Eli Lilly And Company

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Eli Lilly And Company Drugs

Livalo

Livalo

2.1 General Dosing Information

The dose range for LIVALO is 1 to 4 mg orally once daily at any time of the day with or without food. The recommended starting dose is 2 mg and the maximum dose is 4 mg. The starting dose and maintenance doses of LIVALO should be individualized according to patient characteristics, such as goal of therapy and response.

After initiation or upon titration of LIVALO, lipid levels should be analyzed after 4 weeks and the dosage adjusted accordingly.

2.2 Dosage in Patients with Renal Impairment

Patients with moderate and severe renal impairment (glomerular filtration rate 30 – 59 mL/min/1.73 m2 and 15 – 29 mL/min/1.73 m2 not receiving hemodialysis, respectively) as well as end-stage renal disease receiving hemodialysis should receive a starting dose of LIVALO 1 mg once daily and a maximum dose of LIVALO 2 mg once daily.

2.3 Use with Erythromycin

In patients taking erythromycin, a dose of LIVALO 1 mg once daily should not be exceeded [see Drug Interactions (7.2)].

2.4 Use with Rifampin

In patients taking rifampin, a dose of LIVALO 2 mg once daily should not be exceeded [see Drug Interactions (7.3)].
Humulin R

Humulin R

Humulin R U-100, when used subcutaneously, is usually given three or more times daily before meals. The dosage and timing of Humulin R U-100 should be individualized and determined, based on the physician's advice, in accordance with the needs of the patient. Humulin R U-100 may also be used in combination with oral antihyperglycemic agents or longer-acting insulin products to suit the needs of the individual patients with diabetes. The injection of Humulin R U-100 should be followed by a meal within approximately 30 minutes of administration.

The average range of total daily insulin requirement for maintenance therapy in insulin-treated patients without severe insulin resistance lies between 0.5 and 1 unit/kg/day. However, in pre-pubertal children it usually varies from 0.7 to 1 unit/kg/day, but can be much lower during the period of partial remission. In situations of insulin resistance, e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher. Initial dosages for patients with diabetes are often lower, e.g., 0.2 to 0.4 units/kg/day.

Humulin R U-100 may be administered by subcutaneous injection in the abdominal wall, the thigh, the gluteal region or in the upper arm. Subcutaneous injection into the abdominal wall ensures a faster absorption than from other injection sites. Injection into a lifted skin fold minimizes the risk of intramuscular injection. Injection sites should be rotated within the same region. As with all insulin, the duration of action will vary according to the dose, injection site, blood flow, temperature, and level of physical activity.

Intravenous administration of Humulin R U-100 is possible under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia.

For intravenous use, Humulin R U-100 should be used at concentrations from 0.1 unit/mL to 1 unit/mL in infusion systems with the infusion fluids 0.9% sodium chloride using polyvinyl chloride infusion bags.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Never use Humulin R U-100 if it has become viscous (thickened) or cloudy; use it only if it is clear and colorless. Humulin R U-100 should not be used after the printed expiration date.

Mixing of Insulins
Humulin R U-100 should only be mixed as directed by the physician. Humulin R U-100 is short-acting and is often used in combination with intermediate- or long-acting insulins. The order of mixing and brand or model of syringe should be specified by the physician. A U-100 insulin syringe should always be used. Failure to use the correct syringe can lead to dosage errors. In general, when an intermediate-acting insulin (e.g., NPH insulin isophane suspension) is mixed with short-acting soluble insulin (e.g., regular), the short-acting insulin should be drawn into the syringe first.
Storage

Not in-use (unopened): Humulin R U-100 vials not in-use should be stored in a refrigerator (2° to 8°C [36° to 46°F]), but not in the freezer.

In-use (opened): The Humulin R U-100 vial currently in-use can be kept unrefrigerated as long as it is kept as cool as possible [below 30°C (86°F)] away from heat and light. In-use vials must be used within 31 days or be discarded, even if they still contain Humulin R U-100.

Admixture: Infusion bags prepared with Humulin R U-100 as indicated under DOSAGE AND ADMINISTRATION are stable when stored in a refrigerator (2° to 8°C [36° to 46°F]) for 48 hours and then may be used at room temperature for up to an additional 48 hours.

Do not use Humulin R U-100 after the expiration date stamped on the label or if it has been frozen.
Atacand

Atacand

2.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture

The recommended dose is 20 mcg subcutaneously once a day.

2.2 Increase of Bone Mass in Men with Primary or Hypogonadal Osteoporosis at High Risk for Fracture

The recommended dose is 20 mcg subcutaneously once a day.

2.3 Treatment of Men and Women with Glucocorticoid-Induced Osteoporosis at High Risk for Fracture

The recommended dose is 20 mcg subcutaneously once a day.

2.4 Administration
FORTEO should be administered as a subcutaneous injection into the thigh or abdominal wall. There are no data available on the safety or efficacy of intravenous or intramuscular injection of FORTEO. FORTEO should be administered initially under circumstances in which the patient can sit or lie down if symptoms of orthostatic hypotension occur [see Warnings and Precautions (5.7)]. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. FORTEO is a clear and colorless liquid. Do not use if solid particles appear or if the solution is cloudy or colored. Patients and caregivers who administer FORTEO should receive appropriate training and instruction on the proper use of the FORTEO delivery device from a qualified health professional [see Patient Counseling Information (17.5)].
2.5 Treatment Duration

The safety and efficacy of FORTEO have not been evaluated beyond 2 years of treatment. Consequently, use of the drug for more than 2 years during a patient's lifetime is not recommended.
Alimta

Alimta

2.1 Combination Use with Cisplatin for Nonsquamous Non-Small Cell Lung Cancer or Malignant Pleural Mesothelioma

The recommended dose of ALIMTA is 500 mg/m2 administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle. The recommended dose of cisplatin is 75 mg/m2 infused over 2 hours beginning approximately 30 minutes after the end of ALIMTA administration. See cisplatin package insert for more information.

2.2 Single-Agent Use as Maintenance Following First-Line Therapy, or as a Second-Line Therapy

The recommended dose of ALIMTA is 500 mg/m2 administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle.

2.3 Premedication Regimen and Concurrent Medications

Vitamin Supplementation

Instruct patients to initiate folic acid 400 mcg to 1000 mcg orally once daily beginning 7 days before the first dose of ALIMTA. Continue folic acid during the full course of therapy and for 21 days after the last dose of ALIMTA [see Warnings and Precautions (5.1)].

Administer vitamin B12 1 mg intramuscularly 1 week prior to the first dose of ALIMTA and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with ALIMTA [see Warnings and Precautions (5.1)].

Corticosteroids

Administer dexamethasone 4 mg by mouth twice daily the day before, the day of, and the day after ALIMTA administration [see Warnings and Precautions (5.1)].

2.4 Laboratory Monitoring and Dose Reduction/Discontinuation Recommendations

Monitoring

Complete blood cell counts, including platelet counts, should be performed on all patients receiving ALIMTA. Patients should be monitored for nadir and recovery, which were tested in the clinical study before each dose and on days 8 and 15 of each cycle. Patients should not begin a new cycle of treatment unless the ANC is ≥1500 cells/mm3, the platelet count is ≥100,000 cells/mm3, and creatinine clearance is ≥45 mL/min. Periodic chemistry tests should be performed to evaluate renal and hepatic function [see Warnings and Precautions (5.5)].

Dose Reduction Recommendations

Dose adjustments at the start of a subsequent cycle should be based on nadir hematologic counts or maximum nonhematologic toxicity from the preceding cycle of therapy. Treatment may be delayed to allow sufficient time for recovery. Upon recovery, patients should be retreated using the guidelines in Tables 1-3, which are suitable for using ALIMTA as a single-agent or in combination with cisplatin.
Table 1: Dose Reduction for ALIMTA (single-agent or in combination) and Cisplatin – Hematologic Toxicities
a These criteria meet the CTC version 2.0 (NCI 1998) definition of ≥CTC Grade 2 bleeding.
Nadir ANC <500/mm3 and nadir platelets ≥50,000/mm3. 75% of previous dose (pemetrexed and cisplatin). Nadir platelets <50,000/mm3 without bleeding regardless of nadir ANC. 75% of previous dose (pemetrexed and cisplatin). Nadir platelets <50,000/mm3 with bleedinga, regardless of nadir ANC. 50% of previous dose (pemetrexed and cisplatin).
If patients develop nonhematologic toxicities (excluding neurotoxicity) ≥Grade 3, treatment should be withheld until resolution to less than or equal to the patient's pre-therapy value. Treatment should be resumed according to guidelines in Table 2.
Table 2: Dose Reduction for ALIMTA (single-agent or in combination) and Cisplatin – Nonhematologic Toxicitiesa,b
a NCI Common Toxicity Criteria (CTC).

b Excluding neurotoxicity (see Table 3).
Dose of ALIMTA(mg/m2) Dose of Cisplatin(mg/m2) Any Grade 3 or 4 toxicities except mucositis 75% of previous dose 75% of previous dose Any diarrhea requiring hospitalization (irrespective of Grade) or Grade 3 or 4 diarrhea 75% of previous dose 75% of previous dose Grade 3 or 4 mucositis 50% of previous dose 100% of previous dose
In the event of neurotoxicity, the recommended dose adjustments for ALIMTA and cisplatin are described in Table 3. Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is experienced.
Table 3: Dose Reduction for ALIMTA (single-agent or in combination) and Cisplatin – Neurotoxicity Dose of ALIMTA Dose of Cisplatin CTC Grade (mg/m2) (mg/m2) 0-1 100% of previous dose 100% of previous dose 2 100% of previous dose 50% of previous dose
Discontinuation Recommendation

ALIMTA therapy should be discontinued if a patient experiences any hematologic or nonhematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed.

