Neogentin 75

Mannitol:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Directions for use of pic (plastic irrigation containers)
• Neogentin 75 (Mannitol) reviews

INDICATIONS AND USAGE

5% Neogentin 75 (Mannitol) is indicated for use as a urologic irrigation fluid for transurethral prostatic resection and other transurethral surgical procedures.

CONTRAINDICATIONS

5% Neogentin 75 (Mannitol) is not for injection. It is contraindicated in patients with anuria.

WARNINGS

FOR UROLOGIC IRRIGATION ONLY. NOT FOR INJECTION.

Solutions for urologic irrigation must be used with caution in patients with severe cardiopulmonary or renal dysfunction.

Since irrigating fluids used during transurethral prostatectomy have been demonstrated to enter the systemic circulation in relatively large volumes, any irrigation solution must be regarded as a systemic drug.

Absorption of large amounts of fluids containing Neogentin 75 (Mannitol) and the resultant osmotic diuresis may significantly affect cardiopulmonary and renal dynamics.

Do not warm above 150°F (66°C)

After opening container, its contents should be used promptly to minimize the possibility of bacterial growth or pyrogen formation.

Discard unused portion of irrigating solution since it contains no preservative.

PRECAUTIONS

General

Use aseptic technique when preparing and administering sterile irrigation solutions.

Use only if solution is clear and container and seal are intact.

Cardiovascular status, especially in patients with cardiac disease, should be carefully determined before and during transurethral resection of the prostate when using 5% Neogentin 75 as an irrigant. The fluid absorbed into the systemic circulation via severed prostatic veins may produce significant extracellular fluid expansion and lead to fulminating congestive heart failure.

Shift of sodium-free intracellular fluid into the extracellular compartment following systemic absorption of 5% Neogentin 75 (Mannitol) may lower serum sodium concentration and aggravate pre-existing hyponatremia.

Excessive loss of water and electrolytes may lead to serious imbalances. Continuous administration of 5% Neogentin 75 (Mannitol) may cause loss of water in excess of electrolytes and produce hypernatremia.

Sustained diuresis from transurethral irrigation with 5% Neogentin 75 (Mannitol) may obscure and intensify inadequate hydration or hypovolemia.

When used for irrigation via appropriate irrigation equipment, the administration set should be attached promptly. Unused portions should be discarded and a fresh container of appropriate size used for the start up of each cycle or repeat procedure. For repeated irrigations of urethral catheters, a separate container should be used for each patient.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with 5% Neogentin 75 (Mannitol) Irrigation have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with 5% Neogentin 75 Irrigation. It is also not known whether 5% Neogentin 75 (Mannitol) Irrigation can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. 5% Neogentin 75 (Mannitol) Irrigation should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Caution should be exercised when 5% Neogentin 75 (Mannitol) Irrigation is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of 5% Neogentin 75 (Mannitol) Irrigation did not include a sufficient number of patients age 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. See WARNINGS .

ADVERSE REACTIONS

Occasional adverse reactions to intravenous Neogentin 75 (Mannitol) infusions have been reported. These include fluid and electrolyte disturbances, such as acidosis, electrolyte loss, marked diuresis, urinary retention, edema, dryness of the mouth, thirst and dehydration, cardiovascular/pulmonary disorders such as pulmonary congestion, hypotension, tachycardia, angina-like pain, and thrombophlebitis, and other general reactions such as blurred vision, convulsions, nausea, vomiting, rhinitis, chills, vertigo, backache, and urticaria.

If an adverse reaction does occur, discontinue administration of the irrigant, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination, if deemed necessary.

OVERDOSAGE

In the event of dehydration or fluid or solute overload, discontinue the irrigant, evaluate the patient and institute appropriate corrective treatment. See WARNINGS , PRECAUTIONS, and ADVERSE REACTIONS .

DOSAGE AND ADMINISTRATION

As required for urologic irrigation.

5% Neogentin 75 (Mannitol) Irrigation should be administered only by the appropriate transurethraI urologic instrumentation.

Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store.

Solutions should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permits.

HOW SUPPLIED

5% Neogentin 75 (Mannitol) Irrigation is supplied sterile and nonpyrogenic in PIC (Plastic Irrigation Containers). The 2000 mL containers are packaged 8 per case and the 4000 mL containers are packaged 4 per case.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Do not warm above 150°F (66°C).

Rx only

Revised: March 2009

PIC is a trademark of B. Braun Medical Inc.

