Но-шпа®

General characteristics. Structure:

Pharmacological properties:

Pharmacodynamics. Drotaverinum represents derivative isoquinoline which shows powerful spasmolytic action on smooth muscles at the expense of inhibition of enzyme of phosphodiesterase (FDE). Enzyme phosphodiesterase is necessary for hydrolysis of cyclic adenosinemonophosphate (tsAMF) to adenosinemonophosphate (AMF). The inhibition of enzyme of phosphodiesterase leads to increase in concentration of tsAMF which starts the following cascade reaction: high concentration of tsAMF activate tsAMF dependent phosphorylation of the kinase of light chains of a myosin (KLCM). Phosphorylation of KLTsM leads to decrease in its affinity to Ca - a kalmodulinovy complex therefore the inactivated KLTsM form supports muscular relaxation. tsAMF besides influences cytosolic concentration of an ion of Ca2 + thanks to stimulation of transport of Ca2 + in extracellular space and a sarcoplasmic reticulum. This Ca2 lowering concentration of an ion + effect of Drotaverinum through tsAMF explains antagonistic effect of Drotaverinum in relation to Ca2+.
In vitro Drotaverinum inhibits FDE IV isoenzyme without inhibition of isoenzymes of FDE III and FDE V. Therefore efficiency of Drotaverinum depends on concentration of FDE IV in fabrics which content in different fabrics differs. FDE IV is most important for suppression of sokratitelny activity of smooth muscles in this connection the selection inhibition of FDE IV can be useful to treatment of the hyperkinetic diskineziya and various diseases which are followed by a spastic condition of digestive tract. Hydrolysis of tsAMF in a myocardium and smooth muscles of vessels happens, mainly, by means of FDE III isoenzyme, than the fact that at high spasmolytic activity Drotaverinum has no serious side effects from heart and vessels and the expressed effects concerning cardiovascular system speaks. Drotaverinum is effective at spasms of smooth muscles of both a neurogenic, and muscular origin. Irrespective of type of a vegetative innervation Drotaverinum relaxes smooth muscles of digestive tract,
biliary tract, urinogenital system.

Pharmacokinetics.

Absorption
After intake Drotaverinum is quickly and completely absorbed. After presistemny metabolism 65% of the accepted Drotaverinum dose come to a system blood stream. The maximum plasma concentration (Gmax) is reached in 45-60 minutes.

Distribution
In vitro Drotaverinum has high communication with proteins of plasma (95-98%), especially with albumine, at and in - globuminam.
Drotaverinum is evenly distributed on fabrics, gets into smooth muscle cells. Does not get through a blood-brain barrier. Drotaverinum and/or its metabolites can slightly get through a placental barrier.

Metabolism
At the person Drotaverinum is almost completely metabolized in a liver by O-dezetilirovaniya. Its metabolites quickly conjugate with glucuronic acid. The main metabolite is 4-dezetildrotaverin except which were identified 6-dezetildrotaverin and 4-dezetildrotaveraldin.

Removal
At the person for assessment of indicators of pharmacokinetics of Drotaverinum the two-chamber mathematical model was used. The final elimination half-life of plasma radioactivity made 16 hours.
Within 72 hours Drotaverinum is almost completely brought out of an organism. More than 50% of Drotaverinum are removed by kidneys and about 30% - through digestive tract (excretion in bile). Drotaverinum is mainly excreted in the form of metabolites, not changed Drotaverinum in urine is not found.

Indications to use:

- Spasms of smooth muscles at diseases of biliary tract: cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis.
- Spasms of smooth muscles of an uric path: nephrolithiasis, ureterolithiasis, pyelitis, cystitis, bladder spasms.
As auxiliary therapy
- At spasms of smooth muscles of digestive tract: a peptic ulcer of a stomach and duodenum, gastritis, spasms of the cardia and the gatekeeper, enteritis, colitis, a spastic colitis with a lock and a syndrome of the angry intestines with a meteorism after an exception of the diseases which are shown a syndrome of "acute abdomen" (appendicitis, peritonitis, perforation of an ulcer, acute pancreatitis, etc.).
- At tension headaches.
- At a dysmenorrhea.

Route of administration and doses:

Adults
Usually average daily dose at adults makes 120-240 mg (the daily dose is divided into 2-3 receptions). The maximum single dose makes 80 mg. The maximum daily dose makes 240 mg. Children of Clinical trials with use of Drotaverinum with participation of children it was not carried out.

In case of purpose of Drotaverinum to children:
- for children from 6 to 12 years the maximum daily dose makes 80 mg, divided into 2 receptions.
- for children over 12 years the maximum daily dose makes 160 mg, divided into 2-4 receptions.
Treatment duration without consultation with the doctor At administration of drug without consultation with the doctor the recommended duration of administration of drug usually makes 1-2 days. If during this period the pain syndrome does not decrease, the patient should see a doctor to specify the diagnosis and if necessary to change therapy. In cases when Drotaverinum is used as auxiliary therapy, treatment duration without consultation with the doctor can be more (2-3 days).

