What Do You Need To Know About Diclofenac Interactions

diclofenac interactions

Diclofenac is one of the most prescribed drugs around the globe. It was approved by the FDA in 1988. Since then, It is used for having analgesic, antipyretic & anti-inflammatory properties. Diclofenac is the first NSAID to be approved as a derivative of phenylacetic acid. Thereby, inhibiting cox-1 & cox-2 by competing with arachidonic acid. It is one important drug needed for improving the quality of life. Hence, its importance cannot be neglected nor we can forget about diclofenac interactions and its risky side effects. Hence, it’s the balance that your clinician has to maintain.

Diclofenac is considering safe among other existing NSAIDs with short time use. It is marketed under the following brand names:

  • Voltaren
  • Cataflam
  • Zipsor
  • Dyloject
  • zipsor
  • Cambia
  • Zorvolex

Medical Use

Cyclo-oxygenase 2 is largely responsible for executing pain & inflammation in the body. Diclofenac is a potent inhibitor of Cox-2. Therefore, it is in extensive use in a wide range of disorders. Diclofenac has shown to have similar efficacy as other NSAIDs. It has proved to be a puissant pain killer for managing mild to moderate pain. It starts executing its pain-relieving effect in 20-30 minutes. However, suppositories may take up to a few hours to act.

Also, diclofenac is devoid of producing dangerous CNS side effects. Therefore, it is superior to many narcotic analgesics showing similar efficacy.

Diclofenac is widely using in following inflammatory conditions ,

  • osteoarthritis
  • rheumatoid arthritis
  • psoriatic arthritis
  • ankylosing spondylitis
  • gout

Also indicated for soft tissues injuries due to physical trauma.

Moreover, it is also recommended for acute migraine attacks. Intramuscular diclofenac injections show rapid action against acute migraine attacks.

Unbearable pain emerging from osteoarthritis & rheumatoid arthritis sometimes can greatly disturb a person’s life. Diclofenac sodium gel is a must-have for such people.

The doctor also prescribes diclofenac for managing post-operative pain. This mostly includes dental & eye surgery.

Low doses of diclofenac sodium are very effective in curing primary dysmenorrhea symptoms.

Diclofenac Dosage Forms

Diclofenac has a variety of dosage forms. It is a prescription NSAID. But few of its preparations are also available over the counter.

Below are the available dosage forms of diclofenac:

Oral Forms

Oral diclofenac form includes:

  • Liquid filled Capsule
  • Immediate release Tablet
  • Powder for solution
  • Enteric-coated tablet
  • Modified release tablets
  • Sugar-coated tablet

Topical Form

Low systematic absorption is the main benefit over other forms. Hence, topical forms help us to prevent the unwanted effects of NSAIDs to some extent.

Diclofenac sodium gel, commonly selling as Voltaren is in extensive use by arthritis patients.

Pennsaid, A topical solution, use specifically for osteoarthritis of knee.

People also use transdermal patches & plasters for alleviating short term pain.

Creams & lotions are also available.


They are implying to ease swelling & pain after cataract surgery. One more indication is to lower light sensitivity in patients after lens refractive surgery.


Injectables are using for quick pain relief or to manage post-operative pain.

Diclofenac sodium 75 mg in 3ml solution (25mg/ml) is given via IM injection or infusion to the patients.


Suppository is mainly use when the oral route is not supportive.

  • 12.5mg to 25mg suppositories for children(1-12 years).
  • For adults 75mg to 150 mg in divided doses. The doctor will adjust the dose according to your situation.

Pharmacodynamics & Pharmcokinetics

Diclofenac targets both isoforms of cyclo-oxygenase with the same strength. However, the Inhibition of Cox-2 is clinically significant. Thus this inhibition is needed to ease inflammation & pain in the body.

Diclofenac shows swift absorption from the gut following an oral dose. However, absorption may vary among different dosage forms. After absorption, diclofenac undergoes first-pass metabolism. Therefore, only half of the absorbed dose reaches the systematic circulation unchanged.

The plasma concentration peaks quickly & then started to decline. Making significant concentration in the synovial fluid. And Where diclofenac performs its therapeutic action.

Area under the curve is directly proportional to the dose over the range of 25-150 mg.

Diclofenac possesses a very high affinity for plasma albumin. Which also accounts for its high clearance. It has a very short half-life of about 1.2-2hours.

Excretion is mainly through metabolic pathways. About 65% of the drug eliminates in urine & 35% in feces.

Side Effects

Below are the most common moderate to severe diclofenac side effects. On experiencing any of them, stop using it immediately & seek medical attention right away.

