Clonidine Hydrochloride Oral
FDA Drug Information • Also known as: Javadin
- Brand Names
- Javadin
- Route
- ORAL
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION JAVADIN (clonidine hydrochloride) oral solution is a central alpha-2 adrenergic agonist hypotensive agent available as a 0.02 mg/mL solution for oral administration. Clonidine hydrochloride is an imidazoline derivative and exists as a mesomeric compound. The chemical name is 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride. Its molecular formula is C 9 H 9 Cl 2 N 3 , HCl which corresponds to a molecular weight of 266.5. The following is the structural formula: Clonidine hydrochloride USP is a white or almost white crystalline powder. It is soluble in water, and ethanol and slightly soluble in Chloroform. JAVADIN is a clear colorless oral solution. Each mL contains 0.02 mg of clonidine hydrochloride (equivalent to 0.0173 mg of clonidine). The inactive ingredients are: mixed berry flavor, purified water, sodium chloride, sodium propionate, sucralose. Clonidine Structure
What Is Clonidine Hydrochloride Oral Used For?
1 INDICATIONS AND USAGE JAVADIN is indicated for the treatment of hypertension in adult patients, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. There are no controlled trials demonstrating risk reduction with JAVADIN. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. JAVADIN may be used alone or in combination with other antihypertensive agents. JAVADIN is a central alpha-2 adrenergic agonist, indicated for the treatment of hypertension in adult patients to lower blood pressure. Lowering blood pressure has been shown to reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Initial dosage is 0.1 mg orally twice daily with or without food (morning and bedtime) ( 2.1 ) Titrate in increments of 0.1 mg per day at weekly intervals if necessary until the desired response is achieved. ( 2.1 ) The therapeutic doses most commonly used have ranged from 0.2 mg to 0.6 mg per day, given in divided doses. ( 2.1 ) Maximum recommended daily dose is 2.4 mg. ( 2.1 ) 2.1 Recommended Dosage Dosage should be individualized based on response. The recommended initial dosage is 0.1 mg orally twice daily (morning and bedtime). Dosage can be titrated in increments of 0.1 mg per day at weekly intervals as necessary. Doses should be taken twice a day, with either an equal or higher split dosage being given at bedtime. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day, given in divided doses. Maximum recommended daily dose is 2.4 mg, but doses as high as this have rarely been employed. 2.2 Administration Instructions A calibrated measuring device, such as an oral dosing syringe or oral dosing cup, is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device. Administer JAVADIN (clonidine hydrochloride) oral solution with or without food. [see Clinical Pharmacology ( 12.3 )] JAVADIN may be administered up to 4 hours before surgery and resume as soon as possible post-operatively [see Warning and Precaution ( 5.2 )].
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Bradycardia, Cardiac Conduction Abnormalities, and Symptomatic Hypotension [see Warnings and Precautions ( 5.1 )] Rebound Hypertension [see Warnings and Precautions ( 5.2 )] Sedation and Somnolence [see Warnings and Precautions ( 5.3 )] The most frequent adverse reactions are dry mouth, drowsiness, dizziness, constipation and sedation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc., at 1-800-461-7449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Most adverse effects are mild and tend to diminish with continued therapy. The most frequent (which appear to be dose-related) are dry mouth (40%), drowsiness (33%); dizziness (16%); constipation and sedation (10%, respectively). The following less frequent adverse experiences have also been reported in patients receiving clonidine hydrochloride tablets, but in many cases patients were receiving concomitant medication and a causal relationship has not been established. Body as a Whole: Fatigue, headache, pallor, malaise, weakness, and withdrawal syndrome. Cardiovascular: Bradycardia, congestive heart failure, electrocardiographic abnormalities (i.e., sinus node arrest, junctional bradycardia, high degree AV block and arrhythmias), orthostatic symptoms, palpitations, syncope, and tachycardia. Central Nervous System: Agitation, anxiety, delirium, hallucinations (including visual and auditory), insomnia, mental depression, behavioral changes, paresthesia, sleep disorder, and vivid dreams or nightmares. Gastrointestinal: Anorexia, constipation, nausea, and vomiting. Hematologic: Thrombocytopenia. Hepatobiliary: Hepatitis and transaminitis. Hypersensitivity: Angioedema, hives, pruritus, rash, and urticaria. Metabolic: Transient elevation of blood glucose or serum creatine phosphokinase, and weight gain. Musculoskeletal: Leg cramps and muscle or joint pain. Ophthalmological: Accommodation disorder, blurred vision, burning of the eyes, decreased lacrimation, and dryness of eyes. Renal and Urinary: Difficulty in micturition, nocturia, and urinary retention. Reproductive System and Breast Disorders: Gynecomastia. erectile dysfunction, and loss of libido. Vascular: Raynaud's phenomenon.
