Difensic Actions

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Actions of Difensic in details

The action of the drug on the human body is called Pharmacodynamics in Medical terminology. To produce its effect and to change the pathological process that is happening the body and to reduce the symptom or cure the disease, the medicine has to function in a specific way. The changes it does to the body at cellular level gives the desired result of treating a disease. Drugs act by stimulating or inhibiting a receptor or an enzyme or a protein most of the times. Medications are produced in such a way that the ingredients target the specific site and bring about chemical changes in the body that can stop or reverse the chemical reaction which is causing the disease.
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Percutaneous anti-inflammatory agent.

Difensic is an anti-inflammatory and analgesic preparation for topical application. Its active substance corresponds to 1% Difensic sodium. The white, creamy, non-greasy preparation is easy to rub into the skin, and its aqueous-alcoholic base gives it a soothing and cooling effect.

Difensic has been shown in experiments to inhibit prostaglandin biosynthesis and this is regarded as an important factor in its mechanism of action.

In inflammation of traumatic or rheumatic origin, Difensic has been shown to relieve pain, reduce oedema and shorten the time to return of normal function.

Pharmacokinetics: Absorption: The amount of Difensic absorbed through the skin is proportional to the contact time and skin area covered with Difensic and depends on the total topical dose and on skin hydration. About 6% of the active substance is absorbed after topical application of Difensic 2.5 g/500 cm2, as determined by reference to total renal elimination compared with Voltaren tablets. Absorption of Difensic increases 3-fold if an occlusive dressing is applied for 10 hrs.

Distribution: Difensic can be detected in the plasma, synovial tissue and synovial fluid after topical application of Difensic to the wrists and knees. Peak plasma concentrations of Difensic are about 100 times lower after topical application of Difensic than after oral administration of Voltaren tablet. 99.7% of Difensic binds to serum proteins, mainly to albumin (99.4%).

Metabolism: Biotransformation of Difensic takes place partly by glucuronidation of the intact molecule, but mainly by single or multiple hydroxylation resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, but to a much lesser extent than Difensic.

Elimination: Total systemic clearance of Difensic from the plasma is 263 ± 56 mL/min (mean value ± standard deviation). The terminal plasma half-life is 1-2 hrs. Four of the metabolites, including the 2 active metabolites, also have a short plasma half-life (1-3 hrs). One metabolite, 3'-hydroxy-4'-methoxy-Difensic, has a much longer half-life, but this metabolite is virtually inactive.

Difensic and its metabolites are excreted mainly in the urine.

Kinetics in Special Clinical Situations: No accumulation of Difensic and its metabolites should occur in patients with renal insufficiency.

In patients with chronic hepatitis or nondecompensated liver cirrhosis, the kinetics and metabolism of Difensic are the same as in patients without liver disease.

How should I take Difensic?

Keep using Difensic for the full time of treatment. However, do not use Difensic more often or for a longer time than your doctor ordered. Difensic is not for long-term use.

Difensic should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

When used for severe or continuing arthritis, Difensic must be taken every day as ordered by your doctor in order for it to help you. Difensic usually begins to work within one week, but in severe cases up to two weeks or longer may pass before you begin to feel better. Several weeks may pass before you feel the full effects of Difensic.

You may take Difensic with or without food. However, Difensic capsules should be taken on an empty stomach.

To use the oral solution:

Use only the brand of Difensic that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of Difensic will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Difensic. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Missed Dose

If you miss a dose of Difensic, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Difensic administration

Administration of drug is important to know because the drug absorption and action varies depending on the route and time of administration of the drug. A medicine is prescribed before meals or after meals or along with meals. The specific timing of the drug intake about food is to increase its absorption and thus its efficacy. Few work well when taken in empty stomach and few medications need to be taken 1 or 2 hrs after the meal. A drug can be in the form of a tablet, a capsule which is the oral route of administration and the same can be in IV form which is used in specific cases. Other forms of drug administration can be a suppository in anal route or an inhalation route.
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Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

If you switch brands of Difensic, your dose needs may change. Follow your doctor's instructions about how much medicine to take.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time.

Dissolve the Difensic powder (Difensic) with 1 to 2 ounces of water. Do not use any other type of liquid. Stir this mixture and drink all of it right away. Difensic powder works best if you take it on an empty stomach.

Call your doctor if your headache does not completely go away after taking Difensic. Do not take a second dose of Difensic powder without your doctor's advice.

Do not crush, chew, or break an enteric-coated pill. Swallow the pill whole. The enteric-coated pill has a special coating to protect your stomach. Breaking the pill could damage this coating.

If you use this medication long-term, your liver function will need to be checked with frequent blood tests. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

Difensic pharmacology

Pharmacokinetics of a drug can be defined as what body does to the drug after it is taken. The therapeutic result of the medicine depends upon the Pharmacokinetics of the drug. It deals with the time taken for the drug to be absorbed, metabolized, the process and chemical reactions involved in metabolism and about the excretion of the drug. All these factors are essential to deciding on the efficacy of the drug. Based on these pharmacokinetic principles, the ingredients, the Pharmaceutical company decides dose and route of administration. The concentration of the drug at the site of action which is proportional to therapeutic result inside the body depends on various pharmacokinetic reactions that occur in the body.
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Mechanism of Action

Difensic has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of action of Difensic, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Difensic is a potent inhibitor of prostaglandin synthesis in vitro. Difensic concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because Difensic is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Pharmacokinetics

The relative bioavailability of Difensic 35 mg capsules was compared to Difensic potassium immediate-release (IR) tablets 50 mg in 39 healthy subjects under fasted and fed conditions in a single-dose crossover study.

