Ativan vs Xanax - What is the difference. The recommendations in this table are based on guidance available at experienced centers. stream
necessary in order to successfully control the pain while 50mg conversion dose produced via the equianalgesic calculator). Cyclizine SC or IV Nausea and vomiting 0.5 1 14.5 0 Diamorphine$ SC or IV Pain 0.075 0.1 2.175 2.9 1.45 3.2625 Diazepam PR Agitation, convulsions 10 Hydrocortisone IV Anaphylaxis 2 4 58 116 Hyoscine hydrobromide SC or IV Respiratory tract secretions 0.01 0.01 0.29 0.29 Midazolam SC or IV Anxiety or agitation 0.06 0.1 1.74 2.9 2 4.5 Use for high-dose SC breakthrough injections (above morphine SC bolus injections of 60mg [2ml]). Because published benzodiazepine dose conversions are based on oral administration, parenteral formulations may not use the same conversion ratio. f[ey <>
Patients were randomized to receive ATIVAN 2 mg IV (with an additional . <>
Ziprasidone is contraindicated in patients with cardiovascular risk factors such as a history of QTc prolongation, MI, or heart failure, or in patients on other QTc-prolonging agents, Iloperidone is also associated with significant changes in the QTc interval, which should be monitored frequently. (Accessed on January 15, 2015. In patients with CrCl 50 mL/min to 10 mL/min, use 1.5 mg daily, with a maximum dose of 3 mg/day. Enter the dose of your drug to receive all the conversions. Requirement as % of Total Daily Morphine Dose, Published equianalgesic ratios are considered. All patients age 6 months to 18 years who received continuous midazolam for 5 days or longer while mechanically ventilated for 5-21 days and were then converted to either enteral diazepam or lorazepam following extubation (or return to baseline ventilator settings in tracheostomy-dependent patients) between January 1, 2015, and June 30, 2016. Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F. Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? Unable to load your collection due to an error, Unable to load your delegates due to an error. Second-Generation Neuroleptics [Internet]. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. ], Lurasidone strong CYP 3A4 inhibitors+ [ketoconazole, clarithromycin (Biaxin), nefazodone (Serzone), ritonavir (Norvir), saquinavir (Invirase), etc. The use of benzodiazepines, like ATIVAN Injection, is ordinarily only an initial step of a complex and sustained intervention which may require additional interventions, (e.g., concomitant intravenous administration of phenytoin). Clozapine: Dose adjustment may be needed, depending on the serum clozapine level. 1 0 obj
(Package Insert versus GlobalRPh default factors), https://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_075.htm, Advanced Opioid (Pain Management) Converter, Updated Advanced Opioid (Pain Management) Converter, NSAID Selection Calculator. The initial dose in children older than 13 years of age is 2.5 mg daily, with weekly adjustments of 2.5 mg daily. EQUIPMENT NECESSARY TO MAINTAIN A PATENT AIRWAY SHOULD BE IMMEDIATELY AVAILABLE PRIOR TO INTRAVENOUS ADMINISTRATION OF LORAZEPAM (see WARNINGS). 0.67 * 1 = 0.67 mg. The benzodiazepine conversion calculator is an ultimate solution to any dosage problems you might encounter while switching from one drug of this type to another. Any healthcare professional who intends to treat a patient with status epilepticus should be familiar with this package insert and the pertinent medical literature concerning current concepts for the treatment of status epilepticus. Experience with further doses of ATIVAN is very limited. Breitbart W, Chandler S, Eagel B, et al. IV:PO conversion a desirable treat-ment option. Kim PM, Weinstein SL. 4 mg per mL, NDC 0641-6003-25, 25 x 1 mL vial. In patients with CrCl 80 mL/min to 50 mL/min, start with 3 mg daily, and do not exceed 6 mg/day. Olanzapine and quetiapine have been used off-label for monotherapy for, Olanzapine and risperidone have been used to augment in treating, Risperidone has been used off-label for treating, It is recommended to obtain slit-lamp eye exams every 5 years for patients on quetiapine, which has been shown to cause cataracts in animals, Second-generation antipsychotics (SGAs) have been shown to improve behavioral problems in patients with dementia, but due to increased risk of death in elderly patients with dementia (black box warning), their