COMPOSITION: Each tablet contains naproxen 250 mg.
PHARMACOLOGICAL CLASSIFICATION: A. 3.1 Antirheumatics (Anti-inflammatory Agents)
ADCO-NAPROXEN has been shown to have anti-inflammatory, analgesic and anti-pyretic properties when tested in classical animal test systems. It exhibits its anti-inflammatory effect even in adrenalectomised animals, indicating that its action is not mediated through the pituitary-adrenal axis. It inhibits prostaglandin synthetase.
ADCO-NAPROXEN is indicated for the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis), osteoarthrosis (degenerative arthritis), ankylosing spondylitis, acute gout, acute musculo-skeletal disorders (such as sprains and strains, direct trauma, lumbo-sacral pain, cervical spondylitis, tenosynovitis and fibrositis) and dysmenorrhoea.
Active peptic ulceration.
Hypersensitivity to naproxen or naproxen sodium formulations.
Since the potential exists for cross-sensitivity reactions, ADCO-NAPROXEN should not be given to patients in whom aspirin or other non-steroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis or urticaria.
DOSAGE AND DIRECTIONS FOR USE:
Adults:- For rheumatoid arthritis, osteoarthrosis and ankylosing spondylitis, the starting dose and usual maintenance dose is 500 mg to 1 g per day taken in two doses at twelve hour intervals. Where 1 g per day is needed, the suggested regimen is two ADCO-NAPROXEN 250 mg tablets twice daily.
In the following cases a loading dose of 750 mg or 1g per day for the acute phase is recommended:-
In patients reporting severe night-time pain and/or morning stiffness.
In patients being switched to ADCO-NAPROXEN from a high dose of another anti-rheumatic compound.
In osteoarthrosis where pain is the predominant symptom.
For the patient who requires 750 mg per day and whose night-time pain and/or morning stiffness are most troublesome, 500 mg should be taken before retiring and 250 mg upon awakening. For the patient whose day-time pain and reduced mobility are most troublesome, 500 mg should be taken on awakening and 250 mg upon retiring.
In acute gout, the recommended dosage is 750 mg at once, then 250 mg every eight hours until the attack has passed.
For the treatment of acute musculo-skeletal disorders, the recommended dose is 250 mg twice or thrice daily; most patients will require only seven days' treatment but some patients may require up to fourteen days' treatment.
In dysmenorrhoea the recommended regimen is 500 mg initially, followed by 250 mg every six to eight hours. Children:- For juvenile rheumatoid arthritis in children over five years of age, the usual dosage is 10 mg/kg/day taken in two doses at twelve hourly intervals. ADCO-NAPROXEN is not recommended for use in other indications in children under sixteen years of age.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Gastro-intestinal:- The more frequent reactions are nausea, vomiting, abdominal discomfort, constipation and epigastric distress. More serious reactions which may occur are gastro-intestinal bleeding and peptic ulceration (sometimes with haemorrhage and perforation). Dermatological/hypersensitivity:- Skin rashes, urticaria, angio-oedema. Anaphylactic reactions to naproxen and naproxen sodium formulations and eosinophilic pneumonitis may occur. CNS: Headache, insomnia, inability to concentrate and cognitive dysfunction have been reported. Haematological: Thrombocytopenia, granulocytopenia, aplastic anaemia and haemolytic anaemia may occur. Other: Tinnitus, visual disturbances, hearing impairment, vertigo, mild peripheral oedema. Jaundice, fatal hepatitis, reversible renal failure, nephrotic syndrome, interstitial nephritis and ulcerative stomatitis have been reported.
Special Precautions:- Episodes of gastro-intestinal bleeding have been reported in patients on ADCO-NAPROXEN therapy. ADCO-NAPROXEN should be given under close supervision to patients with a history of gastro-intestinal disease.
Bronchospasm may be precipitated in patients suffering from, or with a history of, bronchial asthma or allergic disease.
Sporadic abnormalities in laboratory tests (e.g. liver function tests) have occurred in patients on ADCO-NAPROXEN therapy.
