Lofene

Lofene Injection Pfizer also contains sodium chloride and water for injections.

Lofene sulfate is bis (1R, 3r, 5S)-3-[(RS)-(3-hydroxy-2-phenylpropionyl)oxy]-8-methyl-8-azabicyclo[3.2.1]octane sulfate. It appears as colourless crystals or a white, crystalline powder. It is very soluble in water, freely soluble in alcohol and practically insoluble in ether. It has a molecular formula of (C₁₇H₂₃NO₃)₂,H₂SO₄,H₂O and a molecular weight of 695.

The Lofene® (Lofene) Auto-injector is indicated for the treatment of poisoning by susceptible organophosphorous nerve agents having cholinesterase activity as well as organophosphorous or carbamate insecticides. The Lofene (Lofene) auto-injector should be used by persons who have had adequate training in the recognition and treatment of nerve agent or insecticide intoxication. Pralidoxime chloride may serve as an important adjunct to Lofene therapy.

The Lofene® (Lofene) is intended as an initial treatment of the muscarinic symptoms of insecticide or nerve agent poisonings (generally breathing difficulties due to increased secretions); definitive medical care should be sought immediately. The Lofene® (Lofene) Auto-injector should be administered as soon as symptoms of organophosphorous or carbamate poisoning appear (usually tearing, excessive oral secretions, wheezing, muscle fasciculations, etc.) In moderate to severe poisoning, the administration of more than one Lofene® (Lofene) may be required until atropinization is achieved (flushing, mydriasis, tachycardia, dryness of the mouth and nose). In severe poisonings, it may also be desirable to concurrently administer an anticonvulsant if seizure is suspected in the unconscious individual since the classic tonic-clonic jerking may not be apparent due to the effects of the poison. In poisonings due to organophosphorous nerve agents and insecticides it may also be helpful to concurrently administer a cholinesterase reactivator such as pralidoxime chloride.

Lofene produces many effects in the body such as reducing muscle spasms and fluid secretions.

Lofene is used to help reduce saliva, mucus, or other secretions in your airway during a surgery. Lofene is also used to treat spasms in the stomach, intestines, bladder, or other organs.

Lofene is sometimes used as an antidote to treat certain types of poisoning.

Lofene may also be used for purposes not listed in this medication guide.

CAUTION! PRIMARY PROTECTION AGAINST EXPOSURE TO CHEMICAL NERVE AGENT AND INSECTICIDE POISONING IS THE WEARING OF PROTECTIVE GARMENTS INCLUDING MASKS, DESIGNED SPECIFICALLY FOR THIS USE.

INDIVIDUALS SHOULD NOT RELY SOLELY UPON THE AVAILABILITY OF ANTIDOTES SUCH AS Lofene AND PRALIDOXIME TO PROVIDE COMPLETE PROTECTION FROM CHEMICAL NERVE AGENT AND INSECTICIDE POISONING.

Immediate evacuation from the contaminated environment is essential. Decontamination of the poisoned individual should occur as soon as possible.

The Lofene® (Lofene) Auto-injector is indicated for the treatment of poisoning by susceptible organophosphorous nerve agents having cholinesterase activity as well as organophosphorous or carbamate insecticides. The Lofene® (Lofene) auto-injector should be used by persons who have had adequate training in the recognition and treatment of nerve agent or insecticide intoxication. Pralidoxime chloride may serve as an important adjunct to Lofene therapy.

The Lofene® (Lofene) is intended as an initial treatment of the muscarinic symptoms of insecticide or nerve agent poisonings (generally breathing difficulties due to increased secretions); definitive medical care should be sought immediately. The Lofene® (Lofene) Auto-injector should be administered as soon as symptoms of organophosphorous or carbamate poisoning appear (usually tearing, excessive oral secretions, wheezing, muscle fasciculations, etc.) In moderate to severe poisoning, the administration of more than one Lofene® (Lofene) may be required until atropinization is achieved (flushing, mydriasis, tachycardia, dryness of the mouth and nose). In severe poisonings, it may also be desirable to concurrently administer an anticonvulsant if seizure is suspected in the unconscious individual since the classic tonic-clonic jerking may not be apparent due to the effects of the poison. In poisonings due to organophosphorous nerve agents and insecticides it may also be helpful to concurrently administer a cholinesterase reactivator such as pralidoxime chloride.

