Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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September 2023

IMPORTANT PRESCRIBING INFORMATION

Subject: 

Temporary Importation of Anticholium® (physostigmine salicylate) Ampules with Foreign, 

non-U.S. Labeling to Address Supply Shortage

Dear Healthcare Provider,

To address the ongoing shortages of physostigmine salicylate injection in the United States, Dr.

Franz Köhler Chemie GmbH (Koehler) in conjunction with Provepharm Inc. (Provepharm) and 

Direct Success, Inc. (Direct Success) is coordinating with the U.S. Food and Drug 

Administration (FDA) to temporarily import Anticholium® (Physostigmine salicylate, 

2mg/5ml, injection solution for intravenous use) into the U.S. market. Koehler’s Anticholium®

(Physostigmine salicylate, 2mg/5ml, injection solution for intravenous use), marketed and 

manufactured in Germany for Koehler, is not FDA-approved.

At this time, no other entity except Provepharm or its distributor Direct Success is authorized 

by the FDA to import or distribute physostigmine salicylate injection in the U.S. 

Effective immediately, Provepharm will distribute the following presentations of Anticholium®

(physostigmine salicylate) to address the critical shortage:

Product 

Description

Strength Packaging NDC 

number

Lot/ 

Batch #

Expiration 

Date

(Labeled)

Anticholium®

(physostigmine 

salicylate) 

2 mg/5 mL (0.4 

mg/mL) injection 

for intravenous use

5 x 5 mL 

ampules

81284-831-05 2315751 2026-05-31

To place an order, please contact Direct Success at Distribution@DSuccess.com or 1-877-

404-3338.

The U.S. imported Anticholium (physostigmine salicylate) injection contains nitrogen even 

though it is not listed on the enclosed Instructions for Use (IFU).

The barcode on the imported product label may not register accurately on the U.S. 

scanning systems. Institutions should manually input the imported product information into 

their systems and confirm that the barcode, if scanned, provides correct information. Alternative 
Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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procedures should be followed to assure that the correct drug product is being used and 

administered to individual patients.

In addition, the packaging of the imported product does not include serialization information. 

Koehler’s Anticholium® does not meet the Drug Supply Chain Security Act (DSCSA) 

requirements for the Interoperable Exchange of Information for Tracing of Human, Finished 

Prescription Drugs.

There are key differences between the U.S. marketed physostigmine salicylate injection and

ANTICHOLIUM® noted in Table 1 below.

Table 1. Key Differences between physostigmine salicylate injection and Anticholium®

Product Names U.S. physostigmine salicylate 

injection

Anticholium®

(German imported product)

Indication To reverse the effect upon the 

central nervous system, caused 

by clinical or toxic dosages of 

drugs capable of producing the 

anticholinergic syndrome.

Indicated for central anticholinergic 

syndrome (CAS), delayed postoperative 

awakening and shivering

Indicated as an antidote and/or 

antagonist in case of intoxication with 

and/or overdose of: alcohol, tropane 

alkaloids, amanita pantherina and 

amanita muscaria, tricyclic 

antidepressants, 

antiemetics/antihistamines, neuroleptic 

drugs, benzodiazepines, antispasmodics, 

parkinson disease medication, baclofen, 4-

hydroxybutyric acid (GHB), inhalation 

anesthetics, ketamine, 3-quinuclidinyl 

benzilate

Administration Injection for intramuscular or 

intravenous use 

Injection solution for intravenous use only

Packaging 2 mL in 1 AMPULE 5 ampules of 5 ml containing 2 mg of 

physostigmine salicylate

When using Anticholium® (Physostigmine) from Koehler the following advice has to be taken 

into account:

Dosing and administration:

For the treatment of postoperative awakening disorders in adults:

Slowly inject physostigmine intravenously at a dose of 0.04 mg/kg body weight (approx. 1 

mg/min), the maximum individual dose is 2 mg. In case of insufficient effect, give subsequent 

injections after 5 to 20 minutes at the earliest, after a positive evaluation of the effect of the first 

injection.
Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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Treatment in cases of intoxication:

Adults: Slowly inject 0.04 mg/kg body weight (2 mg) of physostigmine salicylate intravenously 

and subsequently inject 1-4 mg every 20 minutes. Repeat the effective dose if the intoxication 

symptoms recur, also in the form of a continuous infusion if deemed useful. 

Children and adolescents: Infants: Start with a low dose of 0.5 mg of physostigmine salicylate 

administered intravenously, repeat this dose every 5 minutes up to the overall dose of 2 mg, as 

long as the toxic, anticholinergic symptoms continue to persist and no cholinergic symptoms 

occur.

