Active ingredients: Clonidine
CATAPRESAN TTS-1 2.5 mg transdermal patches
CATAPRESAN TTS-2 5 mg transdermal patches
CATAPRESAN TTS-3 7.5 mg transdermal patches
Why is Catapresan TTS used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Imidazoline receptor agonists
THERAPEUTIC INDICATIONS
Catapresan TTS is indicated in the treatment of all forms of arterial hypertension. Catapresan TTS can be used alone or in combination with other antihypertensive drugs.
Contraindications When Catapresan TTS should not be used
Catapresan TTS should not be used in patients with known hypersensitivity to the active substance or to any other component of the transdermal patch, and in patients with severe bradyarrhythmia resulting from sick sinus disease or second or third degree atrioventricular block.
Precautions for use What you need to know before taking Catapresan TTS
Catapresan TTS should be used with caution in patients with mild to moderate bradyarrhythmia such as in case of reduced sinus rhythm, Raynaud's disease and other peripheral or cerebral perfusion disorders, depression, polyneuropathy and constipation.
In case of hypertension caused by pheochromocytoma, the use of Catapresan TTS has not shown any therapeutic effect.
Clonidine, the active ingredient of Catapresan TTS, and its metabolites are extensively excreted by the kidney. In case of renal insufficiency, a particularly careful dosage adjustment is necessary (see section "Dose, method and time of administration").
In patients with heart failure or severe coronary artery disease, treatment with Catapresan TTS should be monitored with particular care, as with other antihypertensive drugs.
Patients should be advised not to discontinue therapy until after consulting their physician. Suddenly discontinuing prolonged high-dose Catapresan TTS treatment has led to restlessness, palpitations, rapid rise in blood pressure, nervousness, tremors, headache or nausea. If you wish to discontinue Catapresan TTS therapy, the physician should progressively reduce the dose over 2 - 4 days.
An excessive increase in blood pressure following discontinuation of Catapresan TTS therapy can be reversed by administering oral clonidine hydrochloride or intravenous phentolamine (see section "Interactions").
If combined treatment with a beta-blocker requires discontinuation of antihypertensive therapy, the beta-blocker should always be gradually discontinued first and then the clonidine.
In patients who have experienced a local skin reaction to Catapresan TTS, switching to oral clonidine therapy may be associated with the development of a generalized rash.
Promptly consult your doctor about removing the patch if moderate to severe localized erythema and / or blistering of the patch application site or generalized rash is observed.
If local, isolated and minor skin irritation is observed within 7 days of applying the patch, it can be removed and replaced with a new one, applied to another skin area.
Catapresan TTS should not be discontinued during the surgical period. Blood pressure should be carefully monitored during surgery and additional pressure control measures should be available if needed.
When considering initiating therapy with Catapresan TTS during the perioperative period, it should be considered that therapeutic plasma levels are not reached until 2 - 3 days after the initial application of Catapresan TTS (see section "Dose, method and time of administration ").
Catapresan TTS must be removed prior to defibrillation or cardioversion surgery due to the potential alteration of electrical conductivity, which can increase the risk of arcing, a phenomenon associated with the use of defibrillators.
Since Catapresan TTS contains aluminum, it is recommended to remove it before undergoing a magnetic resonance imaging (MRI).
Skin burns at the patch application site have been reported in numerous patients who wore an aluminum-containing transdermal patch during magnetic resonance imaging (MRI). Treatment with Catapresan TTS can lead to reduced lacrimation, this should be taken into account if contact lenses are used.
Pediatric use
The use and safety of use of clonidine in children and adolescents has not been reflected in randomized controlled trials; therefore use in this patient population cannot be recommended.
In particular, when clonidine is used off-label in combination with methylphenidate in children with ADHS (attention deficit hyperactivity disorder), serious adverse reactions, including death, have been observed. Therefore, the use of clonidine in this combination is not recommended.
Interactions Which drugs or foods can modify the effect of Catapresan TTS
The antihypertensive effect of Catapresan TTS can be enhanced by concomitant administration of other drugs used to lower blood pressure. This can be used therapeutically by administering other types of antihypertensive agents such as diuretics, vasodilators, beta-blockers, calcium channel blockers and ACE inhibitors, but not alpha1-blockers.
Substances that raise blood pressure or induce retention of sodium and water ions, such as non-steroidal anti-inflammatories, may reduce the efficacy of clonidine.
Substances with α2-blocking activity, such as phentolamine or tolazoline, may inhibit the α2 receptor mediated effects of clonidine in a dose dependent manner.
