Physostigmine is a parenteral and ophthalmic cholinesterase inhibitor. Physostigmine is similar to neostigmine except that it is a tertiary amine while neostigmine is a quaternary amine. This difference may explain the increased activity of physostigmine in the CNS. Physostigmine most commonly is used as an ophthalmic agent in the treatment of open-angle glaucoma. It has also been used to counteract toxic anticholinergic effects (both central and peripheral) of other drugs which cause anticholinergic toxicity, particularly in overdose situations. Until recently, physostigmine was used to treat tricyclic antidepressant (TCA) overdose, but it is no longer recommended for this purpose due to its own potentially harmful effects including seizures and life-threatening bradyarrhythmias progressing to asystole. Physostigmine has been used to treat Alzheimer's disease and hereditary ataxias. While some improvements were noted in some studies, the drug has not been well established in these diseases. Extracted physostigmine was first used ophthalmically, for glaucoma, in 1875. It was first synthesized in 1935, and is accepted by the FDA as a pre-1938 drug. A sustained-release form of physostigmine salicylate (Synapton(R)) has completed phase III investigation for Alzheimer's disease as of August 1996.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Atropine and resuscitation equipment should always be available when giving physostigmine parenterally.
-No dilution necessary. Do not administer injection solutions containing benzyl alcohol to neonates or premature infants.
-During administration, frequently monitor pulse, respiratory rate, blood pressure, and neurologic status. Monitor ECG during intravenous administration.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration:
Intravenous injection:
-Do not administer rapidly. Rapid administration may lead to bradycardia, increased salivation (which may lead to respiratory distress), or seizures.
-Inject via Y-site or through a 3-way stopcock at a rate of 1 mg per minute for adults and no faster than 0.5 mg per minute for children.
Intramuscular Administration:
Intramuscular injection:
-Inject deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.
Ophthalmic Administration
-Instruct patient on proper instillation of eye ointment or solution (see Patient Information).
-Do not to touch the tip of the dropper or tube to the eye, fingertips, or other surface.
Systemic physostigmine can cause a cholinergic crisis in incidents of overdose or rapid infusion rate. This situation is typically characterized by excessive sweating (hyperhidrosis), hypersalivation, nausea, vomiting, miosis, sinus bradycardia, hypotension, seizures, confusion, muscle weakness, muscle paralysis (including respiratory paralysis). Death can ensue unless treated. Resuscitation equipment and atropine should be on hand when the drug is given IV or IM. Atropine will counteract the drug's muscarinic cholinergic actions but will not counteract its paralytic effects. Adverse reactions commonly associated with physostigmine include nausea, vomiting, stomach cramps or abdominal pain, miosis, hypersalivation, diaphoresis, lacrimation, bronchospasm, dyspnea, and increased urinary frequency. CNS stimulation, restlessness, irregular pulse, palpitations, hallucinations, fasciculations, and myasthenia occur less frequently. Rarely, seizures, collapse, and death have been reported. Because seizures have occurred when IV physostigmine was administered to patients who have overdosed with tricyclic antidepressants, physostigmine is no longer recommended as a treatment for this condition.
Physostigmine should not be used in patients with closed-angle glaucoma because its action on the ciliary muscles can worsen blockage of aqueous humor outflow and increase intraocular pressure.
Physostigmine is contraindicated in patients with GI obstruction/ileus or urinary tract obstruction because it causes spasm of smooth muscle in these systems, which can be damaging and even cause perforation.
Physostigmine should be used with caution in patients with hypotension and/or bradycardia because it can increase vagal tone and worsen both of these conditions. Because of this and its direct stimulatory effect on the heart, physostigmine should not be used in patients with cardiac disease, especially arrhythmias or coronary artery disease.
Patients with asthma should not be given physostigmine because it can worsen bronchoconstriction. Physostigmine can alter insulin requirements so it also should not be used in patients with diabetes mellitus.
Physostigmine should be used with caution in patients with a seizure disorder because it can induce seizures by stimulating the CNS.