Method of administration: 

Anticholium® should be administered intravenously slowly or as brief infusion in 50 ml 

physiological saline solution over 10-15 minutes. A general criterion for adequate 

physostigmine dosing is the recognizable recovery of mental abilities and responsiveness (e.g. 

specifying name, address, date). 

For further Information please refer to the full prescribing information enclosed. 

Prescription and Labeling:

Anticholium® will be available only by prescription in the U.S. However, the imported product 

does not have the statement “Rx only” on the labeling. 

There is no barcode on this product for use with U.S. barcode scanning systems. 

Alternative procedures should be followed to ensure that the correct drug product is being used 

and administered to individual patients. 

Reporting Adverse Events: 

Healthcare providers should report adverse events associated with the use of Koehler’s 

Anticholium® to Provepharm at: 

Phone: 1-833-727-6556 

email: safety-us@provepharm.com 

Adverse reactions or quality problems experienced with the use of this product may be reported 

to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail or by 

fax. 

• Complete and submit the report Online: www.fda.gov/medwatch/report.htm

• Regular Mail or Fax: Download form 

https://www.accessdata.fda.gov/scripts/medwatch/index.cfm or call 1-800-332-1088 

to request a reporting form, then complete and return to the address on the preaddressed form, or submit by fax to 1-800-FDA-0178 (1-800-332-0178). 
Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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You may also contact our medical information department at medicalaffairs@provepharm.com

if you have any questions about the information contained in this letter or the safe and effective 

use of Anticholium®. 

This letter is not intended as a complete description of the benefits and risks related to the use 

of Anticholium®. Please refer to the enclosed full prescribing information. 

For additional information, please contact Dr. Franz Köhler Chemie GmbH at info@koehlerchemie.de or visit www.koehler-chemie.de 

Finally, please ensure that your staff and others in your institution who may be involved 

in the administration of Anticholium® receive a copy of this letter and review the 

information.

Sincerely, 

Frauke Weiß 

CEO

Enclosure: Anticholium® Full Prescribing Information
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US Product Import Product

Product name Physostigmine Salicylate Injection ANTICHOLIUM®

Disclaimer

Disclaimer: This drug has not been found by FDA to be safe 

and effective, and this labeling has not been approved by 

FDA. For further information about unapproved drugs, click 

here.

Disclaimer: Anticholium® (physostigmine salicylate) is not FDA approved, but 

is imported with foreign, non-U.S. labeling under a temporary importation 

license to address supply shortage.

Dosage Form solution for injection solution for injection or infusion

Label 

Composition 

Physostigmine Salicylate Injection is available in 2 mL ampules, 

each mL containing 1 mg of Physostigmine Salicylate in a vehicle 

composed of sodium metabisulfite 0.1%, benzyl alcohol 2.0% as a 

preservative in Water for Injection.

Anticholium® is available in 5 mL ampules, each mL containing 0.4 mg 

physostigmine salicylate in a vehicle composed of sodium edetate (Ph. Eur.), 

nitrogene and water for injection.
Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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Indications 

INDICATIONS AND USAGE: 

To reverse the effect upon the central nervous system, caused by 

clinical or toxic dosages of drugs capable of producing the 

anticholinergic syndrome.

Anticholium® is indicated for:

1. the use as an antidote and/or antagonist in case of intoxication with 

and/or overdose of:

• alcohol

• tropane alkaloids (hyoscyamine, atropine, scopolamine, as e.g. in 

brugmansia, datura, atropa belladonna)

• amanita pantherina and amanita muscaria

• tricyclic antidepressants (amitriptyline, imipramine, trimipramine, 

clomipramine, doxepine)

• antiemetics/antihistamines (phenothiazine, thioridazine, chlorpromazine, 

promethazine, diphenhydramine, dimenhydrinate)

• neuroleptic drugs (especially butyrophenones)

• benzodiazepines

• tolterodine, oxybutynine

• amantadine, diphenhydramine

• baclofen

• 4-hydroxybutyric acid (GHB)

• inhalation anesthetics

• ketamine

• 3-quinuclidinyl benzilate

2. the treatment of postoperative disorders:

• Central anticholinergic syndrome (CAS)

• Delayed postoperative awakening

• Shivering

Contraindications 

Physostigmine Salicylate Injection should not be used in the 

presence of asthma, gangrene, diabetes, cardiovascular disease, 

mechanical obstruction of the intestine or urogenital tract or any 

vagotonic state, and in patients receiving choline esters and 

depolarizing neuromuscular blocking agents (decamethonium, 

succinylcholine). 

