Nicorette Clear 15 Mg/16 H 14 Transdermal Patches 23.62 Mg

Nicorette Clear (15 Mg/16 H 14 Transdermal Patches)

ACTION AND MECHANISM

- [ANTI-SMOKING], [GANGLIOPLEGIC]. Nicotine is an agonist of nicotinic cholinergic receptors, located mainly in the autonomic ganglia, adrenal medulla, neuromuscular junction and central nervous system. The effects of nicotine on the body are multiple and varied, and depend on the dose administered and the vegetative tone of the person.

Nicotine is also responsible for tobacco dependence in smokers, possibly through two mechanisms. At low doses it seems to have a stimulating effect on the cortex through the locus ceruleus, with an increase in cognitive and alertness. At higher doses it seems to give rise to a "reward effect" originating in the limbic system.

Abrupt cessation of tobacco after a prolonged period of use leads to a characteristic withdrawal syndrome, which includes symptoms such as dysphoria, insomnia, irritability, anger, anxiety, difficulty concentrating, agitation, bradycardia, and increased appetite with weight gain. Craving for nicotine is also noted.

The administration of nicotine through patches or chewing gum exerts effects similar to that obtained from tobacco, and provides, to those who wish to quit smoking, the amount of nicotine sufficient to reduce the appearance of withdrawal symptoms. The dose of nicotine is gradually reduced, until the body can do without it.

PHARMACOKINETICS

- Absorption:

* Patches: Nicotine easily passes through the skin and is absorbed, with a bioavailability of 68-90%. The patches produce a sustained release of nicotine over a period of 16 hours. The plasmatic concentration increases progressively, reaching a Cmax of 5-17 ng/ml after 5-10 hours.

- Distribution: Little binds to plasma proteins (5%). Its Vd when administered intravenously is about 2-3 l/kg. Nicotine crosses the blood-brain barrier and the placental barrier. It is excreted with milk.

- Metabolism: Nicotine is intensely metabolized in the liver, and to a lesser extent in the lungs and kidneys, very quickly, giving rise to more than 20 metabolites, less active than the original molecule. The main metabolite is cotinine, which appears in plasma concentrations 10 times higher than nicotine.

- Elimination: Nicotine is eliminated by hepatic metabolism and subsequent urinary excretion of the metabolites. Up to 10% of the dose is recovered unchanged in the urine, although if the urinary pH is less than 5, up to 30% can be obtained. The half-life of nicotine when administered artificially is 1-3 hours, compared to 15-20 hours for nicotine from tobacco. The Cl is about 70 l/hour.

Pharmacokinetics in special situations:

- Elderly: In healthy elderly patients there is a slight decrease in nicotine clearance, but this does not justify a dosage readjustment.

- Renal insufficiency: In patients with renal insufficiency, an increase in nicotine plasma levels is observed depending on the degree of renal functionality.

- Hepatic impairment: The pharmacokinetics of nicotine is not affected in patients with mild hepatic impairment (Child-Pugh scale of 5), while Cl is decreased in cirrhotic patients with moderate hepatic impairment (Child-Pugh scale of 7).

INDICATIONS

- [TOBACCO DEPENDENCE]. Adjuvant treatment in smoking cessation programs, with the aim of alleviating the symptoms of nicotine withdrawal syndrome.

Although these products mimic the effects of tobacco, they should never be used as tobacco substitutes.

POSOLOGY

"NICORETTE PATCHES"

- Adults A 15 mg patch will be applied daily. The duration of treatment is individual, and is usually defined by the person's tobacco dependence and by the number of cigarettes smoked per day.

In patients who smoke more than 20 cigarettes per day, clinical experience has shown that patch administration for a period of 12 weeks is sufficient, while in those who smoke less than 20 cigarettes per day, 8 weeks is usually sufficient.

After this period, the user should gradually reduce the dose of the patches. A 10mg daily patch will begin for a period of 2-4 weeks, and finally a 5mg daily patch will be applied for another 2-4 weeks. Abrupt cessation of administration is not convenient, since the patient could relapse.

RULES FOR CORRECT ADMINISTRATION

The patient should stop smoking completely during nicotine treatment, due to the risk of adverse reactions to nicotine from the increased levels of nicotine in plasma. It is not advisable to combine the patches with chewing gum or tablets in the treatment.

