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Acetylcysteine

Pronunciation

Pronunciation

(a se teel SIS teen)

Index Terms

  • N Acetylcysteine
  • N - Acetyl - L - cysteine
  • N - Acetylcysteine
  • Acetylcysteine Sodium
  • Cetylev
  • Mercapturic Acid
  • Mucomyst
  • NAC

Dosage Forms

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

Injection, solution [preservative free]: 20% (30 mL)

Acetadote: 20% [200 mg/mL] (30 mL)

Solution, for inhalation/oral: 10% [100 mg/mL] (10 mL, 30 mL); 20% [200 mg/mL] (10 mL, 30 mL)

Solution, for inhalation/oral [preservative free]: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)

Tablet Effervescent, Oral:

Cetylev: 500 mg, 2.5 g [contains edetate disodium; lemon mint flavor]

Brand Names: U.S.

  • Acetadote
  • Cetylev

Pharmacologic Category

  • Antidote
  • Mucolytic Agent

Pharmacology

Acetaminophen overdose: Acetylcysteine acts as a hepatoprotective agent by restoring hepatic glutathione, serving as a glutathione substitute, and enhancing the nontoxic sulfate conjugation of acetaminophen.

Mucolytic: Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity.

Prevention of contrast-induced nephropathy (off-label use): The presumed mechanism in preventing contrast-induced nephropathy is its ability to scavenge oxygen-derived free radicals and improve endothelium-dependent vasodilation.

Distribution

Vdss: 0.47 L/kg

Metabolism

Undergoes extensive first pass metabolism to form cysteine and disulfides (N,N-diacetylcysteine and N-acetylcysteine); cysteine is further metabolized to form glutathione and other metabolites

Excretion

Urine (13% to 38%)

Onset of Action

Inhalation: 5 to 10 minutes

Time to Peak

Plasma: Oral solution: 1 to 2 hours; Effervescent tablets: 1 to 3.5 hours (median: 2 hours)

Duration of Action

Inhalation: >1 hour

Half-Life Elimination

Reduced acetylcysteine: 2 hours; Total acetylcysteine: Adults: 5.6 hours, Newborns: 11 hours

Effervescent tablets: Terminal half-life: 18.1 hours

Protein Binding

66% to 87%

Use: Labeled Indications

Acetaminophen overdose: 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 (RSTI).

Mucolytic: Adjunct therapy in patients with abnormal, viscid, or inspissated mucous secretions in conditions such as: chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis, primary amyloidosis of the lung); acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis); pulmonary complications of cystic fibrosis; tracheostomy care; pulmonary complications associated with surgery; use during anesthesia; posttraumatic chest conditions; atelectasis due to mucous obstruction; diagnostic bronchial studies (bronchograms, bronchospirometry, bronchial wedge catheterization).

Use: Unlabeled

Prevention of contrast-induced renal dysfunction (oral, IV); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)

Contraindications

Hypersensitivity to acetylcysteine or any component of the formulation.

Effervescent tablet (Cetylev): There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Acetaminophen overdose: Only the 72-hour oral and 21-hour IV regimens are FDA approved. Ideally, in patients with acute acetaminophen ingestion, treatment should begin within 8 hours of ingestion or as soon as possible after ingestion. In patients with a suspected acute ingestion where the time of ingestion is unknown, the concentration is unobtainable or uninterpretable within 8 hours of ingestion, the patient presents >8 hours after ingestion, or there is clinical evidence of toxicity, initiate treatment immediately and re-evaluate the need for acetylcysteine upon receipt of the results (if applicable). In patients who present following RSTI and treatment is deemed appropriate, acetylcysteine should be initiated immediately. Regardless of the treatment regimen selected, serum acetaminophen concentrations, liver function, and clinical status should be evaluated during and prior to the end of the treatment regimen to determine if treatment discontinuation is appropriate. In patients who continue to experience symptoms of hepatotoxicity or elevated liver function tests at the conclusion of a 72-hour oral or 21-hour IV regimen, extending the treatment course may be appropriate; however, when and to which patients additional doses should be administered is unclear. Possible candidates for extended therapy include patients with a suspected massive overdose, concomitant ingestion of other substances, or patients with preexisting liver disease. In patients with persistently elevated acetaminophen concentrations, persistently elevated liver function tests, or an elevated INR, additional acetylcysteine should be administered. Typically, an additional "third dose" or "third bag" (IV: 100 mg/kg [maximum: 10 g] infused over 16 hours) is administered; however, this dose may be inadequate in some patients (Rumack 2012). Consultation with a poison control center or clinical toxicologist is highly recommended to determine optimal patient care.