The concomitant administration of substances with negative chronotropic or dromotropic activity such as beta-blockers or digitalis glycosides can cause or potentiate rhythm disturbances in bradycardias. It cannot be excluded that concomitant administration of a beta-blocker may cause or potentiate peripheral vascular dysfunction. The antihypertensive effect of clonidine can be reduced or abolished and the phenomena of altered orthostatic regulation can be caused or aggravated by the concomitant administration of tricyclic or neuroleptic antidepressants with alpha-blocking activity.
The effects of CNS inhibitors, or the effects of alcohol, may be enhanced by clonidine.
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those without a prescription.
Warnings It is important to know that:
Fertility, pregnancy and lactation
Ask your doctor or pharmacist for advice before taking any medicine.
No suitable and controlled studies have been conducted in pregnant women.
During pregnancy, Catapresan TTS, like any other medicine, should only be administered when clearly needed. In this case, close monitoring of the mother and baby is recommended.
Clonidine crosses the placental barrier and can slow the heart rate of the fetus.
There is insufficient experience regarding the long-term effects of prenatal drug exposure. Oral forms of clonidine are preferred during pregnancy.
Intravenous administration of clonidine should be avoided.
Preclinical studies conducted with clonidine in rats and rabbits did not show teratogenic effects. In rats, increased resorption values were observed after oral administration of clonidine. A transient increase in postpartum blood pressure in the newborn cannot be excluded.
Due to the lack of supporting data, the use of Catapresan TTS during breastfeeding is not recommended.
No clinical studies concerning the possible effects of clonidine on human fertility have been conducted.
Animal studies with clonidine have not shown direct or indirect harmful effects with respect to fertility indices.
Effects on ability to drive and use machines
No studies have been performed to evaluate the effects on the ability to drive and use machines.
However, the following possible side effects may occur during treatment with Catapresan TTS: dizziness, sedation and disturbances in accommodation. Therefore, special care is recommended when driving a vehicle or operating machinery. If you experience any of the side effects mentioned above, potentially hazardous activities such as driving or operating machinery should be avoided.
Dosage and method of use How to use Catapresan TTS: Dosage
Treatment with Catapresan TTS, to be "adjusted" according to individual therapeutic needs, should be started with Catapresan TTS-1 2.5 mg transdermal patch. If after 1 or 2 weeks the reduction in blood pressure is not sufficient, the dosage can be increased by adding another 2.5 mg patch or by using the Catapresan TTS-2 5 mg transdermal patch.
An increase in dosage above two 7.5 mg Catapresan TTS patches is not usually accompanied by an increase in efficacy.
When Catapresan TTS is applied for the first time as a replacement for oral therapy with clonidine hydrochloride or other antihypertensive medicinal products, the physician should be aware that the antihypertensive effect exerted by Catapresan TTS transdermal patch may not be achieved for 2-3 days. Therefore it is advisable to gradually reduce the dosage of the medicine in use; some or all of the previous antihypertensive therapies may be maintained, especially in patients with more severe forms of hypertension.
Kidney failure
The dose should be adjusted both as a function of the individual response, which can be highly variable in patients with renal insufficiency, and as a function of the degree of renal impairment.
Continuous monitoring is necessary. Since only a minimal amount of clonidine is removed during routine hemodialysis, no further doses of clonidine are needed after dialysis.
Pediatric population
There is insufficient evidence to support the use of clonidine in children and adolescents under the age of 18 years. The use of clonidine is therefore not recommended in pediatric subjects below 18 years of age.
Instructions for Use
The Catapresan TTS transdermal system should be applied to an area of intact, hairless skin located in the upper chest or upper outer arm once every 7 days. Each new application of Catapresan TTS must take place on a different area of the skin from the previous one. Before application, remove the transparent film placed to protect the adhesive layer of the system. If the TTS transdermal system tends to come off during the 7 days of application, the adhesive patch cover must be applied directly on the system itself to ensure good adhesion. rare cases where it was necessary to change the patch before 7 days to keep blood pressure under control.
1) Apply Catapresan TTS transdermal patch every 7 days on the same day of the week.
2) Choose a "hair-free" application area (eg. The outer part of the arm or the upper part of the chest). The chosen area must be free from cuts, abrasions, irritations, calluses and scars and must be perfectly dry before "application of Catapresan TTS transdermal patch. It is advisable not to apply Catapresan TTS transdermal patch in skin folds or in sites where it could be constricted by clothing, to avoid premature detachment of the patch.
3) Wash your hands and dry them thoroughly before removing the transdermal system from the pouch.
4) Wash the selected area with soap and water only and dry it carefully.
5) Open the sachet marked Catapresan TTS (clonidine) and take out the transdermal patch.