It is recommended that three (3) Lofene® (Lofene) auto-injectors be available for use in each person at risk for nerve agent or organophosphate insecticide poisoning; one (1) for mild symptoms plus two (2) more for severe symptoms as described below. No more than three (3) Lofene® (Lofene) injections should be used unless the patient is under the supervision of a trained medical provider. Different dose strengths of the Lofene® (Lofene) are available depending on the recipient's age and weight.

• Adults and children weighing over 90 lbs (generally over 10 years of age)..............Lofene® (Lofene) 2 mg (green)
• Children weighing 40 lbs to 90 lbs (generally 4 to 10 years of age)..............Lofene® (Lofene) 1 mg (dark red)
• Children weighing 15 lbs to 40 lbs (generally 6 months to 4 years of age)..............Lofene® (Lofene) 0.5 mg (blue)

NOTE: Children weighing under 15 lbs (generally younger than 6 months old) should ordinarily not be treated with the Lofene® auto-injector. Lofene doses for these children should be individualized at doses of 0.05 mg/kg.

Treatment of MILD SYMPTOMS

One (1) Lofene® (Lofene) is recommended if two or more MILD symptoms of nerve agent (nerve gas) or insecticide exposure appear in situations where exposure is known or suspected.

Two (2) additional Lofene® (Lofene) injections given in rapid succession are recommended 10 minutes after receiving the first Lofene® (Lofene) injection if the victim develops any of the SEVERE symptoms listed below. If possible, a person other than the victim should administer the second and third Lofene® (Lofene) injections.

Treatment of SEVERE SYMPTOMS:

If a victim is encountered who is either unconscious or has any of the SEVERE symptoms listed below, immediately administer three (3) Lofene® (Lofene) injections into the victim's mid-lateral thigh in rapid succession using the appropriate weight-based Lofene® (Lofene) dose.

MILD SYMPTOMS of nerve agent or insecticide exposure include the following:

-Blurred vision, miosis

-Excessive unexplained teary eyes

-Excessive unexplained runny nose

-Increased salivation such as sudden unexplained excessive drooling

-Chest tightness or difficulty breathing

-Tremors throughout the body or muscular twitching

-Nausea and/or vomiting

-Unexplained wheezing or coughing

-Acute onset of stomach cramps

-Tachycardia or bradycardia

SEVERE SYMPTOMS of exposure to nerve agent or insecticides include the following:

-Strange or confused behavior

-Severe difficulty breathing or severe secretions from your lungs/airway

-Severe muscular twitching and general weakness

-Involuntary urination and defecation (feces)

-Convulsions

-Unconsciousness

All victims should be evacuated immediately from the contaminated environment. Medical help should be sought immediately. Protective masks and clothing should be used when available. Decontamination procedures should be undertaken as soon as possible. If dermal exposure has occurred, clothing should be removed and the hair and skin washed thoroughly with sodium bicarbonate or alcohol as soon as possible.

Emergency care of the severely poisoned individual should include removal of oral and bronchial secretions, maintenance of a patent airway, supplemental oxygen and, if necessary, artificial ventilation. In general, Lofene should not be used until cyanosis has been overcome since Lofene may produce ventricular fibrillation and possible seizures in the presence of hypoxia.

Pralidoxime (if used) is most effective if administered immediately or soon after the poisoning. Generally, little is accomplished if pralidoxime is given more than 36 hours after termination of exposure unless the poison is known to age slowly or re-exposure is possible, such as in delayed continuing gastrointestinal absorption of ingested poisons. Fatal relapses, thought to be due to delayed absorption, have been reported after initial improvement. Continued administration for several days may be useful in such patients.

Close supervision of all moderately to severely poisoned patients is indicated for at least 48 to 72 hours.