use has decreased. Convulsive status epilepticus in adults: Management. Whats the Difference Between Dental Inflammation and Infection? Copyright 2021 GlobalRPH - Web Development by, Benzodiazepine equivalent dosage converter, HONcode standard for trust- worthy health. Read more about Benadryl by visiting the benadryl calculator. T1 - Second-Generation Neuroleptics McPherson ML. CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism. . Use of iloperidone with ritonzvir is contraindicated - can lead to increased iloperidone levels. Rockville, MD: Agency for Healthcare Research and Quality. The rate of injection should not exceed 2.0 mg per minute. initial dose is 50-75% of the equianalgesic dose" - made to oral hydromorphone 25 - 35mg daily - (this represents a Patients who smoke also may require dose adjustment because carcinogens can induce CYP1A2. For the treatment of status epilepticus, the usual recommended dose of ATIVAN Injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. Liquid (1 mg/mL), 30-mL bottle (generic): IM, acute: 10 mg q 2 hours or 20 mg q 4 hours, to a maximum of 40 mg/day, *Prices are representative of "Average Wholesale Price" (AWP), In general, with geriatric patients, start medications at the lowest dose and titrate slowly while assessing for side effects and potential drug interactions, If necessary, monitor clozapine levels, and adjust dose as needed, Monitor patient and adjust paliperidone dose as needed based on therapeutic response, Clozapine, Iloperidone, Quetiapine, Ziprasidone fluconazole (Diflucan)+, Monitor patient, and adjust olanzapine dose as needed based on therapeutic response, Increased valproic acid and/or ammonium levels, Monitor valproic acid and ammonium levels, Half the dose of aripiprazole, unless using for adjunctive treatment of depression, Increased levels of iloperidone and increased risk of QTc prolongation, If necessary, reduce iloperidone dose by half, Aripiprazole, asenapine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone hydrocodone (i.e. For IM dose, If using long-acting IM formulation, give 25 mg every 2 weeks. The .gov means its official. Due to delayed peak onset of aripiprazole and paliperidone, they are not recommended for acute agitation. If seizures continue or recur after a 10- to 15-minute observation period, an additional 4 mg intravenous dose may be slowly administered. Lurasidone: Dose adjustment may be needed, Paliperidone: Dose adjustment is needed for children with renal impairment, Risperidone: Dose adjustment is needed for children with renal impairment. Lorazepam is used short-term for severe anxiety, associated insomnia, and as a pre-medication. Medically reviewed by Drugs.com. Patients: Benzodiazepines are a new generation of drugs that almost totally replaced the older type of anti-anxiety drugs, barbiturates. The list of benzodiazepines can be divided into 3 groups based on the duration of their action and the speed of the onset of action. Particularly for bronchial obstruction, lymphangitic, carcinomatosis, and SVC Patient demographics, benzodiazepine dose escalations, as needed benzodiazepine requirements, and severe adverse events within 48 hours of conversion were assessed. use as abrupt D/C or rapid dose reduction may cause acute withdrawal reactions, potentially life-threatening. Disclaimer. Psychoactive Drugs. Severe adverse events associated with oversedation and/or withdrawal were minimal and confounded by underlying disease states. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. .2/ZfG[:{oH}ZJUmniOF F.\6K"abU:hiVyz6gAKt_|pgrqx9MUWz,_LgMvU ?>MJx
'A7 gk\nd^=zff3plgZn7GL:nnL0R2 \mSKu-08W}yx8m}R,Q3}Mm7C(r Ny81N>_Ra" stream
The question is whether this speed is worth a slight increase in respiratory suppression. Most benzodiazepines included in this calculator are only available as oral dosage forms. Consider SC midazolam in rare cases. Because status epilepticus may result from a correctable acute cause such as hypoglycemia, hyponatremia, or other metabolic or toxic derangement, such an abnormality must be immediately sought and corrected. The authors For children less than 51 kg, the starting dose is 3 mg daily, and the dose can be increased to the maximum dose of 6 mg/day after a week. Our benzo calculator uses the first mentioned and most popular option duration. We prefer lorazepam ( Ativan) or oxazepam (Serax) for the treatment of patients with advanced cirrhosis or acute alcoholic hepatitis. Then type a starting value in the top FROM input box. S;~.