Pharmacological properties
Pharmacodynamics.
drotaverine, an isoquinoline derivative, has an antispasmodic effect on smooth muscles by inhibiting the action of the PDE IV enzyme, which leads to an increase in the concentration of camp and, due to the inactivation of myosin light chain kinase (mlck), leads to relaxation of smooth muscles. In vitro, drotaverine inhibits the action of the PDE IV enzyme and inhibits PDE III and V isoenzymes. PDE IV is of great functional importance for reducing the contractile activity of smooth muscles, therefore selective inhibitors of this enzyme may be useful for the treatment of patients with diseases that are accompanied by hypermobility, as well as various diseases that cause gastrointestinal spasms.
In the smooth muscle cells of the myocardium and blood vessels, cAMP is hydrolyzed mainly by the PDE III isoenzyme, therefore drotaverine is an effective antispasmodic agent, does not cause significant side effects on the cardiovascular system and does not have a pronounced therapeutic effect on this system.
Drotaverine is effective against smooth muscle spasms of both nervous and muscular origin. Drotaverine acts on the smooth muscles of the digestive, biliary, genitourinary and vascular systems, regardless of the type of their autonomous innervation. The product increases blood circulation in tissues due to its ability to dilate blood vessels.
The effect of drotaverine is stronger than that of papaverine, absorption is faster and more complete, it binds less to blood plasma proteins. The advantage of drotaverine is also that, unlike papaverine, after its parenteral administration there is no such side effect as stimulation of respiration.
Pharmacokinetics. Drotaverine is quickly and completely absorbed after oral administration. In many ways (95–98%) binds to blood plasma proteins, especially albumin, gamma and beta globulins. Cmax in the blood after oral administration is achieved within 45–60 minutes. After primary metabolism, 65% of the dose taken enters the bloodstream unchanged. Metabolized in the liver. T½ is 8–10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body, more than 50% is excreted in the urine, 30% in feces. Drotaverine is mainly excreted in the form of metabolites and is not detected unchanged in the urine.
Drotaverine hydrochloride tablets 40 mg No. 10x2
Name
Drotaverine hydrochloride, tablets, 40 mg in container cells, 20 pcs.
Description
Transparent yellow with a greenish tint solution.
Main active ingredient
Drotaverine.
Release form
Solution.
Dosage
40 mg.
pharmachologic effect
Drotaverine is an isoquinoline derivative that exhibits an antispasmodic effect on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV). Inhibition of the PDE IV enzyme results in increased concentrations of cAMP, which inactivates myosin light chain kinase and leads to smooth muscle relaxation. Drotaverine inhibits PDE IV in vitro without inhibiting the isoenzymes PDE III and PDE V. To reduce smooth muscle contractility, PDE IV is functionally very important, and its selective PDE IV inhibitors may be useful in the treatment of hyperkinetic diseases and various symptoms caused by spastic conditions of the gastrointestinal tract. tract. Drotaverine has no side effects on the cardiovascular system, because the smooth muscle cells of the myocardium and blood vessels mainly contain the PDE III isoenzyme. The enzyme that hydrolyzes cAMP in myocardial and vascular smooth muscle cells is mainly a PDE III isoenzyme, which explains why drotaverine is an effective antispasmodic agent without serious cardiovascular side effects and strong cardiovascular therapeutic activity. The drug is effective for spasms of smooth muscles of both nervous and muscular etiology. Regardless of the type of autonomic innervation, drotaverine acts on smooth muscles located in the gastrointestinal, biliary, urogenital and vascular systems. Thanks to its vasodilating effect, it enhances tissue blood circulation. Its effect is stronger than that of papaverine, and absorption is faster and more complete; it binds less to plasma proteins. The advantage of drotaverine is that it does not have a stimulating effect on the respiratory system, which was observed after parenteral administration of papaverine.
Indications for use
spasms of smooth muscles associated with diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis; spasms of smooth muscles of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder tenesmus. As an adjuvant treatment (if the patient cannot take tablets):
- for spasms of smooth muscles of gastrointestinal origin: peptic ulcer of the stomach and duodenum, gastritis, spasms of the cardia and pylorus, enteritis;
- in gynecology: algodismenorrhea.
Directions for use and doses
Unless otherwise directed by the physician, the usual average dose for adults is 40 to 240 mg of drotaverine hydrochloride (divided into 1 to 3 doses per day) intramuscularly daily. For acute colic (cholelithiasis and urolithiasis) 40-8() mg intravenously.
Use during pregnancy and lactation
As shown by the results of preclinical studies in animals and retrospective studies of clinical data, oral use of drotaverine during pregnancy does not lead to either teratogenic or embryotoxic effects. However, caution is required when prescribing the drug during pregnancy. Drotaverine should not be used during childbirth. Due to the lack of necessary clinical data, it is not recommended to prescribe during breastfeeding.
Impact on the ability to drive vehicles and potentially dangerous mechanisms
After parenteral, and especially intravenous administration of the drug, patients are advised to refrain from driving and working on machines.
Precautionary measures
Clinical studies of the drug in children are not presented. With low blood pressure, the use of the drug requires caution. When administering drotaverine intravenously, due to the risk of loss of consciousness, the patient must lie down! In case of hypersensitivity to sodium metabisulfite, parenteral use of the drug should be avoided. Caution should be exercised when taking the drug parenterally by pregnant women.