Renally Impaired Patients

In clinical studies, patients with creatinine clearance ≥45 mL/min required no dose adjustments other than those recommended for all patients. Insufficient numbers of patients with creatinine clearance below 45 mL/min have been treated to make dosage recommendations for this group of patients [see Clinical Pharmacology (12.3)]. Therefore, ALIMTA should not be administered to patients whose creatinine clearance is <45 mL/min using the standard Cockcroft and Gault formula (below) or GFR measured by Tc99m-DTPA serum clearance method:
Males: [140 - Age in years] × Actual Body Weight (kg) = mL/min 72 × Serum Creatinine (mg/dL) Females: Estimated creatinine clearance for males × 0.85
Caution should be exercised when administering ALIMTA concurrently with NSAIDs to patients whose creatinine clearance is <80 mL/min [see Drug Interactions (7.1)].

2.5 Preparation and Administration Precautions

As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of infusion solutions of ALIMTA. The use of gloves is recommended. If a solution of ALIMTA contacts the skin, wash the skin immediately and thoroughly with soap and water. If ALIMTA contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available [see References (15)].

ALIMTA is not a vesicant. There is no specific antidote for extravasation of ALIMTA. To date, there have been few reported cases of ALIMTA extravasation, which were not assessed as serious by the investigator. ALIMTA extravasation should be managed with local standard practice for extravasation as with other non-vesicants.

2.6 Preparation for Intravenous Infusion Administration
Use aseptic technique during the reconstitution and further dilution of ALIMTA for intravenous infusion administration. Calculate the dose of ALIMTA and determine the number of vials needed. Vials contain either 100 mg or 500 mg of ALIMTA. The vials contain an excess of ALIMTA to facilitate delivery of label amount. Reconstitute each 100-mg vial with 4.2 ml of 0.9% Sodium Chloride Injection (preservative free). Reconstitute each 500-mg vial with 20 mL of 0.9% Sodium Chloride Injection (preservative free). Reconstitution of either size vial gives a solution containing 25 mg/mL ALIMTA. Gently swirl each vial until the powder is completely dissolved. The resulting solution is clear and ranges in color from colorless to yellow or green-yellow without adversely affecting product quality. The pH of the reconstituted ALIMTA solution is between 6.6 and 7.8. FURTHER DILUTION IS REQUIRED. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter is observed, do not administer. An appropriate quantity of the reconstituted ALIMTA solution must be further diluted into a solution of 0.9% Sodium Chloride Injection (preservative free), so that the total volume of solution is 100 ml. ALIMTA is administered as an intravenous infusion over 10 minutes. Chemical and physical stability of reconstituted and infusion solutions of ALIMTA were demonstrated for up to 24 hours following initial reconstitution, when stored refrigerated. When prepared as directed, reconstitution and infusion solutions of ALIMTA contain no antimicrobial preservatives. Discard any unused portion.
Reconstitution and further dilution prior to intravenous infusion is only recommended with 0.9% Sodium Chloride Injection (preservative free). ALIMTA is physically incompatible with diluents containing calcium, including Lactated Ringer's Injection, USP and Ringer's Injection, USP and therefore these should not be used. Coadministration of ALIMTA with other drugs and diluents has not been studied, and therefore is not recommended. ALIMTA is compatible with standard polyvinyl chloride (PVC) administration sets and intravenous solution bags.
Zyprexa Relprevv

Zyprexa Relprevv

2.1 Dosage

ZYPREXA RELPREVV is intended for deep intramuscular gluteal injection only and should not be administered intravenously or subcutaneously.

Be aware that there are two ZYPREXA intramuscular formulations with different dosing schedules. ZYPREXA IntraMuscular (10 mg/vial) is a short-acting formulation and should not be confused with ZYPREXA RELPREVV. Refer to the package insert for ZYPREXA IntraMuscular for more information about that product.

Establish tolerability with oral olanzapine prior to initiating treatment.

ZYPREXA RELPREVV should be administered by a healthcare professional every 2 to 4 weeks by deep intramuscular gluteal injection using a 19-gauge, 1.5-inch needle. Following insertion of the needle into the muscle, aspiration should be maintained for several seconds to ensure that no blood is drawn into the syringe. If any blood is aspirated into the syringe, it should be discarded and fresh drug should be prepared using a new convenience kit. The injection should be performed at a steady, continuous pressure. Do not massage the injection site.

Dose Selection — The efficacy of ZYPREXA RELPREVV has been demonstrated within the range of 150 mg to 300 mg administered every 2 weeks and with 405 mg administered every 4 weeks. Dose recommendations considering oral ZYPREXA and ZYPREXA RELPREVV are shown in Table 1.
Table 1: Recommended Dosing for ZYPREXA RELPREVV Based on Correspondence to Oral ZYPREXA Doses Target Oral ZYPREXA Dose Dosing of ZYPREXA RELPREVV During the First 8 Weeks Maintenance Dose After 8 Weeks of ZYPREXA RELPREVV Treatment 10 mg/day 210 mg/2 weeks or405 mg/4 weeks 150 mg/2 weeksor 300 mg/4 weeks 15 mg/day 300 mg/2 weeks 210 mg/2 weeksor 405 mg/4 weeks 20 mg/day 300 mg/2 weeks 300 mg/2 weeks
ZYPREXA RELPREVV doses greater than 405 mg every 4 weeks or 300 mg every 2 weeks have not been evaluated in clinical trials.

Post-Injection Delirium/Sedation Syndrome — During premarketing clinical studies, adverse events that presented with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium, were reported in patients following an injection of ZYPREXA RELPREVV [see Boxed Warning, Warnings and Precautions (5.1), and Overdosage (10.1)]. Patients should be informed of this risk and how to recognize related symptoms [see Patient Counseling Information (17.1, 17.2)]. ZYPREXA RELPREVV must be administered in a registered healthcare facility with ready access to emergency response services. After each ZYPREXA RELPREVV injection, a healthcare professional must continuously observe the patient at the healthcare facility for at least 3 hours for symptoms consistent with olanzapine overdose, including sedation (ranging from mild in severity to coma) and/or delirium (including confusion, disorientation, agitation, anxiety, and other cognitive impairment). Other symptoms noted include extrapyramidal symptoms, dysarthria, ataxia, aggression, dizziness, weakness, hypertension, and convulsion. The potential for onset of an event is greatest within the first hour. The majority of cases have occurred within the first 3 hours after injection; however, the event has occurred after 3 hours. Following the 3-hour observation period, healthcare professionals must confirm that the patient is alert, oriented, and absent of any signs and symptoms of post-injection delirium/sedation syndrome prior to being released. All patients must be accompanied to their destination upon leaving the facility. For the remainder of the day of each injection, patients should not drive or operate heavy machinery, and should be advised to be vigilant for symptoms of post-injection delirium/sedation syndrome and be able to obtain medical assistance if needed. If post-injection delirium/sedation syndrome is suspected, close medical supervision and monitoring should be instituted in a facility capable of resuscitation [see Overdosage (10)].

Dosing in Specific Populations — Tolerance of oral ZYPREXA should be established prior to initiating treatment with ZYPREXA RELPREVV. The recommended starting dose is ZYPREXA RELPREVV 150 mg/4 wks in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients ≥65 years of age), or who may be more pharmacodynamically sensitive to olanzapine. When indicated, dose escalation should be undertaken with caution in these patients [see Warnings and Precautions (5.16), Drug Interactions (7), and Clinical Pharmacology (12.3)].

ZYPREXA RELPREVV has not been studied in subjects under 18 years of age [see Warnings and Precautions (5.6)].

Maintenance Treatment — Although no controlled studies have been conducted to determine how long patients should be treated with ZYPREXA RELPREVV, efficacy has been demonstrated over a period of 24 weeks in patients with stabilized schizophrenia. Additionally, oral ZYPREXA has been shown to be effective in maintenance of treatment response in schizophrenia in longer-term use. Patients should be periodically reassessed to determine the need for continued treatment.

Switching from Other Antipsychotics — There are no systematically collected data to specifically address how to switch patients with schizophrenia from other antipsychotics to ZYPREXA RELPREVV.

2.2 Instructions to Reconstitute and Administer ZYPREXA RELPREVV

For deep intramuscular gluteal injection only. Not to be injected intravenously or subcutaneously.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Step 1: Preparing Materials

Convenience kit includes:
Vial of ZYPREXA RELPREVV powder 3-mL vial of diluent One 3-mL syringe with pre-attached 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro® needle with needle protection device Two 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needles with needle protection device — For obese patients, a 2-inch (50 mm), 19-gauge or larger needle (not included in convenience kit) may be used for administration.
ZYPREXA RELPREVV must be suspended using only the diluent supplied in the convenience kit.

It is recommended that gloves are used when reconstituting, as ZYPREXA RELPREVV may be irritating to the skin. Flush with water if contact is made with skin.

See additional insert entitled “Instructions to Reconstitute and Administer ZYPREXA RELPREVV” (included) for more information regarding the safe and effective use of the Hypodermic Needle-Pro syringe and needle.

Step 2: Determining Reconstitution Volume

Refer to the table below to determine the amount of diluent to be added to powder for reconstitution of each vial strength.

