INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
RANFEN 200 Tablets
RANFEN 400 Tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

RANFEN 200 Tablets
RANFEN 400 Tablets

COMPOSITION:
Ranfen 200 Tablets
Each film coated tablet contains ibuprofen 200 mg
Ranfen 400 Tablets
Each film coated tablet contains ibuprofen 400 mg

PHARMACOLOGICAL CLASSIFICATION:
A 3.1 Antirheumatics (anti-inflammatory agents)

PHARMACOLOGICAL ACTION:
Mechanism of Action
Ibuprofen acts by inhibiting the activity of enzyme cyclo-oxygenase, resulting in decreased formation of precursors of prostaglandins and thromboxanes from arachidonic acid.
Pharmacokinetics and Metabolism
Ibuprofen is rapidly absorbed after oral administration and peak concentrations in plasma are observed after 1 to 2 hours. The half- life in plasma is about 2 hours. Ibuprofen is extensively (99%) bound to plasma proteins. Ibuprofen passes slowly into synovial spaces and may remain there in higher concentration as the concentrations in plasma decline. The excretion of ibuprofen is rapid and complete. More than 90% of an ingested dose is excreted in the urine as metabolites or their conjugates, and no ibuprofen per se is found in the urine. The major metabolites are a hydroxylated and a carboxylated compound.

INDICATIONS:
Ibuprofen is indicated:
For the treatment of rheumatic diseases such as:
* Rheumatoid arthritis
* Osteoarthritis
* Ankylosing spondylitis
* Juvenile rheumatoid arthritis
For the relief of mild to moderate pain especially when anti- inflammatory actions may also be desired e.g., following dental or obstetric surgery, and for relief of musculoskeletal pain due to soft tissue athletic injuries (strains or sprains).
For the relief of pain and inflammation of acute gouty arthritis.
In the treatment of painful nonrheumatic inflammatory conditions such as athletic injuries, bursitis, capsulitis, synovitis, tendinitis or tenosynovitis.
For reduction of fever.
For the relief of pain associated with primary dysmenorrhoea.

CONTRA-INDICATIONS:
Except under special circumstances this medication should not be used when the following medical problems exist:-

-	History of severe allergic reaction such as anaphylaxis or angioedema, induced by aspirin or other NSAIDs. Because of the possibility of cross-sensitivity due to structural relationships which exists among non-steroidal anti-inflammatory medicines, acute allergic reactions are likely to occur in patients who have exhibited allergic reactions to these compounds.
-	Aspirin-induced nasal polyps associated with bronchospasm. (high risk of severe allergic reactions because of cross sensitivity).
-	Children under the age and 2 years.
-	Active peptic ulceration.
-	Safety in pregnancy and lactation has not been established.

WARNINGS:
Regular use of NSAID's during the third trimester of pregnancy may result in premature closure of the foetal ductus arteriosus in utero and possibily in persistent pulmonary hypertension of the new born. The onset of labour may be delayed and its duration increased.