Interaction with other drugs
When taken together with levodopa, the drug reduces the effect of the latter on the symptoms of Parkinson's disease, while increasing muscle stiffness and shaking (tremor).
Contraindications
hypersensitivity to the active substance or to any of the excipients of the drug (especially to sodium metabisulfite); severe liver, kidney or heart failure (low cardiac output syndrome); childhood.
Compound
active substance - drotaverine hydrochloride - 40.0 mg; excipients - sodium metabisulfite, rectified ethyl alcohol from food raw materials 95%, water for injection.
Overdose
An overdose of drotaverine can cause cardiac arrhythmia and conduction disturbances, including complete bundle branch block and cardiac arrest, which can be fatal. In case of overdose, the patient should be monitored and receive symptomatic and supportive treatment.
Side effect
During clinical trials, the following side effects were reported by investigators as being associated with drotaverine and presented the following incidence: very common (> 1/10); common (> 1/100, 1/1000, 1/10000,
Storage conditions
In a place protected from light at a temperature not exceeding 25 °C. Keep out of the reach of children.
Buy Drotaverine g / cold tablet 40 mg in container pack No. 10x2 in the pharmacy
Price for Drotaverine g/cold tablet 40 mg in container pack No. 10x2
Instructions for use for Drotaverine g/chlor tablet 40 mg in container pack No. 10x2
Indications
For therapeutic purposes for smooth muscle spasms associated with diseases of the biliary tract (cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis); spasms of smooth muscles in diseases of the urinary tract (nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder tenesmus).
As an auxiliary treatment for spasms of smooth muscles of the gastrointestinal tract (stomach and duodenal ulcers, gastritis, cardio- and/or pylorospasm, enteritis, colitis, spastic colitis with constipation and irritable bowel syndrome accompanied by flatulence); tension headache; gynecological diseases (dysmenorrhea).
Application
Pills. apply the drug internally.
Adults: the average daily dose is 120–240 mg (3–6 tablets), divided into 2–3 doses.
Children aged 6–12 years: the maximum daily dose is 80 mg, divided into 2 doses.
Children over 12 years of age: the maximum daily dose is 160 mg, divided into 2–4 doses.
The duration of treatment is determined individually.
R-r. The drug is used for adults intramuscularly at a dose of 40–240 mg in 1–3 administrations.
For acute colic, the drug should be administered to adults intravenously slowly at a dose of 40–80 mg.
The place of drotaverine among modern antispasmodics
Most often, pain and spasms are observed in diseases of the gastrointestinal tract (gastrointestinal spasms due to dyspepsia, colitis, cholecystitis, irritable bowel syndrome, etc.). A disorder of contraction of the smooth muscles of the gastrointestinal tract explains many of the symptoms encountered by therapists and gastroenterologists. Symptoms of spasmodic gastrointestinal dysfunction occur in almost 30% of people. Spastic pains are observed not only in diseases of the gastrointestinal tract, but also in urological and gynecological diseases. Understanding the pathophysiology of visceral spasm can facilitate a rational approach to treatment and choice of antispasmodic. Review of antispasmodics Antispasmodics represent a heterogeneous group of drugs; they differ in their mechanism of action and selectivity of action on different organs. Depending on the mechanisms of action, antispasmodics are divided into two groups: neurotropic and myotropic (Table 1) [1,2]. Neurotropic antispasmodics produce an antispasmodic effect by disrupting the transmission of nerve impulses in the autonomic ganglia or nerve endings that stimulate smooth muscles. The most important neurotropic antispasmodics are M-anticholinergic blockers. M-cholinergic blockers (atropine-like drugs) have a variety of effects on the muscle tone of various organs and the secretion of glands in which these receptors are localized. Thus, M-anticholinergics reduce the tone of the smooth muscles of internal organs (gastrointestinal tract, biliary tract, urinary tract, bronchi), reduce the secretion of hydrochloric acid in the stomach and other excretory glands (salivary, mucous, sweat), increase heart rate, cause mydriasis, paralysis of accommodation and increased intraocular pressure. The antispasmodic effect of M-cholinergic blockers on the gastrointestinal tract is carried out unevenly - mainly in the upper parts of the gastrointestinal tract (they reduce the tone of the stomach, pyloric sphincter, duodenum, gall bladder), which is associated with the unequal density of M-cholinergic receptors in the gastrointestinal tract and noncholinergic mechanisms for regulating the tone of the distal parts. Quaternary ammonium compounds that do not penetrate the BBB (methacin, chlorosyl) and have low systemic bioavailability when taken orally (hyoscine butyl bromide) have a more selective effect. Hyoscine butyl bromide exhibits its antispasmodic activity through its effect on the M1 and M3 subtypes of receptors, localized mainly in the walls of the upper gastrointestinal tract, gallbladder and biliary ducts, as well as blockade of H-cholinergic receptors (ganglionic blocking effect). For spasms of the lower gastrointestinal tract, it acts in doses 10 times higher than therapeutic doses. It is a relatively selective drug, since with increasing dose it loses selectivity, with the likely manifestation of typical atropine-like peripheral effects. Despite the minimal systemic availability of selective M-anticholinergics, they have unfavorable pharmacodynamic drug interactions with other drugs