It is important to note that there is more diluent in the vial than is needed to reconstitute.
Dose Vial Strength Diluent to Add 150 mg 210 mg 1.3 mL 210 mg 210 mg 1.3 mL 300 mg 300 mg 1.8 mL 405 mg 405 mg 2.3 mL
Step 3: Reconstituting ZYPREXA RELPREVV

Please read the Hypodermic Needle-Pro Instructions for Use before proceeding with Step 3. Failure to follow these instructions may result in a needlestick injury.
Loosen the powder by lightly tapping the vial. Open the prepackaged Hypodermic Needle-Pro syringe and needle with needle protection device. Withdraw the pre-determined diluent volume ( Step 2) into the syringe. Inject the diluent into the powder vial. Withdraw air to equalize the pressure in the vial by pulling back slightly on the plunger in the syringe. Remove the needle from the vial, holding the vial upright to prevent any loss of material. Engage the needle safety device (refer to complete Hypodermic Needle-Pro Instructions for Use). Pad a hard surface to cushion impact ( see Figure 1). Tap the vial firmly and repeatedly on the surface until no powder is visible.
Figure 1: Tap firmly to mix.
Visually check the vial for clumps. Unsuspended powder appears as yellow, dry clumps clinging to the vial. Additional tapping may be required if large clumps remain ( see Figure 2).
Figure 2: Check for unsuspended powder and repeat tapping if needed.
Shake the vial vigorously until the suspension appears smooth and is consistent in color and texture. The suspended product will be yellow and opaque ( see Figure 3).
Figure 3: Vigorously shake vial.
If foam forms, let vial stand to allow foam to dissipate. If the product is not used right away, it should be shaken vigorously to re-suspend. Reconstituted ZYPREXA RELPREVV remains stable for up to 24 hours in the vial.
Step 4: Injecting ZYPREXA RELPREVV

Before administering the injection, confirm there will be someone to accompany the patient after the 3-hour observation period. If this cannot be confirmed, do not give the injection.

Refer to the table below to determine the final volume to inject. Suspension concentration is 150 mg/mL ZYPREXA RELPREVV.
Dose Final Volume to Inject 150 mg 1 mL 210 mg 1.4 mL 300 mg 2 mL 405 mg 2.7 mL Attach a new safety needle to the syringe. Slowly withdraw the desired amount into the syringe. Some excess product will remain in the vial. Engage the needle safety device and remove needle from syringe. For administration, select the 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needle with needle protection device. For obese patients, a 2-inch (50 mm), 19-gauge or larger needle (not included in convenience kit) may be used. To help prevent clogging, a 19-gauge or larger needle must be used. Attach the new safety needle to the syringe prior to injection. Once the suspension has been removed from the vial, it should be injected immediately. For deep intramuscular gluteal injection only. Do not inject intravenously or subcutaneously. Select and prepare a site for injection in the gluteal area. After insertion of the needle into the muscle, aspirate for several seconds to ensure that no blood appears. If any blood is drawn into the syringe, discard the syringe and the dose and begin with a new convenience kit. The injection should be performed with steady, continuous pressure. Do not massage the injection site. Engage the needle safety device. Dispose of the vials, needles, and syringe appropriately after injection. The vial is for single-use only.
Glucagon Kit

Glucagon Kit

General Instructions for Use:
The diluent is provided for use only in the preparation of glucagon for parenteral injection and for no other use. Glucagon should not be used at concentrations greater than 1 mg/mL (1 unit/mL). Reconstituted glucagon should be used immediately. Discard any unused portion. Reconstituted glucagon solutions should be used only if they are clear and of a water-like consistency. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Directions for Treatment of Severe Hypoglycemia:

Severe hypoglycemia should be treated initially with intravenous glucose, if possible.
If parenteral glucose can not be used, dissolve the lyophilized glucagon using the accompanying diluting solution and use immediately. For adults and for pediatric patients weighing more than 44 lb (20 kg), give 1 mg (1 unit) by subcutaneous, intramuscular, or intravenous injection. For pediatric patients weighing less than 44 lb (20 kg), give 0.5 mg (0.5 unit) or a dose equivalent to 20 to 30 μg/kg.2-6 Discard any unused portion. An unconscious patient will usually awaken within 15 minutes following the glucagon injection. If the response is delayed, there is no contraindication to the administration of an additional dose of glucagon; however, in view of the deleterious effects of cerebral hypoglycemia emergency aid should be sought so that parenteral glucose can be given. After the patient responds, supplemental carbohydrate should be given to restore liver glycogen and to prevent secondary hypoglycemia.
Directions for Use as a Diagnostic Aid:

Dissolve the lyophilized glucagon using the accompanying diluting solution and use immediately. Discard any unused portion.

The doses in the following table may be administered for relaxation of the stomach, duodenum, and small bowel, depending on the onset and duration of effect required for the examination. Since the stomach is less sensitive to the effect of glucagon, 0.5 mg (0.5 units) IV or 2 mg (2 units) IM are recommended.

* Administration of 2 mg (2 units) doses produces a higher incidence of nausea and vomiting than do lower doses.
Dose Route of Administration Time of Onset of Action Approximate Duration of Effect 0.25-0.5 mg (0.25-0.5 units) IV 1 minute 9-17 minutes 1-mg (1 unit) IM 8-10 minutes 12-27 minutes 2 mg* (2 units) IV 1 minute 22-25 minutes 2 mg* (2 units) IM 4-7 minutes 21-32 minutes

For examination of the colon, it is recommended that a 2 mg (2 units) dose be administered intramuscularly approximately 10 minutes prior to the procedure. Colon relaxation and reduction of patient discomfort may allow the radiologist to perform a more satisfactory examination.
Reopro

Reopro

The safety and efficacy of Abciximab have only been investigated with concomitant administration of heparin and aspirin as described in CLINICAL STUDIES.

In patients with failed PCIs, the continuous infusion of Abciximab should be stopped because there is no evidence for Abciximab efficacy in that setting.

In the event of serious bleeding that cannot be controlled by compression, Abciximab and heparin should be discontinued immediately.

The recommended dosage of Abciximab in adults is a 0.25 mg/kg intravenous bolus administered 10-60 minutes before the start of PCI, followed by a continuous intravenous infusion of 0.125 μg/kg/min (to a maximum of 10 μg/min) for 12 hours.

Patients with unstable angina not responding to conventional medical therapy and who are planned to undergo PCI within 24 hours may be treated with an Abciximab 0.25 mg/kg intravenous bolus followed by an 18- to 24-hour intravenous infusion of 10 μg/min, concluding one hour after the PCI.

Instructions for Administration
Parenteral drug products should be inspected visually for particulate matter prior to administration. Preparations of Abciximab containing visibly opaque particles should NOT be used. Hypersensitivity reactions should be anticipated whenever protein solutions such as Abciximab are administered. Epinephrine, dopamine, theophylline, antihistamines and corticosteroids should be available for immediate use. If symptoms of an allergic reaction or anaphylaxis appear, the infusion should be stopped and appropriate treatment given (see WARNINGS: Allergic Reactions). As with all parenteral drug products, aseptic procedures should be used during the administration of Abciximab. Withdraw the necessary amount of Abciximab for bolus injection into a syringe. Filter the bolus injection using a sterile, non-pyrogenic, low protein-binding 0.2 or 5 μm syringe filter (Millipore SLGV025LS or SLSV025LS or equivalent). Withdraw the necessary amount of Abciximab for the continuous infusion into a syringe. Inject into an appropriate container of sterile 0.9% saline or 5% dextrose and infuse at the calculated rate via a continuous infusion pump. The continuous infusion should be filtered either upon admixture using a sterile, non-pyrogenic, low protein-binding 0.2 or 5 μm syringe filter (Millipore SLGV025LS or SLSV025LS or equivalent) or upon administration using an in-line, sterile, non-pyrogenic, low protein-binding 0.2 or 0.22 μm filter (Abbott #4524 or equivalent). Discard the unused portion at the end of the infusion. No incompatibilities have been shown with intravenous infusion fluids or commonly used cardiovascular drugs. Nevertheless, Abciximab should be administered in a separate intravenous line whenever possible and not mixed with other medications. No incompatibilities have been observed with glass bottles or polyvinyl chloride bags and administration sets.
Humulin 7030

Humulin 7030

2.1 Important Administration Instructions

Inspect HUMULIN N visually before use. It should not contain particulate matter and should appear uniformly cloudy after mixing. Do not use HUMULIN N if particulate matter is seen.

2.2 Route of Administration

HUMULIN N should only be administered subcutaneously.

Administer in the subcutaneous tissue of the abdominal wall, thigh, upper arm, or buttocks. To reduce the risk of lipodystrophy, rotate the injection site within the same region from one injection to the next [see Adverse Reactions (6)].

Do not administer HUMULIN N intravenously or intramuscularly and do not use HUMULIN N in an insulin infusion pump.

2.3 Dosage Information

Individualize and adjust the dosage of HUMULIN N based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.

Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2, 5.3), and Use in Specific Populations (8.6, 8.7)].

2.4 Dosage Adjustment due to Drug Interactions

Dosage adjustment may be needed when HUMULIN N is coadministered with certain drugs [see Drug Interactions (7)].

Dosage adjustment may be needed when switching from another insulin to HUMULIN N [see Warnings and Precautions (5.2)].