Physostigmine also can increase gastric secretions and should be used with cautioning patients with peptic ulcer disease.
Parenteral physostigmine contains sodium bisulphite and should be used with caution in patients with known sulfite hypersensitivity. Asthmatic patients are more likely to have sulfite hypersensitivity than non-asthmatic patients.
Physostigmine injection contains benzyl alcohol as a preservative and should be avoided in neonates because benzyl alcohol has been associated with a fatal toxic (gasping) syndrome.
Use of physostigmine during pregnancy is rare. No well-controlled human reproductive studies involving physostigmine have been performed, and it is unknown whether or not physostigmine is teratogenic. There is a possibility that neonates born to myasthenic mothers can have a transient muscle weakness if physostigmine is used during pregnancy. The manufacturer recommends use during pregnancy only if the benefits to the mother outweigh the potential risks to the fetus.
It is not known whether physostigmine is excreted in human milk. The manufacturer recommends use during breast-feeding only if the benefits to the mother outweigh the potential risks to the fetus. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
For antagonism of toxic anticholinergic effects which manifest as the 'anticholinergic syndrome':
Intravenous or Intramuscular dosage:
Adults: 0.5 to 2 mg IM or slow IV (not to exceed 1 mg/minute IV). May repeat every 10 to 30 minutes as needed. For overdosages of drugs that cause toxic anticholinergic effects, the manufacturer recommends a dose of 2 mg IM or slow IV; repeat if life-threatening signs such as arrhythmia, convulsions or coma occur. For post anesthesia care, the manufacturer recommends a dose of 0.5 to 1 mg IM or slow IV; may repeat every 10 to 30 minutes as needed.
Children: 0.02 mg/kg (range, 0.01 to 0.03 mg/kg) IM or slow IV (not to exceed 0.5 mg/minute IV); may repeat at 5- to 10-minute intervals as needed until a total dose of 2 mg is reached or an adverse cholinergic reaction occurs. Reserve use for life-threatening situations only.
For the treatment of open-angle glaucoma:
Ophthalmic dosage:
Adults, Adolescents, and Children: Instill 1 to 2 drops of 0.25% or 0.5% solution into eye(s) up to 4 times per day or apply 0.25% ointment to lower fornix 1 to 3 times per day.
Maximum Dosage Limits:
-Adults
8 drops/day total of 0.5% ophthalmic solution for glaucoma; maximum dosage for anticholinergic syndrome is not well defined; maximum dosage is dependent upon individual response.
-Elderly
8 drops/day total of 0.5% ophthalmic solution for glaucoma; maximum dosage for anticholinergic syndrome is not well defined; maximum dosage is dependent upon individual response.
-Adolescents
8 drops/day total of 0.5% ophthalmic solution for glaucoma; maximum dosage for anticholinergic syndrome is not well defined; maximum dosage is dependent upon individual response.
-Children
8 drops/day total of 0.5% ophthalmic solution for glaucoma; 2 mg/day IV or IM cumulative dosage for anticholinergic syndrome.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acetaminophen; Ibuprofen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Acetylcholine 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.
Albuterol; Budesonide: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Amifampridine: (Moderate) Coaministration of amifampridine and physostigmine may increase the risk for adverse reactions due to additive cholinergic effects. Monitor patients closely for new or worsening side effects such as headache, visual disturbances, watery eyes, excessive sweating, shortness of breath, nausea, vomiting, diarrhea, bradycardia, loss of bladder control, confusion, or tremors.
Amitriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Amlodipine; Celecoxib: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
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 physostigmine. Consider alternatives if concurrent therapy is needed.
Articaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Atracurium: (Moderate) A higher atracurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as physostigmine.
Atropine: (Major) Coadministration of atropine and physostigmine may produce a mutually antagonistic effect.
Atropine; Difenoxin: (Major) Coadministration of atropine and physostigmine may produce a mutually antagonistic effect.
