Salagen

Other Agents for Local Oral Treatment
Other Miotics-Antiglaucoma Agents

Administer pilocarpine with a full glass of water.

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.

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

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
hypoglycemia / Early / 0-1.0
migraine / Early / 0-1.0
peripheral edema / Delayed / 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

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 pain / Early / 5.0
ocular irritation / Rapid / 5.0
miosis / Early / Incidence not known

Adsorbocarpine, Akarpine, Isopto Carpine, Pilocar, Salagen, Vuity

Rx

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

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.

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.

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

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

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

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.

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.

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

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.

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

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.

1 drop instilled in each eye once daily. An additional dose in each eye may be administered 3 to 6 hours after the first dose.

5 mg PO 3 times daily, initially. Titrate dose according to response and tolerance. Usual dose: 15 to 30 mg/day. Max: 10 mg/dose.

5 mg PO once daily for 1 to 2 weeks, then 5 mg PO twice daily for 1 to 2 weeks, then 5 mg PO 3 times daily for 1 to 2 weeks, then 5 mg PO 4 times daily.

†Indicates off-label use

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.

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

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.
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; 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.
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.
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.
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.
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.
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.
Neostigmine; Glycopyrrolate: (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.
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.
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.
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.

Adsorbocarpine/Akarpine/Isopto Carpine/Pilocar/Pilocarpine/Pilocarpine Hydrochloride/Vuity Ophthalmic Sol: 1%, 1.25%, 2%, 4%
Pilocarpine/Pilocarpine Hydrochloride/Salagen Oral Tab: 5mg, 7.5mg

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

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

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

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

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.

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

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.

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.

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.