- Patches: Nicomax and Nicorette patches will be administered in the morning and removed at bedtime, keeping them in contact with the skin for 16 hours. Nicotinell, Nicotinell TTS and Niquitin Clear patches are prepared to be applied for 24 hours. In the case of Niquitin Clear, it is recommended that it be applied after getting up in the morning, and can be removed if desired at bedtime, although its use is recommended for the recommended 24 hours. The patches will be applied to any area of ​​the trunk, upper part of the arm or hip, recommending areas that do not have hair. It is recommended that women do not apply the patches to the chest.
The skin must be clean, dry and without creams, lotions, oils or powders, to favor the patch sticking. There should be no lesions, irritations or inflammations on the skin, since the amount of nicotine absorbed could be altered.
It is recommended to alternate the administration areas, allowing several days to elapse before using the same area again.
To place the patch, the following recommendations should be followed:
1. Cut one of the lateral ends of the bag containing the patch with scissors.
2. Remove the patch and detach the transparent sheets by folding it, trying not to touch the inside.
3. Press the patch on the selected part, pressing for about 10 seconds.
4. Wash hands immediately after administration.
5. Remove the patches 16 hours after their application by pulling.
6. Discard the used patch by folding it in half, sticky side in.
The person can bathe or shower with the patch on.
If for any reason the patch comes off, it should be replaced immediately with a new one, keeping the patch for the remaining time to reach 16 hours of administration.

CONTRAINDICATIONS

- Hypersensitivity to any component of the drug.

- Non-smokers or occasional smokers.

- Dermopathies. In case of [WOUNDS], [SKIN IRRITATION] or [DERMATITIS], a change in the absorption of nicotine from the patches may occur. It is recommended to apply the patches on undamaged skin.

PRECAUTIONS

- [RENAL INSUFFICIENCY]. Nicotine and its metabolites are excreted in the urine, so a decrease in renal functionality could lead to its accumulation. Since the metabolites are also active, adverse reactions could occur. No significant differences in the incidence of adverse reactions have been described in patients with mild or moderate renal insufficiency (CLcr between 30-90 ml/minute), but close monitoring of these patients is recommended. In patients with severe renal insufficiency (CLcr less than 30 ml/minute) safety and efficacy have not been evaluated, therefore its use is not recommended (See Contraindications).

- [LIVER FAILURE]. Nicotine is extensively metabolized in the liver, so in case of hepatic insufficiency an accumulation of nicotine could occur. Extreme precautions are recommended in patients with mild or moderate hepatic insufficiency, monitoring the possible appearance of adverse reactions. The safety and efficacy in patients with severe hepatic insufficiency have not been evaluated, therefore its use is not recommended (See Contraindications).

- Heart disease. Nicotine has cardiac stimulant and vasoconstrictor effects, so it can worsen cardiovascular conditions. Cardiovascular adverse reactions with nicotine have occasionally been described. However, it seems that the administration of nicotine by oral or transdermal route does not seem to be related to a particularly significant risk of suffering a cardiovascular condition. Patients with heart disease should be advised to stop smoking, if possible without nicotine replacement therapy. However, if this is not possible, it is recommended to properly assess the need for treatment, studying the benefits and risks, and take extreme precautions in patients with [HEART FAILURE], [ISCHEMIC HEART DISEASE] such as recent [ACUTE MYOCARDIAL INFARCTION] or [ANGINA PECTOR], [CARDIAC ARRHYTHMIA], [Stroke] and vasospastic diseases such as [TROMBOANGEITIS OBLITERANTES], [PRINZMETAL'S ANGINA] or [RAYNAUD'S SYNDROME]. In the same way, special caution is recommended in the case of patients with [ARTERIAL HYPERTENSION], since nicotine could increase blood pressure. In the event that the patient experiences a worsening of any of these symptoms, it is advisable to suspend the treatment (See Contraindications).

- [PHEOCHROMOCYTOMA], [HYPERTHYROIDISM] or any condition that can be worsened by catecholamines, such as [TYPE 1 DIABETES MELLITUS]. Nicotine stimulates the production and release of catecholamines in the adrenal medulla. This can lead to a worsening of symptoms such as pheochromocytoma, hyperthyroidism, or diabetes. In general, the administration of nicotine presents fewer risks than continuing to smoke, but it is recommended to previously evaluate the benefit-risk ratio in these patients.

- [PEPTICA ULCERA] and other inflammatory processes of the stomach, such as [GASTRITIS]. Nicotine delays the healing of gastroduodenal ulcerations, so it is recommended to use it in these patients only if the benefits outweigh the possible risks.

