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CYCLOPENTOLATE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Cyclopentolate is an anticholinergic ophthalmic agent used to produce mydriasis and cycloplegia by blocking the responses of the sphincter muscle of the iris and the stimulation of the ciliary body muscle. Onset of maximal cycloplegia is up to 75 minutes after instillation of the ophthalmic solution, and complete recovery is generally 6 to 24 hours later.

Specific Substances

    1) Ciclopentalato
    2) Dimethylaminoethyl (l-hydroxycyclopentyl)phenylacetate HCL
    3) CLORIDRATO DE CICLOPENTOLATO
    4) CYCLOPENTOLATE HYDROCHLORIDE

Available Forms Sources

    A) FORMS
    1) Cyclopentolate is available as 0.5%, 1%, and 2% ophthalmic solution (Prod Info cyclopentolate HCl ophthalmic solution, 2011; Prod Info cyclopentolate hydrochloride ophthalmic solution, 2004).
    B) USES
    1) Cyclopentolate hydrochloride is used to produce mydriasis and cycloplegia (Prod Info cyclopentolate HCl ophthalmic solution, 2011).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) This is a parasympatholytic drug with actions similar to atropine and homatropine, but with a demethylated side chain that is also located in some tranquilizers and psychoactive drugs. Atropine-like toxicity has occurred in children, but is considered a rare event.
    2) In adults signs and symptoms noted were tachycardia, nausea, weakness, headache, delusions, dizziness, dry mouth, light-headedness, mood swings, loss of balance, incoordination, and mental depression. Symptom onset was 20 minutes to one hour, and duration one hour to 3 days.
    3) Children may develop clouding of the sensorium, hallucinations, disorientation, slurred speech, ataxia, and hyperactivity.
    B) WITH POISONING/EXPOSURE
    1) Toxic effects can include tachycardia, fever, hypertension, vasodilation, urinary retention, behavioral disturbances, slowed GI motility, decreased sweating and decreased salivation.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Tachycardia may occur.
    0.2.4) HEENT
    A) WITH THERAPEUTIC USE
    1) Blurred vision, increased intraocular pressure, ophthalmic irritation, keratitis, hyperemia, conjunctivitis, and blepharoconjunctivitis may occur. The administration of cyclopentolate to eyes with narrow angles may cause an acute attack of glaucoma.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Tachycardia and vasodilatation may occur from systemic absorption.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Anticholinergics such as cyclopentolate are characteristically associated with central nervous system side effects consisting of sedation and drowsiness, inability to concentrate, and fatigue.
    2) Cyclopentolate may also produce CNS stimulatory activity consisting of psychotic reactions, behavioral disturbances, irritability, vertigo, disorientation, dementia, hallucinations, and tremor, which is more frequently observed in children than adults.
    3) Two cases of grand mal seizures were reported in children.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Xerostomia may occur from systemic absorption.
    2) Necrotizing enterocolitis was reported in a neonate receiving cyclopentolate ophthalmic solution.
    3) Gastroenteritis and feeding intolerance may occur in infants with therapeutic amounts. Nausea and vomiting were reported as part of a toxic reaction to cyclopentolate eye drops.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Anticholinergic drugs such as cyclopentolate may cause skin rash and facial flushing.
    0.2.18) PSYCHIATRIC
    A) WITH THERAPEUTIC USE
    1) Isolated cases of psychotic reactions have been reported in both adults and children following ophthalmic administration of cyclopentolate.
    0.2.20) REPRODUCTIVE
    A) Cyclopentolate is classified as FDA pregnancy category C. Animal reproduction studies have not been conducted, and it is unknown whether cyclopentolate will cause fetal harm if administered to a pregnant woman.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    0.2.22) OTHER
    A) WITH POISONING/EXPOSURE
    1) Habituation may be observed with drug misuse. Withdrawal has produced nausea, vomiting, rigidity, tremors, and a sense of urgency in several cases of drug abuse.

