Analdim® [Diphenhydramine, Metamizole Sodium]

Actual information

Analdim - a drug used to treat fever, pain. in its composition it contains two active substances - metamizole sodium and diphenhydramine hydrochloride. metamizole sodium - a derivative of pyrazolone, has a pronounced analgesic and antipyretic effect, which are realized due to its inhibition of the synthesis of prostaglandins and bradykinin. diphenhydramine hydrochloride exhibits antihistamine, sedative effects, and also acts as a central anticholinergic and has some anti-inflammatory properties. in a combination of metamizole sodium / diphenhydramine hydrochloride, the latter potentiates the action of metamizole sodium.

Both active substances of the drug Analdim they are well absorbed during rectal administration and form peak concentrations in the blood (within 1-2 hours). Both active substances Analdima penetrate the central nervous system. Metamizole sodium is excreted by the kidneys partially in the form of metabolites, partially in an unchanged state. The metabolism of diphenhydramine hydrochloride occurs in the liver. The drug is valid for up to 6 hours.

Metamizole sodium has been withdrawn from the market in the United States and some European countries after reports of several fatal agranulocytosis cases among patients receiving it. However, this drug remains available in many countries of Europe, South America and Asia, including in Ukraine. Over the past few decades, a number of studies have been conducted to assess the risk of side effects associated with taking non-narcotic analgesics. There are a number of studies on the safety of metamizole sodium, and above all the risk of developing fatal agranulocytosis when taken. The risk of developing gastrointestinal bleeding, anaphylaxis, hepatotoxicity, and congenital anomalies was also evaluated. So, in 2016, a group of scientists from the United States and Germany conducted a retrospective review of 22 such studies. They came to the conclusion that the data are ambiguous and further study of the issue is necessary for the possibility of a comparative assessment of the risk of adverse outcomes when taking sodium metamizole compared with other non-narcotic analgesics, since most of the studies analyzed showed an increase in risk, three did not suggest a connection between methamizole sodium and agranulocytosis. Five case-control studies were analyzed that evaluated the risk of bleeding from the upper gastrointestinal tract. Four studies showed an increased risk of gastrointestinal bleeding associated with taking metamizole sodium, and data were insufficient in most studies to evaluate other outcomes, such as hepatotoxicity, anaphylaxis, embryo or fetotoxicity (Andrade S. et al., 2016 )

So, a group of European scientists conducted an interesting double-blind, randomized, controlled study of the effectiveness of metamizole sodium compared with ibuprofen in the postoperative period. They compared the efficacy of a combination of paracetamol and ibuprofen with another combination of metamizole sodium and paracetamol. When comparing undesirable adverse reactions and overall patient satisfaction, they were the same in both groups, and it was also shown that both of these combinations have comparable levels of effectiveness. As a rationale for the need for such a study, scientists emphasize the favorable gastrointestinal and cardiovascular profile of this drug, unlike many other NSAIDs (Stessel B. et al., 2019).

Non-opioid analgesics are often used for pain relief during surgical procedures and in the postoperative period in children. In many countries, metamizole sodium is used as an alternative to paracetamol and traditional non-steroidal anti-inflammatory drugs such as ibuprofen and diclofenac.A study of the effectiveness and safety of metamizole sodium, conducted in Germany, Austria, Switzerland and the Netherlands, in which 2284 anesthesiologists took part, showed that this is a very widely used drug, but it requires close monitoring of the development of side effects, especially the control of a clinical blood test. So, 65.6% of anesthetists reported no side effects associated with it. Allergic reactions / anaphylaxis and a decrease in blood pressure requiring intervention were observed in 3-4% of respondents. 73.1% of respondents reported no change in the number of blood cells over the past 2 years, while 17 anesthetists (1.3%) observed children with an altered number of blood cells, with 2 (0.14%) reporting agranulocytosis. No serious complications or deaths have been reported. Few respondents (5.5%) performed routine blood cell counts to monitor metamizole therapy. In addition, only a minority always (3.5%) or sometimes (6.1%) informed the childs parents about the possible side effects of sodium metamizole treatment, from which the authors concluded that patients should be better informed about the side effects associated with this a drug administered intraoperatively for the prevention of pain (Witschi L. et al., 2019). The clinical symptoms of agranulocytosis should also be controlled.

In addition, studies were conducted in which the goal was to identify a genetic and ethnic predisposition to metamizole-induced agranulocytosis. According to their data, it cannot be ruled out that British, Irish, and Scandinavians have a higher risk of agranulocytosis during sodium metamizole therapy, which is associated with specific alleles of the HLA system (Shah R.R., 2019). If these data are confirmed in further studies, they may be useful to reduce the risk of agranulocytosis caused by sodium metamizole by screening.

The possibility of using metamizole sodium in patients with contraindications / intolerance to classical non-steroidal anti-inflammatory drugs is also being discussed in scientific circles. Recent Dutch anesthesiology guidelines advocate the use of metamizole sodium in these patients. It causes fewer gastric and duodenal ulcers than other non-selective NSAIDs, and the risk of bleeding from the upper gastrointestinal tract is lower when taken compared to other NSAIDs. Although the drug appears to be safe for renal function in healthy volunteers, data on high-risk patients (such as heart or kidney failure) are not available. The incidence of metamizole-induced agranulocytosis is controversial, but the risk may be limited by short-term postoperative use in patients with an increased risk of stomach or kidney disease (Konijnenbelt-Peters et al., 2017).