that cause anticholinergic effects (tricyclic antidepressants, antihistamines, quinidines). Anticholinergics are successfully used for abdominal pain caused by spasm in the upper gastrointestinal tract: dysfunction of the sphincter of Oddi, biliary dyskinesia, and pylorospasm [2,3]. However, some authors argue that hyoscine butylbromide has low effectiveness for biliary and renal colic and recommend it as an addition to analgesics [4]. Myotropic antispasmodics reduce muscle tone by directly influencing the biochemical intracellular processes that provide contractile activity: 1) change the content of intracellular cyclic nucleotides that regulate the concentration of intracellular Ca2+ (cAMP, cGMP); 2) directly change the current of Ca2+ ions into the cell through voltage-dependent or receptor-dependent calcium channels; 3) change the current of Na+ ions into the cell. The first mechanism includes phosphodiesterase (PDE) inhibitors (papaverine, drotaverine, etc.), the second - calcium channel blockers (pinaverium bromide, otilonium bromide), the third - sodium channel blockers (mebeverine hydrochloride). Myotropic antispasmodics exhibit a certain selectivity of action towards individual smooth muscle organs: they include gastrointestinal antispasmodics, bronchodilators, vasodilators, etc. PDE inhibitors are the most universal class of myotropic antispasmodics. Although they differ in selectivity and selectivity of action, which is ensured by the existence of numerous PDE isoenzymes in various types of tissues (tissue-specific and species-specific). Along with the antispasmodic effect on the gastrointestinal tract, urinary system, genital organs, bronchi and other organs, they have a minimal effect on the cardiovascular system. Drotaverine is a selective inhibitor of the PDE IV isoform, which is involved in the regulation of contractile activity of the intestine, urinary tract, and myometrium, which provides a high antispasmodic effect and selectivity of action. Drotaverine has additional mechanisms of antispasmodic action: blocking slow calcium channels, antagonism to calmodulin, blocking Na+ channels [5]. The pharmacodynamic effects of drotaverine underlie the pathogenetic action for the relief of acute spasmodic syndrome and long-term pharmacotherapy, for example, in chronic gastrointestinal diseases with spastic syndrome accompanied by colicky pain, dyskinesia of the bile ducts, cholelithiasis, as well as spasmodic syndromes in diseases of the urinary tract and pathologies of the genital organs. The lack of anticholinergic activity has a positive effect on the tolerability and safety of drotaverine, expanding the range of people to whom it can be prescribed, in particular, in elderly men with prostate pathology, as well as with concomitant pathology and co-administration with other drugs. Calcium antagonists with a predominant effect on the gastrointestinal tract include pinaverium bromide and otilonium bromide. The drugs have selective action on the gastrointestinal tract as a result of low systemic bioavailability (less than 10%), which practically does not cause systemic side effects characteristic of selective calcium antagonists. All of them have an antispasmodic effect not only on the upper gastrointestinal tract (stomach, pyloric sphincter), biliary system (sphincter of Oddi), but also effectively suppress peristalsis and spasms of the colon. The main use of calcium channel blockers, which act selectively on the gastrointestinal tract, is associated with irritable bowel syndrome (IBS). In the treatment of biliary pain they have no advantages over other antispasmodics. Myotropic antispasmodics include sodium channel blockers - mebeverine hydrochloride. By reducing the permeability of smooth muscle cells to Na+ ions through sodium channels, it helps limit the influx of Na+ and prevent the subsequent muscle spasm, thereby achieving an antispastic effect. Mebeverine also blocks the filling of the depot with extracellular Ca2+, which exhibits the properties of a calcium antagonist and complements the antispastic effect [2]. Mebeverine has the most selective effect predominantly on the gastrointestinal tract as a result of low systemic bioavailability, therefore it is used mainly for functional diseases of the gastrointestinal tract (non-ulcer dyspepsia, IBS), as well as for secondary spasms caused by organic diseases of the intestines and biliary tract. Results of clinical studies of drotaverine (No-Shpa) Clinical studies of No-Shpa in gastroenterology. The very first placebo-controlled studies showed the effectiveness of No-Shpa for relieving acute pain in three groups of diseases: diseases of the biliary tract, gastrointestinal diseases (peptic ulcer, gastritis, etc.), renal colic. According to the results of these studies, a complete immediate antispasmodic effect with intravenous or intramuscular administration was observed in 60% and was absent in only 17.5% of patients, while in the placebo group the absence of effect occurred in 73% of cases [6]. Subsequent studies revealed the effectiveness of oral use of No-Shpa in the treatment of spastic pain in patients with gastric and duodenal ulcers. It was noted that the effect began in most cases within 5–6 minutes, and complete pain relief developed after 12 minutes. Long-term oral administration of No-Shpa at a dose of 80 mg 3 times a day. within 5–20 days in 78% of patients it led to the disappearance of pain. A Shanghai study (n=180) compared the effectiveness of drotaverine (No-Shpy) and atropine in the treatment of abdominal pain associated with diseases of the gastrointestinal tract and biliary system (1998). Drotaverine was prescribed intramuscularly at a dose of 40 mg, atropine at a dose of 0.5 mg; pain