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The Medicines Company Drugs
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![Cleviprex (Clevidipine) Emulsion [The Medicines Company]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=095081a0-1398-11dc-82e1-0002a5d5c51b&name=cleviprex-figure-10.jpg)
Cleviprex
2.1 Monitoring
Monitor blood pressure and heart rate continually during infusion, and then until vital signs are stable. Patients who receive prolonged Cleviprex infusions and are not transitioned to other antihypertensive therapies should be monitored for the possibility of rebound hypertension for at least 8 hours after the infusion is stopped. These patients may need follow-up adjustments in blood pressure control.
2.2 Recommended Dosing
Cleviprex is intended for intravenous use. Titrate drug to achieve the desired blood pressure reduction. Individualize dosage depending on the blood pressure to be obtained and the response of the patient.
Initial dose: Initiate the intravenous infusion of Cleviprex at 1-2 mg/hour.
Dose titration: The dose may be doubled at short (90 second) intervals initially. As the blood pressure approaches goal, the increase in doses should be less than doubling and the time between dose adjustments should be lengthened to every 5-10 minutes. An approximately 1-2 mg/hour increase will generally produce an additional 2-4 mmHg decrease in systolic pressure.
Maintenance dose: The desired therapeutic response for most patients occurs at doses of 4-6 mg/hour. Patients with severe hypertension may require doses up to 32 mg/hour, but there is limited experience at this dose rate.
Maximum dose: Most patients were treated with maximum doses of 16 mg/hour or less.There is limited short-term experience with doses up to 32 mg/hour. Because of lipid load restrictions, no more than 1000 mL or an average of 21 mg/hour of Cleviprex infusion is recommended per 24 hour period. In clinical trials, 55 hypertensive patients were treated with >500mL of Cleviprex infusion per 24 hour period. There is little experience with infusion durations beyond 72 hours at any dose.
Transition to an oral antihypertensive agent: Discontinue Cleviprex or titrate downward while appropriate oral therapy is established. When an oral antihypertensive agent is being instituted, consider the lag time of onset of the oral agent’s effect. Continue blood pressure monitoring until desired effect is achieved.
Special populations: Special populations were not specifically studied. In clinical trials, 78 patients with abnormal hepatic function (one or more of the following: elevated serum bilirubin, AST/SGOT, ALT/SGPT) and 121 patients with moderate to severe renal impairment were treated with Cleviprex. An initial Cleviprex infusion rate of 1-2 mg/hour is appropriate in these patients.
Table 1 is a guideline for dosing conversion from mg/hour to mL/hour.
Table 1. Dose conversion Dose (mg/hour) Dose (mL/hour) 1 2 2 4 4 8 6 12 8 16 10 20 12 24 14 28 16 32 18 36 20 40 22 44 24 48 26 52 28 56 30 60 32 642.3 Instructions for Administration
Maintain aseptic technique while handling Cleviprex. Cleviprex is a single-use parenteral product. Do not use if contamination is suspected. Once the stopper is punctured, use within 12 hours and discard any unused portion.
Cleviprex is supplied in sterile, pre-mixed, ready-to-use 50 mL, or 100 mL, or 250 mL vials. Invert vial gently several times before use to ensure uniformity of the emulsion prior to administration. Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. Administer Cleviprex using an infusion device allowing calibrated infusion rates. Commercially available standard plastic cannulae may be used to administer the infusion. Administer Cleviprex by a central line or a peripheral line.
Cleviprex should not be administered in the same line as other medications.
Cleviprex should not be diluted, but it can be administered with the following:
Water for Injection, USP Sodium Chloride (0.9%) Injection, USP Dextrose (5%) Injection, USP Dextrose (5%) in Sodium Chloride (0.9%) Injection, USP Dextrose (5%) in Ringers Lactate Injection, USP Lactated Ringers Injection, USP 10% amino acid -
![Ondansetron (Ondansetron Hydrochloride) Injection [The Medicines Company]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=dc3dc0e4-b7da-4da4-afa6-d57e4ee42339&name=ondansetron-injection-usp-figure-3-MC370302-vial.jpg)
Ondansetron
Prevention of Chemotherapy-Induced Nausea and Vomiting
Adult Dosing:
The recommended IV dosage of Ondansetron Injection for adults is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. The recommended infusion rate should not be exceeded (see OVERDOSAGE). With the three-dose (0.15 mg/kg) regimen, the first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Ondansetron Injection.
Ondansetron Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.
DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY–INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.
Pediatric Dosing:
On the basis of the available information (see CLINICAL TRIALS: Pediatric Studies and CLINICAL PHARMACOLOGY: Pharmacokinetics), the dosage in pediatric cancer patients 6 months to 18 years of age should be three 0.15 mg/kg doses. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy, subsequent doses (0.15 mg/kg are administered 4 and 8 hours after the first dose of ondansetron injection. The drug should be infused intravenously over 15 minutes. Little information is available about dosage in pediatric cancer patients younger than 6 months of age.
DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY - INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.
Geriatric Dosing:
The dosage recommendation is the same as for the general population.
Prevention of Postoperative Nausea and Vomiting
Adult Dosing:
The recommended IV dosage of Ondansetron Injection for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, IV dose of ondansetron 4 mg, administration of a second IV dose of 4 mg ondansetron postoperatively does not provide additional control of nausea and vomiting.
REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.
Pediatric Dosing:
The recommended IV dosage of Ondansetron Injection for pediatric surgical patients (1 month to 12 years of age) is a single 0.1 mg/kg dose for patients weighing 40 kg or less, or a single 4 mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic ondansetron injection.
REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.
Geriatric Dosing:
The dosage recommendation is the same as for the general population.
Dosage Adjustments for Patients With Impaired Renal Function
The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.
Dosage Adjustment for Patients With Impaired Hepatic Function
In patients with severe hepatic impairment (Child- Pugh2 score of 10 or greater), a single maximal daily dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron.
Prevention of Chemotherapy-Induced Nausea and Vomiting
Adult Dosing:
The recommended IV dosage of Ondansetron Injection for adults is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. The recommended infusion rate should not be exceeded (see OVERDOSAGE). With the three-dose (0.15 mg/kg) regimen, the first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Ondansetron Injection.
Ondansetron Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.
DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY–INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.
Pediatric Dosing:
On the basis of the available information (see CLINICAL TRIALS: Pediatric Studies and CLINICAL PHARMACOLOGY: Pharmacokinetics), the dosage in pediatric cancer patients 6 months to 18 years of age should be three 0.15 mg/kg doses. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy, subsequent doses (0.15 mg/kg are administered 4 and 8 hours after the first dose of ondansetron injection. The drug should be infused intravenously over 15 minutes. Little information is available about dosage in pediatric cancer patients younger than 6 months of age.
DILUTE BEFORE USE FOR PREVENTION OF CHEMOTHERAPY - INDUCED NAUSEA AND VOMITING. Ondansetron Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.
Geriatric Dosing:
The dosage recommendation is the same as for the general population.
Prevention of Postoperative Nausea and Vomiting
Adult Dosing:
The recommended IV dosage of Ondansetron Injection for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, IV dose of ondansetron 4 mg, administration of a second IV dose of 4 mg ondansetron postoperatively does not provide additional control of nausea and vomiting.
REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.
Pediatric Dosing:
The recommended IV dosage of Ondansetron Injection for pediatric surgical patients (1 month to 12 years of age) is a single 0.1 mg/kg dose for patients weighing 40 kg or less, or a single 4 mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic ondansetron injection.
REQUIRES NO DILUTION FOR ADMINISTRATION FOR POSTOPERATIVE NAUSEA AND VOMITING.
Geriatric Dosing:
The dosage recommendation is the same as for the general population.
Dosage Adjustments for Patients With Impaired Renal Function
The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.
Dosage Adjustment for Patients With Impaired Hepatic Function
In patients with severe hepatic impairment (Child- Pugh2 score of 10 or greater), a single maximal daily dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron.
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![Midazolam (Midazolam Hydrochloride) Injection, Solution [The Medicines Company]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=ccf2b7bd-b282-420e-b929-bf82384ab4a7&name=midazolam-injection-usp-figure-10-MC410110-vial.jpg)
Midazolam
Midazolam injection is a potent sedative agent that requires slow administration and individualization of dosage. Clinical experience has shown midazolam to be 3 to 4 times as potent per mg as diazepam. BECAUSE SERIOUS AND LIFE-THREATENING CARDIORESPIRATORY ADVERSE EVENTS HAVE BEEN REPORTED, PROVISION FOR MONITORING, DETECTION AND CORRECTION OF THESE REACTIONS MUST BE MADE FOR EVERY PATIENT TO WHOM MIDAZOLAM INJECTION IS ADMINISTERED, REGARDLESS OF AGE OR HEALTH STATUS. Excessive single doses or rapid intravenous administration may result in respiratory depression, airway obstruction and/or arrest. The potential for these latter effects is increased in debilitated patients, those receiving concomitant medications capable of depressing the CNS, and patients without an endotracheal tube but undergoing a procedure involving the upper airway such as endoscopy or dental (see BOXED WARNING and WARNINGS).
Reactions such as agitation, involuntary movements, hyperactivity and combativeness have been reported in adult and pediatric patients. Should such reactions occur, caution should be exercised before continuing administration of midazolam (see WARNINGS).
Midazolam injection should only be administered IM or IV (see WARNINGS).
Care should be taken to avoid intra-arterial injection or extravasation (see WARNINGS).
Midazolam injection may be mixed in the same syringe with the following frequently used premedications: morphine sulfate, meperidine, atropine sulfate or scopolamine. Midazolam, at a concentration of 0.5 mg/mL, is compatible with 5% dextrose in water and 0.9% sodium chloride for up to 24 hours and with lactated Ringer’s solution for up to 4 hours. Both the 1 mg/mL and 5 mg/mL formulations of midazolam may be diluted with 0.9% sodium chloride or 5% dextrose in water.
Monitoring
Patient response to sedative agents, and resultant respiratory status, is variable. Regardless of the intended level of sedation or route of administration, sedation is a continuum; a patient may move easily from light to deep sedation, with potential loss of protective reflexes. This is especially true in pediatric patients. Sedative doses should be individually titrated, taking into account patient age, clinical status and concomitant use of other CNS depressants. Continuous monitoring of respiratory and cardiac function is required (ie, pulse oximetry).
Adults and Pediatrics: Sedation guidelines recommend a careful presedation history to determine how a patient’s underlying medical conditions or concomitant medications might affect their response to sedation/analgesia as well as physical examination including a focused examination of the airway for abnormalities. Further recommendations include appropriate presedation fasting.
Titration to effect with multiple small doses is essential for safe administration. It should be noted that adequate time to achieve peak central nervous system effect (3 to 5 minutes) for midazolam should be allowed between doses to minimize the potential for oversedation. Sufficient time must elapse between doses of concomitant sedative medications to allow the effect of each dose to be assessed before subsequent drug administration. This is an important consideration for all patients who receive intravenous midazolam.