6) Remove the protective plastic from the patch avoiding touching the medicated part with your hands
7) Apply with light pressure on the edges Catapresan TTS transdermal patch on the selected skin area. Immediately after application, wash your hands.
8) After 7 days, remove the old patch and apply another one in a different area of the skin, repeating the procedure from point 2 onwards.
How to use the bumper cover
Warning: the adhesive patch cover does not contain any drugs and must not be used alone. The adhesive patch cover should be applied directly over the Catapresan TTS transdermal patch only if the patch detaches from the skin.
1) Wash your hands with soap and water and dry them carefully.
2) Clean with a dry cloth around the area where the Catapresan TTS transdermal patch is applied and with light pressure make sure that the edges of the Catapresan TTS transdermal patch are in contact with the skin.
3) Open the sachet labeled "Adhesive patch cover" and remove the protective plastic
4) Apply the adhesive patch cover with light pressure, especially on the edges, directly on Catapresan TTS transdermal patch taking care to position the adhesive patch cover in such a way that Catapresan TTS transdermal patch occupies its center
If you have any questions about the use of the medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Catapresan TTS
Symptoms
Clonidine is characterized by a wide therapeutic range. Clonidine intoxication is manifested by a general depression of the sympathetic nervous system, which can cause constriction of the pupil, lethargy, bradycardia, hypotension, hypothermia, somnolence up to coma, respiratory depression including apnea. Paradoxical hypertension may also occur following stimulation of peripheral α1 receptors.
Rarely, there have been reports of Catapresan TTS poisoning due to accidental or intentional ingestion of patches. Most of these cases involve children.
Treatment
Careful monitoring and symptomatic measures.
There is no specific antagonist for clonidine overdose. If symptoms of overdose occur following skin application of the patch, all transdermal patches should be removed. After removal of the patch, plasma levels of clonidine persist for approximately 8 hours, then decline slowly over a period of several days.
In case of accidental intake of an excessive dose of the medicine, notify your doctor immediately or go to the nearest hospital.
Side Effects What are the side effects of Catapresan TTS
Like all medicines, this can cause side effects, although not everybody gets them.
Most of the side effects experienced during treatment with Catapresan TTS were mild and tended to decrease with continued therapy.
Adverse reactions are listed below by system organ class and frequency, according to the following categories:
Very common ≥ 1/10
Common ≥ 1/100 <1/10
Uncommon ≥ 1 / 1,000 <1/100
Rare ≥ 1 / 10,000 <1 / 1,000
Very rare <1 / 10,000
Not known frequency cannot be estimated from the available data.
Psychiatric disorders:
Common: Depression, sleep disturbances.
Uncommon: Confusional state, delusional perception, hallucinations, decreased libido, nightmares.
Nervous system disorders:
Very common: Vertigo, sedation.
Common: Headache, somnolence.
Uncommon: Paresthesia.
Eye disorders:
Uncommon: Accommodation disorders
Rare: Tearing reduction.
Cardiac disorders:
Uncommon: Bradyarrhythmia, sinus bradycardia.
Rare: Atrioventricular block.
Vascular disorders:
Very common: Orthostatic hypotension.
Uncommon: Raynaud's syndrome.
Respiratory, thoracic and mediastinal disorders:
Rare: Dryness of the nasal mucosa.
Gastrointestinal disorders:
Very common: Dry mouth.
Common: Constipation, nausea, salivary gland pain, vomiting.
Rare: Pseudo-obstruction of the colon.
Skin and subcutaneous tissue disorders:
Very common: Application site erythema.
Common: Application site irritation, application site burning, application site discoloration.
Uncommon: Application site papules, application site dermatitis, urticaria, pruritus, rash.
Rare: Alopecia.
Reproductive system and breast disorders:
Common: Erectile dysfunction.
Rare: Gynecomastia.
General disorders and administration site conditions:
Common: Application site pain, tiredness.
Uncommon: Malaise.
Diagnostic tests
Rare: Increased blood sugar.
Compliance with the instructions in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored. Warning: do not use the medicine after the expiry date indicated on the package.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
COMPOSITION
Catapresan TTS is a clonidine-based transdermal patch that determines a continuous and constant systemic release of the active ingredient for 7 days. Clonidine is an imidazolidine derivative whose chemical name is 2,6-dichloro-N-2-imidazolidinylidenebenzenamine.
CATAPRESAN TTS-1 2.5 mg transdermal patches (3.5 cm2 of surface area) Scheduled for in vivo release of 0.1 mg per day of clonidine for 7 days, contains:
Active ingredient: 2.5 mg clonidine
Excipients and support: light mineral oil; polyisobutylene 1,200,000; polyisobutylene 35,000; precipitated silica.
