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|Please see package insert for additional information and possible updates. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. [ Read the disclaimer | <<Back ]|
acetylcysteine (Mucomyst ®, CETYLEV™ )
|Mechanism of action:
Acetaminophen is absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. It is extensively metabolized in the liver to form principally the sulfate and glucoronide conjugates which are excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by isozyme CYP2E1 of the cytochrome P-450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite. The toxic metabolite preferentially conjugates with hepatic glutathione to form nontoxic cysteine and mercapturic acid derivatives, which are then excreted by the kidney. Recommended therapeutic doses of acetaminophen are not believed to saturate the glucuronide and sulfate conjugation pathways and therefore are not expected to result in the formation of sufficient reactive metabolite to deplete glutathione stores. However, following ingestion of a large overdose, the glucuronide and sulfate conjugation pathways are saturated resulting in a larger fraction of the drug being metabolized via the cytochrome P-450 pathway and therefore, the amount of acetaminophen metabolized to the reactive intermediate increases. The increased formation of the reactive metabolite may deplete the hepatic stores of glutathione with subsequent binding of the metabolite to protein molecules within the hepatocyte resulting in cellular necrosis.
Acetylcysteine I.V. Treatment:
Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. It is most effective when given early, with benefit seen principally in patients treated within 8-10 hours of the overdose. Acetylcysteine likely protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.
Acetaminophen poisoning: Children and Adults:
Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until all doses are administered even though the acetaminophen plasma level has dropped below the toxic range
I.V. (Acetadote®): Loading dose: 150 mg/kg over 60 minutes. Maintenance dose: 50 mg/kg infused over 4 hours followed by 100 mg/kg infused over 16 hours. Note: To avoid fluid overload in patients <40 kg and those requiring fluid restriction, decrease volume of D5W proportionally.
Adjuvant therapy in respiratory conditions:
Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine.
Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (Mucomyst®) (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted
Children and Adults: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours
Inhalation, nebulization (tent, croupette): Children and Adults: Dose must be individualized; may require up to 300 mL solution/treatment
Direct instillation: Adults:
Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours
Diagnostic bronchogram: Nebulization or intrathecal: Adults: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Mucolytic: nebulize 1-10 ml of 20% solution or 2 to 20 ml of 10% solution every 2-6 hr. Usual dose: 6-10 ml of 10% solution or 3-5 ml of 20% solution.
Decrease risk of contrast-induced nephropathy: (4 doses total): 600 mg (3ml) po BID on the day before the contrast injection, then 600 mg (3ml) in a.m. on the day of the contrast injection (immediately before) and 600 mg (3ml) in the evening. In all cases the patient should be well hydrated. This is particularly important in patients with underlying renal dx or diabetes mellitus.
Oral administration: dilute to 5% with soft drinks.
Oral: For treatment of acetaminophen overdosage, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister.
Injection, solution (Acetadote®): 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, as sodium (Mucomyst®): 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
Drug UPDATES: CETYLEV™ (acetylcysteine) effervescent tablets for oral solution
[Drug information / PDF]
Package insert - Dosing: Click (+) next to Dosage and Administration section (drug info link)
Initial U.S. Approval: 2016
Mechanism of Action:
Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity. Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite of acetaminophen.
INDICATIONS AND USAGE:
CETYLEV is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion.
DOSAGE AND ADMINISTRATION:
See links above
DOSAGE FORMS AND STRENGTHS
Effervescent tablets: 500 mg and 2.5 grams
Activated Charcoal: Activated charcoal is produced by pyrolysis of organic material, such as wood, and an activation process which cleanses and fragments the charcoal by exposure to an oxidizing gas compound of steam, oxygen, and acids at high temperatures resulting in increased surface area through the creation of numerous external and internal pores. These pores serve as reservoirs to adsorb substances admixed with activated charcoal, making it a useful adsorbent for specified toxins.
Activated charcoal is pharmacologically inert and is not absorbed in the gastrointestinal tract.Activated charcoal will adsorb a variety of organic and inorganic substances, but is especially effective in adsorbing compounds within a molecular weight range of l00 to 1,000 Daltons (AMU's). Several other physiologic and physicochemical factors influence the adsorptive capacity of activated charcoal including: pH, charcoal:drug ratio, gastric contents, and adsorption kinetics.