Laboratory Monitoring

    A) No specific laboratory measures are indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Ingested drops are likely to be absorbed rapidly, GI decontamination is probably not helpful.
    B) AGITATION - Benzodiazepines may be used to control agitation secondary to anticholinergic effects.
    C) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    D) PHYSOSTIGMINE
    1) Physostigmine is indicated to reverse the CNS effects caused by clinical or toxic dosages of agents capable of producing anticholinergic syndrome; however, long lasting reversal of anticholinergic signs and symptoms is generally not achieved because of the relatively short duration of action of physostigmine (45 to 60 minutes). It is most often used diagnostically to distinguish anticholinergic delirium from other causes of altered mental status. CAUTION: If tricyclic antidepressants are coingested, physostigmine may precipitate seizures and dysrhythmias.
    2) ADULT: 2 mg IV at a slow controlled rate, no more than 1 mg/min. May repeat doses at intervals of 10 to 30 min if severe symptoms recur. For patients with prolonged anticholinergic delirium consider a continuous infusion, start at 2 mg/hr and titrate to effect. CHILD: 0.02 mg/kg by slow IV injection, at a rate no more than 0.5 mg/minute. Repeat dosage at 5 to 10 minute intervals as long as the toxic effect persists and there is no sign of cholinergic effects. MAXIMUM DOSAGE: 2 mg total.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

Range Of Toxicity

    A) TOXICITY: ADULT: As little as 1 drop of solution has caused CNS toxicity in some individuals. The higher the concentration of the drops, and the more often they are used, the greater the chance of toxicity. CHILDREN: Therapeutic use of a 2% solution in 40 children resulted in 5 cases of acute psychotic reactions.
    B) THERAPEUTIC: ADULT/CHILDREN: Instill 1 or 2 drops of 1% or 2% solution in the eye and may be repeated 5 to 10 min later with a 1% solution if needed. INFANTS: Instill 1 drop of 0.5% solution and apply pressure to nasolacrimal sac for 2 to 3 min in order to minimize absorption. Monitor closely for adverse effects for at least 30 minutes following instillation.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) This is a parasympatholytic drug with actions similar to atropine and homatropine, but with a demethylated side chain that is also located in some tranquilizers and psychoactive drugs. Atropine-like toxicity has occurred in children, but is considered a rare event.
    2) In adults signs and symptoms noted were tachycardia, nausea, weakness, headache, delusions, dizziness, dry mouth, light-headedness, mood swings, loss of balance, incoordination, and mental depression. Symptom onset was 20 minutes to one hour, and duration one hour to 3 days.
    3) Children may develop clouding of the sensorium, hallucinations, disorientation, slurred speech, ataxia, and hyperactivity.
    B) WITH POISONING/EXPOSURE
    1) Toxic effects can include tachycardia, fever, hypertension, vasodilation, urinary retention, behavioral disturbances, slowed GI motility, decreased sweating and decreased salivation.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Tachycardia may occur.
    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) Fever has been reported following instillation of cyclopentolate eye drops (Prod Info cyclopentolate HCl ophthalmic solution, 2011; Bhatia et al, 2000).
    3.3.5) PULSE
    A) WITH POISONING/EXPOSURE
    1) Tachycardia may occur in overdose (Derinoz & Emeksiz, 2012; Prod Info cyclopentolate HCl ophthalmic solution, 2011).

