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Morphine (Liposomal)

Pronunciation

(MOR feen)

Index Terms

  • Extended Release Epidural Morphine
  • Liposomal Morphine
  • MS (error-prone abbreviation and should not be used)
  • MSO4 (error-prone abbreviation and should not be used)

Dosage Forms

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

Suspension, Epidural, as sulfate:

DepoDur: 10 mg/mL (1 mL); 15 mg/1.5 mL (1.5 mL)

Brand Names: U.S.

  • DepoDur

Pharmacologic Category

  • Analgesic, Opioid

Pharmacology

Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression

Distribution

Vd: 1 to 6 L/kg; binds to opioid receptors in the CNS and periphery (eg, GI tract)

Metabolism

Hepatic via conjugation with glucuronic acid primarily to morphine-6-glucoronide (active analgesic) morphine-3-glucuronide (inactive as analgesic; may contribute to CNS stimulation [Lugo 2002]); minor metabolites include morphine-3-6-diglucuronide; other minor metabolites include normorphine (active) and morphine 3-ethereal sulfate

Excretion

Urine (primarily as morphine-3-glucuronide, ~2% to 12% excreted unchanged); feces (~7% to 10%). It has been suggested that accumulation of morphine-6-glucuronide might cause toxicity with renal insufficiency. All of the metabolites (ie, morphine-3-glucuronide, morphine-6-glucuronide, and normorphine) have been suggested as possible causes of neurotoxicity (eg, myoclonus).

Duration of Action

Patient dependent; dosing must be individualized: Epidural: 48 hours (Bujedo 2012)

Protein Binding

20% to 35%

Use: Labeled Indications

Surgical anesthesia: Epidural (lumbar) single-dose management of pain following major surgery

Contraindications

Hypersensitivity to morphine, morphine salts or any component of the formulation; respiratory depression; acute or severe bronchial asthma; upper airway obstruction; known or suspected paralytic ileus; head injuries or increased intracranial pressure; circulatory shock.

Dosing: Adult

Surgical anesthesia: Lumbar epidural: Note: If a test dose of a local anesthetic is used to determine proper placement of needle/catheter, administer test dose of local anesthetic at least 15 minutes prior to administration of morphine (liposomal). Do not administer morphine (liposomal) with or coadminister with any other medications (including local anesthetics). Once morphine (liposomal) is administered, no other medication should be administered into the epidural space for at least 48 hours.

Cesarean section: 10 mg single dose (after clamping umbilical cord)

Lower abdominal/pelvic surgery: 10 to 15 mg single dose; Note: Some patients may benefit from a 20 mg dose; however, the incidence of adverse effects may be increased.

Major orthopedic surgery of lower extremity: 15 mg single dose; Note: Some patients may benefit from a 20 mg dose; however, the incidence of adverse effects may be increased.

Dosing: Geriatric

Refer to adult dosing. Use with caution.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

No dosage adjustment necessary.

Reconstitution

May dilute in preservative-free NS to a volume up to 5 mL. Gently invert vial to suspend particles prior to removal from vial.

Administration

Epidural: For lumbar administration only; not for IV, IM, or intrathecal administration. Thoracic administration is not recommended (has not been studied). Check freeze indicator before administration; do not administer if the bulb of the freeze indicator is pink or purple. May be administered undiluted or diluted up to 5 mL total volume in preservative-free NS. Gently invert vial to suspend particles prior to removal from vial. Do not use an in-line filter during administration. Do not mix with or co-administer with any other medications (including local anesthetics). Once administered, no other medication should be administered into the epidural space for at least 48 hours.

Detection of improper needle/catheter placement: Local anesthetic test dose: Administration of an epidural test dose (preservative-free lidocaine 1.5% and epinephrine 1:200,000) may affect the release of morphine from the liposomal preparation. Delaying administration of the morphine (liposomal) dose for at least 15 minutes following the local anesthetic test dose and flushing the epidural catheter with NS preservative-free minimizes this pharmacokinetic interaction. Except for the local anesthetic test dose, other epidural local anesthetics or medications should not be administered epidurally before or after morphine (liposomal) for a minimum of 48 hours.

Storage

Store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F); keep vials in carton during refrigeration; do not freeze. Check freeze indicator before administration; do not administer if the bulb of the freeze indicator is pink or purple. May also store intact vials at controlled room temperature for up to 30 days; do not return to refrigerator. Following withdrawal from the vial, may be held at 15°C to 30°C (59°F to 86°F) and use within 4 hours.