Film consisting of: medium density polyethylene, polyester aluminum and ethylene vinyl acetate; polypropylene film; polyester film coated with fluorocarbon diacrylate.
CATAPRESAN TTS-2 5 mg transdermal patches (7.0 cm2 of surface area) Scheduled for in vivo release of 0.2 mg clonidine per day for 7 days, contains:
Active ingredient: clonidine 5 mg
Excipients and support: light mineral oil; polyisobutylene 1,200,000; polyisobutylene 35,000; precipitated silica.
Film consisting of: medium density polyethylene, polyester aluminum and ethylene vinyl acetate; polypropylene film; polyester film coated with fluorocarbon diacrylate.
CATAPRESAN TTS-3 7.5 mg transdermal patches (10.5 cm2 of surface area) Scheduled for in vivo release of 0.3 mg per day of clonidine for 7 days, contains:
Active ingredient: 7.5 mg clonidine
Excipients and support: light mineral oil; polyisobutylene 1,200,000; polyisobutylene 35,000; precipitated silica.
Film consisting of: medium density polyethylene, polyester aluminum and ethylene vinyl acetate; polypropylene film; polyester film coated with fluorocarbon diacrylate.
PHARMACEUTICAL FORM AND CONTENT
2 transdermal patches + 2 patch covers. Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CATAPRESAN TTS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Catapresan TTS is a clonidine-based transdermal patch that determines a continuous and constant systemic release of the active ingredient for 7 days.
Clonidine is an imidazolidine derivative whose chemical name is 2,6-dichloro-N-2-imidazolidinylidenebenzenamine.
CATAPRESAN TTS-1 2.5 mg transdermal patches (3,5 cm2 of surface)
Scheduled for in vivo release of 0.1 mg per day of clonidine for 7 days, it contains:
Active ingredient: 2.5 mg clonidine
CATAPRESAN TTS-2 5 mg transdermal patches (7.0 cm2 of surface)
Scheduled for in vivo release of 0.2 mg per day of clonidine for 7 days, it contains:
Active ingredient: clonidine 5 mg
CATAPRESAN TTS-3 7.5 mg transdermal patches (10.5 cm2 of surface)
Scheduled for in vivo release of 0.3 mg per day of clonidine for 7 days, it contains:
Active ingredient: 7.5 mg clonidine
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Transdermal patches
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Catapresan TTS is indicated in the treatment of all forms of arterial hypertension. Catapresan TTS can be used alone or in combination with other antihypertensive drugs.
04.2 Posology and method of administration
Treatment with Catapresan TTS, to be "adjusted" according to individual therapeutic needs, should be started with Catapresan TTS-1 2.5 mg transdermal patch.
If after 1 or 2 weeks the reduction in blood pressure is not sufficient, the dosage can be increased by adding another 2.5 mg patch or by using the Catapresan TTS-2 5 mg transdermal patch.
An increase in dosage above two 7.5 mg Catapresan TTS patches is not usually accompanied by an increase in efficacy.
When Catapresan TTS is applied for the first time as a replacement for oral therapy with clonidine hydrochloride or other antihypertensive medicinal products, the physician should be aware that the antihypertensive effect exerted by Catapresan TTS transdermal patch may not be achieved for 2-3 days. Therefore it is advisable to gradually reduce the dosage of the medicine in use; some or all of the previous antihypertensive therapies may be maintained, especially in patients with more severe forms of hypertension.
Kidney failure
The dose should be adjusted both as a function of the individual response, which can be highly variable in patients with renal insufficiency, and as a function of the degree of renal impairment.
Continuous monitoring is necessary. Since only a minimal amount of clonidine is removed during routine hemodialysis, no further doses of clonidine are needed after dialysis.
Pediatric population
There is insufficient evidence to support the use of clonidine in children and adolescents under the age of 18 years. The use of clonidine is therefore not recommended in pediatric subjects below 18 years of age.
Instructions for Use
The Catapresan TTS transdermal system should be applied to an area of intact, hairless skin located in the upper chest or upper outer arm once every 7 days. Each new application of Catapresan TTS must take place on a different area of the skin from the previous one. Before application, remove the transparent film placed to protect the adhesive layer of the system. If the TTS transdermal system tends to come off during the 7 days of application, the adhesive patch cover must be applied directly on the system itself to ensure good adhesion. rare cases where it was necessary to change the patch before 7 days to keep blood pressure under control.
1) Apply Catapresan TTS transdermal patch every 7 days on the same day of the week.
