Clonidine
Patch, Extended Release · Transdermal, Oral, Epidural
Uses
Clonidine extended-release tablets are indicated in the treatment of hypertension. Clonidine extended-release tablets may be employed alone or concomitantly with other antihypertensive agents. Clonidine extended-release tablets are a central alpha-adrenergic agonist indicated for: Treatment of hypertension ( 1 )
Dosage and administration
The dose of clonidine extended-release tablets must be adjusted according to the patient's individual blood pressure response. The following is a general guide to its administration in adults. Initial dose: 0.17 mg once daily. Elderly patients may benefit from a lower initial dose. Initial dose is recommended to be administered at bedtime. ( 2.1 ) Maintenance dose: Further increments of 0.09 mg once daily may be made at weekly intervals if necessary until the desired response is achieved. The therapeutic doses most commonly employed have ranged from 0.17 mg to 0.52 mg once daily. ( 2.2 ) Patients with renal impairment: Up-titrate slowly (2.4) 2.1 Initial Dose Dosing with clonidine extended-release tablets should be initiated at 0.17 mg once daily. Elderly patients may benefit from a lower initial dose [ see Use in Specific Populations (8.4) ]. Initial dose is recommended to be administered at bedtime. 2.2 Maintenance Dose Further increments of 0.09 mg once daily may be made at weekly intervals if necessary until the desired response is achieved. The therapeutic doses most commonly employed have ranged from 0.17 mg to 0.52 mg once daily. Clonidine extended-release tablets were studied at doses of 0.17 to 0.52 mg once daily. Doses higher than 0.52 mg per day were not evaluated and are not recommended. 2.3 Patients Currently Using Clonidine Hydrochloride Immediate-Release Tablets The recommended dose of clonidine extended-release tablets for patients who are currently taking clonidine hydrochloride immediate-release tablets is provided in the table below. Clonidine Extended-Release Tablets Equivalent dose of Clonidine HCl Immediate-Release Tablets Initial Dose 0.17 mg once daily 0.1 mg twice daily Maintenance Dose Titration Increments 0.09 mg once daily 0.05 mg twice daily Common Doses Used for Blood Pressure Effect 0.17 mg once daily 0.1 mg twice daily 0.34 mg once daily 0.2 mg twice daily 0.52 mg once daily 0.3 mg twice daily 2.4 Renal Impairment Adjust dosage according to the degree of impairment. In patients with end stage kidney disease on maintenance dialysis, start at 0.09 mg per day and up-titrate slowly to minimize dose related adverse events. Monitor patients carefully, especially for bradycardia, sedation and hypotension. Only a minimal amount of clonidine is removed during routine hemodialysis. In patients with moderate to severe kidney impairment not undergoing dialysis, initiate clonidine at the same dose as for patients without renal impairment. Up-titrate slowly and monitor for dose-related adverse events.
Dosage forms and strengths
0.17 mg Extended-Release Tablets (clonidine base) 0.26 mg Extended-Release Tablets (clonidine base) Extended-Release Tablets: 0.17, 0.26 mg clonidine base
Contraindications
Clonidine extended-release tablets should not be used in patients with known hypersensitivity to clonidine [ see Warnings and Precautions (5.2) ]. Known hypersensitivity to clonidine (rash, angioedema) (4)
Warnings and precautions
Patients should not discontinue therapy without consulting a physician. Dose reduction should be performed gradually over a 2- to 4-day period to avoid withdrawal symptomatology. Rare instances of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after clonidine withdrawal. ( 5.1 ) Monitor closely and up-titrate slowly in patients with severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease, or chronic renal failure. ( 5.2 ) Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of a possible sedative effect of clonidine. ( 5.2 ) In perioperative use, clonidine extended-release tablets may be administered up to 28 hours prior to surgery and resumed the following day. ( 5.3 ) 5.1 Withdrawal Instruct patients not to discontinue therapy without consulting their physician. Sudden cessation of clonidine treatment has resulted in symptoms such as nervousness, agitation, headache, and tremor accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma. The likelihood of such reactions to discontinuation of clonidine therapy appears to be greater after administration of higher doses or continuation of concomitant beta-blocker treatment and special caution is therefore advised in these situations. Rare instances of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after clonidine withdrawal. When discontinuing therapy with clonidine extended-release tablets, reduce the dose gradually over 2 to 4 days to avoid withdrawal symptoms. An excessive rise in blood pressure following discontinuation of clonidine extended-release tablets can be reversed by administration of oral clonidine hydrochloride or by intravenous phentolamine. If therapy is to be discontinued in patients receiving a beta-blocker and clonidine concurrently, the beta-blocker should be withdrawn several days before the gradual discontinuation of clonidine extended-release tablets. Because children commonly have gastrointestinal illnesses that lead to vomiting, they may be particularly susceptible to hypertensive episodes resulting from abrupt inability to take medication. 5.2 General Precautions In patients who have developed localized contact sensitization to a clonidine transdermal system, substitution of oral clonidine therapy may be associated with the development of a generalized skin rash. In patients who develop an allergic reaction to a clonidine transdermal system, substitution of oral clonidine may also elicit an allergic reaction (including generalized rash, urticaria, or angioedema). Monitor carefully and up-titrate slowly in patients with severe coronary insufficiency, conduction disturbances, recent myocardial infarction, cerebrovascular disease, or chronic renal failure. Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of a possible sedative effect of clonidine. The sedative effect may be increased by concomitant use of alcohol, barbiturates, or other sedating drugs. 5.3 Perioperative Use Clonidine extended-release tablets may be administered up to 28 hours prior to surgery and resumed the following day. Blood pressure should be carefully monitored during surgery and additional measures to control blood pressure should be available if required.