Immediate availability of resuscitative drugs and age- and size-appropriate equipment and personnel trained in their use and skilled in airway management should be assured (see WARNINGS).
Pediatrics: For deeply sedated pediatric patients a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure.
Intravenous access is not thought to be necessary for all pediatric patients sedated for a diagnostic or therapeutic procedure because in some cases the difficulty of gaining IV access would defeat the purpose of sedating the child; rather, emphasis should be placed upon having the intravenous equipment available and a practitioner skilled in establishing vascular access in pediatric patients immediately available.
Monitoring
Patient response to sedative agents, and resultant respiratory status, is variable. Regardless of the intended level of sedation or route of administration, sedation is a continuum; a patient may move easily from light to deep sedation, with potential loss of protective reflexes. This is especially true in pediatric patients. Sedative doses should be individually titrated, taking into account patient age, clinical status and concomitant use of other CNS depressants. Continuous monitoring of respiratory and cardiac function is required (ie, pulse oximetry).
Adults and Pediatrics: Sedation guidelines recommend a careful presedation history to determine how a patient’s underlying medical conditions or concomitant medications might affect their response to sedation/analgesia as well as physical examination including a focused examination of the airway for abnormalities. Further recommendations include appropriate presedation fasting.
Titration to effect with multiple small doses is essential for safe administration. It should be noted that adequate time to achieve peak central nervous system effect (3 to 5 minutes) for midazolam should be allowed between doses to minimize the potential for oversedation. Sufficient time must elapse between doses of concomitant sedative medications to allow the effect of each dose to be assessed before subsequent drug administration. This is an important consideration for all patients who receive intravenous midazolam.
Immediate availability of resuscitative drugs and age- and size-appropriate equipment and personnel trained in their use and skilled in airway management should be assured (see WARNINGS).
Pediatrics: For deeply sedated pediatric patients a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure.
Intravenous access is not thought to be necessary for all pediatric patients sedated for a diagnostic or therapeutic procedure because in some cases the difficulty of gaining IV access would defeat the purpose of sedating the child; rather, emphasis should be placed upon having the intravenous equipment available and a practitioner skilled in establishing vascular access in pediatric patients immediately available.
Continous Intravenous Infusion
Usual Pediatric Dose (Non-Neonatal)
For sedation/anxiolysis/ amnesia in critical care settings.
To initiate sedation, an intravenous loading dose of 0.05 to 0.2 mg/kg administered over at least 2 to 3 minutes can be used to establish the desired clinical effect IN PATIENTS WHOSE TRACHEA IS INTUBATED. (Midazolam should not be administered as a rapid intravenous dose.) This loading dose may be followed by a continuous intravenous infusion to maintain the effect. An infusion of midazolam has been used in patients whose trachea was intubated but who were allowed to breathe spontaneously. Assisted ventilation is recommended for pediatric patients who are receiving other central nervous system depressant medications such as opioids. Based on pharmacokinetic parameters and reported clinical experience, continuous intravenous infusions of midazolam should be initiated at a rate of 0.06 to 0.12 mg/kg/hr (1 to 2 mcg/kg/min). The rate of infusion can be increased or decreased (generally by 25% of the initial or subsequent infusion rate) as required, or supplemental intravenous doses of midazolam can be administered to increase or maintain the desired effect. Frequent assessment at regular intervals using standard pain/sedation scales is recommended. Drug elimination may be delayed in patients receiving erythromycin and/or other P450 3A4 enzyme inhibitors (see PRECAUTIONS: Drug Interactions) and in patients with liver dysfunction, low cardiac output (especially those requiring inotropic support), and in neonates. Hypotension may be observed in patients who are critically ill, particularly those receiving opioids and/or when midazolam is rapidly administered.
When initiating an infusion with midazolam in hemodynamically compromised patients, the usual loading dose of midazolam should be titrated in small increments and the patient monitored for hemodynamic instability (eg, hypotension). These patients are also vulnerable to the respiratory depressant effects of midazolam and require careful monitoring of respiratory rate and oxygen saturation.
Continous Intravenous Infusion
For sedation in critical care setting.
Usual Neonatal Dose
Based on pharmacokinetic parameters and reported clinical experience in preterm and term neonates WHOSE TRACHEA WAS INTUBATED, continuous intravenous infusions of midazolam injection should be initiated at a rate of 0.03 mg/kg/hr (0.5 mcg/kg/min) in neonates <32 weeks and 0.06 mg/kg/hr (1 mcg/kg/min) in neonates >32 weeks. Intravenous loading doses should not be used in neonates, rather the infusion may be run more rapidly for the first several hours to establish therapeutic plasma levels. The rate of infusion should be carefully and frequently reassessed, particularly after the first 24 hours so as to administer the lowest possible effective dose and reduce the potential for drug accumulation. This is particularly important because of the potential for adverse effects related to metabolism of the benzyl alcohol (see WARNINGS: Usage in Preterm Infants and Neonates). Hypotension may be observed in patients who are critically ill and in preterm and term infants, particularly those receiving fentanyl and/or when midazolam is administered rapidly. Due to an increased risk of apnea, extreme caution is advised when sedating preterm and former preterm patients whose trachea is not intubated.
Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
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![Rocuronium (Rocuronium Bromide) Injection, Solution [The Medicines Company]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=6ec8c417-6613-45e0-bc86-293a8b1ee83f&name=rocuronium-bromide-injection-figure-10-MC402610-tray.jpg)
Rocuronium
Rocuronium Bromide Injection is for intravenous use only. This drug should only be administered by experienced clinicians or trained individuals supervised by an experienced clinician familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents. Doses of Rocuronium Bromide Injection should be individualized and a peripheral nerve stimulator should be used to monitor drug effect, need for additional doses, adequacy of spontaneous recovery or antagonism, and to decrease the complications of overdosage if additional doses are administered.
The dosage information which follows is derived from studies based upon units of drug per unit of body weight. It is intended to serve as an initial guide to clinicians familiar with other neuromuscular blocking agents to acquire experience with Rocuronium Bromide Injection.
In patients in whom potentiation of, or resistance to, neuromuscular block is anticipated, a dose adjustment should be considered [see Dosage and Administration (2.5), Warnings and Precautions (5.9, 5.12), Drug Interactions (7.2, 7.3, 7.4, 7.5, 7.6, 7.8, 7.10) , and Use in Specific Populations (8.6)].
2.1 Dose for Tracheal Intubation
The recommended initial dose of Rocuronium Bromide Injection, regardless of anesthetic technique, is 0.6 mg/kg. Neuromuscular block sufficient for intubation (80% block or greater) is attained in a median (range) time of 1 (0.4 to 6) minute(s) and most patients have intubation completed within 2 minutes. Maximum blockade is achieved in most patients in less than 3 minutes. This dose may be expected to provide 31 (15 to 85) minutes of clinical relaxation under opioid/nitrous oxide/oxygen anesthesia. Under halothane, isoflurane, and enflurane anesthesia, some extension of the period of clinical relaxation should be expected [see Drug Interactions (7.3)].
A lower dose of Rocuronium Bromide Injection (0.45 mg/kg) may be used. Neuromuscular block sufficient for intubation (80% block or greater) is attained in a median (range) time of 1.3 (0.8 to 6.2) minute(s), and most patients have intubation completed within 2 minutes. Maximum blockade is achieved in most patients in less than 4 minutes. This dose may be expected to provide 22 (12 to 31) minutes of clinical relaxation under opioid/nitrous oxide/oxygen anesthesia. Patients receiving this low dose of 0.45 mg/kg who achieve less than 90% block (about 16% of these patients) may have a more rapid time to 25% recovery, 12 to 15 minutes.
A large bolus dose of 0.9 or 1.2 mg/kg can be administered under opioid/nitrous oxide/oxygen anesthesia without adverse effects to the cardiovascular system [see Clinical Pharmacology (12.2)].
2.2 Rapid Sequence Intubation
In appropriately premedicated and adequately anesthetized patients, Rocuronium Bromide Injection 0.6 to 1.2 mg/kg will provide excellent or good intubating conditions in most patients in less than 2 minutes [see Clinical Studies (14.1)].
2.3 Maintenance Dosing
Maintenance doses of 0.1, 0.15, and 0.2 mg/kg Rocuronium Bromide Injection, administered at 25% recovery of control T1 (defined as 3 twitches of train-of-four), provide a median (range) of 12 (2 to 31), 17 (6 to 50), and 24 (7 to 69) minutes of clinical duration under opioid/nitrous oxide/oxygen anesthesia [see Clinical Pharmacology (12.2)]. In all cases, dosing should be guided based on the clinical duration following initial dose or prior maintenance dose and not administered until recovery of neuromuscular function is evident. A clinically insignificant cumulation of effect with repetitive maintenance dosing has been observed [see Clinical Pharmacology (12.2)].
2.4 Use by Continuous Infusion
Infusion at an initial rate of 10 to 12 mcg/kg/min of Rocuronium Bromide Injection should be initiated only after early evidence of spontaneous recovery from an intubating dose. Due to rapid redistribution [see Clinical Pharmacology (12.3)] and the associated rapid spontaneous recovery, initiation of the infusion after substantial return of neuromuscular function (more than 10% of control T1) may necessitate additional bolus doses to maintain adequate block for surgery.
Upon reaching the desired level of neuromuscular block, the infusion of Rocuronium Bromide Injection must be individualized for each patient. The rate of administration should be adjusted according to the patient’s twitch response as monitored with the use of a peripheral nerve stimulator. In clinical trials, infusion rates have ranged from 4 to 16 mcg/kg/min.
Inhalation anesthetics, particularly enflurane and isoflurane, may enhance the neuromuscular blocking action of nondepolarizing muscle relaxants. In the presence of steady-state concentrations of enflurane or isoflurane, it may be necessary to reduce the rate of infusion by 30% to 50%, at 45 to 60 minutes after the intubating dose.
Spontaneous recovery and reversal of neuromuscular blockade following discontinuation of rocuronium bromide infusion may be expected to proceed at rates comparable to that following comparable total doses administered by repetitive bolus injections [see Clinical Pharmacology (12.2)].
Infusion solutions of Rocuronium Bromide Injection can be prepared by mixing Rocuronium Bromide Injection with an appropriate infusion solution such as 5% glucose in water or lactated Ringers [see Dosage and Administration (2.6)]. These infusion solutions should be used within 24 hours of mixing. Unused portions of infusion solutions should be discarded.
