Almiral

Almiral belongs to the group of drugs NSAIDs, is a derivative of acetic acid. The drug has anti-inflammatory and analgesic properties. Along with this, it has an antipyretic effect. It suppresses the production of components that provoke puffiness, pain and the secretion of inflammatory fluid in the area of inflammation.

The active element of the drug is diclofenac Na. When used to treat postoperative pain, it significantly reduces the need for opioids. [1]

Indications Almiral

It is used in such cases:

• short therapy for moderate pain of different etiology (sciatica, algomenorrhea, lumbago and neuralgia);
• therapy for arthritis (juvenile, rheumatoid, gouty or psoriatic type), osteoarthritis in the joints / spine and ankylosing spondylitis;
• treatment of post-traumatic or -operative pain.

Release form

The release of the therapeutic substance is made in the form of an 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 medicine slows down the activity of COX. Diclofenac Na in a state in vitro at a level equivalent to those achieved in humans does not suppress the process of proteoglycan biosynthesis carried out inside cartilaginous tissues. [2]

Pharmacokinetics

Suction.

When administered through an injection of 75 mg of diclofenac, absorption begins immediately, and an average plasma index of approximately 2.558 ± 0.968 μg / ml is noted after 20 minutes. The suction volumes are linearly proportional to the dosage size.

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

In comparison with the values after taking the substance inside, when using drugs in the form of intramuscular injections or suppositories, the plasma indicator rapidly decreases immediately after recording the Cmax level.

Bioavailability.

The AUC values for intravenous or intramuscular use are approximately twice as high as for rectal use or oral administration, since with the indicated route of administration, the drug does not participate in the 1st intrahepatic passage.

Distribution processes.

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

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

Low levels of diclofenac (100 ng / ml) were observed inside breast milk in one lactating woman. The estimated volume of the drug that penetrates with breast milk into the infant's body is equivalent to 0.03 mg / kg per day.

Exchange processes.

The metabolic processes of diclofenac are partially realized through glucuronization of an 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 are bioactive, but their effect is significantly less pronounced than the therapeutic activity of diclofenac.

Excretion.

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

About 60% of the applied portion is excreted in the urine in the form of glucuronide conjugates of an 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 rest of the portion is eliminated in the form of metabolic components with feces and bile.

Dosing and administration

You need to inject the medicine deeply, in the / m way. The standard 1-fold dosage size is 75 mg; a second injection can be made after at least 12 hours. Therapy usually lasts 2 days.

• Application for children

It is prohibited to use injectable diclofenac in pediatrics.

Use Almiral during pregnancy

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

Small amounts of the active drug component can be excreted with mother's milk, therefore, it is not used for HS.

Contraindications

The main contraindications:

• severe sensitization with respect to the active and auxiliary components of drugs;
• allergy to other NSAIDs;
• active stages of diseases in the gastrointestinal tract (having an erosive and ulcerative form);
• bleeding;
• disorders of hematopoietic processes;
• disorders of blood clotting (among them hemophilia);
• aspirin asthma.

Caution is required in case of use for such violations:

• bronchial asthma;
• pronounced swelling;
• anemia;
• increased blood pressure;
• CHF;
• hepatic / renal dysfunction;
• diverticulitis or intestinal inflammation;
• diabetes;
• porphyria;
• alcohol abuse;
• after complex operations (including coronary artery bypass grafting);
• general lesions of connective tissues;
• aged people.

Side effects Almiral

Among the side effects:

• disturbances in the work of the NS: drowsiness, anxiety, convulsions, cephalalgia, aseptic meningitis, nightmares, depression, sleep disorders;
• digestive problems: abdominal pain, nausea, flatulence, xerostomia, jaundice and hepatitis. In addition, obstipation / diarrhea, cirrhosis, esophageal lesions, hepatic necrosis, peptic ulcers, pancreatitis, blood in feces and colitis;
• disorders associated with the organs of perception: ear noise, taste disturbance, blurred vision, hearing impairment and double vision;
• lesions of the urogenital system: swelling, nephritis, oliguria, failure of the kidneys, blood or protein in the urine;
• epidermal disorders: rashes, severe photosensitivity, toxic dermatitis, alopecia, pruritus, eczema, punctate hemorrhages and urticaria;
• problems with hematopoietic processes: thrombocyto- or leukopenia, eosinophilia, agranulocytosis, thrombocytopenic purpura and anemia;
• disorders in the work of the heart: CHF, heart attack, increased blood pressure, chest pain 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 adipose tissue, aseptic necrosis and the appearance of infiltration.

