Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).ustekinumabMonitor Closely (1)ustekinumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.verapamilMonitor Closely (2)clonidine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine. verapamil, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.vilazodoneMonitor Closely (1)clonidine, vilazodone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.vildagliptinMinor (2)clonidine decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, vildagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.voclosporinMonitor Closely (1)voclosporin will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Coadministration of voclosporin (a P-gp inhibitor) increases exposure and risk of adverse reactions of P-gp substrates. For certain P-gp substrates with a narrow therapeutic window, refer to prescribing information of these substrates for dosage modifications, if needed.vortioxetineMonitor Closely (1)clonidine, vortioxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.xipamideMonitor Closely (1)xipamide increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor.yohimbeSerious - Use Alternative (1)yohimbe decreases effects of clonidine by pharmacodynamic antagonism. Contraindicated.ziprasidoneMonitor Closely (1)clonidine, ziprasidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.zolpidemSerious - Use Alternative (1)clonidine, zolpidem. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.zotepineMonitor Closely (1)clonidine, zotepine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium. >10% Skin reactions; patch (15-50%) Dry mouth (40%) Somnolence (19-38%) Headache (19-29%) Fatigue (13-24%) Drowsiness (33%) Dizziness (13-16%) Hypotension, epidural (45%) Postural hypotension, epidural (32%) Anxiety (11%) 1-10% Constipation (10%) Sedation (10%) Nausea/vomiting, PO (5%) Malaise (3%) Orthostatic hypotension (3%) Anorexia, PO (1%) Abnormal LFTs (1%) Rash (1%) Weight gain, PO (1%) Frequency Not Defined Children with ADHD Upper respiratory tract infection Irritability Throat pain Nightmares Insomnia Emotional disorder Constipation Nasal congestion Postmarketing Reports Hallucinations AV block Black Box Warnings Epidural clonidine is not recommended for obstetric postpartum or perioperative pain management because the risk of hemodynamic instability (eg, hypotension, bradycardia) may be unacceptable in this population Dilute product with strength of 500 mcg/mL prior to useContraindications Hypersensitivity Epidural Concurrent anticoagulants, bleeding diathesis Presence of injection site infections Administration above C4 dermatome, due to lack of adequate safety data Obstetric/perioperative pain Cautions Epidural: Hemodynamically unstable patients (risk of severe hypotension) Do not discontinue suddenly (risk of rebound hypertension) Patch: May need to remove if severe erythema and/or localized vesicle formation develop at application site or generalized rash; consult physician Severe coronary insufficiency May cause xerostomia Recent MI Cerebrovascular disease Chronic renal failure Raynaud's disease Thromboangiitis obliterans History of depression (may exacerbate depression in cancer patients) May impair ability to perform hazardous tasks Remove patch before MRI (may cause burns) Hypotension may occur; usually responsive to IV fluids and, if necessary, appropriate parenterally administered pressor agents Cardiac conduction abnormalities: Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block, especially if coadministered with other sympatholytic drugs Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease or chronic renal failure; measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy; avoid concomitant use of drugs with additive effects unless clinically indicated; advise patients to avoid becoming dehydrated or overheated Epidural administration may result in mild respiratory depression (usually with higher than recommended dose) Use with caution in cerebrovascular disease Avoid as first line antihypertensive in the elderly due to high risk for adverse side effects Children may be particularly susceptible to hypertensive episodes when experiencing GI illnesses that lead to vomiting Discontinue oral immediate release formulations within 4 hr of surgery; restart as soon as possible following surgery Due to different pharmacokinetic profiles, oral formulations are not interchangeable with extended release on a mg-mg basis due to different pharmacokinetic profiles Pregnancy There is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866- 961-2388 or visiting https://womensmentalhealth.org/adhd-medications Prolonged experience with clonidine in pregnant women over several decades, based on published literature, including controlled trials, a retrospective cohort study and case reports, have not identified a drug associated risk of major birth defects, miscarriage, and adverse maternal or fetal outcomes Based on findings in animal studies revealed that drug may impair fertility in females and males of reproductive potential Animal data In animal embryofetal studies, increased resorptions were seen in rats and mice administered oral clonidine hydrochloride from implantation through organogenesis at 10 and 5 times, respectively, the maximum recommended human dose (MRHD) given to adolescents on a mg/m2 basis; no developmental effects were seen in rabbits administered drug during organogenesis at doses up to 3 times the MRHD Lactation Based on published lactation studies, clonidine hydrochloride is present in human milk at relative infant doses ranging from 4.1 to 8.4% of 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; if an infant is exposed to clonidine hydrochloride through breastmilk, monitor for symptoms of hypotension and bradycardia, such as sedation, lethargy, tachypnea and poor feeding Consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition; exercise caution when drug is administered to a nursing