Diclowal Supp

Diclofenac sodium.

Ivory-coloured, homogeneous torpedo sized suppositories.
Each suppository contains: Diclofenac sodium 100 mg.
Excipients/Inactive Ingredients: Hard fat.

Pharmacotherapeutic group: Nonsteroidal anti-inflammatory drugs. ATC code: M01AB05.
Pharmacology: Pharmacodynamics: Diclofenac, a derivative of phenylacetic acid, is a primitive non-steroidal anti-inflammatory drug (NSAID). Diclofenac is structurally related to meclofenamate sodium and meclofenamic acid and pharmacologically similar to other primary NSAIDs. The drug inhibits angiogenesis and degrades nascent blood vessels in inflammatory tissues of animals. NSAIDs, including diclofenac, are predicted to inhibit angiogenesis through inhibition of substrate P or inhibition of the angiogenic effects of prostaglandin E (PEG). The drug has anti-inflammatory, analgesic and antipyretic effects. The exact mechanism has not been clearly established, but many effects are associated primarily with inhibition of prostaglandin synthesis. Diclofenac inhibits prostaglandin synthesis in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2) (prostaglandin G/H synthase-1 [PGHS-1] and -2 [PGHS-2], respectively), which catalyze the synthesis of prostaglandin formation in the arachidonic acid pathway. Diclofenac, like other primary NSAIDs, inhibits both COX-1 and COX-2. Although the exact mechanism has not been clearly established, NSAIDs exert their anti-inflammatory, analgesic and antipyretic effects mainly through inhibition of the COX-2 isoenzyme; COX-1 inhibition is probably responsible for the undesirable effects of the drug on the gastrointestinal mucosa and platelet aggregation.
Pharmacokinetics: Absorption: Diclofenac is rapidly and efficiently absorbed after conventional oral, rectal or intramuscular administration.
Maximal plasma concentrations after rectal administration are attained after approximately thirty minutes. Peak plasma concentrations and area under the plasma concentration-time curve (AUC) are linearly related to a dose over the range of 25 - 150 mg, regardless of administration route; after oral, rectal or intramuscular doses no accumulation occurred after repeated doses.
In elderly patients of more than 62 years of age and patients aged 2 - 7 years with juvenile rheumatoid arthritis peak plasma concentrations, time to peak plasma concentrations (tmax) and AUC values are similar to those produced in adult patients without arthritic conditions.
Bioavailability: The systemic bioavailability of diclofenac from the delayed-release dosage form is averaging about 82% of that of enteric coated tablets at the same dose (possibly depending on the rate of release due to first-pass metabolism). As a result of the slower release of the active substance, peak plasma concentrations are lower than that of the corresponding enteric coated tablets.
Pharmacokinetic behaviour does not change on repeated administration. Accumulation does not occur, provided the recommended dosage intervals are observed. The trough concentration of diclofenac in plasma after administration of 100 mg/day extended-release tablets is approximately 22 ng/ml (70 nmol/l).
Distribution: The active substance is 99.7% protein bound, mainly to albumin (99.4%).
Diclofenac enters the synovial fluid, where maximum concentrations are measured 2-4 hours after the peak plasma values have been attained. The apparent half-life for elimination from the synovial fluid is 3-6 hours. Two hours after reaching the peak plasma values, concentrations of the active substance are already higher in the synovial fluid than they are in the plasma and remain higher for up to 12 hours.
Metabolism: Biotransformation of diclofenac takes place partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and methoxylation, resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.
Elimination: The total systemic clearance of diclofenac in plasma is 263 ± 56 mL/min (mean value ± SD). The terminal half-life in plasma is 1-2 hours. Four of the metabolites, including the two active ones, also have short plasma half-lives of 1-3 hours.
About 60% of the administered dose is excreted in the urine in the form of the glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% is excreted as unchanged substance. The rest of the dose is eliminated as metabolites through the bile in the faeces.