- Unit. Any preparation with nicotine presents a risk of producing dependence, although due to the lower plasmatic levels reached, it is less likely than with tobacco itself. However, abrupt withdrawal of treatment may lead to a withdrawal syndrome similar to that which occurs when smoking is stopped. For this reason, it is recommended to gradually discontinue the administration of nicotine, and not suspend treatment until it is relatively certain that a withdrawal syndrome will not occur.

- [HYPERSENSITIVITY REACTIONS]. Caution in patients susceptible to developing [ANGIOEDEMA] or [URTICARIA].

INTERACTIONS

Tobacco smoke seems to behave as an enzyme-inducing agent, probably due to the polycyclic aromatic hydrocarbons in the smoke, generated during the partial combustion of the vegetable fiber, and perhaps to nicotine. By inducing metabolism, mainly the cytochrome P450 isoenzyme CYP1A2, a decrease in pharmacological effects can be produced. In the same way, when smoking is stopped, the plasmatic concentrations of drugs that are metabolized by this route can increase, for which reason toxic effects could sometimes appear. It may therefore be necessary to readjust the dosage of drugs such as oral anticoagulants, benzodiazepines that are metabolized in the liver, caffeine, chlorpromazine, dextropropoxyphene, estrogens, phenacetin, phenazone, flecainide, fluphenazine, haloperidol,

Other reported effects of smoking include reduced diuretic response to furosemide, modification of the pharmacological effect of propranolol, and altered response rates in ulcer healing with H2 antagonists.

In diabetic smoking patients, there is the possibility of a decrease in the antidiabetic effect of insulin, probably due to the increase in catecholamine levels, which oppose its hypoglycemic action, and to the difficulty of subcutaneous insulin absorption due to peripheral vasoconstriction. Smokers usually require a 15-30% higher dose to control their blood glucose levels. When quitting smoking, a decrease in insulin dose is usually necessary.

These enzyme-inducing effects have not been observed when nicotine is administered in the form of preparations for smoking cessation, so a dosage readjustment of these drugs may be necessary.

Nicotine could interact with the following drugs:

- Adrenergic agonists and antagonists. Nicotine stimulates the adrenal production of cortisol and catecholamines, so it can modify the effects of adrenergic drugs. Similarly, the administration of a vasoconstrictor drug such as an adrenergic agonist, or a vasodilator such as a beta-blocker, may alter the transdermal absorption of nicotine.

- Bupropion. The efficacy and safety of the combination of bupropion with nicotine have not been studied. In fact, the use of nicotine was an exclusion criterion in the first clinical trials conducted with bupropion. The manufacturers of this drug have described a possible increased risk of hypertension, with 6.1% versus 2.5% for bupropion alone.

However, limited clinical data suggests that the combination of bupropion with nicotine patches might achieve better results in smoking cessation. In the event that it is decided to combine nicotine patches with bupropion tablets, it is recommended to assess blood pressure on a weekly basis, given the risk of hypertensive crisis.

PREGNANCY

Animal Safety: In studies with monkeys, administration of a 2 mg/kg bolus of intravenous nicotine has resulted in fetal acidosis, hypoxia, hypercapnia, and hypotension. Uterine blood flow was reduced by 30% by administering an infusion of 0.1 mcg/kg/minute.

Safety in humans: Smoking during the last trimester in pregnant women can cause fetal harm, such as growth retardation, risk of spontaneous abortion, and increased perinatal mortality, although its teratogenic potential has not been clearly established. It has been found that tobacco can also reduce fetal respiratory movements. These effects have also been seen with nicotine gum.

Therefore, the pregnant woman should be counseled to completely quit smoking before the third trimester of pregnancy. Due to the inherent risk that the administration of nicotine replacement therapy also presents, it is recommended that educational and behavioral programs be used before starting this treatment.

However, in highly dependent pregnant women, it may be necessary to resort to nicotine replacement therapy. This therapy presents fewer risks than smoking, since the plasma concentrations of nicotine achieved are lower and also there is no exposure to polycyclic hydrocarbons and carbon monoxide.

Smoking cessation, with or without nicotine replacement therapy, should not be undertaken individually by the patient, but rather as part of a medically supervised smoking cessation program.

In the third trimester, nicotine has hemodynamic effects, such as changes in fetal heart rate, which can affect the fetus near delivery. Therefore, after the sixth month of pregnancy, nicotine should only be used in pregnant smokers who have not been able to quit smoking in the third trimester, and always under medical supervision.

