Class: General Anesthetics, Miscellaneous
VA Class: CN203
Chemical Name: 2,6-Bis(1-methylethyl) phenol
Molecular Formula: C12H18O
CAS Number: 2078-54-8
Brands: Diprivan
- Microbial Contamination
Propofol injectable emulsion can support microbial growth.1 (See Potential for Microbial Contamination under Cautions.)
Use strict aseptic technique at all times during handling; failure to use aseptic technique may result in microbial contamination and possible fever, infection/sepsis, other life-threatening illness, and/or death.1 2 103 113 194 195 197 198 199
Discard unused portions within the required time limits.1 2 (See Stability and Sterility Considerations under Dosage and Administration.)
Do not use if contamination is suspected.1 2 194
Introduction
Sedative and hypnotic.1 2
Uses for Propofol
Induction and Maintenance of Anesthesia
Induction and/or maintenance of anesthesia as the sedative and hypnotic component of balanced anesthesia (benzodiazepines, anticholinergic agents, depolarizing and nondepolarizing skeletal muscle relaxants, opiate analgesics, inhalation and/or regional anesthetic) or total IV anesthesia (balanced anesthesia in which the IV anesthetic completely replaces the inhalation anesthetic) in patients undergoing inpatient or outpatient surgery.1 2 6 7 8 9 118 192
Produces adequate general anesthesia in patients undergoing various types of surgery, including neurosurgery (e.g., craniotomy, intracranial aneurysm);1 2 6 cardiovascular (e.g., CABG);1 2 6 7 abdominal;6 ocular;6 ear, nose, and throat (ENT);8 orthopedic;8 and general surgery.1 2
Considered the hypnotic of choice by some clinicians for patients undergoing outpatient surgery.118 Usually is associated with similar or faster early recovery (time to awakening and eye opening) from anesthesia, more rapid recovery of psychomotor performance and time to discharge, and lower incidence of adverse effects (e.g., nausea, vomiting, cough, hiccups) compared with other IV anesthetic agents (e.g., etomidate, methohexital, thiopental) or conventional combinations (e.g., an IV induction agent and an inhalation anesthetic).6 7 9 10 118
Monitored Anesthesia Care (MAC)
Initiation and maintenance of MAC sedation (alone or in combination with an opiate analgesic and/or a benzodiazepine) in adults undergoing diagnostic procedures or in conjunction with local or regional anesthesia for surgical procedures.1 2 6 7 152 153 154 155 156 157 158
Provides sedation, analgesia, anxiolysis, and/or amnesia without assisted respiration or loss of consciousness6 7 131 when administered prior to and/or during dental,6 endoscopic (e.g., gastroscopy, bronchoscopy, colonoscopy),6 7 diagnostic,7 oral,7 or other procedures such as extracorporeal lithotripsy,6 7 transvaginal oocyte retrieval,6 7 central venous catheter placement,7 herniorrhaphy,7 and electrical cardioversion.6
Used in conjunction with local or regional anesthesia for surgical procedures, including orthopedic (hip or knee arthoplasty),6 30 abdominal,6 or urologic6 surgery.
