Medicinal effect of the drug tramadol, indications and side effects. Tramadol is a narcotic analgesic that can cause severe dependence. What are tramadol tablets prescribed for?

Tramal is considered one of the best painkillers. This is a medication that is a synthetic analgesic. Refers to opioid drugs. Its action is defined as mixed. Tramal is available in various forms.

Tramadol is considered the most active component of the drug. According to research, this substance has proven itself to be a weak analogue of morphine. Taking tramadol in small doses most likely does not have any side effects on the human body. It is used for therapy for patients of different ages; there are also dosages developed for children. The basic rule for obtaining a good effect is to carefully follow the recommendations of a specialist when treating with the drug and not exceed the dose indicated by him.

Based on the results of examining the patient, the doctor may prescribe medicine in a certain form. The difference between them is the quality of the assimilation process. The decision is made depending on the patient's condition.

The medicine is produced in the following forms:

Using the drug Tramal according to the instructions

Indications for use Medicines Tramal in the form of tablets and other forms may be different. Basically, Tramal, according to the instructions for use, in the form of intramuscular injections and taking the medicine in other forms, is prescribed in the following cases:

• Recovery from injuries of varying severity;
• Postoperative periods;
• Pain after a myocardial infarction;
• Oncological diseases;
• Procedures accompanied by severe pain.

Contraindications for use

The painkiller Tramal can be used with restrictions. Contraindications to the use of the drug are:

1. Poisoning with drugs (sleeping pills, opioids with analgesic properties, psychotropic substances), alcohol;
2. Tramal should not be used during drug withdrawal;
3. Impaired kidney and liver function;
4. It is unacceptable to use Tramal Retard at the same time as treatment with monoamine oxidase inhibitors and after their withdrawal - for two weeks.

During pregnancy and breastfeeding, Tramal tablets instructions for use allow use if there are vital indications. In this case, therapy should be limited to a one-time dose of medication.

If the patient has renal or liver failure, there is a possibility that the effect of the drug will be prolonged. In this case, it may be necessary to increase the interval between prescribed doses.

Directions for use, dosage

Tramal injections instructions for use can be administered intravenously, subcutaneously and intramuscularly.

Tramal tablets and other oral forms instructions for use allow use regardless of meal time. When using capsules, they must be washed down; the drops are mixed in a small amount of liquid. You can also drop the required number of drops onto a piece of refined sugar and eat it.

Rectal suppositories are used for insertion into the rectum.

Doses for taking Tramal 200 should be determined by the doctor observing the disease. They are selected depending on how severe the pain syndrome is and where it is localized. It should be noted that the duration of therapy should not be longer than the pain relief occurs.

What kind of drug this is - Tramal, people find out mainly when it is necessary to get rid of serious pain. To relieve pain even at high intensity, a dose of 400 mg of tramadol hydrochloride per day is often sufficient. You can start with a dose of 100 mg to achieve immediate strong effects. Increased doses of Tramal in injections and other forms can be used during periods after operations and for the purpose of treating pain syndromes, which is often necessary in cancer patients.

Side effects of the medicine

Do not forget that Tramal is a drug with a narcotic effect.

If used irrationally, as well as when using Tramal according to the instructions for use in the form of intramuscular injections, the cost of treatment can be considerable. Side effects may appear unexpectedly and for no particular reason.

Tramal tablets should be taken according to the instructions. Otherwise, there is a danger of overdose. Its main symptoms are conditions such as epileptic convulsions, fainting, and coma. Due to an overdose of tramadol, blood pressure can greatly decrease, the pupils constrict and dilate, tachycardia occurs, breathing becomes difficult, and apnea may occur.

The drug Tramal is an opiate agonist. If effects are observed that suggest an overdose, relief can be carried out using morphine agonists. When convulsions occur due to taking doses with an apparent toxic effect, the elimination of convulsions is carried out using drugs belonging to the group of benzodiazepines.

Cost of the drug

For Tramal tablets, the price may vary depending on the policy of the distributor and the purchasing batch. To be allowed to purchase Tramal, a prescription is written in Latin.

In online pharmacies on Tramal, the price may differ from that set in regular branches, to a lesser extent. But those who prefer purchasing online should be reminded that this increases the risk of purchasing a counterfeit or low-quality product with a weak effect.

Additional instructions

Due to the likelihood of complications, in some cases, Tramal is prescribed subject to treatment under the supervision of a physician. This may be the case if the patient has impaired liver and kidney function, with increased intracranial pressure and head injury, or with epilepsy. It is known that opioids cause addiction; drug addicts use Tramal as an opportunity to provide the body with a certain efficiency.

In case of opioid addiction, Tramal is prescribed with caution. The same applies to pain of unknown origin in the abdominal cavity, problems with the functionality of the respiratory organs, and confusion for unknown reasons.

For the drug Tramal Retard, the instructions for use recommend enhanced monitoring of the patient’s condition if he has generalized seizures, but therapy using this drug is recognized as necessary.

If Tramal therapy is prolonged, drug dependence may develop. Therefore, the duration of therapy should be determined by the doctor. The patient should be warned about the need to comply with the dosage prescribed by the healthcare professional during administration and that the drug should not be transferred to other persons. Long-term treatment for chronic pain syndrome can be prescribed only if indicated.

Alcohol consumption during therapy should be avoided. You should also avoid carrying out activities that require intense concentration, since the drug has a strong effect on psychophysical abilities.

Tramal interacts with other medications as follows:

• The substance tramadol can enhance the effect of ethanol, as well as drugs that depress the central nervous system.
• The duration of action of Tramal is reduced if inducers of microsomal oxidation are taken simultaneously with therapy.
• Naloxone can increase respiration and reduce analgesia from opioid use.
• Barbiturates and opioid drugs with long-term use can stimulate cross-tolerance. Barbiturates prolong the effect of anesthesia, anxiolytics can enhance the severity of the effect of drugs containing tramadol.
• Quinidine can increase plasma concentrations of tramadol.

Medicines similar in action to Tramal are Tramal Retard, Tramadol Stada, Tramaclosidol, Tramadol, Plazodol and others.

The active ingredient in these drugs is the same. The price for 20 capsules starts from 224 rubles.

