Clonidine

Clinical trial experience with CATAPRES-TTS (clonidine)

Most systemic adverse effects during Catapres-TTS (clonidine) transdermal therapeutic system therapy have been mild and have tended to diminish with continued therapy. In a 3-month multi-clinic trial of Catapres-TTS (clonidine) transdermal therapeutic system in 101 hypertensive patients, the systemic adverse reactions were, dry mouth (25 patients) and drowsiness (12), fatigue (6), headache (5), lethargy and sedation (3 each), insomnia, dizziness, impotence/sexual dysfunction, dry throat (2 each) and constipation, nausea, change in taste and nervousness (1 each).

In the above mentioned 3-month controlled clinical trial, as well as other uncontrolled clinical trials, the most frequent adverse reactions were dermatological and are described below.

In the 3-month trial, 51 of the 101 patients had localized skin reactions such as erythema (26 patients) and/or pruritus, particularly after using an adhesive cover throughout the 7-day dosage interval. Allergic contact sensitization to Catapres-TTS (clonidine) transdermal therapeutic system was observed in 5 patients. Other skin reactions were localized vesiculation (7 patients), hyperpigmentation (5), edema (3), excoriation (3), burning (3), papules (1), throbbing (1), blanching (1), and a generalized macular rash (1).

In additional clinical experience, contact dermatitis resulting in treatment discontinuation was observed in 128 of 673 patients (about 19 in 100) after a mean duration of treatment of 37 weeks. The incidence of contact dermatitis was about 34 in 100 among white women, about 18 in 100 in white men, about 14 in 100 in black women, and approximately 8 in 100 in black men. Analysis of skin reaction data showed that the risk of having to discontinue Catapres-TTS (clonidine) transdermal therapeutic system treatment because of contact dermatitis was greatest between treatment weeks 6 and 26, although sensitivity may develop either earlier or later in treatment.

In a large-scale clinical acceptability and safety study by 451 physicians in a total of 3539 patients, other allergic reactions were recorded for which a causal relationship to Catapres-TTS (clonidine) transdermal therapeutic system was not established: maculopapular rash (10 cases); urticaria (2 cases); and angioedema of the face (2 cases), which also affected the tongue in one of the patients.

Marketing Experience with Catapres-TTS (clonidine)

The following adverse reactions have been identified during post-approval use of Catapres-TTS (clonidine) transdermal therapeutic system. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Catapres-TTS (clonidine) transdermal therapeutic system.

Body as a Whole: Fever; malaise; weakness; pallor; and withdrawal syndrome.

Cardiovascular: Congestive heart failure; cerebrovascular accident; electrocardiographic abnormalities (i.e., bradycardia, sick sinus syndrome disturbances and arrhythmias); chest pain; orthostatic symptoms; syncope; increases in blood pressure; sinus bradycardia and atrioventricular (AV) block with and without the use of concomitant digitalis; Raynaud's phenomenon; tachycardia; bradycardia; and palpitations.

Central and Peripheral Nervous System/Psychiatric: Delirium; mental depression; hallucinations (including visual and auditory); localized numbness; vivid dreams or nightmares; restlessness; anxiety; agitation; irritability; other behavioral changes; and drowsiness.

Dermatological: Angioneurotic edema; localized or generalized rash; hives; urticaria; contact dermatitis; pruritus; alopecia; and localized hypo or hyper pigmentation.

Gastrointestinal: Anorexia and vomiting.

Genitourinary: Difficult micturition; loss of libido; and decreased sexual activity.

Metabolic: Gynecomastia or breast enlargement and weight gain.

Musculoskeletal: Muscle or joint pain; and leg cramps.

Ophthalmological: Blurred vision; burning of the eyes and dryness of the eyes.

Adverse Events Associated with Oral Catapres Therapy

Most adverse effects are mild and tend to diminish with continued therapy. The most frequent (which appear to be dose-related) are dry mouth, occurring in about 40 of 100 patients; drowsiness, about 33 in 100; dizziness, about 16 in 100; constipation and sedation, each about 10 in 100. The following less frequent adverse experiences have also been reported in patients receiving Catapres (clonidine hydrochloride, USP) tablets, 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 AV block have been reported, both with and without the use of concomitant digitalis.

Central Nervous System: 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 the eyes.