syndrome was assessed on a 4-point scale, the effectiveness criterion was a decrease in pain severity by 1 point within 60 minutes. According to the study results, drotaverine led to a decrease in pain severity from 2.21 to 0.43 points (p<0.01), atropine - from 2.15 to 0.51 points (p<0.01). Differences in the main criterion of effectiveness between drugs were not significant; at the same time, pain relief developed faster with the use of drotaverine than with atropine: the average speed of the effect was 18.3 and 29.7 minutes. respectively (p<0.05), and the range of time to achieve effects was 5–40 and 15–60 minutes. respectively. There were also significant differences in the tolerability of the two drugs: the use of atropine was accompanied by a high frequency of characteristic side effects (dry mouth - 68%, hot flashes - 46%, palpitations - 31%, dizziness - 8%), while the use of drotaverine was only in 4% of cases accompanied by side effects (p<0.01). In a small study of 30 patients with abdominal pain syndrome caused by various gastrointestinal diseases (gastritis/gastroduodenitis, biliary dyskinesia, cholecystitis, colitis, pancreatitis), the dynamics of pain were assessed (on a 5-point scale) using No-Shpa 80 mg [ 7]. The severity of pain in patients averaged 3.2 points and was mostly moderate (73.3%). No-Shpa was prescribed in injection form at 80 mg once or in tablet form (No-Shpa forte 80 mg) for 7 days (the average daily dose was 140 mg). The dynamics of pain syndrome during treatment with No-Spa 80 mg showed a significant decrease in pain intensity on the first day both after intramuscular administration of No-Spa to 1.8 points, and after oral administration to 1.8 points. A course of taking No-Shpa forte for 7 days was accompanied by complete relief of pain within 2 days (up to 1 point – no pain). As a result, clinical effectiveness (excellent and good) was 80% according to doctors and 73% according to patients. The high rate of onset of the antispasmodic effect is ensured by the pharmacokinetics of drotaverine. After oral administration, the peak concentration of the drug in plasma occurs between 45 and 60 minutes, and 50% absorption is achieved in 12 minutes, which characterizes drotaverine as a rapidly absorbed drug (Fig. 1) [8]. Thus, the tablet dosage form of No-Shpa is characterized by high bioavailability (60%) and a rapid onset of action, which also allows its use for relief purposes. Efficacy of No-Shpa for diseases of the biliary system. Dyskinesia in the biliary and pancreatic systems is a common cause of acute pain (biliary colic) and chronic pain. The mechanism of pain development is primarily associated with dysfunction of the sphincter of Oddi, spasm of the sphincter muscle fibers of which leads to increased pressure in the bile and/or pancreatic duct system. In a pilot study, the antispasmodic effect of drotaverine was studied in 6 patients with biliary/pancreatic dyskinesia who underwent a functional test with morphine [9]. The use of drotaverine at a dose of 80 mg before the administration of morphine showed relaxation of the sphincter of Oddi and prevented the development of pain. In a double-blind, placebo-controlled clinical study, the effectiveness of drotaverine was studied in 42 patients with pain syndrome due to sphincter of Oddi stenosis. Drotaverine was prescribed 80 mg 3 times a day. for 4 months; in the control group, patients received placebo. The use of No-Shpa showed a significant reduction in pain in 61% of patients and a small effect in another 22%, while in the placebo group the effect was observed in 47 and 17%, respectively. The results of these studies showed that No-Shpa is an effective remedy for spasms of the muscles of the biliary tract, and can be used both in monotherapy and in combination with antibiotics and surgical treatment methods. Clinical studies of No-Shpa in irritable bowel syndrome (IBS). IBS is a very common gastrointestinal disease and is observed in 10–15% of the population. IBS is a common reason for visiting doctors. Among drug treatment methods, antispasmodics occupy a leading position: the frequency of their use is 42%. Antispasmodics are used in all clinical variants of IBS and help control the symptoms of the disease (abdominal pain, stool frequency). Pain syndrome in IBS is not the main one and is associated with intestinal transit disorders; a likely cause of pain may be a decrease in the threshold of pain sensitivity. The effectiveness of No-Shpa in patients with IBS was studied in two studies. A randomized, double-blind, placebo-controlled study included 62 patients (age 50.8 years) with IBS and constipation [10]. Patients recorded their complaints daily for 2 weeks. before the start of treatment and for 8 weeks. treatment with No-Spa in tablets 80 mg 3 times a day. or placebo. During No-Shpa therapy, a significant decrease in abdominal pain was observed by 47%, while in the placebo group, pain decreased by 3% (p < 0.05). While taking No-Shpa, other symptoms also decreased, including flatulence (by 21% versus 6% on placebo). The effectiveness of treatment with No-Shpa, according to patients and doctors, was 62.5 and 70.8%, respectively, and in the placebo group – 48% each. In another randomized, double-blind study, the effectiveness of No-Shpa was studied in 70 patients aged 18–60 years with a diagnosis of IBS [11]. Patients received No-Shpu in tablets of 80 mg 3 times a day. compared with placebo for 4 weeks, and then patients were observed for an additional 4 weeks. after discontinuation of therapy. The results of the study showed that the use of No-Shpa significantly reduced the frequency and intensity of pain by 47% (p<0.001) and the severity of dyspepsia by 20% compared to