Produces less postoperative sedation, drowsiness, confusion, clumsiness, and nausea and a more rapid recovery of psychomotor performance than IV midazolam; however, midazolam has been associated with less pain at the injection site, less frequent oxygen requirements for decreased oxygen saturation, and more effective intraoperative amnesia.6 7 9 23 42 43 170 171 Quality of intraoperative sedation and time to discharge appear to be similar.6 7 23
Sedation in Critical Care Settings
Short-term sedation and control of stress responses in intubated and mechanically ventilated adults in a critical care setting1 2 5 33 34 35 36 37 39 40 41 47 69 132 133 135 when used alone or in combination with an opiate analgesic (e.g., morphine, fentanyl, hydromorphone) and/or peridural analgesia with local anesthetics.1 2 5 8 33 35 36 38 39 41 69 132 133 135 136 159 160 162
Some experts state that midazolam or diazepam should be used for rapid sedation in acutely agitated patients, while propofol is the preferred sedative when rapid awakening (e.g., for neurologic assessment or extubation) is important.136
Seizures
Has been used in patients with refractory status epilepticus†.4 17 48 49 134 137 168 169
Nausea and Vomiting
Has been used for the management of postoperative nausea and vomiting†.17 50
Has been used in combination with conventional antiemetics for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy†.17 51 52
Pruritus
Has been used effectively for relief of pruritus† associated with use of spinal opiates or with cholestasis.17 53 54 55 56
Misuse and Abuse
Abuse and dependence, sometimes resulting in death, have been reported.57 65 66 83 109 200 201 202 203 204 206 207 208 209 Most reports involved health-care professionals (principally anesthesiology personnel),57 109 201 202 203 204 209 but abuse by lay persons also reported.200 206 208 209
Currently not subject to control under the Federal Controlled Substances Act of 1970; however, some clinicians have suggested such control or some other means of ensuring greater accountability (e.g., restriction of access, drug accounting procedures, routine testing for propofol in drug screenings of at-risk individuals).1 65 67 83 194 204 205 Prevalence of abuse and related deaths appears to be greater at institutions with no established system to control or monitor propofol use.204 205
Propofol Dosage and Administration
Administration
IV Administration
Administer by IV infusion1 2 4 6 8 9 10 102 118 or IV injection.1 2 3 4 6 8 9 10 102 118
For IV infusion, use a controlled-infusion device (pump), preferably a volumetric pump.1 2 In patients undergoing magnetic resonance imaging (MRI), use metered controlled devices when mechanical pumps are not suitable.1 2
Use the larger veins of the forearm or antecubital fossa (rather than hand veins) in adults and children to minimize pain at the injection site; may also administer IV lidocaine prior to administration of propofol to minimize pain.1 2 144 (See Local Effects under Cautions.) Administer 1 mL of 1% lidocaine hydrochloride solution 30–120 seconds prior to propofol administration or add lidocaine to propofol immediately prior to administration in quantities not exceeding 20 mg of lidocaine hydrochloride per 200 mg of propofol.1 2 4 6 8 9 144 194
Transfer contents of the vial into a sterile, single-use syringe immediately after the vial is opened and after cleaning the rubber stopper with 70% isopropyl alcohol; use a sterile venting spike when withdrawing propofol from vials.1 2 7
Prepare propofol for single patient use only.1 194 Label syringes with appropriate information, including the date and time the vial was opened.1 194
Shake well just prior to administration.1 2
Clinical experience with use of inline filters for administration during general anesthesia, MAC sedation, or sedation in critical care settings is limited.1 2 An inline membrane filter may be used; however, the mean pore diameter of the filter should be ≥5 mcm unless it has been demonstrated that the filter does not restrict the flow and/or cause breakdown of the emulsion.1 2 11 Use filters with caution and only when clinically appropriate.1 194 Monitor continuously for restricted flow and breakdown of the emulsion.1 194
Stability and Sterility Considerations
For solution and drug compatibility, see Compatibility under Stability.
Manufacturers state that propofol should not be admixed with other therapeutic agents prior to administration.1 2 12 Do not administer through the same catheter as blood, serum, or plasma.1 2
Observe strict aseptic technique.1 2 3 Although commercially available preparations contain ingredients that retard growth of microorganisms (e.g., Diprivan contains edetate disodium 0.005%), the emulsion still may support growth of microorganisms.1 3 194 Do not use the emulsion if contamination is suspected.1 2 194
General anesthesia or MAC sedation: Start administration promptly and complete within 12 hours after opening the vials or syringes.1 2 7 194 Prepare propofol for use immediately prior to initiation of each individual anesthetic/sedative procedure.1 Discard any unused portion, reservoirs, dedicated administration tubing, and/or solutions containing propofol at the end of the anesthetic procedure or after 12 hours (whichever occurs sooner).1 194 FDA recommends completing administration from a single vial or syringe within 6 hours of opening when propofol is used for general anesthesia or procedural sedation (see Potential for Microbial Contamination under Cautions).195 Flush the IV line every 12 hours (one manufacturer recommends flushing with 5% dextrose)192 and at the end of the procedure to remove residual propofol emulsion.1 2 181 194
Sedation in critical care settings: Minimize manipulations of IV lines; start administration promptly and complete within 12 hours after inserting spike in vial.1 2 7 Use a sterile vent spike and sterile tubing.1 194 Discard any unused portion and the IV tubing at the end of the procedure or after 12 hours.1
Dilution
May administer as a 1% (10 mg/mL) emulsion without dilution.1 2
If dilution is necessary, the emulsion should be diluted only with 5% dextrose injection; concentration should be ≥0.2% (2 mg/mL) in order to maintain the emulsion.1 2 4 Discard if there is evidence of separation of the emulsion.1 2
Rate of Administration
Administer slowly to minimize adverse effects (e.g., hypotension, respiratory depression).1 2 (See Respiratory and Cardiovascular Effects under Cautions.)
