Clonidine is a centrally acting alpha-2 agonist used transdermally for the treatment of hypertension, orally for the treatment of hypertension or attention-deficit hyperactivity disorder (ADHD), and parenterally as an epidural agent for refractory cancer pain. Synthesized in the early 1960s for use as a nasal decongestant, clonidine was serendipitously found to produce hypotension, bradycardia, and sedation at remarkably low doses. Clonidine has been used successfully for a variety of other conditions 'off-label', including alcohol withdrawal and opioid withdrawal as examples. Clonidine has also been used 'off-label' for Tourette's syndrome, particularly when comorbid ADHD is present. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders. For those with comorbid ADHD, clonidine may provide benefits for both conditions. Clonidine is not considered a first-line agent for ADHD due to the potential for toxic cardiac effects and the availability of safer and more effective agents (i.e., methylphenidate, amphetamines). When clonidine is used for the treatment of ADHD, the American Heart Association recommends careful cardiovascular screening and monitoring of patients; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). Single doses of clonidine have been used in the diagnosis of pheochromocytoma. Clonidine is effective in the treatment of severe pain in cancer patients refractory to opiate agonists. Epidural clonidine seems to be more effective in patients with neuropathic pain rather than visceral pain. The use of epidural clonidine has resulted in decreases in opiate requirements when used in combination with epidural opiate agonists and increases the duration of response to anesthetic agents used in peripheral nerve blocks.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer last dose of the day immediately prior to bedtime to ensure maximum overnight blood pressure control; the largest portion of the daily dose should also be taken just before bedtime.
Oral Solid Formulations
-Immediate-release tablets (e.g., Catapres): May be taken with or without food. Upon discontinuation, slowly taper dose over 2-4 days to avoid withdrawal symptoms and rebound hypertension.
-Extended-release tablets (e.g., Kapvay): May be taken with or without food. Swallow whole; do not crush, cut, or chew. Upon discontinuation, slowly taper dose every 3-7 days to avoid withdrawal symptoms and rebound hypertension.
Oral Liquid Formulations
NOTE: Enteral administration of clonidine solution for injection is not approved by the FDA.
-The 100 mcg/mL clonidine solution for epidural administration, diluted to a concentration of 5 mcg/mL, has been administered orally to neonatal patients for the treatment of neonatal abstinence syndrome.
Extemporaneous Compounding-Oral
Extemporaneous 0.02 mg/mL Clonidine Oral Solution Preparation
-Triturate six (6) 0.1-mg clonidine hydrochloride tablets (total: 0.6 mg) in a glass mortar.
-Levigate with 1 to 2 mL Simple Syrup NF and combine with sufficient additional syrup to yield 30 mL.
-Storage: The resulting solution is stable in an amber plastic bottle for 35 days under refrigeration (2 to 8 degrees C).
Extemporaneous 0.01 mg/mL Clonidine Oral Suspension Preparation
-Crush and grind twenty-five (25) 0.1-mg clonidine hydrochloride tablets (total: 2.5 mg clonidine) to a fine powder using a mortar and pestle.
-Add Ora-Blend in geometric amounts until approximately half of the total volume (125 ml) is added.
-Transfer the suspension to a graduated cylinder, rinse the mortar and pestle with additional Ora-Blend, and continue to add Ora-Blend to a final volume of 250 ml.
-Shake until well suspended before transferring to appropriate storage container.
-Storage: The resulting suspension is stable for 91 days when stored in clear plastic syringes at either 4 or 25 degrees C.
Extemporaneous 0.1mg/mL Clonidine Oral Suspension Preparation
-Crush and grind thirty (30) 0.2-mg clonidine hydrochloride tablets (total: 6 mg clonidine) to a fine powder in a glass mortar.
-Add enough Purified Water, USP to form a paste (roughly 2 mL).
-Add 15 mL Simple Syrup, NF to the paste and triturate well.
-Transfer mortar contents to a 60 mL amber glass bottle.
-Continue to add Simple Syrup, NF in increments to a total of 60 mL; shake after each increment until well suspended.
-Storage: The resulting suspension is stable for 28 days when stored in 60 mL amber glass bottles at 4 degrees C and protected from light.
Injectable Administration
Other Injectable Administration
Epidural Injection
-Epidural clonidine is preservative-free.
-Epidural clonidine is usually administered in combination with other opiate analgesics such as fentanyl or morphine.
-Health care professionals should be familiar with epidural infusion devices when administering epidural infusions.
Topical Administration
Transdermal Patch Formulations
NOTE: The amount of active drug released after application of a clonidine transdermal system is directly proportional to the area covered by the system. 'Patches' are available as 3.5 cm2 (total clonidine content 2.5 mg, delivering 100 mcg/day); 7 cm2 (total clonidine content 5 mg, delivering 200 mcg/day); and 10.5 cm2 (total clonidine content 7.5 mg, delivering 300 mcg/day) over a period of 7 days. The total amount of drug in each system is greater than that delivered, to ensure constant release of the drug over 7 days.
-Do not cut or trim patch.
-Clonidine is absorbed better from the patch if applied on the upper arm or torso.
-Apply to any hairless site at the same time each week. Avoid applying to areas with cuts or calluses. Wash area with soap and water. Dry thoroughly. Apply patch using firm pressure over patch to ensure contact with skin, especially around edges. If patch becomes loose during the 7-day wearing period, apply the adhesive overlay over the patch. If patch is overly loose or falls off, apply another patch. Rotate sites each week.
-Instruct patient on proper application of patch. Patches should not be affected by showering, bathing, or swimming.
-Patches must be removed prior to cardioversion or defibrillation to prevent burns to the patient. Also, removal of the Catapres-TTS patch before undergoing magnetic resonance imaging (MRI) is recommended because the patch contains aluminum.
Transient blood glucose elevations have been reported, although clonidine has been administered safely to diabetic patients. In addition, clonidine has been used in the treatment of loose stools in diabetic patients.
Central nervous system (CNS) adverse effects have been commonly reported during clonidine therapy. Adverse events noted during adult trials with the immediate-release tablets include drowsiness/somnolence (33%), dizziness (16%), and sedation (10%). Adverse events reported less frequently include fever, fatigue, headache, weakness, agitation, anxiety, delirium, delusional perception, hallucinations (visual and auditory), insomnia, mental depression, nervousness, other behavioral changes, paresthesias, restlessness, sleep disorder, and vivid dreams or nightmares. These effects generally subside as therapy progresses or as dosages are reduced. Many of these effects will diminish with continued therapy. In pediatric patients receiving extended-release clonidine tablets for attention-deficit hyperactivity disorder (ADHD), 31-38% of patients receiving monotherapy and 19% of those receiving adjunctive therapy with a stimulant reported somnolence compared to 4% and 7%, respectively, of those receiving placebo. During the monotherapy trial taper period, 2-3% of patients reported somnolence. Fatigue (13-16%), headache (2-20%), dizziness (3-7%), insomnia (4-6%), and nightmare (4-9%) were also commonly reported. Other CNS events reported in pediatric trials include tremor (1-4%), night terror (<= 3%), poor quality sleep (<= 3%), abnormal sleep-related events (1-3%), irritability (2-9%), emotional disorder (2-4%), aggression (1-3%), tearfulness (1-3%), and emotional lability (2% when used as an adjunct to stimulant therapy). Hallucinations have also been reported with post-marketing use of extended-release clonidine. Transdermal therapy typically results in less severe adverse systemic effects including drowsiness (12%), fatigue (6%), headache (5%), lethargy (3%), sedation (3%), insomnia (2%), dizziness (2%), and nervousness (1%). Weakness, fever, malaise, delirium, depression, hallucinations, localized numbness, vivid dreams or nightmares, restlessness, anxiety, agitation, irritability, behavioral changes, and drowsiness were noted post-marketing for the transdermal system. The most common CNS adverse reactions to epidural clonidine that may also be related to concomitant morphine administration include anxiety (38%), somnolence (13-25%), asthenia, confusion (13-38%), diaphoresis (5%), dizziness (13%), hallucinations (5%), hypoventilation (2.6%), hyperesthesia, drowsiness, and fever. Adverse events associated with any form of clonidine include weakness (10%), fatigue (4%), headache (1%), nervousness and agitation (3%), depression (1%), insomnia (0.5%), and cerebrovascular accident or stroke (rare).
Adverse cardiovascular effects of clonidine therapy include heart failure, EKG abnormalities (e.g., sinus node arrest, junctional bradycardia, high degree AV block, arrhythmias [arrhythmia exacerbation], sick sinus syndrome), Raynaud's phenomenon with peripheral vasoconstriction, syncope, chest pain (unspecified) (5.3% epidural), increased blood pressure, hypotension (44-47% epidural, n = 38), orthostatic hypotension (32-47% epidural), palpitations (0.5%), sinus tachycardia (2.6% epidural; 0.5% any formulation), and sinus bradycardia (0.5%). The hypotension associated with epidural clonidine is usually responsive to fluids and is observed more commonly in women and in lower weight patients, but no dose-response relationship has been established. Chest pain has also been reported to occur after the administration of epidural clonidine. Bradycardia (<= 4%) and sinus tachycardia (<= 3%) have been reported in patients receiving extended-release (ER) clonidine during pediatric clinical trials for attention-deficit hyperactivity disorder (ADHD). QT prolongation has been reported with post-marketing use of clonidine ER for ADHD.