Infusion rates of Rocuronium Bromide Injection can be individualized for each patient using the following tables for 3 different concentrations of rocuronium bromide solution as guidelines:
TABLE 1: Infusion Rates Using Rocuronium Bromide Injection (0.5 mg/mL)*
Patient
Weight
Drug Delivery Rate (mcg/kg/min)
(kg)
(lbs)
4
5
6
7
8
9
10
12
14
16
Infusion Delivery Rate (mL/hr)
10
22
4.8
6
7.2
8.4
9.6
10.8
12
14.4
16.8
19.2
15
33
7.2
9
10.8
12.6
14.4
16.2
18
21.6
25.2
28.8
20
44
9.6
12
14.4
16.8
19.2
21.6
24
28.8
33.6
38.4
25
55
12
15
18
21
24
27
30
36
42
48
35
77
16.8
21
25.2
29.4
33.6
37.8
42
50.4
58.8
67.2
50
110
24
30
36
42
48
54
60
72
84
96
60
132
28.8
36
43.2
50.4
57.6
64.8
72
86.4
100.8
115.2
70
154
33.6
42
50.4
58.8
67.2
75.6
84
100.8
117.6
134.4
80
176
38.4
48
57.6
67.2
76.8
86.4
96
115.2
134.4
153.6
90
198
43.2
54
64.8
75.6
86.4
97.2
108
129.6
151.2
172.8
100
220
48
60
72
84
96
108
120
144
168
192
* 50 mg Rocuronium Bromide Injection in 100 mL solution
TABLE 2: Infusion Rates Using Rocuronium Bromide Injection (1 mg/mL)*
Patient
Weight
Drug Delivery Rate (mcg/kg/min)
(kg)
(lbs)
4
5
6
7
8
9
10
12
14
16
Infusion Delivery Rate (mL/hr)
10
22
2.4
3
3.6
4.2
4.8
5.4
6
7.2
8.4
9.6
15
33
3.6
4.5
5.4
6.3
7.2
8.1
9
10.8
12.6
14.4
20
44
4.8
6
7.2
8.4
9.6
10.8
12
14.4
16.8
19.2
25
55
6
7.5
9
10.5
12
13.5
15
18
21
24
35
77
8.4
10.5
12.6
14.7
16.8
18.9
21
25.2
29.4
33.6
50
110
12
15
18
21
24
27
30
36
42
48
60
132
14.4
18
21.6
25.2
28.8
32.4
36
43.2
50.4
57.6
70
154
16.8
21
25.2
29.4
33.6
37.8
42
50.4
58.8
67.2
80
176
19.2
24
28.8
33.6
38.4
43.2
48
57.6
67.2
76.8
90
198
21.6
27
32.4
37.8
43.2
48.6
54
64.8
75.6
86.4
100
220
24
30
36
42
48
54
60
72
84
96
* 100 mg Rocuronium Bromide Injection in 100 mL solution
TABLE 3: Infusion Rates Using Rocuronium Bromide Injection (5 mg/mL)*
Patient
Weight
Drug Delivery Rate (mcg/kg/min)
(kg)
(lbs)
4
5
6
7
8
9
10
12
14
16
Infusion Delivery Rate (mL/hr)
10
22
0.5
0.6
0.7
0.8
1
1.1
1.2
1.4
1.7
1.9
15
33
0.7
0.9
1.1
1.3
1.4
1.6
1.8
2.2
2.5
2.9
20
44
1
1.2
1.4
1.7
1.9
2.2
2.4
2.9
3.4
3.8
25
55
1.2
1.5
1.8
2.1
2.4
2.7
3
3.6
4.2
4.8
35
77
1.7
2.1
2.5
2.9
3.4
3.8
4.2
5
5.9
6.7
50
110
2.4
3
3.6
4.2
4.8
5.4
6
7.2
8.4
9.6
60
132
2.9
3.6
4.3
5
5.8
6.5
7.2
8.6
10.1
11.5
70
154
3.4
4.2
5
5.9
6.7
7.6
8.4
10.1
11.8
13.4
80
176
3.8
4.8
5.8
6.7
7.7
8.6
9.6
11.5
13.4
15.4
90
198
4.3
5.4
6.5
7.6
8.6
9.7
10.8
13
15.1
17.3
100
220
4.8
6
7.2
8.4
9.6
10.8
12
14.4
16.8
19.2
* 500 mg Rocuronium Bromide Injection in 100 mL solution
2.5 Dosage in Specific Populations
Pediatric Patients:
The recommended initial intubation dose of Rocuronium Bromide Injection is 0.6 mg/kg; however, a lower dose of 0.45 mg/kg may be used depending on anesthetic technique and the age of the patient.
For sevoflurane (induction) Rocuronium Bromide Injection doses of 0.45 mg/kg and 0.6 mg/kg in general produce excellent to good intubating conditions within 75 seconds. When halothane is used, a 0.6 mg/kg dose of Rocuronium Bromide Injection resulted in excellent to good intubating conditions within 60 seconds.
The time to maximum block for an intubating dose was shortest in infants (28 days up to 3 months) and longest in neonates (birth to less than 28 days). The duration of clinical relaxation following an intubating dose is shortest in children (greater than 2 years up to 11 years) and longest in infants.
When sevoflurane is used for induction and isoflurane/nitrous oxide for maintenance of general anesthesia, maintenance dosing of Rocuronium Bromide Injection can be administered as bolus doses of 0.15 mg/kg at reappearance of T3 in all pediatric age groups. Maintenance dosing can also be administered at the reappearance of T2 at a rate of 7 to 10 mcg/kg/min, with the lowest dose requirement for neonates (birth to less than 28 days) and the highest dose requirement for children (greater than 2 years up to 11 years).
