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  • CLASSES

    Other Agents for Local Oral Treatment
    Other Miotics-Antiglaucoma Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Cholinergic agonist that activates muscarinic receptors on smooth muscles
    Ophthalmic formulation used for glaucoma and as a miosis inducting agent; a 1.25% ophthalmic solution (Vuity) used for presbyopia
    Oral formulation used for symptoms of xerostomia caused by radiotherapy and for symptoms associated with Sjogren's syndrome

    COMMON BRAND NAMES

    Adsorbocarpine, Akarpine, Isopto Carpine, Pilocar, Salagen

    HOW SUPPLIED

    Adsorbocarpine/Akarpine/Isopto Carpine/Pilocar/Pilocarpine/Pilocarpine Hydrochloride Ophthalmic Sol: 1%, 2%, 4%
    Pilocarpine/Pilocarpine Hydrochloride/Salagen Oral Tab: 5mg, 7.5mg

    DOSAGE & INDICATIONS

    For the treatment of increased intraocular pressure (IOP) in patients with glaucoma or ocular hypertension or for the prevention of increased IOP associated with laser surgery.
    For the treatment of open-angle glaucoma or ocular hypertension.
    Ophthalmic dosage (ophthalmic solution)
    Adults

    Instill 1 drop into the eye(s) up to 4 times per day. Pilocarpine-naive patients should be started on the lowest available concentration as higher concentrations are often not tolerated initially. The frequency of administration and concentration of the ophthalmic solution administered are determined by the severity of the elevated intraocular pressure and the miotic response of the patient. To limit systemic exposure to pilocarpine, patients may be instructed to perform punctal occlusion for 2 minutes after administration.

    Children and Adolescents 2 years and older

    Instill 1 drop into the eye(s) up to 4 times per day. Pilocarpine-naive patients should be started on the lowest available concentration as higher concentrations are often not tolerated initially. The frequency of administration and concentration of the ophthalmic solution administered are determined by the severity of the elevated intraocular pressure and the miotic response of the patient. To limit systemic exposure to pilocarpine, patients may be instructed to perform punctal occlusion for 2 minutes after administration.

    Infants and Children younger than 2 years

    Instill 1 drop of the 1% ophthalmic solution into affected eye(s) 3 times daily.

    Ophthalmic dosage (ophthalmic gel)
    Adults

    Apply a one-half inch ribbon in the lower conjunctival sac of the affected eye(s) once daily at bedtime.

    Ophthalmic dosage (ocular insert)
    Adults

    Apply 1 ocular system delivering 20 or 40 mcg/hour, once every 7 days.

    For treatment of acute angle-closure glaucoma.
    NOTE: Prior to treatment with pilocarpine ophthalmic solution, secretory suppressants and hyperosmotic agents may be needed to lower intraocular pressure below 50 mmHg and relieve iris ischemia.
    Ophthalmic dosage (ophthalmic solution)
    Adults

    For initial management, instill 1 drop of 1% or 2% solution into affected eye(s) up to 3 times over a 30 minute period. If laser iridoplasty or iridomy is used to break the attack, instill 1 drop of 4% solution prior to the procedure. After laser iridoplasty, instill 1 drop of 1% solution 4 times daily until an iridotomy can be performed.

    Children and Adolescents 2 years and older

    For initial management, instill 1 drop of 1% or 2% solution into affected eye(s) up to 3 times over a 30 minute period. If laser iridoplasty or iridomy is used to break the attack, instill 1 drop of 4% solution prior to the procedure. After laser iridoplasty, instill 1 drop of 1% solution 4 times daily until an iridotomy can be performed.

    Infants and Children younger than 2 years

    Instill 1 drop of the 1% ophthalmic solution into affected eye(s) 3 times daily.

    For the prevention of increased intraocular pressure associated with laser surgery.
    Ophthalmic dosage (ophthalmic solution)
    Adults

    Instill 1 drop (or 2 drops 5 minutes apart) of 1%, 2%, or 4% ophthalmic solution into the affected eye(s) 15 to 60 minutes prior to surgery.

    For miosis induction.
    Ophthalmic dosage (ophthalmic solution)
    Adults

    Instill 1 drop (or 2 drops 5 minutes apart) of 1%, 2%, or 4% ophthalmic solution into the eye(s).

    Infants, Children, Adolescents

    For the induction of miosis prior to goniotomy or trabeculectomy, instill 1 drop of 1% or 2% ophthalmic solution into the eye 15 to 60 minutes prior to surgery.