DOSAGE AND ADMINISTRATION
Prior to administration of Actidose with Sorbitol or Actidose-Aqua, shake the container thoroughly for a minimum of 30 seconds. After administration of either Actidose with Sorbitol or Actidose-Aqua, the container should be thoroughly rinsed with water and any residue should be administered to the patient to ensure that the entire dose has been delivered.
Single Dose - Actidose-Aqua
Under one year of age: 1gm/kg (5 ml/kg)
1 - 12 years of age: 25-50 gm (120-240 ml)
Adults (over 12 yrs. of age): 50-100 gm (240-480 ml)
Single Dose - Actidose with Sorbitol
Under one year of age: DO NOT USE ACTIDOSE WITH SORBITOL IN CHILDREN LESS THAN ONE YEAR OF AGE.
1 - 12 years of age:
DO NOT USE ACTIDOSE WITH SORBITOL 25 GM/120 ML IN CHILDREN WEIGHING
LESS THAN 16 KG.
DO NOT USE ACTIDOSE WITH SORBITOL 50 GM/240 ML IN CHILDREN WEIGHING
LESS THAN 32 KG
Adults (over 12 yrs.): 50 gm [96 gm sorbitol] (240 ml)
Multiple Dose - Actidose-Aqua
Under one year of age: 1 gm/kg (5 ml/kg) q 4-6H (every 4-6 hrs)
1 - 12 years of age: 25-50 gm (120-240 ml)
q 4-6H (every 4-6 hrs)
Adults (over 12 yrs.): 50-100 gm (240-480 ml)
q 4-6H (every 4-6 hrs)
Multiple Dose - Actidose with Sorbitol
ACTIDOSE WITH SORBITOL IS NOT RECOMMENDED FOR CHILDREN OR ADULTS IN MULTIPLE DOSE ACTIVATED CHARCOAL THERAPY DUE TO EXCESSIVE CATHARTIC ACTION.
Acute poisoning: Note: ~10 g of activated charcoal for each 1 g of toxin is considered adequate; this may require multiple doses. If sorbitol is also used, sorbitol dose should not exceed 1.5 g/kg. When using multiple doses of charcoal, sorbitol should be given with every other dose (not to exceed 2 doses/day).
Children: 1 g/kg as a single dose; if multiple doses are needed, additional doses can be given as 0.25 g/kg every hour or equivalent (ie, 0.5 g/kg every 2 hours) or
>1 year-12 years: 25-50 g as a single dose; smaller doses (10-25 g) may be used in children 1-5 years due to smaller gut lumen capacity
Children >12 years and Adults: 25-100 g as a single dose; if multiple doses are needed, additional doses may be given as 12.5 g/hour or equivalent (ie, 25 g every 2 hours)
Capsule, activated (Char-Caps, Charcocaps®): 260 mg
Actidose-Aqua®: 15 g (72 mL); 25 g (120 mL); 50 g (240 mL)
Kerr Insta-Char®: 25 g (120 mL) [cherry flavor]; 50 g (240 mL)
Liquid, activated [with sorbitol]:
Actidose® with Sorbitol: 25 g (120 mL); 50 g (240 mL)
Kerr Insta-Char®: 25 g (120 mL); 50 g (240 mL)
Pellets, activated (EZ-Char™): 25 g
Powder for suspension, activated: 30 g, 240 g
Tablets, activated (Charcol Plus® DS): 250 mg
deferasirox - JADENU® tablets
Drug UPDATES: JADENU® (deferasirox) tablets
[Drug information / PDF] Click link for the latest monograph
Dosing: Click (+) next to Dosage and Administration section (drug info link)
Initial U.S. Approval: 2015
Mechanism of Action: JADENU (deferasirox) is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.
INDICATIONS AND USAGE:
1.1 Treatment of Chronic Iron Overload Due to Blood Transfusions (Transfusional Iron Overload)
JADENU is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older. This indication is approved under accelerated approval based on a reduction of liver iron concentrations and serum ferritin levels [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
1.2 Treatment of Chronic Iron Overload in Non-Transfusion-Dependent Thalassemia Syndromes
JADENU is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron concentration (LIC) of at least 5 milligrams of iron per gram of liver dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L. This indication is approved under accelerated approval based on a reduction of liver iron concentrations (to less than 5 mg Fe/g dw) and serum ferritin levels [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
1.3 Limitation of Use
Controlled clinical trials of JADENU with myelodysplastic syndromes (MDS) and chronic iron overload due to blood transfusions have not been performed [see Clinical Studies (14)].
The safety and efficacy of JADENU when administered with other iron chelation therapy have not been established.