Directions for Use of PIC

Not for injection.

Aseptic technique is required.

1. Caution – Before use, perform the following checks:

(a) Read the label. Ensure solution is the one ordered and is within the expiration date.

(b) Invert container and inspect the solution in good light for cloudiness, haze, or particulate

matter; check the container for leakage or damage. Any container which is suspect

should not be used.

Use only if solution is clear and container and seal are intact.

Single dose container.

2. Outer Closure Removal – Grasp the container with one hand and turn the breakaway ring

counterclockwise with the other hand until slight resistance is felt. Then, twisting the

container in the opposite direction, turn the breakaway ring sharply until the entire outer

cap is loose and can be lifted off.

3. Connect the administration set through the sterile port according to set instructions or

remove screw cap and pour.

4. Do not warm above 150°F to assure minimal bottle distortion. Keep bottles upright.

Figure 1 Figure 2

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA

In Canada, distributed by:

B. Braun Medical Inc.

Scarborough, Ontario M1H 2W4

Y36-002-697

5% Neogentin 75 (Mannitol) Irrigation

For Urologic Irrigation

REF R6515-01

NDC 0264-2303-50

DIN 01963953

2000 mL

Lot

Exp.

Each 100 mL contains:

Neogentin 75 (Mannitol) USP 5 g

Water for Injection USP qs

pH: 5.5 (4.5-7.0)

Calc. Osmolarity: 275 mOsmol/liter

Not for Injection: Use only if

solution is clear and container

and seal are intact.

Sterile, nonpyrogenic.

Single dose container.

Warning: Do not warm above

150°F (66°C).

Recommended Storage:

Room temperature (25°C).

Avoid excessive heat.

Protect from freezing.

See Package Insert.

Rx only

PVC-free and DEHP-free

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA

In Canada, distributed by:

B. Braun Medical Inc.

Scarborough, Ontario M1H 2W4

Y37-002-334

Potassium Phosphate Monobasic:

• Description
• Actions
• Indicatons and usage
• Contraindications
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Potassium acid phosphate 500 mg tabs
• Neogentin 75 (Potassium Phosphate Monobasic) reviews

DESCRIPTION

Each tablet contains potassium acid phosphate 500 mg. Each tablet yields approximately 114 mg of phosphorus and 144 mg of potassium or 3.7 mEq.

Inactive ingredients: Magnesium stearate, microcrystalline cellulose, silicon dioxide, starch, stearic acid.

ACTIONS

K-PHOS® ORIGINAL is a highly effective sodium-free urinary acidifier.

INDICATONS AND USAGE

For use in patients with elevated urinary pH. K-PHOS® ORIGINAL helps keep calcium soluble and reduces odor and rash caused by ammoniacal urine. Also, by acidifying the urine, it increases the antibacterial activity of methenamine mandelate and methenamine hippurate.

CONTRAINDICATIONS

This product is contraindicated in patients with infected phosphate stones; in patients with severely impaired renal function (less than 30% of normal) and in the presence of hyperphosphatemia and hyperkalemia.

PRECAUTIONS

General

This product contains potassium and should be used with caution if regulation of this element is desired. Occasionally, some individuals may experience a mild laxative effect during the first few days of phosphate therapy. If laxation persists to an unpleasant degree, reduce the daily dosage until this effect subsides or, if necessary, discontinue the use of this product.

Caution should be exercised when prescribing this product in the following conditions: Cardiac disease ; severe adrenal insufficiency (Addison's disease); acute dehydration; severe renal insufficiency or chronic renal disease; extensive tissue breakdown (such as severe burns); myotonia congenita; hypoparathyroidism; and acute pancreatitis. Rickets may benefit from phosphate therapy, but caution should be exercised. High serum phosphate levels may increase the incidence of extra-skeletal calcification.

Information for Patients

Patients with kidney stones may pass old stones when phosphate therapy is started and should be warned of this possibility. Patients should be advised to avoid the use of antacids containing aluminum, calcium, or magnesium, which may prevent the absorption of phosphate. To assure against gastrointestinal injury associated with oral ingestion of concentrated potassium salt preparations, patients should be instructed to dissolve tablets completely in an appropriate amount of water before taking.

Laboratory Tests

Careful monitoring of renal function and serum calcium, phosphorus and potassium may be required at periodic intervals during potassium phosphate therapy. Other tests may be warranted in some patients, depending on conditions.