For IV injection, administer in incremental doses.1 2 3 4 6 8 9 10 102 118 (See Dosage.)
Adjust rate of continuous IV infusions according to individual requirements.1 2 (See Dosage.) In the absence of clinical signs indicating light anesthesia and until a mild response to surgical stimulation develops, titrate infusion rate downward to avoid administration at rates higher than clinically necessary.1 2
Allow sufficient time between dosage adjustments for onset of peak response.1 2 (See Dosage.)
Dosage
Individual response to propofol is variable; therefore, adjust dosage (including infusion rate or amount and frequency of incremental doses) according to individual requirements and response, age, weight, clinical status (e.g., ASA physical status, degree of debilitation), blood lipid profile, underlying pathologic conditions (e.g., shock, intestinal obstruction, malnutrition, anemia, burns, advanced malignancy, ulcerative colitis, uremia, alcoholism), and type and amount of premedication or concomitant medication(s) used.1 2 118 Use the smallest effective dosage.1 2
Pediatric Patients
Induction and Maintenance of General Anesthesia
IV
Induction of anesthesia in children 3–16 years of age (following no premedication or premedication with oral benzodiazepines or IM opiate agonists): 2.5–3.5 mg/kg over 20–30 seconds in those with ASA physical status of I or II.1 2 Within this dosage range, younger patients may require higher induction dosages than older patients.1 2 A lower dosage is recommended for induction of anesthesia in patients with ASA physical status of III or IV.1 2
Maintenance of anesthesia in children 2 months to 16 years of age: Initially, 125–300 mcg/kg per minute (7.5–18 mg/kg per hour) administered concomitantly with inhaled 60–70% nitrous oxide and oxygen in those with ASA physical status of I or II.1 2 Dosage of 200–300 mcg/kg per minute may be required for the first 30 minutes after induction, then decrease dosage to 125–150 mcg/kg per minute (unless clinical signs of light anesthesia develop) by titration, according to the patient’s response.1 2 Within this dosage range, younger patients may require higher infusion rates than older patients.1 2
Adults
Induction and Maintenance of General Anesthesia
General Surgery
IV
Induction of anesthesia (following no premedication or premedication with oral benzodiazepines or IM opiate agonists) in adults <55 years of age with ASA physical status of I or II: 40 mg (2–2.5 mg/kg) every 10 seconds according to the patient’s response until the onset of induction.1 2
Maintenance of anesthesia in adults <55 years of age: Initially, 100–200 mcg/kg per minute (6–12 mg/kg per hour) administered concomitantly with inhaled 60–70% nitrous oxide and oxygen.1 2 Higher IV infusion rates of 150–200 mcg/kg per minute may be required for the first 10–15 minutes after induction, then decrease the infusion rate by 30–50% during the first 30 minutes of maintenance anesthesia.1 2
Alternatively, for maintenance of anesthesia in adults <55 years of age: 20–50 mg by intermittent IV injection in combination with inhaled nitrous oxide.1 2 192 Additional IV doses of 25–50 mg may be given, if necessary, as determined by clinical signs (increases in pulse rate, BP, sweating, and/or lacrimation) indicating a stress response to surgical stimulation or emergence from anesthesia.1 2 194
Cardiac Anesthesia
IV
Induction of anesthesia: 20 mg (0.5–1.5 mg/kg) every 10 seconds, administered by slow IV injection until the onset of induction.1 2 192 Dosage of 25 mcg/kg per minute may be used for management of anxiolysis prior to induction.1 2
Maintenance of anesthesia: 100–150 mcg/kg per minute as a continuous IV infusion when used as the primary agent and supplemented with a continuous infusion of an opiate agonist (e.g., alfentanil, fentanyl, sufentanil) administered to provide analgesia.1 2 Higher propofol dosages will reduce opiate analgesic dosage requirements.1 2
When an opiate agonist is used as the primary agent for maintenance of anesthesia, administer propofol at a rate of ≥50 mcg/kg per minute; ensure adequate amnesia.1 2 194
Neurosurgery
IV