When halothane is used for general anesthesia, patients ranging from 3 months old through adolescence can be administered Rocuronium Bromide Injection maintenance doses of 0.075 to 0.125 mg/kg upon return of T1 to 0.25% to provide clinical relaxation for 7 to 10 minutes. Alternatively, a continuous infusion of Rocuronium Bromide Injection initiated at a rate of 12 mcg/kg/min upon return of T1 to 10% (one twitch present in train-of-four) may also be used to maintain neuromuscular blockade in pediatric patients.
Additional information for administration to pediatric patients of all age groups is presented elsewhere in the label [see Clinical Pharmacology (12.2)].
The infusion of Rocuronium Bromide Injection must be individualized for each patient. The rate of administration should be adjusted according to the patient’s twitch response as monitored with the use of a peripheral nerve stimulator. Spontaneous recovery and reversal of neuromuscular blockade following discontinuation of rocuronium bromide infusion may be expected to proceed at rates comparable to that following similar total exposure to single bolus doses [see Clinical Pharmacology (12.2)].
Rocuronium Bromide Injection is not recommended for rapid sequence intubation in pediatric patients.
Geriatric Patients:
Geriatric patients (65 years or older) exhibited a slightly prolonged median (range) clinical duration of 46 (22 to 73), 62 (49 to 75), and 94 (64 to 138) minutes under opioid/nitrous oxide/oxygen anesthesia following doses of 0.6, 0.9, and 1.2 mg/kg, respectively. No differences in duration of neuromuscular blockade following maintenance doses of Rocuronium Bromide Injection were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.2, 12.3)].
Patients with Renal or Hepatic Impairment:
No differences from patients with normal hepatic and kidney function were observed for onset time at a dose of 0.6 mg/kg Rocuronium Bromide Injection. When compared to patients with normal renal and hepatic function, the mean clinical duration is similar in patients with end-stage renal disease undergoing renal transplant, and is about 1.5 times longer in patients with hepatic disease. Patients with renal failure may have a greater variation in duration of effect [see Use in Specific Populations (8.6, 8.7) and Clinical Pharmacology (12.3)].
Obese Patients:
In obese patients, the initial dose of Rocuronium Bromide Injection 0.6 mg/kg should be based upon the patient’s actual body weight [see Clinical Studies (14.1)].
An analysis across all US controlled clinical studies indicates that the pharmacodynamics of Rocuronium Bromide Injection are not different between obese and nonobese patients when dosed based upon their actual body weight.
Patients with Reduced Plasma Cholinesterase Activity:
Rocuronium metabolism does not depend on plasma cholinesterase so dosing adjustments are not needed in patients with reduced plasma cholinesterase activity.
Patients with Prolonged Circulation Time:
Because higher doses of Rocuronium Bromide Injection produce a longer duration of action, the initial dosage should usually not be increased in these patients to reduce onset time; instead, in these situations, when feasible, more time should be allowed for the drug to achieve onset of effect [see Warnings and Precautions (5.7)].
Patients with Drugs or Conditions Causing Potentiation of Neuromuscular Block:
The neuromuscular blocking action of Rocuronium Bromide Injection is potentiated by isoflurane and enflurane anesthesia. Potentiation is minimal when administration of the recommended dose of Rocuronium Bromide Injection occurs prior to the administration of these potent inhalation agents. The median clinical duration of a dose of 0.57 to 0.85 mg/kg was 34, 38, and 42 minutes under opioid/nitrous oxide/oxygen, enflurane and isoflurane maintenance anesthesia, respectively. During 1 to 2 hours of infusion, the infusion rate of Rocuronium Bromide Injection required to maintain about 95% block was decreased by as much as 40% under enflurane and isoflurane anesthesia [see Drug Interactions (7.3)].
2.6 Preparation for Administration of Rocuronium Bromide Injection
Diluent Compatibility:
Rocuronium Bromide Injection is compatible in solution with:
0.9% NaCl solution sterile water for injection
5% glucose in water lactated Ringers
5% glucose in saline
Rocuronium Bromide Injection is compatible in the above solutions at concentrations up to 5 mg/mL for 24 hours at room temperature in plastic bags, glass bottles, and plastic syringe pumps.
Drug Admixture Incompatibility:
Rocuronium Bromide Injection is physically incompatible when mixed with the following drugs:
amphotericin hydrocortisone sodium succinate
amoxicillin insulin
azathioprine intralipid
cefazolin ketorolac
cloxacillin lorazepam
dexamethasone methohexital
diazepam methylprednisolone
erythromycin thiopental
famotidine trimethoprim
furosemide vancomycin
If Rocuronium Bromide Injection is administered via the same infusion line that is also used for other drugs, it is important that this infusion line is adequately flushed between administration of Rocuronium Bromide Injection and drugs for which incompatibility with Rocuronium Bromide Injection has been demonstrated or for which compatibility with Rocuronium Bromide Injection has not been established.
Infusion solutions should be used within 24 hours of mixing. Unused portions of infusion solutions should be discarded.
Rocuronium Bromide Injection should not be mixed with alkaline solutions [see Warnings and Precautions (5.10)].
Visual Inspection:
Parenteral drug products should be inspected visually for particulate matter and clarity prior to administration whenever solution and container permit. Do not use solution if particulate matter is present.
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![Angiomax (Bivalirudin) Injection, Powder, Lyophilized, For Solution [The Medicines Company]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=911cd48f-01ea-4dec-b30c-95e7e0ea9d2a&name=angiomax-02.jpg)
Angiomax
2.1 Recommended Dose
Angiomax is for intravenous administration only.