An anticonvulsant such as diazepam may be administered to treat convulsions if suspected in the unconscious individual. The effects of nerve agents and some insecticides can mask the motor signs of a seizure.

IMPORTANT: PHYSICIANS AND/OR OTHER MEDICAL PERSONNEL ASSISTING EVACUATED VICTIMS OF NERVE AGENTS AND INSECTICIDE POISONING SHOULD AVOID EXPOSING THEMSELVES TO CONTAMINATION BY THE VICTIM'S CLOTHING. AGGRESSIVE AND SAFE DECONTAMINATION IS STRONGLY SUGGESTED.

Instructions for administering Lofene® (Lofene) (please refer to the illustrated Self Aid and Caregiver Directions for Use elsewhere):

Warning: Giving additional Lofene® (Lofene) injections by mistake in the absence of actual nerve agent or insecticide poisoning may cause an overdose of Lofene which could result in temporary incapacitation (inability to walk properly, see clearly or think clearly for several or more hours). Patients with cardiac disease may be at risk for serious adverse events, including death.

How supplied

The Lofene® (Lofene) is supplied in three strengths. The Lofene® 0.5 mg provides Lofene Injection (Lofene, 0.42 mg/0.7 ml), Lofene® 1 mg provides Lofene Injection (Lofene, 0.84 mg/0.7 ml), and Lofene® 2 mg provides Lofene Injection (Lofene, 1.67 mg/0.7 ml) in sterile solution for intramuscular injection. The Lofene® (Lofene) is a self-contained unit designed for self or caregiver administration.

Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F)

Keep from freezing. Protect from light.

Manufactured by: MERIDIAN MEDICAL TECHNOLOGIES, INC., 10240 Old Columbia Road, COLUMBIA, MD 21046. FDA Rev date: 9/17/2004

See also:
What is the most important information I should know about Lofene?

Known hypersensitivity to Lofene or other anticholinergic agents.

Severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; gastrointestinal obstruction eg, pyloroduodenal stenosis, achalasia, cardiospasm, paralytic ileus, intestinal atony; closed-angle glaucoma; obstructive uropathy eg, bladder neck obstruction caused by prostatic hypertrophy; myasthenia gravis; tachycardia secondary to cardiac insufficiency or thyrotoxicosis; acute hemorrhage with unstable cardiovascular status; febrile patients or patients exposed to elevated ambient temperature due to risk of provoking hyperpyrexia and heat prostration; prostatic enlargement; pregnancy-induced hypertension.

Use Lofene drops as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Lofene drops. Talk to your pharmacist if you have questions about this information.
• To use Lofene drops in the eye, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eyelid for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean, dry tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.
• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.
• If you miss a dose of Lofene drops, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Lofene drops.

Use: Labeled Indications

Antidote: Antidote for anticholinesterase poisoning (carbamate insecticides, nerve agents, organophosphate insecticides); antidote for muscarine-containing mushroom poisoning.

Adjuvant use with anticholinesterases (eg, edrophonium, neostigmine) to decrease their adverse effects during reversal of neuromuscular blockade.

Cardiovascular conditions: Treatment of symptomatic sinus bradycardia, atrioventricular (AV) nodal block.

Note: Likely not effective for type II second-degree or third-degree AV block (AHA [Hazinski 2015]). Use is no longer recommended in the management of asystole or pulseless electrical activity (PEA) (ACLS 2010).

Respiratory tract: Preoperative/preanesthetic medication to inhibit salivation and secretions.

Off Label Uses

Rapid sequence intubation (premedication)

Clinical experience suggests the utility of Lofene in adults who are at risk of developing bradycardia during rapid sequence intubation, such as those receiving conduction-altering drugs (eg, beta-blockers).

Based on the American Heart Association 2015 Handbook of Emergency Cardiovascular Care for Healthcare Providers, the use of Lofene is effective and recommended as a premedication to prevent bradycardia in adults undergoing rapid sequence intubation.

Based on the American Society of Nuclear Cardiology, Lofene may be administered as an adjunctive agent to increase heart rate in patients who do not achieve target heart rate with dobutamine alone.

See also:
What other drugs will affect Lofene?

