Ketoplast

Ketoprofen Plaster

Each plaster (7 cm X 10 cm) contains :

Ketoprofen IP 30 mg

Excipients q.s.

Medicated Transdermal Patch, 30 mg

4.1. Therapeutic indication

For the relief of musculoskeletal pain and inflammation.

4.2. Posology and method of administration

One patch to be applied for one day or as directed by the Physician.

Method of administration

Clean and dry the affected area before applying the patch. Remove the protective film and apply the adhesive part directly to the skin. If the patch is to be applied to very mobile joints such as the elbow or knee, a bandage can be applied to the joint when bent, to keep the patch in place.

4.3. Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in the formulation
• known hypersensitivity reactions, such as symptoms of asthma, allergic rhinitis to ketoprofen, fenofibrate, tiaprofenic acid, acetylsalicylic acid, or to other NSAID history of any photosensitivity reaction
• history of skin allergy to ketoprofen, tiaprofenic acid, fenofibrate, UV blockers or perfumes
• sun exposure, even in case of hazy sun, including UV light from solarium, should be avoided during the treatment and 2 weeks after its discontinuation.
• patients in whom substances with a similar mechanism of action (e.g. acetylsalicylic acid or other NSAIDs) cause attacks of asthma, bronchospasm or acute rhinitis, or cause nasal polyps, urticaria or angioedema. • active or suspected gastrointestinal ulcer or a history of gastrointestinal ulcer
• gastrointestinal bleeding or other active bleeding or bleeding disorders
• severe heart failure
• severe hepatic or renal dysfunction
• haemorrhagic diathesis and other coagulation disorders, or patients receiving anticoagulant therapy
• third trimester pregnancy
• children under 12 years of age
• The use on open wounds or on skin with pathological changes such as eczema, acne, dermatitis, inflammation or infection of any nature or on mucous membranes of body orifices is contraindicated.

4.4. Special warnings and precautions for use

• The systemic bioavailability of ketoprofen applied via the transdermal route is significantly lower than that following oral administration. However, it is not possible to exclude completely the onset of systemic side effects, although it is much less likely that these side effects will occur at this level of plasma binding.
• Analgesics, antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs) can cause potentially serious hypersensitivity reactions, including anaphylactic reactions, even in subjects with no previous exposure to this type of drug. The risk of hypersensitivity reactions after the use of ketoprofen is greater in subjects who have already had this type of reaction after using other analgesics, antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs).
• Administer with caution to patients with allergic conditions or a history of allergy. Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyposis have a higher risk of allergy to aspirin and/or NSAIDs than the rest of the population.
• Treatment should be discontinued immediately upon development of any skin reaction including cutaneous reactions. There have been some reported cases of photosensitivity that occurred a few days, and in rare cases a few months, after the use of the drug. If symptoms of dermatitis are observed, discontinue treatment and keep the affected area away from sunlight.
• The recommended length of treatment should not be exceeded due the risk of developing contact dermatitis and photosensitivity reactions increases over time.
• It is recommended to protect treated areas by wearing clothing during all the application of the product and two weeks following its discontinuation to avoid the risk of photosensitisation.
• Special care should be taken for patients with Crohn’s disease or ulcerative colitis, chronic dyspepsia, history of bronchial asthma.
• Patients currently suffering from or with a previous history of gastrointestinal disease should be carefully monitored for digestive disorders, in particular gastrointestinal bleeding. In the rare cases where gastrointestinal bleeding or ulceration occur in patients receiving treatment with ketoprofen, treatment should be discontinued immediately. Like all NSAIDs, the drug can increase plasma urea nitrogen and creatinine.
• As with other inhibitors of prostaglandin synthesis, the drug may be associated with adverse effects on the renal system, which can lead to glomerular nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure. As with other NSAIDs, the drug can cause transient small increases in some liver parameters, and also significant increases in SGOT and SGPT. In case of a relevant increase in such parameters, therapy must be discontinued.
• Ketoprofen should be used with caution in patients suffering from haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disorders. Like other NSAIDs, ketoprofen can mask the symptoms of infectious diseases. Caution should be exercised in patients with impairment of hepatic, renal or cardiac functions, as well as in patients and with other conditions predisposing to fluid retention. In such cases, the use of NSAIDs can cause a deterioration of renal function and fluid retention. Caution is also required in patients receiving diuretic therapy or those who are likely to be hypovolaemic, as there is an increased risk of nephrotoxicity. Caution should be exercised in the treatment of elderly patients, who are generally more prone to adverse events. The consequences of gastrointestinal bleeding and/or intestinal perforation, for example, are dose-dependent and are often more serious in the elderly; they can also occur without warning symptoms or previous history at any time during treatment.
• Elderly patients are more likely to be suffering from impaired renal, cardiovascular or hepatic function. As with any drug that inhibits prostaglandin and cyclo-oxygenase synthesis, the use of ketoprofen is not recommended in women who intend to become pregnant.
• The use of Ketoplast should be discontinued in women who have fertility problems or who are undergoing fertility investigations. Prolonged or repeated use of the product can cause sensitisation. Treatment must be stopped if hypersensitivity reactions occur. Do not use occlusive bandages. Hands should be washed thoroughly after each application of the product.

