Diclofenac, rectal suppositories 100 mg, 10 pcs.

Pharmgroup:

NSAIDs.

Pharmic action:

Penylacetic acid derivative NSAID; has anti-inflammatory, analgesic and antipyretic effects. By indiscriminately inhibiting COX1 and COX2, it disrupts arachidonic acid metabolism, decreases amount of Pg in inflamed area.
It is most effective for pain of inflammatory nature. Like all NSAIDs, the drug has antiaggregant activity.

Pharmacokinetics:

Absorption is fast and complete, food slows the rate of absorption. After oral administration of 50 mg, Cmax is 1.5 mcg/ml, TCmax is 2-3 h.

Diclofenac prolonged action: as a result of delayed drug release, the Cmax in plasma is lower than that of short-acting drugs; however, it remains high for a long time after administration. Cmax is 0.5-1 mcg/ml, TCmax is 5 h after administration of 100 mg long-acting tablets.

After an IV infusion of 75 mg, Cmax is 1.9 µg/mL (5.9 µmol/L). After intravenous administration, Cmax is 2.5 µg/mL (8 µmol/L), TCmax is 20 min.
With rectal administration, TCmax is 30 min.

The plasma concentration is in a linear relationship to the amount of dose administered.

There is no change in pharmacokinetics of diclofenac on repeated administration. It does not cumulate if the recommended interval between meals is observed.

The bioavailability is 50%. Binding to plasma proteins is more than 99% (most of it is bound to albumin). Transfers to breast milk and synovial fluid; Cmax in synovial fluid is observed 2-4 hours later than in plasma. T1/2 from synovial fluid is 3-6 h (the drug concentrations in synovial fluid are higher 4-6 h after administration than in plasma and remain higher during 12 h).

50% of the drug is metabolized during the “first passage” through the liver; AUC is half as much after oral administration than after parenteral administration of the same dose. Metabolism occurs as a result of multiple or single hydroxylation and conjugation to glucuronic acid. The CYP2C9 isoenzyme is also involved in the metabolism of the drug. The pharmacological activity of the metabolites is less than that of diclofenac.

The systemic clearance is 260 ml/min. T1/2 from plasma is 1-2 hours. 60% of the administered dose is excreted as metabolites through the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites in the bile.

In patients with significant renal insufficiency (CKD less than 10 ml/min) excretion of metabolites in bile is increased, while there is no increase of their concentrations in blood.

In patients with chronic hepatitis or compensated liver cirrhosis pharmacokinetic parameters do not change.

Indications

Inflammatory and inflammation-activated degenerative forms of rheumatism:

Active ingredient

Composition

Active substance:

diclofenac 100 mg;

Supplementary substances:

1,2-propylene glycol,

aerosil,

vitepsol

How to take, the dosage

Rectally. Adults: 100 mg once daily, 50 mg twice daily or 25 mg 3-4 times daily.

The maximum daily dose is 150 mg.

Children over 12 years of age: 50 mg 1-2 times a day or 25 mg 2-3 times a day.

Interaction

In concomitant use of the drug Diclofenac with digoxin, phenytoin or lithium drugs may increase plasma concentrations of these drugs; with diuretics and hypotensive agents – possible decrease in the effect of these drugs; with potassium-saving diuretics – possible development of hyperkalemia; with acetylsalicylic acid – decrease of diclofenac concentration in blood plasma and increased risk of side effects.

Diclofenac may increase the toxic effects of cyclosporine on the kidneys.

Diclofenac may cause hypo- or hyperglycemia, therefore concomitant use with hypoglycemic agents requires control of blood glucose concentration.

When using methotrexate for 24 hours before or after taking Diclofenac it is possible to increase the concentration of methotrexate and increase its toxic effect.

When concomitant use with anticoagulants regular monitoring of blood clotting is required.

Special Instructions

In order to reduce the risk of gastrointestinal adverse events, the lowest effective dose should be used for the shortest possible course.

In order to quickly achieve the desired therapeutic effect, the tablets are taken 30 min before meals. Otherwise, they are taken before, during or after meals, without chewing and with plenty of water.

Because of the important role of Pg in maintaining renal blood flow, special caution should be exercised when prescribing in patients with cardiac or renal insufficiency, as well as in therapy in elderly patients taking diuretics, and in patients who for any reason have a decrease in the BOD (including after extensive surgical intervention). If diclofenac is prescribed in these cases, it is recommended to monitor renal function as a precautionary measure.

If the increase in “hepatic” transaminase activity persists or increases while taking the drug, if clinical symptoms of hepatotoxicity (including nausea, fatigue, drowsiness, diarrhea, skin itching, jaundice) are noted, treatment should be stopped.
Diclofenac (like other NSAIDs) may cause hyperkalemia.

When prolonged therapy it is necessary to monitor liver function, peripheral blood count, fecal occult blood test.

Due to the negative effect on fertility, the drug is not recommended for women who want to get pregnant. In patients with infertility (including those undergoing examination) it is recommended to discontinue the drug.

When taking the drug, mental and motor reactions may decrease; therefore, it is necessary to refrain from driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

Hypersensitivity (including to other NSAIDs), complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis and intolerance to ASA or other NSAIDs. NSAIDs (including history), erosive-ulcerative lesions of the gastrointestinal tract and 12 duodenum, active gastrointestinal bleeding, inflammatory bowel disease, severe liver and heart failure; period after coronary artery bypass grafting; severe renal insufficiency (CKR less than 30 ml/min), progressive renal disease, active liver disease, confirmed hyperkalemia, pregnancy (III trimester), lactation, children (under 14 years of age – for enteric coated tablets 50 mg and rectal suppositories 50 mg, under 18 years – for sustained release tablets and suppositories 100 mg).

In rectal administration (additionally): proctitis.

For FP containing lactose (optionally): hereditary lactose intolerance, impaired glucose-galactose absorption, lactase deficiency.

With caution. Gastric and 12-duodenal ulcer, ulcerative colitis, Crohn’s disease, liver diseases in anamnesis, hepatic porphyria, CHF, arterial hypertension, significant reduction of the blood circulation (including After major surgery,
elderly patients (including those treated with diuretics, debilitated patients and patients with low body weight),

Bronchial asthma, concomitant use of GCS (including prednisolone), anticoagulants (including warfarin).anticoagulants (including warfarin), antiplatelet agents (including ASA, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline),
CHD, cerebrovascular disease, dyslipidemia/hyperlipidemia,

Diabetes mellitus, peripheral arterial disease, smoking, CKD (IQ 30-60 ml/min), presence of Helicobacter pylori infection, long-term use of NSAIDs, alcoholism, severe medical conditions.

Side effects

Digestive system disorders: nausea, vomiting, epigastric pain, anorexia, flatulence, constipation, gastritis up to erosive with bleeding, increased transaminase activity, drug-induced hepatitis, pancreatitis.

Urinary system disorders: interstitial nephritis.

CNS disorders: headache, dizziness, disorientation, agitation, insomnia, irritability, fatigue, aseptic meningitis.

Respiratory system: bronchospasm.

Hematopoietic system: anemia, thrombocytopenia, leukopenia, agranulocytosis.

Dermatological reactions: exanthema, erythema, eczema, hyperemia, erythrodermia, photosensitization.

Allergic reactions: erythema multiforme, Lyell’s syndrome, Stevens-Johnson syndrome, anaphylactic reactions, including shock.

Local reactions: burning, infiltrate formation, necrosis of adipose tissue possible at the injection site.

Others: fluid retention in the body, edema, increased BP.

Similarities