Hypersensitivity reactions, including generalized rash, urticaria, and angioedema have occurred with systemic use of clonidine. Transient, localized, dermatological effects have occurred following the administration of clonidine patches (n = 101) and include erythema (26%), pruritus (26%), contact dermatitis (5%), vesicular rash (7%), edema (3%), excoriation (3%), burning (3%), papules (1%), throbbing (1%), blanching (1%), generalized macular rash (1%), and skin hyperpigmentation (5%). Contact dermatitis resulted in the discontinuation of the transdermal clonidine patch in 19% of patients in trials (n = 673) and was greatest between weeks 6 and 26. In another study (n = 3539), maculopapular rash, urticaria, and angioedema of the face/tongue were reported in < 1% of patients. Alopecia (0.2%), angioneurotic edema (0.5%), hives, pruritus (0.7%), rash (unspecified) (1%), pallor, and urticaria (0.5%) have been reported in patients receiving other forms clonidine. Skin ulcer (0.5%) has been noted with the epidural use of clonidine. Rash (unspecified) was reported in 2% of pediatric patients receiving extended-release clonidine adjunctive to stimulant therapy during clinical trials.
Several urogenital adverse effects have been associated with clonidine therapy. Sexual dysfunction including impotence (erectile dysfunction) (2-3%), libido decrease (3%), and decreased sexual activity (3%) have been reported with clonidine therapy, as have urinary retention (0.1%), difficulty in micturition (0.2%), and nocturia (1%). In a clinical trial of pediatric patients receiving extended-release clonidine as monotherapy for the treatment of ADHD, urinary incontinence (enuresis) occurred in <= 4% of patients.
Metabolic adverse event associated with clonidine include gynecomastia (1%), transient elevation of blood glucose (rare), elevation of serum creatine phosphokinase (rare), and weight gain (0.1%). Weight gain is commonly associated with fluid retention, especially during the initiation of clonidine treatment.
The most common gastrointestinal (GI) adverse effects associated with clonidine therapy in adult clinical trials (n = 32-101) are constipation (1-10%) and xerostomia (13-40%). Other adverse effects include ileus, abdominal pain, anorexia (1%), mild transient abnormalities in liver function tests, nausea (1-13%), salivary gland pain, vomiting (5-10.5%), dry throat (2%), change in taste (dysgeusia) (1%), and mildly elevated hepatic enzymes (1%). Rarely, hepatitis, parotitis, ileus, and pseudo-GI obstruction (including colonic pseudo-obstruction) have occurred. In a clinical trial of pediatric patients receiving extended-release clonidine as monotherapy for the treatment of ADHD, the most common GI adverse effects were upper abdominal pain (<= 15%), nausea (4-5%), constipation (1-6%), xerostomia (<= 5%), anorexia (3-4% with monotherapy, 6% with adjunctive stimulant use), and viral gastroenteritis (<= 5%).
Nasal congestion (2-4%) and throat irritation/pain (3%) were both reported during pediatric clinical trials when extended-release clonidine was used as an adjunct to stimulant therapy in patients with attention-deficit hyperactivity disorder (ADHD). The administration of epidural clonidine has been associated with dyspnea (6%). Rarely, nasal dryness has been associated with clonidine therapy.
Rarely, thrombocytopenia has been reported in clinical trials with clonidine.
Leg cramps (muscle cramps), and musculoskeletal pain or joint pain (arthralgia) have been reported in clonidine clinical trials.
Ocular adverse events associated with clonidine therapy include accommodation disorder, blurred vision, ocular burning, decreased lacrimation, and xerophthalmia.
Catheter-related infection, including meningitis and epidural abscess, occurs in 5-20% of patients receiving epidural clonidine. General infection (6%) and urinary tract infection (22%) were also noted with epidural clonidine. In addition, acute otitis media (<= 3%) was reported during extended-release clonidine trials for pediatric attention-deficit hyperactivity disorder (ADHD).
Severe rebound hypertension can occur during withdrawal from clonidine. This reaction is more likely to occur if clonidine is abruptly discontinued regardless of route of administration. Symptoms associated with withdrawal may include nervousness, agitation, headache, tremor, sinus tachycardia, nausea, flushing, lightheadedness, chest pain/tightness, and anxiety. This effect is probably due to a drug-induced increase in the level of circulating catecholamines that follows abrupt cessation of therapy. Slowly tapering clonidine over several days will prevent this problem, and resumption of clonidine therapy will alleviate the symptoms. If it is necessary to discontinue immediate-release (IR) clonidine, slowly taper doses over 2-4 days to avoid withdrawal symptoms. If it is necessary to discontinue extended-release (ER) clonidine, reduce the dose by increments of <= 0.1 mg every 3-7 days. Chronic clonidine therapy should not be interrupted for surgery; transdermal systems may be left in place during surgery.
Clonidine is contraindicated in patients with a hypersensitivity to clonidine. Generalized rash, urticaria, and angioedema have occurred with clonidine use.
Administration of epidural clonidine above the C4 dermatome is contraindicated because there are no adequate safety data to support such use.
Abrupt discontinuation of clonidine, regardless of route of administration, can precipitate a withdrawal syndrome consisting of rebound increases in both serum and urine catecholamines. Symptoms of nervousness, agitation, headache, tremor, and rebound hypertension have been associated with clonidine withdrawal. Rarely, hypertensive encephalopathy, cerebrovascular accidents, and death have been reported. Patients at higher risk of experiencing adverse consequences of withdrawal include those with a history of hypertension or other cardiovascular disorders, receiving higher doses of clonidine, or receiving concomitant beta-blocker therapy. Pediatric patients receiving oral clonidine who experience gastrointestinal illness associated with vomiting may also be at risk for withdrawal due to abrupt inability to take medication. Careful monitoring of infusion pump function and catheter tubing for obstruction or dislodgement is recommended in patients receiving epidural clonidine to prevent inadvertent abrupt discontinuation.If it is necessary to discontinue clonidine, doses should be slowly tapered over 2-4 days to avoid withdrawal symptoms. Patients who have received clonidine therapy for greater than 4 weeks may require slower dosage tapers (i.e., dosage reduction every 3 days). If it is necessary to discontinue extended-release clonidine (Kapvay), reduce the dose by increments of <= 0.1 mg every 3-7 days. Monitoring of blood pressure and heart rate during weaning is recommended, even when clonidine is used for psychotropic indications.
The hypotensive effects of clonidine may decrease perfusion and worsen ischemia in patients with cerebrovascular disease, recent myocardial infarction, or severe heart failure. The sympatholytic action of clonidine may worsen sinus node dysfunction and AV block, especially in patients taking other sympatholytic agents. Because clonidine decreases blood pressure and heart rate, use clonidine extended-release tablets for ADHD with caution in patients with a history of hypotension, AV block, bradycardia, or cardiovascular disease. Patients with a history of syncope or conditions that may increase the risk of syncope such as hypotension, orthostatic hypotension, bradycardia, or dehydration should also be treated with caution. The American Heart Association (AHA) has recommended that pediatric patients receiving clonidine be monitored for changes in blood pressure at treatment initiation, periodically during treatment, and when tapering the drug, even when clonidine is used for psychotropic indications. In addition, the AHA recommends obtaining a detailed patient and family history and physical examination prior to the therapy initiation; obtaining a baseline electrocardiogram (ECG) is also a reasonable addition to the initial evaluation.
Adequate and well-controlled studies of oral clonidine have not been performed during pregnancy in humans. Consider the risk-benefit before use in pregnant patients; use only if clearly needed. One study found that clonidine crosses the placenta easily, and its concentrations were equal in maternal serum, and umbilical cord serum and amniotic fluid concentrations were up to 4 times that found in serum. There is one case report suggesting that an infant who is exposed to long-term clonidine (more than 300 mcg/day) during pregnancy may be more likely to develop a sleep disorder later in life. There is a pregnancy registry that monitors pregnancy outcomes in women exposed to ADHD medications, including clonidine, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or by visiting the worldwide web at womensmentalhealth.org/adhd-medications/. Epidural clonidine is not recommended as an analgesic during labor and obstetric delivery, or for post-partum or peri-operative analgesia due to the risks of hemodynamic instability, especially hypotension and bradycardia. However, the potential benefits of epidural clonidine may rarely outweigh the possible risks in such patients. Several trials examining the efficacy, safety, or dosing of epidural clonidine in obstetrics have been reported. In a study comparing a combination of epidural clonidine with bupivacaine and bupivacaine alone for analgesia during labor, there was no difference in maternal blood pressure reductions and infant Apgar scores at 1 and 5 minutes between the two groups. The duration of labor was prolonged in patients receiving clonidine.