Heent

    3.4.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Blurred vision, increased intraocular pressure, ophthalmic irritation, keratitis, hyperemia, conjunctivitis, and blepharoconjunctivitis may occur. The administration of cyclopentolate to eyes with narrow angles may cause an acute attack of glaucoma.
    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) Blurred vision has been reported with therapeutic doses (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    2) Increased intraocular pressure may occur with therapeutic use (Prod Info cyclopentolate HCl ophthalmic solution, 2011). In one study of 21 eyes dilated with 0.5% cyclopentolate, 9 developed a significantly increased ocular pressure at some stage of the dilation and subsequent miosis (Mapstone, 1977). Prolonged mydriasis lasting several days has been reported in children following instillation of 1% cyclopentolate (Bhatia et al, 2000).
    a) Harris (1968) stated that if a cyclopentolate solution of sufficient strength were used (1%), about 23% of individuals with proven chronic open angle glaucoma would experience increases in intraocular pressure, whereas only 2% of the normal population would experience this effect. Lower concentrations were less likely to produce this effect (Harris, 1968).
    3) Temporary ophthalmic irritation and conjunctivitis may occur (Prod Info cyclopentolate HCl ophthalmic solution, 2011; S Sweetman , 2000). The higher the concentration, the greater the ocular irritation upon instillation (Awan, 1976).
    4) Hyperemia may occur (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    5) Blepharoconjunctivitis may occur (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    6) The administration of cyclopentolate to eyes with narrow angles may cause an acute attack of glaucoma (Awan, 1976).
    B) WITH POISONING/EXPOSURE
    1) CASE REPORT: A blotchy, epithelial keratitis developed in a man who abused a cyclopentolate-tropicamide solution. He was using 100 to 200 drops/day (Ostler, 1975).
    2) CASE REPORT: A woman abusing cyclopentolate 1% eye drops, 200 to 400 drops per day, experienced a toxic-type keratitis. Both eyes had marked conjunctival injection, diffuse corneal epithelial punctate keratitis, and the pupils were widely dilated and unresponsive to light (Sato et al, 1992).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Tachycardia and vasodilatation may occur from systemic absorption.
    3.5.2) CLINICAL EFFECTS
    A) TACHYCARDIA
    1) WITH THERAPEUTIC USE
    a) Tachycardia may occur from systemic absorption (Awan, 1976a; Adcock, 1971). In one study, tachycardia was not associated with significant changes in blood pressure (S Sweetman , 2000).
    2) WITH POISONING/EXPOSURE
    a) Tachycardia may develop after excessive dosing (Derinoz & Emeksiz, 2012; Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    B) VASODILATATION
    1) WITH THERAPEUTIC USE
    a) Vasodilation may occur following systemic absorption (Prod Info cyclopentolate HCl ophthalmic solution, 2011).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY DISTRESS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A neonate, born at 28 weeks gestation, received cyclopentolate eye drops 1%, instilled 6 times in each eye at 5 minute intervals, at 90 days of age (corrected postterm age of 12 days). Approximately 30 minutes post-instillation, the patient developed vomiting, cyanosis, and respiratory distress. A physical exam indicated abdominal distension, and vital signs demonstrated fever (40 degrees C), tachypnea (60 breaths per minute), tachycardia (250 bpm), and an O2sat of 90%. A chest radiograph revealed diffuse pulmonary infiltration, and blood gas results indicated respiratory acidosis. Following administration of physostigmine, the patient gradually recovered with resolution of clinical symptoms and normalization of vital signs (Derinoz & Emeksiz, 2012). It is unclear whether the patient's respiratory distress was a direct result of the cyclopentolate overdose or secondary due to the vomiting and abdominal distension, resulting in aspiration of gastric contents.