Diclofenac sodium is used for symptomatic treatment of pain and inflammation in case of musculo-skeletal-arthritis disorders such as rheumatoid arthritis, chronic arthritis.

Rectal administration only.
Keep the hands clean before and after inserting the drug.
Remove the suppository out of blister.
The suitable position: the patient lies on one side, one leg bent.
Thumb and index finger hold the pill, gently insert the tip of the tablet into the rectum.
The drug shouldn't be inserted deeply, it should be inserted to be suitable with the length of suppository.
Keep the position constant within 15 minutes.
Adults: one suppository daily.
Elderly patients: Non-steroidal anti-inflammatory drugs should be used with particular caution in such patients who, generally, are more prone to adverse reactions. In particular, it is recommended that the lowest effective dosage be used in frail, elderly patients or those with a low body weight (see also Precautions) and the patient should be monitored for GI bleeding during NSAID therapy.
Renal impairment: Diclofenac is contraindicated in patients with severe renal impairment. No specific studies have been carried out in patients with renal impairment, therefore, no specific dose adjustment recommendations can be made. Caution is advised when administering diclofenac to patients with mild to moderate renal impairment.
Hepatic impairment: Diclofenac is contraindicated in patients with severe renal impairment. No specific studies have been carried out in patients with hepatic impairment, therefore, no specific dose adjustment recommendations can be made. Caution is advised when administering diclofenac to patients with mild to moderate hepatic impairment.
Children (aged 1-12 years): Suppositories are not suitable for children.

Symptoms: Overdosage can cause symptoms like headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, dizziness, disorientation, excitation, coma, drowsiness, tinnitus, fainting, or convulsions. In rare cases of significant poisoning acute renal failure and liver damage are possible.
Management: Supportive measures and symptomatic treatment should be used for complications such as hypotension, renal failure, convulsions, gastrointestinal disturbances, and respiratory failure.
Special measures such as diuresis, hemodialysis, or blood transfusion are unlikely to be effective in removing NSAIDs, including diclofenac, due to their high protein binding and extensive metabolism.
Activated charcoal can be used after overdose, potentially toxic, and gastric detox (eg, induce vomiting, gastric lavage) after a potentially life-threatening overdose.
Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient's clinical condition.

Hypersensitivity to diclofenac, aspirin or other NSAIDS (asthma, rhinitis, urticaria after taking aspirin) or any of the excipients.
Gastric ulcers, bleeding or perforation.
History of gastrointestinal bleeding or perforation, relating to previous NSAID therapy.
History of recurrent peptic ulcer/haemorrhage.
Last trimester of pregnancy.
Severe hepatic, renal or cardiac failure.
Like other non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac is also contraindicated in patients in whom attacks of asthma, angioedema, urticaria or acute rhinitis are precipitated by ibuprofen, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs.
Proctitis.
Established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

Use with caution in patients with active/progressive peptic ulcer or gastrointestinal bleeding/bleeding.
Diclofenac couldn't be alternative for corticosteroids or for the treatment of corticosteroid deficiency.
The antipyretic and anti-inflammatory pharmacological effects of diclofenac may hide the benefit of diagnostic signs of fever and inflammation in detecting complications of pain and are presumed to be noninfectious.
Patients who have symptoms and/or signs of hepatic function disorders, or patients have abnormal liver function tests should be evaluated for signs of progression of liver reactions during treatment with diclofenac. If clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (eosinophilia, rash), diclofenac should be discontinued.
Patients on long-term treatment with NSAIDs, including diclofenac, should have their hemoglobin/hemoglobin or hematocrit/solid red blood cell ratio checked if any signs or symptoms of anemia are observed.
Diclofenac should be used with caution in patients who may experience adverse effects from altered platelet function, such as those with coagulopathy or those taking anticoagulants.
Diclofenac should be used with caution in patients with pre-existing asthma.
Like other NSAIDs, diclofenac may mask the signs and symptoms of the infection due to its pharmacodynamic properties.
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
Appropriate monitoring and counseling is required for patients with a history of hypertension and/or mild to moderate congestive heart failure due to fluid retention and edema associated with NSAIDs treatment including diclofenac.
Patients with a history of visual disturbances, dizziness, somnolence, central nervous system disturbances, drowsiness or fatigue, should not drive or operate machinery while taking NSAIDs.
Effects on Ability to Drive and Use Machines: Can get headache, the patients should be careful when driving or using machines.