Induction of anesthesia: 20 mg (1–2 mg/kg) every 10 seconds until the onset of induction.1 2
Maintenance of anesthesia: 100–200 mcg/kg per minute (6–12 mg/kg per hour).1 2
Monitored Anesthesia Care
IV
Initiation of MAC sedation in adults <55 years of age: Infusion of 100–150 mcg/kg per minute (6–9 mg/kg per hour) for 3–5 minutes; alternatively, injection of 0.5 mg/kg over 3–5 minutes.1 2 Slow rate of infusion or injection recommended to reduce the risk of apnea and hypotension.1 2
Maintenance dosage in adults <55 years of age: Infusion of 25–75 mcg/kg per minute (1.5–4.5 mg/kg per hour) for the first 10–15 minutes, then decrease the infusion rate to 25–50 mcg/kg per minute.1 2 Adjust dosage according to clinical effect, allowing approximately 2 minutes for onset of peak drug response.1 2
Alternatively, for maintenance therapy, administer intermittent IV injections of 10 or 20 mg; however, a variable-rate IV infusion is preferred.1 2 (See Monitored Anesthesia Care under Cautions.)1 2
In neurosurgical patients, reduce maintenance dosage by 20%.1 2 Rapid IV injection is not recommended in these patients because of an increased risk of adverse cardiorespiratory effects.1 2
Sedation in Critical Care Settings
IV
Initially, 5 mcg/kg per minute (0.3 mg/kg per hour) for ≥5 minutes in patients with residual effects from anesthetic or sedative drugs.1 2 5 Increase the infusion rate slowly in increments of 5–10 mcg/kg per minute (0.3–0.6 mg/kg per hour) over 5–10 minutes until desired sedation is achieved.1 2 5 Initiate and increase the infusion rate slowly in these patients to minimize the risk of hypotension or acute overdosage.1 2 5
For maintenance of sedation: 5–50 mcg/kg per minute (0.3–3 mg/kg per hour); higher maintenance infusion rates occasionally required.1 2 5 Rapid IV (“bolus”) administration of 10- or 20-mg doses may be used to rapidly increase depth of sedation in patients in whom development of hypotension is unlikely.1 2
Use the lowest effective dosage in patients with residual effects from anesthetic drugs or in those currently receiving other sedatives or opiates.1 2 181 192
Assess level of sedation and CNS function at regular intervals (at least daily during maintenance sedation); adjust infusion rate accordingly to ensure adequate titration of the sedation level.1 2 136 181 192
Do not administer Diprivan injectable emulsion as a continuous IV infusion for >5 days without a drug-free interval to allow replacement of estimated or measured urinary zinc losses.1 2 136 (See Edetate Disodium Content under Cautions.)
Some tolerance to the drug’s sedative effects may occur during long-term (>7 days) therapy; increasing the infusion rate may be necessary.5 64 However, such effects also may be associated with changes in drug elimination or an improved health status of the patient.64
Seizures†
Refractory Status Epilepticus†
IV
Initially, 1- to 2-mg/kg doses by IV injection over 5 minutes; repeat when seizure activity no longer is adequately controlled.4 137 Maintenance infusion of 2–10 mg/kg per hour; adjust the infusion rate until the lowest rate of infusion needed to suppress epileptiform activity is achieved.4 137 Gradually decrease the dosage to prevent withdrawal seizures.137
Nausea and Vomiting†
Postoperative Nausea and Vomiting†
IV
Doses of 10–15 mg have been used.17 50
Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy†
IV
Dosage of 1 mg/kg per hour as a continuous IV infusion has been used.17 51 52
Pruritus†
Pruritus Associated with Use of Spinal Opiates†
IV
Doses of 10 mg administered by direct IV injection have been used; alternatively, IV infusions of 0.5–1 mg/kg per hour have been used.17 53 54
Pruritus Associated With Cholestasis†
IV
Doses of 15 mg administered by direct IV injection have been used; alternatively, IV infusions of 1–1.5 mg/kg per hour have been used.17 53 54
Special Populations
Geriatric Patients (≥55 Years of Age), Debilitated Patients, and Patients with ASA Physical Status of III or IV
Induction and Maintenance of General Anesthesia
Induction of anesthesia: 20 mg (1–1.5 mg/kg) every 10 seconds according to the individual patient’s condition and response until the onset of induction.1 2