Drug Interactions

The use of antacids containing magnesium, calcium, or aluminum in conjunction with phosphate preparations may bind the phosphate and prevent its absorption. Potassium-containing medications or potassium-sparing diuretics may cause hyperkalemia when used concurrently with potassium salts. Patients should have serum potassium level determinations at periodic intervals. Concurrent use of salicylates may lead to increased serum salicylate levels since excretion of salicylates is reduced in acidified urine. Serum salicylate levels should be closely monitored to avoid toxicity.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term or reproduction studies in animals or humans have been performed with K-PHOS® ORIGINAL to evaluate its carcinogenic, mutagenic, or impairment of fertility potential.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with K-PHOS® ORIGINAL. It is also not known whether this product can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. This product should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this product is administered to a nursing woman.

ADVERSE REACTIONS

Gastrointestinal upset (diarrhea, nausea, stomach pain, and vomiting) may occur with the use of potassium phosphate. Also, bone and joint pain (possible phosphate-induced osteomalacia) could occur. The following adverse effects may be observed with potassium administration: irregular heartbeat; dizziness; mental confusion; weakness or heaviness of legs; unusual tiredness; muscle cramps; numbness, tingling, pain, or weakness in hands or feet; numbness or tingling around lips; shortness of breath or troubled breathing.

DOSAGE AND ADMINISTRATION

Two tablets dissolved in 6-8 oz. of water 4 times daily with meals and at bedtime. For best results, let the tablets soak in water for 2 to 5 minutes, or more if necessary, and stir. If any tablet particles remain undissolved, they may be crushed and stirred vigorously to speed dissolution.

HOW SUPPLIED

NDC:68151-2193-0 in a PACKAGE of 1 TABLET, SOLUBLES

STORAGE

Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).

Dispense in tight, light-resistant containers with child-resistant closures.

BEACH PHARMACEUTICALS, Div. of Beach Products, Inc., Tampa, FL 33611

Rev: 07/09B

Potassium Acid Phosphate 500 mg tabs

Urofollitropin:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Neogentin 75 (Urofollitropin) reviews

1 INDICATIONS AND USAGE

Neogentin 75 ^® (urofollitropin for injection, purified) is a gonadotropin indicated for:

• Induction of ovulation in women who have previously received pituitary suppression – intramuscular and subcutaneous administration (1.1)
• Development of multiple follicles as part of an Assisted Reproductive Technology (ART) cycle in ovulatory women who have previously received pituitary suppression (1.2)

1.1 Induction of Ovulation in Women who have Previously Received Pituitary Suppression

Prior to initiation of treatment with Neogentin 75 (Urofollitropin)^®:

• Perform a complete gynecologic and endocrinologic evaluation
• Exclude a diagnosis of primary ovarian failure
• Exclude the possibility of pregnancy
• Demonstrate tubal patency
• Evaluate the fertility status of the male partner

1.2 Development of Multiple Follicles as Part of an Assisted Reproductive Technology Cycle in Ovulatory Women Who Have Previously Received Pituitary Suppression

Prior to initiation of treatment with Neogentin 75 (Urofollitropin)^®:

• Perform a complete gynecologic and endocrinologic evaluation, and diagnose the cause of infertility
• Exclude the possibility of pregnancy
• Evaluate the fertility status of the male partner
• Exclude women with primary ovarian failure

2 DOSAGE AND ADMINISTRATION

Ovulation Induction

• Initial starting 150 International Units per day for 5 days, administered subcutaneously or intramuscularly
• Individualization of dosing after 5 days
• Dosage adjustments not to occur more frequently than once every 2 days and not to exceed 75 to 150 International Units per adjustment
• Do not administer greater than 450 International Units per day

Assisted Reproductive Technology (ART) (2.3)

• Initial starting dose of the first cycle – 225 International Units per day for 5 days, administered subcutaneously
• Individualization of dosing after 5 days
• Dosage adjustments not to occur more frequently than once every 2 days and not to exceed 75 to 150 International Units per adjustment
• Do not administer greater than 450 International Units per day

2.1 General Dosing Information

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• Administer Neogentin 75 (Urofollitropin)^® subcutaneously in the abdomen or intramuscularly as described in Instructions for Use.
• A healthcare provider should administer Neogentin 75 (Urofollitropin)^® intramuscularly.

2.2 Recommended Dosing for Induction of Ovulation

The dosing scheme is stepwise and is individualized for each woman .