Side effects
The following serious adverse reactions are discussed in detail elsewhere in the labeling: Withdrawal [ see Warnings and Precautions (5.1) ] Allergic reactions [ see Warnings and Precautions (5.2) ] There is very little experience with clonidine extended-release tablets in controlled trials. Based on this limited experience, the adverse event profile appears similar with the immediate-release clonidine formulation. The most commonly expected adverse reactions are dry mouth, drowsiness, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact TruPharma, LLC at 1-877-541-5504 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clonidine Extended-Release Tablets Clinical Trial Experience There is very limited experience with clonidine extended-release tablets in controlled trials. Based on this limited experience, the adverse event profile appears similar with to the immediate-release clonidine formulation. 6.2 Experience with Immediate-Release Clonidine Most adverse reactions are mild and tend to diminish with continued therapy. The most frequent (which also appear to be dose-related) are dry mouth (approximately 40%); drowsiness (approximately 33%); dizziness (approximately 16%); constipation and sedation (approximately 10% each). The following less frequent adverse reactions have also been reported in patients receiving immediate-release clonidine, but in many cases patients were receiving concomitant medication and a causal relationship has not been established. Body as a Whole: Fatigue, fever, headache, pallor, weakness, and withdrawal syndrome. Also reported were a weakly positive Coombs’ test and increased sensitivity to alcohol. Cardiovascular: Bradycardia, congestive heart failure, electrocardiographic abnormalities (i.e., sinus node arrest, junctional bradycardia, high degree AV block and arrhythmias), orthostatic symptoms, palpitations, Raynaud’s phenomenon, syncope, and tachycardia. Cases of sinus bradycardia and atrioventricular block have been reported, both with and without the use of concomitant digitalis. Central Nervous System (CNS): Agitation, anxiety, delirium, delusional perception, hallucinations (including visual and auditory), insomnia, mental depression, nervousness, other behavioral changes, paresthesia, restlessness, sleep disorder, and vivid dreams or nightmares. Dermatological: Alopecia, angioneurotic edema, hives, pruritus, rash, and urticaria. Gastrointestinal: Abdominal pain, anorexia, constipation, hepatitis, malaise, mild transient abnormalities in liver function tests, nausea, parotitis, pseudo-obstruction (including colonic pseudo-obstruction), salivary gland pain, and vomiting. Genitourinary: Decreased sexual activity, difficulty in micturition, erectile dysfunction, loss of libido, nocturia, and urinary retention. Hematologic: Thrombocytopenia. Metabolic: Gynecomastia, transient elevation of blood glucose or serum creatine phosphokinase, and weight gain. Musculoskeletal: Leg cramps and muscle or joint pain. Oro-otolaryngeal: Dryness of the nasal mucosa. Ophthalmological: Accommodation disorder, blurred vision, burning of the eyes, decreased lacrimation, and dryness of eyes.