    For the treatment of presbyopia.
    Ophthalmic dosage (Vuity only)
    Adults

    1 drop instilled in each eye once daily.

    For the treatment of xerostomia and/or xerophthalmia†.
    For xerostomia due to salivary gland hypofunction secondary to radiotherapy for cancer of the head and neck.
    Oral dosage
    Adults

    Initially, 5 mg PO 3 times daily. Dosage may be titrated up to 10 mg PO 3 times daily, if needed. The lowest effective maintenance dose should be used.

    For xerostomia and/or xerophthalmia† in patients with Sjogren's syndrome.
    Oral dosage
    Adults

    5 mg PO 4 times daily. The maximum recommended dosage is 10 mg/dose and 30 mg/day. Doses of 2.5 to 7.5 mg PO 4 times per day have studied and optimum responses were seen with the 5 mg dose (personal communication 2/12/97). In 1 randomized, single-blinded study, pilocarpine 2% ophthalmic solution 4 drops PO 3 times per day for 6 weeks was effective in stimulating salivary flow and relieved xerostomia in patients with Sjogren's syndrome. This dose was approximately equivalent to 2.5 mg 3 times per day. NOTE: The drops were administered orally in this study. The subjects were instructed to swish and swallow each dose.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    10 mg/dose or 30 mg/day PO; ophthalmic maximum is dependent on indication and dosage form.

    Elderly

    10 mg/dose or 30 mg/day PO; ophthalmic maximum is dependent on indication and dosage form.

    Adolescents

    Safety and efficacy of the oral formulation has not been established; ophthalmic solution maximum is dependent on indication.

    Children

    Safety and efficacy of the oral formulation has not been established; ophthalmic solution maximum is dependent on indication.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Regardless of the indication, the initial dosage of oral pilocarpine in patients with moderate hepatic impairment is 5 mg PO twice daily; adjust dosage based on response. Patients with mild hepatic impairment do not require dosage adjustment. Data are lacking in patients with severe hepatic impairment; oral pilocarpine is not recommended.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Administer pilocarpine with a full glass of water.

    Ophthalmic Administration

    Instruct patient on proper application of ocular system, eye gel, or eye solution. Apply ocular system at bedtime in order to reach a stable level of pilocarpine-induced myopia by morning.
    Do not to touch the tip of the dropper or tube to the eye, fingertips, or other surface.
    If administering ophthalmic solution with other topical ophthalmic agents, allow at least 5 minutes between administration times.
    Remove contact lenses prior to instilling the ophthalmic solution, and wait 10 minutes after dosing before reinserting the lenses.

    STORAGE

    Adsorbocarpine:
    - Protect from freezing
    - Store between 59 to 77 degrees F
    Akarpine:
    - Protect from freezing
    - Store between 59 to 77 degrees F
    Isopto Carpine:
    - Protect from freezing
    - Store between 59 to 77 degrees F
    Ocu-Carpine:
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in original container
    - Store upright
    Pilocar:
    - Protect from freezing
    - Store between 59 to 77 degrees F
    Pilopine HS:
    - Avoid excessive heat (above 104 degrees F)
    - Do not freeze
    Salagen:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    NOTE: Absolute contraindications for pilocarpine are related to dosage form and can be relevant to the condition being treated. Some contraindications may not be applicable to ophthalmic use and others not applicable to oral use.
     
    In February 2006, it was reported that the brand name Salagen (generic name pilocarpine), used to treat the dry mouth symptoms caused by Sjogren's syndrome or radiation therapy was being confused with the generic name, selegiline (brand name Eldepryl) an MAO-inhibitor used to treat Parkinson's disease. Both drugs are available in 5 mg tablets. Drug name confusion has occurred with both verbal and written prescription orders. In order to lessen drug name confusion, it may be prudent to list both the brand and generic names on prescriptions.
     
    There have been no overall differences in safety and efficacy observed between elderly and younger patients with any of the pilocarpine preparations.

    Retinal detachment

    As with all miotics, rare cases of retinal detachment have been reported with ophthalmic pilocarpine when used in certain susceptible individuals and those with pre-existing retinal disease. Miotics can precipitate detachment of the retina, which may manifest as a sudden drop in intraocular pressure. A thorough examination of the retina including funduscopy is advised prior to the initiation of ophthalmic pilocarpine. Instruct drug recipients to seek immediate medical care for sudden onset of vision loss.  It is not known whether this association may occur with oral pilocarpine use, as the systemic blood level related to retinal detachment is unknown.