Oral: (Effervescent tablets [Cetylev]; solution for oral administration): Note: Consultation with a poison control center or clinical toxicologist is highly recommended when considering the discontinuation of oral acetylcysteine prior to the conclusion of a full 18-dose course of therapy.

72-hour regimen: Consists of 18 doses; total dose delivered: 1,330 mg/kg

Loading dose: 140 mg/kg

Maintenance dose: 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration

IV (Acetadote):

21-hour regimen: Consists of 3 doses; total dose delivered: 300 mg/kg

Loading dose: 150 mg/kg (maximum: 15 g) infused over 1 hour

Second dose: 50 mg/kg (maximum: 5 g) infused over 4 hours

Third dose: 100 mg/kg (maximum: 10 g) infused over 16 hours

Note: The fluid volume should be reduced in patients weighing ≤40 kg according to the following table:

Acetadote Dosing / Fluid Volume Guidelines for Patients ≤40 kg

Body Weight

(kg)

Loading Dose

150 mg/kg over 1 hour

Second Dose

50 mg/kg over 4 hours

Third Dose

100 mg/kg over 16 hours

Acetadote

(mL)

Diluent

(mL)

Acetadote

(mL)

Diluent

(mL)

Acetadote

(mL)

Diluent

(mL)

40

30

100

10

250

20

500

30

22.5

100

7.5

250

15

500

21

15.75

100

5.25

250

10.5

500

20

15

60

5

140

10

280

15

11.25

45

3.75

105

7.5

210

10

7.5

30

2.5

70

5

140

5

3.75

15

1.25

35

2.5

70

Table has been converted to the following text.

Acetadote Dosing / Fluid Volume Guidelines for Patients ≤40 kg

Body weight 40 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 30 mL in 100 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 10 mL in 250 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 20 mL in 500 mL diluent

Body weight 30 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 22.5 mL in 100 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 7.5 mL in 250 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 15 mL in 500 mL diluent

Body weight 21 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 15.75 mL in 100 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 5.25 mL in 250 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 10.5 mL in 500 mL diluent

Body weight 20 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 15 mL in 60 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 5 mL in 140 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 10 mL in 280 mL diluent

Body weight 15 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 11.25 mL in 45 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 3.75 mL in 105 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 7.5 mL in 210 mL diluent

Body weight 10 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 7.5 mL in 30 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 2.5 mL in 70 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 5 mL in 140 mL diluent

Body weight 5 kg:

Loading dose (150 mg/kg over 1 hour): Acetadote 3.75 mL in 15 mL diluent

Second dose (50 mg/kg over 4 hours): Acetadote 1.25 mL in 35 mL diluent

Third dose (100 mg/kg over 16 hours): Acetadote 2.5 mL in 70 mL diluent

Obesity: In patients who weigh >100 kg, the following dosing regimen is recommended:

Oral: Effervescent tablets (Cetylev): Limited information exists regarding the oral dosing requirements of patients >100 kg

72-hour regimen: Consists of 18 doses; total dose delivered: 142.5 g

Loading dose: 15 g

Maintenance dose: 7.5 g every 4 hours

IV (Acetadote): 21-hour regimen: Consists of 3 doses; total dose delivered: 30 g

Loading dose: 15 g infused over 1 hour

Second dose: 5 g infused over 4 hours

Third dose: 10 g infused over 16 hours

Adjuvant therapy in respiratory conditions:

Note: Patients should receive an aerosolized bronchodilator 10 to 15 minutes prior to dose.

Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3 to 5 mL of 20% solution or 6 to 10 mL of 10% solution until nebulized given 3 to 4 times/day; dosing range: 1 to 10 mL of 20% solution or 2 to 20 mL of 10% solution every 2 to 6 hours

Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment

Direct instillation:

Into tracheostomy: 1 to 2 mL of 10% to 20% solution every 1 to 4 hours

Through percutaneous intratracheal catheter: 1 to 2 mL of 20% or 2 to 4 mL of 10% solution every 1 to 4 hours via syringe attached to catheter

Diagnostic bronchogram: Nebulization or intratracheal: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution administered 2 to 3 times prior to procedure

Prevention of contrast-induced nephropathy (off-label use): Oral: 1,200 mg every 12 hours starting the day prior to the procedure and on the day of procedure for a total of 4 doses. (ACT Investigators 2011). Note: No longer recommended for use prior to left ventricular angiography or percutaneous coronary intervention; instead adequate hydration is preferred (ACCF/AHA/SCAI [Levine 2011]; AHA/ACC [Amsterdam 2014]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Acetaminophen overdose: Infants, Children, and Adolescents: Refer to adult dosing.

Adjuvant therapy in respiratory conditions:

Note: Patients should receive an aerosolized bronchodilator 10 to 15 minutes prior to acetylcysteine

Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted.

Infants: 1 to 2 mL of 20% solution or 2 to 4 mL 10% solution until nebulized given 3 to 4 times/day

Children: Refer to adult dosing.

Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.

Dosing: Renal Impairment

Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Obesity

Refer to indication-specific dosing for obesity-related information (may not be available for all indications).

Reconstitution

Effervescent tablets (Cetylev): Dissolve the effervescent tablets in the volume of water indicated below based upon patient weight; administer immediately:

1 to <20 kg: Dissolve two 2.5 g tablets in 100 mL of water to create a 50 mg/mL solution; administer an appropriate amount of this solution to deliver the calculated dose.

20 to <60 kg: Dissolve an appropriate number of tablets to deliver the calculated dose in 150 mL of water.

≥60 kg: Dissolve an appropriate number of tablets to deliver the calculated dose in 300 mL of water.

Solution for inhalation: The 20% solution may be diluted with sodium chloride or sterile water; the 10% solution may be used undiluted.

Intravenous administration of solution for inhalation/oral (off-label route): Using D5W, dilute acetylcysteine 20% inhalation/oral solution to a 3% solution.

Solution for injection (Acetadote): Note: Volume of diluent based on weight; compatible diluents include D5W, 1/2NS, or SWFI:

Patient weight 5 to 20 kg:

Loading dose: Dilute dose in 3 mL/kg diluent

Second dose: Dilute dose in 7 mL/kg diluent

Third dose: Dilute dose in 14 mL/kg diluent

Patient weight 21 to 40 kg:

Loading dose: Dilute dose in 100 mL diluent

Second dose: Dilute dose in 250 mL diluent

Third dose: Dilute dose in 500 mL diluent

Patient weight: ≥41 kg: Note: In patients requiring fluid restriction, decrease diluent volume.

Loading dose: Dilute dose in 200 mL diluent

Second dose: Dilute dose in 500 mL diluent

Third dose: Dilute dose in 1,000 mL diluent

Note: Clinicians should be aware that undiluted injection solution (Acetadote) is hyperosmolar (2,600 mOsmol/L); when the diluent volume is decreased for patients ≤40 kg or requiring fluid restriction, the osmolarity of the solution may remain higher than desirable for intravenous infusion. To ensure tolerance of the infusion, osmolarity should be adjusted to a physiologically safe level (eg, ≥150 mOsmol/L in children).

Acetadote concentration: 7 mg/mL

Osmolarity in D5W: 343 mOsmol/L

Osmolarity in 1/2NS: 245 mOsmol/L

Osmolarity in SWFI: 91 mOsmol/L

Acetadote concentration: 24 mg/mL

Osmolarity in D5W: 564 mOsmol/L

Osmolarity in 1/2NS: 466 mOsmol/L

Osmolarity in SWFI: 312 mOsmol/L

Solution for oral administration: Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink to prepare a 5% solution. If being administered via a nasogastric tube or Miller-Abbott tube, water may be used as the diluent. Use within 1 hour of preparation.

Administration

Inhalation: Acetylcysteine is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.

