What Is Clonidine Transdermal?

Clonidine transdermal patch, the indication is Tourette syndrome (voicing combined with multiple motor tics disorder). .

Drug Name: Clonidine transdermal patch

Drug type: prescription
Use classification: Sympathetic inhibitor

Clonidine transdermal patch ingredients

The main ingredient of this product is clonidine, and its chemical name is [2- (2,6-dichlorophenyl) imino] imidazolidine.
Structural formula:

Molecular formula: C ₉ H ₉ Cl ₂ N ₃
Molecular weight: 230.10

Clonidine transdermal patch properties

This product is a round patch with an adhesive film on the application surface.

Clonidine Transdermal Patch Indication

Tourette syndrome (voicing combined with multiple motor tic disorders).

Clonidine transdermal patch specifications

There are 3 specifications: 1mg / tablet, 1.25cm; 1.5mg / tablet, 1.88cm; 2.0mg / tablet, 2.5cm.

Clonidine transdermal patch usage dosage

usage:

1. Application site: under the scapula of the back (preferred); upper chest; hairless intact skin such as mastoid process behind the ear or outside of upper arm. Replacing a new patch means replacing a new patch with a new patch to facilitate skin respiration and reduce skin irritation.

2. Change every 7 days. Whether to eat or not does not affect the application of this product.

Dosage:

The medication for adolescent patients should start with a small dose of 1.0mg / tablet · day, and gradually increase the dose according to body weight. The maximum dose should not exceed 2.0mg / tablet × 3 tablets.

20 kg weight 40 kg, use 1.0 mg / tablet · week;

40kg weight 60kg, use 1.5mg / tablet · week;

For weights> 60 kg, use 2.0 mg / tablet · week.