placebo (p<0.001). In Russian practice, a retrospective analysis of the effectiveness of 3 antispasmodics was carried out in 120 patients with IBS in hospital conditions: drotaverine, mebeverine and hyoscine [12]. The dynamics of spasticity and pain syndrome were assessed in total scores after 24 hours, 3 and 7 days. The results of the study showed that No-Shpa had the most pronounced and rapid effect, which was significantly different from the effects of other drugs after 24 hours; with further treatment there were no significant differences in the severity of the effects. At the same time, pharmacoeconomic analysis revealed the advantages of using No-Shpa in patients with IBS during the entire period of hospitalization of patients: the costs of the drug and the total costs of treatment were less than when using mebeverine and hyoscine by 52 and 83%, respectively. Clinical studies of No-Shpa in urology. The use of antispasmodics in urology is associated with the relief of renal colic against the background of urolithiasis. Stones located in the ureters cause painful spasms, block the flow of urine and lead to stretching of the kidney capsule, causing severe pain. In these cases, antispasmodics can not only relieve renal colic, but also promote the evacuation of stones (lithokinetic therapy). The antispasmodic effect of No-Shpa in patients with renal colic caused by nephro- and urethrolithiasis was shown in early clinical studies. The peculiarity of the drug’s action was not only the relief of renal colic, but also the restoration of the passage of urine through the urinary tract. In a controlled study in 208 hospitalized patients with urethrolithiasis, the effectiveness of drotaverine and atropine was compared; in all cases, patients additionally received analgesics [13]. In patients, stones were detected mainly in the lower part of the ureters; the size of the stones ranged from 7 to 26 mm (maximum dimension). Spontaneous evacuation of stones occurred in 68% of patients receiving drotaverine and 55.6% of patients receiving atropine. Moreover, with the use of drotaverine, even large stones (more than 17 mm) passed away in 24%, while in the control group - only in 2% of cases (Table 2). The average frequency of attacks of renal colic per 1 patient in both groups did not differ (1.6 and 1.7, respectively); At the same time, the duration of the period before the evacuation of the stones was significantly shorter against the background of the use of no - shpa compared to control (4.6 days against 5.7 days, respectively). In 1999–2000 A large multicenter placebo -controlled clinical study was carried out to study the effectiveness of NO -SHPA for urolithiasis [14]. The study included 140 patients (an average age of 42.5 years) with ultrasound or radiological studies in kidneys and ureters. To stop renal colic, the drutaverin of iv at a dose of 80 mg or placebo was used. The analysis included 102 patients: 48 received drutaverin, 54 - a placebo. The main endpoint of the study was the assessment of the antispasmodic effect of the NO - ShPA for 3 hours. Efficiency was evaluated using the visual -analogue scale (range 0–10), a 5 -point scale of pain intensity and a 5 -point pain reduction scale; Efficiency criteria were a decrease in pain by 40% in your or 50% on a 5 -point pain of pain reduction. The effectiveness of the antispasmodic action of the NO - ShPA was 79%, in the placebo group - 46% (p = 0.001), and the decrease in the intensity of pain on 5- points scales was reliably more pronounced against the background of the use of NO -SHPA than on placebo (Fig. 2) . Reducing your pain in your own had reliable differences only after 20 minutes. According to a survey of patients, but - shpa was also more effective than placebo (81% versus 65%, respectively); The frequency of repeated administrations amounted to 42 and 65%, respectively (p <0.05). Clinical studies of but - gynecology. Gynecological disorders are often accompanied by severe pain due to spasm of the genitals. In a 4 -year observation study, the effectiveness of the use of drotaverine in 1400 women with various gynecological disorders (Table 3) was evaluated [15]. But - shpa was used in the form of injections or orally in doses up to 120 mg/day. The effectiveness of the NO - ShPA was noted in 81% of cases. It should be noted that the average daily dose can be 240 mg. In a recent multicenter, comparative double -blind study of Dorota in 323 women with dysmenorrhea, accompanied by severe or moderate pain, studied the effectiveness of NO -SHPA at a dose of 240 mg/day. and ibuprofen at a dose of 1200 mg/day. Within 3 days of the menstrual cycle (16). The severity of the pain was evaluated on a 4 -point scale for 6 hours after taking the drugs. The total decrease in the severity of the pain for the 6th hour of the period did not significantly differ in groups: –1.2 ± 1.18 amid the reception of NO -SHPA and -1.7 ± 0.99 against the background of Ibuprofen, although the proportion of patients with a good effect was more against the background of Ibuprofen (68% versus 42%). These results indicate the effectiveness of antispasmodics with dysmenorrhea in women. Pharmacoepidemiology of drotaverine (NO -SHPs) in Hungary conducted 2 consecutive large pharmacoepidemiological studies devoted to the study of the effectiveness of NO -SHPA in the pre -heating treatment of spasm of smooth muscles of various organs [17,18]. Research was carried out by analyzing medical documentation of the ambulance for the period 1982–83. (1st study, n = 4946) and since 1996–1997. (2nd study, n = 5934). The efficiency of but - for the relief of spasmodic symptoms and pain in emergency clinical practice was more than 70%. The greatest efficiency of