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Remifentanil

Pronunciation

(rem i FEN ta nil)

Index Terms

  • GI87084B

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Ultiva: 1 mg (1 ea); 2 mg (1 ea); 5 mg (1 ea)

Brand Names: U.S.

  • Ultiva

Pharmacologic Category

  • Analgesic, Opioid
  • Anilidopiperidine Opioid

Pharmacology

Binds with stereospecific mu-opioid receptors at many sites within the CNS, increases pain threshold, alters pain reception, inhibits ascending pain pathways

Distribution

Pediatric patients (Ross 2001): Vdss:

Neonates ≤2 months: 453 ± 145 mL/kg

Infants and Children >2 months to <2 years: 308 ± 89 mL/kg

Children 2 to 6 years: 240 mL/kg ± 131 mL/kg

Children 7 to 12 years: 249 mL/kg ± 91 mL/kg

Adolescents 13 to <16 years: 223 ± 31 mL/kg

Adolescents 16 to 18 years: 243 ± 109 mL/kg

Adults: Vd: Initial: 100 mL/kg; Vdss: 350 mL/kg

Metabolism

Rapid via blood and tissue esterases; not metabolized by plasma cholinesterase (pseudocholinesterase) and is not appreciably metabolized by the liver

Excretion

Urine

Clearance:

Pediatric patients (Ross 2001):

Neonates ≤2 months of age: 90.5 ± 36.8 mL/minute/kg

Infants and Children >2 months to <2 years: 92.1 ± 25.8 mL/minute/kg

Children 2 to 6 years: 76.0 ± 22.4 mL/minute/kg

Children 7 to 12 years: 59.7 ± 22.5 mL/minute/kg

Adolescents 13 to <16 years: 57.2 ± 21.2 mL/minute/kg

Adolescents 16 to 18 years: 46.5 ± 2.1 mL/minute/kg

Adults: ~40 mL/minute/kg

Onset of Action

IV: 1 to 3 minutes; Peak effect: 3 to 5 minutes

Time to Peak

Intranasal: Children ≤7 years: ~3.5 minutes (Verghese 2008)

Duration of Action

3 to 10 minutes (Scott 2005)

Half-Life Elimination

Dose dependent:

Pediatric patients (Ross 2001): Effective:

Neonates ≤2 months: 5.4 minutes (range: 3 to 8 minutes)

Infants and Children >2 months to <2 years: 3.4 minutes (range: 2 to 6 minutes)

Children 2 to 6 years: 3.6 minutes (range: 1 to 6 minutes)

Children 7 to 12 years: 5.3 minutes (range: 3 to 7 minutes)

Adolescents: 13 to <16 years: 3.7 minutes (range: 2 to 5 minutes)

Adolescents 16 to 18 years: 5.7 minutes (range: 5 to 6 minutes)

Adults: Terminal: 10 to 20 minutes; Effective: 3 to 10 minutes

Protein Binding

~70% (primarily alpha1 acid glycoprotein)

Special Populations: Elderly

The clearance is reduced approximately 25%.

Use: Labeled Indications

Analgesic for use during the induction and maintenance of general anesthesia; for continued analgesia into the immediate postoperative period; analgesic component of monitored anesthesia

Use: Unlabeled

Management of pain in mechanically-ventilated patients

Contraindications

Not for intrathecal or epidural administration, due to the presence of glycine in the formulation; hypersensitivity to remifentanil, fentanyl, or fentanyl analogs, or any component of the formulation

Dosing: Adult

Anesthesia: IV continuous infusion:

Induction of anesthesia: 0.5-1 mcg/kg/minute; if endotracheal intubation is to occur in <8 minutes, an initial dose of 1 mcg/kg may be given over 30-60 seconds

Coronary bypass surgery: 1 mcg/kg/minute

Maintenance of anesthesia: Supplemental bolus dose of 1 mcg/kg may be administered every 2-5 minutes. Consider increasing concomitant anesthetics with infusion rate >1 mcg/kg/minute. Infusion rate can be titrated upward in increments of 25% to 100% or downward in decrements of 25% to 50%. May titrate every 2-5 minutes.