Drug Tramal - reviews

Irina, 43 years old“The drug Tramal was prescribed to relieve pain resulting from cancer. The action, surprisingly, was not always the same. Sometimes after an injection it seems that consciousness is confused, sometimes everything remains unchanged. Painful attacks are stopped properly. But sometimes breathing difficulties arise when you have to use a nebulizer.”

Kirill, 28 years old“The drug absolutely did not suit me. I experienced the reaction of respiratory depression, when you can’t do anything at all - your lungs just give out. Fortunately, I started taking the drug in the hospital, and the doctors managed to provide assistance in time. My therapy was then changed.”

Marina, 38 years old“Tramal can help relieve pain for a long time. It was prescribed to me during the recovery process after a major operation. At first I recovered under the supervision of doctors, the pain was terrible. Tramal injections were prescribed. Everything worked out, the drug helped a lot.”

Tramadol is a synthetic opioid analgesic. The drug is included in list No. 1 of potent drugs by the Standing Committee for Drug Control of the Ministry of Health of the Russian Federation. It can only be purchased with a prescription from your doctor; it is prohibited from being sold over the counter.

Group

Tramadol is one of the phenylperidine derivatives and other opioid analgesics. It belongs to group B medications.

Composition of the drug

The active ingredient is tramadol hydrochloride along with excipients.

• Lactose
• Microcrystalline cellulose
• Magnesium stearate
• Crospovidone
• Macrogol 4000
• Sodium saccharin
• Colloidal silicon oxide
• Flavoring

​​Issue form

Tramadol is available in tablets of 50 and 100 mg, available in packs of 10, 30 and 50 pieces. They have a rounded, slightly flattened, rough surface. White tablets with finely defined inclusions. They may have a special strawberry smell.

Pharmacological features:

• Pharmacodynamics is that tramadol is an analgesic opioid drug with a mixed mechanism. It is a strong analgesic drug that has a dual effect on the body: central and on the spinal cord. The drug is able to increase the effect of sedatives and relieve severe paroxysmal cough. The initial doses prescribed by the doctor cannot cause respiratory depression; this can only occur when they are increased. When used, the disturbances in digestive function are insignificant, and the effect on the cardiovascular system is weak. If we compare tramadol with opioid receptors, its effect is 10 times less than codeine and 6 thousand times less than morphine.
• Pharmacokinetics. The drug is absorbed from the gastrointestinal tract almost immediately after administration. It is detected in the blood only after 2 hours. Bioavailability is achieved up to 68% at the first dose, and then increases markedly. The drug can penetrate the blood-brain and placental barrier. A small part of tramadol, namely 0.1% of the substance, can be found in breast milk. The volume of distribution reaches 306 l, the connection with plasma proteins is 20%. Almost 90% of the drug is excreted in the urine and only 10% through the intestines. The drug is completely eliminated within 5-6 hours after taking it.

Indications for use

Instructions for use tramadol, consists of relieving any types of pain syndromes, regardless of their nature of occurrence, for example:

• Post-traumatic pain syndrome. It implies a disorder of the body of a different nature after an acquired injury to the upper or lower extremities. There are two types of post-traumatic pain syndrome:
  • Reflex sympathetic dystrophy, which manifests itself as a result of both minor and severe injuries.
  • Pain resulting from peripheral nerve damage

TBI (traumatic brain injury) is considered one of the most important medical social problems. According to statistics, the disease ranks second in prevalence among the Russian population. is considered one of the mild TBIs, which is accompanied by a triad of symptoms: loss of consciousness, vomiting, con- or anterograde amnesia. Depending on the severity of the injury, cerebral circulation, lymph circulation, and the permeability of the blood-brain barrier are disrupted. The intensity of the pain depends on the severity of the injury. Most often after TBI they complain of severe headaches, nausea and vomiting, and dizziness. Tramadol successfully copes with pain relief. Tramadol tablets will also help:

• For oncological pathologies. The intensity of pain depends on the affected organ. The cause of pain is considered to be tumor growth and metastasis, which disrupt neighboring structures, blood circulation, and lymph circulation. The pain also intensifies during acute radiation reactions, the postoperative period, etc. Pain treatment is based on a three-step regimen of analgesics. Starting with simpler ones and ending with narcotic painkillers. The use of tramadol allows one to achieve a satisfactory pain relief effect.
• . Unlike angina, the pain of a heart attack does not subside from taking nitroglycerin or simple analgesics. Severe pain is felt simultaneously in the back, epigastric region, neck and lower jaw. The patient should not be given small doses of painkillers; the pain for him can become life-threatening. Heart pain is relieved only by taking opioid analgesics.
• As pain relief during therapeutic and diagnostic procedures. This includes long-term x-ray and endoscopic studies, which require patient immobility
• The use of tramadol is allowed for continuous cough syndrome.

​​Contraindications

Like any drug, tramadol also has contraindications for use, which must be carefully read.

Tramadol tablets cannot be used for the following body conditions:

• Hypersensitivity to the drug or to one of its components
• Epilepsy, severe and uncontrollable
• Depressed state of the respiratory system and central nervous system, the cause of which is the use of psychotropic and anxiolytic drugs, alcohol.
• For pathologies of the liver and kidneys
• During pregnancy
• Children under 14 years old

Tramadol is prescribed with caution for the following diseases:

• Minor dysfunction of the liver and kidneys
• Post-traumatic syndromes
• For acute abdomen
• Opioid addiction

Tramadol dosage and methods of administration

The drug can be taken only with the prescription of the attending physician. The daily dosage of the drug is selected individually based on the patient’s clinical picture. A single dose depends on the intensity of the pain syndrome and the patient’s sensitivity to the drug. Tramadol should not be taken for a long time; you must strictly adhere to the dosage required for therapy. If long-term treatment is unavoidable, then it is necessary to evaluate the general condition of the patient and the consequences that may arise from long-term use of the drug.

Adults and children over 14 years of age are prescribed 50 mg orally. If no improvement is observed from one tablet, then to enhance the effect of pain relief, you can repeat taking the tablet after half an hour. For unbearable pain, you can take 100 mg once. The analgesic effect lasts up to 8 hours. Per day, the number of tramadol tablets taken should reach a maximum of 400 mg.

In elderly people with impaired liver and kidney function, if there is an indication for prescribing the drug, then the intervals between doses should be increased.

During the entire period of treatment with tramadol, you should not drive or perform complex work that requires special attention.