Pregnancy: Diclofenac shouldn't be used in the third trimester of pregnancy because it could get closure of the ductus arteriosus soon; do not use drug at the end of pregnancy as it could delay uterine contractions or prolong labor.
Lactation: Diclofenac should not be administered during breast feeding in order to avoid undesirable effects in the infant.

Common: 1-10%; uncommon: 0,1-1%; rare: 0.01-0.1%; very rare: less than 0.01%, individually cases.
Gastrointestinal system: Nausea, vomiting, diarrhoea, dyspepsia, flatulence.
Sense: Vertigo; very rare: Visual disturbance.
Cardiac system: Very rare: Palpitations, chest pain, hypertension.
Any adverse drug reactions should be immediately reported to the physician or pharmacist.

Diclofenac shouldn't combine with: Oral anticoagulants and heparin: Increase the risk of bleeding (as warfarin and NSAIDs have a synergistic effect on gastrointestinal bleeding).
Quinolones: Diclofenac and other NSAIDs could get increasing side effects on central nervous system of quinolones, leading to seizures (need more research).
Aspirin or glucocorticoids: Reduces diclofenac plasma concentrations and increases the risk and severity of gastrointestinal injury.
Diflunisal: Concomitant administration of diflunisal with diclofenac may increase diclofenac plasma concentrations, decrease diclofenac clearance, and may cause fatal gastrointestinal bleeding.
Lithium: Diclofenac may increase serum lithium concentrations to toxic levels. If co-administration is required, the patient should be carefully monitored for early signs of lithium toxicity and blood levels of lithium should be monitored on a regular basis. The dose of lithium must be adjusted during and after diclofenac treatment.
Digoxin: Diclofenac may increase serum digoxin concentrations and prolong the half-life of digoxin. Concetration of digoxin should be measured and digoxin dose should be reduced if both drugs are used concurrently.
Ticlopidine: Increase the risk of bleeding.
Intrauterine contraceptive device: There are reports that the use of diclofenac reduces the effectiveness of contraception.
Methotrexate: NSAIDs competitively inhibit methotrexate accumulation in the kidney of rabbits. This suggests that they may increase methotrexate toxicity.
Diclofenac could be concomitantly used with following drugs but the patients should be monitored: Cyclosporine: Risk of cyclosporine toxicity. The renal function should be monitored.
Diuretics: Diclofenac reduces the urinary sodium excretion efficiency of furosemide and thiazides. Diclofenac and diuretics may increase the risk of developing secondary renal failure due to decreased renal blood flow because diclofenac inhibits prostaglandins. When this drug is used in combination with NSAIDs, patients should be closely monitored for signs of renal failure, as well as to ensure the diuretic effect of the drug.
Antihypertensives (ACE inhibitors, beta-blockers, diuretics): NSAIDs may reduce the antihypertensive effect of ACE inhibitors.
Administration of antacids may reduce intestinal irritation caused by diclofenac but may decrease serum diclofenac concentrations.
Cimetidine may slightly decrease serum diclofenac concentrations but does not reduce the anti-inflammatory effect of the drug. Cimetidine protects the duodenum from the harmful effects of diclofenac.
Probenecid may double diclofenac concentrations if used concurrently. This may be clinically beneficial in people with joint disease, but diclofenac toxicity can occur, particularly in those with impaired renal function. The effect of uric acid excretion - urine is not affected. If necessary, reduce the dose of diclofenac.

Store below 30°C, protect from light and moisture.
Shelf-Life: 36 months from manufacturing date.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AB05 - diclofenac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.