Lesflam 25 and 50
Each film-coated tablet contains: Diclofenac Potassium 25mg and 50mg
Diclofenac, as the potassium salt, is a benzeneacetic acid derivative,
designated chemically as 2-[(2,6- dichlorophenyl) amino] benzeneacetic acid,
monopotassium salt. The structural formula is shown in Figure l.
R=K: Lesflam, diclofenac potassium
Diclofenac as the potassium salt, is a faintly yellowish white to light
beige, virtually odorless, slightly hygroscopic crystalline powder.
Molecular weight of potassium is 334.25. It is freely soluble in methanol,
soluble in ethanol, and practically insoluble in chloroform and in dilute
acid and soluble in water. The n-octanol / water partition coefficient is
13.4 at pH 7.4 and 1545 at pH 5.2. It has a single dissociation constant (pKa)
of 4.0 ± 0.2 at 25°C in water.
Lesflam is a non-steroidal anti-inflammatory agent and contains the
potassium salt of diclofenac. In Lesflam the sodium ion of diclofenac sodium
has been replaced by a potassium ion. The active principle is thus the same
as in Voltaren. The preparation possesses pronounced analgesic,
anti-inflammatory, and antipyretic properties. The fact that the active
substance is quickly absorbed from the coated tablets of Lesflam makes them
suitable for the treatment of acute painful and inflammatory conditions in
which importance is attached to a prompt onset of effect (within 30
minutes). Inhibition of prostaglandin biosynthesis, which has been
demonstrated experimentally, is regarded as having a major bearing on the
drug mechanism of action. Prostaglandins play a prominent role in the
causation of inflammation, pain, and fever. Lesflam like Voltaren exerts a
pronounced analgesic effect in moderately and severely painful states. In
post-traumatic and post-operative inflammatory conditions, Lesflam quickly
relieves both spontaneous pain and pain on movement and diminished
inflammatory swelling and wound oedema. In primary dysmenorrhea it is
capable of relieving the pain and also reducing the extent of bleeding. At
concentration corresponding to those attained in man, Lesflam in vitro does
not suppress proteoglycan biosynthesis in cartilage.
Diclofenac is rapidly and completely absorbed from the coated tablets. When
the tablets are taken with a meal, the quantity of active substance absorbed
is not diminished, although the speed of its absorption may possibly be
Following ingestion of one coated tablet of 50 mg, the plasma concentrations
of diclofenac attain a mean peak value of 1.2 µg/mL (3.9 µmol/L) after 20-60
minutes. The plasma concentrations show a linear relationship to the size of
the dose. Repeated oral administration in daily doses of 50mg GA. for a week
does not lead to cumulation of diclofenac in the plasma. Diclofenac becomes
bound to serum proteins at a rate of 99.7%; chiefly to albumin (99.4%).
Roughly half of the active substance is metabolised during its first passage
through the liver (<<first-pass>> effect); consequently, the areas under the
concentration curves (AUCs) after an oral dose are only about one-half as
large as after a parenteral dose of the same size. The biotransformation of
diclofenac involves partly-glucuronidation of the intact molecule but mainly
single and multiple hydroxylation followed by glucuronidation. Approx. 60%
of the dose administered is excreted in the urine than 1% as unchanged
substance. The remainder of the dose is eliminated as metabolites through
the bile in the faeces.
No relevant age-dependent differences in the drug's absorption, metabolism,
or excretion have been observed.
The total systemic clearance of diclofenac in plasma is 263±56mL/min (x ±
SD). The terminal half-life in plasma is 1-2 hours.
Kinetics in special
In patients suffering from renal impairment, no accumulation of the
unchanged active substance can be inferred from the singled-dose kinetics
when applying the usual dosage schedule. At a creatinine clearance of less
than 10mL/min, the theoretical steady-state plasma level of metabolites is
about four times higher than in normal subjects.
However, the metabolites
are ultimately cleared through the bile.
In the presence of impaired hepatic function (chronic hepatitis, compensated
cirrhosis), the kinetics and metabolism of diclofenac are the same as in
patients without liver disease.