Maintenance of anesthesia: 50–100 mcg/kg per minute (3–6 mg/kg per hour) administered concomitantly with inhaled 60–70% nitrous oxide and oxygen.1 2
Monitored Anesthesia Care
Initiation of MAC sedation: Dosages similar to those for healthy adults are required.1 2 192
Maintenance of MAC sedation: Reduce dosage by 20%.1 2 Rapid IV injection is not recommended because of an increased risk of adverse cardiorespiratory effects.1 2
Cautions for Propofol
Contraindications
Known hypersensitivity to propofol or any ingredient in the formulation.1 194
Known hypersensitivity to eggs, egg products, soybeans, or soy products.1 194
Warnings/Precautions
Warnings
Respiratory and Cardiovascular Effects
Can depress respiration;1 2 5 6 8 9 apnea occurs frequently during induction of anesthesia.1 2 4 6 8 9 10 118
Cardiovascular depressant1 2 4 5 6 7 8 9 10 118 with effects greater than or equal to those associated with other IV anesthetic induction agents.6 8 9 10 118 The main adverse cardiovascular effect during induction of anesthesia is hypotension, with ≥30% decreases in systolic and diastolic BP.1 2 4 6 7 118
Patients with impaired myocardial function, intravascular volume depletion, or abnormally low vascular tone (sepsis) may be more susceptible to hypotension.1 2
Management of hypotension may include discontinuance of propofol, increasing the rate of IV fluid administration (except when additional fluid therapy is contraindicated), elevation of the lower extremities, and/or use of vasopressors.1 2
Possible bradycardia, asystole, and rarely, cardiac arrest, especially in pediatric patients receiving fentanyl concomitantly.1 2 (See Specific Drugs under Interactions.) Consider intervention with anticholinergic agents (e.g., atropine, glycopyrrolate) to modify potential increases in vagal tone associated with surgical stimuli or concomitant use of certain drugs (e.g., succinylcholine).1 2
Pulmonary edema reported rarely; causal relationship not established.1 2
Monitor sedated patients continuously for early signs of hypotension and bradycardia;1 2 194 also monitor for adverse respiratory effects (e.g., apnea, airway obstruction, oxyhemoglobin desaturation), especially in those undergoing MAC sedation.1 2 194
Cardiorespiratory effects are more likely to occur following administration of rapid IV (“bolus”) injections, especially in patients with ASA physical status of III or IV and in geriatric or debilitated patients.1 2 194 (See Special Populations under Dosage and Administration.)
Facilities necessary for intubation, assisted respiration, administration of oxygen, and cardiopulmonary resuscitation should be readily available.1 2 6 7 130 131 192
Supervised Administration
Should be administered for general anesthesia or MAC sedation only by individuals experienced in the use of general anesthesia who are not involved in the conduct of the surgical and/or diagnostic procedure.1 2 6 7 130 131
Should be administered for sedation of intubated, mechanically ventilated patients in critical care settings only by individuals qualified in the management of patients in these settings and trained in cardiovascular resuscitation and airway management.1 2 7 192
Potential for Microbial Contamination
Potential for microbial contamination of the injection and consequent development of fever, infection, sepsis, other life-threatening illness, or death with improper aseptic technique in handling propofol.1 2 103 194
Although commercially available preparations contain ingredients that retard growth of microorganisms, they are not considered antimicrobially preserved products by USP standards.1 103 194 Contamination of propofol with even very small numbers of microorganisms may result in clinical disease;197 strict aseptic technique and strict adherence to the manufacturer’s preparation and handling instructions are required.1 103 113 194 195 197 198 199 (See Stability and Sterility Considerations under Dosage and Administration.)
Do not use the emulsion if contamination is suspected; discard unused portions as recommended by the manufacturers.1 2 (See Stability and Sterility Considerations under Dosage and Administration.)