    Closed-angle glaucoma

    Use of pilocarpine oral tablets is contraindicated when miosis is undesirable, such as in patients who have closed-angle glaucoma.]

    Iritis

    Use of pilocarpine oral tablets and ophthalmic gel is contraindicated when miosis is undesirable, such as in patients with acute iritis. Use of the ophthalmic solution is not recommended when iritis is present because adhesions (synechiae) may form between the iris and the lens.

    Contact lenses

    Contact lenses should be removed before treatment with pilocarpine ophthalmic solution and can be reinserted 10 minutes after the dose has been instilled.

    Asthma, bronchitis, chronic obstructive pulmonary disease (COPD), sulfite hypersensitivity

    Oral pilocarpine is contraindicated in patients with uncontrolled asthma and should be used with caution in patients with controlled asthma or chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis) requiring pharmacotherapy. Pilocarpine may stimulate the mucous cells of the respiratory tract and increase bronchial smooth muscle tone and airway resistance. Some combination preparations of pilocarpine contain sodium bisulfite and should be used with caution in patients with a known sulfite hypersensitivity, especially in patients with a history of asthma.

    Pregnancy

    There are no adequate and well-controlled studies of pilocarpine in pregnant patients to determine a drug-associated risk; therefore, use pilocarpine during pregnancy only if the benefits to the mother outweigh the potential risks to the fetus. Data from a retrospective case series identified no drug-related adverse effects in 4 patients or their infants following exposure to ophthalmic pilocarpine either pre-pregnancy, during pregnancy, or postpartum. In animal studies, systemically-administered pilocarpine was associated with a reduction in the mean fetal body weight and an increase in the incidence of skeletal variations when given to pregnant rats at a dosage of 90 mg/kg/day [approximately 26 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area (BSA) estimates]. These effects may have been secondary to maternal toxicity. In another study, oral administration of pilocarpine to female rats during gestation and lactation at a dosage of 36 mg/kg/day (approximately 10 times the maximum recommended dose for a 50 kg human when compared on the basis of BSA estimates) resulted in an increased incidence of stillbirths; decreased neonatal survival and reduced mean body weight of pups were observed at dosages of 18 mg/kg/day (approximately 5 times the maximum recommended dose for a 50 kg human when compared on the basis of BSA estimates) and above. Animal reproduction studies have not been conducted with ophthalmic pilocarpine hydrochloride.

    Breast-feeding

    It is not known whether pilocarpine is excreted in human milk. According to the manufacturer of oral pilocarpine, because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breast-feeding infants from pilocarpine, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. The manufacturers of ophthalmic pilocarpine recommend caution if the drug is administered to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. To minimize the amount of drug that reaches systemic circulation, apply pressure over the tear duct by the corner of the eye for 1 minute after each application to the eye.

    Biliary tract disease, cholelithiasis

    Pilocarpine should be used with caution in patients with biliary tract disease or cholelithiasis. Pilocarpine causes contractions of the gallbladder or biliary smooth muscle and biliary obstruction, cholangitis, or cholecystitis may occur.

    Hepatic disease

    Oral pilocarpine should be used with caution in patients with hepatic disease. Dosage reduction is recommended for patients with moderate hepatic impairment. Data are lacking in patients with severe hepatic impairment (Child-Pugh score 10 to 15); pilocarpine is not recommended in these patients.

    Cardiac disease

    Pilocarpine should be used with caution in patients with cardiac disease. Pilocarpine induces transient changes in heart rhythm or hemodynamics and patients with cardiac disease may not be able to compensate for these changes. Pulmonary edema can occur in patients being treated with ophthalmic pilocarpine in high doses for acute closed-angle glaucoma.

    Nephrolithiasis

    Pilocarpine should be used cautiously in patients with nephrolithiasis. Pilocarpine increases ureteral smooth muscle tone and may precipitate renal colic, especially in patients with nephrolithiasis.

    Psychosis

    Oral pilocarpine may have dose-related central nervous system effects which could exacerbate conditions of psychiatric disturbances (e.g., psychosis) or cognitive disturbances.

    Driving or operating machinery

    Patients using pilocarpine should be advised to exercise caution during night driving or other hazardous occupations in poor illumination. Patients should not be driving or operating machinery if vision is not clear. Miotics may also cause accommodative spasm.