With nitrous oxide (66%): 0.4 mcg/kg/minute (range: 0.1-2 mcg/kg/minute)

With isoflurane: 0.25 mcg/kg/minute (range: 0.05-2 mcg/kg/minute)

With propofol: 0.25 mcg/kg/minute (range: 0.05-2 mcg/kg/minute)

Coronary bypass surgery: 1 mcg/kg/minute (range: 0.125-4 mcg/kg/minute); supplemental dose: 0.5-1 mcg/kg

Continuation as an analgesic in immediate postoperative period: 0.1 mcg/kg/minute (range: 0.025-0.2 mcg/kg/minute). Infusion rate may be adjusted every 5 minutes in increments of 0.025 mcg/kg/minute. Bolus doses are not recommended. Infusion rates >0.2 mcg/kg/minute are associated with respiratory depression.

Coronary bypass surgery, continuation as an analgesic into the ICU: 1 mcg/kg/minute (range: 0.05-1 mcg/kg/minute)

Analgesic component of monitored anesthesia care:

Note: Supplemental oxygen is recommended:

Single IV dose given 90 seconds prior to local anesthetic:

Remifentanil alone: 1 mcg/kg over 30-60 seconds

With midazolam: 0.5 mcg/kg over 30-60 seconds

Continuous infusion beginning 5 minutes prior to local anesthetic:

Remifentanil alone: 0.1 mcg/kg minute

With midazolam: 0.05 mcg/kg/minute

Continuous infusion given after local anesthetic:

Remifentanil alone: 0.05 mcg/kg/minute (range: 0.025-0.2 mcg/kg/minute)

With midazolam: 0.025 mcg/kg/minute (range: 0.025-0.2 mcg/kg/minute)

Note: Following local or anesthetic block, infusion rate should be decreased to 0.05 mcg/kg/minute; rate adjustments of 0.025 mcg/kg/minute may be done at 5-minute intervals

Critically-ill patients (off-label dose): Loading dose: 1.5 mcg/kg; followed by 0.008-0.25 mcg/kg/minute (or 0.5-15 mcg/kg/hour) (SCCM [Barr, 2013])

Dosing: Geriatric

Elderly patients have an increased sensitivity to effect of remifentanil; doses should be decreased by 50% and titrated. Refer to adult dosing.

Dosing: Pediatric

Maintenance of anesthesia with nitrous oxide (70%): Children Birth to 2 months: Continuous IV infusion: 0.4 mcg/kg/minute (range: 0.4-1 mcg/kg/minute); supplemental bolus dose of 1 mcg/kg may be administered, smaller bolus dose may be required with potent inhalation agents, potent neuraxial anesthesia, significant comorbidities, significant fluid shifts, or without atropine pretreatment. Clearance in neonates is highly variable; dose should be carefully titrated.

Maintenance of anesthesia with halothane, sevoflurane, or isoflurane: Continuous IV infusion: Children 1-12 years: 0.25 mcg/kg/minute (range: 0.05-1.3 mcg/kg/minute); supplemental bolus dose of 1 mcg/kg may be administered every 2-5 minutes. Consider increasing concomitant anesthetics with infusion rate >1 mcg/kg/minute. Infusion rate can be titrated upward in increments up to 50% or titrated downward in decrements of 25% to 50%. May titrate every 2-5 minutes.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

No dosage adjustment necessary.

Dosing: Obesity

Dose should be based on ideal body weight (IBW) in obese patients (>30% over IBW).

Reconstitution

Prepare solution by adding 1 mL of D5LR, D5NS, D5W, 1/2NS, NS, SWFI per 1 mg of remifentanil. Shake well. Further dilute to a final concentration of 20, 25, 50, or 250 mcg/mL.

Administration

An infusion device should be used to administer continuous infusions. During the maintenance of general anesthesia, IV boluses may be administered over 30-60 seconds. Injections should be given into IV tubing close to the venous cannula; tubing should be cleared after treatment to prevent residual effects when other fluids are administered through the same IV line.

Compatibility

Stable in D5LR, D5NS, D5W, 1/2NS, NS.

Incompatible with blood products.

Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex.

Compatibility in syringe: Incompatible with ceftriaxone.

Storage

Prior to reconstitution, store at 2°C to 25°C (36°F to 77°F). Stable for 24 hours at room temperature after reconstitution and further dilution in D5LR, D5NS, D5W, 1/2NS, or NS to concentrations of 20 to 250 mcg/mL (4 hours if diluted with LR).