Oral:

Effervescent tablets (Cetylev): Use within 2 hours of preparation. If the patient vomits within 1 hour of administration, repeat that dose. If the patient is persistently unable to retain the orally administered acetylcysteine, acetylcysteine may be administered by nasoduodenal tube. An intravenous formulation of acetylcysteine may also be considered.

Solution for oral administration: For the treatment of acetaminophen overdose, administer orally as a 5% solution. Use within 1 hour of preparation. The unpleasant odor (sulfur-like) becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put the acetylcysteine on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).

Prevention of contrast induced nephropathy (off-label use): Using the 20% solution, each 1,200 mg dose should be diluted immediately prior to use in a minimum of 20 mL of a cola drink or other soft drink (or water if administered via NG tube); use within 1 hour of preparation (Massicotte 2008).

IV (Acetadote): Acetaminophen overdose:

Loading dose: Administer over 1 hour.

Second dose: Administer over 4 hours.

Third dose: Administer over 16 hours.

If the commercial IV form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Yip 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.

Compatibility

Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, oxytetracycline, erythromycin.

Intravenous: Stable in D5W, 1/2 NS, SWFI.

Y-site administration: Incompatible: Metals (particularly iron, copper, and nickel); cefepime, ceftazidime

Storage

Effervescent tablets (Cetylev): Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture. Following dissolution in water, the solution should be used within 2 hours.

Solution for inhalation/oral administration: Store unopened vials at room temperature; once opened, store under refrigeration and use within 96 hours. A color change may occur in opened vials (light purple) and does not affect the safety or efficacy.

Solution for injection (Acetadote): Store intact vials at 20°C to 25°C (68°F to 77°F). Following reconstitution, solution is stable for 24 hours at room temperature. A color change may occur in opened vials (light pink or purple) and does not affect the safety or efficacy. Discard unused portion.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Intravenous:

>10%:

Immunologic: Autoimmune disease (14% to 18%)

Miscellaneous: Anaphylactoid reaction (1% to 18%)

1% to 10%:

Cardiovascular: Flushing (1% to 3%), tachycardia (1% to 4%), edema (1% to 2%)

Dermatologic: Urticaria (≤21%), rash (2% to ≤21%), pruritus (1% to ≤21%)

Gastrointestinal: Vomiting (2% to 10%), nausea (1% to 6%)

Respiratory: Pharyngitis (≤1%), rhinorrhea (≤1%), rhonchi (≤1%), throat tightness (≤1%)

<1% (Limited to important or life-threatening): Anaphylaxis, angioedema, bronchospasm, chest tightness, cough, dizziness (Sandilands 2008), dyspnea (Sandilands 2008), hypotension, respiratory distress, stridor, wheezing

Oral: Frequency not defined.

Cardiovascular: Chest tightness, hypotension (Bebarta 2010; Sandilands 2008)

Dermatologic: Rash (with or without fever), urticaria

Gastrointestinal: Gastrointestinal symptoms, nausea, vomiting

Hypersensitivity: Hypersensitivity reaction

Respiratory: Bronchospasm, bronchitis

<1% (Limited to important or life-threatening): Angioedema (Bebarta 2010), tachycardia (Bebarta 2010)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Acute flushing and erythema have been reported; usually occurs within 30 to 60 minutes and may resolve spontaneously. Serious anaphylactoid reactions (some fatal) have also been reported and are more commonly associated with IV administration, but also occur with oral administration (Mroz 1997). When used for acetaminophen overdose, the incidence is reduced when the initial intravenous loading dose is administered over 60 minutes. The acetylcysteine infusion may be interrupted until the treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactoid reactions should be immediately available. Conversely, patients with high acetaminophen concentrations (>150 mg/L) may be at a reduced risk for anaphylactoid reactions (Pakravan 2008; Sandilands 2009; Waring 2008).

• Fluid overload: IV administration can cause fluid overload, potentially resulting in hyponatremia, seizure and death. To avoid fluid overload in patients ≤40 kg and those requiring fluid restriction, decrease volume of diluent proportionally (see table in dosing section).

Disease-related concerns:

• Asthma/bronchospasm: Use caution in patients with asthma or history of bronchospasm; these patients may be at increased risk of hypersensitivity reactions.