woman Monitor breastfeeding infants exposed to drug through breast milk for symptoms of hypotension and/or bradycardia such as sedation, lethargy, tachypnea, and poor feedingPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Central sympatholytic via stimulation of central alpha receptors; results in reduced sympathetic outflow, causing decreased PVR, HR, BP, and renal vascular resistance; produces presynaptic and postjunctional alpha-2 adrenoreceptor analgesia by preventing pain signal transmission to brain Postsynaptic alpha2-agonist stimulation may regulate subcortical activity in the prefrontal cortex, which may regulate the area of the brain responsible for attention, emotions, and behaviors, and thereby reduces hyperactivity, distractibility, and impulsiveness Absorption Bioavailability: Immediate release (75-85%); extended release (89%) Onset: <1 hr (2-4 hr peak effect in blood pressure) Duration: 6-10 hr Peak plasma time: 1-3 hr (immediate release); 7-8 hr (extended release) Distribution Protein bound: 20-40% Vd: 2.9 L/kg Metabolism Liver Elimination Half-life: 12-16 hr Excretion: Urine (40-60%) Hypertension Immediate release May administer with or without food The dose must be adjusted according to the patient’s individual blood pressure response Increments of 0.1 mg per day may be made at weekly intervals if necessary until desired response achieved; taking the larger portion of the oral daily dose at bedtime may minimize transient adjustment effects of dry mouth and drowsiness; therapeutic doses most commonly used have ranged from 0.2 mg to 0.6 mg per day given in divided doses; studies have indicated that 2.4 mg is maximum effective daily dose, but rarely used Transdermal patch Apply the transdermal therapeutic system once every 7 days to a hairless area of intact skin on upper outer arm or chest; each new application of transdermal therapeutic system should be on a different skin site from previous location If the system loosens during 7-day wearing, the adhesive cover should be applied directly over system to ensure good adhesion; there have been rare reports of need for patch changes prior to 7 days to maintain blood pressure control To initiate therapy, titrate the transdermal therapeutic system dosage according to individual therapeutic requirements, starting with CATAPRES-TTS-1; if after one or two weeks the desired reduction in blood pressure not achieved, increase dosage by adding another CATAPRES-TTS-1 or changing to a larger system; an increase in dosage above two CATAPRES-TTS-3 is usually not associated with additional efficacy When substituting CATAPRES-TTS transdermal therapeutic system for oral clonidine or for other antihypertensive drugs, physicians should be aware that the antihypertensive effect of CATAPRES-TTS transdermal therapeutic system may not commence until 2-3 days after initial application; gradual reduction of prior drug dosage is advised; some or all previous antihypertensive treatment may have to be continued, particularly in patients with more severe forms of hypertension Conversion of dosage forms Oral to transdermal Day 1: Place Catapress-TTS-1; administer 100% of oral dose Day 2: Administer 50% of oral dose Day 3: Administer 25% of oral dose Day 4: Patch remains, no further oral supplement needed Transdermal to oral Clonidine levels persist for 8 hr after removing transdermal patch and decrease slowly over several days; effects may persist for 24-48 hr after removal Consider a persistent effect on blood pressure when initiating immediate release clonidine; consider initiating immediate release oral clonidine no sooner than 8 hr after patch removal Attention Deficit Disorder Extended-release tablets Substitution of extended-release for other clonidine products on an mg-per-mg basis not recommended Doses 0.2 mg/day or greater should be divided BID, with either an equal or higher split dosage being given at bedtime Tablet must be swallowed whole, never crushed, cut, or chewed, and may be taken with or without food; when initiating treatment, provide dosage escalation instructions Cancer pain Dilute 500 mcg/mL to 100 mcg/mL with 0.9% NaCl before administration Epidural infusion considered as adjunct to intraspinal opiate therapy; epidural administration (Duraclon) is indicated in combination with opiates for the treatment of severe pain in patients with cancer not adequately relieved by opioid analgesics alone More likely to be effective in patients with neuropathic pain than in those with somatic or visceral pain BRAND FORM. UNIT PRICE PILL IMAGE Catapres-TTS-2 transdermal- 0.2 mg/24 hr transdermal systemCatapres-TTS-1 transdermal- 0.1 mg/24 hr transdermal systemCatapres-TTS-3 transdermal- 0.3 mg/24 hr transdermal systemclonidine transdermal- 0.3 mg/24 hr transdermal systemclonidine transdermal- 0.3 mg/24 hr transdermal systemclonidine transdermal- 0.2 mg/24 hr transdermal systemclonidine transdermal- 0.1 mg/24 hr transdermal systemclonidine transdermal- 0.1 mg/24 hr transdermal systemclonidine transdermal- 0.3 mg/24 hr transdermal systemclonidine transdermal- 0.2 mg/24 hr transdermal systemclonidine transdermal- 0.1 mg/24 hr transdermal systemclonidine transdermal- 0.3 mg/24 hr transdermal systemclonidine transdermal- 0.2 mg/24 hr transdermal systemCopyright © 2010 First DataBank, Inc.Print Patient Educationclonidine transdermal CLONIDINE - TRANSDERMAL (KLON-i-deen) COMMON BRAND NAME(S): Catapres-TTS USES: This medication is used alone or with other medications to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Clonidine belongs to a class of drugs (central alpha agonists) that act in the brain to lower blood pressure. It works by relaxing blood vessels so blood can flow more easily. HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking clonidine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Peel off the backing from the patch and apply the patch to a clean, dry, and hairless area of the skin on the upper