Females and lower weight patients may be more susceptible to the hypotensive effects of epidural clonidine.
Clonidine should be administered cautiously to breast-feeding women. Clonidine is excreted in human breast milk. Based on published lactation studies, clonidine is present in human milk at relative infant doses ranging from 4.1% to 8.4% of the maternal weight-adjusted dosage. Although in most cases, there were no reported adverse effects in breastfed infants exposed to clonidine, there is one case report of sedation, hypotonia, and apnea in an infant exposed to clonidine through breast milk. Monitor exposed breastfed infants for symptoms of hypotension and bradycardia, such as sedation, lethargy, tachypnea, and poor feeding. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breastfed child from clonidine or from the underlying maternal condition.
Safety and efficacy of clonidine extended-release tablets have not been established in infants or children less than 6 years. Safe and effective use of immediate-release oral clonidine and transdermal clonidine have not been established in pediatric patients less than 18 years of age. Because clonidine decreases blood pressure and heart rate, use clonidine with caution in pediatric patients with a history of hypotension, AV block, bradycardia, or cardiovascular disease. Pediatric patients with a history of syncope or conditions that may increase the risk of syncope such as orthostatic hypotension, bradycardia, or dehydration should also be treated with caution. The American Heart Association (AHA) has recommended that all children and adolescents receiving clonidine be monitored for changes in blood pressure at treatment initiation, periodically during treatment, and when tapering the drug, even when clonidine is used for psychotropic indications. In addition, the AHA recommends obtaining a detailed patient and family history and physical examination prior to the therapy initiation; obtaining a baseline electrocardiogram (ECG) is also a reasonable addition to the initial evaluation. The safety and effectiveness of epidural clonidine in pediatric patients are based on limited data and have been established in patients old enough to tolerate placement and management of an epidural catheter, based on evidence from adequate and well-controlled studies in adults and experience with the use of clonidine in the pediatric age group for other indications. The use of epidural clonidine should be restricted to those children with severe intractable pain from a malignancy that is unresponsive to epidural or spinal opiates or other more conventional analgesic techniques. Dosing should be weight-based (e.g., 0.5 mcg/kg/hour initially) and adjusted to clinical response.
Use clonidine cautiously in patients with a history of major depression because the drug can induce depressive episodes.
Warn patients of the potential sedative and hypotensive effects of clonidine and advised against driving or operating machinery, or performing other hazardous tasks, until they are aware of how the medication affects them.
Use clonidine cautiously in patients with sinus node function impairment such as sick sinus syndrome, although its effects on cardiac conduction appear to be slight.
Use clonidine cautiously in patients with Raynaud's phenomenon or thromboangiitis obliterans (Buerger's disease). Clonidine may exacerbate these conditions.
Clonidine should be used cautiously in patients with diabetes mellitus because transient elevations in blood glucose have been noted. It has, however, been used safely in many diabetic patients.
Clonidine has been used safely in patients with renal disease. Clonidine is 45% renally excreted and drug concentrations may accumulate in renal failure. Therefore, the manufacturer recommends careful monitoring and that patients with renal impairment may benefit from a lower initial dose. In clinical practice, dosage adjustments are usually not clinically needed in patients with renal failure or renal disease, and the dosage of clonidine is titrated to achieve clinical goals.
Clonidine epidural injection is contraindicated in patients receiving anticoagulant therapy or in patients with a coagulopathy. Epidural clonidine is also contraindicated in patients with an infection at the site of injection.
Epidural clonidine should be used cautiously in patients with severe cardiac disease or who are hemodynamically unstable due to the potential for severe hypotension. When clonidine is administered into the upper thoracic spinal segments more profound decreases in blood pressure may be seen.
The inadvertent intrathecal administration of clonidine has not been associated with significantly increased adverse events; however, there are inadequate safety and efficacy data to support the use of intrathecal clonidine.
Clonidine transdermal systems should be removed prior to defibrillation (cardioversion) because the drug can alter electrical conductivity, increasing the likelihood that electrical arcing will occur. In addition, because some clonidine transdermal systems (e.g., Catapres-TTS, others) contain aluminum or other metal components, patients should be instructed to remove the patch before undergoing magnetic resonance imaging (MRI). Metal components contained in the backing of some transdermal systems can overheat during an MRI scan and cause skin burns in the area where the patch is adhered.
Absorption of transdermal clonidine can be decreased in patients with polyarteritis nodosa, scleroderma, or systemic lupus erythematosus (SLE), and the patches should not be placed on affected areas.
Absorption of transdermal clonidine can be increased in areas of skin irritation or skin abrasion, so placement of the patches in these areas should be avoided.
Careful consideration should be given to the scheduling of clonidine doses near the time of surgery; specific recommendations are available that are dependent on the dosage form. Oral administration of immediate-release clonidine should be continued to within 4 hours of surgery and resumed as soon as possible thereafter. Although the manufacturers of clonidine injection and Kapvay brand extended-release clonidine for ADHD do not provide specific recommendations regarding dosing near surgery, these formulations should not be abruptly discontinued due to the risk of withdrawal symptoms. Transdermal clonidine therapy should not be interrupted during the surgical period. Blood pressure should be carefully monitored during surgery; additional measures to control blood pressure should be readily available if necessary. If transdermal clonidine therapy is initiated during the perioperative period, clinicians must be aware that therapeutic plasma clonidine concentrations are not achieved until 2-3 days after initial application of the transdermal therapeutic system.
Clonidine is not expected to have a therapeutic effect on hypertension caused by pheochromocytoma.
Geriatric adults may be more susceptible to the hypotensive and sedative effects of clonidine. A reduction of the normal initial adult dosage may be considered when using clonidine for hypertension. Data are limited for the use of clonidine epidural injection for pain management in the older adult. There are no data to support efficacy and safety for the use of clonidine (e.g., Kapvay) in the treatment of older adults with attention-deficit disorder (ADHD). According to the Beers Criteria, clonidine is considered a potentially inappropriate medication for use as an antihypertensive in geriatric adults; avoid clonidine as a first-line antihypertensive and as routine treatment of hypertension due to the high risk of adverse CNS effects and the possibility of bradycardia or orthostatic hypotension.
For the treatment of hypertension:
Oral dosage (immediate-release tablets):
Adults: 0.1 mg PO twice daily, initially. May increase dose by 0.1 mg/day every 7 days if further control is needed. Usual dosage range: 0.1 to 0.8 mg/day. Max: 2.4 mg/day.
Children and Adolescents 12 years and older*: 0.1 mg PO twice daily, initially. May increase dose by 0.1 mg/day every 7 days if further control is needed. Usual adult dosage range: 0.1 to 0.8 mg/day. Max: 2.4 mg/day.
Children younger than 12 years*: Generally not recommended in children younger than 12 years. Initial doses of 5 to 10 mcg/kg/day PO in divided doses every 8 to 12 hours then titrated based on clinical response (Max: 25 mcg/kg/day or 0.9 mg/day) has been reported.
Transdermal dosage:
Adults: 0.1 mg/24 hours transdermally every 7 days. May increase dose by 0.1 mg/24 hours after 7 to 14 days if further control is needed. Usual dosage range: 0.1 to 0.3 mg/24 hours every 7 days. Max: 0.6 mg/24 hours every 7 days.
Children* and Adolescents*: Initial dosing recommendations for pediatric patients are not available. Although not studied specifically in children with hypertension, in children with psychiatric disorders such as Tourette's and ADHD, it has been suggested that once patients are stabilized on an oral dose, they can be converted to the transdermal patch that provides an approximately equivalent daily dose. While the manufacturer recommends patches be changed once every 7 days in adult patients, it is suggested that patches may need to be changed earlier (i.e., every 5 days) in pediatric patients due to variable absorption in this population. Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction.
For the treatment of hypertensive urgency* or hypertensive emergency*:
Oral dosage (immediate-release tablets):
Adults: 0.1 to 0.2 mg PO every hour as required to a total of 0.6 mg. Consider dosage reduction in elderly patients, as they may be more sensitive to the effects (sedation and hypotension) of the usual dosage.
Children and Adolescents: 2 to 5 mcg/kg/dose PO every 6 to 8 hours as needed (Max: 10 mcg/kg/dose) for severely hypertensive patients with non-life-threatening symptoms. Alternatively, 0.05 to 0.1 mg/dose PO, which can be repeated hourly as needed, up to a total dose of 0.8 mg PO.
For the treatment of attention-deficit hyperactivity disorder (ADHD) as monotherapy or as adjunctive therapy to a psychostimulant:
Oral dosage (extended-release; Kapvay):
Children and Adolescents 6 to 17 years: 0.1 mg PO once daily at bedtime, initially. Increase the dose by 0.1 mg/day at weekly intervals based on clinical response. Max: 0.4 mg/day. Administer doses more than 0.1 mg/day in 2 divided doses, with either an equal or higher split dosage being given at bedtime. When extended-release clonidine is added to a psychostimulant, the dosage of the psychostimulant may be adjusted according to response. When discontinuing clonidine, taper the dose by no more than 0.1 mg/day every 3 to 7 days to avoid rebound hypertension. Due to the lack of controlled clinical trial data and differing pharmacokinetic profiles, substitution of extended-release clonidine for other clonidine products on a mg-per-mg basis is not recommended.