HOW SUPPLIED: 90mg, 180mg, 360 mg tablets
deferoxamine (Desferal ®)
Acute iron intoxication: 1 gram IV/IM initially, then 500 mg every 4 hr for 2 doses, then subsequent doses of 500 mg every 4-12 hr as needed. MAX 6 g/day. Note: IV route is used when severe toxicity is evidenced by systemic symptoms (coma, shock, metabolic acidosis, or severe gastrointestinal bleeding) or potentially severe intoxications (serum iron level >500 mcg/dl). When severe symptoms are not present, the I.M. route may be preferred (per manufacturer).
Chronic iron overload: 0.5-1 g/day IM, plus 2 g IV per unit of blood. Max of 1 g/day with no transfusion, 6 g/day if 3 or more units of infused blood or packed red blood cells. Alternative: 1-2 g SC (20-40 mg/kg/day) infused over 8-24 hr .
Administration: IM route preferred for all patients with acute iron intoxication not in shock. IV administration only for patients in state of cardiovascular collapse and then only by slow infusion. Maximum IV rate: 15 mg/kg/hr for first 1000 mg. Subsequent IV dosing, if needed - Maximum rate 125 mg/hr.
Renal Dosing: crcl <10 ml/min: Administer 50% of dose.
Supplied: Injection (powder for reconstitution): 500 mg, 2 g
digoxin immune fab (Digibind ®)
Reconstitution: Dissolve each vial with 4 ml sterile water
(do not shake). May be further diluted with normal saline. Infuse over
30 minutes-- must use 0.22 micron filter. If cardiac arrest is imminent,
may give as a bolus.
After intravenous injection of Digoxin Immune Fab (Ovine) in the baboon, digoxin-specific Fab fragments are excreted in the urine with a biological half-life of about 9 to 13 hours.1 In humans with normal renal function, the half-life appears to be 15 to 20 hours.2 Experimental studies in animals indicate that these antibody fragments have a large volume of distribution in the extracellular space, unlike whole antibody which distributes in a space only about twice the plasma volume.1 Ordinarily, following administration of DIGIBIND, improvement in signs and symptoms of digitalis intoxication begins within one-half hour or less.2,3,4,5
The affinity of DIGIBIND for digoxin is in the range of 109 to 1011 M-1, which is greater than the affinity of digoxin for (sodium, potassium) ATPase, the presumed receptor for its toxic effects. The affinity of DIGIBIND for digitoxin is about 108 to 109 M-1.
DIGIBIND binds molecules of digoxin, making them unavailable for binding at their site of action on cells in the body. The Fab fragment-digoxin complex accumulates in the blood, from which it is excreted by the kidney. The net effect is to shift the equilibrium away from binding of digoxin to its receptors in the body, thereby reversing its effects.
INDICATIONS AND USAGE
DIGIBIND, Digoxin Immune Fab (Ovine), is indicated for treatment of potentially life-threatening digoxin intoxication.3 Although designed specifically to treat life-threatening digoxin overdose, it has also been used successfully to treat life-threatening digitoxin overdose.3 Since human experience is limited and the consequences of repeated exposures are unknown, DIGIBIND is not indicated for milder cases of digitalis toxicity.
Manifestations of life-threatening toxicity include severe ventricular arrhythmias such as ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias such as severe sinus bradycardia or second or third degree heart block not responsive to atropine.
Ingestion of more than 10 mg of digoxin in previously healthy adults or 4 mg of digoxin in previously healthy children, or ingestion causing steady-state serum concentrations greater than 10 ng/mL, often results in cardiac arrest. Digitalis-induced progressive elevation of the serum potassium concentration also suggests imminent cardiac arrest. If the potassium concentration exceeds 5 mEq/L in the setting of severe digitalis intoxication, therapy with DIGIBIND is indicated.
There are no known contraindications to the use of DIGIBIND
Each vial of Digibind® 38 mg or DigiFab™ 40 mg will bind ~0.5 mg of digoxin or digitoxin.
Estimation of the dose is based on the body burden of digitalis. This may be calculated if the amount ingested is known or the postdistribution serum drug level is known (round dose to the nearest whole vial). See table.
Fab dose based on serum drug level postdistribution:
Digoxin Immune Fab
Fab dose based on serum drug level postdistribution:
Digoxin: No. of vials = level (ng/mL) x body weight (kg) divided by 100
Digitoxin: No. of vials = digitoxin (ng/mL) x body weight (kg) divided by 1000
If neither amount ingested nor drug level are known, dose empirically as follows:
For acute toxicity: 20 vials, administered in 2 divided doses to decrease the possibility of a febrile reaction, and to avoid fluid overload in small children.