2) Choose a "hairless" application area (eg the outer arm or upper chest)
The chosen area must be free from cuts, abrasions, irritations, calluses and scars and must be perfectly dry before applying Catapresan TTS transdermal patch.
It is advisable not to apply Catapresan TTS transdermal patch in skin folds or in sites where it could be constricted by clothing, to avoid premature detachment of the patch.
3) Wash your hands and dry them thoroughly before removing the transdermal system from the wrapping.
4) Wash the selected area with soap and water only and dry it carefully.
5) Open the sachet marked Catapresan TTS (clonidine) and take out the transdermal patch.
6) Remove the protective plastic from the patch avoiding touching the medicated part with your hands.
7) Apply with light pressure on the edges Catapresan TTS transdermal patch on the selected skin area.
Immediately after application, wash your hands.
8) After 7 days, remove the old patch and apply a new one in a different area of the skin, repeating the procedure from step 2 onwards.
How to use the bumper cover
Attention: The adhesive patch cover does not contain any drugs and should not be used alone.
The adhesive patch cover should be applied directly over the Catapresan TTS transdermal patch only if the patch detaches from the skin.
1) Wash your hands with soap and water and dry them carefully.
2) Clean with a dry cloth around the area where the Catapresan TTS transdermal patch is applied and with light pressure make sure that the edges of the Catapresan TTS transdermal patch are in contact with the skin.
3) Open the sachet labeled "Adhesive patch cover" and remove the protective plastic.
4) Apply the adhesive patch cover with light pressure, especially on the edges, directly on Catapresan TTS transdermal patch taking care to position the adhesive patch cover in such a way that Catapresan TTS transdermal patch occupies its center.
04.3 Contraindications
Catapresan TTS should not be used in patients with known hypersensitivity to the active substance or to any other component of the transdermal patch and in patients with severe bradyarrhythmia resulting from sick sinus disease or second or third degree atrioventricular block.
04.4 Special warnings and appropriate precautions for use
Catapresan TTS should be used with caution in patients with mild to moderate bradyarrhythmia such as in case of reduced sinus rhythm, Raynaud's disease and other peripheral or cerebral perfusion disorders, depression, polyneuropathy and constipation.
In case of hypertension caused by pheochromocytoma, the use of Catapresan TTS has not shown any therapeutic effect.
Clonidine, the active ingredient of Catapresan TTS, and its metabolites are extensively excreted by the kidney. In case of renal insufficiency, a particularly careful dosage adjustment is necessary (see section 4.2).
In patients with heart failure or severe coronary artery disease, treatment with Catapresan TTS should be monitored with particular care, as with other antihypertensive drugs.
Patients should be advised not to discontinue therapy until after consulting their physician. Suddenly discontinuing prolonged high-dose Catapresan TTS treatment has led to restlessness, palpitations, rapid rise in blood pressure, nervousness, tremors, headache or nausea. If you wish to discontinue Catapresan TTS therapy, the physician should progressively reduce the dose over 2 - 4 days.
An excessive increase in blood pressure following discontinuation of Catapresan TTS therapy can be reversed by administering oral clonidine hydrochloride or intravenous phentolamine (see section 4.5).
If combined treatment with a beta-blocker requires discontinuation of antihypertensive therapy, the beta-blocker should always be gradually discontinued first and then the clonidine.
In patients who have experienced a local skin reaction to Catapresan TTS, switching to oral clonidine therapy may be associated with the development of a generalized rash.
Patients should be instructed to consult their physician promptly about the removal of the patch if they observe moderate to severe localized erythema and / or blistering of the patch application site or a generalized rash.
If a patient observes minor, isolated, local skin irritation within 7 days of applying the patch, it can be removed and replaced with a new one applied to another skin area.
Catapresan TTS should not be discontinued during the surgical period. Blood pressure should be carefully monitored during surgery and additional pressure control measures should be available if needed.
When considering initiating therapy with Catapresan TTS during the perioperative period, it should be considered that therapeutic plasma levels are not reached until 2 - 3 days after the initial application of Catapresan TTS (see section 4.2).
Catapresan TTS must be removed prior to defibrillation or cardioversion surgery due to the potential alteration of electrical conductivity, which can increase the risk of arcing, a phenomenon associated with the use of defibrillators. Since Catapresan TTS contains aluminum, it is recommended that it be removed prior to use. MRI Patient Skin burns have been reported at the patch application site in several patients who wore an aluminum-containing transdermal patch during magnetic resonance imaging (MRI).
Patients using contact lenses should be advised that treatment with Catapresan TTS may result in reduced lacrimation.