Lofene may cause increased anticholinergic activity when administered concomitantly with other anticholinergic drugs eg, phenothiazines, antispasmodics, antiparkinsonian drugs, antiarrhythmics with anticholinergic activity eg, disopyramide and quinidine, some antihistamines, tricyclic antidepressants or butyrophenones.

The absorption of other drugs may be affected by the reduction in gastric motility caused by Lofene.

Lofene antagonises the actions of a number of compounds including synthetic choline esters eg, bethanechol and carbachol, anticholinesterase drugs eg, physostigmine, neostigmine and pyridostigmine and cholinomimetic alkaloids eg, pilocarpine.

Ketoconazole: Anticholinergics may increase gastrointestinal pH, possibly resulting in a marked reduction in ketoconazole absorption during concurrent use with anticholinergics; patients should be advised to take these medications at least 2 hrs after ketoconazole.

Cisapride and Metoclopramide: Concurrent use with anticholinergics may antagonise the gastrointestinal motility of cisapride and metoclopramide.

Opioid (Narcotic) Analgesics: Concurrent use with anticholinergics may result in increased risk of severe constipation, which may lead to paralytic ileus and/or urinary retention.

Haloperidol: Antipsychotic effectiveness of haloperidol may be decreased in schizophrenic patients.

Cholinesterase Inhibitors: In view of the pharmacodynamic effects of Lofene, Lofene may interfere with the activity of cholinesterase inhibitors eg, rivastigmine, donepezil.

Incompatibilities: Lofene Injection Pfizer has been shown to be incompatible with solutions containing adrenaline HCl, amylobarbitone sodium, pentobarbitone sodium, promazine HCl, ampicillin sodium, chloramphenicol sodium succinate, chlortetracycline HCl, heparin sodium, metaraminol tartrate, methicillin sodium, nitrofurantoin, novobiocin, oxacillin sodium, sodium bicarbonate, sulfadiazine sodium, sulfafurazole diethanolamine, tetracycline HCl, thiopentone sodium, vitamin B complex with ascorbic acid and warfarin sodium. This list is not exhaustive.

See also:
What are the possible side effects of Lofene?

Mild to moderate pain may be experienced at the site of injection.

The major and most common side effects of Lofene can be attributed to its antimuscarinic action. These include dryness of the mouth, blurred vision, photophobia, confusion, headache, dizziness, tachycardia, palpitations, flushing, urinary hesitance or retention, constipation, abdominal distention, nausea, vomiting, loss of libido and impotency. Anhidrosis may produce heat intolerance and impairment of temperature regulation especially in a hot environment. Larger or toxic doses may produce such central effects as restlessness, tremor, fatigue, locomotor difficulties, delirium, followed by hallucinations, depression and ultimately, medullary paralysis and death. Large doses can also lead to circulatory collapse. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma. Hypersensitivity reactions will occasionally occur with Lofene: these are usually seen as skin rashes, on occasion progressing to exfoliation. Adverse events seen in pediatrics are similar to those that occur in adult patients although central nervous system complaints are often seen earlier and at lower doses.

When Lofene and pralidoxime are used together, the signs of atropinization may occur earlier than might be expected than when Lofene is used alone. This is especially true if the total dose of Lofene has been large and the administration of pralidoxime has been delayed. Excitement and manic behavior immediately following recovery of consciousness have been reported in several cases. However, similar behavior has occurred in cases of organophosphate poisoning that were not treated with pralidoxime.

Amitai et el (JAMA 1990) evaluated the safety of Lofene® (Lofene) 0.5 mg, 1 mg and 2 mg in a case series of 240 children who received Lofene® (Lofene) inappropriately (i.e., no nerve agent exposure) during the 1990 Gulf War Period. Overall, severity of atropinization followed a nonlinear correlation with dose. Estimated doses up to 0.045 mg/kg produced no signs of atropinization. Estimated doses between 0.045 mg/kg to 0.175 mg/kg and even greater than 0.175 mg/kg were associated with mild and severe effects respectively. Actual dosage received by children may have been considerably lower than estimated since incomplete injection in many cases was suspected. Regardless, adverse events reported were generally mild and self-limited. Few children required hospitalization. Adverse reactions reported were dilated pupils (43%), tachycardia (39%), dry membranes (35%), flushed skin (20%), temperature 37.8° C or 100° F (4%) and neurologic abnormalities (5%). There was also local pain and swelling. In 91 children with ECGs, no abnormalities were noted other than sinus tachycardia; 22 children had severe tachycardia of 160-190 bpm. Neurologic abnormalities consisted of irritability, agitation, confusion, lethargy, and ataxia.

