Tramal. 100 mg.2ml. 5 ampules
Tramal. 100 mg./2ml. 5 ampules
QUALITATIVE AND QUANTITATIVE COMPOSITION Active substance
Active substance: Tramadol Hydrochloride ampoule 100 mg (2 ml)
For the treatment of moderate to severe pain.
Dosage and method of administration
The dose is determined by the intensity of the pain and sensitivity of each patient. If not prescribed otherwise, Tramal 100 shall apply as follows:
Adults and adolescents over 12 years:
50-100 mg (l-2ml) of 4-6 hours. The daily dose should not exceed 8 mi Tramal 100 (400 mg tramadol hydrochloride). For the treatment of pain in cancer patients or severe postoperative pain may require a higher dose.
Children older than 1 year:
Single dose: 1-2 mg / mg body weight. Ampoules are suitable administration form.
In such cases TRAMAL 100 injection was dissolved in water for injections. The following table shows what concentrations must be achieved (1 ml TRAMAL 100 injection contains 50 mg tramadol hydrochloride):
Dissolution of TRAMAL 100 injection:
in water for injection showed the following concentrations:
2 ml + 2 ml 25.0 mg / ml
2 ml + 4 ml 16.7 mg / ml
2 ml + 6 ml 12.5 mg / ml
2 ml-f 8 ml 10.0 mg / ml
2 ml + 10 ml 8.3 mg / ml
2 ml + 12 ml 7.1 mg / ml
2 ml + 14 ml 6.3 mg / ml
2 ml + 16 ml 5.6 mg / ml
2 ml + 18 ml 5.0 mg / ml
An example. The doctor prescribed 1.5 mg tramadol hydrochloride per kg of body weight of a child weighing 27 kg. For that purpose, were dissolved 2 ml TRAMAL 100 injectable solution in 4 ml of water for injections. The result is a concentration of 16,7 mg tramadol hydrochloride per mi. Apply 4 ml (67 mg tramadol hydrochloride) reconstituted drug.
Chronic pain is usually not necessary particularly, dosing in the elderly patients (75 years) with symptomatic unexpressed hepatic or renal failure. In very elderly patients (over 75 years) elimination may be prolonged. Therefore, if necessary, the dosing interval can be extended in accordance with the needs of the patient.
Hepatic and renal failure / dialysis
In patients with severe renal and / or hepatic insufficiency elimination Tramal is extended. These patients should be carefully considered extension of the interval between two doses in accordance with the need of the patient.
Method of administration:
Ampoules: injectable solution is slowly injected or mixed into an infusion solution, and infused. Can be given intramuscularly and subcutaneously.
Duration of use:
Tramal not apply in any event longer than absolutely necessary. If necessary, by a treatment with tramadol, in view of the type and severity of the disease is required a careful and regular monitoring (if necessary intermittent treatment) in order to determine whether and to what extent it is necessary to further treatment.
Tramal is contraindicated in known hypersensitivity to tramadol or any of the excipients; hypersensitivity to other narcotic analgesics in acute alcohol intoxication, hypnotics, analgesics, opioid and other psychotropic agents; and in patients receiving MAO inhibitors or taken them within the last 14 days.
Tramal should not be used for the treatment of drug dependence.
Special warnings and precautions for use
Tramal should be used with caution in patients with head injuries, shock, impaired consciousness of uncertain origin, disorders of the respiratory center or function, increased intracranial pressure. Tramal should not be administered to patients with drug dependence.
In patients sensitive to opiates the product should be used with caution.
Convulsions was reported in patients receiving Tramal at the recommended dose. This risk is increased when doses of tramadol exceeded the recommended upper limit for daily intake (400 mg). Addition, tramadol may increase the risk of epileptic seizures in patients taking another medicine to reduce the seizure threshold (see "Interactions with other medicines'). Patients with epilepsy or those susceptible to seizures be treated with tramadol if unavoidable circumstances. "
Tramal has a low potential for creating dependency. Prolonged use may develop tolerance, physical and psychological dependence. In patients with a tendency to abuse or dependency on drugs is not recommended treatment with Tramal.
Tramal is inappropriate replacement in patients with drug dependence. Although tramadol is an opioid agonist, it can suppress the symptoms of withdrawal in the treatment of addiction to morphine.
Tramal 100 solution for injection should not be given to children under the age of 1 year.
Interaction with other medicinal products and other forms of interaction
Tramadol should not be combined with MAO inhibitors.
Co-administration of Tramal and other central depressants, including alcohol, may potentiate the CNS effects.
Results of pharmacokinetic studies conducted so far have shown that simultaneous or preliminary use of cimetidine / cimetidine / (enzyme inhibitor) is not likely to cause clinically significant interactions. Concomitant or prior administration of carbamazepine / carbamazepine / (enzyme inducer) may reduce the analgesic effect and shorten the duration of its effect.