Effects on fertility: Smoking increases the risk of infertility in women and men. In vitro studies have shown that nicotine can negatively affect the quality of human sperm. Impaired sperm quality and decreased fertility have been observed in rats.

LACTATION

Safety in animals: no data available.

Safety in humans: Nicotine and its metabolites are excreted in milk for up to 2 hours after the last cigarette. The levels reached in milk are 2.9 times higher than those in plasma. It must be borne in mind that the amount of nicotine present in breast milk is lower in users of nicotine medications than in smokers. Nicotine can be absorbed orally by the infant to a greater extent than in the adult, due to the immaturity of hepatic metabolic mechanisms and the consequent reduction of the first-pass effect.

Breast-feeding patients should be advised not to smoke or use nicotine to quit. However, in highly dependent patients who have not been able to quit smoking, the risk to the infant from using nicotine should be assessed and compared with that of exposure to tobacco.

If replacement therapy is followed, it is recommended to use only chewing gum or tablets, and administer them after having breastfed the baby. At least another two hours should elapse before the child can be breastfed again.

A pregnant woman should never start a smoking cessation program with nicotine without consulting her doctor.

CHILDREN

The safety and efficacy of nicotine preparations in children under 18 years of age have not been evaluated, so their use is not recommended.

Doses of nicotine well tolerated by adult smokers during treatment can cause symptoms of severe and even fatal intoxication in young children. Patients should be warned that nicotine preparations should be handled with care and not stored or disposed of in such a way that children could accidentally use or consume them.

ADVANCED AGE

Specific pharmacokinetic studies in the elderly have not been performed, but the adverse effects and relapse rate in patients older than 60 years is similar to that in young people. However, in these patients the presence of heart disease tends to be more frequent, and a slight increase in the incidence of asthenia, body aches and dizziness has been described.

ADVERSE REACTIONS

This medication may cause adverse reactions that are related to the pharmacological effects of nicotine or withdrawal effects related to smoking cessation. Certain reported symptoms such as depression, irritability, nervousness, restlessness, moodiness, anxiety, drowsiness, loss of concentration, insomnia, and sleep disturbances may be related to withdrawal symptoms associated with smoking cessation.

The most common adverse reactions to the patches are those that occur at the application site, including transient rash, itching, burning sensation, tingling, numbness, swelling, pain, and hives. Most of these topical reactions are minor and are quickly resolved by removing the patch. Pain or a feeling of heaviness in the extremities or in the area around where the patch is applied (for example on the chest) has been reported. Hypersensitivity reactions, including contact dermatitis and allergic reactions, have been reported. In the case of severe or persistent local reactions at the application site (for example, severe erythema, pruritus or edema) or generalized skin reactions (for example, urticaria, or generalized rash), patients should stop using the patches and consult their doctor. The dose of this drug should be reduced or discontinued if there is a clinically significant increase in cardiovascular or other effects attributed to nicotine.

The most characteristic adverse reactions are:

- Digestive: It is normal (20-40%) for [DYSPEPSIA], [NAUSEA], [VOMITING] or [GASTRIC HYPERACIDITY] to appear. Less frequent is the appearance of [DRY MOUTH], [ANOREXIA], [DIARRHEA], [CONSTIPATION], [ABDOMINAL PAIN], [FLATULENCE] or [HYPO].

Chewing gum can also produce [HYPERSALIVATION], symptoms of inflammation of the oral cavity, such as [STOMATITIS], [GLOSSITIS], [PERIODONTITIS], [PHARYNGITIS], [ESOPHAGITIS] and pain in the jaw muscles, due to its high viscosity. These adverse reactions appear at the beginning of the treatment, and can be reduced with a correct administration of the chewing gum.

- Neurological/psychological. It is common (1-25%) to produce [DIZZINES] (3-9%), [HEADACHE] (17-29%), [INSOMNIA] (3-23%), [DECREASED CONCENTRATION] (1-3%) and [IRRITABILITY]. On more rare occasions (<1%), [EUPHORIA], [SLEEP], [CONFUSION], [DEPRESSION], [PARESTHESIA] and [SEIZURES] have been described. [TOBACCO DEPENDENCE] syndrome may occur if the withdrawal is sudden or premature.