    Children, infants, neonates, uveitis

    Pilocarpine ophthalmic solution should be used with caution when using it in infants, children, and adolescents with primary congenital glaucoma for control of intraocular pressure (IOP) as cases of paradoxical increase in IOP have been reported. Also, the ophthalmic solution is not recommended in pediatric patients with glaucoma secondary to anterior segment dysgenesis or uveitis (especially with active uveitis). The safety and efficacy of the ophthalmic gel or oral tablets have not been established in pediatric patients, including neonates, infants, children, and adolescents.

    ADVERSE REACTIONS

    Severe

    exfoliative dermatitis / Delayed / 0-1.0
    erythema nodosum / Delayed / 0-1.0
    pancreatitis / Delayed / 0-1.0
    bradycardia / Rapid / 0-1.0
    myocardial infarction / Delayed / 0-1.0
    thrombosis / Delayed / 0-1.0
    bone fractures / Delayed / 0-1.0
    laryngospasm / Rapid / 0-1.0
    visual impairment / Early / 5.0
    retinal detachment / Delayed / Incidence not known
    night blindness / Delayed / Incidence not known

    Moderate

    blurred vision / Early / 0-5.0
    edema / Delayed / 0-5.0
    amblyopia / Delayed / 4.0-4.0
    hypertension / Early / 0-3.0
    conjunctivitis / Delayed / 0-2.0
    dysphagia / Delayed / 1.0-2.0
    sinus tachycardia / Rapid / 1.0-2.0
    contact dermatitis / Delayed / 0-1.0
    skin ulcer / Delayed / 0-1.0
    cholelithiasis / Delayed / 0-1.0
    esophagitis / Delayed / 0-1.0
    colitis / Delayed / 0-1.0
    melena / Delayed / 0-1.0
    gastritis / Delayed / 0-1.0
    hepatitis / Delayed / 0-1.0
    palpitations / Early / 0-1.0
    angina / Early / 0-1.0
    hypotension / Rapid / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    peripheral edema / Delayed / 0-1.0
    migraine / Early / 0-1.0
    hypoglycemia / Early / 0-1.0
    leukopenia / Delayed / 0-1.0
    thrombocytopenia / Delayed / 0-1.0
    hematuria / Delayed / 0-1.0
    lymphadenopathy / Delayed / 0-1.0
    aphasia / Delayed / 0-1.0
    depression / Delayed / 0-1.0
    confusion / Early / 0-1.0
    myasthenia / Delayed / 0-1.0
    dyspnea / Early / 0-1.0
    dysuria / Early / 0-1.0
    pyuria / Delayed / 0-1.0
    vaginal pain / Early / 0-1.0
    conjunctival hyperemia / Early / 5.0
    ciliary body spasm / Rapid / Incidence not known
    myopia / Delayed / Incidence not known
    photophobia / Early / Incidence not known