Lesflam is indicated as short-term treatment for the following acute
conditions in cases where particular importance is attached to a prompt
onset of effect (within 30 minutes):
– Post-operative inflammation and pain,
e.g. following dental or orthopaedic surgery
– Painful and/or inflammatory conditions in gynaecology, e.g. primary
dysmenorrhoea or adnexitis
– Non-articular rheumatism
Adults: As a rule, the daily dosage for adults is 100-150 mg. In milder
cases, as well as for children over 14 years of age, 75-100 mg daily is
usually sufficient. The daily dosage should always be prescribed in 2-3
In primary dysmenorrhoea the daily dosage, which should be individually
adapted, is generally 50-150 mg. Initially a dose of 50-150 mg should be
given; if necessary, this can be raised in the course of several menstrual
cycles up to the maximum of 200 mg daily. Treatment should be started upon
appearance of the first symptoms and, depending on the symptomatology,
continued for a few days. The tablets should be taken with liquid,
preferably before meals.
Children: The dosage strengths are such that
Lesflam tablets are not recommended for use in children.
After assessing the risk/benefit ratio in each individual patient, the
lowest effective dose for the shortest possible duration should be used.
Peptic ulcer. Known hypersensitivity to the active substance. Like other
non-steroidal anti-inflammatory agents, Lesflam is also contraindicated in
patients in whom attacks of asthma, urticaria, or acute rhinitis are
precipitated by acetylsalicylic acid or by other drngs with prostaglandin-synthetase
Risk of GI ulceration, bleeding and perforation with NSAID
Serious GI toxicity such as bleeding, ulceration and perforation can occur
at any time, with or without warning symptoms, in patients treated with
NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common,
usually developing early in therapy, prescribers should remain alert for
ulceration and bleeding in patients treated with NSAIDs even in the absence
of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of
developing peptic ulceration and bleeding. Patients with prior history of
serious GI events and other risk factors associated with peptic ulcer
disease (e.g. alcoholism, smoking, and corticosteroid therapy) are at
increased risk. Elderly or debilitated patients seem to tolerate ulceration
or bleeding less than other individuals and account for most spontaneous
reports for fatal GI events.
Strict accuracy of diagnosis and close medical surveillance are imperative
in patients with symptoms indicative of gastro-intestinal disease, with a
case history suggestive of gastro-intestinal ulceration, with ulcerative
colitis, or with Crohn's disease, as well as in patients suffering from
severe impairment of hepatic function.
Gastro-intestinal bleeding or
ulceration/ perforations generally have more serious consequences in elderly
patients. This can occur at any time during the treatment, even without
warning symptoms or a previous history.
In the rare instances where gastro-intestinal ulceration or bleeding occur
in patients under treatment with Lesflam, the drug should be withdrawn.
Owing to the importance of prostaglandin for maintaining renal blood flow,
particular caution is called for in patients with impaired cardiac or renal
function, in the elderly, in patients taking diuretics, and in those with
extracellular volume depletion form any cause, e.g. in the peri-operative or
post-operative phase of major surgical operation. Monitoring of renal
functioning as a precautionary measure is recommended when using Lesflam in
such cases. Discontinuation of the medication is normally followed by
recovery to the pre-treatment state. In patients of advanced age, caution is
indicated on basic medical grounds. In particular it is recommended that the
lowest effective dosage be used in frail elderly patients or those with a
low body weight.
As with other non-steroidal anti-inflammatory drugs, elevations of one or
more liver enzymes may occur with Lesflam. During prolonged treatment with
Lesflam, monitoring of hepatic function is recommended as precautionary
If impairment of liver function persists or worsens, if clinical signs or
symptoms consistent with liver disease develop, or if other manifestation
occur (e.g. eosinophilia, skin rashes, etc.) Lesflam should be withdrawn,
Hepatitis may set in without prodromal symptoms. Caution is called for when
using Lesflam in patients with hepatic porphyria, since the drug may trigger
Lesflam in the afore-mentioned indications generally proves necessary only
for a few days. But if, contrary to the recommendations for its use, Lesflam
is administered over a more prolonged period it is advisable as with other
highly active non-steroidal anti-inflammatory agents to perform blood
As in the ease of other non-steroidal ants-inflammatory drugs,
allergic reactions, including anaphylactic/anaphylactoid reactions, can
occur, even without earlier exposure to the drug.
Discontinue Lesflam tablet immediately if rash occurs.
Special points to note
Patients experiencing dizziness or other central nervous disturbances should
refrain from driving a vehicle or operating machines.