The use and safety of use of clonidine in children and adolescents has not been reflected in randomized controlled trials; therefore, use in this patient population cannot be recommended. In particular, when clonidine is used off-label in combination with methylphenidate in children with ADHS (attention deficit hyperactivity disorder), serious adverse reactions have been observed , including death. Therefore, the use of clonidine in this combination is not recommended.
04.5 Interactions with other medicinal products and other forms of interaction
The antihypertensive effect of Catapresan TTS can be enhanced by concomitant administration of other drugs used to lower blood pressure. This can be used therapeutically by administering other types of antihypertensive agents such as diuretics, vasodilators, beta-blockers, calcium channel blockers and ACE inhibitors, but not alpha1-blockers.
Substances that raise blood pressure or induce retention of sodium and water ions, such as non-steroidal anti-inflammatories, may reduce the efficacy of clonidine.
Substances with α2-blocking activity, such as phentolamine or tolazoline, may inhibit the α2 receptor mediated effects of clonidine in a dose dependent manner.
Concomitant administration of substances with negative chronotropic or dromotropic activity such as beta-blockers or digitalis glycosides may cause or potentiate rhythm disturbances in bradycardias.
It cannot be excluded that concomitant administration of a beta-blocker may cause or potentiate peripheral vascular dysfunction.
The antihypertensive effect of clonidine can be reduced or abolished and the phenomena of altered orthostatic regulation can be caused or aggravated by the concomitant administration of tricyclic or neuroleptic antidepressants with alpha-blocking activity.
The effects of CNS inhibitors, or the effects of alcohol, may be enhanced by clonidine.
04.6 Pregnancy and lactation
No suitable and controlled studies have been conducted in pregnant women.
During pregnancy, Catapresan TTS, like any other medicine, should only be administered when clearly needed. In this case, close monitoring of the mother and baby is recommended.
Clonidine crosses the placental barrier and can slow the heart rate of the fetus.
There is insufficient experience regarding the long-term effects of prenatal drug exposure. Oral forms of clonidine are preferred during pregnancy.
Intravenous administration of clonidine should be avoided.
Preclinical studies conducted with clonidine in rats and rabbits did not show teratogenic effects. In rats, increased resorption values were observed following oral administration of clonidine (see section 5.3).
A transient increase in blood pressure cannot be excluded post partum in the newborn.
Due to the lack of supporting data, the use of Catapresan TTS during breastfeeding is not recommended.
No clinical studies concerning the possible effects of clonidine on human fertility have been conducted.
Animal studies with clonidine have not shown direct or indirect harmful effects with respect to fertility indices.
04.7 Effects on ability to drive and use machines
No studies have been performed to evaluate the effects on the ability to drive and use machines.
However, during treatment with Catapresan TTS, patients should be warned of the possible side effects that they may experience, such as: dizziness, sedation and disturbed accommodation. Therefore, special care should be recommended when driving a vehicle or operating machinery. If patients experience any of the aforementioned side effects, potentially hazardous activities such as driving or operating machinery should be avoided.
04.8 Undesirable effects
Most of the side effects experienced during treatment with Catapresan TTS were mild and tended to decrease with continued therapy.
Adverse reactions are listed below by system organ class and frequency, according to the following categories:
very common ≥ 1/10;
common ≥ 1/100
uncommon ≥ 1 / 1,000
rare ≥ 1 / 10,000
very rare
not known frequency cannot be estimated from the available data.
Psychiatric disorders:
Common: depression, sleep disturbances.
Uncommon: confusional state, delusional perception, hallucinations, decreased libido, nightmares.
Nervous system disorders:
Very common: dizziness, sedation.
Common: headache, somnolence.
Uncommon: paraesthesia.
Eye disorders:
Uncommon: accommodation disturbances.
Rare: reduced lacrimation.
Cardiac pathologies:
Uncommon: bradyarrhythmia, sinus bradycardia.
Rare: atrioventricular block.
Vascular pathologies:
Very common: orthostatic hypotension.
Uncommon: Raynaud's syndrome.
Respiratory, thoracic and mediastinal disorders:
Rare: dryness of the nasal mucosa.
Gastrointestinal disorders:
Very common: dry mouth.
Common: constipation, nausea, salivary gland pain, vomiting.
Rare: colonic pseudo-obstructions.
Skin and subcutaneous tissue disorders:
Very common: application site erythema.
Common: Application site irritation, application site burning, application site discoloration.
Uncommon: application site papules, application site dermatitis, urticaria, pruritus, rash.
Rare: alopecia.
Reproductive system and breast disorders:
Common: erectile dysfunction.
Rare: gynecomastia.
General disorders and administration site conditions:
Common: application site pain, fatigue.
Uncommon: malaise.
Diagnostic tests:
Rare: increase in blood sugar.