ADCO-NAPROXEN decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined.
Mild peripheral oedema has been observed in a few patients receiving ADCO-NAPROXEN. Although sodium retention has not been reported in metabolic studies, it is possible that patients with questionable or compromised cardiac function may be at greater risk when taking ADCO-NAPROXEN.
The use of ADCO-NAPROXEN should be avoided in patients who are breast-feeding. Use in patients with impaired renal function:- As naproxen is eliminated to a large extent (95%) by urinary excretion via glomerular filtration, it should be used with great caution in patients with impaired renal function. The monitoring of serum creatinine and/or creatinine clearance is advised in these patients. ADCO-NAPROXEN is not recommended in patients having baseline creatinine clearance less than 20 mL/minute.
Certain patients, specifically those where renal blood flow is compromised, such as in extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure and pre-existing renal disease, should have renal function assessed before and during ADCO-NAPROXEN therapy. Elderly patients in whom impaired renal function may be expected could also fall within this category. A reduction in daily dosage is recommended to avoid the possibility of excessive accumulation of naproxen metabolites in these patients. Use in patients with impaired liver function:- Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen but the plasma concentration of unbound naproxen is increased. Caution is advised and lower doses might be required when using ADCO-NAPROXEN in patients with hepatic diseases. Use in the elderly:- Although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised and lower doses might be required. For the effect of reduced elimination in the elderly, refer to the section - Use in patients with impaired renal function. Interactions with other drugs:- Due to the high plasma protein binding of ADCO-NAPROXEN, patients simultaneously receiving hydantoins, anti-coagulants or other highly protein-bound drugs, should be observed for signs of potentiation or overdosage of these drugs. No interactions have been observed between ADCO-NAPROXEN and warfarin or tolbutamide. Caution is nevertheless advised since interaction has been seen with other non-steroidal agents of this class.
ADCO-NAPROXEN can reduce the anti-hypertensive effect of propranolol and possibly other beta-blockers.
The natriuretic effect of furosemide has been reported to be inhibited by ADCO-NAPROXEN.
Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has also been reported.
Probenecid given concurrently increases ADCO-NAPROXEN plasma levels and extends its plasma half-life considerably.
Caution is advised where methotrexate is administered concurrently due to the possible enhancement of its toxicity, which is probably caused by the reduction of tubular secretion of methotrexate.
It is suggested that ADCO-NAPROXEN therapy be temporarily discontinued forty eight hours before adrenal function tests are performed because ADCO-NAPROXEN may artificially interfere with some tests for 17-ketogenic steroids. Similarly, ADCO-NAPROXEN may interfere with some assays of urinary 5-hydroxyindoleacetic acid.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: Significant overdosage of the drug may be characterised by drowsiness, heartburn, indigestion, nausea and vomiting. No toxicity or late sequelae have been reported after five to fifteen months following ingestion of up to 3 g daily for 3 to 7 days. One patient ingested a single dose of 25 g of naproxen and experienced mild nausea and indigestion. It is not known what dose of the drug would be life-threatening.
Should a patient ingest a large amount of ADCO-NAPROXEN accidentally or purposefully, the stomach may be emptied and usual supportive measures employed. Animal studies indicate that the prompt administration of activated charcoal in adequate amounts would tend to markedly reduce the absorption of the drug.
250 mg Tablets: Flat, yellow, round, bevelled-edge tablets scored on one side and with ADCO embossed on the other side.
PRESENTATION: Tablets 250 mg in securitainers of 30 and 250 tablets.
STORAGE INSTRUCTIONS: Store below 25°C. Protect from light. Keep out of reach of children.
REGISTRATION NUMBER: X/3.1/156
NAME AND BUSINESS ADDRESS OF THE APPLICANT: Adcock Ingram Limited
Adcock Ingram Park
17 Harrison Avenue
Private Bag X69, Bryanston, 2021
DATE OF PUBLICATION OF THIS PACKAGE INSERT: January 1990
New addition to this site: April 2004
Source: Pharmaceutical Industry