For chronic toxicity: 6 vials; for infants and small children </=( 20kg), a single vial may be sufficient
Continuous I.V. infusion over >/= 30 minutes is preferred. May give by bolus injection if cardiac arrest is imminent. Small doses (infants/small children) may be administered using tuberculin syringe. Stopping the infusion and restarting at a slower rate may help if infusion-related reactions occur.
Injection, powder for reconstitution:
Digibind®: 38 mg
DigiFab™: 40 mg
flumazenil (Romazicon ®)
Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.
Flumazenil does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids.
In animals pretreated with high doses of benzodiazepines over several weeks, flumazenil injection elicited symptoms of benzodiazepine withdrawal, including seizures. A similar effect was seen in adult human subjects.
INDICATIONS AND USAGE
Flumazenil injection is indicated for the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures, and for the management of benzodiazepine overdose.
Pediatric Patients (aged 1 to 17)
Flumazenil injection is indicated for the reversal of conscious sedation induced with benzodiazepines (see package insert: PRECAUTIONS: Pediatric Use).
Flumazenil injection is contraindicated:
-in patients with a known hypersensitivity to flumazenil or benzodiazepines.
-in patients who have been given a benzodiazepine for control of a potentially life-threatening condition (e.g., control of intracranial pressure or status epilepticus).
-in patients who are showing signs of serious cyclic antidepressant overdose.
Sedation reversal: 0.2 mg IV over 15 seconds, then 0.2 mg every minute as needed up to 1 mg total (most patients respond to doses of 0.6-1 mg). If re-sedation occurs, repeated doses may be administered at 20-minute intervals as needed. For repeat treatment, no more than 1 mg (given as 0.2 mg/min) should be administered at any one time, and no more than 3 mg should be given in any one hour.
Overdose reversal: 0.2 mg IV over 30 seconds. If the desired level of consciousness is not obtained after waiting 30 seconds, a further dose of 0.3 mg IV over another 30 seconds may be given. Additional doses of 0.5 mg IV over 30 seconds at 1 minute intervals may be given up to a cumulative dose of 3 mg. In the event of re-sedation, repeated doses may be given at 20 minute intervals if needed. For repeat treatment, no more than 1 mg (given as 0.5 mg/min) should be given at any one time and no more than 3 mg should be given in any one hour.
Parenteral: For I.V. use only; administer via freely running I.V. infusion into larger vein to decrease chance of pain, phlebitis
Resedation: Repeated doses may be given at 20-minute intervals as needed; repeat treatment doses of 1 mg (at a rate of 0.5 mg/minute) should be given at any time and no more than 3 mg should be given in any hour. After intoxication with high doses of benzodiazepines, the duration of a single dose of flumazenil is not expected to exceed 1 hour; if desired, the period of wakefulness may be prolonged with repeated low intravenous doses of flumazenil, or by an infusion of 0.1-0.4 mg/hour. Most patients with benzodiazepine overdose will respond to a cumulative dose of 1-3 mg and doses >3 mg do not reliably produce additional effects. Rarely, patients with a partial response at 3 mg may require additional titration up to a total dose of 5 mg. If a patient has not responded 5 minutes after receiving a cumulative dose of 5 mg, the major cause of sedation is not likely to be due to benzodiazepines.
Injection, solution: 0.1 mg/mL (5 mL, 10 mL)
fomepizole (Antizol ®)
Mechanism of Action: Antizol® (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.
Ethylene glycol, the main component of most antifreezes and coolants, is metabolized to glycoaldehyde, which undergoes subsequent sequential oxidations to yield glycolate, glyoxylate, and oxalate. Glycolate and oxalate are the metabolic byproducts primarily responsible for the metabolic acidosis and renal damage seen in ethylene glycol toxicosis. The lethal dose of ethylene glycol in humans is approximately 1.4 mL/kg.
Methanol, the main component of windshield wiper fluid, is slowly metabolized via alcohol dehydrogenase to formaldehyde with subsequent oxidation via formaldehyde dehydrogenase to yield formic acid. Formic acid is primarily responsible for the metabolic acidosis and visual disturbances (e.g., decreased visual acuity and potential blindness) associated with methanol poisoning. A lethal dose of methanol in humans is approximately 1-2 mL/kg.