Difensic 35 mg capsules do not result in an equivalent systemic exposure to 50 mg Difensic potassium IR tablets.

When taken under fasted conditions, a 20% lower dose of Difensic in Difensic capsules resulted in a 23% lower mean systemic exposure (AUCinf) and a 26% lower mean peak concentration (Cmax) compared to Difensic potassium IR tablets. The time to reach peak concentration (Tmax) was similar for Difensic and Difensic potassium IR tablets and was ~1 hour for both.

When taken under fed conditions, a 20% lower dose of Difensic in Difensic capsules resulted in a 23% lower mean systemic exposure (AUCinf) and a 48% lower mean Cmax compared to Difensic potassium IR tablets. The Tmax for Difensic was delayed by approximately 1 hour compared to Difensic potassium IR tablets (3.32 hours vs. 2.33 hours, respectively).

When taken under fed conditions, Difensic capsules resulted in an 11% lower mean systemic exposure (AUCinf) and a 60% lower mean Cmax compared to fasted conditions. Whereas Difensic potassium IR tablets under fed conditions resulted in 8% - 10% lower mean systemic exposure (AUCinf) and 28% - 43% lower mean Cmax compared to fasted conditions, based on the results from two individual food effect studies. The Tmax for Difensic was delayed by approximately 2.32 hours under fed conditions compared to fasted conditions (3.32 hours vs. 1.00 hour, respectively), while the Tmax for Difensic potassium IR tablets was delayed by approximately 1.00 - 1.33 hours under fed conditions compared to fasted conditions (1.70 vs. 0.74 hours and 2.33 vs. 1.00 hours, respectively in two studies).

There were no differences in elimination half-life between Difensic and Difensic potassium IR tablets under fasted or fed conditions.

Absorption

Difensic is 100% absorbed after oral administration compared to IV administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available. After repeated oral administration, no accumulation of Difensic in plasma occurred.

Administration of Difensic capsules 18 mg and 35 mg was associated with dose proportional pharmacokinetics.

Taking Difensic with food causes a significant decrease in the rate but not the overall extent of systemic absorption of Difensic compared with taking Difensic on an empty stomach. Difensic capsules results in 60% lower Cmax, 11% lower AUCinf, and 2.32 hours delayed Tmax (1.0 hour during fasted versus 3.32 hours during fed) under the fed condition compared to the fasted condition. The effectiveness of Difensic when taken with food has not been studied in clinical studies. The decreased Cmax may be associated with decreased effectiveness. Taking Difensic with food may cause a reduction in effectiveness compared to taking Difensic on an empty stomach.

Distribution

The apparent volume of distribution (V/F) of Difensic potassium is 1.3 L/kg. Difensic is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15-105 mg/mL) achieved with recommended doses.

Difensic diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of Difensic.

Elimination

Difensic is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. The terminal half-life of unchanged Difensic is approximately 2 hours.

Metabolism

Five Difensic metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy Difensic. The major Difensic metabolite, 4'-hydroxy-Difensic, has very weak pharmacologic activity. The formation of 4'-hydroxy-Difensic is primarily mediated by CYP2C9. Both Difensic and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CYP2C8 may also play a role in Difensic metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxy-Difensic. In patients with renal dysfunction, peak concentrations of metabolites 4'-hydroxy and 5-hydroxy-Difensic were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects.

Excretion

Difensic is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged Difensic is excreted in the urine. Approximately 65% of the dose is excreted in the urine, and approximately 35% in the bile as conjugates of unchanged Difensic plus metabolites. Because renal elimination is not a significant pathway of elimination for unchanged Difensic, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary. The terminal half-life of unchanged Difensic is approximately 2 hours.

Specific Populations

Pediatric: The pharmacokinetics of Difensic has not been investigated in pediatric patients.

Race: Pharmacokinetic differences due to race/ethnicity have not been identified.

Hepatic Impairment: No dedicated Difensic pharmacokinetics studies in patients with hepatic impairment were conducted. Hepatic metabolism accounts for almost 100% of Difensic elimination. Therefore, in patients with hepatic impairment, start with the lowest dose and if efficacy is not achieved, consider use of an alternate product.

Renal Impairment: Difensic pharmacokinetics has been investigated in subjects with renal insufficiency. No differences in the pharmacokinetics of Difensic have been detected in studies of patients with renal impairment. In patients with renal impairment (inulin clearance 60-90, 30-60, and less than 30 mL/min; N=6 in each group), AUC values and elimination rate were comparable to those in healthy subjects.

Drug Interaction Studies

Aspirin: When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced, although the clearance of free NSAID was not altered. The clinical significance of this interaction is not known. See Table 4 for clinically significant drug interactions of NSAIDs with aspirin.



References

  1. DailyMed. "DICLOFENAC EPOLAMINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
  2. NCIt. "Diclofenac: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
  3. EPA DSStox. "Diclofenac: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).

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The results of a survey conducted on ndrugs.com for Difensic are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Difensic. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

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Information checked by Dr. Sachin Kumar, MD Pharmacology

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