Egypt - English - EDA (Egyptian Drug Authority)
20/07/2011 16:28 - VISTAlink folder 730160 - Page 1/4
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 cardiovascular disease
may be at greater risk NSAIDs is contraindicated for the treatment
of peri-operative pain in the setting of coronary artery bypass graft
NSAIDs cause an increased risk of serious gastrointestinal adverse
events including inflammation, 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.
Each capsule contains
Active ingredient: Ketoprofen ………..50mg
Inactive ingredient: Lactose & magnesium stearate.
Pharmacodynamics: Ketoprofen is a non-steroidal, anti-inflammatory
arylcarboxylic acid derivative belonging to the propionic acid group of
NSAIDs. Ketoprofen has anti-inflammatory, antipyretic properties and has
central and peripheral analgesic activity. However, its mode of action is
not fully explained. It inhibits prostaglandin synthetase and platelet
Absorption: Ketoprofen is rapidly and completely absorbed from the
gastrointestinal tract. Maximal plasma levels are reached within 60 to 90
minutes after oral administration (45 to 60 minutes after rectal
administration). When ketoprofen is administered with food, the rate of
absorption is slowed, resulting in delayed and reduce peak concentration
(Cmax); however, its total bioavailibility is not altered.
*Sustained-released formulations: when administered with high caloric
food, a slight decrease of bioavailibility (13%) has been observed. For the
different slow-release formulations available in the different countries, a
specific statement should be provided by each affiliate to describe the
particular absorption characteristics.
Distribution: The drug is 99% bound to plasma protein. Ketoprofen diffuses
into synovial fluid and in intraarticular, capsular, synovial and tendon
tissues. Ketoprofen crosses the blood brain barrier and the placental
barrier. The plasma elimination half-life is approximately 2 hours.The
volume of distribution is approximately 7 L.
*Sustained-release formulations (i.e. Profenid L.P. 200 mg): after the
plateau (fifth to twelfth hour), ketoprofen levels decrease with an
apparent half-life of 3 to 4 hours. No accumulation of the drug was
found after repeated doses.
Metabolism: The biotransformation of ketoprofen is characterised by
two main processes, hydroxylation and conjugation with glucuronic acid,
the latter being the main pathway in man. Excretion of ketoprofen as
unchanged drug is very low (less than 1%). Almost all administered
ketoprofen is excreted as metabolites in urine, of which 65 to 85% of
administered dose is excreted as a glucuronide metabolite.
Elimination: 50% of the administered dose is excreted in the urine within
6 hours following drug administration. Within five days following the
oral administration, approximately 75 to 90% of the dose is mainly
excreted in the urine. Fecal excretion is very low (1 to 8%).
The indications of ketoprofen are based on its anti-inflammatory,
analgesic and antipyretic properties. Ketoprofen is indicated for
symptomatic treatment of:
- Rheumatoid arthritis
- Degenerative joint diseases
- Musculoskeletal and joint disorders such as tendinitis and sprain
- Pain, regardless of the origin, such as dental pain, headache and
Dosage and administration
Anti-inflammatory dosage: The recommended starting dose is 150 to
300 mg/day in 3 divided doses. Once the maintenance dosage has been
established (usually 100 to 200 mg/day), the patient may be tried on a
twice daily dose regimen. Alternatively, switching to the once daily form
at the same dosage may be considered. The recommended maximum
daily dose is 300mg.
Management of pain and primary dysmenorrhea: The usual
recommended dose is 25 to 50 mg, every 6 to 8 hours as necessary. The
total daily dose should not exceed 300mg.
Patients with impaired renal function and the elderly: It is advisable to
reduce the initial dosage and maintain such patients on the minimal
effective dose. Individual adjustment may be considered, only after good
individual tolerance has been ascertained.
Patients with impaired hepatic function: These patients should be
carefully monitored and kept at the minimal effective daily dosage.
Children: The safety and effectiveness of ketoprofen suppositories have
not been established.
Administration: Food effect: The oral forms should be taken with ﬂuids,
preferably with food.
Ketoprofen is contraindicated in patients, who have a history of
hypersensitivity reactions such as asthmatic attacks or other allergic-type
reactions to ketoprofen, ASA or other NSAIDs. Severe, rarely fatal,
anaphylactic reactions have been reported in such patients. Ketoprofen
is also contraindicated in the following cases:
- Severe heart failure
- Active or history of peptic ulcer/hemorrhage
- History of gastrointestinal bleeding or perforation, related to
previous NSAIDs therapy
- Severe hepatic insufficiency
- Severe renal insufficiency
- Third trimester of pregnancy
− Gastralgia, dyspepsia, abdominal pain, nausea, vomiting,
diarrhea, constipation, flatulence.
− Gastritis, stomatitis, exacerbation of colitis and Crohn’s disease.
− Peptic ulcer, gastrointestinal bleeding and perforation.
− Dermatological reactions: rash, pruritus, urticaria, angioedema
− Respiratory reactions: asthmatic attack, bronchospasm
(particularly in patients with known hypersensitivity to ASA and
− Anaphylactic reactions (including shock).
Skin reactions: Photosensitivity, alopecia, bullous eruptions including
Stevens-Johnson and toxic epidermal necrolysis.
Peripheral and central nervous system: Dizziness, paresthesia,
Psychotic disorders: Somnolence, mood disorders.
Vision disorders: Visual disturbances such as blurred vision (see section 6).
Hearing disorders: Tinnitus.
Renal system: Abnormal renal function tests, acute renal failure,
interstitial nephritis, nephritic syndrome.
Liver system: Elevation of transaminase levels, rare cases of hepatitis.
Haematology: Thrombocytopenia, anemia due to bleeding,
agranulocytosis, bone marrow aplasia.