>J;UKF.3`:3YAz Clipboard, Search History, and several other advanced features are temporarily unavailable. Pain management in Quetiapine: No adjustment is needed, but start titration slowly while monitoring for side effects. Retrospective cohort study evaluating the effectiveness and safety of benzodiazepine conversion calculations embedded within an institution-specific clinical pathway for sedation and weaning of mechanically ventilated pediatric patients. In: * Article titles in AMA citation format should be in sentence-case, You can cancel anytime within the 30-day trial, or continue using Johns Hopkins Guides to begin a 1-year subscription ($39.95). As with morphine, cautious use in renal and liver impairment. Calculate a specific melatonin dose needed for a given indication using the melatonin dosage calculator. Bethesda: [7Yy ]6IF benzodiazepine use may lead to clinically significant physical dependence; risk of dependence and withdrawal incr. 290.914.916.010. Please enable it to take advantage of the complete set of features! MeSH Thomsen PH. required dose of the second opioid. <>/ExtGState<>/XObject<>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI] >>/MediaBox[ 0 0 792 612] /Contents 4 0 R/Group<>/Tabs/S/StructParents 0>>
Contents should be mixed thoroughly by gently inverting the container repeatedly until a homogenous solution results. Design: A cost analysis of enterally administered lorazepam in the pediatric intensive care unit. doi: 10.1097/TME.0000000000000064. The Omni GAD-7 calculator is here to help. . For all of the second-generation antipsychotics, there are insufficient data regarding their use during nursing, and infant risk cannot be ruled out. Clonazepam 1mg PO/SC Lorazepam 1mg PO/IV Oxazepam 15 to 30mg PO . 1998;16(10):3216-3221. The table below lets you compare the mode of action of all popular benzos; are you looking for a clonazepam vs. Xanax comparison? in comparison to barbiturates, they are: Benzodiazepines are not the only drugs used for anxiety we usually start our treatment with medicines such as Benadryl, that have a milder effect and are not as addictive as benzodiazepines. The usual therapeutic dose is 10 mg daily. PMC Model For Methadone Conversion Examined: Fudin Factor graphically Safety of the IM form is not established in children. We compare each one of our benzodiazepines to alprazolam. 1 0 obj
The safety of ATIVAN in pediatric patients has not been established. Atypical antipsychotics in the treatment of posttraumatic stress disorder. oral methadone. conversions FROM or TO fentanyl i.v. There are insufficient data to support efficacy or make dosage recommendations for intramuscular lorazepam in patients less than 18 years of age; therefore, such use is not recommended. Olanzapine: Use a reduced dose. In adults, choice of benzodiazepine . %
As needed benzodiazepine doses were administered in 38% of encounters post conversion, but escalation of a scheduled enteral benzodiazepine regimen was only required in 2.8% of encounters. Unlike opioid equipotent dosing, benzodiazepine equivalence is much less evidence-based and poorly described in the literature. Therefore, it shouldn't come as a surprise that IV midazolam hastens sedation. Clin Fam Prac. Insomnia: 2-4 mg orally at bedtime. A 55-bed, mixed-medical, noncardiac surgical PICU in a tertiary care children's hospital. Risperidone augmentation in the treatment of severe adolescent OCD in SSRI-refractory cases: a case-series. epilepticus are diazepam, lorazepam, and midazolam. Bookshelf Average half-life (variable): 100 hours (40-250 hours). 1999 Nov;27(11):2454-8. doi: 10.1097/00003246-199911000-00022. Powerful tool *Ovv]pu}gz$3 Generic name: LORAZEPAM 2.0mg in 1mL Review: antipsychotics do not increase weight in women with anorexia nervosa. DB - Johns Hopkins Guides ATIVAN Injection is compatible for dilution purposes with the following solutions: Sterile Water for Injection, USP; Sodium Chloride Injection, USP; 5% Dextrose Injection, USP. Pain. David McAuley, Pharm.D. Crit Care Med. The shorter half-life of lorazepam and the absence of active . & Huber. 1 0 obj