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Anticholinergics such as cyclopentolate are characteristically associated with central nervous system side effects consisting of sedation and drowsiness, inability to concentrate, and fatigue.
    2) Cyclopentolate may also produce CNS stimulatory activity consisting of psychotic reactions, behavioral disturbances, irritability, vertigo, disorientation, dementia, hallucinations, and tremor, which is more frequently observed in children than adults.
    3) Two cases of grand mal seizures were reported in children.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH THERAPEUTIC USE
    a) Anticholinergics such as cyclopentolate are characteristically associated with central nervous system side effects consisting of sedation and drowsiness, inability to concentrate, and fatigue (Prod Info cyclopentolate HCl ophthalmic solution, 2011). Clouding of the sensorium, ataxia, and slurred speech may occur, especially in children (Prod Info cyclopentolate HCl ophthalmic solution, 2011; Bauer et al, 1973).
    b) In many of the cases reported, the CNS side effects observed after instillation of a several drops of a 1% to 2% solution usually lasted 1 to 8 hours, and almost always resolved by 24 hours (Awan, 1976; Beswick, 1962; Binkhorst, 1963; Mach, 1963; Missiroli, 1969; Praeger & Miller, 1964; Simcoe, 1962). Some signs (e.g., mydriasis, cycloplegia) and symptoms may not clear for 3 to 4 days (Awan, 1976a; Bhatia et al, 2000).
    c) CASE REPORT (CHILD): A 4-year-old boy presented to the emergency department with an inability to walk, dysarthria, and disorientation approximately 3 hours after administration of 6 drops of 1% cyclopentolate eyedrops in both eyes during a routine eye exam. Pupils were mydriatic with no reflex. The patient's signs and symptoms improved within 6 hours following presentation, and he was subsequently discharged (Derinoz & Er, 2012).
    B) DELIRIUM
    1) WITH THERAPEUTIC USE
    a) Cyclopentolate may also produce CNS stimulatory activity consisting of psychotic reactions, behavioral disturbances, irritability, hyperactivity, disorientation, hallucinations, delusions, and tremor, which is more frequently observed in children than adults (Prod Info cyclopentolate HCl ophthalmic solution, 2011; Awan, 1976a; Bauer et al, 1973; Bhatia et al, 2000). Inappropriate speech has also been reported in a child (Bhatia et al, 2000).
    2) WITH POISONING/EXPOSURE
    a) Excessive doses may cause behavioral disturbances (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    C) DEMENTIA
    1) WITH THERAPEUTIC USE
    a) Although the CNS effects are generally thought to be short lived (Beswick, 1962; Binkhorst, 1963; Praeger & Miller, 1964). Carpenter (1967) reported a case of an 82-year-old that developed dementia and did not recover his prior mental balance over the 11 months he was followed (Carpenter, 1967). The effects are more common in children than adults, and with the higher concentration (Awan, 1976).
    D) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) Vertigo may be experienced in some cases after even therapeutic amounts given ocularly (Awan, 1976a; Missiroli, 1969).
    E) SEIZURE
    1) WITH THERAPEUTIC USE
    a) CASE SERIES: Two cases of grand mal seizures were reported in children (11 months and 12 years) who were given one drop of 2% cyclopentolate in each eye. The seizures occurred 30 to 60 minutes post instillation of the drops. No other cause for the seizures was determined (Kennerdell & Wucher, 1972).
    b) CASE REPORT: A 4-year-old boy with a history of cerebral palsy and paraplegia developed tonic-clonic seizures, tachycardia and flushing 70 minutes after receiving a drop of 1% cyclopentolate solution into each eye. On 2 previous occasions, the child had received cyclopentolate without incident (Fitzgerald et al, 1990).
    F) ATAXIA
    1) WITH THERAPEUTIC USE
    a) Dysarthria, incoordination, imbalance, and broad gait have been noted within minutes of exposure to 1% to 2% solutions, and are thought to be due to cerebellar dysfunction (Awan, 1976a; Carpenter, 1967; Adcock, 1971; Mark, 1963).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Xerostomia may occur from systemic absorption.
    2) Necrotizing enterocolitis was reported in a neonate receiving cyclopentolate ophthalmic solution.
    3) Gastroenteritis and feeding intolerance may occur in infants with therapeutic amounts. Nausea and vomiting were reported as part of a toxic reaction to cyclopentolate eye drops.
    3.8.2) CLINICAL EFFECTS
    A) APTYALISM
    1) WITH THERAPEUTIC USE
    a) Xerostomia may occur from systemic absorption of cyclopentolate (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    2) WITH POISONING/EXPOSURE
    a) Decreased salivation may develop after excessive dosing (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    B) DRUG-INDUCED ILEUS
    1) WITH THERAPEUTIC USE
    a) Paralytic ileus was observed in neonates receiving cyclopentolate ophthalmic solution (Bauer et al, 1973; Hermansen & Sullivan, 1985; Isenberg et al, 1985).
    2) WITH POISONING/EXPOSURE
    a) Excessive dosing may decrease GI motility(Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    C) GASTROENTERITIS
    1) WITH THERAPEUTIC USE
    a) In a study conducted by Isenberg et al (1985), cyclopentolate 0.25% and placebo eye drops had no significant effect on tested gastric functions in 20 preterm infants; however, cyclopentolate 0.5% ophthalmic solution significantly decreased gastric acid secretion and volume in these patients. This effect may predispose patients to gastroenteritis (Isenberg et al, 1985).
    D) FEEDING PROBLEM
    1) WITH THERAPEUTIC USE
    a) Due to feeding intolerance which may occur in infants after administration of cyclopentolate, feeding should be withheld for 4 hours (Prod Info cyclopentolate HCl ophthalmic solution, 2011; Hermansen & Sullivan, 1985) .
    E) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting were reported as part of a toxic reaction to cyclopentolate drops in the eyes (Derinoz & Emeksiz, 2012; Awan, 1976; Awan, 1976a; Adcock, 1971; S Sweetman , 2000), and with neonates (Bauer et al, 1973).
    F) ABDOMINAL DISTENSION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Abdominal distension was reported in a neonate who received 1% cyclopentolate eye drops, 1 drop instilled 6 times in each eye at 5-minute intervals (Derinoz & Emeksiz, 2012).