Oral dosage (immediate-release)*:
Children and Adolescents 6 to 17 years weighing more than 45 kg: 0.1 mg PO once daily at bedtime, initially. Increase the dose by 0.1 mg/day to 0.1 mg PO twice daily, then 0.1 mg PO 3 times daily, and then 0.1 mg PO 4 times daily. Max: 0.4 mg/day. In a 16-week, multicenter, randomized, controlled clinical trial of children with ADHD and a chronic tic disorder (n = 136), clonidine doses were 0.25 mg/day PO as monotherapy and 0.28 mg/day PO with methylphenidate. The greatest ADHD benefit and improved tic severity compared to baseline was seen with the combined treatment of clonidine plus methylphenidate. Worsening of tics occurred in 20% to 26% of each treatment group, including placebo. Sedation was common (28%) with clonidine.
Children and Adolescents 6 to 17 years weighing 40.5 to 45 kg: 0.05 mg PO once daily at bedtime, initially. Increase the dose by 0.05 mg/day to 0.05 mg PO twice daily, then 0.05 mg PO 3 times daily, and then 0.05 mg PO 4 times daily. Max: 0.3 mg/day. In a 16-week, multicenter, randomized, controlled clinical trial of children with ADHD and a chronic tic disorder (n = 136), clonidine doses were 0.25 mg/day PO as monotherapy and 0.28 mg/day PO with methylphenidate. The greatest ADHD benefit and improved tic severity compared to baseline was seen with the combined treatment of clonidine plus methylphenidate. Worsening of tics occurred in 20% to 26% of each treatment group, including placebo. Sedation was common (28%) with clonidine.
Children and Adolescents 6 to 17 years weighing 27 to 40.4 kg: 0.05 mg PO once daily at bedtime, initially. Increase the dose by 0.05 mg/day to 0.05 mg PO twice daily, then 0.05 mg PO 3 times daily, and then 0.05 mg PO 4 times daily. Max: 0.2 mg/day. In a 16-week, multicenter, randomized, controlled clinical trial of children with ADHD and a chronic tic disorder (n = 136), clonidine doses were 0.25 mg/day PO as monotherapy and 0.28 mg/day PO with methylphenidate. The greatest ADHD benefit and improved tic severity compared to baseline was seen with the combined treatment of clonidine plus methylphenidate. Worsening of tics occurred in 20% to 26% of each treatment group, including placebo. Sedation was common (28%) with clonidine.
Transdermal dosage*:
Children and Adolescents 6 to 17 years: Initial dosing recommendations are not available; however, it has been suggested that once children are stabilized on an oral dose they may be converted to the transdermal patch that provides an approximately equivalent daily dose (e.g., 0.1, 0.2, or 0.3 mg/day). Patches are changed once every 7 days in adults; however, due to variable absorption in children, patches may need to be changed earlier (i.e., every 5 days). Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction.
For the treatment of severe pain:
-in cancer patients when the pain is not adequately relieved by opiate analgesics alone including neuropathic pain:
NOTE: Clonidine has been designated an orphan drug by the FDA for this indication.
NOTE: Epidural clonidine has been effective primarily in the subgroup of patients with neuropathic pain.
Epidural dosage:
Adults: Initially, 30 mcg/hour by continuous epidural infusion in combination with opioid analgesics, is recommended by the manufacturer. Dosage may be titrated up or down depending on pain relief and occurrence of adverse events; however, there is limited experience above the maximum rate of 40 mcg/hour. In clinical trials, bolus doses of epidural clonidine range from 100 to 900 mcg per dose. The dosage should be titrated to pain relief and incidence of side effects. Consider dosage reduction in elderly patients, as they may be more sensitive to the effects (sedation and hypotension) of the usual dosage.
Children and Adolescents: Initially, 0.5 mcg/kg/hour by continuous epidural infusion and adjusted cautiously based upon pain relief and incidence of side effects. It is recommended that epidural clonidine be restricted to pediatric patients with severe intractable pain from malignancy that is unresponsive to epidural or spinal opiates or other more conventional analgesic techniques. Epidural clonidine has been effective primarily in the subgroup of patients with neuropathic pain.
-in postoperative patients in combination with opiate analgesics:
NOTE: FDA-approved labeling does not recommend the use of epidural clonidine in obstetrical, post-partum, or peri-operative analgesia due to the risk of hemodynamic instability.
Epidural dosage:
Adults: Epidural clonidine 150 mcg in combination with fentanyl has been studied. This dose provided similar pain relief and increased the analgesia duration as compared to epidural fentanyl alone as a single dose. Epidural clonidine 450 mcg/day has been studied in combination with morphine. This dose resulted in improved pain relief and less rescue doses of morphine in comparison to epidural morphine alone in patients with postoperative pain. Consider dosage reduction in elderly patients, as they may be more sensitive to the sedative and hypotensive effects.
For the treatment of opiate agonist withdrawal*:
Oral dosage (immediate-release):
Adults: 0.1 to 0.2 mg PO every 4 to 6 hours, initially, as needed or as a standing dose in cases of severe withdrawal. Adjust dose until withdrawal symptoms are reduced. Monitor blood pressure and withhold dose if blood pressure is 90/60 mmHg or lower. Dose range: 0.1 to 0.3 mg PO every 4 to 8 hours. Max: 1.2 mg/day on day 1, then 2 mg/day. To discontinue, taper dose over several days while monitoring for signs of withdrawal.
Infants, Children, and Adolescents: Limited data available. 2 to 4 mcg/kg/dose PO every 4 to 6 hours as needed.
For the treatment of neonatal abstinence syndrome*:
Oral dosage:
Neonates: 0.5 to 1 mcg/kg/dose PO every 3 to 6 hours (Max: 8 mcg/kg/day PO) is recommended by the American Academy of Pediatrics (AAP). Dosages of 2 to 6 mcg/kg/day PO given in divided doses every 4 to 6 hours have been effective in treating opiate agonist withdrawal symptoms in neonates addicted to opiates secondary to intrauterine exposure to methadone or heroin and in neonates being weaned from opiate infusions. Premature neonates (n = 11, gestational age 24 to 35 weeks) were included in 1 small study.
For pheochromocytoma diagnosis*:
Oral dosage:
Adults: A single 0.3 mg PO dose administered after 30 minutes of inactivity successfully differentiated 10 patients with pheochromocytoma from 15 hypertensive patients without pheochromocytoma. Blood pressure, heart rate, and plasma catecholamines were assessed at 30, 60, 120, and 180 minutes post-dose. At 3 hours post-dose, norepinephrine concentrations were suppressed to normal or below normal in all patients without pheochromocytoma but in none of the 10 patients with the disease.
For the symptomatic treatment of diabetic neuropathy*:
Oral dosage:
Adults: Initially, 0.1 mg PO at bedtime. Gradually increase to 0.5 mg PO each night.
Elderly: Consider dosage reduction (see adult dosage). Elderly patients may be more sensitive to the effects (sedation and hypotension) of the usual dosage.
For the treatment of diabetic diarrhea*:
Oral dosage:
Adults: 0.1 mg PO every 12 hours, initially. Increase dose over 3 days up to 0.5 to 0.6 mg PO every 12 hours.
For the treatment of alcohol withdrawal*:
Oral dosage:
Adults: 0.2 mg PO at 9PM on day 1; at 9AM, 1PM, and 6PM on day 2; at 9AM and 6PM on day 3; and a final dose at 9AM on day 4.
For use as an adjunct to psychosocial interventions in the management of tobacco cessation* (smoking cessation*):
Oral dosage:
Adults: 0.1 mg PO once or twice daily initially. Dose range in clinical trials: 0.1 mg/day to 0.75 mg/day, in divided doses. Begin clonidine shortly before (up to 3 days) or on the quit date. The dose may be increased by 0.1 mg/day per week if needed. Dividing the total daily dose is suggested to increase tolerability. Consider a dosage reduction in elderly patients due to greater sensitivity to clonidine at usual dosages. Treatment duration has varied across clinical trials, generally ranging from 3 to 10 weeks. Common side effects include dry mouth, sedation, dizziness, drowsiness, and constipation. There is no clear dose-response relationship; however, dose-related adverse effects limit the clinical usefulness of the drug. DISCONTINUATION: Reducing the dose gradually over 2 to 4 days may mitigate a rebound phenomenon of rapid increase in blood pressure, agitation, confusion, and/or tremor. According to the Agency for Healthcare Research and Quality (AHRQ) treatment guidelines, clonidine is appropriate as a second-line medication for treating tobacco use.