Angiomax is intended for use with aspirin (300-325 mg daily) and has been studied only in patients receiving concomitant aspirin.
For patients who do not have HIT/HITTS
The recommended dose of Angiomax is an intravenous (IV) bolus dose of 0.75 mg/kg, followed by an infusion of 1.75 mg/kg/h for the duration of the PCI/PTCA procedure. Five min after the bolus dose has been administered, an activated clotting time (ACT) should be performed and an additional bolus of 0.3 mg/kg should be given if needed.
GPI administration should be considered in the event that any of the conditions listed in the REPLACE-2 clinical trial description [see Clinical Studies (14.1)] is present.
For patients who have HIT/HITTS
The recommended dose of Angiomax in patients with HIT/HITTS undergoing PCI is an IV bolus of 0.75 mg/kg. This should be followed by a continuous infusion at a rate of 1.75 mg/kg/h for the duration of the procedure.
For ongoing treatment post procedure
Continuation of the Angiomax infusion following PCI/PTCA for up to 4 hours post-procedure is optional, at the discretion of the treating physician. After four hours, an additional IV infusion of Angiomax may be initiated at a rate of 0.2 mg/kg/h (low-rate infusion), for up to 20 hours, if needed.
2.2 Dosing in Renal Impairment
No reduction in the bolus dose is needed for any degree of renal impairment. The infusion dose of Angiomax may need to be reduced, and anticoagulant status monitored in patients with renal impairment. Patients with moderate renal impairment (30-59 mL/min) should receive an infusion of 1.75 mg/kg/h. If the creatinine clearance is less than 30 mL/min, reduction of the infusion rate to 1 mg/kg/h should be considered. If a patient is on hemodialysis, the infusion rate should be reduced to 0.25 mg/kg/h [see Use in Specific Population (8.6)].
2.3 Instructions for Administration
Angiomax is intended for intravenous bolus injection and continuous infusion after reconstitution and dilution. To each 250 mg vial, add 5 mL of Sterile Water for Injection, USP. Gently swirl until all material is dissolved. Each reconstituted vial should be further diluted in 50 mL of 5% Dextrose in Water or 0.9% Sodium Chloride for Injection to yield a final concentration of 5 mg/mL (e.g., 1 vial in 50 mL; 2 vials in 100 mL; 5 vials in 250 mL). The dose to be administered is adjusted according to the patient's weight (see Table 1).
If the low-rate infusion is used after the initial infusion, a lower concentration bag should be prepared. In order to prepare this bag, reconstitute the 250 mg vial with 5 mL of Sterile Water for Injection, USP. Gently swirl until all material is dissolved. Each reconstituted vial should be further diluted in 500 mL of 5% Dextrose in Water or 0.9% Sodium Chloride for Injection to yield a final concentration of 0.5 mg/mL. The infusion rate to be administered should be selected from the right-hand column in Table 1.
Table 1: Dosing Table Weight (kg) Using 5 mg/mL Concentration Using 5 mg/mL Concentration Bolus 0.75 mg/k (mL) Infusion 1.75 mg/kg/h (mL/h) Subsequent Low-rate Infusion 0.2 mg/kg/h (mL/h) 43-47 7 16 18 48-52 7.5 17.5 20 53-57 8 19 22 58-62 9 21 24 63-67 10 23 26 68-72 10.5 24.5 28 73-77 11 26 30 78-82 12 28 32 83-87 13 30 34 88-92 13.5 31.5 36 93-97 14 33 38 98-102 15 35 40 103-107 16 37 42 108-112 16.5 38.5 44 113-117 17 40 46 118-122 18 42 48 123-127 19 44 50 128-132 19.5 45.5 52 133-137 20 47 54 138-142 21 49 56 143-147 22 51 58 148-152 22.5 52.5 60Angiomax should be administered via an intravenous line. No incompatibilities have been observed with glass bottles or polyvinyl chloride bags and administration sets. The following drugs should not be administered in the same intravenous line with Angiomax, since they resulted in haze formation, microparticulate formation, or gross precipitation when mixed with Angiomax: alteplase, amiodarone HCl, amphotericin B, chlorpromazine HCl, diazepam, prochlorperazine edisylate, reteplase, streptokinase, and vancomycin HCl. Dobutamine was compatible at concentrations up to 4 mg/mL but incompatible at a concentration of 12.5 mg/mL.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Preparations of Angiomax containing particulate matter should not be used. Reconstituted material will be a clear to slightly opalescent, colorless to slightly yellow solution.
2.4 Storage after Reconstitution
Do not freeze reconstituted or diluted Angiomax. Reconstituted material may be stored at 2-8°C for up to 24 hours. Diluted Angiomax with a concentration of between 0.5 mg/mL and 5 mg/mL is stable at room temperature for up to 24 hours. Discard any unused portion of reconstituted solution remaining in the vial.
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![Orbactiv (Oritavancin) Injection, Powder, Lyophilized, For Solution [The Medicines Company]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=085d6d1a-21c2-11e4-8c21-0800200c9a66&name=oritavancin-03.jpg)
Orbactiv
2.1 Recommended Dosage
The recommended dosing for ORBACTIV is a single 1200 mg dose administered by intravenous infusion over 3 hours in patients 18 years and older.
2.2 Preparation of ORBACTIV for Intravenous Infusion
ORBACTIV is intended for intravenous infusion, only after reconstitution and dilution.
Three ORBACTIV 400 mg vials need to be reconstituted and diluted to prepare a single 1200 mg intravenous dose.