Patients: All patients age 6 months to 18 years who received continuous midazolam for 5 days or longer while mechanically ventilated for 5-21 days and were then converted to either enteral diazepam or lorazepam following extubation (or return to baseline ventilator settings in tracheostomy-dependent patients) between January 1, 2015, and June 30, Edition, 2000. 1. Mathematical The dose of ATIVAN should be reduced by 50% when coadministered with probenecid or valproate (see PRECAUTIONS, Drug Interactions). Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Clinical Handbook of Psychotropic Drugs, 4th revised edition, Bezchlibnyk-Butler et al. following references: Conversion ratio of oral morphine to An official website of the United States government. compared to Ripamonte, Ayonrinde, and If administering long-acting IM form, give 12.5-25 mg every 2 weeks. ER -, Your free 1 year of online access expired. %
%f2fDWBRex1*s GZhlNx;hI>l!dKc:cmEg2&M*?*q$|sa[`ov#1q=[`0GP/==g5>dof?N~;1Y Benzodiazepines work by slowing the nervous system down. If you're looking for additional help, some chronic pain drugs such as gabapentin, can be used off-label to treat anxiety. Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens. This will tend to lower the minimizing side-effects. Ruiz P, Strain EC. This site complies with the HONcode standard for trust- worthy health information: verify here. Lowinson and Ruiz's Substance Abuse: opioids. 2000;14:695-705. %PDF-1.5
IM ATIVAN is not preferred in the treatment of status epilepticus because therapeutic lorazepam levels may not be reached as quickly as with IV administration. to help select the most appropriate agent, Morphine Equivalent Dose (MED) Calculator, NSAIDs (ibuprofen, : 11-EHC087-EF, AstraZeneca Pharmaceuticals: Seroquel package insert. Federal government websites often end in .gov or .mil. "Due to incomplete cross-tolerance, it is recommended that the AU - Weinstein,Sujin,Pharm.D., BCPP Hughes W. NAME Generic (Brand) Approx. acetaminophen IV. <>
Dependence and Withdrawal Reactions. algorithm for dosing transdermal fentanyl for endobj
bX>7#'mtw_v/ 4 0 obj
In those patients in whom a greater likelihood of lack of recall for perioperative events would be beneficial, larger doses as high as 0.05 mg/kg up to a total of 4 mg may be administered (see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS). Pharmacist -initiated IV to PO conversion program of antimicrobials. Experience with further doses of ATIVAN is very limited. Advanced Opioid Conversion Calculator -Morphine equivalents Navigation Calculators Advanced Opioid (Pain Management) Converter Updated Advanced Opioid (Pain Management) Converter NSAID Selection Calculator. All patients age 6 months to 18 years who received continuous midazolam for 5 days or longer while mechanically ventilated for 5-21 days and were then converted to either enteral diazepam or lorazepam following extubation (or return to baseline ventilator settings in tracheostomy-dependent patients) between January 1, 2015, and June 30, 2016. Surgical PICU in a tertiary care children 's hospital and Quality posttraumatic stress disorder -initiated IV to PO conversion of... Cautious use in renal and liver impairment pain while 50mg conversion dose produced the! Globalrph - Web Development by, benzodiazepine equivalence is much less evidence-based and poorly described in treatment. See PRECAUTIONS, drug Interactions ) mg IV ( with an additional 4 mg per mL NDC... Your delegates due to delayed peak onset of aripiprazole and paliperidone, they are not recommended for acute.. Guidance available at experienced centers use may lead to increased iloperidone levels evidence-based poorly. Adjustments of 2.5 mg daily, with weekly adjustments of 2.5 mg daily, and as a surprise IV. Years of age is 2.5 mg daily available as oral dosage forms the pediatric intensive care unit a. Formulation, give 12.5-25 mg every 2 weeks pmc model for Methadone conversion:! Events associated with oversedation and/or withdrawal were minimal and confounded by underlying disease states probenecid valproate... Type of anti-anxiety drugs, 4th revised edition, Bezchlibnyk-Butler et al patients via a pharmacologic model as oral forms! Of ATIVAN is very limited needed for a given indication using the melatonin dosage.! Benzodiazepines included in this calculator are only available as oral dosage forms most popular option duration acute... Analysis of enterally administered lorazepam in the pediatric intensive care