Other warnings/precautions:

• Acute acetaminophen overdose: Appropriate use: Acetylcysteine is indicated in patients with a serum acetaminophen concentration that indicates they are at "possible" risk or greater for hepatotoxicity when plotted on the Rumack-Matthew nomogram. There are several situations where the nomogram is of limited use. Serum acetaminophen concentrations obtained <4 hours postingestion are not reliable, except to document the presence of acetaminophen (Seifert 2015). Patients presenting late may have undetectable serum concentrations, despite having received a toxic dose. The nomogram is less predictive of hepatic injury following an acute overdose with an extended release acetaminophen product. The nomogram also does not take into account patients who may be at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients, concurrent use of CYP2E1 enzyme-inducing agents [eg, isoniazid]). Nevertheless, acetylcysteine should be administered to any patient with signs of hepatotoxicity, even if the serum acetaminophen concentration is low or undetectable. Patients who present >24 hours after an acute ingestion or patients who present following an acute ingestion at an unknown time may be candidates for acetylcysteine therapy; consultation with a poison control center or clinical toxicologist is highly recommended.

• Repeated supratherapeutic ingestion (RSTI) of acetaminophen: Appropriate use: The Rumack-Matthew nomogram is not designed to be used following RSTIs. In general, an accurate past medical history, including a comprehensive acetaminophen ingestion history, in conjunction with AST concentrations and serum acetaminophen concentrations, may give the clinician insight as to the patient's risk of acetaminophen toxicity. Some experts recommend that acetylcysteine be administered to any patient with "higher than expected" serum acetaminophen concentrations or serum acetaminophen concentration >10 mcg/mL, even in the absence of hepatic injury; others recommend treatment for patients with laboratory evidence and/or signs and symptoms of hepatotoxicity (Hendrickson 2006; Jones 2000). Consultation with a poison control center or a clinical toxicologist is highly recommended.

Dosage form specific issues:

• Effervescent tablets (Cetylev): Contains sodium; consider acetylcysteine treatment as a source of sodium in patients who may be sensitive to excess sodium intake (eg, heart failure, hypertension, renal impairment).

• Oral administration: Gastrointestinal hemorrhage: Oral administration of acetylcysteine may result in nausea and vomiting, which may exacerbate vomiting associated with acetaminophen overdose. Therefore, patients at risk of gastrointestinal hemorrhage (eg, esophageal varices, peptic ulcer) may experience an even higher risk of gastrointestinal hemorrhage during therapy.

• Inhalation: Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow. If bronchospasm occurs, administer a bronchodilator; discontinue acetylcysteine if bronchospasm progresses.

Monitoring Parameters

Acetaminophen overdose: Monitor patient for the development of anaphylaxis or anaphylactoid reactions; monitor serum acetaminophen concentrations, AST, ALT, bilirubin, PT, INR, serum creatinine, BUN, serum glucose, hemoglobin, hematocrit, and electrolytes. Assess patient for nausea, vomiting, and skin rash following oral administration. Reassess LFTs for possible hepatotoxicity every 4 to 6 hours. An early elevation in the INR may be related to acetylcysteine therapy (Schmidt 2002).

Acute ingestion: Obtain the first acetaminophen concentration 4 hours postingestion (or as soon as possible thereafter); plot on the Rumack-Matthew nomogram. In patients who have ingested an extended release formulation of acetaminophen or have coingested an agent known to delay gastric emptying, obtain a repeat serum acetaminophen measurement 4 to 6 hours following the first measurement if the original concentration (taken at 4 to 8 hours postingestion) when plotted on the Rumack-Matthew nomogram indicated that treatment was not necessary.

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Based on limited reports using acetylcysteine to treat acetaminophen overdose in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective concentrations in the fetus.

Acetylcysteine may be used to treat acetaminophen overdose in during pregnancy (Wilkes 2005). In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).

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 mouth sores, rhinorrhea, fatigue, clammy skin, or flushing. Have patient report immediately to prescriber shortness of breath; severe nausea; black, tarry, or bloody stools; severe vomiting; vomiting blood; severe dizziness; or passing out (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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