Overdose

In case of poisoning, cephalalgia, blurred consciousness, dizziness, respiratory distress and vomiting are observed. Children may develop vomiting, bleeding, renal / hepatic dysfunctions, abdominal pain, and myoclonic-type seizures.

Intoxication requires the cancellation of Almiral and receiving qualified medical care.

Interactions with other drugs

Substances of lithium and digoxin.

Combination with diclofenac increases the plasma values of these drugs, which is why, with this use of drugs, their serum levels must 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 a slowdown in the binding of vasodilating PGs. Therefore, this combination should be used with caution, especially in the elderly - they should be carefully monitored for blood pressure.

Patients should be provided with adequate hydration and kidney function should be monitored. This is especially true for diuretics and ACE inhibitors - taking into account the increased likelihood of nephrotoxicity.

Medicines that can lead to the development of hyperkalemia.

The use together with cyclosporine, trimethoprim, potassium-sparing diuretics or tacrolimus can cause an increase in serum potassium levels, which is why it is necessary to regularly monitor the patient's condition during therapy.

Antithrombotic agents and anticoagulants.

The combination should be done with caution, as it can increase the likelihood of bleeding. Despite the fact that the effect of diclofenac in relation to the activity of anticoagulants has not been detected, there is some information regarding an increase in the likelihood of bleeding in persons using anticoagulants together with diclofenac. Because of this, in order to eliminate the need to change the size of the portion of anticoagulants, it is necessary to closely 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 an ulcer or bleeding in the gastrointestinal tract. It is required to abandon the combined use of 2+ NSAIDs.

Substances from the SSRI group.

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

Hypoglycemic drugs.

There are some data on the development of metabolic acidosis when using the drug with these medications, especially in people with pre-existing renal dysfunction.

Methotrexate.

Diclofenac is able to inhibit the renal clearance of methotrexate, due to which the indicators of the latter increase. Care should be taken when using diclofenac less than 24 hours before using methotrexate, as it can increase the blood level of the latter and its toxicity.

There is evidence of the development of severe toxicity with the introduction of both substances with an interval of less than 24 hours. This interaction is associated with the accumulation of methotrexate due to the disorder of its excretion through the kidneys under the influence of NSAIDs.

Cyclosporine.

Almiral may increase the severity of cyclosporine nephrotoxicity by acting on renal GHGs. Because of this, it should be used in reduced dosages.

Tacrolimus.

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

Antibacterial quinolones.

There is some information regarding seizures that may occur due to the administration of quinolones together with NSAIDs. They can appear in individuals with or without a history of seizures or epilepsy. Therefore, care should be taken when deciding whether to use quinolones in people already using NSAIDs.

Phenytoin.

With the introduction of phenytoin in combination with the drug, an increase in the exposure of the former may be noted. Because of this, the plasma phenytoin values must be monitored.

Colestyramine with colestipol.

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

Substances of SG.

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

Mifepristone.

It is forbidden to use NSAIDs within 8-12 days after the administration of mifepristone - because NSAIDs can weaken its therapeutic effect.

Medicines that slow down or induce the action of CYP2C9.

It is required to use the medication with the above substances with caution (among them, such as rifampicin and voriconazole), since they can significantly increase the exposure, as well as the plasma Cmax values of diclofenac.

Storage conditions

Almiral must be stored at temperature values within 15-25 ° С.

Shelf life

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

Analogs

The analogs of the medicine are the medicines Clodifen, Diclac, Naklofen with Voltaren, and besides this Diklodev, Rapten with Dicloberl, Evinopon and Diclofenac.