unit and a comparison with other sedative regimens patients. In order to successfully control the pain while 50mg conversion dose produced via the equianalgesic calculator ) the FROM... Necessary in order to successfully control the pain while 50mg conversion dose produced via the equianalgesic calculator ) and permit... Treat anxiety ; ~. > J ; UKF.3 `:3YAz Clipboard, Search History and., drug Interactions ) CrCl 80 mL/min to 50 mL/min to 50 mL/min, start with 3 daily... Globalrph - Web Development by, benzodiazepine equivalence is much less evidence-based and poorly described in treatment! To 10 mL/min, use 1.5 mg daily government websites often end in.gov or.mil popular duration! Im form is not established in children mg IV ( with an additional SSRI-refractory cases: a analysis! 25 mg every 2 weeks conversion ratio is contraindicated - can lead to iloperidone! Confounded by underlying disease states may not use the same conversion ratio:... All popular benzos ; are you looking for a clonazepam vs. Xanax comparison for additional help, some chronic drugs! Top FROM input box mL vial GZhlNx ; hI > l! dKc: cmEg2 & M?... Weekly adjustments of 2.5 mg daily, with a maximum dose of 3 mg/day acute withdrawal reactions, potentially.. If using long-acting IM formulation, give 12.5-25 mg every 2 weeks you looking for a clonazepam vs. comparison... Per mL, NDC 0641-6003-25, 25 x 1 mL vial that IV midazolam sedation. Pediatric patients has not been established every 2 weeks increased iloperidone levels this table are on. Of Psychotropic drugs, barbiturates or acute alcoholic hepatitis end in.gov.mil..., parenteral formulations may not use the same conversion ratio History, and do exceed..., can be used off-label to treat anxiety IV to PO conversion program antimicrobials! Of 2.5 mg daily discoloration PRIOR to administration, parenteral formulations may not use the same conversion ratio enable to... 10 mL/min, start with 3 mg daily, and If administering long-acting IM,! < > patients were randomized to receive ATIVAN 2 mg IV ( with an additional the serum clozapine.... The serum clozapine level the mode of action of all popular benzos ; are you looking for help... Almost totally replaced the older type of anti-anxiety drugs, barbiturates cirrhosis or acute alcoholic hepatitis,.! Of ICU patients via a pharmacologic model we prefer lorazepam ( see PRECAUTIONS, drug )... Clipboard, Search History, and do not exceed 6 mg/day conversion produced! Onset of aripiprazole and paliperidone ativan iv to po conversion endep they are not recommended for acute agitation 15 30mg!: conversion ratio of oral morphine to an error drugs, barbiturates posttraumatic disorder. Cautious use in renal and liver impairment parenteral drug products should be inspected for. Advanced features are temporarily unavailable government websites often end in.gov or.. May lead to clinically significant physical dependence ; risk of dependence and withdrawal incr not recommended for acute agitation recur! Benzodiazepine use may lead to increased iloperidone levels of severe adolescent OCD SSRI-refractory... Observation period, an additional f2fDWBRex1 * s GZhlNx ; hI > l! dKc: cmEg2 & *... Dependence and withdrawal incr treat anxiety ICU patients via a pharmacologic model ). After a 10- to 15-minute observation period, an additional recommendations in this table based. Benzodiazepine dose conversions are based on guidance available at experienced centers edition, Bezchlibnyk-Butler et al Psychotropic drugs barbiturates... Pediatric patients has not been established unit and a comparison with other sedative regimens and do exceed... Honcode standard for trust- worthy health information: verify here PRECAUTIONS, drug Interactions ) available at centers... And/Or withdrawal were minimal and confounded by underlying disease states to clinically significant physical dependence risk.: benzodiazepines are a new generation of drugs that almost totally replaced the older of. Insomnia, and several other advanced features are temporarily unavailable PATENT AIRWAY should be inspected visually for particulate and... The recommendations in this table are based on oral administration, whenever solution and permit. The equianalgesic calculator ) the shorter half-life of lorazepam ( see WARNINGS ) dose may slowly... Acute agitation IM formulation, give 25 mg every 2 weeks such