Efficiency assessment method
If the patient can diagnose easily independently symptoms of the disease as they are for it well-known, then efficiency of treatment, namely disappearance of pains, also easily gives in to assessment by the patient. If within several hours after reception of the maximum single dose moderate reduction of pain or lack of reduction of pain is observed or if pain significantly does not decrease after reception of the maximum daily dose, it is recommended to see a doctor.

Features of use:

The tablets Но-шпа® 40 of mg contain 52 mg of lactose. It can cause gastrointestinal complaints in the persons having a lactose intolerance. This form is unacceptable for the patients suffering from deficit of lactose, a galactosemia or a syndrome of the broken absorption of a glucose/galactose (see the section "Contraindications").
Influence on ability to drive the car and other mechanisms
At intake in therapeutic doses Drotaverinum does not exert impact on ability to drive the car and to perform the works requiring special attention. At manifestation of any side effects the question of driving of transport and work with mechanisms demands individual consideration. In case of dizziness after administration of drug, it is necessary to avoid occupation potentially dangerous types of activity, such as driving and work with mechanisms.

Side effects:

The adverse reactions observed in clinical trials, divided on systems of bodies with the indication of the frequency of their emergence according to the following gradation are given below: very frequent (> 10%), frequent (> 1%, <10); infrequent (> 0,1%, <1%); rare (> 0,01%, <0,1%) and very rare, including separate messages (<0,01%), the unknown frequency (according to the available data frequency cannot be determined). From cardiovascular system
Rare - heartbeat increase, a lowering of arterial pressure.
From a nervous system
Rare - a headache, dizziness, sleeplessness. From digestive tract Rare - nausea, a lock. From immune system
Rare - allergic reactions (a Quincke's disease, a small tortoiseshell, rash, an itch) (see the section "Contraindications").

Interaction with other medicines:

Phosphodiesterase inhibitors, similar to a papaverine, reduce antiparkinsonichesky action of a levodopa. At purpose of Drotaverinum along with a levodopa strengthening of rigidity and a tremor is possible.
With other antispasmodics, including m-holinoblokatory Mutual strengthening of spasmolytic action.
The drugs considerably contacting proteins of plasma (more than 80%) Drotaverinum considerably contacts proteins of plasma, preferential albumine, at - and in - globulins (see the section "Pharmacokinetics"). There are no data on interaction of Drotaverinum with the drugs considerably contacting proteins of plasma, however there is a hypothetical possibility of their interaction with Drotaverinum at the level of communication with protein (replacement of one of drugs by other of communication with protein and increase in concentration of free fraction in drug blood with less strong communication with protein) that can hypothetically increase risk of emergence of pharmakodinamichesky and/or toxic side effects of this drug.

Contraindications:

- Hypersensitivity to active ingredient or to any of drug excipients.
- Heavy liver or renal failure.
- Heavy heart failure (syndrome of low cordial emission).
- Children's age up to 6 years.
- Feeding period breast (lack of clinical data).
- Rare hereditary intolerance of a galactose, deficit of lactase and a sprue of glucose galactose (because of presence at composition of drug of lactose).

With care
- At arterial hypotension.
- At children (insufficiency of clinical experience of use).
- At pregnant women (see the section "Pregnancy and Period of a Lactation").

Pregnancy and period of a lactation.
As showed reproductive researches at animals and retrospective data on a clinical use of Drotaverinum, use of Drotaverinum during pregnancy did not render either teratogenic, nor embriotoksichesky action. Despite it, at use of drug during pregnancy it is necessary to correlate potential advantage for mother and possible risk for a fruit. Due to the lack of necessary clinical data, in the period of a lactation it is not recommended to appoint.

Overdose:

Data on overdose of drug are absent.
  In case of  overdose  patients  have to  be  under  medical observation, and if necessary, by it the symptomatic and directed to maintenance of the main functions of an organism treatment, including artificial calling of vomiting or a gastric lavage has to be carried out.

Storage conditions:

For tablets in blisters Aluminium/aluminium: 5 years. For tablets in blisters PVC/aluminium: 3 years.

For tablets in bottles: 5 years.
Not to use drug after the expiry date specified on packaging.

For tablets in blisters Aluminium/aluminium: to store at a temperature not above 30 °C.
For tablets in blisters PVC/aluminium: to store at a temperature not above 25 °C.

For tablets in bottles: to store in the place protected from light at a temperature from 15 °C to 25 °C.
To store in the place, unavailable to children.

Issue conditions:

Without recipe

Packaging:

Tablets of 40 mg.
On 6, 10, 12, 20 or 24 tablets in the blister PVC/aluminium.
On 1, 2, 4 or 5 blisters on 6 tablets with the application instruction in a cardboard pack.
On 3 blisters on 10 tablets with the application instruction in a cardboard pack. On 2 blisters on 12 tablets with the application instruction in a cardboard pack. On 1 blister on 20 or 24 tablets with the application instruction in a cardboard pack.
On 10 tablets in the blister Aluminium/aluminium (it is laminated by polymer).
On 2 blisters with the application instruction in a cardboard pack.
On 60 tablets in a bottle from polypropylene with a polyethylene stopper,
supplied with the piece doser.
On 1 bottle with the application instruction in a cardboard pack.
On 100 tablets in a bottle from polypropylene with a polyethylene stopper.
On 1 bottle with the application instruction in a cardboard pack.