but - was observed in patients with nephrolytias and renal colic, gastritis, abdominal colic, holes, dysmenorrhea (Table 4) [18]. The analysis of the dose dependence of the antispasmodic action of the NO -SHPA showed that for diseases of the gastrointestinal tract and gynecological disorders, effectiveness was achieved in most patients at a dose of 40 mg, while with spasms of bile and urinary tract, the most often required a dose of 80 mg (Table 5) [18]. An analysis of the velocity of the onset of the antispasmodic effect of NO -ShPA showed that the most rapid disappearance of spasm symptoms and pain was observed in the vast majority of patients for 20 minutes. (Table 6) [12]. The safety of but - in clinical studies, the safety analysis of the NUSSIA SAMS was carried out on clinical research for the period from 1964 to 1998. General and serious side effects were evaluated by organs and systems based on WHO classification. The analysis included 37 clinical studies, which included 14,818 patients - 12,111 received no - shpa. But - shpa was prescribed orally in doses of 120–240 mg/day., Injection in doses of 40–80 mg (maximum 120 mg) to stop symptoms or 20–40 mg/day. for supporting treatment. 108 side effects were described, the distribution of side effects by organs and systems is presented in Figure 3. The most frequent side effects, the frequency of which is more than 5%, were allergic reactions (17.6%), dizziness (11.1%), arrhythmia/palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (palpitations (heartbeat 6.5%), ataxia (6.5%), hemorrhage from the injection site (5.6%). The total frequency of side effects in accordance with the classification of WHO does not exceed 0.9%. There were no serious side effects associated with the use of NO - SHPA. Thus, over 76 clinical, observation and pharmacoepidemiological studies with the participation of 30,502 patients (30,034 adults and 468 children), of which 26,531, the patient received NO -ShPU were conducted [19]. The high efficiency and safety of the drug is convincingly proved. For the entire time of use of NO - more than 20 countries of the world, not a single case of a serious side effect has been registered. The conclusion of the NO - ShPA remains the most popular antispasmodic in clinical practice both for stopping spasms and pain, and for the treatment of diseases, accompanied by increased tone of smooth muscles. Drotaverin has a universal spectrum of action, regardless of the pathogenesis of pain and localization of spasms. The pharmacokinetics of the drug provides a high speed of achieving a bought antispasmodic effect even with oral use. Along with the high efficiency of NO - shpa, it differs in the best safety, tolerate well and does not cause significant cardiovascular reactions. In addition, the high efficiency of NO - SHPs is combined with efficiency with prolonged use.
Literature 1. Functional diseases of the intestines and biliary tract: issues of classification and therapy./ Int. Bulletin Gastroenterology 2001, no. 5, pp. 1–4. 2. Rational pharmacotherapy of diseases of the digestive system. / Ed. V.T.Ivashkina. M.: Litterra, 2003, 1046 p. 3. Shulpekova Yu.O. Comparative characteristics of antispasmodic drugs used in gastroenterologist practice. / Wedge. prospects for gastroenterol., hepatol. 2002, no. 5, pp. 6–11. 4. Holdgate A, Oh CM. Is there a role for antimuscarinics in renal colic? A randomized controlled trial. J Urol (Baltimore) 2005; 174:572–5. PubMed. 5. Tomoskozi Z., Finance O., Aranyi P. Drotaverine interacts with L-type Ca2+ channel in pregnant rats uterine membranes./ Eur. J. Pharmacol. 2002, v.449, p. 55–60. 6. Juhasz I., Palos LA Clinical value of No–Spa®./ Gyogyszereink 1964, v.14, p.219–225. 7. Leonova M.V., Shishkina T.I., Belousov Yu.B. New dosage form no-shpa forte in clinical practice. / Farmateka 2001, no. 12, pp. 20–21. 8. Bolaji OO, Onyeji CO, Ogundaini AO et al. Pharmacokinetics and bioavailability of drotaverine in humans./ Eur.J.Drug Metab.Pharmacokinet. 1996, v. 21, p. 217–221. 9. Pap A., Topa L., Balgha V. et al./ Gastroenterology 1997, v.112 (suppl), p. A519 (Abs). 10. Pap A., Hamvas J., Filiczky I., Burai M. Beneficial effect of drotaverine in irritable bowel syndrome./ Gastroenterology 1998, v. 114, p. G3359 (AGA Abs). 11. Misra SC, Pandey RM Efficacy of drotaverine in irritable bowel syndrome: a double-blind, randomized, placebo-controlled clinical trial./ Am.J.Gastroenterology 2000, v. 95, p. 2544 (Abs 455). 12. Afonin A.V., Drapkina O.M., Kolbin A.S. and others. Clinical and economic analysis of antispasmodics for the relief of abdominal pain caused by intestinal spasm. / RMJ 2010, vol. 18, no. 13, pp. 845–849. 13. Vecsey D. Results achieved by combined analgesic and spasmolytic treatment of patients with ureterolithiasis./ Urol. Nephrol. 1983, v.10, p.187–190. 14. Romics I., Molnar DL, Timberg G. et al. The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones./ BJU International 2003, v. 92, p. 92–96. 15. Czinkan T., Szabo S. Evaluation of NO–SPA® in the treatment of obstetric and gynecological cases./ Med.Univ. 1971, v. 22 (suppl. 4), p. 189–192. 16. Debski R., Niemiec T., Mazurec M., Debska M. Comparative efficacy and tolerability of drotaverine 80 mg and ibuprofen 400 mg in patients with primary dysmenorrhea – protocol DOROTA./ Ginec.Pol. 2007, v. 78, p. 933–938. 17. Maklari L., Tury P. NO–SPA® in the oxyological practice for the treatment of abdominal spastic conditions and acute cardiovascular cases. / Ther. Hung. 1989, Special issue, p. 3–20. 18. Maklari L., Tury P. Drotaverine (no-spa) in emergency medicine practice./ Klin. Pharmacology and therapy 1999, No. 2, 48–49. 19. Tar A., Singer J. Safety profile of NO–SPA®./ Orv. Hetil. 2002, v. 143, p. 559–562.
