Nicotinell TTC 30 21 mg. / 24h. 52.5 mg. 7 patches
Chemical name and nomenclature of the bioactive ingredient and the excipients: s (-) (3- (1-Methyl-2-pyrroIidinyI) pyridine] == S (-) - nicotine. S - (-) - Nicotine is pharmacologically the most active form of nicotine, the principal alkaloid of tobacco.
3. PHARMACEUTICAL FORM Transdermal patch
Nicotinell TTS is round, flat, matrix-type transdermal drug delivery system designed for sustained release of the S - (-) - Nicotine is placed on intact skin surface . S - (-) - Nicotine penetrates through the skin by diffusion, thereby achieving a direct bioavailability in the systemic circulation.
In order to ensure a constant concentration of the ingredients of diffusion, Nicotinell TTS contains more S - (-) - Nicotine, than is delivered in 24 hours. Nicotinell TTS released S - (-) - Nicotine approximately 0.7 mg / cm2 / 24 hours transdermal patch every Nicotinell TTS 10 = 7 mg / 24 hours, Nicotinell TTS 20 = 14 mg / 24 h, Nicotinell TTS 30 = 21 mg / 24 hours. Therefore received an average daily dose is determined primarily by the size of the contact surface of the system.
The following diagram presents the structure of Nicotinell TTS.
4. Clinical data
Symptomatic treatment of nicotine dependence, as an aid in smoking cessation.
4.2. Dosage and method of administration
Consumers should stop smoking completely during treatment with Nicotinell TTS. It is recommended that those who smoke more than 20 cigarettes a day, start treatment with Nicotinell TTS 30 cm2 daily, hairy area of skin on the body or forearm. Those who smoke less than 20 cigarettes per day should start with Nicotinell TTS 20 cm2. Sizes 30, 20 and 10 cm2 are provided in order to achieve a gradual withdrawal of nicotine replacement, using treatment periods of 3-4 weeks. The size can be adapted to individual response, the dose to maintain or increase, if not achieved abstinence or exhibit symptoms of nicotine cravings.
The dosage can be adjusted by cutting the transdermal system. No studies in treatment duration of 3 months and doses of more than 30 cm2. Nicotinell TTS system is ustaychiva for children packaging. The bag must be cut along the dotted line, to facilitate removal of the system. After removing the protective film system you should get stuck on a non-hairy, clean, dry skin surface of the body or forearm. The tape must be pressed at the selected point of 10-20 seconds with the palm of the hand. Every day you should use a different location for the application. The same place can be used again after a few days.
There were no efficacy and safety of persons under 18 years of age.
Experience in the use of Nicotinell TTS in persons over 65 years is limited. Nicotinell
TTS does not show any particular problems in this age group.
Drug abuse and dependence
Nicotinell TTS is used as an aid in smoking cessation as substitute contained in tobacco nicotine. Transdermal nicotine has a very low potential for abuse because of its slow onset of action, low blood levels of fluctuation, inability to cause higher concentration of nicotine and the rare use (once daily). Moreover, the treatment schedule gradually reduce the intake of Nicotinell TTS, so the risk of dependence after therapy is minimal. The effect of abrupt termination of Nicotinell TTS is similar to the effect of rapid cessation comparable nicotine concentration. Patients should be encouraged to taper off in the course of therapy.
Nicotinell TTS should not be used by non-smokers, children or nepristrasteni smokers (see Warnings). Nicotinell TTS is contraindicated in pregnant and lactating women (see Pregnancy and lactation).
Other contraindications are acute myocardial infarction, unstable or worsening angina pectoris, severe cardiac arrhythmias, recent myocardial cerebrovascular accident, a skin disease, which can complicate the use of stickers, and known hypersensitivity to nicotine or any component of the system.
4.4. Special precautions for use and precautions
Nicotine is a toxic substance, and even milligrams thereof are potentially fatal in faster absorption. Treatment with Nicotinell TTS should be discontinued if symptoms of overdose. Mild intoxication causes nausea, vomiting, abdominal pain, diarrhea, headache, sweating and pallor (see Overdose).
Doses of nicotine that are tolerated by adult smokers during treatment may prove fatal to young children. Before and after use Nicotinell TTS contains a substantial amount of nicotine. Patients should be aware that the systems should not be left within the reach of children. Caution should be handled with both new and used systems with, so does not fall into the hands of children.
Patients should be encouraged to stop smoking completely during the use of Nicotinell TTS.
Patients should be warned that if they continue to smoke during treatment with Nicotinell TTS, the risk of side effects, including heart, increases considerably.
Given the pharmacological effects of S - (-) - Nicotine and still insufficient observations Nicotinell TTS can be used in the following conditions only careful consideration of risks and benefits: hypertension; stable angina; cerebrovascular disease; occlusive peripheral arterial disease; heart failure; hyperthyroidism; diabetes mellitus; renal or hepatic impairment; peptic ulcer.