Azelastine; Fluticasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Beclomethasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Benztropine: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of benztropine. Benztropine might also antagonize some of the effects of the parasympathomimetics.
Betamethasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Bethanechol: (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.
Budesonide: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Budesonide; Formoterol: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy. (Minor) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Bupivacaine Liposomal: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Bupivacaine; Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Bupivacaine; Meloxicam: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Celecoxib: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Celecoxib; Tramadol: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Cevimeline: (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.
Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Chloroprocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Cholinergic agonists: (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.
Ciclesonide: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Cisatracurium: (Moderate) A higher cisatracurium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as physostigmine.
Clomipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Cocaine: (Major) cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine's effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued. Additionally, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis.
Corticosteroids: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Cortisone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Deflazacort: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Desflurane: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Desipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Dexamethasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Diclofenac: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Diclofenac; Misoprostol: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Dicyclomine: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of dicyclomine and vice-versa.
Diflunisal: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Digoxin: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as digoxin. In one study involving multiple doses of galantamine at 24 mg/day with digoxin at a dose of 0.375 mg/day, there was no effect on the pharmacokinetics of digoxin, except one healthy subject was hospitalized due to second and third degree heart block and bradycardia.
Diphenhydramine; Ibuprofen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Diphenhydramine; Naproxen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Diphenoxylate; Atropine: (Major) Coadministration of atropine and physostigmine may produce a mutually antagonistic effect.
Doxepin: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Etodolac: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Etomidate: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Fenoprofen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Fludrocortisone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Flunisolide: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Flurbiprofen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Fluticasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Fluticasone; Salmeterol: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Fluticasone; Vilanterol: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Formoterol; Mometasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Glycopyrrolate: (Minor) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Glycopyrrolate; Formoterol: (Minor) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Guanidine: (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.
Halogenated Anesthetics: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Homatropine; Hydrocodone: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of homatropine.
Hydrocodone; Ibuprofen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Hydrocortisone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Hyoscyamine: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Ibuprofen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ibuprofen; Famotidine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ibuprofen; Oxycodone: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ibuprofen; Pseudoephedrine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Imipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Indacaterol; Glycopyrrolate: (Minor) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Indomethacin: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Isoflurane: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Ketamine: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Ketoprofen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Ketorolac: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Lidocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Lidocaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Lidocaine; Prilocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary. (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
Meclofenamate Sodium: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Mefenamic Acid: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Meloxicam: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Mepivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of hyoscyamine.
Methocarbamol: (Moderate) Methocarbamol may inhibit the effect of cholinesterase inhibitors. Methocarbamol also has sedative properties that may interfere with cognition. Therefore, methocarbamol should be used with caution in patients receiving cholinesterase inhibitors.
Methylprednisolone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Mometasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Nabumetone: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Naproxen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Naproxen; Esomeprazole: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Naproxen; Pseudoephedrine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Neostigmine: (Moderate) Neostigmine and physostigmine are both parasympathomimetics. Coadministration results in additive effects and should be done cautiously.
Neostigmine; Glycopyrrolate: (Moderate) Neostigmine and physostigmine are both parasympathomimetics. Coadministration results in additive effects and should be done cautiously. (Minor) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of glycopyrrolate.
Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Nortriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Olopatadine; Mometasone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Oxaprozin: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Oxybutynin: (Moderate) Oxybutynin is an antimuscarinic; the muscarinic actions of physostigmine could be antagonized when used concomitantly with oxybutynin.
Pancuronium: (Moderate) A higher pancuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as physostigmine.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of atropine and physostigmine may produce a mutually antagonistic effect. (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of hyoscyamine. (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of scopolamine.
Pilocarpine: (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.
Piroxicam: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Pralidoxime: (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.
Prednisolone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Prednisone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Prilocaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Prilocaine; Epinephrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Propantheline: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of propantheline.
Propofol: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Protriptyline: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Pyridostigmine: (Major) Pyridostigmine and physostigmine are both parasympathomimetics. Coadministration results in additive effects and should be done cautiously.
