cloNIDine HCl 0.3 MG Oral Tablet
WARNINGS
Withdrawal Patients should be instructed not to discontinue therapy without consulting their physician.
Sudden cessation of clonidine treatment has, in some cases, 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 hydrochloride tablets, the physician should reduce the dose gradually over 2 to 4 days to avoid withdrawal symptomatology.
An excessive rise in blood pressure following discontinuation of clonidine hydrochloride tablets therapy 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is to be discontinued in patients receiving a beta-blocker and clonidine concurrently, the beta-blocker should be withdrawn several days before the gradual discontinuation of clonidine hydrochloride tablets.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.
DRUG INTERACTIONS
Drug Interactions 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.
If a patient receiving clonidine is also taking neuroleptics, orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue) may be induced or exacerbated.
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 Toxicology ).
Based on observations in patients in a state of alcoholic delirium it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT-prolongation, ventricular fibrillation) of high intravenous doses of haloperidol.
Causal relationship and relevance for clonidine oral tablets have not been established.
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 hydrochloride, USP is a centrally acting alpha-agonist hypotensive agent available as tablets for oral administration in three dosage strengths: 0.1 mg, 0.2 mg and 0.3 mg.
The 0.1 mg tablet is equivalent to 0.087 mg of the free base.
The inactive ingredients are dibasic calcium phosphate, FD&C Yellow #6 aluminum lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, sodium starch glycolate.
The clonidine hydrochloride 0.1 mg tablet also contains FD&C Blue #1 aluminum lake and FD&C Red #40 aluminum lake.
Clonidine hydrochloride 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: Clonidine hydrochloride is an odorless, bitter, white, crystalline substance soluble in water and alcohol.
This is an image of the structural formula for clonidine hydrochloride.
HOW SUPPLIED
Clonidine Hydrochloride Tablets, USP are available as: 0.1 mg: light tan, oval, scored, convex, debossed “25” bisect “41” on one side and debossed “V” on the reverse side, supplied as follows: Bottles of 10: NDC 0603-2957-10 Bottles of 90: NDC 0603-2957-02 Bottles of 100: NDC 0603-2957-21 Bottles of 180: NDC 0603-2957-04 Bottles of 500: NDC 0603-2957-28 Bottles of 1000: NDC 0603-2957-32 Bottles of 2500: NDC 0603-2957-30 0.2 mg: orange, oval, scored, convex, debossed “25” bisect “42” on one side and debossed “V” on the reverse side, supplied as follows: Bottles of 10: NDC 0603-2958-10 Bottles of 100: NDC 0603-2958-21 Bottles of 500: NDC 0603-2958-28 Bottles of 1000: NDC 0603-2958-32 Bottles of 2500: NDC 0603-2958-30 0.3 mg: peach, oval, scored, convex, debossed “25” bisect “43” on one side and debossed “V” on the reverse side, supplied as follows: Bottles of 10: NDC 0603-2959-10 Bottles of 100: NDC 0603-2959-21 Bottles of 500: NDC 0603-2959-28 Bottles of 1000: NDC 0603-2959-32 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Dispense in a tight, light-resistant container.
INDICATIONS AND USAGE
Clonidine hydrochloride tablets, USP are indicated in the treatment of hypertension.
Clonidine hydrochloride tablets, USP may be employed alone or concomitantly with other antihypertensive agents.
PEDIATRIC USE
Pediatric Use Safety and effectiveness in pediatric patients have not been established in adequate and well-controlled trials (see WARNINGS, Withdrawal ).
PREGNANCY
Pregnancy Teratogenic Effects: 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 tablets, USP produced no evidence of a teratogenic or embryotoxic potential in rabbits.
In rats, however, doses as low as ⅓ 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.
Clonidine crosses the placental barrier (see CLINICAL PHARMACOLOGY, Pharmacokinetics ).
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
NUSRING MOTHERS
Nursing Mothers As clonidine hydrochloride is excreted in human milk, caution should be exercised when clonidine hydrochloride tablets are administered to a nursing woman.
INFORMATION FOR PATIENTS
Information for Patients Patients should be cautioned against interruption of clonidine hydrochloride tablets therapy without their physician’s advice.
Since patients may experience a possible sedative effect, dizziness, or accommodation disorder with use of clonidine, caution patients about engaging in activities such as driving a vehicle or operating appliances or machinery.
Also, inform patients that this sedative effect may be increased by concomitant use of alcohol, barbiturates, or other sedating drugs.
Patients who wear contact lenses should be cautioned that treatment with clonidine hydrochloride tablets may cause dryness of eyes.
INACTIVE INGREDIENTS
The inactive ingredients are dibasic calcium phosphate, FD&C Yellow #6 aluminum lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, sodium starch glycolate.
The clonidine hydrochloride 0.1 mg tablet also contains FD&C Blue #1 aluminum lake and FD&C Red #40 aluminum lake.
DOSAGE AND ADMINISTRATION
Adults The dose of clonidine hydrochloride tablets, USP must be adjusted according to the patient’s individual blood pressure response.
The following is a general guide to its administration.
Initial Dose 0.1 mg tablet twice daily (morning and bedtime).
Elderly patients may benefit from a lower initial dose.
Maintenance Dose Further increments of 0.1 mg per day may be made at weekly intervals if necessary until the desired response is achieved.
Taking the larger portion of the oral daily dose at bedtime may minimize transient adjustment effects of dry mouth and drowsiness.
The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day given in divided doses.
Studies have indicated that 2.4 mg is the maximum effective daily dose, but doses as high as this have rarely been employed.
Renal Impairment Patients with renal impairment may benefit from a lower initial dose.
Patients should be carefully monitored.
Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.