Common side effects of clonidine tablets and extended-release include:

• fatigue
• upper airway tract infection
• irritability
• sore throat
• insomnia
• nightmares
• emotional disorder
• constipation
• nasal congestion
• increased body temperature
• dry mouth
• ear pain

Common side effects of the clonidine patch include:

• dry mouth
• drowsiness
• fatigue
• headache
• insomnia
• dizziness
• dry throat
• constipation
• nausea
• change in taste
• nervousness

Common side effects of clonidine injectable include:

• drop in blood pressure
• dry mouth
• drowsiness
• fatigue
• headache
• insomnia
• dizziness

This is not a complete list of clonidine side effects. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with clonidine. See “Drug Precautions” section.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of clonidine, there are no specific foods that you must exclude from your diet when receiving clonidine.

Alcohol may intensify some of the side effects of this medication.

Tell your doctor if you are breastfeeding or plan to breastfeed.

The active ingredient in clonidine is excreted in human breast milk. The effect of clonidine on the nursing infant is not known.

Take clonidine exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

Oral:

• To start therapy, 0.1 mg tablet is given twice daily (morning and bedtime). Elderly patients may need to start from a lower dose. Further increments of 0.1 mg per day may be made at weekly intervals if necessary until the desired response is achieved. The typical dose range for clonidine tablet is 0.2 to 0.6 mg per day, divided into a morning and an evening dose. Maximum effective dose is 2.4 mg per day, but this dose amount is not commonly used.

Topical:

• To start therapy, the patch dosage should be adjusted according to individual needs, starting with the lowest patch dose (0.1 mg). If after one or two weeks the desired decrease in blood pressure is not achieved, your dose may be increased by your doctor by adding another clonidine 0.1 mg patch or changing to a larger system (0.2 or 0.3 mg).

Injectable:

• The recommended starting dose of clonidine for epidural infusion is 30 mcg/hour. Dosage may be increased or decreased depending on pain relief and occurrence of side effects.

If you take too much clonidine call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If clonidine is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

You should not take this medication if you are allergic to clonidine.

To make sure clonidine is safe for you, tell your doctor if you have:

• heart disease or severe coronary artery disease;
• heart rhythm disorder, slow heartbeats;
• low blood pressure;
• a history of heart attack or stroke;
• pheochromocytoma (tumor of the adrenal gland);
• kidney disease; or
• if you have ever had an allergic reaction to a clonidine transdermal skin patch (Catapres TTS).

FDA pregnancy category C. It is not known whether clonidine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Clonidine can pass into breast milk and may harm a nursing baby. Do not take this medication without telling your doctor if you are breast-feeding a baby.

Do not give Kapvay to a child younger than 6 years old.

Storage

Oral

Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).114

Parenteral

25°C (may be exposed to15–30°C);151 any unused should be discarded.151

Transdermal

<30°C.101

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Injections containing a preservative should not be used to dilute the epidural injection.151

Do not dilute with bacteriostatic sodium chloride injection.151

Clonidine hydrochloride 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.

Clonidine hydrochloride tablets USP contain the following inactive ingredients: lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium starch glycolate. The 0.1 mg also contains D&C yellow #10 aluminum lake, and the 0.3 mg contains D&C yellow #10 aluminum lake and FD&C blue #1 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:

C9H9Cl2N3 • HCl       Mol. Wt. 266.56

Clonidine hydrochloride is an odorless, bitter, white, crystalline substance soluble in water and alcohol.

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 LD50 of Clonidine is 206 and 465 mg/kg, respectively.

NDC 52817-180-10
Clonidine
Hydrochloride
Tablets, USP
0.1 mg
Rx Only
100 Tablets

• Clonidine HCl
• Clonidine Hydrochloride

The half-life increases up to 41 hours in patients with severe renal impairment.

Adults: Oral (immediate release), transdermal, epidural: The manufacturer recommends dosage adjustment according to degree of renal impairment; however, no specific dosage adjustment provided in manufacturer’s labeling. Bradycardia, sedation, and hypotension may be more likely to occur in patients with renal failure; half-life significantly prolonged in patients with severe renal failure; consider use of lower initial doses and monitor closely.

Children: Oral (extended release), epidural: The manufacturer recommends dosage adjustment according to degree of renal impairment; however, no specific dosage adjustment provided (has not been studied).

Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary. Oral antihypertensive drugs given preferentially at night may reduce the nocturnal surge of blood pressure and minimize the intradialytic hypotension that may occur when taken the morning before a dialysis session (K/DOQI 2005).