For post-anesthesia, the concomitant use of atropine with 

physostigmine salicylate is not recommended, since the atropine 

antagonizes the action of physostigmine.

Anticholium® should not be used in the presence of hypersensitivity to 

physostigmine salicylate, bronchial asthma, ulcers associated with tissue 

destruction (gangrene), coronary heart disease, constipation (mechanical 

obstipation), mechanical ischuria (urinary retention), hereditary form of muscle 

atrophy (myotonic dystrophy), closed traumatic brain injuries, intestinal 

obstruction, spasms in the urinary tract collection system, inactivation of nerve and 

muscle cells after administration of drugs to relax the muscles (depolarization 

block after depolarizing muscle relaxants), in case of intoxication due to 

“irreversibly acting” cholinesterase inhibitors (drugs used to treat dementia), 

intoxication with phosphoric acid esters or barbiturates.
Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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Precautions

PRECAUTIONS: 

Because of the possibility of hypersensitivity in an occasional 

patient, atropine sulfate injection should always be at hand since it 

is an antagonist and antidote for physostigmine.

Talk to your doctor before you are given Anticholium® if you suffer from diabetes 

mellitus, slowed heart rate (bradycardia), disturbances of the atrioventricular 

conduction system, Parkinson’s disease or ulcerative colitis.

Hypersensitivity reactions may occur after administration of this medicine. These 

reactions may vary individually and may also cause life-threatening conditions. It 

is recommended to have emergency medication and medical aids ready. A 

risk/benefit analysis should be performed, and discontinuation of treatment should 

be considered.

Acute cardiac arrest may be possible during treatment with tricyclic 

antidepressants; therefore, Anticholium® should only be considered as an antidote 

for this indication while the patient has continuous ECG monitoring.

Interactions -

Tell your doctor or pharmacist if you are taking/using, have recently taken/used or 

intend to take/use any other medicines.

In case of simultaneous administration of other cholinesterase inhibitors (e.g. 

medicines for the treatment of dementia), caution should be exercised because of 

the potentiating effect. In intoxication with depolarizing muscle relaxants of the 

suxamethonium type, Anticholium® is contraindicated!

Warnings 

Contains sodium bisulfite, a sulfite that may cause allergic-type 

reactions including anaphylactic symptoms and life-threatening or 

less severe asthmatic episodes in certain susceptible people. The 

overall prevalence of sulfite sensitivity in the general population 

is unknown and probably low. Sulfite sensitivity is seen more 

frequently in asthmatic than in non-asthmatic people. 

If excessive symptoms of salivation, emesis, urination and 

defecation occur, the use of Physostigmine Salicylate Injection 

should be terminated. If excessive sweating or nausea occur, the 

dosage should be reduced. 

Intravenous administration should be at a slow, controlled rate, no 

more than 1 mg per minute (see dosage). Rapid administration can 

cause bradycardia, hypersalivation leading to a respiratory 

difficulties and possible convulsions. 

An overdosage of Physostigmine Salicylate Injection can cause a 

cholinergic crisis.

Talk to your doctor before you are given Anticholium® if you suffer from diabetes 

mellitus, slowed heart rate (bradycardia), disturbances of the atrioventricular 

conduction system, Parkinson’s disease or ulcerative colitis.

Hypersensitivity reactions may occur after administration of this medicine. These 

reactions may vary individually and may also cause life-threatening conditions. It 

is recommended to have emergency medication and medical aids ready. A 

risk/benefit analysis should be performed and discontinuation of treatment should 

be considered. 

Acute cardiac arrest may be possible during treatment with tricyclic 

antidepressants; therefore, Anticholium® should only be considered as an antidote 

for this indication while the patient has continuous ECG monitoring. 
Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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Dosage and 

Administration

Past Anesthesia Care: 0.5 to 1.0 mg intramuscularly or 

intravenously. INTRAVENOUS ADMINISTRATION SHOULD 

BE AT A SLOW CONTROLLED RATE OF NO MORE THAN 

1 MG PER MINUTE. Dosage may be repeated at intervals of 10 

to 30 minutes if desired patient response is not obtained.

PEDIATRIC DOSAGE: 

Recommended dosage is 0.02 mg/kg; intramuscularly or by slow 

intravenous injection, no more than 0.5 mg per minute. If the 

toxic effects persist, and there is no sign of cholinergic effects, the 

dosage may be repeated at 5 to 10 minute intervals until a 

therapeutic effect is obtained or a maximum of 2 mg dosage is 

attained. 

IN ALL CASES OF POISONING, THE USUAL SUPPORTIVE 

MEASURES SHOULD BE UNDERTAKEN.