Cardiovascular system: Hypertension, vasodilatation.
Body as a whole: Headache, oedema, weight gain, taste perversion.
Not recommended drug associations: Other NSAIDs (including
cyclooxygenase-2 selective inhibitors) and high dose salicylates:
Increased risk of gastrointestinal ulceration and bleeding.
Anticoagulants (heparin and warfarin) and platelet aggregation inhibitors
(i.e.ticlopidine, clopidogrel): Increased risk of bleeding. If coadministration
is unavoidable, patient should be closely monitored.
Lithium: Risk of elevation of lithium plasma levels, sometimes reaching
toxic levels due to decreased lithium renal excretion. Where necessary,
plasma lithium levels should be closely monitored and the lithium
dosage levels adjusted during and after NSAID therapy.
Methotrexate at doses greater than 15mg/week: Increased risk of
haematologic toxicity of methotrexate, particularly if administered at
high doses (> 15 mg/week), possibly related to displacement of
protein-bound methotrexate and to its decreased renal clearance.
Drug associations requiring precautions for use.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.
Diuretics: Patients and particularly dehydrated patients taking diuretics
are at a greater risk of developing renal failure secondary to a decrease
in renal blood flow caused by prostaglandin inhibition. Such patients
should be rehydrated before initiating coadministration therapy and
renal function monitored when the treatment is started.
ACE inhibitors and Angiotensin II Antagonists: In patients with
compromised renal function (e.g. dehydrated patients or elderly patients
the co-administration of an ACE inhibitor or Angiotensin II antagonist
and agents that inhibit cyclo-oxygenase may result in further
deterioration of renal function, including possible acute renal failure.
Methotrexate at doses lower than 15mg/week: During the first weeks of
combination treatment, full blood count should be monitored weekly. If
there is any alteration of the renal function or if the patient is elderly,
monitoring should be done more frequently.
Pentoxifyllin: There is an increased risk of bleeding. More frequent
clinical monitoring and monitoring of bleeding time is required.
Drug associations to be taken into account
Antihypertensive agents (beta-blockers, angiotensin converting enzyme
inhibitors, diuretics): Risk of decreased antihypertensive potency
(inhibition of vasodilator prostaglandins by NSAIDs).
Thrombolytics: Increased risk of bleeding.
Probenecid: Concomitant administration of probenecid may markedly
reduce the plasma clearance of ketoprofen.
Selective serotonin reuptake inhibitors (SSRIs): Increased risk of
During the first and second trimester: In mice and rats, there is no
evidence of teratogenic or embryotoxicity. In the rabbit, slight
embryotoxicity likely related to maternal toxicity has been reported.
As the safety of ketoprofen in pregnant women has not been evaluated,
the use of ketoprofen during the first and second trimester of pregnancy
should be avoided.
During the third trimester of pregnancy: All prostaglandin synthetase
inhibitors including ketoprofen may induce cardiopulmonary and renal
toxicity in the fetus. At the end of the pregnancy, prolonged bleeding
time in both the mother and child may occur. Therefore, ketoprofen is
contraindicated during the last trimester of pregnancy.
No data are available on excretion of ketoprofen in human milk.
Ketoprofen is not recommended in nursing mothers.
Undesirable effects may be minimized by using the minimum effective
dose for the shortest duration necessary to control symptoms. Caution
should be advised in patients receiving concomitant medications which
could increase the risk of ulceration or bleeding, such as oral corticoster-
oids, anticoagulants such as warfarin, selective serotonin-reuptake
inhibitors or antiplatelet agents such as aspirin.
Gastrointestinal bleeding, ulceration and perforation: GI bleeding,
ulceration or perforation, which can be fatal, has been reported with all
NSAIDs at anytime during treatment, with or without warning symptoms
or a previous history of serious GI events.
Elderly: The elderly have an increased frequency of adverse reactions to
NSAIDs especially gastrointestinal bleeding and perforation which may
be fatal. 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 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.
Patients with active or a past history of peptic ulcer. 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.
At the start of treatment, renal function must be carefully monitored in
patients with heart failure, cirrhosis and nephrosis, in patients receiving
diuretic therapy, in patients with chronic renal impairment, particularly
if the patient is elderly. In these patients, administration of ketoprofen
may induce a reduction in renal blood flow caused by prostaglandin
inhibition and lead to renal decomposition. Caution is required in
patients with a history of hypertension and/or mild to moderate
congestive heart failure as fluid retention and oedema have been
reported in association with NSAID therapy. As with all NSAIDs, careful
consideration should be given when treating patients with existing
uncontrolled hypertension, congestive heart failure, established
ischaemic heart disease, peripheral arterial disease, and/or cerebrovascu-
lar disease, as well as, before initiating long term treatment in patients
with risk factors for cardiovascular disease (e.g. hypertension, hyperlipi-
daemia, diabetes mellitus, smoking). As with other NSAIDs, in the
presence of an infectious disease, it should be noted that the
anti-inflammatory, analgesic and the antipyretic properties of
ketoprofen may mask the usual signs of infection progression such as
fever. In patients with abnormal liver function tests or with a history of
liver disease, transaminase levels should be evaluated periodically,
particularly during long term therapy. Rare cases of jaundice and
hepatitis have been described with ketoprofen. If visual disturbances
such a blurred vision occur, treatment should be discontinued. The use
of NSAIDs 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 the NSAIDs should be considered.
Store at a temperature not exceeding 30º C in a dry place.
Keep all medicines out of reach of children
Profenid ® 50mg: Cartoon box containing 2 strips, each strip
contains 12 capsules and an inner leaflet
Economy pack: Cartoon box containing 50 strips, each strip
contains 4 capsules and an inner leaflet
Produced by sanofi-aventis Egypt s.a.e.
Under license of sanofi-aventis / France