The tablets are swallowed whole, washed down with any liquid. You can also dissolve the tablet in advance and then drink it.

Side effects

Often people undergoing treatment with tramadol notice some changes in the body.

• 30% of people complain of dizziness, headache, nausea, and drowsiness.
• 15% report itching, diarrhea,...
• Only 5% experience weight loss under the influence of the drug; they complain of hallucinations, tachycardia and hypotension, and urinary retention. Manifestation of an allergic reaction in the form.

The occurrence of side effects depends on the duration of use of the drug. With prolonged use in large dosages, the patient may become addicted to the drug, which is extremely undesirable. It is also not advisable to abruptly stop taking tramadol; withdrawal syndrome may develop.

Any changes in the body while taking tramadol should be reported to your doctor.

Interaction with other drugs

• The opioid analgesic should not be taken together with drugs such as: diclofenac, indomethacin, diazepam, nitroglycerin, flunitrazepam. They are incompatible.
• The effect of the drug is reduced when taken together with carbazepine or other metabolic enzyme inducers.
• Regular use of barbiturates, namely phenobarbital, also stops the effect of tramadol.
• Cross-tolerance may occur with long-term use of barbiturates or opioid analgesics.
• The effect of drugs that suppress the central nervous system may be enhanced by tramadol.
• Plasma concentrations of tramadol increase when quinidine is co-administered.

special instructions

• Alcohol consumption is strictly prohibited during the entire period of treatment with tramadol.
• The use of the drug together with narcotic drugs is prohibited because their interaction is difficult to predict;

Overdose

In case of tramadol poisoning, in patients:

• Pupils constrict
• A gag reflex appears
• Depressed breathing
• Convulsions
• The patient may fall into a coma

The patient should be hospitalized first; if help is not provided in time, then everything may end sadly. Treatment in such cases is based on maintaining mechanical ventilation (artificial pulmonary ventilation). Symptomatic therapy is also carried out. For mild cases, gastric lavage is sufficient. Seizures can be relieved by intravenous drips of diazepam.

Tramadol addiction treatment

Treatment is carried out using the same methods as drug addiction. Regardless of the condition, the patient must be rehabilitated in a medical center. But the patient himself must give consent to hospitalization. The patient must undergo several stages of treatment.

• Detoxification and restorative therapy, lasting about 4 weeks. During this time, the patient takes blood substitutes and glucose. The patient also receives symptomatic treatment.
• An important condition for treatment is the patient’s decisive refusal to further use the drug. If during abstinence the patient exhibits certain clinical signs, they are relieved with clonidine and pyrroxane. Tranquilizers eliminate psychosis.
• Maintenance therapy is the longest stage of the entire period of addiction treatment. It is aimed at maintaining the achieved effect and preventing breakdowns.

Tramadol shelf life

Should be stored indoors where the temperature does not exceed 25 degrees. Do not forget that we are talking about a potent drug, so it is necessary to hide it far out of reach of everyone. The shelf life of the tablets is indicated on the packaging, usually 5 years from the date of issue. Tramadol tablets should not be used after the expiration date.

Tramadol analogues

Cost of the drug

The price of tramadol depends on the dose and the number of tablets in the package. The cost of the drug in different parts of Russia varies, ranging from 70 rubles and above.

Many people ask if they can buy tramadol tablets online and have them delivered to their home. Using this method, the drug can be purchased only if the pharmacy that sells medications online has permission to sell prescription drugs. Then there will be no problems with ordering and delivering a medicine included in group B via the Internet.

Higher education (Cardiology). Cardiologist, therapist, functional diagnostics doctor. I am well versed in the diagnosis and treatment of diseases of the respiratory system, gastrointestinal tract and cardiovascular system. Graduated from the academy (full-time), with extensive work experience behind her.

Specialty: Cardiologist, Therapist, Functional diagnostics doctor.

INN: Tramadol

Manufacturer: Protech Biopharma Pvt. Ltd.

Anatomical-therapeutic-chemical classification: Tramadol

Registration number in the Republic of Kazakhstan: No. RK-LS-5No. 121793

Registration period: 19.11.2015 - 19.11.2020

ALO (Included in the List of free outpatient drug provision)

Instructions

Tradename

Tramadol

International nonproprietary name

Tramadol

Dosage form

Capsules 50 mg

Compound

One capsule contains

active substance- tramadol hydrochloride 50 mg,

Excipients: starch, calcium dihydrogen phosphate, lactose, sodium methyl parahydroxybenzoate, sodium propyl parahydroxybenzoate, polyvinylpyrrolidone (PVP K30), talc,

capsule shell composition: gelatin, iron (III) oxide yellow (E172), brilliant blue (E133).

Description

Size 2 hard gelatin capsules, light green/light green. The contents of the capsules are white or almost white powder.

Pharmacotherapeutic group

Analgesics. Opioids. Opioids are different. Tramadol.

ATX code N02AX02

Pharmacological properties

Pharmacokinetics

Suction

After oral administration, tramadol is quickly and almost completely absorbed from the gastrointestinal tract. Average oral bioavailability is approximately 68%. Food intake does not have a significant effect on the rate and extent of absorption. A serum concentration of 100 ng/L (minimum effective analgesic concentration) is achieved approximately 0.7 hours after administration and persists for 9 hours.

Distribution The volume of distribution after oral and intravenous administration is approximately 306 and 203 liters, respectively. Plasma protein binding is about 20%. Tramadol crosses the placenta and its concentration in cord blood is 80% of the concentration in maternal blood.

Metabolism Approximately 85% of tramadol is metabolized. Tramadol is metabolized by N- and O-demethylation. With the exception of the O-demethylated metabolite (M1), all metabolites are pharmacologically inactive.

Removal

90% of tramadol and its metabolites are excreted through the kidneys, the rest is excreted in feces. The half-life is 5-6 hours and is the same for both tramadol and its metabolites.

In case of impaired renal function, the volume and rate of excretion decreases; therefore, in patients with creatinine clearance less than 0.5 ml/s, it is recommended to reduce the dosage and increase the intervals between dosing.

The metabolism of tramadol and M1 is reduced in patients with severe liver cirrhosis, and therefore the dosage should be adjusted.

In patients over 75 years of age, the peak plasma concentration of tramadol increases slightly and the half-life is longer, so dose adjustment is required.