Patients with these diseases should be encouraged to stop smoking if possible without Nicotinell TTS. Only if this proves impossible, may be considered the use of Nicotinell TTS. It is generally considered that the risk associated with the use of Nicotinell TTS, is always much less than that associated with continued smoking.
In case of severe persistent skin reactions recommended discontinuation.
Allergic reactions: reported for contact sensitization in several patients using transdermal nicotine systems in the clinical trial process. Patients who develop skin sensitization must be warned that they may experience more severe side effects from products containing nicotine and smoking.
There is no information about the interactions between Nicotinell TTS and other medicines. Smoking cessation, with or without Nicotinell TTS can change individual response to concomitant treatment with other agents and require dosage adjustment. It is estimated that smoking accelerates metabolism by induction of the enzyme system, which lowers the blood levels of drugs such as antipyrine, caffeine, estrogens desmetildiazepam, imipramine, lidocaine, oxazepam, pentazocine, phenacetin, theophylline, and warfarin. Therefore, smoking cessation may result in an increase in the concentration of these drugs. Other reported effects of smoking include reduced analgesic efficacy of propoxyphene, reduced diuretic response but furosemide and altered pharmacological response to propranolol, as well as altered levels of H2-antagonists used to treat ulcers.
And smoking and nicotine can increase circulating levels of cortisol in the bloodstream and catecholamines. You may need dosage of nifedipine, adrenergic agonists or adrenergic blocking agents can be corrected.
4.6. Pregnancy and lactation
Smoking has adverse effects in pregnant women, and nicotine itself has adverse effects in pregnant animals. This product is contraindicated in pregnant women (see Contraindications).
4.7. Effects on ability to drive and use machines
When Nicotinell TTS is used as recommended, the risk when driving or operating machinery is minimal.
4.8. adverse reactions
Generally Nicotinell TTS can cause side effects similar to those associated with smoking. As the peak plasma concentrations caused by Nicotinell TTS, are lower and vary less than those during smoking, nicotine-related adverse events during the treatment with Nicotinell TTS is expected to be less pronounced in comparison with those of tyutnopusheneto.
Some of the following symptoms are difficult to distinguish from the usual withdrawal symptoms, when compared with placebo. The placebo used contains about 13% of the amount of nicotine in Nicotinell TTS, in order to imitate the color and odor for blinding purposes.
The main side effect of Nicotinell TTS is skin redness. They led to premature discontinuation in 6% of participants in clinical trials. Skin reactions including erythema and pruritus at the site of the tape. Marked are also swelling, burning, rash, redness and tingling at the site of application. Most of the time these events were mild. Most skin reactions resolved within 48 hours, but in extreme cases the erythema and infiltration continued until 1-3 weeks. Occurrence of serious skin reactions begins between the 3rd and 8th week of treatment. In isolated cases, skin reactions extended beyond the application sites. Isolated cases of urticaria, angioedema, and dyspnea.
The following side effects / withdrawal symptoms are most often reported in three double-blind clinical trials regardless of causal relationship to study drug.
Reaction of the application site 34.9%
Symptoms similar to a cold 12.0%
Dysmenorrhea 6.6% **
**% Of women
The following adverse effects, regardless of causal relationship to treatment with Nicotinell TTS and a frequency of <6%:
Reactions> 2%, and more frequent than placebo (at least 0.5%)
Abdominal pain, dyspepsia, allergy, motor dysfunction, cough, abnormal dreams, arthritis.
Reactions> 2%, and similar or less frequent than placebo
Agitation, emotional lability, irritability, constipation, diarrhea, toothache, arthralgia, back pain, pharyngitis, rhinitis, sinusitis, symptoms of upper respiratory tract.
Reactions between 1 and 2%
Drowsiness, impaired concentration, vomiting, chest pain, fatigue, pain, changes in blood pressure, bronchitis, rash herpetiformis rash, pain in the ear.
Effects <1% *
Hot flushes, local swelling, weight gain, beats, hypertension, palpitations, stomach ulcer, dry mouth, flatulence, gingivitis, dysphagia, abnormal stools, disturbances in the function of the thyroid gland, the occurrence of lymph nodes, taste disturbance, changes in vision , dyspnea, cystitis, paraesthesia, memory impairment, tremor, confusion, agitation, increased appetite, muscle leg cramps, migraine, itching, increased sweating, urticaria, acne.
* Includes only effects that the investigator's opinion could be related to treatment with Nicotinell TTS and a frequency of <1% regardless of relationship to study medication A similar profile was observed in previous clinical trials ..
The toxicity of nicotine can not be compared directly to that of the cigarettes, for tobacco smoke contains other harmful substances (such as carbon monoxide and tar). Chronic smokers can tolerate doses which are toxic to smoking due to addiction.