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Anticholinergic drugs such as cyclopentolate may cause skin rash and facial flushing.
    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Anticholinergic drugs such as cyclopentolate may cause skin rash (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    b) CASE REPORT: A generalized pruritic rash, involving the face, trunk, and extremities, developed in a 20-year-old woman approximately 30 minutes following topical application of cyclopentolate 1% eye drops to her left eye. The rash resolved within hours following administration of IV steroids and oral antihistamines; however, a mild form of the rash recurred the following day (Newman & Jordan, 1996).
    B) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Contact dermatitis was reported in an adult following the use of cyclopentolate eye drops; burning and itching of the eyes, eyelids and upper cheek occurred (Camarasa & Pla, 1996). Patch testing was positive with cyclopentolate hydrochloride.
    C) FLUSHING
    1) WITH THERAPEUTIC USE
    a) Flushing of the face (S Sweetman , 2000) and extremities has been observed following systemic absorption of cyclopentolate eye drops (Adcock, 1971; Bhatia et al, 2000).

Reproductive

    3.20.1) SUMMARY
    A) Cyclopentolate is classified as FDA pregnancy category C. Animal reproduction studies have not been conducted, and it is unknown whether cyclopentolate will cause fetal harm if administered to a pregnant woman.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) It is unknown whether fetotoxicity will occur if cyclopentolate is administered to a woman during pregnancy (Prod Info cyclopentolate HCl 1% ophthalmic solution, 2013; Prod Info Cyclomydril(R) ophthalmic solution, 2013)..
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) It is unknown whether fetotoxicity will occur if cyclopentolate is administered to a woman during pregnancy (Prod Info cyclopentolate HCl 1% ophthalmic solution, 2013; Prod Info Cyclomydril(R) ophthalmic solution, 2013)..
    B) PREGNANCY CATEGORY
    1) The manufacturers have classified cyclopentolate and cyclopentolate/phenylephrine as FDA pregnancy category C (Prod Info cyclopentolate HCl 1% ophthalmic solution, 2013; Prod Info Cyclomydril(R) ophthalmic solution, 2013).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) It is unknown whether cyclopentolate is excreted in human milk (Prod Info cyclopentolate HCl 1% ophthalmic solution, 2013; Prod Info Cyclomydril(R) ophthalmic solution, 2013)..
    B) BREAST MILK
    1) Exercise caution when administering cyclopentolate or cyclopentolate/phenylephrine to a lactating woman (Prod Info cyclopentolate HCl 1% ophthalmic solution, 2013; Prod Info Cyclomydril(R) ophthalmic solution, 2013).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory measures are indicated.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) No specific laboratory measures are indicated.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No specific laboratory measures are indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Most cases of exposure occur from ocular administration. If the drops were to be ingested, more anticholinergic effects might be expected because of the greater volume ingested than received via the eyes. CNS depression signs and delirium may occur rapidly making emesis a poor choice. Because of these factors, emesis is not recommended.
    2) Ingested drops are likely to be absorbed rapidly, GI decontamination is probably not helpful.
    6.5.2) PREVENTION OF ABSORPTION
    A) Ingested drops are likely to be absorbed rapidly, GI decontamination is probably not helpful.
    6.5.3) TREATMENT
    A) SUPPORT
    1) SUMMARY - Most patients recover without specific treatment. The CNS depression has not been reported to result in respiratory depression. Oral or intravenous benzodiazepines may be used to control agitation secondary to anticholinergic effects.