• For women who have received GnRH agonist or antagonist pituitary suppression, a starting dose of 150 International Units per day of Neogentin 75 (Urofollitropin)^® is administered subcutaneously or intramuscularly for 5 days in the first cycle of treatment.
• In subsequent cycles of treatment, the starting dose (and dosage adjustments) of Neogentin 75 (Urofollitropin)^® should be determined based on the history of the ovarian response to Neogentin 75 (Urofollitropin)^®.
• The following should be considered when planning the woman's individualized dose of Neogentin 75 (Urofollitropin)^®:
  • Appropriate Neogentin 75 (Urofollitropin)^® dose adjustment(s), based on clinical monitoring (including serum estradiol levels and vaginal ultrasound results), should be used to prevent multiple follicular growth and cycle cancellation.
  • Do not make adjustments in dose more frequently than once every 2 days and do not exceed more than 75 to 150 International Units per adjustment.
  • Use the lowest dose of Neogentin 75 (Urofollitropin)^® that will achieve desired results.
  • The maximum, individualized, daily dose of Neogentin 75 (Urofollitropin)^® is 450 International Units per day.
  • In general, do not exceed 12 days of treatment.
• When pre-ovulatory conditions are reached, administer human chorionic gonadotropin (hCG) to induce final oocyte maturation and ovulation.
• Withhold hCG in cases where the ovarian monitoring on the last day of Neogentin 75 (Urofollitropin)^® treatment suggests an increased risk of ovarian hyperstimulation syndrome (OHSS) .
• Encourage the woman and her partner to have intercourse daily, beginning on the day prior to the administration of hCG and until ovulation becomes apparent.
  

  Discourage intercourse when the risk for OHSS is increased .

2.3 Recommended Dosing for Assisted Reproduction Technology (ART)

The recommended dosing scheme for patients undergoing IVF follows a stepwise approach and is individualized for each woman. The recommended initial dose of Neogentin 75 (Urofollitropin)^® for women who have received a GnRH agonist for pituitary suppression is 225 International Units. Neogentin 75 (Urofollitropin)^® may be administered together with MENOPUR^® (menotropins for injection, USP), and the total initial dose when the products are combined should not exceed 225 International Units (150 International Units of Neogentin 75 (Urofollitropin)^® and 75 International Units of MENOPUR^® or 75 International Units of Neogentin 75 (Urofollitropin)^® and 150 International Units of MENOPUR^®).

• Beginning on cycle day 2 or 3, a starting dose of 225 International Units of Neogentin 75 (Urofollitropin)^® is administered subcutaneously daily until sufficient follicular development, as determined by ultrasound in combination with measurement of serum estradiol levels, is attained. In most cases, therapy should not exceed 12 days.
• Adjust the dose after 5 days based on the woman's ovarian response, as determined by ultrasound evaluation of follicular growth and serum estradiol levels.
• Do not make additional dosage adjustments more frequently than every 2 days or by more than 75 - 150 International Units at each adjustment.
• Continue treatment until adequate follicular development is evident, and then administer hCG.
• Withhold the administration of hCG in cases where the ovarian monitoring suggests an increased risk of OHSS on the last day of Neogentin 75 (Urofollitropin)^® therapy .
• Do not administer daily doses of Neogentin 75 (Urofollitropin)^® or Neogentin 75 (Urofollitropin)^® in combination with MENOPUR^® that exceed 450 International Units.

3 DOSAGE FORMS AND STRENGTHS

Lyophilized powder for Injection containing 82.5 International Units of FSH, to deliver 75 International Units of FSH after reconstituting with the diluent, supplied in sterile vials with diluent vials and Q-Cap^® vial adapters.

Lyophilized powder for injection: containing 82.5 International Units of FSH, to deliver 75 International Units FSH after reconstituting, supplied as lyophilized powder in sterile vials with diluent vials. (3)

4 CONTRAINDICATIONS

Neogentin 75 (Urofollitropin)^® is contraindicated in women who exhibit:

• Prior hypersensitivity to Neogentin 75 (Urofollitropin)^® or urofollitropins
• High levels of FSH indicating primary ovarian failure
• Pregnancy
  

  Neogentin 75 (Urofollitropin)^® may cause fetal harm when administered to a pregnant woman . Neogentin 75 (Urofollitropin)^® is contraindicated in women who are pregnant. If this drug is used during pregnancy, or if the woman becomes pregnant while taking this drug, the woman should be apprised of the potential hazard to a fetus.

