Clonidine Hcl (clonidine HCl/PF)

Regardless of the route of administration, to avoid the possibility of precipitating the withdrawal syndrome, clonidine therapy should not be discontinued abruptly.

Dosage of clonidine is expressed in terms of clonidine and clonidine hydrochloride.

Clonidine hydrochloride is administered orally or by epidural infusion; clonidine is administered orally or percutaneously by topical application of a transdermal system.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Clonidine/Beta-Blockers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Withdrawal of clonidine triggers increased catecholamine release. Beta-blockers inhibit the vasodilation mediated by the beta 2 receptor, leaving the vasoconstriction mediated by the alpha 2 receptor unopposed. In addition, concurrent use is expected to produce additive effects on blood pressure and heart rate requiring standard monitoring precautions.

CLINICAL EFFECTS: Severe hypertension may occur upon abrupt discontinuation of clonidine in patients receiving both clonidine and beta-blockers. In addition, concurrent use is expected to produce additive effects on blood pressure and heart rate requiring standard monitoring precautions.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In a patient receiving both drugs, discontinuation of the beta-blocker prior to clonidine may decrease the occurrence of rebound hypertension. If clonidine is discontinued first, rebound hypertension can be treated by restarting the clonidine or by the IV administration of phentolamine, phenoxybenzamine or prazosin. When adding either of these agents to the drug regimen of the patient, monitor blood pressure. Since labetalol has both alpha and beta activity, administration of labetalol may prevent rebound hypertension in patients undergoing clonidine withdrawal, although conflicting reports exist. In addition, concurrent use is expected to produce additive effects on blood pressure and heart rate requiring standard monitoring precautions.

DISCUSSION: Increased blood pressure has been observed in patients following: 1) the discontinuation of clonidine in patients receiving beta-blockers, 2) the replacement of clonidine therapy with beta-blockers, 3) the simultaneous discontinuation of both drugs. Conflicting reports exist on the development of increased blood pressure after clonidine withdrawal in patients receiving labetalol. Patients receiving labetalol who are being withdrawn from clonidine should still be closely monitored.

Clonidine/Tricyclic Compounds; Mirtazapine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Clonidine decreases blood pressure via alpha-2 agonism.(1) Tricyclic compounds(2) and mirtazapine(3) antagonize alpha-2, which may result in a loss of effect of clonidine.

CLINICAL EFFECTS: The concurrent use of clonidine and tricyclic compounds(1,3,4-16) and mirtazapine(3,17) may result in decreased effectiveness of clonidine and hypertensive crisis.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid concurrent use of clonidine with tricyclic compounds or mirtazapine. Consider using an alternative agent in patients maintained on clonidine. If concurrent administration is warranted, blood pressure should be carefully monitored, particularly in the first two weeks of therapy, when this interaction is most likely to occur. The dosage of clonidine may need to be adjusted or the tricyclic compound or mirtazapine may need to be discontinued.

DISCUSSION: This interaction has been reported in patients receiving amitriptyline,(6) clomipramine,(7,8) desipramine,(2,9-11) imipramine(12-16), and protriptyline.(11) In one patient, a hypertensive crisis resulted. Other patients experienced a decrease in blood pressure control. A controlled trial demonstrated a decrease in anti-hypertensive effect when desipramine was added to a clonidine regimen. This decrease in hypertensive-control may be overcome by increasing the dose of clonidine and monitoring blood pressure closely. Cyclobenzaprine is structurally related to the tricyclic antidepressants and, especially at higher dosages, has similar effects.(18) Therefore, it is prudent to consider cyclobenzaprine in this interaction. Hypertensive crisis has been reported during concurrent clonidine and mirtazapine therapy.(3,17) Mianserin(19,20) and maprotiline,(21) tetracyclic antidepressants, have been shown not to affect the antihypertensive effects of clonidine.

*Clonidine is contraindicated in patients with known hypersensitivity to the drug or to any ingredient or component in the formulation.

*Administration of epidural clonidine is contraindicated in patients receiving anticoagulant therapy, in those with a bleeding diathesis, and in the presence of an injection site infection.

*Administration of epidural clonidine above the C4 dermatome is contraindicated because of inadequate safety data supporting such use.

*Administration of epidural clonidine also is not recommended in most patients with severe cardiovascular disease or in patients who are hemodynamically unstable.

• Increased risk of bleeding due to coagulation disorder

• Bradycardia
• Hypotension
• Perioperative care
• Respiratory depression

• Cerebrovascular disorder
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Myocardial ischemia

Most adverse effects with clonidine are mild in nature and tend to decrease with continuation of therapy. The most common, dose-related adverse effects include dry mouth, drowsiness, dizziness, constipation, and sedation.

Adverse effects with transdermal clonidine are generally similar to those with oral therapy. The most frequent adverse effects with transdermal clonidine were dry mouth, drowsiness, and local adverse dermatologic effects.