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

Antiplatelet Agents (P2Y12 Inhibitors): Morphine (Liposomal) may diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Morphine (Liposomal) may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Management: Consider alternative anti-ischemic/analgesic therapies (eg, beta-blockers, nitroglycerin) in patients with acute coronary syndromes treated with a P2Y12 inhibitor when possible. The risks associated with other opioids are unknown. Consider therapy modification

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

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

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

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

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

MAO Inhibitors: May enhance the adverse/toxic effect of Morphine (Liposomal). Avoid combination

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

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

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

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. 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

>10%:

Cardiovascular: Hypotension, oxygen saturation decreased

Central nervous system: Dizziness, headache

Dermatologic: Pruritus

Gastrointestinal: Constipation, nausea, vomiting

Genitourinary: Urinary retention

Hematologic & oncologic: Anemia

Miscellaneous: Fever

1% to 10%:

Cardiovascular: Tachycardia (5% to 10%), bradycardia (2% to 5%), hypertension (2% to 5%)

Central nervous system: Insomnia (5% to 10%), anxiety (2% to 5%), drowsiness (2% to 5%), hypoesthesia (2% to 5%), paresthesia (2% to 5%), rigors (2% to 5%)

Dermatologic: Diaphoresis (2% to 5%)

Endocrine & metabolic: Hypokalemia (2% to 5%)

Gastrointestinal: Flatulence (5% to 10%), abdominal distention (2% to 5%), dyspepsia (2% to 5%), paralytic ileus (2% to 5%)

Genitourinary: Bladder spasm (2% to 5%), oliguria (2% to 5%)

Hematologic & oncologic: Decreased hematocrit (2% to 5%)

Neuromuscular & skeletal: Back pain (2% to 5%)

Respiratory: Dyspnea (2% to 5%), hypercapnia (2% to 5%), hypoxia (5% to 10%), respiratory depression (2% to 5%; required narcotic antagonists: 4%; onset >48hours post dose: <1%)

<1% (Limited to important or life-threatening): Apnea (higher risk with subarachnoid puncture), central nervous depression, confusion, hypogonadism (Brennan 2013; Debono 2011), lethargy, obtundation, respiratory arrest, unresponsive to stimuli

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

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

• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).

• Respiratory depression: May cause respiratory depression. Risk increased in elderly patients, debilitated patients, and patients with conditions associated with hypoxia or hypercapnia. Prolonged, serious respiratory depression has been associated with nonapproved routes of administration (subarachnoid puncture and intrathecal). Although respiratory depression is reversible with naloxone, patients must be monitored for at least 48 hours due to the duration of action of the liposomal formulation and the potential for rebound sedation. Patients at increased risk of respiratory depression (such as those with impaired respiratory drive, sleep apnea, concomitant sedation or the elderly) may require monitoring >48 hours.

Disease-related concerns:

• Abdominal conditions: Opioids may obscure diagnosis or clinical course of patients with acute abdominal conditions. May worsen gastrointestinal ileus due to the effects on GI motility. Contraindicated in patients with paralytic ileus; avoid use in patients with GI obstruction.

• Abuse/misuse/diversion: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists.

• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction including acute pancreatitis. Use may cause constriction of sphincter of Oddi diminishing biliary and pancreatic secretions.

• CNS depression/coma: Avoid use of opioids in patients with CNS depression or coma as these patients are susceptible to intracranial effects of CO2 retention.

• Obstructive sleep apnea: Administration can worsen airway obstruction in patients with obstructive sleep-apnea syndrome. Patients who are obese are at particular risk.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, patients having a substantially decreased respiratory reserve, preexisting respiratory compromise (hypoxia and/or hypercapnia), and kyphoscoliosis or other skeletal disorder which may alter respiratory function; even at therapeutic dosage may decrease respiratory drive to the point of apnea. Contraindicated in patients with respiratory depression, acute or severe asthma and upper airway obstruction.

• Seizure disorders: Use with caution in patients with seizure disorders, may cause seizures if high doses used.

• Thyroid dysfunction: Use opioids with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Cachectic or debilitated patients: Use opioids with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Use with caution in elderly patients; may be more sensitive to adverse effects. Reduced dosage may be required.

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

Other warnings/precautions:

• Appropriate use: For lumbar administration only; not intended for intrathecal, intravenous, or intramuscular administration. Administer prior to surgery or after clamping the umbilical cord during cesarean section. Not for use in vaginal labor and delivery. Administration into the thoracic epidural space or higher is not recommended (has not been evaluated). Intrathecal administration has resulted in prolonged respiratory depression. Prolonged and serious respiratory depression or apnea has occurred when administration was associated with subarachnoid puncture.

• Detection of improper needle/catheter placement: Local anesthetic test dose: To minimize the pharmacokinetic interaction resulting in higher peak serum concentrations of morphine, administer the test dose of the local anesthetic at least 15 minutes prior to administration of morphine (liposomal).

• Patient evaluation: Health care provider should evaluate patient for contraindications for epidural injection (eg, anticoagulant therapy, bleeding, diathesis, infection at the injection site) prior to administration.

Monitoring Parameters

Pain relief, respiratory and mental status, blood pressure; patient should be monitored for at least 48 hours following administration

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Morphine (liposomal) is administered as a single dose for acute, surgery-induced pain. It may be used in women undergoing cesarean section following clamping of the umbilical cord; not for use in vaginal labor and delivery.

Refer to the Morphine (Systemic) monograph for additional information.

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 nausea, vomiting, insomnia, or flatulence. Have patient report immediately to prescriber signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), sexual dysfunction (males), amenorrhea, decreased libido, fertility problems, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), severe dizziness, passing out, angina, tachycardia, bradycardia, difficulty breathing, slow breathing, shallow breathing, burning or numbness feeling, seizures, difficult urination, severe abdominal pain, severe constipation, severe loss of strength and energy, chills, severe headache, or sweating a lot (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 healthcare 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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