Transdermal dosage:
Adults: Initially, 0.1 mg/24 hours applied transdermally once weekly. May increase the dose by 0.1 mg/24 hours weekly if needed. Transdermal doses ranging from 0.1 mg/24 hours to 0.2 mg/24 hours strength patch applied once weekly have been used in clinical trials. Consider low doses and slow titration in elderly patients because they may be more sensitive to common side effects of clonidine at usual dosages. Treatment duration has varied across clinical trials, generally ranging from 3 to 10 weeks. Common side effects include dry mouth, sedation, dizziness, drowsiness, and constipation. There is no clear dose-response relationship; however, dose-related adverse effects limit the clinical usefulness of the drug. According to the Agency for Healthcare Research and Quality (AHRQ) treatment guidelines, clonidine is appropriate as a second-line medication for treating tobacco use.
For the treatment of hot flashes* due to menopause*:
Oral dosage (immediate-release tablets):
Adult females: Initially, 0.05 mg PO twice daily or 0.1 mg PO once daily at bedtime. Higher doses of 0.1 mg PO twice daily or more may be necessary for some patients. Max studied: 0.2 mg PO twice daily. In a study of 194 postmenopausal women with breast cancer receiving tamoxifen, clonidine 0.1 mg PO once daily at bedtime reduced the number of hot flashes per day compared with placebo (p = 0.006); quality of life also improved. A meta-analysis estimates clonidine provides approximately a 1 hot flash/day reduction when compared to control groups; improvements in quality of life are also reported. The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy consider clonidine effective for vasomotor symptoms of menopause; however, it is typically not used as a first-line agent in the treatment of hot flashes as it is less effective and associated with more adverse effects compared to other non-hormonal pharmacologic therapies (e.g., paroxetine, gabapentin, venlafaxine).
Transdermal dosage:
Adult females: A dose of one Catapres TTS-1 patch (delivers clonidine 0.1 mg/24 hours) once weekly has been suggested. A meta-analysis estimates clonidine (oral or transdermal) provides approximately a 1 hot flash/day reduction when compared to control groups; improvements in quality of life are also reported. The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy consider clonidine effective for vasomotor symptoms of menopause; however, it is typically not used as a first-line agent in the treatment of hot flashes as it is less effective and associated with more adverse effects compared to other non-hormonal pharmacologic therapies (e.g., paroxetine, gabapentin, venlafaxine).
For the treatment of hypertension and the subsequent decline in renal function associated with scleroderma renal crisis (SRC)*:
Oral dosage:
Adults: Initially, 0.1 mg PO twice daily, increased by 0.1-0.2 mg/day PO to attain blood pressure response.
Elderly: Consider dosage reduction (see adult dosage). Elderly patients may be more sensitive to the effects (sedation and hypotension) of the usual dosage.
For minimization of nephrotoxicity in patients receiving cyclosporine (i.e., cyclosporine nephrotoxicity prophylaxis*) and low-dose methotrexate for allogeneic bone marrow transplant:
Transdermal dosage:
Adults: A small study compared the effect of transdermal clonidine patches on cyclosporine-induced nephrotoxicity in allogeneic bone marrow transplant patients. Transdermal clonidine 0.1 mg/day (from 4 days prior to 31 days after transplantation), titrated to 0.2 mg/day (if DBP not < 90 mm Hg), has been studied in 8 transplant patients. Twenty-three allogeneic BMT patients did not receive clonidine. Data from 23 autologous BMT patients were also included in the evaluation. At the end of the study, mean serum creatinine in the allogeneic group receiving clonidine was significantly lower than the allogeneic group not receiving clonidine (1.1 mg/dL vs 1.6 mg/dL) and was not significantly different from the autologous BMT group (0.9 mg/dL). NOTE: The Catapres-TTS-1 transdermal patch delivers clonidine 0.1 mg/day over 7 days; whereas the Catapres-TTS-2 patch delivers clonidine 0.2 mg/day over 7 days.
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects (sedation and hypotension) of the usual dosage.
For use in peripheral nerve block* including brachial plexus*, intercostal* and peribulbar* blocks in combination with local anesthetics:
Peripheral nerve block dosage:
Adults: Epidural clonidine 30 to 150 mcg has been used to enhance the effects of lidocaine in peripheral nerve blocks. In cataract surgery, clonidine 2 mcg/kg in combination with 3 to 4 mL of 2% lidocaine resulted in decreased intraocular pressure and longer post-operative analgesia and akinesia than lidocaine alone. Consider dosage reduction in elderly patients, as they may be more sensitive to the effects (sedation and hypotension) of the usual dosage.
Children and Adolescents 2 years and older: Limited data available; 1 mcg/kg/dose (Max: 100 mcg) as a single-shot nerve block in combination with a local anesthetic significantly prolonged the mean duration of sensory blockade (17.2 hours vs. 13.2 hours) and the mean duration of analgesia (10 hours vs. 6.8 hours) compared to nerve block with a local anesthetic alone in patients undergoing various surgeries.
For the treatment of tics associated with Tourette's syndrome* and chronic tic disorders*:
Oral dosage (immediate-release tablets):
Adults: Initially, 0.025 to 0.05 mg/day PO. Gradually titrate according to blood pressure and heart rate. Range: 0.025 to 0.6 mg/day PO. Max: 0.6 mg/day PO, usually given in 3 to 4 divided doses. Clonidine is recommended in evidence-based guidelines (strong recommendation, moderate-quality evidence). Consider a dose reduction in elderly patients, as they may be more sensitive to adverse effects at the usual dosages. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions.
Children and Adolescents 6 years and older: Initially, 0.025 to 0.05 mg/day PO; titrate gradually in increments of 0.025 mg to the target dose of 0.2 to 0.3 mg/day PO given in 3 to 4 divided doses. Max: 0.4 mg/day. In a 16-week, multicenter, randomized, controlled clinical trial of patients with ADHD and a chronic tic disorder (n = 136), clonidine doses were 0.25 mg/day PO (alone) and 0.28 mg/day PO (with methylphenidate about 26 mg/day PO). The greatest ADHD benefit and improved tic severity compared to baseline were seen with the combined treatment of clonidine plus methylphenidate. Worsening of tics occurred in 20% to 26% of each treatment group, including placebo. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions. The effect size of clonidine on tics appears larger in children with tics and ADHD compared to individuals with tics and without ADHD.
Oral dosage (extended-release tablets):
Children and Adolescents 6 years and older: Initially 0.1 mg/day PO at bedtime. Increase the dose in 0.1 mg/day increments weekly as needed to attain the desired response (Max: 0.4 mg/day). Divide doses larger than 0.1 mg/day into 2 doses taken in the morning and at bedtime. If the morning and bedtime doses are not equal, the larger dose should be given at bedtime. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions.
Transdermal dosage:
Children and Adolescents 6 years and older: Initial dosing recommendations for pediatric patients are not available; however, some patients stabilized on an oral dose may then be converted to the transdermal patch that provides an approximately equivalent daily dose (i.e., 0.1, 0.2, or 0.3 mg/day). Patches are changed once every 7 days in adults; however, due to variable absorption, patches may need to be changed earlier (i.e., every 5 days) in pediatric patients. Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction. The American Academy of Neurology practice guideline states that clonidine is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; weigh the benefits of treatment against the risks (e.g., sedation, hypotension). For those with comorbid attention-deficit hyperactivity disorder (ADHD), clonidine may provide benefits for both conditions. The effect size of clonidine on tics appears larger in children with tics and ADHD compared to individuals with tics and without ADHD.
For the treatment of aggressive behavior and hyperactivity/inattentiveness associated with autistic disorder*:
Oral dosage (immediate-release):
Children and Adolescents 5 to 17 years: 0.05 mg PO once daily in the evening for 3 days, then increase the dose to 0.05 mg PO twice daily. May further increase the dose by 0.05 mg/day every 3 days as needed. Usual dose: 0.1 to 0.4 mg/day in 3 to 4 divided doses. Max: 0.4 mg/day.
Transdermal dosage:
Children and Adolescents 5 to 17 years: Initial doses of 0.005 mg/kg/day rounded to the nearest available patch strength (patches are available in 3 strengths delivering doses of approximately 0.1, 0.2, or 0.3 mg/day over 7 days) were used in a small study including 7 pediatric patients (age range 5 to 12 years, weight range 19.1 to 52.7 kg). Patients weighing less than 25 kg were started on half a 0.1 mg/day patch for 3 days to minimize adverse reactions. The mean dose of clonidine used in the study was 0.16 +/- 0.09 mg/day. Although patches in this study were changed every 7 days, other authors have suggested that pediatric patients may require patches be changed earlier (i.e., every 5 days) due to variable absorption. Partial doses of patches may be administered by placing impermeable material (e.g., adhesive bandage) on the skin under the patch proportionate to the desired dose reduction.
For growth hormone deficiency diagnosis*:
Oral dosage:
Children and Adolescents: 5 mcg/kg PO as a single dose (Max: 250 mcg PO). Maximal growth hormone secretion usually occurs 60 minutes after the dose. Blood should be drawn at 0, 30, 60, and 90 minutes after the dose of clonidine is given. Similarly, blood pressure should be measured at these same time intervals.