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta-Blockers: Anilidopiperidine Opioids may enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): Anilidopiperidine Opioids may enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Anilidopiperidine Opioids may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

Frequency of adverse events may vary based on surgical procedures and rate of infusion.

>10%:

Cardiovascular: Hypotension (2% to 19%), bradycardia (1% to 7%; dose dependent)

Central nervous system: Headache (<2% to 18%)

Dermatologic: Pruritus (<2% to 18%)

Gastrointestinal: Nausea (<36% to 44%), vomiting (<16% to 22%)

Neuromuscular & skeletal: Muscle rigidity (<1% to 11%; includes chest wall rigidity)

1% to 10%:

Cardiovascular: Hypertension (1% to 2%; dose dependent), tachycardia (≤1%; dose dependent), flushing (1%)

Central nervous system: Fever (<5%), dizziness (<5%), postoperative pain (<2%), chills (1%), agitation (≤1%)

Local: Pain at injection site (1%)

Respiratory: Respiratory depression (<7%), apnea (<3%), hypoxia (≤1%)

Miscellaneous: Diaphoresis (6%), shivering (<5%), warm sensation (1%)

<1% (Limited to important or life-threatening): Abdominal discomfort, amnesia, anaphylaxis, anxiety, arrhythmias, awareness under anesthesia without pain, bronchitis, bronchospasm, chest pain, confusion, constipation, cough, CPK increased, diarrhea, disorientation, dysphagia, dysphoria, dyspnea, dysuria, ECG changes, electrolyte disorders, erythema, gastroesophageal reflux, hallucinations, heart block, heartburn, hiccups, hyperglycemia, ileus, incontinence, involuntary movement, laryngospasm, leukocytosis, liver dysfunction, lymphopenia, nasal congestion, nightmares, nystagmus, oliguria, paresthesia, pharyngitis, pleural effusion, prolonged emergence from anesthesia, pulmonary edema, rales, rapid awakening from anesthesia, rash, rhinorrhea, rhonchi, seizure, sleep disturbance, stridor, syncope, temperature regulation impaired, thrombocytopenia, tremors, twitching, urine retention, urticaria, xerostomia

Warnings/Precautions

Concerns related to adverse effects:

• Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).

• Intraoperative awareness: In patients <55 years of age, intraoperative awareness has been reported when used with propofol rates of ≤75 mcg/kg/minute.

• Opioid agonist toxicities: Shares the toxic potentials of opioid agonists, and precautions of opioid agonist therapy should be observed.

Disease-related concerns:

• Bradycardia: Use with caution when administering to patients with bradycardia.

• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.

• Obesity: Use with caution in patients who are morbidly obese.

Other warnings/precautions:

• Discontinuation of therapy: Interruption of an infusion will result in offset of effects within 5-10 minutes; the discontinuation of infusion should be preceded by the establishment of adequate postoperative analgesia orders, especially for patients in whom postoperative pain is anticipated.

• General anesthesia use: Not recommended as the sole agent for induction of anesthesia, because the loss of consciousness cannot be assured.

• Rapid infusion: Rapid IV infusion (single dose >1 mcg/kg over 30-60 seconds and infusion rates >0.1 mcg/kg/minute) should only be used during maintenance of general anesthesia; may result in skeletal muscle and chest wall rigidity, impaired ventilation, or respiratory distress/arrest; nondepolarizing skeletal muscle relaxant may be required. Chest wall rigidity may resolve by decreasing the infusion rate or temporarily stopping the infusion.

• Trained individuals: Due to the high incidence of respiratory depression, apnea, hypotension, tachycardia and muscle rigidity, remifentanil should only be administered by individuals specifically trained in the use of anesthetic agents. Should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; resuscitative and intubation equipment should be readily available.

• Appropriate use: Inadequate clearing of IV tubing following remifentanil administration could result in chest wall rigidity, respiratory depression, and apnea when another fluid is administered through the same line.

Monitoring Parameters

Respiratory and cardiovascular status, blood pressure, heart rate

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Remifentanil has been shown to cross the placenta; fetal and maternal concentrations may be similar.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience itching, nausea, vomiting, headache, or muscle rigidity. Have patient report immediately to prescriber signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), sexual dysfunction (males), amenorrhea, decreased libido, fertility problems, severe dizziness, passing out, or arrhythmia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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