04.9 Overdose
Symptoms
Clonidine is characterized by a wide therapeutic range. Clonidine intoxication is manifested by a general depression of the sympathetic nervous system, which can cause constriction of the pupil, lethargy, bradycardia, hypotension, hypothermia, somnolence up to coma, respiratory depression including apnea. Paradoxical hypertension may also occur following stimulation of peripheral α1 receptors.
Rarely, there have been reports of Catapresan TTS poisoning due to accidental or intentional ingestion of patches. Most of these cases involve children.
Treatment
Careful monitoring and symptomatic measures.
There is no specific antagonist for clonidine overdose. If symptoms of overdose occur following skin application of the patch, all transdermal patches should be removed. After removal of the patch, plasma levels of clonidine persist for approximately 8 hours, then decline slowly over a period of several days.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: imidazoline receptor agonists, ATC code: C02AC01.
Clonidine stimulates the alpha-adrenoreceptors of the brainstem, causing a reduction in sympathetic outflow and consequently a decrease in peripheral resistance, renal vascular resistance, heartbeat and blood pressure. Renal blood flow and glomerular filtration rate remain essentially unchanged Normal postural reflexes are not altered, so orthostatic effects are mild and infrequent.
During long-term therapy with clonidine, cardiac output tends to return to standard values, while peripheral resistance remains low. A decrease in heart rate has been observed in most patients treated with clonidine, but the drug does not alter the normal haemodynamic response to exercise.
Tolerance to the antihypertensive effect of clonidine may develop in some patients; in such cases, therapy should be re-evaluated.
The efficacy of clonidine in the treatment of hypertension was evaluated in 5 clinical studies in the pediatric population.
The efficacy data confirm the properties of clonidine in reducing systolic and diastolic blood pressure.
However, due to limited data and methodological shortcomings, no definitive conclusions can be drawn on the use of clonidine in hypertensive children.
The efficacy of clonidine has also been evaluated in some clinical trials in pediatric patients with ADHS, Tourette's syndrome and stuttering. The efficacy of clonidine in these situations has not been demonstrated.
Clonidine was not shown to be effective in two small pediatric clinical trials in the treatment of migraine.
In pediatric clinical trials the most frequent undesirable effects were somnolence, dry mouth, headache, dizziness and insomnia. Such side effects could have a serious impact on children's daily activities.
Overall, the safety and efficacy of clonidine in children and adolescents have not been established (see section 4.2).
05.2 Pharmacokinetic properties
Clonidine is released from Catapresan TTS at a relatively constant rate of 4.32 ± 1.68 mcg / h over 7 days. Steady-state blood clonidine levels are reached within three days after applying the patch to the upper, outer arm, and increase proportionally to the size of the patch. Using 3.5 cm2 patches, 7, 0 cm2 and 10.5 cm2 mean steady-state plasma concentrations are approximately 0.4 ng / mL, 0.8 ng / mL, and 1.1 ng / mL, respectively. Similar steady-state concentrations are achieved by applying the patch in the chest area. Effective plasma concentrations of clonidine are reached 2-3 days after applying the first patch. After removing the patch and applying a new one of the same size, steady-state blood clonidine levels remain unchanged.
The kinetic parameters of clonidine were calculated based on plasma concentrations following intravenous administration. The absolute bioavailability of clonidine released from a Catapresan TTS patch is approximately 60%. The apparent volume of distribution (Vz) of clonidine is 197 L (2.9 L / kg). The medicine crosses both the blood brain barrier and the placental barrier. Plasma protein binding is 30 - 40%.
Clonidine has a total clearance of 177 ml / min and a renal clearance of 102 ml / min.
The plasma elimination half-life of clonidine following intravenous administration is approximately 13 hours. After removal of the patch, plasma concentrations of clonidine slowly decrease with a half-life of approximately 20 hours, indicating slower absorption of clonidine. released by Catapresan TTS. In patients with severely impaired renal function, the elimination half-life from the blood may increase up to 41 hours.
In an excretion balance study, the cumulative renal excretion (3-5 days) of the radioactive tracers bound to the active substance (parent compound and all metabolites) accounted for 65% and the total radioactivity excreted in the faeces, subsequently at oral administration, it was 22%.
About 40-60% of the total radioactivity recovered in the urine in 24 hours is attributable to the unchanged parent compound.The remainder of the radioactivity in the urine is represented by 5 metabolites of clonidine, which are mainly formed in the liver and which are pharmacologically inactive.