DOSAGE AND DIRECTIONS FOR USE:
Usual adult dose:
Adults: The recommended dosage is 1200 mg daily in divided doses. In severe cases the initial dose in the acute phase may be increased, until the acute phase has been brought under control. Maximum daily dose: 2,4 g per day.
Acute gout: 2400 mg daily either as 800 mg, 8 hourly or 600 mg, 6 hourly until acute symptoms have been relieved. If acute symptoms do not resolve within 3 days, consult a doctor.
Juvenile Rheumatoid Arthritis: Total daily dose is 20 mg/kg of body weight in divided doses.
Pyrexia and pain: 20 mg/kg/day in divided doses.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side effects:
Cardiovascular system: Tachycardia, flushing, increase in blood pressure.
Central nervous system: Confusion, hallucinations, mental depression, peripheral neuropathy, tinnitus, drowsiness, insomnia.
Gastro-intestinal system: Epigastric pain or discomfort, gastritis, haematemesis, gastro-intestinal perforation, gastro-intestinal ulceration
Dermatological: Allergic dermatitis, erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis.
Renal: Haematuria, cystitis, renal impairment or failure, polyuria, fluid retention/ oedema,. acute renal failure, interstitial nephritis, nephrotic syndrome
Haematological: Agranulocytosis, anaemia, aplastic anaemia, eosinophilia, haemolytic anaemia, leukopaenia, thrombocytopaenia.
Hypersensitivity reactions: Angiitis, angioedema, bronchospastic allergic reactions, allergic rhinitis, serum sickness like reaction, systemic lupus erythematosus, aseptic meningitis.
Ophthalmic: Amblyopia, blurred or double vision, conjunctivitis, dry irritated or swollen eyes, scotomata.
Oral: Aphthous stomatitis, gingival ulcerations.
Ear, Nose and Throat: Decreased hearing or any change in hearing, epistaxis,
Hepatic effects: Hepatitis
Pancreatic effects: Pancreatitis
Precautions
Cross-sensitivity and/or related problems
Patients sensitive to one of the NSAIDs, may also be sensitive to any of the other NSAIDs.
NSAIDs may cause bronchoconstriction or anaphylaxis in aspirin-sensitive asthmatics, especially those with aspirin induced nasal polyps, asthma, and other allergic reactions (the “aspirin triad”).
Geriatrics
NSAID-induced gastro-intestinal ulceration and/or bleeding may be more likely to cause serious consequences, including fatalities, in geriatric patients than in younger adults. In addition, elderly patients are more likely to have age-related renal function impairment, which may increase the risk of NSAID-induced hepatic and renal toxicity and may also require dosage reduction to prevent accumulation of the medication. Also, careful monitoring of the patient is recommended.
Dental
NSAIDs may cause soreness, irritation, or ulceration of oral mucosa. Ibuprofen may rarely cause leukopaenia and/or thrombocytopaenia, which may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. If leukopaenia or thrombocytopaenia occurs, dental work should be deferred until blood counts have returned to normal, and patients should be instructed in proper oral hygiene, including caution in use of regular tooth brushes, dental floss and toothpicks.
Surgical
Caution is recommended in patients who require surgery. Most NSAIDs inhibit platelet aggregation and may prolong bleeding time, which may increase intra- and postoperative bleeding. Recovery of platelet function may occur within one day after discontinuation of ibuprofen. Consideration should be given to discontinuing NSAID treatment for an appropriate length of time prior to elective surgery, depending on the potency and duration of effect of the individual agent on platelet aggregability.
Special precautions

-	Mild allergic reaction such as allergic rhinitis, urticaria or skin rash induced by aspirin or other NSAIDs
-	Anaemia
-	Asthma
-	Conditions such as compromised cardiac function, congestive heart disease, pre-existing oedema, renal function impairment.
-	Conditions predisposing to gastrointestinal toxicity, such as alcoholism, inflammatory or ulcerative disease of upper or lower GI tract, including crohn’s disease, diverticulitis, peptic ulcer disease, or ulcerative colitis.
-	Haemophilia or other bleeding problems including coagulation or platelet function disorders.
-	Hepatic cirrhosis or hepatic function impairment.
-	Renal function impairment
-	Stomatitis
-	Systemic lupus erythematosus

In view of the product's inherent potential to cause fluid retention, heart failue may be precipitated in some compromised patients.

