Carbachol (Ophthalmic)


VA CLASSIFICATION
Primary: OP118

Commonly used brand name(s): Carbastat; Carboptic; Isopto Carbachol; Miostat.

Another commonly used name is
carbamylcholine . {11}
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiglaucoma agent (ophthalmic)—Carbachol Ophthalmic Solution USP—

Miotic—Carbachol Intraocular Solution USP; Carbachol Ophthalmic Solution USP—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Miosis induction, during surgery—Carbachol intraocular solution is indicated to produce pupillary miosis during surgery. {06} {12} {24}

Glaucoma, open-angle (treatment)—Carbachol ophthalmic solution is indicated for lowering intraocular pressure in the treatment of chronic open-angle glaucoma. {12} {19} {23} It is especially useful as a replacement drug, particularly in eyes that have become intolerant of, or resistant to, pilocarpine.

[Glaucoma, angle-closure (treatment) ]1—Carbachol ophthalmic solution is used for emergency treatment of angle-closure glaucoma; however, pilocarpine is usually preferred.

[Glaucoma, angle-closure, during or after iridectomy (treatment) ]1—Carbachol ophthalmic solution is used in the treatment of angle-closure glaucoma during or after iridectomy. {01} {02}

[Glaucoma, secondary (treatment)]1—Carbachol ophthalmic solution is used in the treatment of secondary glaucoma if there is no active intraocular inflammation present. {01} {02}

Hypertension, ocular, postsurgical (treatment) {27} {28}1—Carbachol intraocular solution is indicated to reduce the intensity of intraocular pressure elevation in the first twenty-four hours after cataract surgery. {27} {28}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    182.65 {25}

Mechanism of action/Effect:

Carbachol is a parasympathomimetic that directly stimulates cholinergic receptors. It may also act indirectly by promoting release of acetylcholine and by a weak anticholinesterase action. {23} Carbachol produces contraction of the iris sphincter muscle resulting in pupillary constriction (miosis), constriction of the ciliary muscle resulting in increased accommodation, and a reduction in intraocular pressure associated with decreased resistance to aqueous humor outflow.

In chronic open-angle glaucoma, the exact mechanism by which carbachol lowers intraocular pressure is not precisely known; however, contraction of the ciliary muscle apparently opens the intertrabecular spaces and facilitates aqueous humor outflow.

In angle-closure glaucoma, constriction of the pupil apparently pulls the iris away from the trabeculum, thereby relieving blockage of the trabecular meshwork.

Onset of action:

Ophthalmic solution—Miosis: Within 10 to 20 minutes.

Time to peak effect:

Intraocular solution—Miosis: Within 2 to 5 minutes. {10} {12} {24}

Ophthalmic solution—Reduction in intraocular pressure: Within 4 hours.

Duration of action:


Intraocular solution:

Miosis: About 24 hours.



Ophthalmic solution:

Miosis: About 4 to 8 hours.

Reduction in intraocular pressure: About 8 hours.



Precautions to Consider

Carcinogenicity

Long-term animal studies have not been done. {23}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans. However, carbachol may be systemically absorbed. {23}

Studies have not been done in animals. {23}

FDA Pregnancy Category C. {23}

Breast-feeding

Carbachol may be systemically absorbed. {23} It is not known whether carbachol is distributed into breast milk. {23} However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of carbachol have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


Appropriate studies on the relationship of age to the effects of carbachol have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Belladonna alkaloids, ophthalmic or{16}
Cyclopentolate{16}    (concurrent use of these medications may interfere with the antiglaucoma action of carbachol. Also, concurrent use with carbachol counteracts the mydriatic effects of these medications; this counteraction may be used to therapeutic advantage)


Flurbiprofen, ophthalmic{08}{16}    (ophthalmic carbachol may be ineffective when administered following ophthalmic flurbiprofen; the pharmacologic basis for this interference is not known)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Asthma, bronchial{12}{24}
Cardiac failure, acute{12}{23}{24}
Corneal abrasion or injury{12}{23}    (possible excessive absorption of medication, which can produce systemic toxicity {12} {23})


Gastrointestinal spasm{12}{23}{24}
Hyperthyroidism{12}{23}{24}
» Iritis, acute, or other conditions in which pupillary constriction is undesirable{12}{23}
Parkinson's disease{12}{23}{24}
Peptic ulcer, active{12}{23}{24}
Sensitivity to carbachol{23}
Urinary tract obstruction{12}{23}{24}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Intraocular pressure determinations    (recommended at periodic intervals during therapy when carbachol is used in the treatment of glaucoma)




Side/Adverse Effects

Note: Corneal clouding, persistent bullous keratopathy, and post-operative iritis following cataract extraction have been reported occasionally when carbachol intraocular solution was used during cataract surgery. {24}
With the exception of retinal detachment, {24} the following side effects have not been reported following the use of carbachol intraocular solution. {24}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Retinal detachment{23} (veil or curtain appearing across part of vision)

Symptoms of systemic absorption
    
Asthma{12}{23} (shortness of breath, wheezing, or tightness in chest)
    
cardiac arrhythmia{23} (irregular heartbeat)
    
diarrhea,{12}{18}{23} stomach cramps or pain,{12}{18}{23} or vomiting{12}{18}{23}
    
flushing or redness of face{12}
    
frequent urge to urinate{23}
    
hypotension{23} (unusual tiredness or weakness)
    
increased sweating{12}{18}{23}
    
syncope{23} (fainting)
    
watering of mouth{12}{23}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Blurred vision or change in near or distance vision{23}
    
eye pain{12}{18}
    
stinging or burning of the eye{23}

Incidence less frequent
    
Headache{12}{23}
    
irritation{18}{23} or redness{23} of eyes
    
twitching of eyelids





Overdose
For specific information on the agents used in the management of ophthalmic carbachol overdose, see:
   • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Atropine sulfate injection is used as an antidote to the systemic effects of carbachol. {05} {12} {23} {24}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Carbachol (Ophthalmic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to carbachol
Other medical problems, especially acute iritis or other conditions in which pupillary constriction is undesirable