Several clusters of patients experiencing chills, fever, and body aches shortly after receiving propofol for sedation or general anesthesia reported.195 Symptoms developed 6–18 hours after propofol administration and lasted up to 3 days.195 Several patients were hospitalized and one experienced seizures; all patients recovered without apparent sequelae.195 Evaluate patients who develop these symptoms shortly after receiving propofol for bacterial sepsis and report such cases to the FDA MedWatch program.195
Specific lots of propofol (Teva) were recalled secondary to the presence of elevated endotoxin levels.196
Dependence, Tolerance, and Abuse
Dependence and abuse, sometimes resulting in death, have been reported.57 83 109 200 201 202 203 204 206 207 208 209 Most reported cases have involved health-care professionals (principally anesthesiology personnel),57 65 66 109 201 202 203 204 209 but abuse by lay persons also reported.200 206 208 209
Psychological dependence (e.g., intense craving for the drug, loss of control over amount and frequency of use) reported in cases of propofol abuse.57 200 202 206 207 Withdrawal symptoms (e.g., insomnia, anxiety, difficulty concentrating), suggesting physical dependence, observed rarely.202 Signs of tolerance also observed.109 200 206
Sensitivity Reactions
Sulfite Sensitivity
Some formulations contain sulfites that may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.2 163 194
Hypersensitivity Reactions
Anaphylactoid and/or anaphylactic reactions (e.g., angioedema, bronchospasm, erythema, hypotension) and flushing, possibly related to propofol, reported in <1% of adults undergoing anesthesia or MAC sedation with the drug; may be fatal or life-threatening.1 2 4 6 194
General Precautions
Local Effects
Pain at the injection site occurs in up to 70% of patients144 following peripheral IV administration.1 4 5 6 7 8 9 89 118 144 Thrombosis or phlebitis reported rarely.1 2
Pain, but no evidence of major sequelae, reported following inadvertent intra-arterial injection.1 2 8 118 Local pain, swelling, blisters and/or tissue necrosis reported rarely following inadvertent extravasation.1 2
To minimize pain at the injection site, use the larger veins of the forearm or antecubital fossa rather than hand veins; may also administer lidocaine prior to IV administration of propofol1 2 4 6 8 9 144 (see IV Administration under Dosage and Administration). Other methods have been used: prior administration of opiates or metoclopramide, prior application of a tourniquet, topical nitroglycerin or a local anesthetic cream, or administration of propofol at low temperatures (4–5°C).6
Metabolic Effects
Propofol infusion syndrome reported in patients receiving propofol for sedation in a critical care setting.1 194 211 Characterized by severe metabolic acidosis, hyperkalemia, lipidemia, rhabdomyolysis, hepatomegaly, and cardiac, renal, or circulatory failure.1 194 211 Occurs most frequently in patients receiving prolonged, high-dose infusions (>5 mg/kg per hour for >48 hours) but has occurred following short-term, high-dose infusions during surgical anesthesia.1 194 211
Closely monitor patients for development of unexplained acidosis, rhabdomyolysis, and cardiac or renal failure.211 Consider alternate means of sedation in the setting of prolonged need for sedation, increasing propofol dosage requirements to maintain a constant level of sedation, or onset of metabolic acidosis during propofol infusion.1 194
Effects on Lipids
Commercial propofol preparations are oil-in-water emulsions; use with caution in patients with disorders of lipid metabolism (e.g., primary hyperlipoproteinemia, diabetic hyperlipemia, pancreatitis).1 2
Prolonged administration may result in increased serum lipid concentrations (e.g., hypertriglyceridemia); monitor patients undergoing sedation in a critical care setting who are at risk of developing hyperlipidemia for increases in serum triglyceride concentrations or serum turbidity.1 2
Reduce the quantity of concurrently administered lipids (e.g., fat emulsions for parenteral nutrition) in these patients in order to compensate for the amount of lipids contained in the propofol formulation (1 mL of propofol injectable emulsion contains 0.1 g of fat [1.1 kcal]).1 2
Edetate Disodium Content
Certain formulations (Diprivan) contain 0.005% of edetate disodium, a heavy metal antagonist that can chelate many divalent and trivalent cations.1 136
Patients receiving continuous infusions for sedation in critical care settings should not receive formulations containing edetate disodium for >5 days without a drug-free interval to allow replacement of estimated or measured urinary zinc losses.1
In patients who are predisposed to zinc deficiency