Adverse reactions to clonidine transdermal patch

Adverse reactions in clinical trials were treated with clonidine transdermal patches. Most of the adverse reactions were mild. As the treatment progressed, the adverse reactions decreased. In a 3-month, multi-clinical trial involving 101 patients with hypertension, adverse reactions occurred: dry mouth (25), doze (12), fatigue (6), headache (4) , Lethargy and sedation (3 each), insomnia, dizziness, inability / sexual dysfunction, dry throat (2 each), and constipation, nausea, change in taste, nervousness (1 each).
In the aforementioned 3-month clinical trial and other non-controlled trials, the most common adverse reaction was a skin reaction, as described below.
In the 3-month trial, 51 of 101 patients experienced local skin reactions such as erythema (26) and pruritus. Five were allergic to clonidine transdermal patches. Other skin reactions include local blistering (7 persons), hyperpigmentation (5 persons), puffiness (3 persons), epidermal exfoliation (3 persons), burning pain (3 persons), pimples (1 person), and pulsation (1 person) ), Whitening (1 person), and generalized skin rash (1 person).
In other clinical trials, after an average of 37 weeks of treatment, 128 of the 673 subjects (approximately 19 of 100) discontinued the trial due to contact dermatitis. The incidence of contact dermatitis is approximately 34 of 100 white women, approximately 18 of 100 white men, approximately 14 of 100 black women, and approximately 8 of 100 black men. Analysis of skin response data indicates that at 6 and 26 weeks of treatment, the risk of discontinuation of treatment due to contact dermatitis is greatest, although sensitivity may increase early or late in treatment.
In a large-scale clinical trial of the safety and desirability of a patch involving 451 doctors and 3539 subjects, a causal relationship with clonidine transdermal patches was not established.Other allergic reactions recorded include: Papules (10 cases); Rubella (2 cases); Facial edema that affected one subject's speech (2 cases).
Post-marketing adverse reactions to clonidine transdermal patches. Other adverse reactions reported after marketing of the patch are listed below. The incidence or causality of these adverse reactions has not been determined, and the frequency of adverse reactions does not exceed 0.5%.
Systemic reaction fever; discomfort; weakness; paleness; withdrawal symptoms.
Congestive heart failure of the cardiovascular system; cerebrovascular accidents; abnormal electrocardiograms (such as slow heartbeat, sick sinus disorder and arrhythmia, etc.); chest pain; orthostatic symptoms; syncope; elevated blood pressure; blood necrosis; tachycardia; Slow heartbeat; palpitations.
Central and peripheral nervous system / psychiatric transient psychotic disorder; mental depression; audiovisual hallucinations; local numbness; dreaming or nightmares; restlessness; anxiety; agitation; irritability; other behavioral changes;
Dermatological angioedema; local or systemic rash; measles; rubella; contact dermatitis; pruritus; alopecia; local irritation or hyperpigmentation.
Anorexia and vomiting.
Difficulty urinating the urogenital system; loss of sexual desire; reduced sexual activity.
Metabolic male breast development, breast hyperplasia, and weight gain.
Muscle and skeletal muscle or joint pain; leg cramps.
Ophthalmic vision is blurred; burning eyes and dry eyes.
Most of the adverse events associated with oral clonidine were mild, and the side effects decreased as treatment progressed. The most common adverse reactions (probably dose-related) were dry mouth (approximately 40 of 100 patients), drowsiness (approximately 33 of 100 patients), dizziness (approximately 16 of 100 patients), constipation (Approximately 10 out of 100 patients) and sedation (approximately 10 out of 100 patients). The following are reports of adverse reactions that occur infrequently when patients are treated with clonidine transdermal patches. However, the causal relationship of uncommon adverse reactions when combined with other drugs has not been determined. Systemic reactions are weak (approximately 100 patients 10); fatigue (approximately 4 of 100 patients); headache (approximately 1 in 100 patients); withdrawal symptoms (approximately 1 in 100 patients). There are also reports of pale and weak positive Coomb tests, alcohol allergies, and fever.
Cardiovascular orthostatic hypotension (approximately 3 out of 100 patients); palpitations, tachycardia, and bradycardia (approximately 5 of 1000 patients). Fainting, blood necrosis, congestive heart failure, and abnormal electrocardiograms (such as sinus node arrest, slow functional heartbeat, high AV block, and arrhythmia) are rarely reported. Whether combined with digitalis or not, reports of slow sinus beats and AV block are rare.
CNS nervousness and agitation (approximately 3 of 100 patients); depression (approximately 1 of 100 patients); insomnia (approximately 5 of 100 patients); other behavioral changes, dreaming or evil Dreams, irritability, anxiety, audiovisual hallucinations, and temporary mental turmoil are rarely reported.
Skin rash (approximately 1 in 100 patients); pruritus (approximately 7 in 1000 patients); measles, angioedema, and rubella (approximately 5 in 1000 patients); alopecia (1000) There are approximately 2 patients).
Nausea and vomiting in the gastrointestinal tract (approximately 5 out of 100 patients); discomfort and anorexia (approximately 1 in 100 patients); slight anal function (approximately 1 in 100 patients); rarely There have been reports of hepatitis, mumps, constipation, false obstruction, and abdominal pain.
Reduced urogenital sexual activity, impotence and loss of libido (approximately 3 out of 100 patients); nocturia (approximately 1 in 100 patients); difficulty urinating (approximately 2 in 1000 patients); urinary retention (Approximately 1 in 1000 patients).
There are few reports of thrombocytopenia in hematology.
Metabolic weight gain (approximately 1 in 100 patients), male mammary gland development (approximately 1 in 1000 patients), elevated blood glucose or creatine phosphokinase concentrations.
Muscle and skeletal muscle or joint pain (approximately 6 out of 1000 patients), leg cramps (approximately 3 in 1000 patients).
There are few reports of dry mouth, ear, nose, throat, and nasal mucosa.
Ophthalmology has reported dry eyes, burning eyes, and blurred vision.

Clonidine Transdermal Patch Taboo

Those who are allergic to clonidine or inactive ingredients in the patch are contraindicated.
Disabled patients with depression.