Side effects
Side effects that were observed during clinical studies and may have been caused by drotaverine are divided by organ system and frequency of occurrence: very common (1/10), common (1/100, 1/10), uncommon (1/1000, 1/100), rare (1/10,000, 1/1000), very rare (1/10,000).
From the gastrointestinal tract: rarely - nausea, vomiting, constipation.
From the nervous system: rarely - headache, dizziness, insomnia.
From the cardiovascular system: rarely - rapid heartbeat, arterial hypotension.
From the immune system: rarely - allergic reactions, including angioedema, urticaria, skin rashes, itching, skin flushing, fever, chills, increased body temperature, weakness.
The drug in the form of a solution contains metabisulfite, which can cause allergic reactions, including symptoms of anaphylactic shock and bronchospasm in sensitive patients, especially with a history of asthma or allergies.
General disorders: hypersensitivity reactions at the injection site.
special instructions
Use the drug with caution in case of arterial hypotension.
Excipients. Drotaverine-Darnitsa contains 64 mg of lactose, so patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use the drug.
Hypersensitivity reactions. Drotaverine is a histamine liberator drug and can cause non-allergic (false-allergic) reactions that do not have immunological mechanisms, but imitate allergic symptoms (the phenomenon of mimicry). They are usually associated with non-immune release of histamine, bradykinin, activation of complement, induction of leukotriene synthesis, which, in turn, induces bronchospasm and skin manifestations. The drug should be prescribed with caution to patients with allergic reactions or a history of asthma. If symptoms of a hypersensitivity reaction appear after taking drotaverine (rash, itching, swelling of the tissues of the upper respiratory tract), the drug should be immediately discontinued and appropriate therapy should be prescribed. If symptoms of angioedema or urticarial rash occur, oral antihistamines should be used.
If the patient is known to have asthma, an inhaled β2-agonist should be administered. It is necessary to monitor the patient's condition over the next 4 hours. If there is continuous vomiting and/or abdominal pain, the possibility of administering epinephrine intramuscularly should be considered.
When administering the drug intravenously, the patient should be in a horizontal position due to the risk of collapse.
Use the drug with caution in case of arterial hypotension.
Caution should be exercised when administering the drug parenterally to pregnant women (see Use during pregnancy and lactation).
The drug in the form of a solution contains metabisulfite, which can cause allergic reactions, including symptoms of anaphylactic shock and bronchospasm in sensitive patients, especially those with a history of asthma or allergies.
In case of hypersensitivity to sodium metabisulfite, parenteral administration of the drug should be avoided.
Use during pregnancy and lactation. As shown by the results of animal studies, oral administration of the drug did not cause any signs of any direct or indirect effect on pregnancy, embryonic development, childbirth or postpartum development. However, it is necessary to use the drug with caution during pregnancy. Do not use drotaverine during childbirth.
Due to the lack of relevant research data, use of the drug during breastfeeding is not recommended.
Children. The use of the drug is contraindicated for children under 6 years of age. The use of drotaverine in children has not been evaluated in clinical studies. The drug in solution form is not used in children.
The ability to influence reaction speed when driving vehicles or working with other mechanisms. If patients experience dizziness after using the drug, they should avoid potentially hazardous activities such as driving and performing tasks that require increased alertness. You should refrain from driving vehicles or operating other machinery while using (especially IV) the drug.
Drotaverine solution for IV and IM administration 20 mg/ml in 2 ml ampoules No. 10
Name
Drotaverina-Borimed solution 2% 2ml No. 10
Description
Transparent liquid from yellow to yellowish-green. The presence of the smell of acetic acid is allowed.
Compound
One ampoule (2 ml of solution) contains: active substance – drotaverine hydrochloride – 40 mg; excipients: sodium metabisulfite, sodium acetate trihydrate, glacial acetic acid, ethyl alcohol, water for injection.
Pharmacotherapeutic group
A drug for the treatment of functional disorders of the gastrointestinal tract. Papaverine and its derivatives. ATX code: A03AD02.