    B) PHYSOSTIGMINE
    1) PHYSOSTIGMINE/INDICATIONS
    a) Physostigmine is indicated to reverse the CNS effects caused by clinical or toxic dosages of agents capable of producing anticholinergic syndrome; however, long lasting reversal of anticholinergic signs and symptoms is generally not achieved because of the relatively short duration of action of physostigmine (45 to 60 minutes) (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008). It is most often used diagnostically to distinguish anticholinergic delirium from other causes of altered mental status (Frascogna, 2007; Shannon, 1998).
    b) Physostigmine should not be used in patients with suspected tricyclic antidepressant overdose, or an ECG suggestive of tricyclic antidepressant overdose (eg, QRS widening). In the setting of tricyclic antidepressant overdose, use of physostigmine has precipitated seizures and intractable cardiac arrest (Stewart, 1979; Newton, 1975; Pentel & Peterson, 1980; Frascogna, 2007).
    2) DOSE
    a) ADULT: BOLUS: 2 mg IV at slow controlled rate, no more than 1 mg/min. May repeat doses at intervals of 10 to 30 min, if severe symptoms recur (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008). INFUSION: For patients with prolonged anticholinergic delirium, a continuous infusion of physostigmine may be considered. Starting dose is 2 mg/hr, titrate to effect (Eyer et al, 2008)
    b) CHILD: 0.02 mg/kg by slow IV injection, at a rate no more than 0.5 mg/minute. Repeat dosage at 5 to 10 minute intervals as long as the toxic effect persists and there is no sign of cholinergic effects. MAXIMUM DOSAGE: 2 mg total (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
    c) AVAILABILITY: Physostigmine salicylate is available in 2 mL ampules, each mL containing 1 mg of physostigmine salicylate in a vehicle containing sodium metabisulfite 0.1%, benzyl alcohol 2%, and water (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
    3) CAUTIONS
    a) Relative contraindications to the use of physostigmine are asthma, gangrene, diabetes, cardiovascular disease, intestinal or urogenital tract mechanical obstruction, peripheral vascular disease, cardiac conduction defects, atrioventricular block, and in patients receiving choline esters and depolarizing neuromuscular blocking agents (decamethonium, succinylcholine). It may cause anaphylactic symptoms and life-threatening or less severe asthmatic episodes in patients with sulfite sensitivity (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
    b) Too rapid IV administration of physostigmine has resulted in bradycardia, hypersalivation leading to respiratory difficulties, and possible seizures (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008).
    4) ATROPINE FOR PHYSOSTIGMINE TOXICITY
    a) Atropine should be available to reverse life-threatening physostigmine-induced, toxic cholinergic effects (Prod Info physostigmine salicylate intravenous injection, intramuscular injection, 2008; Frascogna, 2007). Atropine may be given at half the dose of previously given physostigmine dose (Daunderer, 1980).
    C) SEIZURE
    1) Seizures and extreme agitation may be treated with diazepam.
    2) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    3) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    4) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    5) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    6) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    7) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    D) INEFFECTIVE THERAPEUTIC REGIMEN MANAGEMENT
    1) MYDRIASIS - Using pilocarpine to reverse the mydriasis caused by the parasympatholytic agent, cyclopentolate, is often not effective (Davidson, 1979; Mapstone, 1977; Anastasi et al, 1968).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) OCULAR ABSORPTION
    1) Cyclopentolate may produce systemic symptoms after ocular administration.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