Pharmacodynamics

Tramadol is a centrally acting analgesic. It is a non-selective agonist at the μ, δ and κ opioid receptors, with a higher affinity for the μ receptors. Tramadol inhibits the neuronal uptake of norepinephrine and also enhances the release of serotonin, which leads to the analgesic effect of the drug.

Tramadol in therapeutic doses has virtually no effect on the cardiovascular system (does not have a depressing effect and does not increase pressure in the pulmonary artery), does not cause spasm of smooth muscles, release of histamine, therefore, anaphylactic reactions rarely occur. The effects on breathing are minimal and may only occur at higher doses. The development of dependence and addiction is also very rare.

Indications for use

Pain syndrome of moderate to severe intensity

Directions for use and doses

The dose is selected individually depending on the intensity of pain and sensitivity of the patient. The lowest effective analgesic dose is usually used. The maximum permissible dose of the drug per day is 400 mg.

Unless otherwise indicated, the drug should be taken as follows:

Adults

Acute pain: 1-2 tablets (50-100 mg) 3-4 times a day. For patients with low body weight, the dose is calculated at 0.7 mg/kg. The duration of treatment depends on clinical need.

Pain associated with chronic diseases: The recommended starting dose is 50 mg or 100 mg, followed by dose titration every 4-6 hours, depending on the intensity of pain. It is important to regularly assess the need for continued treatment, as there is evidence of withdrawal symptoms and the development of dependence.

Children

The drug is not intended for the treatment of children and adolescents under 18 years of age.

Elderly patients

Usually, when treating patients under the age of 75 years, no dose adjustment is required if they do not have clinical manifestations of hepatic or renal failure. In patients over 75 years of age, the elimination period may be prolonged. Therefore, if necessary, the interval between doses of the drug is increased in accordance with the needs of the patient.

Kidney failure

In patients with renal impairment, drug elimination may be delayed. The starting dose may be standard. These patients should consider the need to lengthen the interval between doses of the drug in accordance with the individual characteristics of the patient.

For patients with creatinine clearance<30 мл/мин интервал между приемом препарата должен быть увеличен до 12 часов.

Tramadol is not recommended for patients with severe renal impairment with creatinine clearance<10 мл/мин. При гемодиализе или гемофильтрации трамадол выводится очень медленно и поэтому пост-диализное назначение трамадола для поддержания анальгезирующего эффекта нецелесообразно.

Liver failure

In patients with impaired liver function, prolonged elimination of the drug is observed. The standard dose should be divided into 2 parts or the interval between doses of the drug should be increased to 12 hours.

These patients should consider the need to lengthen the interval between doses of the drug in accordance with the individual characteristics of the patient. Tramadol is not recommended for patients with severe liver failure

Mode of application

Capsules must be taken whole, without breaking or chewing, with sufficient liquid, with or without food.

Duration of admission

The duration of treatment with tramadol should under no circumstances exceed the period of urgent need to take it. If long-term use of tramadol for pain relief is necessary due to the nature and severity of the disease, regular monitoring should be carried out (if necessary, with breaks during treatment) to determine the further need and extent of therapy.

Side effects

The most common side effects are nausea and vomiting, which develop in 10% of patients.

The following frequency is observed:

Very common: ≥1/10

Often: ≥1/100,<1/10

Uncommon: ≥1/1000,<1/100

Rare: ≥1/10,000,<1/1000

Very rarely:<1/10 000

Cardiovascular system disorders:

Infrequently

Rapid heartbeat, tachycardia, orthostatic hypotension, cardiovascular collapse. Such adverse reactions may occur, in particular, with intravenous administration, as well as in physically weakened patients.

Rarely

Bradycardia, increased blood pressure

Respiratory disorders

Rarely

Respiratory depression, shortness of breath

From the nervous system

Often

Dizziness

Often

Headache, drowsiness

Changes in appetite, speech disturbances, paresthesia, tremor, epileptiform convulsions, involuntary muscle contractions, coordination problems, fainting.

Seizures developed mainly after taking high doses of tramadol or after concomitant use of drugs that lower the seizure threshold.

Mental disorders:

Rarely

Hallucinations, sleep disturbances, delirium, anxiety and nightmares. After the administration of tramadol, a variety of undesirable mental phenomena may occur, the intensity of which varies in each individual case (depending on the individual characteristics and duration of treatment). These include changes in mood (usually euphoria, sometimes dysphoria), changes in motor activity (usually depression, sometimes increased), and cognitive and sensory disturbances (eg, impaired decision-making and perceptual disturbances). Drug dependence may develop. Symptoms associated with withdrawal may develop in the same way as with opiate withdrawal: agitation, restlessness, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal disturbances. Very rarely, when stopping tramadol, symptoms such as panic attacks, severe anxiety, hallucinations, paresthesia, tinnitus and central nervous system dysfunction (i.e. confusion, delusions, depersonalization, derealization, paranoia) occur.

Visual impairment

Rarely

Constriction of pupils, dilation of pupils, blurred vision

Gastrointestinal disorders

Often

Nausea

Often

Constipation, dry mouth, vomiting

Infrequently

Belching, gastrointestinal discomfort (feeling of tightness in the stomach, bloating), diarrhea

Diseases of the skin and subcutaneous fat

Often

Hyperhidrosis

Infrequently

Skin reactions (eg, itching, rash, hives)

Lesions of the musculoskeletal system and connective tissues

Rarely

Motor weakness

From the hepatobiliary system

In several unrelated cases, elevated liver enzymes were observed that coincided with the use of tramadol.

Renal and urinary system disorders

Difficulty urinating, urinary disturbances (dysuria and urinary retention)

Immune system disorders

Rarely

Allergic reactions (eg, difficulty breathing, bronchospasm, wheezing, angioedema) and anaphylactic reaction

Metabolism and nutrient absorption disorders

Unknown

Hypoglycemia

General violations

Often

Fatigue

Contraindications

hypersensitivity to tramadol and/or auxiliary ingredients of the drug and other opioid analgesics

acute intoxication with central nervous system depressants

(alcohol, centrally acting analgesics, opioids, psychotropic drugs, hypnotics)

severe renal failure (creatinine clearance less than 10 ml/min)

severe liver failure

simultaneous use of MAO inhibitors (and within 14 days

after their cancellation)

patients suffering from epilepsy, the course of which cannot be adequately

be controlled

children and teenagers up to 18 years of age

pregnancy and lactation

Drug interactions

Tramadol should not be used in combination with MAO inhibitors.