Drug interactions
No drug interaction studies have been conducted with clonidine extended-release tablets. The following have been reported with other oral formulations of clonidine. Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. If a patient receiving clonidine hydrochloride is also taking tricyclic antidepressants, the hypotensive effect of clonidine may be reduced, necessitating an increase in the clonidine dose. Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction, e.g., digitalis, calcium channel blockers, and beta-blockers. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil. Amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats [ see Nonclinical Toxicology (13.2) ]. Alcohol: Based on in vitro studies, high concentration of alcohol may increase the rate of release of clonidine extended-release tablets. Sedating drugs: Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. ( 7 ) Tricyclic antidepressants: May reduce the hypotensive effect of clonidine, necessitating an increase in clonidine dose. ( 7 ) Drugs known to affect sinus node function or AV nodal conduction (e.g., digitalis, calcium channel blockers, beta-blockers): Additive effects such as bradycardia and AV block. ( 7 )
Use in specific populations
Pregnancy Category C ( 8.1 ) Clonidine is secreted in human milk. ( 8.2 ) Safety and effectiveness in children have not been established. ( 8.3 ) Renal impairment: Dose may need adjustment. ( 2.4 ) 8.1 Pregnancy Pregnancy Category C. Reproduction studies performed in rabbits at doses up to approximately 3 times the oral maximum recommended daily human dose (MRDHD) of clonidine hydrochloride produced no evidence of a teratogenic or embryotoxic potential in rabbits. In rats, however, doses as low as 1/3 the oral MRDHD (1/15 the MRDHD on a mg/m 2 basis) of clonidine were associated with increased resorptions in a study in which dams were treated continuously from 2 months prior to mating. Increased resorptions were not associated with treatment at the same time or at higher dose levels (up to 3 times the oral MRDHD) when the dams were treated on gestation days 6 to 15. Increases in resorption were observed at much higher dose levels (40 times the oral MRDHD on a mg/kg basis; 4 to 8 times the MRDHD on a mg/m 2 basis) in mice and rats treated on gestation days 1 to 14 (lowest dose employed in the study was 500 mcg/kg). No adequate, well-controlled studies have been conducted in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. 8.2 Nursing Mothers Clonidine is secreted in human milk. 8.3 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.4 Geriatric Use Elderly patients may benefit from a lower initial dose [ see Dosage and Administration (2) ]. 8.5 Patients with Renal Impairment The initial dosage should be based on the degree of impairment. Monitor patients carefully for hypotension and bradycardia, and titrate to higher doses cautiously. Only a minimal amount of clonidine is removed during routine hemodialysis.
Overdosage
Hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, weakness, irritability and miosis. The frequency of CNS depression may be higher in children than adults. Large overdoses may result in reversible cardiac conduction defects or dysrhythmias, apnea, coma, and seizures. Signs and symptoms of overdose generally occur within 30 minutes to two hours after exposure. As little as 0.1 mg of clonidine has produced signs of toxicity in children. There is no specific antidote for clonidine overdosage. Clonidine overdosage may result in the rapid development of CNS depression; therefore, induction of vomiting with ipecac syrup is not recommended. Gastric lavage may be indicated following recent and/or large ingestions. Administration of activated charcoal and/or a cathartic may be beneficial. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension and vasodilators for hypertension. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension and/or coma; blood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Tolazoline administration has yielded inconsistent results and is not recommended as first-line therapy. Dialysis is not likely to significantly enhance the elimination of clonidine. The largest overdose reported to date involved a 28-year old male who ingested 100 mg of clonidine hydrochloride powder. This patient developed hypertension followed by hypotension, bradycardia, apnea, hallucinations, semicoma, and premature ventricular contractions. The patient fully recovered after intensive treatment. Plasma clonidine levels were 60 ng/mL after 1 hour, 190 ng/mL after 1.5 hours, 370 ng/mL after 2 hours, and 120 ng/mL after 5.5 and 6.5 hours. In mice and rats, the oral LD 50 of clonidine is 206 and 465 mg/kg, respectively.
Description
Clonidine extended-release tablets are available for oral administration in two dose strengths: 0.17 mg and 0.26 mg. The 0.17 mg and 0.26 mg tablets are equivalent to 0.2 mg and 0.3 mg of immediate-release clonidine hydrochloride, respectively. Clonidine hydrochloride, a centrally active alpha-adrenergic agonist, is an imidazoline derivative and exists as a mesomeric compound. The chemical name is 2-(2.6-dichlorophenylamino)-2-imidazoline hydrochloride. The following is the structural formula: C 9 H 9 C l2 N 3 ·HCl Mol. Wt. 266.56 Clonidine hydrochloride is an odorless, bitter, white crystalline substance soluble in water and alcohol. The inactive ingredients are: crospovidone, dental-type silica, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl acetate, povidone, sodium polystyrene sulfonate, triacetin. The 0.17 mg tablet also contains hypromellose, polyethylene glycol, and titanium dioxide. The 0.26 mg tablet also contains D&C yellow #10 aluminum lake, FD&C yellow #6 aluminum lake, fractionated coconut oil, maltodextrin, polydextrose, talc, and titanium dioxide. molecularstructure
How supplied
Clonidine Extended-Release Tablets are scored, splitable, capsule-shaped coated tablets that are supplied in bottles of 30. Strength Color Markings NDC 0.17 mg White NP 2 52817-375-30 Store at 20º to 25ºC (68º to 77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container with a child-resistant closure.