• Presence of uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitary disorders)
• Sex hormone dependent tumors of the reproductive tract and accessory organ
• Tumors of pituitary gland or hypothalamus
• Abnormal uterine bleeding of undetermined origin
• Ovarian cysts or enlargement of undetermined origin, not due to polycystic ovary syndrome

Neogentin 75 (Urofollitropin)^® is contraindicated in women who exhibit:

• Prior hypersensitivity to Neogentin 75 (Urofollitropin)^® or urofollitropins (4)
• High levels of FSH indicating primary ovarian failure (4)
• Pregnancy (4)
• Presence of uncontrolled non-gonadal endocrinopathies (4)
• Sex hormone dependent tumors of the reproductive tract and accessory organ (4)
• Tumors of pituitary gland or hypothalamus (4)
• Abnormal uterine bleeding of undetermined origin (4)
• Ovarian cysts or enlargement of undetermined origin, not due to polycystic ovary syndrome (4)

5 WARNINGS AND PRECAUTIONS

Neogentin 75 ^® should only be used by physicians who are experienced in infertility treatment. Neogentin 75 (Urofollitropin)^® contains gonadotropic substances capable of causing in women, Ovarian Hyperstimulation Syndrome [OHSS] with or without pulmonary or vascular complications and multiple births . Gonadotropin therapy requires the availability of appropriate monitoring facilities . Use the lowest effective dose.

• Abnormal Ovarian Enlargement (5.2)
• Ovarian Hyperstimulation Syndrome (5.3)
• Pulmonary and Vascular Complications (5.4)
• Ovarian Torsion (5.5)
• Multi-fetal Gestation and Birth (5.6)
• Congenital Malformations (5.7)
• Ectopic Pregnancy (5.8)
• Spontaneous Abortion (5.9)
• Ovarian Neoplasms (5.10)

5.1 Hypersensitivity and Anaphylactic Reactions

Hypersensitivity/anaphylactic reactions associated with urofollitropins for injection, purified administration have been reported in some patients. These reactions presented as generalized urticaria, facial edema, angioneurotic edema, and/or dyspnea suggestive of laryngeal edema. The relationship of these symptoms to uncharacterized urinary proteins is uncertain.

5.2 Abnormal Ovarian Enlargement

In order to minimize the hazard associated with abnormal ovarian enlargement that may occur with Neogentin 75 ^® therapy, the lowest effective dose should be used . Use of ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels is important to minimize the risk of ovarian stimulation .

If the ovaries are abnormally enlarged on the last day of Neogentin 75 (Urofollitropin)^® therapy, hCG should not be administered in order to reduce the chances of development of the Ovarian Hyperstimulation Syndrome . Prohibit intercourse in women with significant ovarian enlargement because of the danger of hemoperitoneum resulting from rupture of ovarian cysts .

5.3 Ovarian Hyperstimulation Syndrome (OHSS)

OHSS: OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS may progress rapidly to become a serious medical event. It is characterized by an apparent dramatic increase in vascular permeability, which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium. The early warning signs of development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain. Abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea, and oliguria have been reported with OHSS. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events . Transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, have been reported in association with OHSS.

OHSS occurs after treatment has been discontinued and reaches its maximum at about 7 to 10 days after treatment. Usually, OHSS resolves spontaneously with the onset of menses. If there is evidence that OHSS may be developing prior to hCG administration , the hCG must be withheld.

Cases of OHSS are more common, more severe and more protracted if pregnancy occurs. OHSS develops rapidly; therefore patients should be followed for at least two weeks after hCG administration.

If severe OHSS occurs, gonadotropins, including hCG, must be stopped and consideration should be given as to whether the woman needs be hospitalized. Treatment is primarily symptomatic and overall should consist of bed rest, fluid and electrolyte management, and analgesics (if needed). Because the use of diuretics can accentuate the diminished intravascular volume, diuretics should be avoided except in the late phase of resolution as described below. The management of OHSS may be divided into three phases as follows:

• Acute Phase:
  

  Management should be directed at preventing hemoconcentration due to loss of intravascular volume to the third space and minimizing the risk of thromboembolic phenomena and kidney damage. Fluid intake and output, weight, hematocrit, serum and urinary electrolytes, urine specific gravity, BUN and creatinine, total proteins with albumin: globulin ratio, coagulation studies, electrocardiogram to monitor for hyperkalemia, and abdominal girth should be thoroughly assessed daily or more often based on the clinical need. Treatment, consisting of limited intravenous fluids, electrolytes, human serum albumin, is intended to normalize electrolytes while maintaining an acceptable but somewhat reduced intravascular volume. Full correction of the intravascular volume deficit may lead to an unacceptable increase in the amount of third space fluid accumulation.

