Catapres (clonidine HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Clonidine hydrochloride, an imidazoline-derivative hypotensive agent, is a centrally acting alpha2-adrenergic agonist.
Clonidine appears to stimulate alpha2-adrenergic receptors in the brainstem, which reduces sympathetic outflow from the CNS and decreases peripheral resistance. The central effects of the drug also reduce renal vascular resistance, heart rate, and blood pressure, although renal blood blow and glomerular filtration rate remain unchanged. Use of clonidine maintains normal postural reflexes, therefore, orthostatic symptoms are mild and infrequent.
In the supine position, a 15-20% decrease in cardiac output with no change in peripheral resistance has been demonstrated in patients receiving clonidine in short-term studies. When tilted to 45 degrees, smaller reductions in cardiac output are observed. During long-term therapy, cardiac output during clonidine therapy tends to return to normal values, while peripheral resistance remains diminished.
Although the pulse rate is slowed in patients receiving clonidine, normal hemodynamic responses to exercise remain unchanged. Tolerance to the antihypertensive effects of clonidine may occur, which can necessitate a reevaluation of therapy. While clonidine causes a reduction in plasma renin activity and reduced excretion of aldosterone and catecholamines, it has not been fully elucidated how these pharmacologic actions contribute to the antihypertensive effect of the drug.
The mechanism of action of clonidine in ADHD management is not known. Acute administration of clonidine stimulates release of growth hormone in children and adults, but the drug does not produce sustained elevation of growth hormone during chronic administration.
Clonidine produces analgesia at presynaptic and postjunctional spinal alpha2-adrenergic receptors by inhibiting the transmission of pain signals to the brain. Clonidine-mediated analgesia is dose-dependent and is limited to regions of the body that are innervated by spinal segments containing analgesic concentrations of the drug. Analgesia resulting from clonidine therapy is not antagonized by opiate antagonists.
Following topical application of a clonidine transdermal system, the absolute bioavailability of clonidine is 60%. The absolute oral bioavailability of oral clonidine is 70-80%. Peak plasma concentrations following oral administration of clonidine (conventional) tablets occur in approximately 3-5 hours.
Peak plasma concentrations following administration of the extended-release oral suspension occur in a median of 7.5 hours. Immediate-release tablets, extended-release tablets, and extended-release oral suspension are not dose-substitutable on a milligram for milligram basis because of pharmacokinetic differences. Peak plasma concentrations of extended-release tablets are approximately 50% lower compared to the immediate-release tablets.
The relative oral bioavailability of clonidine extended-release tablets is 89% of the immediate-release product. The relative oral bioavailability of the extended-release oral suspension is 96.1% compared to an equivalent dose of the extended-release tablet. Food does not influence the pharmacokinetic parameters of immediate or extended-release oral clonidine preparations.
Following initial application of a transdermal system of clonidine, the initial release of the drug saturates skin sites beneath the system. The transdermal system delivers clonidine at an approximately constant rate for 7 days. Steady-state plasma concentrations of clonidine are attained within 3 days after application to the upper arm, and increase linearly with increasing size of the transdermal system.
Mean steady-state concentrations of clonidine are approximately 0.4 ng/mL, 0.8 ng/mL, and 1.1 ng/mL following application of the 3.5 cm2, 7 cm2, and 10.5 cm2 transdermal patch, respectively. Comparable steady-state plasma concentrations are attained after application to the chest. To provide the concentration gradient necessary for controlled release and percutaneous absorption of drug, clonidine transdermal systems contain an excess amount of drug.
Replacement of a transdermal system of the same size at weekly intervals continuously maintains steady-state plasma clonidine concentrations. Following discontinuance of transdermal therapy, therapeutic plasma drug concentrations persist for about 8 hours and then decline slowly over several days; over this time period, blood pressure returns gradually to pretreatment levels.
Blood pressure begins to decrease within 30-60 minutes after an oral dose of clonidine hydrochloride; the maximum decrease occurs in approximately 2-4 hours. The pharmacokinetics of oral clonidine are dose proportional over the dosage range of 0.1-0.6 mg.
Following epidural administration of a single 700 mcg dose of clonidine hydrochloride given over 5 minutes, a mean peak plasma clonidine concentration of 4.4 ng/mL (range: 3-5.8 ng/mL) was reported on average 19 minutes following the epidural injection in healthy individuals. In cerebrospinal fluid (CSF), mean peak clonidine concentrations of 418 ng/mL (range: 163-673 ng/mL) were attained in 26 minutes (range: 15-37 minutes). Mean peak plasma concentrations of clonidine were reported to be higher in women than in men.