Diphenhydramine Hydrochloride is an Antagonist of H₁-histamine receptors of the first generation. Diphenhydramine hydrochloride is most often used by the oral, local, intramuscular and intravenous routes, not only to treat allergic reactions such as urticaria, but also to alleviate itching, treat extrapyramidal symptoms, and parkinsonism. It can also be used in the treatment of insomnia, dizziness and motion sickness, in various conditions it can be included in the complex treatment of dystonia and used to prevent them. Diphenhydramine hydrochloride also has some local anesthetic properties (Sicari V. et al., 2019). There are studies showing the efficacy of diphenhydramine hydrochloride for the treatment of motion sickness in transport at doses lower than those that can cause drowsiness in a patient (Valoti M. et al., 2003).

Pain of various origins.It must be remembered that pain is primarily a protective reaction of the body in response to damage, and it always indicates a malfunction in the human body. The use of painkillers does not eliminate the need to find out the cause of the pain and the main treatment should be aimed at the disease or condition that caused it. The use of pain medication is especially dangerous in the so-called acute abdomen - a group of surgical diseases that require immediate treatment, when masking the symptoms can have fatal consequences. Taking the drug to reduce the severity of headache or toothache, you must remember that anesthesia in this case does not mean a cure. The drug can be recommended as part of complex therapy for pain caused by radicular syndrome in osteochondrosis, neuralgia, radiculitis, myositis. It can also be prescribed to reduce the severity of pain during burns or postoperative pain, usually when narcotic analgesics are no longer needed.

Another condition in which application is indicated Analdima, is hyperthermia (fever), which can also be caused by various reasons. Hyperthermia is also a symptom of many diseases and conditions of the body, and not an independent nosological unit, and usually requires an integrated approach, identifying the causes of fever, and not just taking antipyretic drugs. At the same time, when the body temperature rises above 38.5 ° С (and sometimes even at lower values ​​on the thermometer), we are talking about the need to lower the temperature. Lets see why, what happens in our body with hyperthermia? Against a background of high temperature reaching 40 ° C, compensatory hyperventilation occurs as a response to developing metabolic acidosis. However, with a further increase in temperature, the minute volume of ventilation of the lungs drops sharply and respiratory acidosis occurs, which exacerbates the existing metabolic. Also, there is a sharp loss of fluid through the skin and respiratory tract, and the kidneys, due to a decrease in vascular resistance, begin to produce a large amount of hypotonic urine, all this leads to a loss of ions, a decrease in BCC and blood clotting. Many enzyme systems of the liver are inactivated, since the temperature range necessary for their normal operation is disrupted. The formation of lactic acid increases. There is tachycardia, but vascular tone decreases, which leads to a decrease in blood pressure. The metabolism of the brain increases, however, due to a decrease in blood pressure and blood clotting, blood supply to the brain decreases and there are phenomena of ischemia. Based on the foregoing, hyperthermia requires appropriate correction, but even “knocking down” the temperature, do not ignore the need for a doctors consultation and examination.

Do not forget that an increase in body temperature in infectious diseases is not just a symptom of a disease, but a protective physiological mechanism. It aims to increase the resistance of infection. At elevated body temperature, many infectious agents (viruses, bacteria) slow down their growth and reproduction. Also, fever affects the function of the immune system - there is an increase in the formation of neutrophils, T-lymphocytes, acute phase reactions are intensified. There is no reliable data on the need for prescribing antipyretics to reduce the number of complications in infectious diseases or mortality. To the forefront in the appointment of lowering body temperature means is the elimination of discomfort from fever in the patient, improving his well-being in the acute period of the disease. An exception, perhaps, is weakened patients, children with reduced protective reserves due to concomitant chronic diseases.

At reception Analdima it should be remembered that, first of all, in case of hyperthermia, paracetamol and ibuprofen are recommended for lowering body temperature (Sullivan J.E., 2011). Analdim can be recommended primarily in case of their inefficiency.

Before starting treatment, it is necessary to warn the patient about symptoms that mean that something has gone wrong and he should stop taking the drug and consult a doctor immediately. The patient should be informed that symptoms such as unreasonable chills, fever, difficulty swallowing and sore throat, bleeding gums, as well as previously not observed pallor, general weakness and fatigue, discomfort, bleeding, soreness of the vagina or rectum, the appearance of any rashes on the skin and mucous membranes may indicate the development of severe complications of the use of metamizole sodium. Metamizole sodium is myelotoxic, therefore, its regular use is contraindicated. It is also worth warning the patient that the reddish color of urine when taken Analdima not a threat. This staining is not due to bleeding, but to the excretion of metamizole sodium derivatives in the urine.

Diphenhydramine hydrochloride and preparations containing this substance are used with extreme caution in patients with COPD, hyperthyroidism, increased intraocular pressure, and in elderly patients. The medicine can cause discomfort in patients using contact lenses, as it can lead to dry eyes. During treatment with diphenhydramine hydrochloride, alcohol is prohibited. It is also recommended to avoid exposure to ultraviolet radiation. The use of diphenhydramine hydrochloride can complicate the diagnosis of acute appendicitis and other conditions, combined by the term "acute abdomen." It may also be difficult to detect poisoning or an overdose of other medicines due to its antiemetic effect.

Please note that Analdim may slow down the reaction rate and disturb attention span.

The drug is used in adults, in pediatric practice.

Analdim administered rectally with a frequency of 1-3 injections per day. Childrens age (1–4 years) - suppositories are recommended, which include 100 mg of metamizole sodium and 10 mg of diphenhydramine hydrochloride. In children older than 5 years and adults, suppositories are used containing 250 mg of metamizole sodium and 20 mg of diphenhydramine hydrochloride, for children 1 suppository, adults, if necessary (depending on the severity of pain, hyperthermia), 2 suppositories can be prescribed for 1 dose at a time . The duration of treatment is determined by the attending physician depending on the dynamics of the disease, the severity of symptoms. Usually the drug is used in the acute period and is not prescribed for more than a few days.