Instructions for Mixing with Other Insulins

HUMULIN N may be used with a prandial insulin if indicated. HUMULIN N may be mixed with HUMULIN R or HUMALOG before injection.
If HUMULIN N is mixed with HUMULIN R, HUMULIN R should be drawn into the syringe first. Injection should occur immediately after mixing. If HUMULIN N is mixed with HUMALOG, HUMALOG should be drawn into the syringe first. Injection should occur immediately after mixing.
Humalog

Humalog

2.1 Important Administration Instructions
Always check insulin labels before administration [see Warnings and Precautions (5.4)]. Inspect HUMALOG visually before use. It should appear clear and colorless. Do not use HUMALOG if particulate matter or coloration is seen. Do NOT mix HUMALOG U-100 with other insulins when administering using a continuous subcutaneous infusion pump. Do NOT transfer HUMALOG U-200 from the KwikPen to a syringe for administration [see Warnings and Precautions (5.4)]. Do NOT perform dose conversion when using either the HUMALOG U-100 or U-200 KwikPens. The dose window shows the number of insulin units to be delivered and no conversion is needed. Do NOT mix HUMALOG U-200 with any other insulins. Do NOT administer HUMALOG U-200 using a continuous subcutaneous infusion pump (i.e., insulin pump). Do NOT administer HUMALOG U200 intravenously.
2.2 Route of Administration

Subcutaneous Injection: HUMALOG U-100 or U-200
Administer the dose of HUMALOG U-100 or HUMALOG U-200 within fifteen minutes before a meal or immediately after a meal by injection into the subcutaneous tissue of the abdominal wall, thigh, upper arm, or buttocks. To reduce the risk of lipodystrophy, rotate the injection site within the same region from one injection to the next [see Adverse Reactions (6)]. HUMALOG administered by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
Continuous Subcutaneous Infusion (Insulin Pump); HUMALOG U-100 ONLY
Do NOT administer HUMALOG U-200 using a continuous subcutaneous infusion pump. Administer HUMALOG U-100 by continuous subcutaneous infusion into the subcutaneous tissue of the abdominal wall. Rotate infusion sites within the same region to reduce the risk of lipodystrophy [see Adverse Reactions (6.1)]. Follow healthcare provider recommendations when setting basal and meal time infusion rate. Do NOT dilute or mix HUMALOG U-100 when administering by continuous subcutaneous infusion. Change HUMALOG U-100 in the pump reservoir at least every 7 days. Change the infusion sets and the infusion set insertion site at least every 3 days. Do NOT expose HUMALOG U-100 in the pump reservoir to temperatures greater than 98.6°F (37°C). Use HUMALOG U-100 in pump systems suitable for insulin infusion [see Patient Counseling Information (17.7)].
Intravenous Administration; HUMALOG U-100 ONLY
Do NOT administer HUMALOG U-200 intravenously. Dilute HUMALOG U-100 to concentrations from 0.1 unit/mL to 1.0 unit/mL using 0.9% sodium chloride. Administer HUMALOG U-100 intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels to avoid hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6) and How Supplied/Storage and Handling (16.4)].
2.3 Dosage Information
Individualize and adjust the dosage of HUMALOG based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.6, 8.7)]. Do NOT perform dose conversion when using either the HUMALOG U-100 or U-200 KwikPens. The dose window shows the number of insulin units to be delivered and no conversion is needed.
2.4 Dosage Adjustment Due to Drug Interactions
Dosage adjustment may be needed when HUMALOG is coadministered with certain drugs [see Drug Interactions (7)]. Dosage adjustment may be needed when switching from another insulin to HUMALOG [see Warnings and Precautions (5.2)]. Instructions for Mixing with Other Insulins HUMALOG U-100 subcutaneous injection route HUMALOG U-100 may be mixed with NPH insulin preparations ONLY. If HUMALOG U-100 is mixed with NPH insulin, HUMALOG U-100 should be drawn into the syringe first. Injection should occur immediately after mixing. HUMALOG U-100 continuous subcutaneous infusion route (Insulin Pump) Do NOT mix HUMALOG U-100 with any other insulin. HUMALOG U-200 subcutaneous injection route Do NOT mix with any other insulin.
Humalog Mix5050

Humalog Mix5050

Table 1*: Summary of Pharmacodynamic Properties of Insulin Products (Pooled Cross-Study Comparison)
* The information supplied in Table 1 indicates when peak insulin activity can be expected and the percent of the total insulin activity occurring during the first 4 hours. The information was derived from 3 separate glucose clamp studies in nondiabetic subjects. Values represent means, with ranges provided in parentheses.
Insulin Products Dose, U/kg Time of Peak Activity, Hours After Dosing Percent of Total Activity Occurring in the First 4 Hours Humalog 0.3 2.4(0.8 - 4.3) 70%(49 - 89%) Humulin R 0.32(0.26 - 0.37) 4.4(4.0 - 5.5) 54%(38 - 65%) Humalog Mix75/25 0.3 2.6(1.0 - 6.5) 35%(21 - 56%) Humulin 70/30 0.3 4.4(1.5 - 16) 32%(14 - 60%) Humalog Mix50/50 0.3 2.3(0.8 - 4.8) 45%(27 - 69%) Humulin 50/50 0.3 3.3(2.0 - 5.5) 44%(21 - 60%) NPH 0.32(0.27 - 0.40) 5.5(3.5 - 9.5) 14%(3.0 - 48%) NPL component 0.3 5.8(1.3 - 18.3) 22%(6.3 - 40%)
Humalog Mix50/50 is intended only for subcutaneous administration. Humalog Mix50/50 should not be administered intravenously. Dosage regimens of Humalog Mix50/50 will vary among patients and should be determined by the healthcare provider familiar with the patient's metabolic needs, eating habits, and other lifestyle variables. Humalog has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog has the same glucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration. The quicker glucose-lowering effect of Humalog is related to the more rapid absorption rate of insulin lispro from subcutaneous tissue.

Direct comparison between Humalog Mix50/50 and Humulin 50/50 was not performed. However, a cross-study comparison shown in Figure 3 suggests that Humalog Mix50/50 has a duration of activity that is similar to Humulin 50/50.

The rate of insulin absorption and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables. As with all insulin preparations, the time course of action of Humalog Mix50/50 may vary considerably in different individuals or within the same individual. Patients must be educated to use proper injection techniques.

Humalog Mix50/50 should be inspected visually before use. Humalog Mix50/50 should be used only if it appears uniformly cloudy after mixing. Humalog Mix50/50 should not be used after its expiration date.
Amyvid

Amyvid

2.1 Radiation Safety - Drug Handling

Amyvid is a radioactive drug and should be handled with appropriate safety measures to minimize radiation exposure during administration [see Warnings and Precautions (5.1)]. Use waterproof gloves and effective shielding, including syringe shields when handling Amyvid. Radiopharmaceuticals, including Amyvid, should only be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radioactive materials, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.

2.2 Recommended Dosing and Administration Instructions

The recommended dose for Amyvid is 370 MBq (10 mCi), maximum 50 μg mass dose, administered as a single intravenous bolus in a total volume of 10 mL or less. Follow the injection with an intravenous flush of 0.9% sterile sodium chloride.
Inspect the radiopharmaceutical dose solution prior to administration and do not use it if it contains particulate matter or is discolored. Use aseptic technique and radiation shielding to withdraw Amyvid solution. Assay the dose in a suitable dose calibrator prior to administration. Inject Amyvid through a short intravenous catheter (approximately 1.5 inches or less) to minimize the potential for adsorption of the drug to the catheter. Portions of the Amyvid dose may adhere to longer catheters.
2.3 Image Acquisition Guidelines

A 10-minute PET image should be acquired starting 30 to 50 minutes after Amyvid intravenous injection. The patient should be supine and the head positioned to center the brain, including the cerebellum, in the PET scanner field of view. Reducing head movement with tape or other flexible head restraints may be employed. Image reconstruction should include attenuation correction with resulting transaxial pixel sizes between 2 and 3 mm.

2.4 Image Display and Interpretation

Amyvid images should be interpreted only by readers who successfully complete a special training program [see Warnings and Precautions (5.1)]. Training is provided by the manufacturer using either an in-person tutorial or an electronic process.

The objective of Amyvid image interpretation is to provide an estimate of the brain β-amyloid neuritic plaque density, not to make a clinical diagnosis. Image interpretation is performed independently of a patient's clinical features and relies upon the recognition of unique image features.

Image Display

Images should be displayed in the transaxial orientation with access as needed to the sagittal and coronal planes. In reviewing the images, include all transaxial slices of the brain using a black-white scale with the maximum intensity of the scale set to the maximum intensity of all the brain pixels. Initially locate the brain slice with the highest levels of image contrast (highest radioactivity signals for Amyvid uptake) and adjust the contrast appropriately. Start image interpretation by displaying slices sequentially from the bottom of the brain to the top. Periodically refer to the sagittal and coronal plane image display, as needed to better define the radioactivity uptake and to ensure that the entire brain is displayed.

Image Interpretation

Image interpretation is based upon the distribution of radioactive signal within the brain; clinical information is not a component of the image assessment [see Warnings and Precautions (5.1)]. Images are designated as positive or negative by comparing the radioactivity in cortical gray matter with activity in the adjacent white matter. This determination is made only in the cerebral cortex; the signal uptake in the cerebellum does not contribute to the scan interpretation (for example, a positive scan may show retained cerebellar gray-white contrast even when the cortical gray-white contrast is lost).
Negative scans show more radioactivity in white matter than in gray matter, creating clear gray-white contrast. Positive scans show cortical areas with reduction or loss of the normally distinct gray-white contrast. These scans have one or more areas with increased cortical gray matter signal which results in reduced (or absent) gray-white contrast. Specifically, a positive scan will have either: Two or more brain areas (each larger than a single cortical gyrus) in which there is reduced or absent gray-white contrast. This is the most common appearance of a positive scan.
or
One or more areas in which gray matter radioactivity is intense and clearly exceeds radioactivity in adjacent white matter.
Some scans may be difficult to interpret due to image noise, atrophy with a thinned cortical ribbon, or image blur. For cases in which there is uncertainty as to the location or edge of gray matter on the PET scan and a co-registered computerized tomography (CT) image is available (as when the study is done on a PET/CT scanner) the interpreter should examine the CT image to clarify the relationship of the PET radioactivity and the gray matter anatomy.