The following adverse reactions were reported in published literature for Lofene in both adults and children:

Cardiovascular: Sinus tachycardia, supraventricular tachycardia, junctional tachycardia, ventricular tachycardia, bradycardia, palpitations, ventricular arrhythmia, ventricular flutter, ventricular fibrillation, atrial arrhythmia, atrial fibrillation, atrial ectopic beats, ventricular premature contractions, bigeminal beats, trigeminal beats, nodal extrasystole, ventricular extrasystole, supraventricular extrasystole, asystole, cardiac syncope, prolongation of sinus node recovery time, cardiac dilation, left ventricular failure, myocardial infarction, intermittent nodal rhythm (no P wave), prolonged P wave, shortened PR segment, R on T phenomenon, shortened RT duration, widening and flattening of QRS complex, prolonged QT interval, flattening of T wave, repolarization abnormalities, altered ST-T waves, retrograde conduction, transient AV dissociation, increased blood pressure, decreased blood pressure, labile blood pressure, weak or impalpable peripheral pulses.

Eye: Mydriasis, blurred vision, pupils poorly reactive to light, photophobia, decreased contrast sensitivity, decreased visual acuity, decreased accommodation, cycloplegia, strabismus, heterophoria, cyclophoria, acute angle closure glaucoma, conjunctivitis, keratoconjunctivitis sicca, blindness, tearing, dry eyes/dry conjunctiva, irritated eyes, crusting of eyelid, blepharitis.

Gastrointestinal: Nausea, abdominal pain, paralytic ileus, decreased bowel sounds, distended abdomen, vomiting, delayed gastric emptying, decreased food absorption, dysphagia.

General:Hyperpyrexia, lethargy, somnolence, chest pain, excessive thirst, weakness, syncope, insomnia, tongue chewing, dehydration, feeling hot, injection site reaction.

Immunologic: Anaphylactic reaction.

Special Investigations: Leukocytosis, hyponatremia, elevated BUN, elevated hemoglobin, elevated erythrocytes, low hemoglobin, hypoglycemia, hyperglycemia, hypokalemia, increase in photic stimulation on EEG, signs of drowsiness on EEG, runs of alpha waves on EEG, alpha waves (EEG) blocked upon opening eyes.

Metabolic: Failure to feed.

Central Nervous System: Ataxia, hallucinations (visual or aural), seizures (generally tonic clonic), abnormal movements, coma, confusion, stupor, dizziness, amnesia, headache, diminished tendon reflexes, hyperreflexia, muscle twitching, opisthotnos, Babinski's reflex/Chaddock's reflex, hypertonia, dysmetria, muscle clonus, sensation of intoxication, difficulty concentrating, vertigo, dysarthria.

Psychiatric: Agitation, restlessness, delirium, paranoia, anxiety, mental disorders, mania, withdrawn behavior, behavior changes.

Genitourinary: Difficulty in micturation, urine urgency distended urinary bladder, urine retention, bed-wetting.

Pulmonary: Tachypnea, slow respirations, shallow respirations, breathing difficulty, labored respirations, inspiratory stridor, laryngitis, laryngospasm, pulmonary edema, respiratory failure, subcostal recession.

Dermatologic: Dry mucous membranes, dry warm skin, flushed skin, oral lesions, dermatitis, petechiae rash, macular rash papular rash, maculopapular rash, scarlatiniform rash, erythematous rash, sweating/moist skin, cold skin, cyanosed skin, salivation.

Drug Abuse And Dependence

Lofene possesses no known potential for dependence.