Patient information
Caution patients against interruption of clonidine extended-release tablet therapy without their healthcare provider’s advice. Advise patients who engage in potentially hazardous activities, such as operating machinery or driving, of a possible sedative effect of clonidine. The sedative effect may be increased by concomitant use of alcohol, barbiturates, or other sedating drugs.
Label text from the FDA structured product label by TruPharma, LLC (revised Jan 11, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Clonidine in 9 products
- Clonidine Hydrochloride in 3 products
Clonidine NDC products (12)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 75907-023 | Clonidine .1 mg/24h Patch, Extended Release | Dr. Reddy's Labratories Inc. | ANDA |
| 75907-024 | Clonidine .2 mg/24h Patch, Extended Release | Dr. Reddy's Labratories Inc. | ANDA |
| 75907-025 | Clonidine .3 mg/24h Patch, Extended Release | Dr. Reddy's Labratories Inc. | ANDA |
| 50742-247 | Clonidine Hydrochloride .1 mg/1 Tablet, Extended Release | Ingenus Pharmaceuticals, LLC | ANDA |
| 51862-455 | Clonidine .3 mg/24h Patch, Extended Release | Mayne Pharma Inc. | ANDA |
| 0378-0871 | Clonidine .1 mg/d Patch | Mylan Pharmaceuticals Inc. | ANDA |
| 0378-0872 | Clonidine .2 mg/d Patch | Mylan Pharmaceuticals Inc. | ANDA |
| 0378-0873 | Clonidine .3 mg/d Patch | Mylan Pharmaceuticals Inc. | ANDA |
| 39822-2000 | Clonidine Hydrochloride 100 ug/mL Injection, Solution | XGen Pharmaceuticals DJB, Inc. | ANDA |
| 39822-2010 | Clonidine Hydrochloride 500 ug/mL Injection, Solution | XGen Pharmaceuticals DJB, Inc. | ANDA |
| 68134-603 | Clonidine .17 mg/1 Tablet, Extended Release | PALMETTO PHARMACEUTICALS INC. | NDA AUTHORIZED GENERIC |
| 52817-375 | Clonidine .17 mg/1 Tablet, Extended Release | TruPharma, LLC | NDA AUTHORIZED GENERIC |
Clonidine recalls
- D-1152-2022 Jun 29, 2022 · Class II · Terminated
Defective Delivery System: Out of specification for release liner removal force results at the 3-month CRT stability timepoint. - D-1084-2019 Apr 17, 2019 · Class III · Terminated
Labeling: Label Error on Declared Strength: Side carton panel incorrectly lists the concentration as "500 mcg Clonidine Hydrochloride" rather than the correct concentration of "100 mcg Clonidine Hydrochloride" per mL. - D-1444-2014 Jul 30, 2014 · Class III · Terminated
Labeling: Label Error On Declared Strength: The side label description incorrectly states "Each mL contains 500 mcg Clonidine Hydrochloride" instead of stating "Each mL contains 100 mcg Clonidine Hydrochloride".
Frequently asked questions
What is Clonidine used for?
Clonidine extended-release tablets are indicated in the treatment of hypertension. Clonidine extended-release tablets may be employed alone or concomitantly with other antihypertensive agents. Clonidine extended-release tablets are a central alpha-adrenergic agonist indicated for: Treatment of hypertension ( 1 )
What are the side effects of Clonidine?
The following serious adverse reactions are discussed in detail elsewhere in the labeling: Withdrawal [ see Warnings and Precautions (5.1) ] Allergic reactions [ see Warnings and Precautions (5.2) ] There is very little experience with clonidine extended-release tablets in controlled trials. Based on this limited experience, the adverse event profile appears similar with the immediate-release… See the full label for the complete list.
Who makes Clonidine?
Clonidine is listed by 7 labelers in the FDA NDC directory, including Dr. Reddy's Labratories Inc., Ingenus Pharmaceuticals, LLC, Mayne Pharma Inc., Mylan Pharmaceuticals Inc..
Has Clonidine been recalled?
The FDA enforcement database lists 3 recalls for Clonidine, most recently D-1152-2022 (class ii): Defective Delivery System: Out of specification for release liner removal force results at the 3-month CRT stability timepoint.