Not recommended combination of mixed agonist / antagonists (eg buprenorphine, nalbuphine, pentazocine) with tramadol as the analgesic effect of a pure agonist may theoretically be reduced under these circumstances.
Tramadol may induce convulsions and increase the potential for causing seizure of selective inhibitors of serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, and other seizure threshold lowering drugs.
In isolated cases have been reported serotonin in temporal association with the therapeutic use of tramadol in combination with other serotonergic drugs, eg. Selective inhibitors of serotonin reuptake inhibitors (SSRI). Signs of serotininov syndrome may be eg. confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus and diarrhea. Stopping serotonergic drugs usually leads to rapid improvement. Treatment with appropriate medicinal products depends on the nature and severity of the symptoms.
When concomitant treatment with tramadol and coumarin derivatives (eg warfarin) requires particular attention, due to reports of increased INR and ecchymoses in some patients.
Other pharmaceutical preparations, which are known to inhibit CYP3A4, such as ketoconazoie and erythromycin, it is possible to inhibit the metabolism of tramadol (O-demethylation) and possibly also the metabolism of the active metabolite, O-demethylated. Not investigated the clinical significance of this interaction.
Use during pregnancy and lactation
Animal studies with tramadol are shown at very high doses effects on organ development, ossification and neonatal mortality *. No teratogenic effects were observed. Tramadol crosses the placenta. There is insufficient data on the safety of tramadol during pregnancy in humans. Therefore, Tramadol should not be administered to pregnant women.
When administered before or during birth tramadol no effect on uterine contractions. Newborn it can cause changes in respiratory rate, and usually it is not clinically relevant. During lactation about 0.1% of the dose absorbed by the mother, is secreted in human milk. Therefore it is not recommended to use Tramal during lactation. After a single administration of tramadol is usually not necessary interruption of breastfeeding.
Effects on ability to drive and use machines
Even when used as directed Tramal can cause such reactions that disrupt security while driving, working with machines and free healthy 4
support for the body. This applies in particular in the beginning of the treatment, a pass / substitution of other drugs in combination with other centrally acting drugs and especially alcohol.
Most often (over 10% of patients) has been reported nausea and dizziness as a side effect of the drug.
Disorders of the cardiovascular system:
Uncommon (<1%): abnormalities in cardiovascular regulation (palpitation, tachycardia, postural hypotension or cardiovascular collapse). These side effects may occur, in particular when administered intravenously and in patients who are under physical stress.
Rare (<0.1%); bradycardia, hypertension.
Disorders of the central and peripheral nervous systems:
Very common (> 10%): dizziness Common (1-10%): headache, dizziness
Rare (<0.1%): changes in appetite, paraesthesia, tremor, respiratory depression, epileptic seizures.
If recommended doses are significantly increased and are applied simultaneously and other CNS depressant agents (see section 4.5 "Interaction with other medicinal products and other forms of interaction") may appear respiratory depression.
Epileptic convulsions have occurred mainly after administration of high doses of tramadol or after concomitant treatment with drugs that may lower the seizure threshold (see section "Special warnings and precautions for use").
Rare (<0.1%): hallucinations, confusion, sleep disturbances and the occurrence of nightmares. May appear different physical reactions that are highly individual intensity and nature (depending on the individual and the duration of treatment). These include changes in mood (usually high spirits, sometimes dysphoria), changes in activity (usually a reduction in some cases increase) and changes in cognitive and sensorial capacity (eg behavior in decision-making breach of perception). May occur depending.
Disturbances of vision:
Rare (<0.1%): blurred vision.
Disorders of the respiratory system: '
Worsening of asthma, although not a causal link to it.
Gastrointestinal disorders: Very common (> 10%): nausea.
Frequently (1-10%): constipation, dry mouth, nausea.
Uncommon (<1%): nausea; gastrointestinal disturbances (sensation of pressure in the stomach,
Skin and appendages: Common (1-10%): sweating
Uncommon (<1%): skin reactions (eg, pruritus, rash, urticaria),
Disturbance Musculoskeletal: Rare (<0.1%): motor weakness
Disorders of the liver and bile:
In a few isolated cases reported to improve liver enzymes in a temporal relationship with the therapeutic use of tramadol.
Disturbances in the urinary system:
Rare (<0.1%): interference with urination (difficulty in passing urine and urinary retention).
Body as a whole:
Rare (<0.1%): allergic reactions (eg dyspnoea, bronchospasm, wheezing diishane, angioneurotic edema) and anaphylaxis; Symptoms of withdrawal reactions similar to those occurring in drug dependence may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms.
In principle, in case of intoxication with tramadol can be expected symptoms similar to those of other centrally acting analgesics (opioid). These include in particular miosis, vomiting, cardiovascular collapse, impaired consciousness to coma, convulsions and respiratory depression up to respiratory arrest.
