Almiral

Almiral is a member of the NSAID group of drugs and is a derivative of acetic acid. The drug has anti-inflammatory and analgesic properties. At the same time, it has an antipyretic effect. It suppresses the production of components that provoke swelling, pain, and secretion of inflammatory fluid in the area of inflammation.

The active ingredient of the drug is diclofenac Na. When using the drug to eliminate postoperative pain, it significantly reduces the need for opioids. [ 1 ]

Indications Almiral

It is used in the following cases:

• short-term therapy for moderate pain of various etiologies (sciatica, algomenorrhea, lumbago and neuralgia);
• therapy for arthritis (juvenile, rheumatoid, gouty or psoriatic type), osteoarthritis in the joints/spine area and Bechterew's disease;
• treatment of post-traumatic or post-operative pain.

Release form

The therapeutic substance is released in the form of injection liquid - inside ampoules with a volume of 75 mg/3 ml. Inside the cell plate - 5 ampoules; inside the pack - 1 or 2 such plates.

Pharmacodynamics

The drug slows down the activity of COX. Diclofenac Na in vitro at a level equivalent to the levels achieved in humans does not suppress the process of proteoglycan biosynthesis carried out inside cartilage tissue. [ 2 ]

Pharmacokinetics

Suction.

When 75 mg of diclofenac is administered by injection, absorption begins immediately and a mean plasma concentration of approximately 2.558±0.968 μg/ml is observed after 20 minutes. The absorption volumes are linearly proportional to the dose.

When using 75 mg diclofenac via a 2-hour infusion, the average plasma values of the drug are approximately 1.875±0.436 μg/ml. With a shorter infusion, the drug reaches the plasma Cmax value, and with prolonged infusions, a plateau concentration is observed, which is proportional to the level after a 3-4-hour infusion.

Compared to the values after taking the substance orally, when using the drug in the form of intramuscular injections or suppositories, the plasma indicator quickly decreases immediately after recording the Cmax level.

Bioavailability.

AUC values for intravenous or intramuscular administration are approximately twice as high as those for rectal or oral administration, since with this route of administration the drug does not participate in the first intrahepatic passage.

Distribution processes.

Diclofenac is 99.7% involved in protein synthesis, mainly binding to albumin (99.4%).

The substance penetrates into the synovium, reaching its highest values after 2-4 hours from obtaining plasma Cmax. The expected half-life from synovium is 3-6 hours. After 2 hours from obtaining plasma Cmax, diclofenac values inside the synovium exceed the plasma level and remain so for up to 12 hours.

Low levels of diclofenac (100 ng/mL) were observed in breast milk in one nursing mother. The estimated amount of drug excreted in breast milk to a nursing infant is equivalent to 0.03 mg/kg per day.

Exchange processes.

Diclofenac metabolism processes are partially realized through glucuronidation of the intact molecule, but mainly develop with 1-fold and multiple methoxylation and hydroxylation, as a result of which several phenolic metabolic elements are formed (with most of them being transformed into glucuronide conjugates). Two metabolites have bioactivity, but their effect is significantly less pronounced than the therapeutic activity of diclofenac.

Excretion.

The systemic plasma clearance values of diclofenac are 263±56 ml per minute. The terminal plasma half-life is 1-2 hours. The 4 metabolic components (also 2 with activity) also have a short half-life – within 1-3 hours.

About 60% of the administered dose is excreted in the urine in the form of glucuronide conjugates of the intact molecule, as well as in the form of metabolic elements, most of which are also transformed into glucuronide conjugates.

Less than 1% is excreted unchanged. The remainder is eliminated as metabolic components in the feces and bile.

Dosing and administration

The drug should be administered deeply, intramuscularly. The standard 1-time dosage is 75 mg; a repeat injection can be given after at least 12 hours. Therapy usually lasts 2 days.

• Application for children

The use of diclofenac in injectable form in pediatrics is prohibited.

Use Almiral during pregnancy

Diclofenac inhibits the production of PG, which can negatively affect the course of pregnancy and fetal development. In this regard, Almiral is not prescribed to pregnant women.

Small amounts of the active component of the drug can be excreted in breast milk, so it is not used during breastfeeding.

Contraindications

Main contraindications:

• pronounced sensitization to the active and auxiliary components of the drug;
• allergy to other NSAIDs;
• active stages of diseases in the gastrointestinal tract (having an erosive-ulcerative form);
• bleeding;
• disorders of hematopoiesis;
• bleeding disorders (including hemophilia);
• aspirin asthma.

Caution is required when using in the following disorders:

• bronchial asthma;
• pronounced swelling;
• anemia;
• elevated blood pressure;
• ZSN;
• liver/renal dysfunction;
• diverticulitis or intestinal inflammation;
• diabetes mellitus;
• porphyria;
• alcohol abuse;
• after complex operations (including coronary artery bypass grafting);
• general connective tissue lesions;
• elderly people.