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta-Blockers: Alpha2-Agonists may enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Levobunolol; Metipranolol. Consider therapy modification

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Calcium Channel Blockers (Nondihydropyridine): CloNIDine may enhance the AV-blocking effect of Calcium Channel Blockers (Nondihydropyridine). Sinus node dysfunction may also be enhanced. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cardiac Glycosides: CloNIDine may enhance the AV-blocking effect of Cardiac Glycosides. Sinus node dysfunction may also be enhanced. Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

EPHEDrine (Systemic): CloNIDine may enhance the therapeutic effect of EPHEDrine (Systemic). Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Iobenguane I 123: Alpha2-Agonists may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylphenidate: May enhance the adverse/toxic effect of CloNIDine. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the antihypertensive effect of Alpha2-Agonists. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Tricyclic Antidepressants: May diminish the antihypertensive effect of Alpha2-Agonists. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

The 500 mcg/mL strength product should be diluted prior to use in an appropriate solution.

Note: Epidural clonidine is not recommended for obstetrical, postpartum, or perioperative pain management. The risk of hemodynamic instability, especially hypotension and bradycardia, from epidural clonidine may be unacceptable in these patients. However, in a rare obstetrical, postpartum or perioperative patient, potential benefits may outweigh the possible risks.

Administration advice:
-This drug can be taken with or without food.
-The extended release tablets should be swallowed whole and not crushed, chewed, or broken because this will increase the rate of drug release.
-Taking the larger portion of the oral daily dose at bedtime may minimize dry mouth and drowsiness and also minimize the risk of morning-associated cardiovascular events (i.e., stroke, transient ischemic attacks, myocardial infarction, sudden cardiac death).
-The patch formulation should be applied every 7 days to a hairless area of intact skin on the upper outer arm or chest. Each new application should be on a different skin site from the previous location. If the system loosens during 7-day wearing, the adhesive overlay should be applied directly over the system to ensure good adhesion.

Storage requirements:
The manufacturer product information should be consulted.

Reconstitution/preparation techniques:
The manufacturer product information should be consulted.

IV compatibility:
The manufacturer product information should be consulted.

General:
-This drug may be added to other antihypertensive regimens where blood pressure control has not been adequately achieved.
-Concomitant therapy with a thiazide diuretic may minimize associated fluid retention, particularly during therapy initiation.
-Slow IV administration may help minimize the initial pressor phase of 5 to 10 mmHg (lasting approximately 5 minutes) which can occur after IV injection.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Clonidine is usually taken in the morning and at bedtime. If you take different doses of this medicine at each dosing time, it may be best to take the larger dose at bedtime.

Clonidine may be taken with or without food.

Do not use two forms of clonidine at the same time. This medicine is also available as a transdermal patch worn on the skin.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. Tell your doctor if you have trouble swallowing the tablet.

If you need surgery, tell the surgeon ahead of time that you are using clonidine. You may need to stop using the medicine for a short time.

Do not stop using clonidine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using clonidine.

Call your doctor if you are sick with vomiting. Prolonged illness can make it harder for your body to absorb clonidine, which may lead to withdrawal symptoms. This is especially important for a child taking clonidine.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture, heat, and light.

Avoid drinking alcohol. It may increase certain side effects of clonidine.

Clonidine may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Take clonidine exactly as it was prescribed for you. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Clonidine is usually taken in the morning and at bedtime. If you take different doses of this medicine at each dosing time, it may be best to take the larger dose at bedtime.

Clonidine may be taken with or without food.

Do not use two forms of clonidine at the same time. This medicine is also available as a transdermal patch worn on the skin.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. Tell your doctor if you have trouble swallowing the tablet.

If you need surgery, tell the surgeon ahead of time that you are using clonidine. You may need to stop using the medicine for a short time.

Do not stop using clonidine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using this medicine.

Call your doctor if you are sick with vomiting. Prolonged illness can make it harder for your body to absorb this medicine, which may lead to withdrawal symptoms. This is especially important for a child taking clonidine.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture, heat, and light.

Get emergency medical help if you have signs of an allergic reaction to clonidine: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe chest pain, shortness of breath, irregular heartbeats;

• a very slow heart rate;

• severe headache, pounding in your neck or ears, blurred vision;

• nosebleeds;

• anxiety, confusion; or

• a light-headed feeling, like you might pass out.

Serious side effects may be more likely in older adults.

Common clonidine side effects may include:

• drowsiness, dizziness;

• feeling tired or irritable;

• dry mouth, loss of appetite;

• constipation;

• dry eyes, contact lens discomfort; or

• sleep problems (insomnia), nightmares.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.