Life-threatening interactions on the central nervous system, respiratory and cardiovascular systems have been observed in patients receiving MAO inhibitors within 14 days before starting opioid analgesics. Similar interactions with MAO inhibitors cannot be excluded when tramadol is prescribed simultaneously.

When using tramadol simultaneously with drugs that have a depressant effect on the central nervous system, and with ethanol, it is possible that their actions may mutually enhance.

Application carbamazepine, barbiturates and other inducers of microsomal enzymes may lead to a weakening of the analgesic effect of tramadol.

Long-term use of tramadol stimulates the development of cross-tolerance to other opioid analgesics.

When joint or preliminary use of cimetidine (enzyme inhibitor) clinically significant interactions are unlikely. Combination opioid receptor agonists/antagonists(For example, buprenophine, nalbuphine, pentazocine) and tramadol is not recommended as the analgesic effect of the pure agonist is reduced in these conditions.

With simultaneous use of Tramadol with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine serotonin reuptake inhibitors (SNRIs), tri- and tetracyclic antidepressants, antipsychotics and other drugs that lower the seizure threshold , the risk of seizures increases.

When tramadol is used in combination with other serotonergic substances, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine serotonin reuptake inhibitors (SNRIs), MAO inhibitors, tri- and tetracyclic antidepressants, the development of serotonin syndrome may occur. Symptoms of serotonin syndrome include confusion, agitation, pyrexia, sweating, ataxia, hyperreflexia, myoclonus, and diarrhea.

Serotonin syndrome is possible if one of the following symptoms occurs:

Spontaneous seizures

Induced convulsions or twitching of the eye muscles due to agitation and sweating

Tremor and hyperreflexia

Hypertension and body temperature >38°C and induced or ocular muscle twitching.

Withdrawal of serotonergic drugs causes rapid relief of symptoms. Treatment depends on the type and severity of symptoms.

Particular caution should be observed when using tramadol and coumarins ( For example , warfarin) due to the risk of a decrease in prothrombin time with the development of bleeding and bruising.

Other inhibitorsCYP3 A4 , For example , ketoconazole and erythromycin, may inhibit the metabolism of tramadol (N-demethylation) and active O-desmethyltramadol. The clinical significance of this interaction is not well understood.

A limited number of studies have found that pre- or postoperative use of the antiemetic 5-HT3 antagonist ondansetron increased the need for tramadol for postoperative pain.

special instructions

Tramadol should be used with caution and a risk/benefit assessment in the following conditions:

Withdrawal symptoms. Therapeutic doses of tramadol may cause withdrawal symptoms (reported incidence 1/8000)

Drug addiction. Cases of developing symptoms of dependence are rare and much less common than withdrawal symptoms. The clinical need for treatment with tramadol should be monitored by a physician. Tramadol has a low potential for addiction. However, with prolonged use, addiction, mental and physical dependence may develop. In patients with a tendency to abuse drugs or are dependent on drugs, treatment with tramadol should be carried out only for a short period and under strict medical supervision.

Patients with opioid addiction. Tramadol is not suitable as a substitute for opioid dependent patients because it does not suppress morphine withdrawal symptoms.

Tramadol should be used with caution in opioid-sensitive patients.

Tramadol should be prescribed with caution in cases of head injury, increased intracranial pressure, hepatic failure (decreased metabolism of tramadol and its active metabolites) and renal failure (decreased rate and prolongation of excretion of tramadol and its active metabolites), with a reduced level of consciousness and in patients prone to convulsive disorders or in a state of shock.

Patients with convulsive readiness. Cases of the development of convulsive symptoms have been observed when prescribing therapeutic doses of tramadol and the risk of developing seizures may increase when the recommended daily dose is exceeded. Treatment with tramadol in patients with epilepsy or a predisposition to seizures should only be considered when clinically justified. The risk of developing a seizure syndrome increases in patients taking both tramadol and drugs that lower the seizure threshold.

The drug should be prescribed with caution to patients with respiratory failure or when prescribed concomitantly with centrally acting depressants or when doses significantly exceed the recommended doses, because in this case, the development of respiratory depression cannot be excluded.

Because of reports of deaths from unintentional tramadol overdose associated with the use of psychoactive drugs and substances including alcohol, tramadol should be prescribed with caution to patients with alcohol dependence or receiving any active psychoactive substances.

With long-term (more than 3 months) use of analgesics, at intervals of every other day or more often, a headache may develop or intensify. In this case, you should not increase the dose of tramadol. After consulting with a doctor, it is necessary to decide whether to stop using analgesics.

Pregnancy and lactation

Pregnancy

Animal studies have shown that very high doses of tramadol affect organ development, ossification, and neonatal mortality. Tramadol crosses the placenta. There is insufficient data regarding the safety of using tramadol to treat people during pregnancy. For this reason, tramadol should not be used to treat pregnant women.

Administration of tramadol before or during birth does not affect uterine contractility. In newborns, it can cause changes in respiratory rate that are usually not clinically significant.

Chronic use during pregnancy may lead to the development of withdrawal syndrome in the newborn.

Breast-feeding

During lactation, about 0.1% of the dose of the drug taken by the mother is excreted in milk. The drug should not be used during breastfeeding.

Reproductive functions

The results of post-marketing observations did not reveal the effect of tramadol on reproductive functions. The results of studies involving animals did not reveal the effect of tramadol on reproductive functions.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Even when used in accordance with the instructions, tramadol may cause drowsiness and dizziness, which may impair the reaction of drivers and machine operators. This especially applies to the simultaneous use of other psychotropic substances, in particular alcohol.

Overdose

Symptoms of Tramadol overdose are similar to those that may occur with other centrally acting analgesics (opioids).

Symptoms: constriction or dilation of the pupils, vomiting, collapse, drop in blood pressure, palpitations, depression of consciousness (up to coma), epileptic convulsions, difficulty breathing, even stopping (apnea).

Treatment:

Maintenance/restoration of vital functions of breathing and circulation in a specialized department. The antidote for respiratory depression is naloxone; for convulsions, it is advisable to use diazepam.