Interactions
Paracetamol:
Prolonged concurrent use of paracetamol with ibuprofen may increase the risk of adverse renal effects; it is recommended that patients be under close medical supervision while receiving such combined therapy.
Alcohol or corticosteroids or chronic therapeutic use of corticotrophin or potassium supplements:
Concurrent use with ibuprofen may increase the risk of gastrointestinal side effects, including ulceration or haemorrhage.
Anticoagulants (coumarin or indandione derivative) or heparin or thrombolytic agents (e.g. Streptokinase, Urokinase):
Inhibition of platelet aggregation by ibuprofen and possibility of ibuprofen-induced gastrointestinal ulceration or bleeding, may be hazardous to patients receiving anticoagulant or thrombolytic therapy.
Oral antidiabetic agents or insulin:
Ibuprofen may increase the hypoglycemic effect of these medications because prostaglandins are directly involved in regulatory mechanisms of glucose metabolism and possibly because of displacement of the oral antidiabetics from serum proteins. Hence, dosage adjustments of antidiabetic agent may be necessary.
Antihypertensives or diuretics:
Increase monitoring of the response to an antihypertensive agent may be advisable when ibuprofen is used concurrently because it has been shown to reduce or reverse the effects of antihypertensives, possibly by renal prostaglandin synthesis and/or by causing sodium and fluid retention.
Other NSAIDs (used concurrently with ibuprofen):
Concurrent use of two or more NSAIDs is not recommended; concurrent therapy may increase the risk of gastrointestinal toxicity, including ulceration or haemorrhage, without providing additional symptomatic relief.
Concurrent administration of two or more NSAIDs may alter the pharmacokinetic profile of at least one of the medications; which may alter the therapeutic effect and/or increase the risk of adverse effects, specifically aspirin decreases the bioavailability of ibuprofen by 50%.
Bone marrow depressants:
Leukopaenic and/or thrombocytopaenic effects of these medications may be increased with concurrent or recent therapy; dosage adjustment of the bone marrow depressant, if necessary, should be based on blood counts.
Digoxin:
Ibuprofen has been reported to increase digoxin plasma concentration.
Cefamandole or valproic acid:
These medications may cause hypoprothrombinaemia; in addition, valproic acid may inhibit platelet aggregation; concurrent use with ibuprofen may increase the risk of bleeding because of additive interferences with platelet function and/or the potential occurrence of ibuprofen-induced gastrointestinal ulceration or haemorrhage.
Ciclosporin or Gold Compounds and other nephrotoxic compounds:
Inhibition of renal prostaglandin activity by ibuprofen may increase the plasma concentration of ciclosporin and/or the risk of ciclosporin induced nephrotoxicity; patients should be carefully monitored during concurrent use.
Lithium
Ibuprofen has been reported to increase the steady state concentration of lithium possibly by decreasing its renal clearance.
Methotrexate
NSAIDs may decrease protein binding and/or renal elimination of methotrexate, resulting in increased and prolonged methotrexate plasma concentrations and increased risk of toxicity, especially during high dose methotrexate infusion therapy.
Laboratory Value Alterations
Bleeding time may be prolonged with the use of ibuprofen. Decrease in blood glucose concentration has been reported with ibuprofen.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See side-effects and special precautions.
Treatment is symptomatic and supportive.

IDENTIFICATION:
Ranfen 200 Tablets
Peach-red coloured, round biconvex film coated tablets with intact coating.
Ranfen 400 Tablets
Peach-red coloured, round, biconvex film coated tablets with intact coating.

PRESENTATION:
Ranfen 200 Tablets
White HDPE bottle containing 28 tablets
White HDPE bottle containing 500 tablets
White HDPE bottle containing 1000 tablets.
Ranfen 400 Tablets
White HDPE bottle containing 1000 tablets.

STORAGE INSTRUCTIONS:
Ranfen 200 Tablets: Store in well closed containers, below 30°C, protected from moisture.
Ranfen 400 Tablets: Store in well closed containers, below 25°C, protected from moisture.
Keep out of reach of children.

REGISTRATION NUMBER
Ranfen 200 Tablets: 30/3.1/0440
Ranfen 400 Tablets: 34/3.1/0446

NAME AND BUSINESS ADDRESS OF THE APPLICANT
RANBAXY (SA) (PTY) LTD
Third Floor, Outspan House,
1006 Lenchen Avenue North,
Centurion, Pretoria

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

Updated on this site: March 2003
Source: Pharmaceutical Industry
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