Following continuous epidural infusion of clonidine hydrochloride (30 mcg/hour for 14 days in addition to administration of morphine sulfate for patient-controlled analgesia (PCA)) in cancer patients, mean steady-state plasma concentrations were approximately 2.2 and 2.4-2.5 ng/mL on days 7 and 14 of dosing, respectively.
Clonidine is highly lipid soluble and readily distributes into extravascular sites, including the central nervous system. Following epidural infusion, clonidine is rapidly and extensively distributed into CSF and readily partitions into the plasma via epidural veins. In vitro, clonidine is approximately 20-40% bound to plasma proteins, mainly albumin.
Clonidine crosses the placenta and is distributed into milk.
The plasma half-life of clonidine ranges from 12-20 hours in patients with normal renal function. The half-life in patients with severe renal impairment increases up to 41 hours. Compared to men, women have a lower mean plasma clearance and longer mean plasma half-life following epidural clonidine administration.
The elimination half-life from CSF is a mean of 1.3 hours (range: 0.8-1.8 hours).
About 50% of clonidine hydrochloride is metabolized in the liver. In humans, clonidine metabolism results in a major metabolite, p-hydroxyclonidine, which is excreted as unchanged drug in the urine at concentrations <10%.
In humans, 40-60% of an orally administered dose of clonidine hydrochloride (as conventional tablets) is excreted in urine as unchanged drug within 24 hours. Following IV administration of radiolabeled clonidine, 72% of the administered dose is excreted in urine within 96 hours; about 40-50% is excreted as unchanged drug. In humans, less than 10% of a dose usually is excreted as p-hydroxyclonidine.
In patients undergoing hemodialysis, only 5% of a dose was removed into the dialysate. Following continuous epidural infusion of clonidine hydrochloride (30 mcg/hour for 14 days in addition to morphine sulfate administered for patient-controlled analgesia (PCA)) in cancer patients, mean total body clearance of the drug was approximately 279 and 272 mL/minute on days 7 and 14 of dosing, respectively. Body weight normalized clearance of clonidine is higher in pediatric patients 6-17 years of age versus adults and is independent of the dosage over the range of 0.2-0.4 mg per day.
When used as an adjunct to stimulant therapy for ADHD, body-weight normalized clearance of extended-release clonidine was 11% higher in patients receiving concomitant methylphenidate therapy and 44% lower in patients receiving amphetamine therapy.
In vitro studies evaluating the effect of alcohol on the release of clonidine extended-release oral suspension indicated that a significantly faster and more variable release of the drug occurred in the presence of 20% alcohol concentration, but not with 5% or 10% when compared to 0% alcohol.
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Clonidine belongs to a class of drugs known as central alpha agonists.
It works by relaxing blood vessels so blood can flow more easily.
Generic name: clonidine HCl
Pronunciation: (KLON-i-deen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Catapres
Indications
The following indications are listed for Catapres:
- Hypertension
Also known as: Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Systemic Arterial Hypertension.
Dosing
Regardless of the route of administration, to avoid the possibility of precipitating the withdrawal syndrome, clonidine therapy should not be discontinued abruptly.
Dosage of clonidine is expressed in terms of clonidine and clonidine hydrochloride.
Clonidine hydrochloride is administered orally or by epidural infusion; clonidine is administered orally or percutaneously by topical application of a transdermal system.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Clonidine is contraindicated in patients with known hypersensitivity to the drug or to any ingredient or component in the formulation.
*Administration of epidural clonidine is contraindicated in patients receiving anticoagulant therapy, in those with a bleeding diathesis, and in the presence of an injection site infection.
*Administration of epidural clonidine above the C4 dermatome is contraindicated because of inadequate safety data supporting such use.
*Administration of epidural clonidine also is not recommended in most patients with severe cardiovascular disease or in patients who are hemodynamically unstable.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Most adverse effects with clonidine are mild in nature and tend to decrease with continuation of therapy. The most common, dose-related adverse effects include dry mouth, drowsiness, dizziness, constipation, and sedation.
Adverse effects with transdermal clonidine are generally similar to those with oral therapy. The most frequent adverse effects with transdermal clonidine were dry mouth, drowsiness, and local adverse dermatologic effects.