Clonidine transdermal patch considerations

Patients should not stop taking the drug without permission of the physician. In some cases, clonidine treatment was abruptly stopped and symptoms such as nervousness, agitation, headache, dizziness, rapid rise in blood pressure, and elevated catecholamine levels in the blood appeared. These symptoms are more likely to occur after stopping clonidine treatment after high-dose therapy or in combination with other -blockers, and treatment that requires special measures. Cases of encephalopathy, cerebrovascular disease, and death have not been reported after clonidine treatment was discontinued. When deciding to discontinue clonidine treatment, the doctor should gradually reduce the dose for more than 24 days to avoid the symptoms being eliminated.
After stopping clonidine patch treatment, if the blood pressure rises sharply, you should take clonidine hydrochloride or inject fentopramine to suppress it. If you use clonidine and other-blockers in combination, stop clonidine patch. The blockade is discontinued for a few days before the clonidine patch is gradually discontinued.
In general, patients who are sensitized by local contact with clonidine patch, continuous treatment with clonidine patch or oral clonidine hydrochloride may produce a general rash.
For patients allergic to clonidine patches, oral clonidine hydrochloride may also cause allergic reactions (including general rash, urticaria, or angioedema).
Patients with severe coronary atresia, conduction disorders, recent myocardial infarction, cerebrovascular disease, or chronic renal failure should be treated with caution.
Medication during the operation Do not interrupt the clonidine patch treatment during the operation, and test the blood pressure of the patient at the same time, if necessary, take other measures to control the blood pressure. Doctors considering the use of clonidine transdermal patches during surgery must understand that clonidine's effective blood concentration can only be reached 2 to 3 days after the patch is applied (see Dosage and Administration).
Cardiac Defibrillation or Cardioversion Prior to defibrillation or cardioversion, clonidine transdermal patches should be removed, as changes in conductivity may cause arcing of the defibrillator.
Clonidine may have a sedative effect, so patients who may perform hazardous tasks such as operating instruments, driving, etc. should be cautious. Such combination with alcohol, barbiturate or other sedative drugs will strengthen this sedative effect.
If moderate or severe erythema or blisters appear on the patch site, or if a rash appears throughout the body, you should consult your doctor immediately if you need to remove the patch.
If the patient has isolated, slight local skin irritation after applying the patch, the patch should be peeled off and a new patch should be put on a new skin site.
Used clonidine patches also contain large amounts of clonidine, which can be harmful if swallowed by infants and children. Therefore, patients should keep used and unused patches out of the reach of children.
There is insufficient data on the use of drugs in pregnant women. Therefore, during pregnancy, use it only when it is particularly needed. Because the drug clonidine hydrochloride is secreted in breast milk, care should be taken by lactating women.

Clonidine transdermal patch for children

The safety and efficacy of medications for children under 12 years of age have not been determined.

Clonidine transdermal patch drug interactions

Clonidine may enhance CNS inhibition by alcohol, barbiturates or other sedatives. If patients taking clonidine hydrochloride also take tricyclic antidepressants, the antihypertensive effect of clonidine may be reduced, so the dose needs to be increased.
Patients who use clonidine with drugs that affect sinus node function or AV conduction, such as digoxin, calcium channel blockers, and beta-blockers, should be used with caution because they may have additive effects such as bradycardia and AV conduction block Stagnation.
Amitriptyline in combination with clonidine promotes corneal damage in mice (see toxicity study).

Clonidine transdermal patch overdose

Blood pressure rises first, then decreases blood pressure, slow heart rate, respiratory depression, decreased body temperature, drowsiness, reduced or lack of reflexes, weakness, irritability, and dilated pupils. The incidence of CNS suppression is higher in children than in adults. Large drug overdose can cause reversible cardiac conduction disorders or arrhythmia, apnea, coma, and sudden attacks. Symptoms of drug overdose usually appear within 30min to 2h. 0.1mg clonidine can cause poisoning in children.
If symptoms of poisoning occur, remove all clonidine transdermal patches. At this time, clonidine's blood concentration will last for about 8 hours, and then slowly decrease for several days. Few incidents of clonidine transdermal patch poisoning due to inadvertent or deliberate swallowing of patches have been reported, including in children.
There is no specific antidote for clonidine overdose. It is impossible to remove clonidine effective amounts with spit syrup vomiting agent and gastric lavage. If swallowing a patch, consider an enema. Taking activated carbon or laxatives can also help. Auxiliary care includes the use of atropine sulfate for bradycardia, intravenous or vasopressors for hypotension, and vasodilators for hypertension. Naloxone can be used to treat clonidine-induced respiratory depression, hypotension, and coma. Because naloxone can cause abnormal hypertension, naloxone should be monitored for blood pressure. Benzozoline produces incoherent results and is not recommended as a first-line drug. Dialysis is unlikely to significantly improve clonidine elimination.
The largest reported drug overdose incident was a 28-year-old male patient ingesting 100 mg of clonidine hydrochloride powder. This patient first had elevated blood pressure, followed by low blood pressure, slow heartbeat, apnea, hallucinations, and a semi-coma, and his ventricles contracted prematurely. The clonidine plasma concentration was 60 ng / mL after 1 h, 190 ng / mL after 1.5 h, 370 ng / mL after 2 h, and 120 ng / mL after 5.5 h and 6.5 h. For mice and rats, the LD50s of oral clonidine were 206 mg / kg and 465 mg / kg, respectively.