Pharmacological properties
Pharmacodynamics Drotaverine is an isoquinoline derivative that exhibits an antispasmodic effect on smooth muscle by inhibiting the enzyme phosphodiesterase IV (PDE IV). Inhibition of the enzyme phosphodiesterase IV results in increased concentrations of cAMP, which inactivates myosin light chain kinase (MLCK), which in turn leads to smooth muscle relaxation. Drotaverine inhibits the PDE IV enzyme without inhibiting the PDE III and PDE V isoenzymes. PDE IV is functionally very important in reducing smooth muscle contractility and selective PDE IV inhibitors may be useful in the treatment of hyperkinetic diseases and various conditions associated with spastic conditions of the gastrointestinal tract. The enzyme that hydrolyzes cAMP in myocardial and vascular smooth muscle cells is mainly an isoenzyme of PDE III, which explains why drotaverine is an effective antispasmodic agent without serious cardiovascular side effects and pronounced effects on the cardiovascular system. Drotaverine is effective for smooth muscle spasms caused by disturbances in nervous regulation and self-regulation of both nervous and muscular etiologies. Regardless of the type of autonomic innervation, drotaverine acts on smooth muscles located in the gastrointestinal, biliary, urogenital and vascular systems. Thanks to its vasodilating effect, it improves tissue blood circulation. The effect of drotaverine is stronger than that of papaverine, and absorption is faster and more complete; it binds less to plasma proteins. The advantage of drotaverine is that it does not have a stimulating effect on the respiratory system, which was observed after parenteral administration of papaverine. Pharmacokinetics Drotaverine is rapidly and completely absorbed both after oral administration and after parenteral administration. It binds to a high degree (95–98%) to plasma proteins, especially albumin, gamma and beta globulins. After primary metabolism, 65% of the administered dose enters the bloodstream unchanged. Peak serum levels after oral administration are achieved within 45–60 minutes. Metabolized in the liver. The biological half-life is 8–10 hours. Within 72 hours, drotaverine is almost completely eliminated from the body, more than 50% is excreted in the urine, 30% in feces. Drotaverine is mainly excreted in the form of metabolites and is not found unchanged in the urine.
Indications for use
- spasms of smooth muscles associated with diseases of the biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis;
- spasms of smooth muscles of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder tenesmus.
As an adjuvant therapy (when the tablet form cannot be used):
- for spasms of smooth muscles of the gastrointestinal tract: peptic ulcer of the stomach and duodenum, gastritis, spasms of the cardia and pylorus, enteritis, colitis;
- for gynecological diseases: dysmenorrhea.
Contraindications
Hypersensitivity to the active substance or to any of the excipients of the drug (especially sodium methyl bisulfite), severe hepatic, renal or heart failure (low cardiac output syndrome), childhood.
Precautionary measures
Caution should be used in case of arterial hypotension, severe atherosclerosis of the coronary arteries, and during pregnancy. When administering drotaverine intravenously, due to the risk of collapse, the patient must lie down! In case of hypersensitivity to sodium methyl bisulfite, parenteral use of the drug should be avoided. This medicine contains sodium methyl bisulfite, which may cause allergic-type reactions, including anaphylactic shock and bronchospasm in sensitive individuals, especially those with a history of asthma or allergic diseases. Clinical studies on the use of the drug in children have not been conducted.
Pregnancy, breastfeeding and fertility
Parenteral use of drotaverine during pregnancy does not lead to teratogenic and embryotoxic effects. However, caution is required when prescribing the drug during pregnancy. Drotaverine should not be used during childbirth. Due to the lack of necessary clinical data, it is not recommended to prescribe during breastfeeding. There are no data on the effect of the drug on fertility.
Impact on the ability to drive vehicles or other machinery
After parenteral, and especially intravenous, administration of the drug, patients are advised to refrain from driving vehicles and engaging in potentially hazardous activities that require quick physical and mental reactions.
Directions for use and doses
The average daily dose for adults is 40–240 mg drotaverine hydrochloride (divided into 1–3 administrations per day) intramuscularly. For acute colic (cholelithiasis and urolithiasis) - 40–80 mg (2–4 ml of the drug) slowly intravenously.
Side effect
If adverse reactions occur, you should consult a doctor. The assessment of undesirable effects is based on the following data on the frequency of occurrence: very often (?1/10), often (?1/100 to
Interaction with other drugs
Drotaverine may weaken the antiparkinsonian effect of levodopa. Drotaverine enhances the effect of papaverine, bendazole and other antispasmodics (including m-anticholinergics). When tricyclic antidepressants, quinidine and procainamide are used simultaneously with drotaverine, the hypotensive effect is enhanced. Drotaverine reduces the spasmogenic activity of morphine. Phenobarbital increases the severity of the antispasmodic effect of drotaverine.
Overdose
Symptoms: In high doses, it can cause cardiac arrhythmia and conduction disturbances, including complete bundle branch block and cardiac arrest, which can be fatal. Treatment: observation, symptomatic and supportive treatment.
Package
2 ml in glass ampoules. 10 ampoules along with instructions for medical use are placed in a cardboard box (No. 10). 10 ampoules, together with instructions for medical use, are placed in a pack with a cardboard insert for fixing the ampoules (No. 10).
Storage conditions
In a place protected from light, at a temperature from 15? C to 25? C. Keep out of the reach of children.
Best before date
2 years. The medicine cannot be used after the expiration date.
Conditions for dispensing from pharmacies
On prescription.
Note!
Description of the drug Drotaverin-Darnitsa solution d/in. 20mg/ml amp. 2ml No. 5 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