Figures 1, 2, and 3 provide examples of negative and positive scans. Figure 1 demonstrates varying degrees of normal gray-white contrast (negative) and examples where gray-white contrast has been lost (positive). Figure 2 illustrates typical features of a negative scan, while Figure 3 shows the loss of gray-white contrast in different brain regions of a positive scan.

Figure 1: Examples of Amyvid negative scans (top two rows) and positive scans (bottom two rows). Left to right panels show sagittal, coronal, and transverse PET image slices. Final panel to right shows enlarged picture of the brain area under the box. The top two arrows are pointing to normal preserved gray-white contrast with the cortical radioactivity less than the adjacent white matter. The bottom two arrows indicate areas of decreased gray-white contrast with increased cortical radioactivity that is comparable to the radioactivity in the adjacent white matter.

Figure 2: Typical Negative Scan. Images are displayed from a negative scan with upper (top) and lower (bottom) transverse slices both showing good gray-white matter contrast. On the right side of each slice, dotted lines have been used to illustrate the edge of the cortical gray matter (outer line) and the gray-white border (inner line). These dotted lines highlight contrast in uptake between the less intense uptake in the gray matter and the more intense uptake in the white matter. In addition, arrows illustrate the following points:A) White matter tracts can be delineated from the frontal lobe to parietal lobe.B) White matter tracts are clearly identified throughout the occipital / temporal area.C) Scalloped appearance is seen with “fingers” of white matter in the frontal cortex.D) Low levels of tracer in scalp or skull that should be distinguished from gray matter uptake by its shape and position.

Figure 3: Typical Positive Scan: Images from a positive scan showing upper (top) and lower (bottom) transverse slices with loss of gray-white matter contrast in multiple brain regions. On the right side of each slice the edge of the cortical gray matter has been illustrated with a dotted line. Compared to the images from the negative case in Figure 2, the gray matter uptake is more similar to the white matter uptake and the gray-white matter border is more difficult to discern. In addition, arrows show the following points:A) White matter tracts are difficult to fully identify as they travel from frontal to parietal lobe.B) Borders of white matter tracts in occipital / temporal area are lost in places.C) Gray matter in medial parietal cortex (precuneus) has increased uptake.D) Low levels of tracer in scalp or skull that should be distinguished from gray matter uptake by its shape and position.

2.5 Radiation Dosimetry

The estimated radiation absorbed doses for adults from intravenous injection of Amyvid are shown in Table 1.
Table 1: Estimated Radiation Absorbed Dose, Amyvid (Florbetapir F 18 Injection)
a Gastrointestinal

b Assumed radiation weighting factor, wr, (formerly defined as quality factor, Q) of 1 for conversion of absorbed dose (Gray or rads) to dose equivalent (Sieverts or rem) for F 18. To obtain radiation absorbed dose in rad/mCi from above table, multiply the dose in μGy/MBq by 0.0037, (e.g., 14 μGy/MBq x 0.0037 = 0.0518 rad/mCi)
ORGAN/TISSUE MEAN ABSORBED DOSE PER UNIT ADMINISTERED ACTIVITY(μGy/MBq) Adrenal 14 Bone - Osteogenic Cells 28 Bone - Red Marrow 14 Brain 10 Breasts 6 Gallbladder Wall 143 GIa - Lower Large Intestine Wall 28 GI - Small Intestine 66 GI - Stomach Wall 12 GI - Upper Large Intestine Wall 74 Heart Wall 13 Kidneys 14 Liver 64 Lungs 9 Muscle 9 Ovaries 18 Pancreas 14 Skin 6 Spleen 9 Testes 7 Thymus 7 Thyroid 7 Urinary Bladder Wall 27 Uterus 16 Total Body 12 Effective Dose (μSv/MBq)b 19
The effective dose resulting from a 370 MBq (10 mCi) dose of Amyvid is 7.0 mSv in an adult, (19 x 370 = 7030 μSv = 7.030 mSv). The use of a CT scan to calculate attenuation correction for reconstruction of Amyvid images (as done in PET/CT imaging) will add radiation exposure. Diagnostic head CT scans using helical scanners administer an average of 2.2 ± 1.3 mSv effective dose (CRCPD Publication E-07-2, 2007). The actual radiation dose is operator and scanner dependent. The total radiation exposure from Amyvid administration and subsequent scan on a PET/CT scanner is estimated to be 9 mSv.
Cialis

Cialis

Do not split CIALIS tablets; entire dose should be taken.

2.1 CIALIS for Use as Needed for Erectile Dysfunction
The recommended starting dose of CIALIS for use as needed in most patients is 10 mg, taken prior to anticipated sexual activity. The dose may be increased to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. The maximum recommended dosing frequency is once per day in most patients. CIALIS for use as needed was shown to improve erectile function compared to placebo up to 36 hours following dosing. Therefore, when advising patients on optimal use of CIALIS, this should be taken into consideration.
2.2 CIALIS for Once Daily Use for Erectile Dysfunction
The recommended starting dose of CIALIS for once daily use is 2.5 mg, taken at approximately the same time every day, without regard to timing of sexual activity. The CIALIS dose for once daily use may be increased to 5 mg, based on individual efficacy and tolerability.
2.3 CIALIS for Once Daily Use for Benign Prostatic Hyperplasia
The recommended dose of CIALIS for once daily use is 5 mg, taken at approximately the same time every day. When therapy for BPH is initiated with CIALIS and finasteride, the recommended dose of CIALIS for once daily use is 5 mg, taken at approximately the same time every day for up to 26 weeks.
2.4 CIALIS for Once Daily Use for Erectile Dysfunction and Benign Prostatic Hyperplasia

The recommended dose of CIALIS for once daily use is 5 mg, taken at approximately the same time every day, without regard to timing of sexual activity.

2.5 Use with Food

CIALIS may be taken without regard to food.

2.6 Use in Specific Populations

Renal Impairment

CIALIS for Use as Needed
Creatinine clearance 30 to 50 mL/min: A starting dose of 5 mg not more than once per day is recommended, and the maximum dose is 10 mg not more than once in every 48 hours. Creatinine clearance less than 30 mL/min or on hemodialysis: The maximum dose is 5 mg not more than once in every 72 hours [see Warnings and Precautions (5.7) and Use in Specific Populations (8.7)].
CIALIS for Once Daily Use

Erectile Dysfunction
Creatinine clearance less than 30 mL/min or on hemodialysis: CIALIS for once daily use is not recommended [see Warnings and Precautions (5.7) and Use in Specific Populations (8.7)].
Benign Prostatic Hyperplasia and Erectile Dysfunction/Benign Prostatic Hyperplasia
Creatinine clearance 30 to 50 mL/min: A starting dose of 2.5 mg is recommended. An increase to 5 mg may be considered based on individual response. Creatinine clearance less than 30 mL/min or on hemodialysis: CIALIS for once daily use is not recommended [see Warnings and Precautions (5.7) and Use in Specific Populations (8.7)].
Hepatic Impairment

CIALIS for Use as Needed
Mild or moderate (Child Pugh Class A or B): The dose should not exceed 10 mg once per day. The use of CIALIS once per day has not been extensively evaluated in patients with hepatic impairment and therefore, caution is advised. Severe (Child Pugh Class C): The use of CIALIS is not recommended [see Warnings and Precautions (5.8) and Use in Specific Populations (8.6)].
CIALIS for Once Daily Use
Mild or moderate (Child Pugh Class A or B): CIALIS for once daily use has not been extensively evaluated in patients with hepatic impairment. Therefore, caution is advised if CIALIS for once daily use is prescribed to these patients. Severe (Child Pugh Class C): The use of CIALIS is not recommended [see Warnings and Precautions (5.8) and Use in Specific Populations (8.6)].
2.7 Concomitant Medications

Nitrates

Concomitant use of nitrates in any form is contraindicated [see Contraindications (4.1)].

Alpha-Blockers

ED — When CIALIS is coadministered with an alpha-blocker in patients being treated for ED, patients should be stable on alpha-blocker therapy prior to initiating treatment, and CIALIS should be initiated at the lowest recommended dose [see Warnings and Precautions (5.6), Drug Interactions (7.1), and Clinical Pharmacology (12.2)].

BPH — CIALIS is not recommended for use in combination with alpha-blockers for the treatment of BPH [see Warnings and Precautions (5.6), Drug Interactions (7.1), and Clinical Pharmacology (12.2)].

CYP3A4 Inhibitors

CIALIS for Use as Needed — For patients taking concomitant potent inhibitors of CYP3A4, such as ketoconazole or ritonavir, the maximum recommended dose of CIALIS is 10 mg, not to exceed once every 72 hours [see Warnings and Precautions (5.10) and Drug Interactions (7.2)].

CIALIS for Once Daily Use — For patients taking concomitant potent inhibitors of CYP3A4, such as ketoconazole or ritonavir, the maximum recommended dose is 2.5 mg [see Warnings and Precautions (5.10) and Drug Interactions (7.2)].
Extra Strength Pain Rel...

Extra Strength Pain Relief

Do not administer CYRAMZA as an intravenous push or bolus.

