<p>Not recommended drug associations Other NSAIDs (including cyclooxygenase-2 selective inhibitors) and high dose salicylates: Increased risk of gastrointestinal ulceration and bleeding. Anticoagulants Increased risk of bleeding.</p>

<ul>
	<li>Heparin</li>
	<li>Vitamin K antagonists (such as warfarin)</li>
	<li>Platelet aggregation inhibitors (such as ticlopidine, clopidogrel)</li>
	<li>Thrombin inhibitors (such as dabigatran)</li>
	<li>Direct factor Xa inhibitors (such as apixaban, rivaroxaban, edoxaban)</li>
</ul>

<p>If coadministration is unavoidable, patient should be closely monitored.</p>

<ul>
	<li>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.</li>
	<li>Methotrexate at doses greater than 15mg/week: Increased risk of haematologic toxicity of methotrexate, particularly if administered at high doses (&gt;15 mg/week), possibly related to displacement of protein-bound methotrexate and to its decreased renal clearance.</li>
	<li>Drug associations requiring precautions for use Medicinal products and therapeutic categories that can promote hyperkalemia (i.e. potassium salts, potassium-sparing diuretics, ACE inhibitors and angiotensin II antagonists, NSAIDs, heparins (low molecular-weight or unfractioned), cyclosporin, tacrolimus and trimethoprim): The risk of hyperkalemia can be enhanced when the drugs mentioned above are administered concomitantly.</li>
	<li>Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.</li>
	<li>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 co-administration therapy and renal function monitored when the treatment is started.</li>
	<li>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 cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure.</li>
	<li>Nicorandil: In patients concomitantly receiving nicorandil and NSAIDs, there is an increased risk for severe complications such as gastrointestinal ulceration, perforation and hemorrhage.</li>
	<li>Cardiac glycosides: A pharmacokinetic interaction between ketoprofen and digoxin has not been demonstrated. However, caution is advised, in particular in patients with renal impairment, since NSAIDs may reduce renal function and decrease renal clearance of cardiac glycosides.</li>
	<li>Cyclosporin: Increased risk of nephrotoxicity.</li>
	<li>Tacrolimus: Increased risk of nephrotoxicity.</li>
	<li>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.</li>
	<li>Pentoxifylline: There is an increased risk of bleeding. More frequent clinical monitoring and monitoring of bleeding time is required.</li>
	<li>Tenofovir: Concomitant administration of tenofovir disoproxil fumarate and NSAIDs may increase the risk of renal failure.</li>
	<li>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).</li>
	<li>Thrombolytics: Increased risk of bleeding. Probenecid: Concomitant administration of probenecid may markedly reduce the plasma clearance of ketoprofen.</li>
	<li>Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.</li>
</ul>