    A) ADULT
    1) One drop of a 0.2% solution of cyclopentolate hydrochloride (with 1% phenylephedrine and 3% polyvinylpyrrolidone and 0.5% chlorobutanol) caused dementia within 10 minutes of administration in an 82-year-old man with a previous history of progressive mental deterioration, but no dementia (Carpenter, 1967). The patient was subsequently not manageable at home and was placed in a state hospital. No changes occurred over the next 11 months.
    2) One drop of a 2% solution of cyclopentolate was instilled in each eye of a 27-year-old woman for cycloplegia. Within 15 minutes she became somnolent, was crying, had an unstable gait, was tachycardic (120 beats per minute), weak, and disoriented. She was not given any treatment except monitoring of vital signs, and was normal within an hour (Awan, 1976).
    3) A healthy 24-year-old woman was given one drop of a 1% solution in each eye every 15 minutes for 3 doses. Within 15 minutes of the last dose she was reported to have dysarthria, vertigo, and was unable to articulate words. The symptoms persisted for about 2 hours, then she rapidly recovered (Missiroli, 1969).

Range Of Toxicity

Summary

    A) TOXICITY: ADULT: As little as 1 drop of solution has caused CNS toxicity in some individuals. The higher the concentration of the drops, and the more often they are used, the greater the chance of toxicity. CHILDREN: Therapeutic use of a 2% solution in 40 children resulted in 5 cases of acute psychotic reactions.
    B) THERAPEUTIC: ADULT/CHILDREN: Instill 1 or 2 drops of 1% or 2% solution in the eye and may be repeated 5 to 10 min later with a 1% solution if needed. INFANTS: Instill 1 drop of 0.5% solution and apply pressure to nasolacrimal sac for 2 to 3 min in order to minimize absorption. Monitor closely for adverse effects for at least 30 minutes following instillation.

Therapeutic Dose

    7.2.1) ADULT
    A) CYCLOPENTOLATE HYDROCHLORIDE
    1) Instill 1 or 2 drops of 1% or 2% solution into each eye. This dose may be repeated in 5 to 10 minutes if necessary (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    CYCLOPENTOLATE HYDROCHLORIDE/PHENYLEPHRINE HYDROCHLORIDE
    2) Instill 1 drop of solution into each eye and apply pressure over the nasolacrimal sac for two to three minutes. This dose may be repeated in 5 to 10 minutes if necessary (Prod Info Cyclomydril(R) ophthalmic solution, 2013)