2.1 Recommended Dose and Schedule

Gastric Cancer
The recommended dose of CYRAMZA either as a single agent or in combination with weekly paclitaxel is 8 mg/kg every 2 weeks administered as an intravenous infusion over 60 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity. When given in combination, administer CYRAMZA prior to administration of paclitaxel.
Non-Small Cell Lung Cancer
The recommended dose of CYRAMZA is 10 mg/kg administered by intravenous infusion over 60 minutes on day 1 of a 21-day cycle prior to docetaxel infusion. Continue CYRAMZA until disease progression or unacceptable toxicity.
Colorectal Cancer
The recommended dose of CYRAMZA is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes prior to FOLFIRI administration. Continue CYRAMZA until disease progression or unacceptable toxicity.
2.2 Premedication
Prior to each CYRAMZA infusion, premedicate all patients with an intravenous histamine H1 antagonist (e.g., diphenhydramine hydrochloride). For patients who have experienced a Grade 1 or 2 infusion-related reaction, also premedicate with dexamethasone (or equivalent) and acetaminophen prior to each CYRAMZA infusion [see Dosage and Administration (2.3)].
2.3 Dose Modifications

Infusion-Related Reactions (IRR)
Reduce the infusion rate of CYRAMZA by 50% for Grade 1 or 2 IRRs. Permanently discontinue CYRAMZA for Grade 3 or 4 IRRs [see Dosage and Administration (2.2) and Warnings and Precautions (5.4)].
Hypertension
Interrupt CYRAMZA for severe hypertension until controlled with medical management. Permanently discontinue CYRAMZA for severe hypertension that cannot be controlled with antihypertensive therapy [see Warnings and Precautions (5.3)].
Proteinuria
Interrupt CYRAMZA for urine protein levels ≥2 g/24 hours. Reinitiate treatment at a reduced dose (see Table 1) once the urine protein level returns to <2 g/24 hours. If the protein level ≥2 g/24 hours reoccurs, interrupt CYRAMZA and reduce the dose (see Table 1) once the urine protein level returns to <2 g/24 hours. Permanently discontinue CYRAMZA for urine protein level >3 g/24 hours or in the setting of nephrotic syndrome [see Warnings and Precautions (5.9) and Adverse Reactions (6.1)]. Table 1: CYRAMZA Dose Reductions for Proteinuria Initial CYRAMZA Dose First Dose Reduction to: Second Dose Reduction to: 8 mg/kg 6 mg/kg 5 mg/kg 10 mg/kg 8 mg/kg 6 mg/kg
Wound Healing Complications
Interrupt CYRAMZA prior to scheduled surgery until the wound is fully healed [see Warnings and Precautions (5.6)].
Arterial Thromboembolic Events, Gastrointestinal Perforation, or Grade 3 or 4 Bleeding
Permanently discontinue CYRAMZA [see Warnings and Precautions (5.1, 5.2, 5.5)].
For toxicities related to paclitaxel, docetaxel, or the components of FOLFIRI, refer to the current prescribing information.

2.4 Preparation for Administration

Inspect vial contents for particulate matter and discoloration prior to dilution [see Description (11)]. Discard the vial, if particulate matter or discolorations are identified. Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of use. Keep the vial in the outer carton in order to protect from light.
Calculate the dose and the required volume of CYRAMZA needed to prepare the infusion solution. Vials contain either 100 mg/10 mL or 500 mg/50 mL at a concentration of 10 mg/mL solution of CYRAMZA. Withdraw the required volume of CYRAMZA and further dilute with only 0.9% Sodium Chloride Injection in an intravenous infusion container to a final volume of 250 mL. Do not use dextrose containing solutions. Gently invert the container to ensure adequate mixing. DO NOT FREEZE OR SHAKE the infusion solution. DO NOT dilute with other solutions or co-infuse with other electrolytes or medications. Store diluted infusion for no more than 24 hours at 2°C to 8°C (36°F to 46°F) or 4 hours at room temperature (below 25°C [77°F]). Discard vial with any unused portion of CYRAMZA.
2.5 Administration
Visually inspect the diluted solution for particulate matter and discoloration prior to administration. If particulate matter or discolorations are identified, discard the solution. Administer diluted CYRAMZA infusion via infusion pump over 60 minutes through a separate infusion line. Use of a protein sparing 0.22 micron filter is recommended. Flush the line with sterile sodium chloride (0.9%) solution for injection at the end of the infusion.
Prozac Weekly

Prozac Weekly

2.1 Major Depressive Disorder

Initial Treatment

Adult — Initiate PROZAC 20 mg/day orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon).The maximum fluoxetine dose should not exceed 80 mg/day.

In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 to 80 mg/day. Studies comparing fluoxetine 20, 40, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in Major Depressive Disorder in most cases [see Clinical Studies (14.1)].

Pediatric (children and adolescents) — Initiate PROZAC 10 or 20 mg/day. After 1 week at 10 mg/day, increase the dose to 20 mg/day. However, due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day. Consider a dose increase to 20 mg/day after several weeks if insufficient clinical improvement is observed. In the short-term (8 to 9 week) controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Major Depressive Disorder, patients were administered fluoxetine doses of 10 to 20 mg/day [see Clinical Studies (14.1)].

All patients — As with other drugs effective in the treatment of Major Depressive Disorder, the full effect may be delayed until 4 weeks of treatment or longer.

Periodically reassess to determine the need for maintenance treatment.

Weekly Dosing — Initiate PROZAC Weekly capsules 7 days after the last daily dose of PROZAC 20 mg [see Clinical Pharmacology (12.3)].

If satisfactory response is not maintained with PROZAC Weekly, consider reestablishing a daily dosing regimen [see Clinical Studies (14.1)].

Switching Patients to a Tricyclic Antidepressant (TCA) — Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Drug Interactions (7.7)].

2.2 Obsessive Compulsive Disorder

Initial Treatment

Adult — Initiate PROZAC 20 mg/day, orally in the morning. Consider a dose increase after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer. Administer doses above 20 mg/day once daily in the morning or twice daily (i.e., morning and noon). A dose range of 20 to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose should not exceed 80 mg/day.

In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20, 40, or 60 mg of fluoxetine or placebo [see Clinical Studies (14.2)]. In one of these studies, no dose-response relationship for effectiveness was demonstrated.

Pediatric (children and adolescents) — In adolescents and higher weight children, initiate treatment with a dose of 10 mg/day. After 2 weeks, increase the dose to 20 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 60 mg/day is recommended.

In lower weight children, initiate treatment with a dose of 10 mg/day. Consider additional dose increases after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 30 mg/day is recommended. Experience with daily doses greater than 20 mg is very minimal, and there is no experience with doses greater than 60 mg.

In the controlled clinical trial of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.2)].

Periodically reassess to determine the need for treatment.

2.3 Bulimia Nervosa

Initial Treatment — Administer PROZAC 60 mg/day in the morning. For some patients it may be advisable to titrate up to this target dose over several days. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with bulimia. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Bulimia Nervosa, patients were administered fixed daily fluoxetine doses of 20 or 60 mg, or placebo [see Clinical Studies (14.3)]. Only the 60 mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting.

Periodically reassess to determine the need for maintenance treatment.

2.4 Panic Disorder

Initial Treatment — Initiate treatment with PROZAC 10 mg/day. After one week, increase the dose to 20 mg/day. Consider a dose increase after several weeks if no clinical improvement is observed. Fluoxetine doses above 60 mg/day have not been systematically evaluated in patients with Panic Disorder. In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of Panic Disorder, patients were administered fluoxetine doses in the range of 10 to 60 mg/day [see Clinical Studies (14.4)]. The most frequently administered dose in the 2 flexible-dose clinical trials was 20 mg/day.

Periodically reassess to determine the need for continued treatment.

2.5 PROZAC and Olanzapine in Combination: Depressive Episodes Associated with Bipolar I Disorder

When using PROZAC and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.

Adult — Administer fluoxetine in combination with oral olanzapine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Make dosage adjustments, if indicated, according to efficacy and tolerability within dose ranges of fluoxetine 20 to 50 mg and oral olanzapine 5 to 12.5 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination with a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg. Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. Periodically re-examine the need for continued pharmacotherapy.

Children and adolescents (10 -17 years of age) — Administer olanzapine and fluoxetine combination once daily in the evening, generally beginning with 2.5 mg of olanzapine and 20 mg of fluoxetine. Make dosage adjustments, if indicated, according to efficacy and tolerability. Safety of co-administration of doses above 12 mg of olanzapine with 50 mg of fluoxetine has not been evaluated in pediatric clinical studies. Periodically re-examine the need for continued pharmacotherapy.

Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed-dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. The following table demonstrates the appropriate individual component doses of PROZAC and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.
Table 1: Approximate Dose Correspondence Between Symbyax1 and the Combination of PROZAC and Olanzapine
1 Symbyax (olanzapine/fluoxetine HCL) is a fixed-dose combination of PROZAC and olanzapine.
For Symbyax (mg/day) Use in Combination Olanzapine (mg/day) PROZAC (mg/day) 3 mg olanzapine/25 mg fluoxetine 2.5 20 6 mg olanzapine/25 mg fluoxetine 5 20 12 mg olanzapine/25 mg fluoxetine 10+2.5 20 6 mg olanzapine/50 mg fluoxetine 5 40+10 12 mg olanzapine/50 mg fluoxetine 10+2.5 40+10
PROZAC monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder.

2.6 PROZAC and Olanzapine in Combination: Treatment Resistant Depression

When using PROZAC and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.

Administer fluoxetine in combination with oral olanzapine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral olanzapine and 20 mg of fluoxetine. Adjust dosage, if indicated, according to efficacy and tolerability within dose ranges of fluoxetine 20 to 50 mg and oral olanzapine 5 to 20 mg. Antidepressant efficacy was demonstrated with olanzapine and fluoxetine in combination with a dose range of olanzapine 6 to 18 mg and fluoxetine 25 to 50 mg.