4.5. Interaction with other medicinal products and other forms of interaction

The low systemic bioavailability of ketoprofen from Ketoplast means that interaction with other medicaments is unlikely. However, the following interactions apply to NSAIDs in general.

Inadvisable combinations :

• Other NSAIDs, including high doses of salicylates (> 3 g/day) : the administration of several NSAIDs together can increase the risk of gastrointestinal ulcers and bleeding, through a synergistic effect.
• Oral anticoagulants, parenteral heparin and ticlopidine : increased risk of bleeding through inhibition of platelet function and damage to the gastrointestinal mucosa.
• Lithium (described with several NSAIDs) : NSAIDs increase plasma lithium levels (decreased renal excretion of lithium), which can reach toxic levels. This parameter therefore requires monitoring during the initiation, adjustment and withdrawal of treatment with ketoprofen.
• Methotrexate, used at high doses of 15 mg/week or more : increased haematological toxicity of methotrexate through a decrease in its renal clearance by antiinflammatory agents in general.
• Hydantoins and sulphonamides : the toxic effects of these substances can be increased.

Combinations requiring precautions :

• Methotrexate, used in low doses, less than 15 mg/week : increased haematological toxicity of methotrexate through a decrease in its renal clearance by antiinflammatory agents in general. Monitor blood count weekly during the first few weeks of this combination. Increase surveillance in the case of even a slight deterioration of renal function, and in the elderly.
• Diuretics, angiotensin converting enzyme inhibitors : treatment with NSAIDs is associated with the risk of acute renal failure in dehydrated patients (decreased glomerular filtration through reduced renal prostaglandin synthesis). Treatment with an NSAID may decrease their antihypertensive effect. If ketoprofen is prescribed together with a diuretic, it is essential to ensure that the patient is adequately hydrated and to monitor renal function at the start of the treatment.
• Pentoxifylline : increased risk of bleeding. Increase clinical monitoring and check bleeding time more often.
• Zidovudine : risk of increased red cell line toxicity through action on reticulocytes, with severe anaemia occurring one week after the start of NSAID treatment. Check complete blood count and reticulocyte count one or two weeks after starting treatment with NSAIDs.
• Sulphonylureas : NSAIDs can increase the hypoglycaemic effect of sulphonylureas by displacement from plasma protein binding sites.

Associations needing to be taken into account :

• Beta-blockers : treatment with an NSAID can decrease their antihypertensive effect through inhibition of prostaglandin synthesis.
• Cyclosporin and tacrolimus : nephrotoxicity can be enhanced by NSAIDs through renal prostaglandin mediated effects. During combination therapy, renal function must measured.
• Thrombolytics : increased risk of bleeding.
• Probenecid : plasma concentrations of ketoprofen can be increased; this interaction can be due to an inhibitory mechanism at the site of renal tubular secretion and of glucuronic conjugation and necessitates an adjustment of the ketoprofen dose.

4.6. Special Population

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy.

During the first and second trimester : 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 : During the third trimester of pregnancy, all prostaglandin synthetase inhibitors including ketoprofen may induce cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension) and renal dysfunction, which may progress to renal failure with oligo-hydroamniosis in the foetus. At the end of pregnancy, prostaglandin synthetase inhibitors including ketoprofen may lead to possible prolongation of bleeding time (both in mother and child), an anti-aggregating effect which may occur even at very low doses; and inhibition of uterine contractions resulting in delayed or prolonged labour. Therefore, ketoprofen is contraindicated during the third trimester of pregnancy.

If ketoprofen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

Breastfeeding

No data is available, on excretion of ketoprofen in human milk. Ketoprofen is not recommended in nursing mothers.

Paediatric population

Gastrointestinal bleeding, sometimes severe, and peptic ulcers have been observed in some paediatric patients treated with ketoprofen; the product should therefore be administered under the strict supervision of a physician, who should assess the necessary dosage regimen case by case. The safety and efficacy of cutaneous formulations of ketoprofen in children have not been estabilished.