The most frequent adverse effects occurring with clonidine hydrochloride epidural infusion for severe intractable cancer pain were hypotension, postural hypotension, dizziness, anxiety, and dry mouth; asymptomatic bradycardia was also observed in 1 patient. Mean heart rate and blood pressure reductions were also observed in patients receiving clonidine hydrochloride epidural infusion. Upon withdrawal of clonidine, 4 patients also experienced rebound hypertension, of which 1 suffered a cerebrovascular accident.
Adverse effects occurring in >=5% of patients receiving clonidine as monotherapy for ADHD include somnolence, fatigue, irritability, nightmares, insomnia, constipation, and dry mouth. When used as adjunctive therapy to stimulants in ADHD, adverse effects reported in >=5% of patients include somnolence, fatigue, decreased appetite, and dizziness.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
The safety and efficacy of extended-release clonidine tablets and extended-release oral suspension (Onyda(TM) XR) for the treatment of ADHD have been established in pediatric patients 6-17 years of age. Use for this indication is based on evidence from 3 adequate, well-controlled studies, a short-term, placebo-controlled monotherapy study, a short-term, adjunctive therapy study, and a long-term randomized monotherapy study.
Safety and efficacy of oral clonidine hydrochloride, extended-release clonidine (Nexiclon(TM) XR), and clonidine transdermal system for the management of hypertension in children have not been established.
The safety and efficacy of clonidine hydrochloride epidural infusion have been established in pediatric patients who are old enough to tolerate placement and management of an epidural catheter, based on evidence from adequate, well-controlled studies in adults and experience with the use of clonidine in pediatric patients for other indications. Epidural clonidine should be used only in pediatric patients with severe, intractable cancer pain that is unresponsive to epidural or spinal opiates and to other conventional analgesic therapy.
Children may be more likely to experience CNS depression associated with clonidine overdosage than adults. In children, signs of toxicity have occurred with clonidine doses as low as 0.1 mg. Rare cases of clonidine toxicity (many involving children) associated with accidental or deliberate mouthing or ingestion of clonidine transdermal systems have been reported.
The manufacturer of oral clonidine states that because children frequently experience vomiting associated with GI illnesses, they may be particularly susceptible to hypertensive episodes resulting from sudden inability to ingest the drug.
Reproduction studies in rabbits using oral clonidine hydrochloride dosages up to about 3 times the maximum recommended human dosage have not revealed evidence of teratogenicity or embryotoxicity. However, in female rats receiving the drug continuously for 2 months prior to mating, an increased incidence of fetal resorptions occurred with oral dosages as low as one-third the maximum recommended human dosage (1/15th the maximum recommended human dosage on a mg/m2 basis); resorptions were not increased when these or higher dosages (up to 3 times the maximum recommended human dosage) were administered during days 6-15 of gestation. An increased incidence of fetal resorptions was observed when much higher dosages (40 times the maximum recommended human dosage on a mg/kg basis and 4-8 times the maximum recommended human dosage on a mg/m2 basis) were administered to mice and rats during days 1-14 of gestation; the lowest dosage used in the study was 0.5 mg/kg. There are no adequate and controlled studies to date using clonidine in pregnant women, and the drug should be used during pregnancy only when clearly needed.
There is a pregnancy exposure registry available that monitors pregnancy outcomes in women exposed to ADHD medications, including clonidine, during pregnancy. Patients can register by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or by visiting https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/ .
Since clonidine is distributed into milk, the drug should be used with caution in nursing women. The drug is excreted into milk at relative infant doses ranging from 4.1-8.4% of the maternal weight-adjusted dosage. Although in most cases, there were no reported adverse effects in breast-fed infants exposed to clonidine, one infant developed sedation, hypotonia, and apnea after clonidine exposure through breast milk. Monitor infants exposed to clonidine through breast milk for symptoms of hypotension and bradycardia, such as sedation, lethargy, tachypnea and poor feeding. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed infant from exposure to clonidine or the underlying maternal condition.
When conventional clonidine tablets are used for hypertension, the manufacturer states that geriatric patients may benefit from a lower initial dosage of 0.05 mg twice daily. Geriatric patients with hypertension may also benefit from an initial lower dosage when extended-release clonidine tablets (Nexiclon(R) XR) are used.
Geriatric patients may benefit from lower initial dosages of clonidine.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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