Safety and efficacy of fluoxetine in combination with olanzapine was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine and fluoxetine). Symbyax is dosed between 3 mg/25 mg (olanzapine/fluoxetine) per day and 12 mg/50 mg (olanzapine/fluoxetine) per day. Table 1 demonstrates the appropriate individual component doses of PROZAC and olanzapine versus Symbyax. Adjust dosage, if indicated, with the individual components according to efficacy and tolerability.

Periodically re-examine the need for continued pharmacotherapy.

Safety of coadministration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.

PROZAC monotherapy is not indicated for the treatment of treatment resistant depression (Major Depressive Disorder in patients who do not respond to 2 antidepressants of adequate dose and duration in the current episode).

2.7 Dosing in Specific Populations

Treatment of Pregnant Women — When treating pregnant women with PROZAC, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding [see Use in Specific Populations (8.1)].

Geriatric — Consider a lower or less frequent dosage for the elderly [see Use in Specific Populations (8.5)].

Hepatic Impairment — As with many other medications, use a lower or less frequent dosage in patients with hepatic impairment [see Clinical Pharmacology (12.4) and Use in Specific Populations (8.6)].

Concomitant Illness — Patients with concurrent disease or on multiple concomitant medications may require dosage adjustments [see Clinical Pharmacology (12.4) and Warnings and Precautions (5.12)].

PROZAC and Olanzapine in Combination — Use a starting dose of oral olanzapine 2.5 to 5 mg with fluoxetine 20 mg for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine or fluoxetine in combination (female gender, geriatric age, non-smoking status), or those patients who may be pharmacodynamically sensitive to olanzapine. Titrate slowly and adjust dosage as needed in patients who exhibit a combination of factors that may slow metabolism. PROZAC and olanzapine in combination have not been systematically studied in patients over 65 years of age or in patients less than 10 years of age [see Warnings and Precautions (5.16) and Drug Interactions (7.7)].

2.8 Discontinuation of Treatment

Symptoms associated with discontinuation of fluoxetine, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5.15)].

2.9 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with PROZAC. Conversely, at least 5 weeks should be allowed after stopping PROZAC before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.10 Use of PROZAC with Other MAOIs such as Linezolid or Methylene Blue

Do not start PROZAC in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)].

In some cases, a patient already receiving PROZAC therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, PROZAC should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with PROZAC may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with PROZAC is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].
Cymbalta

Cymbalta

Swallow CYMBALTA whole. Do not chew or crush. Do not open the capsule and sprinkle its contents on food or mix with liquids. All of these might affect the enteric coating. CYMBALTA can be given without regard to meals. If a dose of CYMBALTA is missed, take the missed dose as soon as it is remembered. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular time. Do not take two doses of CYMBALTA at the same time.

2.1 Dosage for Treatment of Major Depressive Disorder

Administer CYMBALTA at a total dose of 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily). For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer any additional benefits. The safety of doses above 120 mg/day has not been adequately evaluated. Periodically reassess to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.1)].

2.2 Dosage for Treatment of Generalized Anxiety Disorder

Adults — For most patients, initiate CYMBALTA 60 mg once daily. For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg once daily dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit. Nevertheless, if a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The safety of doses above 120 mg once daily has not been adequately evaluated. Periodically reassess to determine the continued need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2)].

Elderly — Initiate CYMBALTA at a dose of 30 mg once daily for 2 weeks before considering an increase to the target dose of 60 mg. Thereafter, patients may benefit from doses above 60 mg once daily. If a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The maximum dose studied was 120 mg per day. Safety of doses above 120 mg once daily has not been adequately evaluated [see Clinical Studies (14.2)].

Children and Adolescents (7 to 17 years of age) — Initiate CYMBALTA at a dose of 30 mg once daily for 2 weeks before considering an increase to 60 mg. The recommended dose range is 30 to 60 mg once daily. Some patients may benefit from doses above 60 mg once daily. If a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The maximum dose studied was 120 mg per day. The safety of doses above 120 mg once daily has not been evaluated [see Clinical Studies (14.2)].

2.3 Dosage for Treatment of Diabetic Peripheral Neuropathic Pain

Administer CYMBALTA 60 mg once daily. There is no evidence that doses higher than 60 mg confer additional significant benefit and the higher dose is clearly less well tolerated [see Clinical Studies (14.3)]. For patients for whom tolerability is a concern, a lower starting dose may be considered.

Since diabetes is frequently complicated by renal disease, consider a lower starting dose and gradual increase in dose for patients with renal impairment [see Dosage and Administration (2.6), Use in Specific Populations (8.10), and Clinical Pharmacology (12.3)].

2.4 Dosage for Treatment of Fibromyalgia

Administer CYMBALTA 60 mg once daily. Begin treatment at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. Some patients may respond to the starting dose. There is no evidence that doses greater than 60 mg/day confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions [see Clinical Studies (14.4)].

2.5 Dosage for Treatment of Chronic Musculoskeletal Pain

Administer CYMBALTA 60 mg once daily. Begin treatment at 30 mg for one week, to allow patients to adjust to the medication before increasing to 60 mg once daily. There is no evidence that higher doses confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions [see Clinical Studies (14.5)].

2.6 Dosing in Special Populations

Hepatic Impairment — Avoid use in patients with chronic liver disease or cirrhosis [see Warnings and Precautions (5.14) and Use in Specific Populations (8.9)].

Severe Renal Impairment — Avoid use in patients with severe renal impairment, GFR <30 mL/min [see Warnings and Precautions (5.14) and Use in Specific Populations (8.10)].

2.7 Discontinuing CYMBALTA

Adverse reactions after discontinuation of CYMBALTA, after abrupt or tapered discontinuation, include: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see Warnings and Precautions (5.7)].

2.8 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with CYMBALTA. Conversely, at least 5 days should be allowed after stopping CYMBALTA before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4)].

2.9 Use of CYMBALTA with Other MAOIs such as Linezolid or Methylene Blue

Do not start CYMBALTA in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4)].

In some cases, a patient already receiving CYMBALTA therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, CYMBALTA should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with CYMBALTA may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.4)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with CYMBALTA is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.4)].
Evista

Evista

2.1 Recommended Dosing

The recommended dosage is one 60 mg EVISTA (raloxifene hydrochloride tablets) tablet daily, which may be administered any time of day without regard to meals [see Clinical Pharmacology (12.3)].

For the indications in risk of invasive breast cancer the optimum duration of treatment is not known [see Clinical Studies (14.3, 14.4)].

2.2 Recommendations for Calcium and Vitamin D Supplementation

For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Total daily intake of calcium above 1500 mg has not demonstrated additional bone benefits while daily intake above 2000 mg has been associated with increased risk of adverse effects, including hypercalcemia and kidney stones. The recommended intake of vitamin D is 400-800 IU daily. Patients at increased risk for vitamin D insufficiency (e.g., over the age of 70 years, nursing home bound, or chronically ill) may need additional vitamin D supplements. Patients with gastrointestinal malabsorption syndromes may require higher doses of vitamin D supplementation and measurement of 25-hydroxyvitamin D should be considered.
Humatrope

Humatrope

For subcutaneous injection.

Therapy with Humatrope should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with short stature associated with GH deficiency, Turner syndrome, idiopathic short stature, SHOX deficiency, small for gestational age birth, or adult patients with either childhood-onset or adult-onset GH deficiency.

2.1 Reconstitution

Vial — Each 5-mg vial of Humatrope should be reconstituted with 1.5 to 5 mL of Diluent for Humatrope. The diluent should be injected into the vial of Humatrope by aiming the stream of liquid gently against the vial wall. Following reconstitution, the vial should be swirled with a GENTLE rotary motion until the contents are completely dissolved. DO NOT SHAKE. The resulting solution should be clear. If the solution is cloudy or contains particulate matter, the contents MUST NOT be injected.

If sensitivity to the diluent should occur, the vials may be reconstituted with Bacteriostatic Water for Injection (Benzyl Alcohol preserved), USP or Sterile Water for Injection, USP. When Humatrope is reconstituted with Bacteriostatic Water for Injection, USP, the solution should be kept refrigerated at 36° to 46°F (2° to 8°C) and used within 14 days. It is important to note that benzyl alcohol used as a preservative in Bacteriostatic Water has been associated with toxicity in newborns. Therefore, Bacteriostatic Water for Injection must not be used to reconstitute Humatrope for use in a newborn infant. When Humatrope is to be administered to a newborn infant it should be reconstituted with the diluent provided or, if the infant is sensitive to the diluent, Sterile Water for Injection, USP. When reconstituted with Sterile Water for Injection the solution should be kept refrigerated at 36° to 46°F (2° to 8°C) and used within 24 hours.

Cartridge — The Humatrope cartridge has been designed for use only with the Humatrope injection device. Each cartridge of Humatrope should be reconstituted using only the diluent syringe that accompanies the cartridge and should not be reconstituted with the Diluent for Humatrope provided with Humatrope vials. The reconstituted solution should be clear. If the solution is cloudy or contains particulate matter, the contents MUST NOT be injected. Humatrope cartridges should not be used if the patient is allergic to metacresol or glycerin.

The somatropin concentrations for the reconstituted Humatrope cartridges are as follows:
6 mg cartridge (gold) 2.08 mg/mL 12 mg cartridge (teal) 4.17 mg/mL 24 mg cartridge (purple) 8.33 mg/mL
[See How Supplied (16.2) and Information for the Patient for comprehensive directions on Humatrope cartridge reconstitution].