For the treatment of hot flashes* due to prostate cancer* and associated induced androgen deficiency* ("andropause*") in men who have had surgical or medication induced castration:
Transdermal dosage:
Adult males: Apply one Catapres TTS-1 patch (delivers clonidine 0.1 mg/24 hours) once weekly. Limited data from a pilot study indicate that transdermal clonidine may have some benefit in reducing the frequency of hot flashes in men after bilateral orchiectomy; however a randomized clinical trial of transdermal clonidine showed no benefit compared to placebo.
For the treatment of benzodiazepine withdrawal*:
Oral dosage (immediate-release):
Infants, Children, and Adolescents: Limited data available. 2 to 4 mcg/kg/dose PO every 4 to 6 hours as needed.
For the treatment of insomnia* and sleep disturbance* associated with neurodevelopmental disorders, including autism spectrum disorder:
Oral dosage (immediate-release):
Children and Adolescents 4 to 17 years weighing more than 45 kg: 0.025 to 0.05 mg PO once daily at bedtime, initially. Increase the dose by 0.025 mg/day every 1 to 2 weeks as needed and tolerated. Max: 0.4 mg/day.
Children and Adolescents 4 to 17 years weighing 40.6 kg to 45 kg: 0.025 to 0.05 mg PO once daily at bedtime, initially. Increase the dose by 0.025 mg/day every 1 to 2 weeks as needed and tolerated. Max: 0.3 mg/day.
Children and Adolescents 4 to 17 years weighing 27 to 40.5 kg: 0.025 to 0.05 mg PO once daily at bedtime, initially. Increase the dose by 0.025 mg/day every 1 to 2 weeks as needed and tolerated. Max: 0.2 mg/day.
Children and Adolescents 4 to 17 years weighing less than 27 kg: 0.002 to 0.003 mg/kg/dose (Minimum: 0.025 mg/dose) PO once daily at bedtime, initially. Increase the dose by 0.005 to 0.01 mg/kg/day every 1 to 2 weeks as needed and tolerated. Max: 0.01 mg/kg/day or 0.2 mg/day.
For the treatment of short bowel syndrome*:
Oral dosage (immediate-release):
Adults: 0.05 mg PO 2 times daily, initially. May increase the dose by 0.05 mg/day weekly if inadequate response and depending on tolerability. Max: 0.2 mg PO 2 times daily.
Transdermal dosage:
Adults: 0.3 mg/24 hours transdermally every 7 days.
Maximum Dosage Limits:
-Adults
2.4 mg/day PO immediate-release tablets; two Catapres-TTS-3 transdermal patches/week (delivers 0.6 mg/day for 7 days) applied topically to skin; or 40 mcg/hour continuous epidural infusion.
-Geriatric
2.4 mg/day PO immediate-release tablets; two Catapres-TTS-3 transdermal patches/week (delivers 0.6 mg/day for 7 days) applied topically to skin; or 40 mcg/hour continuous epidural infusion.
-Adolescents
0.4 mg/day PO extended-release tablets; safety and efficacy of immediate-release tablets have not been established; however, doses up to 2.4 mg/day for hypertension have been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.
-Children
12 years: 0.4 mg/day PO extended-release tablets; safety and efficacy of immediate-release tablets have not been established; however, doses up to 2.4 mg/day for the treatment of hypertension have been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.
6 to 11 years: 0.4 mg/day PO extended-release tablets; safety and efficacy of immediate-release tablets have not been established; however, doses up to 0.9 mg/day PO for the treatment of hypertension have also been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.
1 to 5 years: Safety and efficacy have not been established; however, doses up 0.9 mg/day PO for the treatment of hypertension have been recommended. Maximum doses of transdermal and epidural clonidine in pediatric patients have not been established.
-Infants
Safety and efficacy have not been established; however, doses up to 4 mcg/kg PO have been recommended for the management of the symptoms of opioid or benzodiazepine withdrawal.
-Neonates
Neonates: Safety and efficacy have not been established; however, doses up to 12 mcg/kg/day PO have been used off-label for the management of neonatal abstinence syndrome.
Premature Neonates: Safety and efficacy have not been established; however, doses up to 12 mcg/kg/day PO have been used off-label for the management of neonatal abstinence syndrome.
Patients with Hepatic Impairment Dosing
No quantitative recommendations are available. Because clonidine is substantially metabolized by the liver, monitor patients for sedation and hypotension and adjust the dose if necessary.
Patients with Renal Impairment Dosing
A lower initial dose may be beneficial; patients should be carefully monitored for bradycardia, sedation, and hypotension.
Intermittent hemodialysis
Clonidine is minimally removed by hemodialysis. In general, no supplemental dosage is needed following hemodialysis. Adjust dosage based on clinical response.
*non-FDA-approved indication
Acarbose: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Acebutolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetazolamide: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alfentanil: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Alogliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alogliptin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alogliptin; Pioglitazone: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alpha-glucosidase Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Alprazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and central-acting antihypertensive agents may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Amiodarone: (Moderate) Monitor for potential bradycardia or atrioventricular block during coadministration with amiodarone. Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate.
Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Amoxapine: (Major) Concurrent use of clonidine with amoxapine should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants; occasionally, the hypertension will occur within the first few days of combined therapy. If coadministration of amoxapine with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed. In addition, concurrent administration of a cyclic antidepressant and clonidine may result in additive CNS depression or other side effects; clonidine produces mental depression as a side effect in roughly 1% of patients. In rats, the coadministration of a cyclic antidepressant (amitriptyline) with clonidine resulted in corneal lesions, but the human implications of these animal study findings are unknown.
Amphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Amphetamine; Dextroamphetamine Salts: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Amphetamine; Dextroamphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Apomorphine: (Moderate) Use of central-acting adrenergic agents and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Aripiprazole: (Minor) Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Atenolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Atenolol; Chlorthalidone: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzodiazepines: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Benzphetamine: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of clonidine. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed.
Beta-blockers: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Betaxolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Bexagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Bisoprolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brimonidine; Timolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Brompheniramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including clonidine. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Canagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Canagliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbidopa; Levodopa; Entacapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including clonidine, due to the possibility of additive sedation and hypotension. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbonic anhydrase inhibitors: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Cardiac glycosides: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Carteolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Carvedilol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and clonidine. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Avoid concomitant use of ceritinib with clonidine if possible due to the risk of additive bradycardia. Both ceritinib and clonidine can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlordiazepoxide: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines. (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Chlordiazepoxide; Clidinium: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpheniramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Chlorpromazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Clomipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Clonazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Clorazepate: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and central-acting adrenergic agents use. Concomitant use may result in additive hypotension.
COMT inhibitors: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including clonidine, due to the possibility of additive sedation and hypotension. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Crizotinib: (Major) Avoid coadministration of crizotinib with agents known to cause bradycardia, such as clonidine, to the extent possible due to the risk of additive bradycardia. If concomitant use is unavoidable, monitor heart rate and blood pressure regularly. An interruption of crizotinib therapy or dose adjustment may be necessary if bradycardia occurs.
Cyclobenzaprine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and cyclobenzaprine; a clonidine dose adjustment may be necessary. Concomitant use may result in decreased clonidine efficacy and/or additive CNS depression. The hypotensive effect of clonidine may be reduced by tricyclic antidepressants, and cyclobenzaprine is structurally related to the tricyclic antidepressants.
Cyclosporine: (Minor) Clonidine can inhibit cyclosporine-induced glomerular vasoconstriction and has been shown to offset cyclosporine-induced nephrotoxicity. Clonidine may adversely affect cyclosporine pharmacokinetics; limited data suggest that cyclosporine concentrations increase - dramatically, in some cases - when clonidine is added. Until more data are available, clinicians should use clonidine cautiously in patients stabilized on cyclosporine.
Dapagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Dapagliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Dapagliflozin; Saxagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Desipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clonidine, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dexmethylphenidate: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Dextroamphetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents. Diazoxide can enhance the hyperglycemic, hyperuricemic and antihypertensive effects of thiazide diuretics.
Diethylpropion: (Major) Sympathomimetics, such as diethylpropion, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Digoxin: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides.
Diltiazem: (Moderate) Avoid concomitant use of diltiazem and extended-release clonidine tablets. Monitor heart rate during concomitant use of diltiazem and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of diltiazem and clonidine.
Dipeptidyl Peptidase-4 Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Diphenhydramine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Dobutamine: (Major) Sympathomimetics, such as dobutamine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dopamine: (Moderate) Sympathomimetics, such as dopamine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Dorzolamide; Timolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Doxepin: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Dulaglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Duloxetine: (Moderate) Monitor blood pressure during concomitant duloxetine and central-acting adrenergic agent use. Concomitant use increases the risk for hypotension, including orthostatic hypotension and syncope. Consider reducing the duloxetine dose or discontinuing duloxetine if symptomatic orthostatic hypotension, falls, or syncope occur during treatment.
Empagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Linagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Linagliptin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Empagliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Entacapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including clonidine, due to the possibility of additive sedation and hypotension. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and clonidine; clonidine augments the pressor effect of ephedrine.
Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and clonidine; clonidine augments the pressor effect of ephedrine.
Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Epoprostenol: (Moderate) The concomitant administration of epoprostenol with other antihypertensive agents can result in additive hypotensive effects. This can be therapeutically advantageous, but dosages must be adjusted accordingly.
Ertugliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ertugliflozin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ertugliflozin; Sitagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Esketamine: (Major) Closely monitor patients receiving esketamine and clonidine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Esmolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Estazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Ethanol: (Major) Advise patients to avoid alcohol use while taking clonidine. Clonidine may potentiate the CNS-depressive effects of alcohol.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Exenatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and clonidine. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Fexinidazole: (Major) Avoid concomitant use of fexinidazole and medications that cause bradycardia, such as clonidine, especially in patients with additional risk factors for torsade de pointes (TdP). Coadministration may increase the risk of QT/QTc prolongation and TdP. Fexinidazole is known to prolong the QT interval and medications that may cause bradycardia can increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Fluphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Flurazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and clonidine. Concomitant use of gabapentin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Glimepiride: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Glipizide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Glipizide; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Glyburide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Glyburide; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Guaifenesin; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Haloperidol: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Hydrocodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydromorphone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Imipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Incretin Mimetics: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Aspart: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Aspart; Insulin Aspart Protamine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Degludec: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Degludec; Liraglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Detemir: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Glargine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Glargine; Lixisenatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Glulisine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Lispro: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin Lispro; Insulin Lispro Protamine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulin, Inhaled: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Insulins: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Intravenous Lipid Emulsions: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Isocarboxazid: (Moderate) Monitor blood pressure closely if clonidine is coadministered with monoamine oxidase inhibitors (MAOIs). Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Isophane Insulin (NPH): (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Isoproterenol: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Labetalol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and clonidine. Concurrent use may result in additive CNS depression. Additionally, monitor heart rate if lasmiditan is coadministered with clonidine as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and clonidine. Dosage adjustments of lemborexant and clonidine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levobunolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and clonidine due to the risk for additive CNS depression.
Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Levomilnacipran: (Moderate) Because levomilnacipran inhibits norepinephrine reuptake, coadministration with clonidine may inhibit clonidine's antihypertensive effect.
Levorphanol: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Linagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Linagliptin; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Liraglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Lisdexamfetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving clonidine and lisdexamfetamine. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Lixisenatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Lofexidine: (Major) Lofexidine is a central alpha-2 adrenergic agonist, and its effects can be additive to other medications in the same class. Monitor for excessive hypotension, bradycardia, and sedation during coadministration. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Lorazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Lumateperone: (Moderate) Monitor for excessive sedation, somnolence, and orthostatic hypotension during coadministration of lumateperone and clonidine. Concurrent use may result in additive CNS depression or orthostasis.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may transiently elevate growth hormone concentrations, such as clonidine. Healthcare providers are advised to discontinue clonidine therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Maprotiline: (Major) Concurrent use of clonidine with maprotiline should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants, such as maprotiline. If coadministration of maprotiline with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed.
Meglitinides: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Meperidine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Repaglinide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Saxagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Metformin; Sitagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Methadone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like clonidine, when clonidine is used for blood pressure control. Close monitoring of blood pressure is advised.
Methazolamide: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Methylphenidate Derivatives: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Methylphenidate: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Metoprolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Midazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Midodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Miglitol: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Milnacipran: (Moderate) Because milnacipran inhibits norepinephrine reuptake, coadministration with clonidine may inhibit clonidine's antihypertensive effect.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mirtazapine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and mirtazapine. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression. Mirtazapine and clonidine have pharmacologic actions that potentially oppose one another. Mirtazapine inhibits central alpha-2 autoreceptors (located presynaptically on noradrenergic neurons) and stimulating norepinephrine and stimulates the serotonergic system through antagonism at alpha-2 heteroreceptors. Clonidine exerts its antihypertensive effect by stimulating the central alpha-2 autoreceptors, thereby causing a reduction in the synthesis and release of norepinephrine.
Monoamine oxidase inhibitors: (Moderate) Monitor blood pressure closely if clonidine is coadministered with monoamine oxidase inhibitors (MAOIs). Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives.
Morphine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Nabilone: (Major) Monitor for excessive sedation and somnolence during coadministration of nabilone and clonidine. Concurrent use may result in additive CNS depression.
Nadolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Naproxen; Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Nateglinide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Nebivolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Nebivolol; Valsartan: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Nitrates: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroglycerin: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Norepinephrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Nortriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Oliceridine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opiate Agonists: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opicapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including clonidine, due to the possibility of additive sedation and hypotension. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Oxazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Oxycodone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by clonidine. If these drugs are used together, closely monitor for changes in blood pressure.
Oxymorphone: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and central-acting adrenergic agents who are susceptible to hypotension.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Perphenazine; Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Phendimetrazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Phenelzine: (Moderate) Monitor blood pressure closely if clonidine is coadministered with monoamine oxidase inhibitors (MAOIs). Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives.
Phenothiazines: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Phentermine: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Phentermine; Topiramate: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Pimozide: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may be induced or exacerbated in patients receiving concomitant clonidine and antipsychotics. Caution patients to avoid hazardous tasks, such as driving or operating machinery, until the effects of concurrent use are known. Also, 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. A causal relationship and relevance for clonidine oral tablets have not been established.
Pindolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Pioglitazone: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Pioglitazone; Glimepiride: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Pioglitazone; Metformin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Ponesimod: (Major) Avoid concomitant use of ponesimod and medications that may decrease heart rate such as clonidine due to the risk for severe bradycardia and heart block. Consider consultation from a cardiologist if concomitant use is necessary.
Pramlintide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and clonidine. Concomitant use of pregabalin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Prochlorperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Dextromethorphan: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Phenylephrine: (Major) The cardiovascular effects of sympathomimetics, such as phenylephrine, may reduce the antihypertensive effects produced by clonidine. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Propranolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Protriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Pseudoephedrine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Quazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Quetiapine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and quetiapine. Coadministration may induce or exacerbate orthostatic regulation disturbances, such as orthostatic hypotension, dizziness, or fatigue, as well as produce additive CNS depression.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rasagiline: (Moderate) Orthostatic hypotension has been reported during administration of rasagiline; caution is advised during concurrent use with antihypertensive agents. Patients receiving rasagiline in combination with an antihypertensive should be instructed to rise slowly from a sitting position, and to report syncope, and changes in heart rate or blood pressure to their health care provider. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, serious hypertensive reactions with agents affecting catecholamine release (e.g., guanabenz, reserpine, guanethidine) are unlikely.
Regular Insulin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Regular Insulin; Isophane Insulin (NPH): (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Remifentanil: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Remimazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Repaglinide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Rosiglitazone: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Saxagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Semaglutide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Monitor blood pressure during concomitant clonidine and methylphenidate use; a clonidine dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of drugs used to treat hypertension.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
SGLT2 Inhibitors: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sitagliptin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Sotagliflozin: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Sotalol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clonidine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Sulfonylureas: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Tapentadol: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Temazepam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thiazolidinediones: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Thioridazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Timolol: (Moderate) Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction (e.g., beta-blockers). Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents. Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis. If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Tirzepatide: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Tizanidine: (Major) The use of tizanidine with other alpha 2-adrenergic agonists (such as central-acting adrenergic agonist antihypertensive agents) should be avoided because hypotensive effects may be cumulative. Tizanidine is an alpha 2-adrenergic agonist that can produce hypotension. Syncope has been reported in the postmarketing setting.
Tolcapone: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including clonidine, due to the possibility of additive sedation and hypotension. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tramadol: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Trandolapril; Verapamil: (Moderate) Avoid concomitant use of verapamil and extended-release clonidine tablets. Monitor heart rate during concomitant use of verapamil and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of verapamil and clonidine.
Tranylcypromine: (Moderate) Monitor blood pressure closely if clonidine is coadministered with monoamine oxidase inhibitors (MAOIs). Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives.
Trazodone: (Moderate) Monitor for unusual drowsiness or excess sedation during coadministration of clonidine and trazodone due to risk for additive CNS depression.
Triazolam: (Moderate) Clonidine has CNS depressive effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Tricyclic antidepressants: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Trifluoperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Trimipramine: (Moderate) Monitor blood pressure and for unusual drowsiness or excess sedation during coadministration of clonidine and tricyclic antidepressants. Concomitant use may result in reduced hypotensive effect of clonidine and additive CNS depression.
Verapamil: (Moderate) Avoid concomitant use of verapamil and extended-release clonidine tablets. Monitor heart rate during concomitant use of verapamil and other clonidine formulations. Concomitant use may potentiate bradycardia and risk of AV block. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported during the use of verapamil and clonidine.