INDICATIONS AND USAGE
Antizol® is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis (see DOSAGE AND ADMINISTRATION).
Antizol® should not be administered to patients with a documented serious hypersensitivity reaction to Antizol® or other pyrazoles.
Dosing: loading dose: 15 mg/kg, followed by 10 mg/kg every 12 hours x 4 doses, then 15 mg/kg every 12 hours thereafter until ethylene glycol levels <20 mg/dl. Dialysis should be considered in addition to fomepizole in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol level >50 mg/dl.
Fomepizole is dialyzable and should be given q4h during hemodialysis.
Injection, solution [preservative free]: 1 g/mL (1.5 mL)
Methylene blue is Phenothiazin-5-ium, 3,7-bis (dimethylamino)-, chloride, trihydrate. It will produce two opposite actions on hemoglobin. Low concentrations will convert methemoglobin to hemoglobin. High concentrations convert the ferrous iron of reduced hemoglobin to ferric iron which results in the formation of methemoglobin.
Drug induced methemoglobinemia.
DOSAGE AND ADMINISTRATION
0.1 to 0.2 mL per kilogram of body weight (0.045 to 0.09 mL per pound of body weight). Inject Methylene Blue intravenously very slowly over a period of several minutes.
Adults: Genitourinary antiseptic: Oral: 65-130 mg 3 times/day with a full glass of water (maximum: 390 mg/day)
Injection, solution: 10 mg/mL (1 mL, 10 mL)
Tablet (Urolene Blue®): 65 mg
naloxone (Narcan ®)
Naloxone prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
Naloxone is an essentially pure opioid antagonist, i.e., it does not possess the “agonistic” or morphine-like properties characteristic of other opioid antagonists. When administered in usual doses in the absence of opioids or agonistic effects of other opioid antagonists, it exhibits essentially no pharmacologic activity.
Naloxone has not been shown to produce tolerance or cause physical or psychological dependence. In the presence of physical dependence on opioids, naloxone will produce withdrawal symptoms. However, in the presence of opioid dependence, withdrawal symptoms will appear within minutes of naloxone administration and will subside in about 2 hours. The severity and duration of the withdrawal syndrome are related to the dose of naloxone and to the degree and type of dependence.
While the mechanism of action of naloxone is not fully understood, in vitro evidence suggests that naloxone antagonizes opioid effects by competing for the mu, kappa, and sigma opiate receptor sites in the CNS, with the greatest affinity for the mu receptor.
When naloxone hydrochloride is administered intravenously (I.V.), the onset of action is generally apparent within two minutes; the onset of action is slightly less rapid when it is administered subcutaneously (S.C.) or intramuscularly (I.M.). The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride. Intramuscular administration produces a more prolonged effect than intravenous administration. Since the duration of action of naloxone may be shorter than that of some opiates, the effects of the opiate may return as the effects of naloxone dissipate.
The requirement for repeat doses of naloxone will also be dependent upon the amount, type and route of administration of the opioid being antagonized.
Adjunctive Use in Septic Shock
Naloxone has been shown in some cases of septic shock to produce a rise in blood pressure that may last up to several hours; however this pressor response has not been demonstrated to improve patient survival. In some studies, treatment with naloxone in the setting of septic shock has been associated with adverse effects, including agitation, nausea and vomiting, pulmonary edema, hypotension, cardiac arrhythmias, and seizures. The decision to use naloxone in septic shock should be exercised with caution, particularly in patients who may have underlying pain or have previously received opioid therapy and may have developed opioid tolerance.
Because of the limited number of patients who have been treated, optimal dosage and treatment regimens have not been established.
INDICATIONS AND USAGE
Naloxone hydrochloride injection is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids including propoxyphene, methadone, and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine, butorphanol, and cyclazocine.