The most frequent adverse effects occurring with clonidine hydrochloride epidural infusion for severe intractable cancer pain were hypotension, postural hypotension, dizziness, anxiety, and dry mouth; asymptomatic bradycardia was also observed in 1 patient. Mean heart rate and blood pressure reductions were also observed in patients receiving clonidine hydrochloride epidural infusion. Upon withdrawal of clonidine, 4 patients also experienced rebound hypertension, of which 1 suffered a cerebrovascular accident.

Adverse effects occurring in >=5% of patients receiving clonidine as monotherapy for ADHD include somnolence, fatigue, irritability, nightmares, insomnia, constipation, and dry mouth. When used as adjunctive therapy to stimulants in ADHD, adverse effects reported in >=5% of patients include somnolence, fatigue, decreased appetite, and dizziness.

More Frequent

• Bradycardia
• Hypotension

Less Frequent

• Chest pain
• Depression
• Fever
• Hallucinations
• Tachycardia
• Vomiting

Rare or Very Rare

• Accidental fall
• Atrioventricular block
• Respiratory depression

More Frequent

• Acute cognitive impairment
• Dizziness
• Drowsy
• Nausea
• Orthostatic hypotension
• Symptoms of anxiety
• Xerostomia

Less Frequent

• Anorexia
• Constipation
• Dyspnea
• Fatigue
• General weakness
• Headache disorder
• Hyperhidrosis
• Libido changes
• Sedation
• Skin rash
• Tinnitus

Rare or Very Rare

• Dysuria
• Insomnia
• Palpitations
• Pruritus of skin
• Urticaria

No enhanced messaging available.

The safety and efficacy of extended-release clonidine tablets and extended-release oral suspension (Onyda(TM) XR) for the treatment of ADHD have been established in pediatric patients 6-17 years of age. Use for this indication is based on evidence from 3 adequate, well-controlled studies, a short-term, placebo-controlled monotherapy study, a short-term, adjunctive therapy study, and a long-term randomized monotherapy study.

Safety and efficacy of oral clonidine hydrochloride, extended-release clonidine (Nexiclon(TM) XR), and clonidine transdermal system for the management of hypertension in children have not been established.

The safety and efficacy of clonidine hydrochloride epidural infusion have been established in pediatric patients who are old enough to tolerate placement and management of an epidural catheter, based on evidence from adequate, well-controlled studies in adults and experience with the use of clonidine in pediatric patients for other indications. Epidural clonidine should be used only in pediatric patients with severe, intractable cancer pain that is unresponsive to epidural or spinal opiates and to other conventional analgesic therapy.

Children may be more likely to experience CNS depression associated with clonidine overdosage than adults. In children, signs of toxicity have occurred with clonidine doses as low as 0.1 mg. Rare cases of clonidine toxicity (many involving children) associated with accidental or deliberate mouthing or ingestion of clonidine transdermal systems have been reported.

The manufacturer of oral clonidine states that because children frequently experience vomiting associated with GI illnesses, they may be particularly susceptible to hypertensive episodes resulting from sudden inability to ingest the drug.

Reproduction studies in rabbits using oral clonidine hydrochloride dosages up to about 3 times the maximum recommended human dosage have not revealed evidence of teratogenicity or embryotoxicity. However, in female rats receiving the drug continuously for 2 months prior to mating, an increased incidence of fetal resorptions occurred with oral dosages as low as one-third the maximum recommended human dosage (1/15th the maximum recommended human dosage on a mg/m2 basis); resorptions were not increased when these or higher dosages (up to 3 times the maximum recommended human dosage) were administered during days 6-15 of gestation. An increased incidence of fetal resorptions was observed when much higher dosages (40 times the maximum recommended human dosage on a mg/kg basis and 4-8 times the maximum recommended human dosage on a mg/m2 basis) were administered to mice and rats during days 1-14 of gestation; the lowest dosage used in the study was 0.5 mg/kg. There are no adequate and controlled studies to date using clonidine in pregnant women, and the drug should be used during pregnancy only when clearly needed.

There is a pregnancy exposure registry available that monitors pregnancy outcomes in women exposed to ADHD medications, including clonidine, during pregnancy. Patients can register by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or by visiting https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/ .

Since clonidine is distributed into milk, the drug should be used with caution in nursing women. The drug is excreted into milk at relative infant doses ranging from 4.1-8.4% of the maternal weight-adjusted dosage. Although in most cases, there were no reported adverse effects in breast-fed infants exposed to clonidine, one infant developed sedation, hypotonia, and apnea after clonidine exposure through breast milk. Monitor infants exposed to clonidine through breast milk for symptoms of hypotension and bradycardia, such as sedation, lethargy, tachypnea and poor feeding. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed infant from exposure to clonidine or the underlying maternal condition.

When conventional clonidine tablets are used for hypertension, the manufacturer states that geriatric patients may benefit from a lower initial dosage of 0.05 mg twice daily. Geriatric patients with hypertension may also benefit from an initial lower dosage when extended-release clonidine tablets (Nexiclon(R) XR) are used.

Geriatric patients may benefit from lower initial dosages of clonidine.