The application of several Nicotinell TTS patches can cause acute overdose. Slower absorption transcutaneous administration favors the development of tolerance to the toxic effects.
Do not expect rapid systemic availability of Nicotinell TTS with chewing or swallowing due to slow
release of the tape and first pass metabolism.
The acute lethal dose in adults smoking is approximately 60 mg.
If the patient shows signs of an overdose, the tape must be removed immediately. Skin surface should be washed with water and dried (do not use soap). The skin will continue to release nicotine over several hours probably due to the formation of nicotine depot.
Other measures for acute nicotine poisoning include assisted breathing in respiratory paralysis, maintaining normal body temperature and treatment of hypotension and cardiovascular collapse.
S - (-) - Nicotine acts primarily on the cholinergic receptors of the nicotinic type in the peripheral and central nervous system. For much of the effects low doses S - (-) - Nicotine have a stimulating effect, while high doses - depressing.
Intermittent administration of S - (-) -Nicotine influence neurohormonal system and causes the release of acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, cortisol and ACTH. These neuroregulators can cause the reported behavioral and subjective effective smoking. Found to improve some parameters such as the speed of the writing machine, after administration of nicotine in smokers who have not smoked for one day.
The effects of nicotine in humans is complex, depending on the dose, the rate of acceptance, self prevalent tone, individual characteristics (tolerance) and previous exposure.
The influence of S - (-) - Nicotine on the cardiovascular system due to the stimulation of central and peripheral sympathetic nervous system. For example, at concentrations achieved in smoking, nicotine causes heart rate, increased systolic and diastolic pressure and cutaneous vasoconstriction.
Rapidly develop partial or complete tolerance to certain effects of nicotine, the second application after 60 to 120 minutes produces less acceleration pulse and subjective effects in spite of the high concentration of intravenous nicotine. When a second application is made more than 210 minutes after the first, the answer is as an initial application.
Application of Nicotinell TTS 20 cm2 in smokers who did not smoke during the night, causing a slight increase in heart rate (up to 6 bpm) and systolic pressure and reduction in stroke volume. Changes in heart rate and stroke volume are still there and the 10th day after repeated applications, which proves that it does not develop a complete tolerance to nicotine. The effects are of lower amplitude than those of tobacco, while the changes in skin temperature and blood flow comparable to that of placebo. In the double blind placebo-controlled trials of nicotine replacement with Nicotinell TTS in the first few weeks and months after stopping smoking increases the chances of successful abstinence with or without maintenance group. Also observed a strong tendency to reduce withdrawal symptoms.
Nicotine is easily absorbed through the skin into the systemic circulation. The absorption profile after a single application of Nicotinell TTS in healthy abstinent smokers (persons preminavishti course transdermal therapeutic systems for smoking cessation) shows initial delay 1-2 hours, followed by a progressive rise in nicotine levels in plasma, as the plateau is reached within 8-10 hours after application.
After removal of plasma concentrations declined slower than it should be suspected in view of the two-hour period polueliminatsiya from the serum of this drug after intravenous infusion. About 10% of the amount of nicotine reaching the systemic circulation, is supplied from the skin after removal of the patch Nicotinell TTS 30 cm2 area under the curve of the change in plasma concentration over time (AUC 0-24) varies proportionally depending on the dose delivered by Nicotinell TTS, which in turn depends on the size of the patch.
In comparison with i.v. 76.8% infusion of nicotine released from Nicotinell TTS, are systematically available. Repeated applications of 20 and 30 cm2 Nicotinell TTS average minimum and maximum plasma concentrations at steady state are 7.1 and 12.0 ng / ml in 20 cm2 patch and 10.3 and 17.7 ng / ml in 30 cm2 patches. These plasma concentrations are within the range observed in moderate smoking.
Analysis of the residual drug content in the system with the 24 hours indicates that the total drug release in the circulation varies by a factor of 2 between individuals. However intra-patient variability of the amount of nicotine delivered is small, indicating high levels of consistency in the system single dose within 24 hours of Nicotinell TTS.
S - (-) - Nicotine has a large volume of distribution in the body - approximately 180 1. It crosses the blood-brain barrier and the placenta and is found in breast milk. The degree of binding to plasma proteins is negligible, only 5%. Total plasma clearance of nicotine varies between 0.92 and 2.43 1 / min. Eliminated predominantly by hepatic metabolism, such as primary metabolites of nicotine are cotinine and nicotine-l'-N-oxide.
Cotinine is largely subject to further metabolism. Some of the metabolites of nicotine have been identified so far. Very small amount of nicotine is eliminated unchanged by the kidneys.
There is considerable individual variation in the distribution, metabolism, bioavailability of nicotine from cigarettes and nicotine gum capsules.
None of the main metabolites is not considered pharmacologically active. Renal excretion of unchanged nicotine is pH-dependent, while alkaline pH was negligible.