- Cardiovascular. Cases of [ARTERIAL HYPERTENSION] and [EDEMA] have been described. Occasionally (1-0.1%) [PALPITATIONS] may occur, and more rarely (<0.1%) [ARRIT MIA CARDIACA]. Some cases of [ACUTE MYOCARDIAL INFARCTION], [AURICULAR FIBRILLATION] and [CITUS] have been described in patients treated with nicotine patches. However, a causal relationship with nicotine could not be established.

- Respiratory. Some cases of [TOS] (3-9%), chest congestion and [DYSPNEA] have been described.

Nicotine administered nasally can cause local irritation phenomena, such as [NASAL CONGESTION], [SNEEZING], mucosal irritation, [PHARYNGITIS], [SINUSITIS], [EPISTAXIS], [CONJUNCTIVITIS], [DYSGEUSIA] and [PAROSMIA]. These effects appear very frequently (94%) at the beginning of treatment, but are reduced with continued use.

- Allergic/dermatological. Nicotine can lead to [HYPERSENSITIVITY REACTIONS], with pruritus and erythema, and even [ANGIOEDEMA].

The patches have given rise to local reactions in certain people, such as [ERYTHEMA] (14-17%), which disappeared after 24 hours, localized edema (3-4%), [PRURITO], burning sensation in the area of ​​application (35-47%), [CONTACT DERMATITIS] (2-3%) and [VASCULITIS]. In case of serious adverse reactions, such as [DERMATITIS] (1-7%) or generalized dermatological reactions such as erythema or severe lesions, it is recommended to suspend treatment. The administration of topical corticosteroids and/or oral antihistamines has been shown to be effective in reversing these symptoms.

- Osteomuscular. The patches have occasionally given rise to [MYALGIA] and [OSTEOMUSCULAR PAIN] (3-9%).

- Generals. Some cases of [CHEST PAIN], [ASTENIA], [BACK PAIN] or [HYPERHIDROSIS] have been described.

OVERDOSE

Symptoms: Nicotine is a very toxic substance, and doses of 0.6-0.9 mg/kg can be lethal in humans. However, there is great interindividual variability, since chronic smokers can tolerate higher doses than children and non-smokers, due to the development of tolerance. In children, a small dose of nicotine can be dangerous and lead to serious and even fatal symptoms, so it is recommended that these medicines be kept out of the reach of children and that in case of suspected poisoning, consult a doctor immediately.

Despite the great toxicity of nicotine, there are very few data available on poisoning with it. Poisoning can occur if several gums are chewed at the same time, several tablets are sucked, several patches are administered or if these devices are combined with each other or with tobacco.

In case of ingestion of nicotine, the risk of overdose is low, since it is released slowly in small amounts, and is inactivated by a first-pass effect. In addition, vomiting often occurs quickly, which prevents the absorption of nicotine.

In general, nicotine poisoning results in the same symptoms as excessive tobacco use. However, it must be borne in mind that tobacco smoke contains other toxic substances such as tar and carbon monoxide. General symptoms of poisoning include nausea, vomiting, diarrhea, abdominal pain, headache, nervousness, irritability, insomnia, dizziness, tachycardia and palpitations, hypertension or hypotension, QT prolongation, paleness, muscle weakness, sweating, excessive salivation, burning throat, visual and hearing disturbances, dyspnea. In the most severe cases, lethargy, circulatory collapse, seizures, coma, and death from central or peripheral respiratory paralysis or occasionally from heart failure may occur.

Treatment:

- Patches: If the patient presents symptoms of overdose, the nicotine patch will be removed immediately. It is recommended to wash the skin with water and then dry it well. The use of soap to clean the skin is not recommended, since it can increase the absorption of nicotine. It should be kept in mind that it is very possible that nicotine will continue to be absorbed from the skin for several hours after the patch is removed, possibly due to nicotine deposits under the epidermis.
If the patient has ingested the patches, the same steps should be followed as in the case of chewing gum poisoning. It must be taken into account that the patches release nicotine in a prolonged manner for several hours, so it is recommended to administer the activated charcoal suspension for as long as the patch remains in the intestine.

An attempt will be made to keep the individual in an appropriate position and warm, to maintain normal body temperature.

Symptoms of poisoning will be treated symptomatically. Seizures and excitability can be treated by administration of benzodiazepines, while tachycardia may require administration of a beta-blocker. Bradycardia responds to atropine administration. Hypotension and vascular collapse must be treated intensively by administration of intravenous fluids or other effective measures.

If necessary, in case of respiratory paralysis, artificial respiration will be instituted.

Leaflet Nicorette Clear 15 Mg/16 H 14 Transdermal Patches 23.62 Mg