Drug Interactions
7 DRUG INTERACTIONS The interactions of JAVADIN with co-administration of other drugs have not been studied. The drug interaction data provided in this section is based on oral immediate-release clonidine formulations. Table 1 displays clinically important drug interactions with JAVADIN. Table 1: Clinically Important Drug Interactions with JAVADIN. Antihypertensive drugs Clinical Implication Concomitant use of antihypertensive drugs with clonidine potentiates the hypotensive effects of clonidine [see Warnings and Precautions ( 5.1 )]. Intervention Monitor blood pressure and heart rate, and adjust dosage of JAVADIN accordingly in patients treated concomitantly with antihypertensives CNS depressants Clinical Implication Concomitant use of CNS depressants with clonidine potentiates the sedating effects [see Warnings and Precautions ( 5.3 )]. Intervention Avoid concomitant use of CNS depressants with JAVADIN. Drugs that affect sinus node function or AV node conduction (e.g., digitalis, calcium channel blockers, beta blockers) Clinical Implication Concomitant use of drugs that affect sinus node function or AV node conduction with clonidine potentiate bradycardia and risk of AV block [see Warnings and Precautions ( 5.1 )]. Intervention Avoid concomitant use of drugs that affect sinus node function or AV node conduction with JAVADIN. Tricyclic antidepressants Clinical Implication Concomitant use of tricyclic antidepressants with clonidine can increase blood pressure and may counteract the hypotensive effects of clonidine. Intervention Monitor blood pressure and adjust dosage of JAVADIN as needed. 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. ( 7 ) Neuroleptics: May induce or exacerbate the orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue). ( 7 ) Drugs Known to Affect Sinus Node Function or AV Nodal Conduction: Caution is warranted 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) due to a potential for additive effects such as bradycardia and AV block. ( 7 )
Contraindications
4 CONTRAINDICATIONS JAVADIN is contraindicated in patients with known hypersensitivity to clonidine. [see Adverse Reactions ( 6 )].
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Prolonged experience with clonidine in pregnant women over several decades, based on published literature, including controlled trials, a retrospective cohort study and case reports, have not identified a drug associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes. In animal embryofetal studies, increased resorptions were seen in rats and mice administered oral clonidine hydrochloride from implantation through organogenesis at approximately 2 times the maximum recommended human dose (MRHD) (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Oral administration of clonidine hydrochloride to pregnant rabbits during the period of embryo/fetal organogenesis at doses of up to 0.08 mg/kg/day (approximately 0.6 times the oral maximum recommended human dose [MRHD] of 2.4 mg/day) produced no developmental effects. In pregnant rats, however, doses as low as 0.015 mg/kg/day (~1/16 the oral MRHD on a mg/kg basis) were associated with increased resorptions in a study in which dams were treated continuously from 2 months prior to mating and throughout gestation. Increased resorptions were not associated with treatment at the same or at higher dose levels when treatment of the dams was restricted to gestation days 6-15. Increases in resorptions were observed in both rats and mice at 0.5 mg/kg/day (2 and 1 times the MRHD in rats and mice, respectively) or higher when the animals were treated on gestation days 1-14; 0.5 mg/kg/day was the lowest dose employed in this study.
Overdosage
10 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 pediatric patients 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. Dialysis is not likely to significantly enhance the elimination of clonidine.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied JAVADIN (clonidine hydrochloride) is a clear, colorless solution supplied in a high-density polyethylene (HDPE) bottle with child-resistant closure. The 0.02 mg/mL oral solution is available in bottles of 250 mL (NDC 24338-115-01). 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86° F) (see USP Controlled Room Temperature ). Discard unused portion 60 days after first opening.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.