4.7. Effects on ability to drive and use machines

The drug has a minor or moderate influence on the ability to drive and use machines, due to the possibility of dizziness or drowsiness occurring.

4.8. Undesirable effects

The prolonged use of products for topical administration may cause hypersensitivity phenomena. In such cases, the treatment should be discontinued and a suitable alternative therapy initiated.

Undesirable effects reported with ketoprofen systemic formulations

Although not associated with the topical use of ketoprofen, the following adverse events are reported for systemic use of ketoprofen : the most frequent adverse events are minor and transient, and consist of gastrointestinal effects such as indigestion, dyspepsia, nausea, constipation, diarrhoea, heartburn and various types of abdominal discomfort. Serious adverse reactions, all of which are very rare, include mainly cases of skin reactions (urticaria, erythema, exanthema, angioedema), gastrointestinal and respiratory tract reactions (bronchospasm, dyspnoea, laryngeal oedema), and occasional cases of allergic/anaphylactoid reactions, anaphylactic shock and mouth oedema. The majority of reactions that occurred in allergic/asthmatic patients and/or in patients with known hypersensitivity to NSAIDs have been serious.

Undesirable effects reported with ketoprofen topic formulations

The following MedDRAfrequency convention and system-organ classis used : Very common (≥1/10); Common (≥1/100 to < 1/10); Uncommon (≥1/1000 to < 1/100) ); rare (≥1/10 000 to < 1/1000); very rare (<1/10000)

Immune system disorders

Not known : anaphylactic shock, angioedema, hypersensitivity reactions.

Skin and subcutaneous tissue disorders

Uncommon : Local skin reactions such as erythema, eczema, pruritis, and burning sensations. Rare: photosensitisation and urticaria. Cases of more severe reactions such as bullous or phlyctenular eczema which may spread or become generalized have occurred rarely.

Renal and urinary disorders

Very rare : Cases of aggravation of previous renal insufficiency.

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

email to: medico@zuventus.com

Website : http://www.zuventus.co.in/safety.aspx

5.1. Mechanism of action

Ketoprofen is an inhibitor of both the cyclo-oxygenase and lipoxygenase pathways. In addition, ketoprofen is a powerful inhibitor of bradykinin (a chemical mediator of pain and inflammation).

5.2. Pharmacodynamic properties

Inhibition of prostaglandin synthesis provides for potent anti-inflammatory, analgesic and antipyretic effects. Lipoxygenase inhibitors appear to attenuate cell-mediated inflammation and thus retard the progression of tissue destruction in inflamed joints. Ketoprofen stabilises the lysosomal membranes against osmotic damage and prevents the release of lysosomal enzymes that mediate tissue destruction in inflammatory reactions.

5.3. Pharmacokinetic properties

Absorption

Ketoprofen can be applied topically in effective concentrations, but with very low plasma concentrations of drug. Therapeutic levels in the affected tissues provide relief from pain and inflammation.

Distribution

Ketoprofen is 95-99% bound to plasma proteins. Significant levels of ketoprofen have been found in tonsillar tissue and in the synovial fluid following systemic administration.

Biotransformation

Ketoprofen is extensively metabolised : approximately 60-80% of the product administered systemically is found in the form of metabolites in the urine.

Elimination

Elimination is rapid and takes place essentially via the renal route : 50% of the product administered systemically is excreted in the urine within 6 hours.

There are no further preclinical data other than those already reported.

Ketoprofen is a non-steroidal anti-inflammatory drug with analgesic and anti pyretic properties. Ketoplast is shown to have inhibitory effects on prostaglandin and leukotriene synthesis, anti bradykinin activity as well as lysosomal membrane - stabilizing action.

The chemical name for Ketoprofen is 2 - (3 - benzoyl phenyl) - propionic acid with the following structural formula :

It is rapidly and well absorbed through skin and has a prolonged pharmacological action.

8.1. Incompatibilities

Not applicable

8.2. Shelf-life

36 months.

8.3. Packaging information

A pouch of 7 plasters.

8.4. Storage and handing instructions

Store in a cool & dry place. Protect from light & moisture.

Keep out of reach of children.

• KetoPlast should be applied on non-hairy area.
• Clean the application area with water & dry it before applying KetoPlast.
• Do not cut KetoPlast plaster. This may reduce the efficacy.
• Apply immediately upon removal from the protective pack.

03-02-2021

Marketed by :

5119, Oberoi Garden Estates, D-Wing, Chandivali, Andheri (E), Mumbai 400 072. Registered Trade Mark of Zuventus.