In case of overdose during oral administration of the drug, it is necessary to take activated charcoal; gastric lavage is recommended in the first 2 hours after taking tramadol. After 2 hours, it is necessary to carry out detoxification measures using a large amount of liquid.

Tramadol is slightly excreted during hemodialysis and hemofiltration, so treatment of acute tramadol intoxication with these types of interventions is inappropriate.

Release form and packaging

10 capsules are placed in a blister pack made of polyvinyl chloride film and aluminum foil.

1 or 2 strip packaging along with instructions for medical use in the state and Russian languages ​​are placed in a cardboard pack.

Storage conditions

In the original packaging, in a dry place at a temperature not exceeding 30 ° C.

Keep out of the reach of children!

Shelf life

Do not use after the expiration date

Conditions for dispensing from pharmacies

On prescription

Name and country of the manufacturing organization

Name and country of the packing organization

Protech Biopharma Pvt. Ltd. India

Name and country of the marketing authorization holder

Protech Biopharma Pvt. Ltd. India

Address of the organization that accepts claims from consumers regarding the quality of products (products) on the territory of the Republic of Kazakhstan

Denovo Impex LLP, Republic of Kazakhstan, Almaty 050062, st. Utegen batyr, 15

tel.: 727 2437415

fax: 727 2437416

In this article you can read the instructions for use of the drug Tramal. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of the painkiller Tramal in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Tramal in the presence of existing structural analogues. Use for the treatment of pain in adults, children, as well as during pregnancy and lactation.

Tramal- opioid analgesic. It has a pronounced analgesic effect, which is due to an agonistic effect on opioid receptors in the central nervous system. Tramadol (the active substance of the drug Tramal) is a synthetic opioid, a racemate of (+) and (-) isomers, which participate in the analgesic effect in different ways. The (+) isomer is a pure opioid receptor agonist, the (-) isomer inhibits the neuronal uptake of norepinephrine, activates the central descending noradrenergic system, which disrupts the transmission of pain impulses into the gelatinous substance of the spinal cord, both isomers act synergistically. Causes a sedative effect.

In therapeutic doses, Tramal has virtually no effect on hemodynamic parameters and does not inhibit respiratory function. With controlled use, addiction and drug dependence develop extremely rarely and are less pronounced compared to morphine.

Compound

Tramadol hydrochloride + excipients.

Pharmacokinetics

When taking the drug orally, absorption is 90%. Bioavailability - 68% (increases with repeated use). Tramal penetrates the blood-brain barrier (BBB) ​​and the placental barrier and is excreted in breast milk (0.1%). Plasma protein binding - 20%. Tramadol is biotransformed in the liver by N- and O-desmethylation followed by conjugation with glucuronic acid. 11 metabolites have been identified, of which mono-O-desmethyltramadol (M1) has pharmacological activity. Excreted by the kidneys, 25-35% unchanged, the average cumulative renal excretion rate is 94%.

Indications

Pain syndrome of moderate and severe intensity of various etiologies:

• in the postoperative period;
• for injuries;
• for pain caused by myocardial infarction (for parenteral use);
• in cancer patients;
• during painful diagnostic or therapeutic procedures.

Release forms

Capsules 50 mg.

Drops for oral administration 100 mg.

Solution for injection (injections in ampoules).

Rectal suppositories 100 mg.

Extended-release tablets 100 mg, 150 mg and 200 mg (Tramal retard).

Instructions for use and dosage regimen

The injection solution is prescribed intravenously, intramuscularly or subcutaneously.

The drug can be taken orally before, during and after meals. Capsules should be taken with a small amount of liquid, drops should be taken on a piece of sugar or dissolved in a small amount of liquid.

Suppositories should be inserted into the rectum.

Doses are set depending on the intensity of the pain syndrome.

Tramal should not be prescribed for longer than therapeutically necessary.

For adults and adolescents over 14 years of age, a single dose is 50-100 mg (1-2 capsules, 20-40 drops, 1 suppository, 1-2 ml injection solution). If after a single use satisfactory analgesia does not occur, then after 30-60 minutes a single dose of 50 mg can be re-administered.

For severe pain, 100 mg of tramadol hydrochloride can be prescribed as an initial dose. To relieve pain, 400 mg per day is usually sufficient.

For the treatment of pain associated with cancer and for severe pain in the postoperative period, the drug can be used in higher doses.

For children over 1 year of age, the drug in the form of an injection solution and drops for oral administration is prescribed in a single dose at the rate of 1-2 mg/kg body weight. A daily dose of 4-8 mg/kg is usually quite sufficient.

In elderly patients (75 years or more), due to the possibility of delayed elimination, the interval between doses of the drug can be increased in accordance with individual characteristics.

In case of kidney and liver diseases, it is possible to prolong the action of Tramal. For this category of patients, it is recommended to increase the interval between single doses.

Tramal retard tablets

The dose is set depending on the intensity of pain and individual sensitivity of the patient. It is enough to take Tramal retard 2 times a day, morning and evening, regardless of meals.

Adults and adolescents over 14 years of age are prescribed 100 mg (1 tablet) 2 times a day, morning and evening. If the analgesic effect is insufficient, the dose can be increased by taking 1 tablet of 150 mg or 200 mg, also in the morning and evening, the intervals between doses are set individually, but must be at least 6 hours. The maximum dose is 400 mg per day.

In elderly patients (over 75 years of age), the elimination of the drug may be slower. In such cases, it is necessary to increase the interval between doses in accordance with the patient’s well-being.

In renal failure/dialysis and liver failure, the elimination of tramadol is slowed down. In this category of patients, it is necessary to individually select the interval between doses of the drug in accordance with the patient’s well-being.

The tablets should be swallowed whole, without chewing with sufficient liquid.

Tramal retard should not be used for longer than therapeutically necessary.

Side effect

• nausea, vomiting;
• dry mouth;
• constipation;
• stomach ache;
• bloating;
• change in appetite;
• dizziness;
• feeling tired;
• drowsiness;
• confusion;
• headache;
• changes in mood (mostly improvement, less often depression);
• change in activity (mainly suppression, less often - increase);
• behavioral disorders;
• disturbance of sensations;
• cerebral spasms (observed in almost all cases when tramadol hydrochloride was administered intravenously in high doses, or when antipsychotics were prescribed at the same time);
• interruptions in heart rhythm;
• tachycardia;
• fainting or collapse (especially if the patient is in an upright position or during physical exertion);
• redness;
• rash;
• muscle weakness (motor weakness);
• increased sweating (especially with rapid intravenous administration);
• difficulty swallowing water.