05.3 Preclinical safety data
Single dose toxicity studies with clonidine have shown oral LD50 values of approximately> 15 mg / kg (dog) to 150 mg / kg (monkey). Following subcutaneous administration the LD50 values were> 3 mg / kg in the dog and 153 mg / kg in the rat. Following intravenous administration the LD50 values ranged from 6 mg / kg (dog) to
Following administration of the drug and regardless of the route of administration, signs of toxicity, exophthalmos, ataxia and tremor have been observed. Furthermore, excitement and aggression alternating with sedation (mouse, rat, dog), salivation and tachypnea (dog), hypothermia and apathy (monkey) were observed.
In repeated oral dose toxicity studies (lasting 18 months in the rat and 52 weeks in the dog), clonidine was well tolerated at oral doses of 0.1 mg / kg / day (rat) and 0.03 mg / kg / day (dog). In a 52-week monkey study, the no observable adverse effect dose (NOAEL) following oral administration was 1.5 mg / kg / day. In a 13-week rat study, the NOAEL following subcutaneous administration was 0.05 mg / kg / day.
In intravenous studies, rabbits and dogs tolerated doses of 0.01 mg / kg / day and 0.1 mg / kg / day of clonidine for 5 and 4 weeks, respectively.
Higher doses caused hyperactivity, aggression, reduced food intake and weight gain (rat), sedation (rabbit) or cardio- and hepato-megalia with increased plasma levels of GPT, alkaline phosphatase and alpha-globulin and focal liver necrosis (dog).
No teratogenic potential was shown following oral administration of 2.0 mg / kg / day in mice and rats and 0.09 mg / kg / day in rabbits or following subcutaneous administration (of 0.016 mg / kg / day in the rat) and following intravenous administration (of 0.15 mg / kg in the rabbit).
In rats, increases in the incidence of resorption were observed at oral doses ≥ 0.015 mg / kg / day (equivalent to approximately 1/8 of the maximum recommended human daily dose (MRHDD) on a mg / m2 basis), depending on the duration of treatment.
In rats, oral doses up to 0.15 mg / kg / day (approximately the maximum recommended daily human dose calculated on a mg / m2 basis) did not alter the fertility index and the peri- and postnatal development of the progeny. .
The Ames and micronucleus tests in mice gave no indication of mutagenic potential. In a rat carcinogenicity study, clonidine was not found to be tumorigenic.
Intravenous and intra-arterial administration in guinea pigs and rabbits did not indicate any tendency to cause local irritation or sensitization.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
CATAPRESAN TTS-1 2.5 mg transdermal patches (3,5 cm2 of surface)
Excipients and support:
light mineral oil; polyisobutylene 1,200,000; polyisobutylene 35,000; precipitated silica.
Film consisting of:
medium density polyethylene, polyester aluminum and ethylene vinyl acetate; polypropylene film; polyester film coated with fluorocarbon diacrylate.
CATAPRESAN TTS-2 5 mg transdermal patches (7.0 cm2 of surface)
Excipients and support:
light mineral oil; polyisobutylene 1,200,000; polyisobutylene 35,000; precipitated silica.
Film consisting of:
medium density polyethylene, polyester aluminum and ethylene vinyl acetate; polypropylene film; polyester film coated with fluorocarbon diacrylate.
CATAPRESAN TTS-3 7.5 mg transdermal patches (10.5 cm2 of surface)
Excipients and support:
light mineral oil; polyisobutylene 1,200,000; polyisobutylene 35,000; precipitated silica.
Film consisting of:
medium density polyethylene, polyester aluminum and ethylene vinyl acetate; polypropylene film; polyester film coated with fluorocarbon diacrylate.
06.2 Incompatibility
Not relevant
06.3 Period of validity
3 years
06.4 Special precautions for storage
None.
06.5 Nature of the immediate packaging and contents of the package
Sachet containing the transdermal therapeutic patch: paper / aluminum / low density polyethylene (LDPE) and metallocene linear low density polyethylene (mLLDPE).
Sachet containing the adhesive patch cover: paper / aluminum / copolymer-ethylene-vinyl acetate (EVA).
06.6 Instructions for use and handling
No special instructions.
Unused medicine and waste from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
BOEHRINGER INGELHEIM ITALIA S.p.A.
Reggello (Florence) - Loc. Prulli n. 103 / c
08.0 MARKETING AUTHORIZATION NUMBER
Catapresan TTS-1 2.5 mg transdermal patches: A.I.C. n. 027393014
Catapresan TTS-2 5 mg transdermal patches: A.I.C. n. 027393026
Catapresan TTS-3 7.5 mg transdermal patches: A.I.C. n. 027393038
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
25.01.1993 / 01.02.2008
10.0 DATE OF REVISION OF THE TEXT
AIFA resolution of 16 September 2011
