clonidine (Catapres, Catapres-TTS, Duraclon, Jenloga, Kapvay, Nexiclon XR)

Dosing and uses of Catapres, Catapres-TTS (clonidine)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

injectable solution

• 100mcg/mL
• 500mcg/mL

patch, extended-release

• 0.1mg/day
• 0.2mg/day
• 0.3mg/day

tablet, immediate-release

• 0.1mg
• 0.2mg
• 0.3mg

tablet, extended-release

• 0.1mg

 

Hypertension

Immediate-release tablets

• 0.1 mg PO q12hr
• Range: 0.1-0.2 mg/day q12hr; not to exceed 2.4 mg/day

TransdermaL

• Apply 1 patch q7Days; start with 0.1 mg; increase by 0.1 mg after q1-2Week interval; usual dose range is 0.1-0.3 mg qWeek

 

Cancer Pain

Epidural infusion

• Severe pain in patients with cancer not adequately relieved by opioid analgesics alone
• Initial: 30 mcg/hr
• Titrate as required for pain relief or presence of side effects
• Limited data on doses exceeding 40 mcg/hr

 

Acute Hypertension (Off-label)

0.1-0.2 mg PO; may follow with additional doses of 0.1 mg qhr PRN to maximum 0.6 mg total dose

 

EtOH Withdrawal (Off-label)

0.3-0.6 mg PO q6hr

 

Smoking Cessation (Off-label)

PO administration: 0.1 mg qDay; increase by 0.1 mg/day to 0.15-0.75 mg/day if required

TD administration: 100-200 mcg/day patch q7Days

 

Restless Legs Syndrome (Off-label)

100-300 mcg PO 2 hours befor bedtime, up to 900 mcg/day

 

Tourette's Syndrome (Off-label)

0.0025-0.015 mg/kg/day PO for 6 weeks to 3 months

 

Cyclosporine Nephrotoxicity (Off-label)

100-200 mcg/day transdermal patch; change q7Days

 

Menopausal Flushing (Off-label)

Apply 100 mcg/day patch; change q7Days, Or

50 mcg PO q12hr initially; may increase up to 400 mcg q12hr

 

Dysmenorrhea (Off-label)

PO administration: 0.025 mg q12hr for 2 weeks prior to menstruation

 

Opioid Withdrawal (Off-label)

PO administration: 0.1-0.3 mg q4-6hr; increase by 0.1 mg/day to 0.15-0.75 mg/day if required; do not exceed 2.4 mg/day

TD administration: 100-200 mcg/day patch q7Days; initiate 0.1-0.3 mg PO q4-6hr for first 2 days to allow for adequate drug levels

 

Postherpetic Neuralgia (Off-label)

PO administration: 0.1 mg q12hr

 

Psychosis (Off-label)

PO administration: 0.4-1.4 mg/day in divided doses

 

Pheochromocytoma Diagnosis (Off-label)

Clonidine suppression testing: 0.3 mg PO for 60-80 kg patient; obtain blood sample 3 hours after administration to supine patient

 

Dosing Considerations

Extended-release is not to be used interchangeably with immediate-release tablets

Conversion from 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

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

 

Dosing Modifications

Renal Impairment

• Impact of renal impairment not assessed
• Initial dose should be based on amount of renal impairment
• Monitor carefully for hypotension and bradycardia
• Removed minimally during hemodialysis; no need to redose following dialysis

 

Pediatric dosage forms and strengths

injectable solution

• 100mcg/mL
• 500mcg/mL

patch

• 0.1mg/day
• 0.2mg/day
• 0.3mg/day

tablet, immediate-release

• 0.1mg
• 0.2mg
• 0.3mg

tablet, extended-release

• 0.1mg

 

Hypertension

>12 years old

• Immediate-release tablets: 0.2 mg/day PO divided q12hr; increase qWeek; maintenance dose range, 0.2-0.6 mg/day q12hr; not to exceed 2.4 mg/day
• Transdermal patch: 0.1 mg patch q7Day initially; may increase by weekly 0.1-mg increments after 1-2 weeks if desired blood pressure reduction not achieved; not to exceed 0.6 mg/week (ie, 2 clonidine 0.3 mg patches)

<12 years old

• Immediate-release tablets and transdermal patch: Safety and efficacy not established

<18 years old

• Extended-release tablets (Jenloga, Nexiclon XR): Safety and efficacy not established

 

ADHD

<6 years old: Not established

≥6 years old (extended-release tablets, Kapvay): 0.1 mg PO qHS initially; may adjust dose by increments of 0.1 mg/day at weekly intervals until desired response; not to exceed 0.4 mg/day

When discontinuing, taper gradually by decrements not to exceed 0.1 mg q3-7Days

Dosing considerations

• May be given as monotherapy or as adjunctive therapy with stimulants
• Extended-release not interchangeable with immediate-release product

 

Cancer Pain

Severe pain in patients with cancer not adequately relieved by opioid analgesics alone

Epidural infusion: 0.5 mcg/kg/hr initially; adjust according to clinical response

Dosing considerations

• 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
• Restrict use to pediatric patients with severe, intractable pain from malignancy that is unresponsive to epidural or spinal opiates or to other, more conventional analgesic techniques
• More likely to be effective in patients with neuropathic pain than in those with somatic or visceral pain
• Safety and effectiveness of epidural administration in this limited indication and clinical population have been established in patients old enough to tolerate placement and management of an epidural catheter; these conclusions are based on evidence from adequate and well-controlled studies in adults and through experience with the use of clonidine in the pediatric age group for other indications

 

Administration

ADHd

• Doses 0.2 mg/day or greater should be divided BID, with either an equal or higher split dosage being given at bedtime
• Swallow tablet whole; do not crush, chew, or split

 

Dosing Modifications

Renal Impairment

• Impact of renal impairment not assessed
• Initial dose should be based on amount of impairment
• Monitor carefully for hypotension and bradycardia
• Removed minimally during hemodialysis, so no need to redose following dialysis

 

Geriatric dosage forms and strengths

 

Hypertension

Immediate-release tablets: 0.1 mg PO qHs

 

Dosing considerations

Not recommended as routine treatment for hypertension (Beers criteria)

Potential for orthostatic hypotension and adverse CNS effects

May cause bradycardia

Immediate release: Lower initial doses than for nongeriatric adult dosing, as well as gradual adjustments, are recommended

Extended release: May require lower initial dose than for nongeriatric adult dosing

 

Catapres, Catapres-TTS (clonidine) adverse (side) effects

>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

 

Warnings

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 use

 

Contraindications

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 and lactation

Pregnancy category: C

Lactation: Distributed in breast milk; caution advised

 

Pregnancy 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.

 

Pharmacology of Catapres, Catapres-TTS (clonidine)

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 alph2-agonist stimulation may regulate subcortical activity in the prefrontal cortex, which may regulate area of the brain responsible for attentions, emotions, and behaviors and causes reduced 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%)