Reconstitution: Aseptic technique should be used to reconstitute three ORBACTIV 400 mg vials.
Add 40 mL of sterile water for injection (WFI) to reconstitute each vial to provide a 10 mg/mL solution per vial. For each vial, gently swirl to avoid foaming and ensure that all ORBACTIV powder is completely reconstituted in solution. Each vial should be inspected visually for particulate matter after reconstitution and should appear to be clear, colorless to pale yellow solution.Dilution: Use ONLY 5% dextrose in sterile water (D5W) for dilution. Do NOT use Normal Saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Use aseptic technique to:
Withdraw and discard 120 mL from a 1000 mL intravenous bag of D5W. Withdraw 40 mL from each of the three reconstituted vials and add to D5W intravenous bag to bring the bag volume to 1000 mL. This yields a concentration of 1.2 mg/mL.Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparing the final intravenous solution.
Diluted intravenous solution in an infusion bag should be used within 6 hours when stored at room temperature, or used within 12 hours when refrigerated at 2 to 8°C (36 to 46°F). The combined storage time (reconstituted solution in the vial and diluted solution in the bag) and 3 hour infusion time should not exceed 6 hours at room temperature or 12 hours if refrigerated.
2.3 Incompatibilities
ORBACTIV is administered intravenously. ORBACTIV should only be diluted in D5W. Do NOT use normal saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Therefore other intravenous substances, additives or other medications mixed in normal saline should not be added to ORBACTIV single-use vials or infused simultaneously through the same IV line or through a common intravenous port. In addition, drugs formulated at a basic or neutral pH may be incompatible with ORBACTIV. ORBACTIV should not be administered simultaneously with commonly used intravenous drugs through a common intravenous port. If the same intravenous line is used for sequential infusion of additional medications, the line should be flushed before and after infusion of ORBACTIV with D5W.
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![Recothrom (Thrombin Topical Recombinant) Kit [The Medicines Company]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=bcf44467-b1eb-479b-8866-a8ac2c780c22&name=recothrom-1.jpg)
Recothrom
For topical use only. DO NOT INJECT.
2.1 Reconstitution of RECOTHROM
The volume of reconstituted RECOTHROM required will vary depending on the size and number of bleeding sites to be treated and the method of application.
Inspect the integrity of the RECOTHROM package and contents. Do not use if the packaging or contents have been damaged or opened.
Reconstitute the lyophilized powder using the supplied diluent.
Use aseptic technique when handling vials and syringes.
5000-unit RECOTHROM Reconstitution
Units used herein represent international units of potency determined using a reference standard that has been calibrated against the World Health Organization Second International Standard for Thrombin.
Remove flip-off cap from the top of the RECOTHROM vial. Attach the needle-free transfer device and snap it into place on the vial by placing the vial on a flat surface and attaching the transfer device straight into the center of the vial stopper. Attach the prefilled diluent syringe to the needle-free transfer device. Inject the 5 mL of diluent from the syringe into the product vial. Keep the syringe plunger depressed. DO NOT reuse the diluent syringe for transfer of the reconstituted product. Remove and discard the diluent syringe. Gently swirl and invert the product vial until the powder is completely dissolved. Avoid excessive agitation. The powder should dissolve in less than one minute at room temperature. Apply the pre-printed "DO NOT INJECT" label to the sterile, empty transfer syringe provided, then draw up the RECOTHROM solution.20,000-unit RECOTHROM Reconstitution
Remove the flip-off cap from the top of the RECOTHROM vial and the diluent vial. Attach a needle-free transfer device (one each) to the RECOTHROM and diluent vials and snap them into place by placing the vial on a flat surface and attaching the transfer device straight into the center of the vial stopper. Open the sterile, empty 20-mL syringe package and apply the pre-printed "DO NOT INJECT" label to the syringe. Attach the labeled 20-mL syringe to the needle-free transfer device on the diluent vial (injection of air into the diluent vial may facilitate withdrawal of the diluent). Draw up 20 mL of diluent from the vial into the syringe. Remove the diluent-filled syringe from the diluent vial and attach it to the transfer device on the RECOTHROM vial. Transfer the 20 mL of diluent from the syringe into the RECOTHROM vial; the vacuum in the vial facilitates transfer. Leave the syringe attached and gently swirl and invert the RECOTHROM vial until the powder is completely dissolved. Avoid excessive agitation. The powder should dissolve in less than one minute at room temperature. With the same syringe, draw up the RECOTHROM solution.2.2 Application Techniques
Topically apply RECOTHROM solution directly or in conjunction with absorbable gelatin sponge onto the bleeding site. DO NOT INJECT.
The amount required depends upon the area of tissue to be treated and the method of application.
Vials are for single use only. Discard unused contents.
Use with Absorbable Gelatin Sponge
Refer to the absorbable gelatin sponge labeling for safety information and instructions on appropriate use.
Transfer solution from syringe to a sterile bowl or basin. Place the desired size pieces of the absorbable gelatin sponge into the bowl containing reconstituted RECOTHROM to completely saturate the sponge(s). Remove the saturated sponge(s) and squeeze gently to remove excess RECOTHROM. Apply the sponge to the bleeding site in a single layer.Use with ZymoGenetics Spray Applicator Kit
Hold the outer sealed tray, peel back the lid, and aseptically transfer the inner sealed sterile tray to the sterile field. Open the inner tray seal and use the sterile bowl as the receptacle for reconstituted RECOTHROM solution. Refer to Spray Applicator Kit instructions for spray pump and syringe spray assembly and use.
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