orally at does of 20mg/kg/day during organogenesis to rats and rabbits.

Perinatal/Postnatal Reproduction

Oral administration of naproxen to pregnant rats at doses of 2, 10 and 20mg/kg/day during the third trimester of pregnancy resulted in difficult labour. These are known effects of this class of compounds and were demonstrated in pregnant rats with aspirin and indometacin.

Tablet Contains:

Lactose Monohydrate,

Maize Starch,

Polyvidone,

Sodium Starch Glycolate (type A),

Magnesium Stearate (E572).

Coating contains:

Lactose Monohydrate:

Hydroxypropyl methylcellulose (E464),

Colloidal silicon dioxide,

Polyethylene glycol,

Polyvinyl acetate phthalate,

Purified stearic acid (E570),

Purified talc (E553(b)),

Sodium alginate (E401),

Sodium bicarbonate (E500),

Triethyl citrate,

Titanium Dioxide (E171),

Antifoam AF emulsion.

Printing Ink:

Shellac,

Black iron oxide (E172),

Propylene glycol (E1520).

36 months

Do not store above 25°C. Store in the original package.

Blister strips in packs of 3, 6, 8 or 9 tablets.

Not applicable

TEVA UK Limited

Eastbourne

BN22 9AG

PL 00289/0699

12/09/2007 / 05/03/2012

20/08/2015