Naloxone hydrochloride is also indicated for the diagnosis of suspected or known acute opioid overdosage. Naloxone hydrochloride injection may be useful as an adjunctive agent to increase blood pressure in the management of septic shock
Naloxone hydrochloride injection is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or any of the other ingredients contained in the formulation
I.M., I.V. (preferred), intratracheal, SubQ:
Postanesthesia narcotic reversal: Infants and Children: 0.01 mg/kg; may repeat every 2-3 minutes, as needed based on response
Birth (including premature infants) to 5 years or <20 kg: 0.1 mg/kg; repeat every 2-3 minutes if needed; may need to repeat doses every 20-60 minutes
>5 years or >/= 20 kg: 2 mg/dose; if no response, repeat every 2-3 minutes; may need to repeat doses every 20-60 minutes
Children and Adults:
Continuous infusion: I.V.: If continuous infusion is required, calculate dosage/hour based on effective intermittent dose used and duration of adequate response seen, titrate dose 0.04 to 0.16 mg/kg/hour for 2-5 days in children, adult dose typically 0.25 to 6.25 mg/hour (short-term infusions as high as 2.4 mg/kg/hour have been tolerated in adults during treatment for septic shock); alternatively, continuous infusion utilizes 2 /3 of the initial naloxone bolus on an hourly basis; add 10 times this dose to each liter of D5W and infuse at a rate of 100 mL/hour; 1 /2 of the initial bolus dose should be readministered 15 minutes after initiation of the continuous infusion to prevent a drop in naloxone levels; increase infusion rate as needed to assure adequate ventilation
Narcotic overdose: Adults: I.V.: 0.4 to 2 mg every 2-3 minutes as needed; may need to repeat doses every 20-60 minutes, if no response is observed after 10 mg, question the diagnosis. Note: Use 0.1-0.2 mg increments in patients who are opioid dependent and in postoperative patients to avoid large cardiovascular changes.
Intratracheal: Dilute to 1-2 mL with normal saline
I.V. push: Administer over 30 seconds as undiluted preparation
I.V. continuous infusion: Dilute to 4 mcg/mL in D5W or normal saline
IV infusion: ( 2 mg/500 ml per manufacturer) - Usual infusion rate: @ 0.4 mg/hr (100 ml/hr)-titrate to respiratory rate/ level of consciousness.
Injection, solution, as hydrochloride: 0.4 mg/mL (1 mL, 10 mL)
Narcan®: 0.4 mg/mL (1 mL)
sodium polystyrene sulfonate (Kayexalate ®)
Hyperkalemia: 15 to 30 grams (60 ml) orally 1 to 4 times daily or 30-50 g rectally every 6 hours. Alternatively: 15 to 50 grams orally (bid-qid).
PK: Onset: within 1 - 2 hours. Duration: 4 - 6 hours.
Rectal route: Adults: 30 to 50 grams q6h. The enema should be retained for least 30 to 60 minutes and followed by a cleansing enema. After the initial cleansing enema, a soft, large rubber tube is inserted and secured at about 20 cm into the rectum with the tip well into the sigmoid colon. The resin suspension is introduced by gravity and flushed by an additional 50 to 100 ml fluid. The tube is clamped and left in place for several hours if possible. The colon is then flushed with up to 2 quarts of a non-sodium containing solution to remove the resin and to prevent necrosis.
Exchange capacity is 1 mEq/gram in vivo, and in vitro capacity is 3.1 mEq/g, therefore, a wide range of exchange capacity exists such that close monitoring of serum electrolytes (potassium, sodium, calcium, magnesium) is necessary; ECG.
Supplied: Suspension: 15 g/60 ml.
Hyperosmotic laxative (as single dose, at infrequent intervals):
Children >12 years and Adults:
Oral: 70% solution 2 to 3 tablespoonfuls (27 to 40.5 g sorbitol) orally x 1.
[reported range: 30-150 mL x 1]
1 tablespoonful (15ml) of 70% sorbitol w/w = 13.5 grams
Rectal enema: 120 mL as 25% to 30% solution
Children 2-11 years:
Oral: 2 mL/kg (as 70% solution)
Rectal enema: 30-60 mL as 25% to 30% solution
Adjunct to sodium polystyrene sulfonate: 15 mL as 70% solution orally until diarrhea occurs (10-20 mL/2 hours) or 20-100 mL as an oral vehicle for the sodium polystyrene sulfonate resin
When administered with charcoal:
Adults: (Sorbitol 70% w/w solution = 0.9 grams/ml): 1 g/kg (range: 1-2 grams/kg) may be given with the initial dose of activated charcoal. Note: NOT recommended in young children- may develop diarrhea ==> potentially dangerous fluid shifts and/or electrolyte imbalances.
Solution, genitourinary irrigation: 3% (1500 mL, 3000 mL); 3.3% (2000 mL, 4000 mL)
Solution, oral: 70% w/w (480 mL, 3840 mL)
Contains 0.9 grams/ml or 13.5 grams/tablespoonful.
Note: activated charcoal with sorbitol (commercial product), if available contains:
96 grams of sorbitol and 50 grams of activated charcoal
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David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.