    Mild

    hyperhidrosis / Delayed / 29.0-68.0
    chills / Rapid / 3.0-15.0
    nausea / Early / 0-15.0
    flushing / Rapid / 8.0-13.0
    headache / Early / 0-13.0
    dizziness / Early / 5.0-12.0
    asthenia / Delayed / 2.0-12.0
    increased urinary frequency / Early / 9.0-12.0
    dyspepsia / Early / 7.0-7.0
    diarrhea / Early / 4.0-7.0
    lacrimation / Early / 0-6.0
    abdominal pain / Early / 3.0-4.0
    vomiting / Early / 0-4.0
    pharyngitis / Delayed / 2.0-3.0
    pruritus / Rapid / 1.0-2.0
    rash / Early / 0-2.0
    epistaxis / Delayed / 1.0-2.0
    tremor / Early / 0-2.0
    drug-induced body odor / Delayed / 0-1.0
    alopecia / Delayed / 0-1.0
    hypothermia / Delayed / 0-1.0
    seborrhea / Delayed / 0-1.0
    xerosis / Delayed / 0-1.0
    xerostomia / Early / 0-1.0
    appetite stimulation / Delayed / 0-1.0
    gingivitis / Delayed / 0-1.0
    anorexia / Delayed / 0-1.0
    eructation / Early / 0-1.0
    syncope / Early / 0-1.0
    emotional lability / Early / 0-1.0
    insomnia / Early / 0-1.0
    anxiety / Delayed / 0-1.0
    hyperkinesis / Delayed / 0-1.0
    paresthesias / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    yawning / Early / 0-1.0
    laryngitis / Delayed / 0-1.0
    hiccups / Early / 0-1.0
    menorrhagia / Delayed / 0-1.0
    urinary urgency / Early / 0-1.0
    ocular irritation / Rapid / 5.0
    ocular pain / Early / 5.0
    miosis / Early / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Ambenonium Chloride: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Amoxapine: (Major) Amoxapine may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants, such as amoxapine, may potentially antagonize the therapeutic actions of cholinergic agonists.
    Anticholinergics: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Atenolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Atenolol; Chlorthalidone: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Atropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Atropine; Difenoxin: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Atropine; Edrophonium: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided. (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Belladonna; Opium: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Bendroflumethiazide; Nadolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Benztropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Beta-blockers: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Betaxolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Bethanechol: (Moderate) Pilocarpine and bethanechol are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
    Bisoprolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Brimonidine; Timolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Budesonide; Glycopyrrolate; Formoterol: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Carteolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Carvedilol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Cevimeline: (Moderate) Cevimeline and pilocarpine are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
    Chlordiazepoxide; Clidinium: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Chlorpromazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Cholinesterase inhibitors: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Codeine; Phenylephrine; Promethazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Codeine; Promethazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Dicyclomine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Diphenoxylate; Atropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Disopyramide: (Moderate) Disopyramide possesses clinically significant antimuscarinic properties and these appear to be dose-related. It is possible that disopyramide could antagonize the muscarinic actions of cholinergic agonists. Clinicians should be alert to this possibility.
    Donepezil: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Donepezil; Memantine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Dorzolamide; Timolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Edrophonium: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Esmolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Flavoxate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Fluphenazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Galantamine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Glycopyrrolate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Glycopyrrolate; Formoterol: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Guanidine: (Moderate) Guanidine and pilocarpine are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
    Homatropine; Hydrocodone: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Hyoscyamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Indacaterol; Glycopyrrolate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Labetalol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Levobetaxolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Levobunolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Maprotiline: (Major) Maprotiline may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants like maprotiline may potentially antagonize the therapeutic actions of the cholinesterase-inhibitors used for the treatment of dementia.
    Mepenzolate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Meperidine; Promethazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Mesoridazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Methscopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Metoprolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Nadolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Nebivolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Nebivolol; Valsartan: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Neostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Oxybutynin: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Penbutolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Perphenazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Perphenazine; Amitriptyline: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Phenothiazines: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Physostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Pindolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Pralidoxime: (Moderate) Pilocarpine and pralidoxime are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
    Prochlorperazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Promethazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Promethazine; Dextromethorphan: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Promethazine; Phenylephrine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Propantheline: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Propranolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Pyridostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Rivastigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Scopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Sotalol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Tacrine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
    Thiethylperazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Thioridazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Timolol: (Moderate) Systemically administered pilocarpine (e.g., when used for the treatment of xerostomia or xerophthalmia) should be administered with caution in patients taking beta-blockers because of the possibility of cardiac conduction disturbances. The risk of conduction disturbances with beta-blockers and ophthalmically administered pilocarpine is low.
    Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
    Trifluoperazine: (Moderate) Avoid using pilocarpine in combination with other drugs known to have anticholinergic effects as the therapeutic efficacy of either agent may be reduced.
    Trihexyphenidyl: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Trospium: (Moderate) Pharmacologically, parasympathomimetic drugs enhance muscarinic/cholinergic function. Because trospium is an antimuscarinic, the muscarinic actions of drugs known as parasympathomimetics, including direct cholinergic agonists, could be antagonized when used concomitantly with trospium.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of pilocarpine in pregnant patients to determine a drug-associated risk; therefore, use pilocarpine during pregnancy only if the benefits to the mother outweigh the potential risks to the fetus. Data from a retrospective case series identified no drug-related adverse effects in 4 patients or their infants following exposure to ophthalmic pilocarpine either pre-pregnancy, during pregnancy, or postpartum. In animal studies, systemically-administered pilocarpine was associated with a reduction in the mean fetal body weight and an increase in the incidence of skeletal variations when given to pregnant rats at a dosage of 90 mg/kg/day [approximately 26 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area (BSA) estimates]. These effects may have been secondary to maternal toxicity. In another study, oral administration of pilocarpine to female rats during gestation and lactation at a dosage of 36 mg/kg/day (approximately 10 times the maximum recommended dose for a 50 kg human when compared on the basis of BSA estimates) resulted in an increased incidence of stillbirths; decreased neonatal survival and reduced mean body weight of pups were observed at dosages of 18 mg/kg/day (approximately 5 times the maximum recommended dose for a 50 kg human when compared on the basis of BSA estimates) and above. Animal reproduction studies have not been conducted with ophthalmic pilocarpine hydrochloride.