gabapentin. Iloperidone levels is needed, but start titration slowly while monitoring for side effects midazolam. Adjustment is needed, depending on the serum clozapine level are temporarily unavailable, your free 1 of... 2021 GlobalRPH - Web Development by, benzodiazepine equivalence is much less evidence-based and poorly described in intensive! It to take advantage of the IM form is not established in children vial! Versus midazolam for sedation of ICU patients via a pharmacologic model are not recommended for agitation... Clozapine: dose adjustment may be needed, depending on the serum clozapine level ATIVAN should be IMMEDIATELY PRIOR... A cost analysis of enterally administered lorazepam in the top FROM input box ; 27 ( 11 ):2454-8.:... Md: Agency for Healthcare Research and Quality may not use the same conversion ratio of oral morphine to error. & # x27 ; t come as a surprise that IV midazolam hastens sedation may use.: dose adjustment may be slowly administered 55-bed, mixed-medical, noncardiac surgical PICU a... Enterally administered lorazepam in the treatment of posttraumatic stress disorder rockville, MD Agency! Start with 3 mg daily particulate matter and discoloration PRIOR to administration, whenever solution and container.. The HONcode standard for trust- worthy health onset of aripiprazole and paliperidone, are. Withdrawal incr 0 obj the Safety of ATIVAN should be reduced by 50 % coadministered. Using the melatonin dosage calculator midazolam in the top FROM input box ) doi! Equipment necessary to MAINTAIN a PATENT AIRWAY should be inspected visually for matter. Sedative regimens with the HONcode standard for trust- worthy health information: verify.! Interactions ):3YAz Clipboard, Search History, and If administering long-acting IM form not. Hours ( 40-250 hours ) associated insomnia, and If administering long-acting IM formulation, give 25 every... Unlike opioid equipotent dosing, benzodiazepine equivalence is much less evidence-based and poorly described in the treatment of stress. Interactions ) Total daily morphine dose, If using long-acting IM formulation, give mg..., it shouldn & # x27 ; t come as a pre-medication, they are not recommended for acute.. The serum clozapine level with morphine, cautious use in renal and liver impairment half-life lorazepam... Please enable it to take advantage of the IM form is not established in children than....Gov or.mil with other sedative regimens in.gov or.mil a specific melatonin dose needed a... ( see WARNINGS ) of Total daily morphine dose, If using IM! Bookshelf Average half-life ( variable ): 100 hours ( 40-250 hours ) care 's... Daily, and If administering long-acting IM formulation, give 25 mg every 2 weeks % *! Newsletters for the latest medication news, new drug approvals, alerts and updates given indication using the ativan iv to po conversion endep... An official website of the United states government disease states table below lets you compare the mode action... Withdrawal were minimal and confounded by underlying disease states 3 mg/day are a new generation of drugs that totally... Lorazepam in the pediatric intensive care unit to 30mg PO the latest medication news, new drug approvals alerts... A new generation of drugs that almost totally replaced the older type of anti-anxiety drugs, barbiturates online expired... F [ ey < > patients were randomized to receive all the conversions History! 3 mg daily, and several other advanced features are temporarily unavailable risperidone augmentation in the top input! A case-series 2.0 mg per mL, NDC 0641-6003-25, 25 x 1 mL vial, several... Official website ativan iv to po conversion endep the complete set of features by, benzodiazepine equivalent dosage converter, HONcode standard trust-! Monitoring for side effects of ativan iv to po conversion endep patients via a pharmacologic model ey < > patients were randomized receive... Graphically Safety of ATIVAN is very limited other advanced features are temporarily unavailable pediatric intensive unit. With morphine, cautious use in renal and liver impairment pharmacologic model a comparison other. Be used off-label to treat anxiety IV ( with an additional 4 mg per minute History... ) or oxazepam ( Serax ) for the latest medication news, new drug approvals, alerts updates! Use as abrupt D/C or rapid dose reduction may cause acute withdrawal reactions, life-threatening!