Vitamin B Complex Supplements: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Clonidine is an agonist at presynaptic alpha2-receptors in the medulla, specifically, the nucleus tractus solitarius (i.e., the depressor area of the vasomotor center of the medulla oblongata). Stimulation of these receptors results in the inhibition of sympathetic outflow and tone. Suppression of efferent sympathetic pathways decreases vascular tone in the heart, kidneys, and peripheral vasculature; lowers peripheral resistance; and reduces blood pressure. Reflex tachycardia usually does not occur. Instead, stimulation of the central alpha-receptors by clonidine results in a reciprocal increase in vagal tone, causing an increase in baroreceptor activity and bradycardia. Clonidine is also a partial agonist at presynaptic alpha2-adrenergic receptors of peripheral nerves in vascular smooth muscle, however, this site of action contributes little, if anything, to its antihypertensive effects. Doses higher than those required to lower blood pressure are necessary to demonstrate agonism at this peripheral site. Further, it has been shown that alpha2-agonists that cannot penetrate the blood-brain barrier do not effectively lower blood pressure. Agonism at peripheral presynaptic alpha2-receptors may interfere with the peripheral regulation of norepinephrine.
Intravenous administration or large oral doses of clonidine also can stimulate alpha1-receptors in peripheral vascular smooth muscle, resulting in acute vasoconstriction and a transient increase in blood pressure. An accurate correlation between clonidine's plasma concentrations and its antihypertensive effects is evident only at lower plasma concentrations. Higher plasma concentrations of clonidine will result in reduced antihypertensive activity because of the increased contribution of the pressor effect.
Inhibition of sympathetic outflow by clonidine results in a variety of pharmacodynamic effects. In the supine position, decreased sympathetic tone reduces heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV), with essentially no change in the total peripheral resistance (TPR), renal blood flow (RBF), renal plasma flow (RPF), glomerular filtration rate (GFR), urinary potassium excretion, or renal vascular resistance (RVR). Urinary sodium and chloride excretion are increased, however. Thus, the principal antihypertensive effect in the supine position is related to the reduction in cardiac output secondary to the reduced stroke volume and heart rate.
In the erect position (45-degree tilt), clonidine reduces MAP, CO, HR, and TPR, with no significant change in stroke volume. Cardiac output due to clonidine decreases less in hypertensive patients than in normal patients, and the antihypertensive effects of the drug appear to be related to a reduction in both cardiac output and TPR, with the effects of the reduced TPR predominating in the erect position. Renin and aldosterone output are reduced. Clonidine appears to decrease catecholamine excretion during prolonged therapy, but it does not deplete catecholamine stores. As an antihypertensive, clonidine reduces LVH and does not cause detrimental effects on glucose tolerance, although sexual dysfunction is a significant problem.
Clonidine is used to treat hypertension and the subsequent decline of renal function in patients with scleroderma renal crisis (SRC). SRC is associated with elevated peripheral renin concentrations. Clonidine reduces plasma renin activity by reducing sympathetic activity while increasing parasympathetic activity.
Because of clonidine's ability to inhibit sympathetic outflow, it has been used successfully to manage withdrawal from opiate agonists, ethanol, or nicotine; and 'hot flashes' associated with menopause. By inhibiting intrarenal vasoconstriction, clonidine has been used to offset cyclosporine-induced nephrotoxicity. Since pheochromocytomas are not under neurologic control, clonidine has been used successfully to differentiate the presence of these tumors from other hypertension-associated disease states.
Clonidine administered epidurally produces a dose-dependent analgesia that is not antagonized by opiate antagonists. By preventing pain signal transmission to the brain, clonidine produces analgesia at presynaptic and postjunctional alpha2-adrenoceptors in the spinal cord. Yohimbine, an alpha2-adrenoreceptor antagonist, will partially reverse the analgesic and sedation effects of epidural clonidine with no effect on clonidine-induced changes in blood pressure or heart rate. Clonidine-induced analgesia occurs only in body regions innervated by spinal segments where analgesic concentrations of clonidine are present. Clonidine enhances epidural or peripheral nerve blocks by blocking the conduction of C and A delta fibers and increasing potassium conductance in neurons and causing local vasoconstriction decreasing the elimination of the local anesthetic.
Clonidine is administered epidurally, orally, and via transdermal patch. Fifty percent (50%) of a circulating dose is metabolized in the liver to inactive compounds. Unchanged drug (40% to 60%) and its metabolites are excreted in the urine and feces.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Oral Route
Immediate- and extended-release clonidine have different pharmacokinetics characteristics; dose substitution on a mg-for-mg basis will result in differences in exposure. Food does not influence the pharmacokinetics of oral clonidine. The pharmacokinetics of clonidine are dose-proportional in the range of 100 to 600 mcg. Elimination half-life of clonidine is approximately 12 to 16 hours.
Immediate-release (IR) formulations
After oral administration of IR formulation, peak plasma concentrations are reached in approximately 1 to 5 hours. The absolute oral bioavailability is 70% to 80%. Blood pressure begins to decrease within 30 to 60 minutes, with maximal hypotensive effects occurring in 2 to 4 hours. Mean single-dose pharmacokinetic parameters in healthy adult patients (fasted-state; n = 15) during clinical trials were as follows: Cmax = 443 pg/mL; AUC = 7,313 hour x pg/mL; Tmax = 2.07 hours; half-life = 12.57 hours.
Extended-release (ER) formulations
After oral administration of ER formulation, peak clonidine concentrations were approximately 50% of those achieved with the IR formulation and occurred approximately 5 hours later. Similar half-lives were observed and total systemic bioavailability after the ER formulation was approximately 89% of that after the IR formulation. Mean single-dose pharmacokinetic parameters in healthy adult patients (fasted-state; n = 14) during clinical were as follows: Cmax = 258 pg/mL; AUC = 6,729 hour x pg/mL; Tmax = 6.5 hours; half-life = 12.65 hours.
Other Route(s)
Transdermal Route
The clonidine transdermal system consists of a patch, or 0.2 mm thick film, that contains four layers of a microporous polypropylene membrane. This patch holds a reservoir of clonidine that is released and absorbed across the skin at a constant rate over a 7-day period. The absolute bioavailability of clonidine from the transdermal patch is approximately 60%. Steady-state clonidine plasma concentrations are reached within 3 days after transdermal application to the upper outer arm and increase linearly with increasing size of the transdermal patch. Mean steady-state plasma concentrations with the 3.5 cm2 (0.1 mg clonidine/day), 7 cm2 (0.2 mg clonidine/day) and 10.5 cm2 (0.3 mg clonidine/day) systems are approximately 0.4 ng/mL, 0.8 ng/mL, and 1.1 ng/mL, respectively. Similar clonidine steady-state concentrations are reached after application to the chest. Steady-state clonidine plasma levels remain constant after removal of one system and application of a new system of the same size. After removal of the transdermal system, clonidine plasma concentrations decline slowly with a half-life of approximately 20 hours.
Epidural Route
Following epidural administration, peak clonidine plasma and cerebrospinal fluid concentrations were achieved in 19 and 26 minutes, respectively. Epidurally administered clonidine distributes into plasma via the epidural veins. Clonidine is highly lipid soluble and distributes widely throughout the body tissues, including the central nervous system. The CSF elimination half-life of clonidine is 1.3 hours. After an epidural dose of clonidine, women had a lower mean plasma clearance, longer mean plasma half-life, and higher mean peak concentration of clonidine in the plasma and CSF compared to men. The pharmacokinetics of epidural clonidine in children 1 to 9 years of age is similar to adults.
-Special Populations
Renal Impairment
The half-life of clonidine increases up to 41 hours in patients with severe renal impairment.
Pediatrics
Children and Adolescents
The pharmacokinetics of epidural clonidine in children 1 to 9 years of age is similar to those of adults. After oral administration of extended-release tablets at doses of 0.1 to 0.2 mg PO twice daily, plasma clonidine concentrations are higher in children and adolescents with ADHD than those of adults with hypertension with the pediatric patients receiving higher doses on a mg/kg basis. Body weight normalized clearance (CL/F) in children and adolescents was higher than observed in adults with hypertension. Clonidine plasma concentrations increased with increases in dose over the dose range of 0.2 to 0.4 mg/day of the extended-release tablets. Clonidine CL/F was independent of dose administered over the 0.2 to 0.4 mg/day dose range and appeared to decrease slightly with increases in age over the range of 6 to 17 years. CL/F was 23% lower in females than males. Clonidine CL/F was also 11% higher in patients who were also receiving methylphenidate and 44% lower in those receiving amphetamine compared to subjects not on adjunctive therapy.
Neonates
The half-life of clonidine is prolonged in neonatal patients (44 to 72 hours) compared to adult patients (12 to 16 hours). However, a pharmacokinetic study in 36 neonatal patients (postnatal age 1 to 25 days, mean gestational age 38.7 +/- 1.4 weeks) showed that clearance increases rapidly with age, achieving 70% of adult values by 1 month of age.
Gender Differences
After an epidural dose of clonidine, women had a lower mean plasma clearance, longer mean plasma half-life, and higher mean peak concentration of clonidine in the plasma and CSF compared to men. In pediatric trials of the extended-release tablets, body weight normalized clearance was 23% lower in and females than males.