Side effects Almiral

Side effects include:

• disorders of the nervous system: drowsiness, anxiety, convulsions, headache, aseptic meningitis, nightmares, depression, sleep disorders;
• Digestive problems: abdominal pain, nausea, flatulence, xerostomia, jaundice and hepatitis. In addition, constipation/diarrhea, cirrhosis, esophageal lesions, liver necrosis, peptic ulcers, pancreatitis, blood in the stool and colitis;
• disorders associated with the organs of perception: tinnitus, taste disturbance, blurred vision, hearing loss and double vision;
• lesions of the urogenital system: edema, nephritis, oliguria, renal failure, blood or protein in the urine;
• epidermal disorders: rashes, severe photosensitivity, toxic dermatitis, alopecia, itching, eczema, punctate hemorrhages and urticaria;
• problems with hematopoietic processes: thrombocytopenia or leukopenia, eosinophilia, agranulocytosis, thrombocytopenic purpura and anemia;
• disorders of the heart: congestive heart failure, infarction, increased blood pressure, pain in the chest area and extrasystole;
• respiratory disorders: cough, pneumonitis, swelling in the larynx and bronchial spasm;
• allergy symptoms: vasculitis and swelling affecting the tongue or lips;
• local signs: burning sensation, necrosis of fatty tissue, aseptic necrosis and the appearance of an infiltrate.

Overdose

In case of poisoning, cephalalgia, clouding of consciousness, dizziness, respiratory distress and vomiting are observed. In children, vomiting, bleeding, renal/hepatic dysfunction, abdominal pain and myoclonic seizures may develop.

Intoxication requires discontinuing Almiral and obtaining qualified medical assistance.

Interactions with other drugs

Lithium substances and digoxin.

Combination with diclofenac increases plasma levels of the indicated drugs, which is why when using the drugs in this way, their serum levels need to be monitored.

Antihypertensive and diuretic drugs.

The introduction of drugs with the above-described agents (for example, ACE inhibitors or β-blockers) can provoke a decrease in their hypotensive activity due to the slowing down of the processes of binding vasodilating PG. Therefore, such a combination should be used with caution, especially in the elderly - they should be closely monitored regarding blood pressure indicators.

Patients should be adequately hydrated and renal function should be monitored, particularly with diuretics and ACE inhibitors, given the increased risk of nephrotoxicity.

Medicines that can lead to the development of hyperkalemia.

Use with cyclosporine, trimethoprim, potassium-sparing diuretics or tacrolimus may cause an increase in serum potassium levels, which is why the patient's condition must be monitored regularly during therapy.

Antithrombotic agents and anticoagulants.

Combination should be done with caution, because it may increase the likelihood of bleeding. Although no effect of diclofenac on the activity of anticoagulants has been detected, there is some information regarding an increased likelihood of bleeding in individuals using anticoagulants together with diclofenac. Therefore, in order to exclude the need to change the dose of anticoagulants, it is necessary to carefully monitor the condition of such patients.

Large doses of diclofenac may temporarily inhibit platelet aggregation.

GCS and other NSAIDs, including selective COX-2 inhibitors.

The introduction of Almiral with GCS or other systemic NSAIDs may increase the likelihood of ulcers or bleeding in the gastrointestinal tract. It is necessary to refuse the combined use of 2+ NSAIDs.

Substances from the SSRI group.

The administration of systemic NSAIDs together with SSRIs increases the likelihood of bleeding in the digestive system.

Hypoglycemic drugs.

There are isolated reports of metabolic acidosis developing when using the drug with the above medications, especially in people with pre-existing renal dysfunction.

Methotrexate.

Diclofenac can inhibit the renal clearance of methotrexate, causing the latter to increase. Caution should be exercised when using diclofenac less than 24 hours before methotrexate, as this may increase the latter's blood levels and toxicity.

There is evidence of severe toxicity when both substances are administered within 24 hours of each other. This interaction is due to the accumulation of methotrexate due to the impairment of its renal excretion under the influence of NSAIDs.

Cyclosporine.

Almiral may increase the severity of cyclosporine nephrotoxicity by affecting renal PG. For this reason, it should be used in reduced dosages.

Tacrolimus.

Administration of tacrolimus with NSAIDs may increase the likelihood of nephrotoxicity due to the antiprostaglandin effect on the kidneys exerted by the calcineurin inhibitor and NSAIDs.

Quinolones are antibacterial drugs.

There are isolated reports of seizures that may occur when quinolones are administered with NSAIDs. These may occur in individuals with or without a history of seizures or epilepsy. Therefore, caution should be exercised when deciding whether to use quinolones in individuals already taking NSAIDs.

Phenytoin.

When phenytoin is administered in combination with the drug, an increase in the exposure of the former may be observed. Therefore, plasma phenytoin values should be monitored.

Cholestyramine with colestipol.

The above substances can reduce or delay the absorption of diclofenac. Therefore, it is necessary to use Almiral at least 1 hour before or 4-6 hours after the administration of cholestyramine/colestipol.

SG substances.

The use of CG together with NSAIDs can potentiate the severity of heart failure, increase plasma CG values and slow down glomerular filtration.

Mifepristone.

It is prohibited to use NSAIDs in the period of 8-12 days after the administration of mifepristone, because NSAIDs can weaken its therapeutic effect.

Medicines that inhibit or induce the action of CYP2C9.

The drug should be used with caution with the above substances (including rifampicin and voriconazole), since they can significantly increase the exposure, as well as plasma Cmax values of diclofenac.

Storage conditions

Almiral must be stored at temperatures between 15-25°C.

Shelf life

Almiral can be used for a period of 36 months from the date of manufacture of the therapeutic substance.

Analogues

Analogues of the drug are Clodifen, Diclac, Naklofen with Voltaren, and also Diklodev, Rapten with Dicloberl, Evinopon and Diclofenac.