2.2 General Administration Guidelines

For all indications, the following general principles for administration should be followed:
When using the Humatrope vial the septum of the vial should be wiped with an alcoholic antiseptic solution before and after each injection to prevent contamination of the contents by repeated needle insertions. Sterile disposable syringes and needles should be used. The volume of the syringe should be small enough so that the prescribed dose can be withdrawn from the vial with reasonable accuracy. When using the Humatrope cartridge a sterile disposable needle should be used for each injection. Humatrope should be administered by subcutaneous injection with regular rotation of injection sites to avoid lipoatrophy. For pediatric patients the calculated weekly Humatrope dosage should be divided into equal doses given either 6 or 7 days per week. For adult patients the prescribed dose should be administered daily.
2.3 Dosing for Pediatric Patients

The Humatrope dosage and administration schedule should be individualized for each patient based on the growth response. Failure to increase height velocity, particularly during the first year of treatment, should prompt close assessment of compliance and evaluation of other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human growth hormone. Response to somatropin treatment tends to decrease with time. Somatropin treatment for stimulation of linear growth should be discontinued once epiphyseal fusion has occurred.

The recommended weekly dosages in milligrams (mg) per kilogram (kg) of body weight for pediatric patients are:

a Recent literature has recommended initial treatment with larger doses of somatropin (e.g., 0.067 mg/kg/day), especially in very short children (i.e., height SDS <–3), and/or older pubertal children, and that a reduction in dosage (e.g., gradually towards 0.033 mg/kg/day) should be considered if substantial catch-up growth is observed during the first few years of therapy. On the other hand, in younger SGA children (e.g., approximately <4 years) (who respond the best in general) with less severe short stature (i.e., baseline height SDS values between -2 and -3), consideration should be given to initiating treatment at a lower dose (e.g., 0.033 mg/kg/day), and titrating the dose as needed over time. In all children, clinicians should carefully monitor the growth response, and adjust the somatropin dose as necessary.
Growth hormone deficiency 0.026 to 0.043 mg/kg/day (0.18 to 0.30 mg/kg/week) Turner syndrome up to 0.054 mg/kg/day (0.375 mg/kg/week) Idiopathic short stature up to 0.053 mg/kg/day (0.37 mg/kg/week) SHOX deficiency 0.050 mg/kg/day (0.35 mg/kg/week) Small for gestational age up to 0.067 mg/kg/day (0.47 mg/kg/week)a
2.4 Dosing for Patients with Adult Growth Hormone Deficiency

Either of two approaches to Humatrope dosing may be followed: a non-weight-based regimen or a weight-based regimen.

Non-weight based — based on published consensus guidelines, a starting dose of approximately 0.2 mg/day (range, 0.15-0.30 mg/day) may be used without consideration of body weight. This dose can be increased gradually every 1-2 months by increments of approximately 0.1-0.2 mg/day, according to individual patient requirements based on the clinical response and serum insulin-like growth factor I (IGF-I) concentrations. The dose should be decreased as necessary on the basis of adverse events and/or serum IGF-I concentrations above the age- and gender-specific normal range. Maintenance dosages vary considerably from person to person, and between male and female patients.

Weight-based — based on the dosing regimen used in the original adult GH deficiency registration trials, the recommended dosage at the start of treatment is not more than 0.006 mg/kg (6 μg/kg) daily. The dose may be increased according to individual patient requirements to a maximum of 0.0125 mg/kg (12.5 μg/kg) daily. Clinical response, side effects, and determination of age- and gender-adjusted serum IGF-I concentrations should be used as guidance in dose titration.

A lower starting dose and smaller dose increments should be considered for older patients, who are more prone to the adverse effects of somatropin than younger individuals. In addition, obese individuals are more likely to manifest adverse effects when treated with a weight-based regimen. Estrogen-replete women may need higher doses than men. Oral estrogen administration may increase the dose requirements in women.
Quinidine Gluconate Sol...

Quinidine Gluconate Solution

Because the kinetics of absorption may vary with the patient's peripheral perfusion, intramuscular injection of quinidine gluconate is not recommended.

Treatment of P. falciparum malaria — Two regimens have each been shown to be effective, with or without concomitant exchange transfusion. There are no data indicating that either should be preferred to the other.

In Regimen A, each patient received a loading dose of 15 mg/kg of quinidine base (that is, 24 mg/kg of quinidine gluconate) in 250 mL of normal saline infused over 4 hours. Thereafter, each patient received a maintenance regimen of 7.5 mg/kg of base (12 mg/kg of quinidine gluconate) infused over 4 hours every 8 hours, starting 8 hours after the beginning of the loading dose. This regimen was continued for 7 days, except that in patients able to swallow, the maintenance infusions were discontinued, and approximately the same daily doses of quinidine were supplied orally, using 300–mg tablets of quinidine sulfate.

In Regimen B, each patient received a loading dose of 6.25 mg/kg of quinidine base (that is, 10 mg/kg of quinidine gluconate) in approximately 5 mL/kg of normal saline over 1–2 hours. Thereafter, each patient received a maintenance infusion of 12.5 μg/kg/min of base (that is, 20 μg/kg/min of quinidine gluconate). In patients able to swallow, the maintenance infusion was discontinued, and eight–hourly oral quinine sulfate was administered to provide approximately as much daily quinine base as the patient had been receiving quinidine base (for example, each adult patient received 650 mg of quinine sulfate every eight hours). Quinidine/quinine therapy was continued for 72 hours or until parasitemia had decreased to 1% or less, whichever came first. After completion of quinidine/quinine therapy, adults able to swallow received a single 1500–mg/75–mg dose of sulfadoxine/pyrimethamine (FANSIDAR®, Roche Laboratories) or a seven–day course of tetracycline (250 mg four times daily), while those unable to swallow received seven–day courses of intravenous doxycycline hyclate (VIBRAMYCIN®, Roerig), 100 mg twice daily. Most of the patients described as having been treated with this regimen also underwent exchange transfusion. Small children have received this regimen without dose adjustment and with apparent good results, notwithstanding the known differences in quinidine pharmacokinetics between pediatric patients and adults (see Clinical Pharmacology).

Even in patients without preexisting cardiac disease, antimalarial use of quinidine has occasionally been associated with hypotension, QTc prolongation, and cinchonism; see Warnings.

Treatment of symptomatic atrial fibrillation/flutter — A patient receiving an intravenous infusion of quinidine must be carefully monitored, with frequent or continuous electrocardiography and blood–pressure measurement. The infusion should be discontinued as soon as sinus rhythm is restored: the QRS complex widens to 130% of its pre–treatment duration; the QTc interval widens to 130% of its pre–treatment duration, and is then longer than 500 ms; P waves disappear; or the patient develops significant tachycardia, symptomatic bradycardia, or hypotension.

To prepare quinidine for infusion, the contents of the supplied vial (80 mg/mL) should be diluted to 50 mL (16 mg/mL) with 5% dextrose. The resulting solution may be stored for up to 24 hours at room temperature or up to 48 hours at 4°C (40°F).

Because quinidine may be absorbed to PVC tubing, tubing length should be minimized. In one study (Am J Health Syst Pharm. 1996; 53:655–8), use of 112 inches of tubing resulted in 30% loss of quinidine, but drug loss was less than 3% when only 12 inches of tubing was used.

An infusion of quinidine must be delivered slowly, preferable under control of a volumetric pump, no faster than 0.25 mg/kg/min (that is, no faster than 1 mL/kg/hour). During the first few minutes of the infusion, the patient should be monitored especially closely for possible hypersensitive or idiosyncratic reactions.

Most arrhythmias that will respond to intravenous quinidine will respond to a total dose of less than 5 mg/kg, but some patients may require as much as 10 mg/kg. If conversion to sinus rhythm has not been achieved after infusion of 10 mg/kg, then the infusion should be discontinued, and other means of conversion (eg, direct–current cardioversion) should be considered.

Treatment of life–threatening ventricular arrhythmias — Dosing regimens for the use of intravenous quinidine gluconate in controlling life–threatening ventricular arrhythmias have not been adequately studied. Described regimens have generally been similar to the regimen described just above for the treatment of symptomatic atrial fibrillation/flutter.
Trulicity

Trulicity

2.1 Dosage

The recommended initiating dose of TRULICITY is 0.75 mg once weekly. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly.

Administer TRULICITY once weekly, any time of day, with or without food. TRULICITY should be injected subcutaneously in the abdomen, thigh, or upper arm.

If a dose is missed, instruct patients to administer as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.

The day of weekly administration can be changed if necessary as long as the last dose was administered 3 or more days before.

2.2 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin

When initiating TRULICITY, consider reducing the dosage of concomitantly administered insulin secretagogues (e.g., sulfonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.3)].

2.3 Dosage in Patients with Renal Impairment

No dose adjustment is recommended in patients with renal impairment including end-stage renal disease (ESRD). Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions. [see Warning and Precautions (5.5), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.4 Important Administration Instructions

Prior to initiation of TRULICITY, patients should be trained by their healthcare professional on proper injection technique. Training reduces the risk of administration errors such as improper injection site, needle sticks, and incomplete dosing. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations. The instructions can also be found at www.trulicity.com.

When using TRULICITY with insulin, instruct patients to administer as separate injections and to never mix the products. It is acceptable to inject TRULICITY and insulin in the same body region but the injections should not be adjacent to each other.

When injecting in the same body region, advise patients to use a different injection site each week. TRULICITY must not be administered intravenously or intramuscularly.

TRULICITY solution should be visually inspected for particulate matter and discoloration prior to administration.

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