Use in adults:

For the treatment of postoperative awakening disorders:

Slowly inject physostigmine intravenously at a dose of 0.04 mg/kg bodyweight 

(approx. 1 mg/min), the maximum individual dose is 2 mg.

In case of insufficient effect, give subsequent injections after 5 to 20 minutes at the 

earliest, after a positive evaluation of the effect of the first injection.

In cases of intoxication:

Adults: Slowly inject 0.04 mg/kg bodyweight (2 mg) of physostigmine salicylate 

intravenously and subsequently inject 1-4 mg every 20 minutes. Repeat the 

effective dose if the intoxication symptoms recur, also in the form of a continuous 

infusion if deemed useful.

Use in children and adolescents:

In cases of intoxication:

Infants: Start with a low dose of 0.5 mg of physostigmine salicylate administered 

intravenously, repeat this dose every 5 minutes up to the overall dose of 2 mg, as 

long as the toxic, anticholinergic symptoms continue to persist, and no cholinergic 

symptoms occur.

Method of administration

Intravenously slowly or as brief infusion in 50 ml physiological saline solution 

over 10-15 minutes. A general criterion for adequate physostigmine dosing is the 

recognizable recovery of mental abilities and responsiveness (e.g. specifying name, 

address, date).

Overdosage Can cause a cholinergic crisis. Appropriate antidote is atropine 

sulfate.

Intravenous administration of atropine up to normalization of the symptoms.

Normally, half the amount of the administered physostigmine salicylate is 

sufficient. In case of intoxication, measures to prevent absorption are to be started 

immediately (such as gastric lavage, administration of medicinal charcoal and 

laxatives).

The following information is intended for healthcare professionals:

Overdose emergency measures, symptoms, antidotes

In cases of intoxication, measures to prevent absorption such as gastric lavage, 

administration of medicinal charcoal and laxatives are to be started immediately.

An overdose of Anticholium® can cause bradycardia, hypersalivation, vomiting, 

and generalized tonic-clonic seizures.

Patients should be closely monitored by ECG.
Dr. Franz Köhler Chemie GmbH Postfach 1352 D-64603 Bensheim

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Adverse Reactions 

Nausea, vomiting and salivation; can be offset by reducing 

dosage. Bradycardia and convulsions, if intravenous 

administration is too rapid. See DOSAGE AND 

ADMINISTRATION.

Like all medicines, Anticholium® can cause side effects, although not everybody 

gets them.

System organ class Frequency: Unknown

Immune system disorders Hypersensitivity reactions

Endocrine disorders Hypersalivation

Heart diseases Changes of the heart rate (both 

bradycardia and tachycardia), 

sinoatrial block

Vascular diseases Low blood pressure (hypotension)

Respiratory, thoracic and mediastinal 

disorders

Spasms of the respiratory tract 

(broncho spasms)

Gastrointestinal disorders Nausea, vomiting

Skin and subcutaneous tissue disorders Sweating

Usage in 

pregnancy

Safe use in pregnancy and lactation has not been established; 

therefore, use in pregnant women, nursing mothers or women who 

may become pregnant requires that possible benefits be weighed 

against possible hazards to mother and child.

Pregnancy and breast-feeding 

Pregnancy:

There is no experience with the use of Anticholium® in pregnant women.

Physostigmine, the active substance contained in Anticholium®, passes into the 

placenta. Animal studies are insufficient with respect to effects on pregnancy, 

embryonal/foetal development, birth and postnatal development. The potential risk 

for humans is unknown.

For this reason, Anticholium® may only be administered to pregnant women if 

deemed absolutely necessary by the attending doctor.

Breast-feeding:

There is no experience with the use of Anticholium® during breastfeeding.

It is not known whether physostigmine, the active substance contained in 

Anticholium®, is excreted in human breast milk. For this reason, Anticholium® may 

only be used during breastfeeding if deemed absolutely necessary by the attending 

doctor. 

Storage 

Conditions

STORAGE: Store at 20° to 25°C (68° to 77°F) [see USP 

Controlled Room Temperature].

Store this medicine protected from light in the outer packaging, not above 25°C.

In undamaged container: 3 years The infusion solution should be used immediately 

after preparation. 

Keep this medicine out of the reach of children.

Do not use this medicine after the expiry date which is stated on the carton/label 

after EXP. The expiry date refers to the last day of that month.

How Supplied NDC 17478-510-02

2 mL Ampules packed 10 per box, 1 mg per mL.

Anticholium® is a clear, colorless to slightly reddish solution in glass ampules.

Pack containing 5 ampules with 5 ml.