  • Headache, drowsiness, dizziness
  • Nausea
  • Diarrhea, constipation, abdominal pain
  • rashes
  • High Blood pressure
  • Stroke
  • Heart attack
  • Severe allergic reactions

Diclofenac Warnings

Always remember that no drug is highly reliable. Likewise, major hazards of  NSAIDs can’t be neglected despite its benefits.
Following are some major diclofenac warnings that you should take under notice prior using :

  • cardiovascular risks are greater with diclofenac use. Don’t use it before or after any heart surgery. Go for your doctor’s approval first.
  • Diclofenac can damage your stomach mucus lining.
  • Asthma exacerbation can also happen with the use of diclofenac.
  • Using diclofenac especially in 3rd trimester of pregnancy can complicate the pregnancy.
  • Diclofenac can pass in breast milk & affects the baby.
  • Using with other drugs can lead to some serious diclofenac interactions.

Diclofenac interactions can be very serious making people’s lives at stake. A detailed account of this risk factor is mentioned below.

Diclofenac Interactions

It’s important to speak with your doctor reporting him all your past & present ailments & therapies. Because the efficacy of the drugs can be greatly affected by interacting with other drugs. In that way intensification of their adverse effects can also occur. As the number of drugs increases the risks of interaction also increases.
Therefore, Drug interaction could be a major problem.

Significant diclofenac interactions are well-known. Some interactions have been deadly too. Always consider major diclofenac warnings prior to use. Do not take diclofenac without your doctor’s approval if you’re already on other drugs. You might not know what troubles you’ll face then.

Diclofenac Interactions With Drugs

More than 300 drugs have known to interact with diclofenac. Major interaction has found with anticoagulants, corticosteroids, diuretics, ACE inhibitors & other NSAIDs.


Warfarin is an anticoagulant drug. It works by reducing the body’s ability to form clots. It blocks vitamin-k dependent clotting factors. Hence, it is indicated in thrombotic events. Blood clots in vessels can cause hindrance in blood flow. Obstruction in blood flow can create potentially fatal conditions. Such as stroke, Heart attack, and hemorrhage.

The international nationalized ratio(INR) is a standard to measure prothrombin time. This helps us to predict the clotting time in a targeted range. The dose of warfarin is adjusted according to it. An escalation in INR points toward an increase in bleeding time.

Diclofenac can increase bleeding time. Therefore, a person can face significant complications with concomitant use of both. It can increase the risk of bleeding & hemorrhage.

Report says that low dose diclofenac sodium gel is less potent for warfarin interaction. Therefore, people using diclofenac sodium gel particularly for knee osteoarthritis are at low risk. This shows that lowering the dose can reduce the risks of diclofenac interaction.

Primarily doctors will try to go for alternate therapies. If needed specifically, the lowest dose for the shortest period of time will be given. Also, INR monitoring will be done weekly.


Lisinopril is an ACE Inhibitor. Inhibition of the ACE enzyme helps to lower angiotensin synthesis. An important phenomenon needed to dilate blood vessels & to increase blood flow towards the heart. Hence, these drugs are using for Hypertensive patients. Lowering BP can minimize the risk of cardiovascular events.

Combining Lisinopril together with diclofenac will cause a decline in its antihypertensive activity. Also, there combine effect will influence the kidney’s function. Hence, concomitant use requires close monitoring from your doctor.


Aspirin is also an NSAID. And hence, its main indication is to ease pain & inflammation. In low doses, aspirin is also using for its antiplatelet activity.  By which it can reduce the risk of heart attack & strokes. However, aspirin overdose can also cause severe toxicity.

It has been studied that low doses of aspirin 150 mg QD along with diclofenac sodium 50mg TID doesn’t show any significant interactions. But anti-inflammatory(high) doses of aspirin reduce the protein binding affinity of diclofenac. Area under curve has also seen to be decreased to one third in the presence of aspirin. Hence, increased biliary excretion of the drug from the body has observed. However, the decrease in therapeutic response has not seen yet.

Well, a very important consequence is the increased risk of GI ulcers & bleeding. Therefore, concomitant use of aspirin with other NSAIDs including diclofenac is contraindicated particularly at higher (anti-inflammatory) doses.

Diclofenac should be avoided with other NSAIDs. Or should use with extreme precautions. Seek medical attention promptly if you notice any odd changes in your health.


Hydrochlorothiazide is a diuretic. It is using in patients having elevated BP due to fluid retention.

Hydrochlorothiazide shows moderate diclofenac interactions that may sometimes become severe. This includes a decrease in the hypotensive effect of hydrochlorothiazide. Because NSAIDs cause increased salt & water retention. Such events can lead to potentially fatal conditions such as heart failure.

Moreover, some studies also reports increase in body weight.

Therefore, while having co-therapy, your clinician should precisely be tracking down your BP & renal function.

Diclofenac Interactions In Diseases

Aging doesn’t have a good effect on our bodies. with time our organs become less functional. And simultaneously become less tolerable to drug’s side effects. People undergoing certain disorders are on multiple medications & procedures. Therefore, it’s the utmost duty of your doctor to wisely prescribe you drugs. As some drugs could complicate pre-existing disorders. Patient counseling is another crucial factor here.