Contraindications

• conditions accompanied by respiratory depression or severe depression of the central nervous system (poisoning with alcohol, sleeping pills, opioid analgesics, psychotropic drugs);
• drug withdrawal syndrome;
• severe renal failure (creatinine clearance less than 10 ml/min);
• severe liver failure;
• simultaneous use of MAO inhibitors and a 2-week period after their withdrawal;
• hypersensitivity to the drug and other opioid analgesics.

Use during pregnancy and breastfeeding

During pregnancy and lactation, Tramal can be prescribed only for health reasons; use should be limited to a single dose only.

special instructions

The drug should be prescribed with caution and under the supervision of a physician to patients with impaired renal and liver function, with traumatic brain injury, increased intracranial pressure, patients with epilepsy, persons with drug dependence on opioids, with pain in the abdominal cavity of unknown origin ("acute abdomen") , with confusion of unknown origin, disorders of the respiratory center or respiratory function.

The condition of patients with seizures of central origin should be carefully monitored during treatment with Tramal.

After long-term use of Tramal, the possibility of developing drug dependence cannot be completely excluded. Therefore, only the doctor should decide on the duration of treatment and its breaks. The patient should be warned about the need to strictly adhere to the dose and duration of treatment prescribed by the doctor and not to transfer the drug to others. Long-term treatment for chronic pain syndrome should be carried out only according to strict indications.

The drug is available with a prescription. Refers to the list of potent substances of the Standing Committee for Drug Control of the Ministry of Health of the Russian Federation.

Alcohol consumption should be avoided during the use of any dosage forms of Tramal.

Impact on the ability to drive vehicles and operate machinery

During treatment with Tramal, the patient must give up all types of activities that require increased attention and speed of psychomotor reactions (including driving a car, working at a machine), because the drug can have a fairly strong effect on psychophysical abilities (including decreased attention, slowed reactions).

Drug interactions

Tramal enhances the effect of drugs that have a depressant effect on the central nervous system, as well as ethanol (alcohol).

Inducers of microsomal oxidation (including carbamazepine, barbiturates) reduce the severity of the analgesic effect and duration of action of tramadol.

Long-term use of opioid analgesics or barbiturates stimulates the development of cross-tolerance.

Anxiolytics increase the severity of the analgesic effect of tramadol, the duration of anesthesia increases when combined with barbiturates. Naloxone activates breathing, eliminating analgesia after the use of opioid analgesics.

When used simultaneously with Tramal, MAO inhibitors, furazolidone, procarbazine, and antipsychotics - there is a risk of developing seizures (lowering the threshold for seizure readiness).

Quinidine increases plasma concentrations of tramadol.

Analogues of the drug Tramal

Structural analogues of the active substance:

• Protradon;
• Sintradon;
• Tramadol;
• Tramadol hydrochloride;
• Tramaclosidol;
• Tramal;
• Tramal retard;
• Tramolin;
• Tramundin retard.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

Tramadol in ampoules is an opioid synthetic analgesic that not only has a central effect, but also acts on the spinal cord. While taking the drug, the effect of synthetic drugs is enhanced. This is a potent medicine, injections of which are used only as prescribed by a doctor.

Composition and release form

The main component of the drug is tramadol. The medicine is also prepared using excipients - anhydrous sodium acetate and water for injection. The production of the medicine is carried out in ampoules. Tramadol is a colorless and clear solution. One ampoule of the drug contains 1 milliliter of medicine.

Pharmacokinetics and pharmacokinetics

Tramadol is a potent opioid analgesic that has central action. If you increase the duration of taking the medication, this will lead to a decrease in its analgesic effect. If there is a need for long-term therapy, a gradual increase in dosage is recommended.

There are two ways to achieve an analgesic effect. The first is that the nerve fibers of the pain perception system bind to opioid receptors in the spinal cord, brain, and digestive tract, which leads to a decrease in pain. The second way is that L-1-2-aminoethanol is reuptaken and descending noradrenergic effects are stimulated. As a result, inhibition of the transmission of pain impulses in the spinal cord is observed.

During the period of use of the drug, potassium and calcium channels open, and the imbalance of ions on both sides of the cells increases. The action of the medication is aimed at inhibiting the transmission of nerve impulses. With its help, the amount of catecholamines in the nervous system is normalized. After intramuscular injection, the maximum concentration of the active substance in the blood is observed within 45 minutes.

Indications for use of Tramadol in ampoules

The administration of Tramadol must be carried out in strict accordance with the indications. The drug is recommended for severe and moderate pain syndromes of various origins:

• for severe pain resulting from injuries;
• surgical intervention;
• for fractures;
• for neuralgia with pain syndrome.

Tramadol is a highly effective medication that provides pain relief of various etiologies. Thanks to the special method of administering the solution, the drug works quickly. The use of Tramadol is recommended only in the presence of severe pain. The medication is characterized by the presence of contraindications, which must be taken into account by the doctor before prescribing. Otherwise, the development of undesirable effects may occur.

Contraindications

Despite the high effect of Tramadol injection solution, it has certain contraindications. If the patient has an individual intolerance to the main or auxiliary components of the drug, then its use is strictly prohibited. Experts do not recommend using the drug in acute forms of intoxication with CNS inhibitors such as:

• Sleeping pills;
• Psychotropic medications;
• Sedatives;
• Psycholeptics;
• Anxiolytic drugs.

If the patient has suicidal tendencies, then the use of the medicine is also not recommended for him. A contraindication to the use of the drug is substance abuse. If there are severe problems with the kidneys or liver, administering Tramadol is strictly prohibited.

In the first trimester of pregnancy, the drug is not used to relieve pain. If a person is undergoing therapy with monoamine oxidase inhibitors, then using Tramadol for therapy is prohibited. If the patient's age is less than 14 years, then the use of the medication is also strictly prohibited. If there are contraindications, it is recommended to use analogues.

Analogues

Side effects

If Tramadol is used or administered incorrectly, if there are contraindications, side effects may occur. In most cases, they manifest themselves in the digestive and nervous systems.