Basic emergency measures consist in maintaining a clear airway and maintain breathing and circulation depending on the symptoms. Antidote in respiratory depression is naloxone. In animal experiments naloxone had no effect on seizures. In this case, should be placed intravenous diazepam.
Tramadol is eliminated only minimally from serum by dialysis. Therefore, the treatment of acute intoxication with Tramal with hemodialysis or hemofiltration is not suitable for detoxification.
Tramadol is a centrally acting analgesic olioiden. It is a non-selective pure agonist m-, b-and k-opioid receptors with high affinity for mu receptors. Other mechanisms that contribute to the achievement of this analgesic effect is inhibition of reuptake of noradrenaline and enhance the release of serotonin.
Tramadol has antitussive effect. Unlike morphine analgesic doses of tramadol in a range no suppressive effect respiration. Not affected also gastrointestinal motility. Effects on the cardiovascular system have shown a tendency towards weak expression. Reportedly, the impact rate of tramadol is 1/10 to 1/6 of that of morphine.
After intramuscular administration in humans tramadol is rapidly and completely absobrira: mean maximum serum concentration (Cmax) is reached after 45 minutes, but the bioavailability is nearly 100%. In humans, about 90% of tramadol is absorbed after oral administration (capsules Tramal). The absorption half-life was 0.38 ± 0.18 h.
Comparing the regions under the curves of the serum concentration of tramadol following oral and intravenous administration show bioavailability 68 +13% of the capsules Tramal.
Tramadol has a high tissue affinity (Vd.B = 203 ± 40 I). Plasma protein binding is about 20%.
Tramadol passes the blood-brain and placental barrier. Very small amounts of the substance and its O-dezmetilov derivative are found in human milk (0.1%, respectively. 0.02% of the administered dose).
Inhibition of either or both types of the CYP3A4 and CYP2D6, involved in the biotransformation of tramadol can influence plasma concentrations of tramadol and its active metabolite. Far not been reported clinically significant interactions.
Tramadol and its metabolites is almost completely removed by the kidneys. The cumulative urinary excretion is 90% of the total radioactivity of the dose ingested. The half-life tl / 2, B is about 6 hours, irrespective of the route of administration. In patients over 75 years it can be extended by 1.4. In patients with hepatic cirrhosis, the half-life was determined to 13.3 ± 4.9 hours (tramadol) and 18.5 ± 9.4 hours (O-desmethyltramadol), in extreme cases, and 22.3 hours respectively. 36 hours. In patients with renal insufficiency (creatinine clearance <5 mi / min) values were 11 ± 3.2 and 16.9 ± 3 hours, in the extreme case - 19.5 hours and 43.2 hours respectively.
In humans, tramadol is mainly metabolized by N-and O-demethylation and bonding of the product from the O-demethylation with glucuronic acid. Only O-desmethyltramadol pharmacologically active. There is considerable interindividual quantitative differences between the other metabolites. So far in the urine were found eleven metabolites. Animal experiments have shown that the O-dezmetiltramadolat is more potent than the starting substance 2 to 4 times. A half-life tl, 2 (3 (b in healthy volunteers) was 7.9 hours (range 5.4 - 9.6) and is close to that of tramadol.
Tramadol has a linear pharmacokinetic profile within the therapeutic dose range.
Vzaimotnoshenieto between serum concentrations and analgesic effect is dose dependent, but varies considerably in isolated cases. Serum concentration of 100-300 ng / m! usually effective.
Preclinical safety data
With repeated oral and parenteral administration of tramadol for 6-26 weeks in the rat and dog, and oral administration for 12 months in dogs haematological, clinical chemistry and histological examinations revealed no cases of changes associated with the active 'ingredient. After high doses well above the therapeutic range, appeared effects CNS: restlessness, salivation, convulsions and weight reduction. Rats and dogs tolerated oral doses of 20 mg / kg, respectively. 10 mg / kg body weight, a dog - rectal doses of 20 mg / kg body weight without any reactions.
In rats tramadol dosages of 50 mg / kg / day upwards caused toxic effects in dams and increased mortality in newborns. For small delay occurred in their development in the form of impaired bone formation and delayed the opening of the vagina and the eyes. Male fertility was not affected. After a higher dose (50 mg / kg / day up) some females showed reduced indicators of pregnancy. In rabbits, there was a toxic effect in the animals at doses of the parent of 125 mg / kg upwards, and skeletal abnormalities in offspring.
In some test systems in vitro has produced evidence of mutagenicity. In vivo studies have not shown this effect. In accordance with current knowledge of tramadol can be classified as non-mutagenic.
Studies on the tumorigenicity of tramadol hydrochloride were conducted with rats and mice. Studies in rats showed no cases of a substance-related increased incidence of newly formed tumors. In the test with mouse there was an increased incidence of hepatic adenomas in males (in a dose dependent manner, a minor increase of 15 mg / kg up) and increase in lung tumors in females of all dose groups (substantially, but not depending on the dose).