Quinine: (Major) The actions of quinine on skeletal muscle are pharmacologically opposite to those of cholinesterase inhibitors. Therefore, quinine may interfere with the actions of cholinesterase inhibitors in treating such conditions as myasthenia gravis. This represents a pharmacodynamic interaction with cholinesterase inhibitors rather than a pharmacokinetic interaction.
Rocuronium: (Moderate) A higher rocuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as physostigmine.
Ropivacaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
Scopolamine: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of scopolamine.
Sevoflurane: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Succinylcholine: (Contraindicated) Physostigmine is contraindicated in patients receiving succinylcholine due to reduced plasma cholinesterase activity and prolonged neuromuscular blockade.
Sulindac: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Sumatriptan; Naproxen: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Tetracaine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine. Dosage adjustment of the cholinesterase inhibitor may be necessary.
Tolmetin: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD.
Triamcinolone: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Trihexyphenidyl: (Major) The muscarinic actions of physostigmine can antagonize the antimuscarinic actions of trihexyphenidyl.
Trimipramine: (Moderate) Tricyclic antidepressants may antagonize some of the effects of cholinesterase inhibitors due to their anticholinergic activity. It may be helpful to choose an alternative antidepressant with lower propensity for anticholinergic activity.
Vecuronium: (Moderate) A higher vecuronium dose may be required to achieve neuromuscular block with concomitant use of a cholinesterase inhibitor, such as physostigmine.
Physostigmine competes with acetylcholine for its binding site on acetylcholinesterase. By interfering with the enzymatic destruction of acetylcholine, physostigmine potentiates the action of acetylcholine on both the skeletal muscle (nicotinic receptor) and the GI tract (muscarinic receptor).
Physostigmine acts primarily at muscarinic cholinergic synapses and within the CNS, having less effect at the myoneural junction at low doses. At higher doses, physostigmine exerts some effects not related to acetylcholinesterase inhibition. Physostigmine may act at the myoneural junction to cause a depolarizing block. It also can exert a direct blocking action within autonomic ganglia and directly potentiate CNS depression.
Specific responses to cholinesterase inhibitors parallel cholinergic stimulation: increased skeletal muscle tone (nicotinic); increased gastric motility and GI tone (muscarinic); bradycardia (muscarinic); ureteral constriction (muscarinic); stimulation of the sweat and salivary glands (muscarinic); and constriction of the bronchi (muscarinic). Some evidence suggests there is also a direct action on skeletal muscle.
Physostigmine causes miosis by stimulating cholinergic responses in the eye. The drug decreases intraocular pressure, presumably by inducing ciliary muscle contraction, which widens the trabecular meshwork, allowing for increased outflow of aqueous humor.
In the past, physostigmine was used to manage TCA overdose. Although some patients regained consciousness after physostigmine administration, physostigmine did not correct the cardiac arrhythmias. Arrhythmias secondary to TCA overdose were determined to be secondary to the quinidine-like effects of the TCA and not to anticholinergic toxicity. Because of this and the fact that physostigmine can induce seizures, the drug is no longer recommended for treatment of TCA overdose.
Physostigmine is administered via intravenous or intramuscular injection or applied topically to the eye. It is distributed widely throughout the body and crosses the blood-brain barrier. The mode of excretion is unknown; a small amount is excreted in the urine.
-Route-Specific Pharmacokinetics
Intravenous Route
Peak effects are seen in approximately 5 minutes when given IV. Cholinesterase hydrolyzes physostigmine, making its duration of action approximately 1 to 2 hours when given IV.
Intramuscular Route
Peak effects of physostigmine are seen in approximately 5 minutes when given IM.
Other Route(s)
Ophthalmic route
Peak effects are seen in within 10 to 30 minutes when applied topically to the eye. Cholinesterase hydrolyzes physostigmine, making its duration of action approximately 12 to 36 hours after ophthalmic use.