Proper use of this medication

For the ophthalmic solution
» Importance of not using more medication than the amount prescribed

Proper administration technique

Washing hands immediately after applying eye drops

Preventing contamination: Not touching applicator tip to any surface; keeping container tightly closed

» Proper dosing
Missed dose: Applying as soon as possible; not applying if almost time for next dose; applying next dose at regularly scheduled time

» Proper storage

Precautions while using this medication

For the ophthalmic solution
Regular visits to physician to check eye pressure during therapy

» Caution if driving or doing anything else at night or in dim light

» Caution if blurred vision or change in near or distance vision occurs


Side/adverse effects
Signs of potential side effects, especially retinal detachment or symptoms of systemic absorption


General Dosing Information

For ophthalmic solution
Although some manufacturers recommend a dose of 2 drops of an ophthalmic solution at appropriate intervals, the conjunctival sac will usually hold only 1 drop. {14} {23}

More frequent instillation or use of a stronger solution may be required to produce an adequate reduction in intraocular pressure in eyes with hazel or brown irides than is needed in eyes with blue or light-colored irides.

To avoid excessive systemic absorption, patient should press finger to the lacrimal sac during and for 1 or 2 minutes following instillation of medication.

Tolerance to carbachol may develop with prolonged use. Effectiveness may be restored by changing to another miotic for a short time and then resuming the original medication.


Ophthalmic Dosage Forms

CARBACHOL INTRAOCULAR SOLUTION USP

Usual adult and adolescent dose
Miotic
Intraocular irrigation, no more than {10} 0.5 mL of a 0.01% solution instilled into the anterior chamber. {12} {20} {24}

Antihypertensive agent, ocular, postsurgical
Intraocular irrigation, no more than 0.5 mL of a 0.01% solution instilled into the anterior chamber. {27} {28}


Note: The intraocular solution may be instilled before or after securing sutures. {27} {28}


Usual pediatric dose
See Usual adult and adolescent dose.

Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


0.01% (Rx) [Carbastat{28}] [Miostat{24}{27}]

Canada—


0.01% (Rx) [Carbastat{29}] [Miostat{22}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a tight container. Protect from freezing.

Auxiliary labeling:
   • For single-dose intraocular use only. {20} {24}
   • Discard unused portion. {20} {24}


CARBACHOL OPHTHALMIC SOLUTION USP

Usual adult and adolescent dose
Antiglaucoma agent (ophthalmic)
Topical, to the conjunctiva, 1 drop of a 0.75 to 3% solution one to three times a day. {04} {12} {19} {23}


Usual pediatric dose
See Usual adult and adolescent dose.

Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


0.75% (Rx) [Isopto Carbachol{19}{23}{26} (benzalkonium chloride 0.005%)]


1.5% (Rx) [Isopto Carbachol{19}{23}{26} (benzalkonium chloride 0.005%)]


2.25% (Rx) [Isopto Carbachol{19}{23}{26} (benzalkonium chloride 0.005%)]


3% (Rx) [Carboptic{03}] [Isopto Carbachol{19}{23}{26} (benzalkonium chloride 0.005%)]

Canada—


1.5% (Rx) [Isopto Carbachol{21}{30} (benzalkonium chloride)]


3% (Rx) [Isopto Carbachol{21}{30} (benzalkonium chloride)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing.

Auxiliary labeling:
   • For the eye.
   • Keep container tightly closed.



Revised: 09/11/1998



References
  1. Per Indications Index.
  1. Reviewers' responses to Ophthalmology Advisory Panel Memo of 9/86.
  1. Carboptic 3% (Optopics). In: Redbook 1994. Montvale, NJ: Medical Economics Data 1994: 128.
  1. Isopto Carbachol package insert (Alcon—US), Rev 9/86, Rec 4/88.
  1. Miostat package insert (Alcon—US), Rev 7/84, Rec 4/88.
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  1. Glaucoma: Its treatment can cause other problems. Health Letter 1990 Mar: 5-7.
  1. Isopto Carbachol (Alcon). In: PDR Physicians' desk reference for ophthalmology. 19th ed. 1991. Oradell, NJ: Medical Economics Company, 1991: 217.
  1. Miostat (Alcon Surgical). In: PDR Physicians' desk reference for ophthalmology. 19th ed. 1991. Oradell, NJ: Medical Economics Company, 1991: 231.
  1. Isopto Carbachol (Alcon). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 26th ed. Ottawa: Canadian Pharmaceutical Association, 1991: 601.
  1. Miostat (Alcon). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 19th ed. Ottawa: Canadian Pharmaceutical Association, 1991: 732.
  1. Isopto Carbachol (Alcon). In: PDR Physicians' desk reference for ophthalmology. 22nd ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 218.
  1. Miostat (Alcon). In: PDR Physicians' desk reference for ophthalmology. 22nd ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 233.
  1. Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1993.
  1. Isopto Carbachol (Alcon). In: PDR Physicians' desk reference for opthalmology. 26th ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 215.
  1. Miostat (Alcon). In: PDR Physicians' desk reference for opthalmology. 26th ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 215-6.
  1. Carbastat (Ciba). In: PDR Physicians' desk reference for opthalmology. 26th ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 253.
  1. Carbastat (Ciba). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 259.
  1. Isopto Carbachol (Alcon). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 812.
  1. Miostat (Alcon). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1008.
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