    It is not known whether pilocarpine is excreted in human milk. According to the manufacturer of oral pilocarpine, because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breast-feeding infants from pilocarpine, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. The manufacturers of ophthalmic pilocarpine recommend caution if the drug is administered to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. To minimize the amount of drug that reaches systemic circulation, apply pressure over the tear duct by the corner of the eye for 1 minute after each application to the eye.

    MECHANISM OF ACTION

    Pilocarpine is a cholinergic muscarinic receptor agonist. By directly stimulating these receptors, pilocarpine causes smooth muscles, such as the iris sphincter muscle and ciliary muscle, to contract. Contraction of the iris sphincter muscle constricts the pupil producing miosis and improving near and intermediate visual acuity while maintaining some pupillary response to light. Contraction of the ciliary muscle may shift the eye to a more myopic or nearsighted state. In glaucoma, the intraocular pressure rises to an unacceptable level, producing pain and abnormal vision; if untreated, it can cause loss of sight. In open-angle glaucoma, pilocarpine contracts the ciliary muscle, increasing the outflow of aqueous humor, which reduces intraocular pressure. In closed-angle glaucoma, pilocarpine-induced miosis opens the angle of the anterior chamber of the eye, through which aqueous humor exits. Pilocarpine also counteracts the mydriatic effects of sympathomimetic agents used in ophthalmologic examinations. By overcoming the mydriatic effect of atropine, pilocarpine has been used alternately with atropine to break adhesions between the iris and the lens. Administered orally, pilocarpine stimulates secretions of the exocrine glands. All secretory glands may be affected, including an increase in salivary flow.

    PHARMACOKINETICS

    Pilocarpine is administered orally and via the ophthalmic route. Pilocarpine does not bind to human plasma proteins over a concentration range of 5 to 25,000 ng/mL. The mechanism for inactivation of pilocarpine is not clear, but thought to occur at the neuronal synapses and in plasma. Pilocarpine and its degradation products are excreted in the urine.
     
    Affected cytochrome P450 isoenzymes: none

    Oral Route

    Following oral administration of pilocarpine the elimination half-life ranges from 0.75 to 1.35 hours. Peak effect is achieved in about 1 hour. This can be longer if the drug is taken with food. The duration of action is 3 to 5 hours.

    Other Route(s)

    Ophthalmic Route
    Following application of a 1% solution to the eye, a drop in pressure occurs within 60 minutes that persists for 4 to 14 hours. Duration of action depends on the strength of pilocarpine used, usually between 0.5% to 4%. Systemic exposure was evaluated in 14 healthy subjects who received 2 drops of the 4% ophthalmic solution in both eyes 4-times daily for 8 days. Plasma concentrations reached steady-state after topical application with a mean Cmax of 3.7 ng/mL and AUC of 7.7 ng x hour/mL on day 8. The Tmax on day 8 ranged from 0.5 to 1 hour. In 22 patients with presbyopia, 1 drop of the 1.25% ophthalmic solution was administered in each eye once daily for 30 days. The mean Cmax and AUC values on Day 30 were 1.95 ng/mL and 4.14 ng x hour/mL, respectively. The median Tmax on Day 30 was 0.3 hours (range: 0.2 to 0.5 hours). The ocular system allows a sustained release of pilocarpine over 7 days, with maximal effect being achieved in 1.5 to 2 hours after the system is applied. A standard rate of release from an ocular system is either 20 mcg or 40 mcg/hour. The ophthalmic gel generally is used once daily, and a 1-time application can reduce the intraocular pressure for 18 to 24 hours. Use of these preparations can cause a period of pilocarpine-induced myopia.
     
    Pilocarpine is bound to serum and ocular tissues. Whether pilocarpine is distributed is not known, but it apparently does not accumulate in ocular tissue. Pilocarpine penetrates into ocular tissue through the cornea, the amount varying according to a number of factors.