    7.2.2) PEDIATRIC
    A) CYCLOPENTOLATE HYDROCHLORIDE
    1) INFANTS: Instill 1 drop of 0.5% solution into each eye. Apply pressure over the nasolacrimal sac for two or three minutes and observe the infant closely for at least 30 minutes following instillation (Prod Info cyclopentolate hydrochloride ophthalmic solution, 2004). It has been suggested that cyclopentolate should NOT be used during the first 3 months of life (S Sweetman , 2000).
    2) CHILDREN: Instill 1 or 2 drops of the 1% or 2% solution into each eye. This dose may be repeated with a 1% solution in 5 to 10 minutes if necessary (Prod Info cyclopentolate HCl ophthalmic solution, 2011).
    CYCLOPENTOLATE HYDROCHLORIDE/PHENYLEPHRINE HYDROCHLORIDE
    3) INFANTS: Instill 1 drop of solution into each eye and apply pressure over the nasolacrimal sac for two to three minutes. Observe the infant closely for at least 30 minutes following instillation (Prod Info Cyclomydril(R) ophthalmic solution, 2013).
    4) CHILDREN: Instill 1 drop of solution into each eye and apply pressure over the nasolacrimal sac for two to three minutes. This dose may be repeated in 5 to 10 minutes if necessary (Prod Info Cyclomydril(R) ophthalmic solution, 2013).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) CASE SERIES: One physician reported that the therapeutic use of a 2% solution in 40 children resulted in 5 cases of acute psychotic reactions. Cases generally recover spontaneously, but sometimes it takes 1 to 5 days (Awan, 1976).
    2) CASE SERIES: In a study of 66 normal, healthy adults who were given 1 drop of a 2% cyclopentolate solution in each eye, 10 developed a reaction. Six of these were considered mild, 4 moderate. Signs and symptoms noted were tachycardia, nausea, weakness, headache, delusions, dizziness, dry mouth, light-headedness, mood swings, loss of balance, incoordination, and mental depression. Symptoms persisted from one hour to 3 days (Awan, 1976a).
    3) As little as one drop of solutions have caused CNS toxicity in some individuals. The higher the concentration of the drops, and the more often they are used, the greater the chance of toxicity (Awan, 1976; Carpenter, 1967). As little as 2 and 3 milligrams, administered topically (in solution) to the eye have produced CNS symptoms in adults (Awan, 1976).
    4) PEDIATRIC: Six milligrams topically to the eye produced CNS and atropinic symptoms in a 4.5-year-old. CNS symptoms persisted for 7 hours, tachycardia and dilated pupils for 36 hours (Adcock, 1971).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CASE REPORTS
    a) Neonatal twins were given identical doses of cyclopentolate (one drop in each eye repeated twice at five minute intervals for a total of about 3 milligrams) for eye testing. At twenty four hours, the plasma level of one twin was 22 micrograms per milliliter (this twin died), and in the other it was 2 micrograms per milliliter (this twin survived) (Bauer et al, 1973).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 314 mg/kg (RTECS, 2000)
    2) LD50- (ORAL)MOUSE:
    a) 960 mg/kg (RTECS, 2000)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 292 mg/kg (RTECS, 2000)
    4) LD50- (ORAL)RAT:
    a) > 4 g/kg (RTECS, 2000)
    5) LD50- (SUBCUTANEOUS)RAT:
    a) 2235 mg/kg (RTECS, 2000)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Cyclopentolate, like atropine, is an antimuscarinic agent which produces competitive antagonism of the actions of acetylcholine, which can be overcome with increasing concentrations of acetylcholine (Gilman et al, 1990; S Sweetman , 2000).
    B) Cyclopentolate produces cycloplegia within 30 to 60 minutes with recovery of accommodation usually occurring within 6 to 24 hours, whereas, maximum cycloplegia with atropine usually occurs within 25 to 75 minutes of administration, and accommodation recovers within 6 to 24 hours (Prod Info cyclopentolate HCl 1% ophthalmic solution, 2013).
    C) The mydriatic action of atropine may persist for up to 10 days while the cycloplegia may last for as long as 5 days. Therefore, cyclopentolate is more convenient to use for the ophthalmologist, and is more attractive to the patient; however, in young patients where maximum cycloplegia is essential for accurate retinoscopy, atropine may be necessary (Milder & Riffenburgh, 1953; Ehrlich, 1953).
    D) Cyclopentolate will dilate pupils with systemic as well as local administration. It causes the dilation by paralysis of the iris sphincter (Gordon & Ehrenberg, 1954). Cyclopentolate has an antispasmodic potency of about 0.5 that of atropine (Gordon & Ehrenberg et al, 1954).

References

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