• Patients complain of disturbances in the digestive tract, which manifest themselves in the form of:
  • nausea;
  • vomiting;
  • constipation;
  • diarrhea.
• In some cases, after administration of the solution, the following may be observed:
  • headache;
  • dizziness;
  • dyspnea;
  • drowsiness;
• During long-term treatment with Tramadol, patients complain of:
  • increased anxiety;
  • euphoria;
  • confusion;
  • emotional lability;
  • insomnia;
  • disturbances in coordination of movements.

Taking the drug may be accompanied by urine retention or increased urination. Patients also complain that they have no appetite and appear.

Side effects of taking the medicine include a rash on the skin. Representatives of the fairer sex may experience changes similar to menopause. Quite serious complications are visual impairment, as well as vascular dilatation.

There are a number of unwanted effects that occur in less than 1 percent of patients. Taking the drug can lead to impairment of cognitive activity, attention control, as well as increased seizure activity. Undesirable effects may manifest themselves in the form of:

• Amnesia;
• Hallucinations;
• Tremors;
• Paresthesia.

Representatives of the fairer sex complain about the appearance of disorders in the menstrual cycle. The use of the medicine can lead to disruption of the functioning of the heart and blood vessels:

• orthostatic hypotension;
• cardiovascular collapse;
• palpitations of the heart.

During treatment, patients may experience an increase in muscle tone, a decrease in body weight, and difficulty swallowing.

Instructions for use

The instructions for using Tramadol state that you must strictly adhere to the rules for administering the medicine in order to exclude the possibility of complications.

The use of drug injections is recommended only after the patient reaches 14 years of age. The dosage of the medication should be determined only by the doctor. In this case, the specialist takes into account the severity of the pain syndrome, the individual characteristics and sensitivity of the patient. The duration of treatment is also prescribed by the doctor, the continuation of which is strictly prohibited for the patient.

The medication is administered into the muscles, veins or subcutaneously. The intravenous medication should be administered as slowly as possible. If the patient's age is more than 14 years, then a single dose is 1-2 milliliters of solution, depending on the severity of pain. If there is no appropriate therapeutic effect within an hour, the patient may be prescribed a second dose. To eliminate pain, an adult patient needs 400 milligrams of the drug per day.

If a patient is prescribed a drug for cancer or after surgery, the dosage of the drug may be increased. If the patient has liver or kidney disease, the effect of the medicine may be longer. That is why these categories of patients are recommended to increase the intervals between the administration of solutions. If the patient's age is more than 75 years, then delayed elimination of the drug components may be observed. In this case, it is recommended to increase the interval of drug administration.

Although the drug is prohibited for children, exceptions have been observed in medical practice. The dosage of Tramadol for children aged 1 to 4 years is selected according to weight. One kilogram requires 1 to 2 milligrams of the drug. The medicine must be administered to children in the same ways as for adult patients. Tramadol should be administered into a vein in young patients as slowly as possible. The medicine is pre-diluted in an infusion solution. The intervals between drug administration should be at least 4 hours.

Features of overdose

The use of Tramadol must be carried out in strict accordance with the doses prescribed by doctors. Otherwise, quite dangerous symptoms may occur. When administering the drug in an increased dose, the following may occur:

• disturbance of consciousness;
• coma;
• convulsions of central origin;
• hypotension.

If the drug is administered incorrectly or in excessive quantities, it may cause respiratory depression. In some cases, patients' pupils narrow or dilate. A fairly serious complication of overdose is. If there is a significant overdose of the drug, this can cause damage to the central nervous system. Such patients are diagnosed with shallow breathing. To eliminate these symptoms, it is recommended that the patient be administered Naloxone. If seizures occur due to an overdose, treatment is carried out with Diazepam.

In case of an overdose of the drug, the corresponding symptoms are observed in the form of:

• seizures;
• respiratory depression;
• coma;
• collapse;
• nausea and vomiting;
• apnea.

Treatment of the pathological condition should be aimed at ensuring airway patency. Patients are prescribed medications that support respiratory function and the cardiovascular system.

Interaction of Tramadol with other drugs

Use at the same time Tramadol and MAO inhibitors is strictly prohibited. If the drug is combined with drugs that affect the central nervous system, this may lead to a synergistic effect. Their development is also observed with the simultaneous use of medicine and alcoholic beverages. In this case, sedation increases and the analgesic effect also increases.

When taken simultaneously Carbamazepine and Tramadol an increase in the metabolism of the latter is observed. This requires increasing its dosage. If taken simultaneously with Tramadol tricyclic antidepressants, SSRIs, psycholeptics, this can lead to seizures. During the period of taking barbiturates, a decrease in the analgesic effect of Tramadol is observed. Cross-tolerance may occur due to prolonged exposure to barbiturates.

During the period of taking anxiolytics, an increase in the severity of the analgesic effect is observed. Thanks to Naloxone, breathing is activated and analgesia is eliminated. During the period of taking Quinidine, an increase in the plasma concentration of Tramadol is observed.

special instructions

Women during pregnancy and lactation

In the first trimester of pregnancy, women are strictly prohibited from taking the medicine. In the second and third trimester, administration of the drug is allowed if possible risks for the child are minimized. During lactation, the drug is prescribed in accordance with vital indications. During treatment with the drug, women are advised to temporarily stop breastfeeding.

For liver failure

If the patient has a dysfunction of the liver, this may lead to a longer effect of the medicine. That is why, during Tramadol therapy, doctors recommend increasing the intervals between its administration. After pain relief, it is necessary to discontinue the medication. In case of severe liver failure, the use of the solution is strictly prohibited.

The active substances may negatively affect the patient's concentration. That is why during the period of treatment with medication it is recommended to refrain from driving vehicles and operating complex mechanisms. It is also recommended to avoid activities that require rapid psychomotor reactions during this period.

Price of Tramadol ampoules

The drug can be purchased at any pharmacy in the country. Since Tramadol belongs to the category of potent opioid drugs, it can only be purchased with a prescription. The drug is released in ampoules, which are packaged in cardboard boxes. The price of one package of the drug averages 110-320 rubles, depending on the city. Due to the low cost of the drug, its availability is ensured for a wide range of patients.

Storage of the drug

The medicine should be stored in places that are protected from excessive humidity and ultraviolet radiation. During storage of the medicine, it is necessary to ensure that children's access to it is limited. It should be stored at a temperature of 15-25 degrees.