Clonidine Transdermal Patch Pharmacology and Toxicology

Pharmacological effects Clonidine stimulates the brain stem alpha-adrenergic receptors. This effect causes a reduction in the impulsive transmission of the sympathetic nerves from the central nervous system, thereby reducing peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Renal blood flow and glomerular filtration rate remained essentially unchanged. Normal orthostatic reflexes do not change; therefore, erect symptoms are mild and rare.
Acute human studies of clonidine hydrochloride have shown that the cardiac output in the supine position is appropriately reduced (15% to 20%), and the peripheral resistance is unchanged. When the tilt is 45 °, the cardiac output is slightly reduced, and the peripheral resistance is reduced. During long-term treatment, cardiac output tends to return to the control value, while peripheral resistance remains reduced. It has been observed that most patients using clonidine have slowed pulse rates, but the drug does not alter the normal hemodynamic response caused by exercise.
Some patients may develop tolerance to hypotensive effects, so it is necessary to re-evaluate the treatment. Other human studies have provided evidence of reduced plasma renin activity and decreased excretion of aldosterone and catecholamines. The exact relationship between these pharmacological effects and the antihypertensive effect of clonidine has not been fully elucidated.
Clonidine strongly stimulates the release of growth hormone in children and adults, but long-term use does not cause a chronic increase in growth hormone.
Toxicity studies Acute toxicity was combined with amitriptyline. Clonidine hydrochloride can cause corneal damage in rats within 5 days.
Chronic Toxicity In oral clonidine hydrochloride tests in rats over 6 months, the incidence of spontaneous retinal degeneration and the severity of the condition were dose-dependent and increased with increasing dose. Tissue distribution tests in dogs and monkeys have shown clonidine in the choroid.
Genotoxicity In the mutant Ames test and murine micronucleus rupture test, no genetic toxicity was observed.
Reproductive toxicity was administered to male or female mice at a dose of up to 150 mcg / kg (approximately 3 times the MRDHD). No reproductive effects were found in the mice. In a separate test, a dose of 500 to 2000 mcg / kg (based on mg / Calculated in kg, 10 to 40 times the oral MRDHD; calculated in mg / m, 2 to 8 times the MRDHD) was administered to female mice, and it was found that female mice's reproductive properties were affected.
The clonidine hydrochloride reproduction test was performed on rabbits at a dose of approximately three times the recommended maximum daily human oral dose (as indicated by MRDHD). No significant fertility defects or potential animal embryo toxicity were found. However, for female mice, continued administration for 2 months before mating, 1/3 of clonidine oral MRDHD (calculated based on mg / m, 1/5 of MRDHD) can increase absorption; for pregnant 6- Rats at 14 days were administered at the same dose or at higher doses (3 times the amount of oral MRDHD), and the results showed that the increased absorption was independent of treatment; however, for mice and rats at 1-14 days of pregnancy, Administration at very high doses (calculated based on mg / kg, 40 times the oral MRDHD; calculated based on mg / m, 4-8 times the amount of MRDHD) showed an increase in absorption (the lowest dose tested was 500 g / kg).
Carcinogenic effects Long-term administration to rats and mice at a dose of 46-70 times the recommended maximum daily dose (in mg / kg) for rats for 132 and 78 weeks, respectively, did not show clonidine to have a carcinogenic effect (based on mg / m Calculated as 6 or 9 times the amount of MRDHD).

Pharmacokinetics of clonidine transdermal patch

The clonidine blood concentration half-life is 12.7 ± 7h. When administered orally, about 40% -60% of the absorbed amount is in the urine, and the drug remains unchanged within 24h, and the remaining absorbed amount is metabolized in the liver.
The clonidine transdermal patch reaches a steady-state blood concentration after 2-3 days of administration, and is released at a constant rate within 7 days. After removing the patch, the plasma clonidine treatment concentration can still be maintained for 24 hours, and then gradually reduced within a few days. This is because after removing the patch, the drug stored in the local skin can still maintain the blood concentration for 24 hours and then gradually decrease. The plasma concentration-time curve after clonidine transdermal patch was administered to 24 subjects is shown below:

Clonidine Transdermal Patch Storage

Shaded and sealed.

Clonidine transdermal patch packaging

Paper / AL / PE composite film bag

Clonidine transdermal patch expiration date

2 years ^[1]