Diclofenac interactions with diseases are very significant. Generally, NSAID should not be considered in the following conditions:


Increased blood pressure has seen in hypertensive patients with diclofenac use. This is because they target the kidney affecting its healthy function.

The cox-2 enzyme is also expressed in macula densa & renal medullary interstitium. Inhibition of it will cause a decrease in PGE2 & prostacyclin. This will lead to anti natriuretic & vasoconstrictor effects. Healthy kidneys are always in act of maintaining homeostatic balance. They will cope up in this situation by increasing salt excretion in a few days. But people with impaired kidney function tends to suffer. This includes hypertension, edema & in severe cases congestive heart failure.

Some experiments also suggested that cox-2 inhibition heightens the effect of Angiotensin-2. Angiotensin 2 tasks for inducing vasoconstrictor effects. Hence, resulting in increased blood pressure.

Effects on aldosterone have also seen. Diclofenac inhibits the glucuronidation of aldosterone by human kidney microsomes. Due to which Blood pressure will rise.

Topical diclofenac sodium gel can also elevate blood pressure. Or it can worsen the preexisting blood pressure.

Your doctor should carefully be monitoring blood pressure during this condition.

Gastric Ulcers

NSAIDs are attributed to serious GI toxicity. This includes bleeding, ulceration & hole in the intestine or stomach. It is because cox-enzymes specially cox-1 are important in maintaining mucosal integrity. Recent studies called both enzymes for contributing in mucosal defense. Since cox-2 accelerates the healing of ulcers.

Therefore, diclofenac is not recommended in patients with a history of ulcers. The probability of ulcers become greater with use. Also, it will interfere in the healing of ulcers. Fatal ulcers in aged people have also seen with NSAID use.

Chances are very high with increase dose & long term therapy.

Diclofenac is not advised in people at higher risks. Risks can be lower by adding stomach protective agents with diclofenac. Cytoprotective agents, antacids, or H₂ receptors antagonists are employing in such people. While your doctor should remain alert for any symptoms related to GI ulcers.


NSAIDs, including diclofenac, must be cautiously used in asthmatic patients Because some individuals suffer from aspirin or other NSAIDs triggered asthma. Generally, it is termed as Aspirin-induced asthma. The likelihood of AIA increases as you age older. It is rare in children.

Inhibition of cox enzymes initiates the lipoxygenase pathway. This will cause an increase in the production of leukotrienes. Simultaneously leading to bronchoconstriction.

Asthma exacerbation following NSAID ingestion can be life-threatening.

Asthmatics with chronic rhinitis or history of nasal polyps are more prone to such incidence. The reaction can occur between 20 minutes to 3 hours after administration.

The symptoms in aspirin-sensitive asthmatics following NSAID ingestion include:

  • Respiratory arrest
  • Bronchoconstriction
  • Rhinorrhea
  • Conjunctival irritation
  • Cutaneous flushing of head & neck

Cross-sensitivity between aspirin & other NSAIDs has also seen in patients with AIA.

Moreover, there was a case of asthma exacerbation following the use of NSAIDs ophthalmic drops.  It shows that any route of administration can cause bronchoconstriction in sensitive asthmatics.

In order to prevent such complications, your doctor first diagnoses your asthma type. To diagnose AIA, NSAID sensitivity tests will be performed.

Recent studies reveal diclofenac interactions in Aspirin-induced asthmatics. Hence, diclofenac should not consider in AIA patients.

Most probably you’ll not be given NSAIDs by your doctor. And if needed specifically your doctor will prescribe cox -2 inhibitors.

Renal Diseases

People with renal diseases are at greater risk for diclofenac interactions.

Renal Prostaglandins play a part in maintaining GFR. And they are of extreme importance during fluid depleted states. Where they are doing a compensating role in preserving renal perfusion. Inhibition by NSAIDs may further complicate the kidney function. Because of low prostaglandin synthesis & renal blood flow.

Individuals with an experience of liver dysfunction, Myocardial infarction, impaired kidney functions, taking ACE inhibitors & diuretics are at major risk.

A case was reported on diclofenac induced acute renal failure in an aged patient. The patient was hypertensive. He was on anti-hypertensive & diuretics prior to diclofenac. Low renal blood flow due to age & volume depletion due to diuretics is further complicated by diclofenac.

Hence, it shows that diclofenac 50mg TID or 150mg QD is enough to precipitate renal failure in volume-depleted patients.

However, this condition is reversible. And depends on the dose and duration of therapy. Immediate withdrawal of NSAID helps in recovery. In the above case, the patient’s kidney began to work within normal range after 1 month.

Thus, sufficient hydration is very important in such patients before giving NSAIDs. Therapy should start with the lowest possible dose. Although it’s better to go for kidney-sparing NSAIDs.

Moreover, diclofenac is contraindicated in patients with advanced renal disease.

Renal toxicity has also seen in patients with healthy kidneys. And chronic use could lead to progressive kidney damage.

Hence, NSAID’s interaction with the kidney has always been a top issue for doctors.

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