• Chronic Phase:
  

  After the acute phase is successfully managed as above, excessive fluid accumulation in the third space should be limited by instituting severe potassium, sodium, and fluid restriction.

• Resolution Phase:
  

  As third space fluid returns to the intravascular compartment, a fall in hematocrit and increasing urinary output are observed in the absence of any increase in intake. Peripheral and/or pulmonary edema may result if the kidneys are unable to excrete third space fluid as rapidly as it is mobilized. Diuretics may be indicated during the resolution phase, if necessary, to combat pulmonary edema.

Do not remove ascitic, pleural, and pericardial fluid unless there is the necessity to relieve symptoms such as pulmonary distress or cardiac tamponade.

OHSS increases the risk of injury to the ovary. Pelvic examination or intercourse may cause rupture of an ovarian cyst, which may result in hemoperitoneum, and should be avoided.

If bleeding occurs and requires surgical intervention, the clinical objective should be to control the bleeding and retain as much ovarian tissue as possible. A physician experienced in the management of this syndrome, or who is experienced in the management of fluid and electrolyte imbalances, should be consulted.

In a clinical study of induction of ovulation indication, 6 of 72 (8.33%) Neogentin 75 (Urofollitropin)^® treated women developed OHSS and 2 were classified as severe. In a clinical study for the development of multiple follicles as part of an IVF cycle, 3 of 60 women treated with Neogentin 75 (Urofollitropin)^® developed OHSS and 1 was classified as severe.

5.4 Pulmonary and Vascular Complications

Serious pulmonary conditions have been reported in women treated with gonadotropins. In addition, thromboembolic events both in association with, and separate from, the Ovarian Hyperstimulation Syndrome have been reported in women treated with gonadotropins. Intravascular thrombosis and embolism, which may originate in venous or arterial vessels, can result in reduced blood flow to critical organs or the extremities. Women with generally recognized risk factors for thrombosis, such as personal or family history, severe obesity, or thrombophilia, may have an increased risk of venous or arterial thromboembolic events during or following treatment with gonadotropins. Sequelae of such reactions have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb and rarely in myocardial infarctions. In rare cases, pulmonary complications and/or thromboembolic events have resulted in death. In women with recognized risk factors, the benefits of ovulation induction and assisted reproductive technology need to be weighed against the risks. Pregnancy also carries an increased risk of thrombosis.

5.5 Ovarian Torsion

Ovarian torsion has been reported after treatment with gonadotropins. This may be related to OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

5.6 Multi-fetal Gestation and Birth

Multi-fetal gestation and births have been reported with all gonadotropin therapy including therapy with Neogentin 75 ^®.

In a controlled study of 72 patients undergoing induction of ovulation, 66.7% of pregnancies of women treated with subcutaneous Neogentin 75 (Urofollitropin)^® were multiples, while 28.6% of pregnancies in women treated with intramuscular Neogentin 75 (Urofollitropin)^® were multiples.

In a controlled study of 60 patients undergoing IVF, 34.8% of pregnancies of women treated with subcutaneous Neogentin 75 (Urofollitropin)^® were multiples.

Before beginning treatment with Neogentin 75 (Urofollitropin)^®, advise the woman and her partner of the potential risk of multi-fetal gestation and birth.

5.7 Congenital Malformations

The incidence of congenital malformations after some ART [specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)] may be slightly higher than after spontaneous conception. This slightly higher incidence is thought to be related to differences in parental characteristics (e.g., maternal age, maternal and paternal genetic background, sperm characteristics) and to the higher incidence of multi-fetal gestations after IVF or ICSI. There are no indications that the use of gonadotropins during IVF or ICSI is associated with an increased risk of congenital malformations.

5.8 Ectopic Pregnancy

Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased. Early confirmation of intrauterine pregnancy should be determined by β-hCG testing and transvaginal ultrasound.

5.9 Spontaneous Abortion

The risk of spontaneous abortion is increased with gonadotropin products. However, causality has not been established. The increased risk may be a factor of the underlying infertility.

5.10 Ovarian Neoplasms

There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have had multiple drug therapy for controlled ovarian stimulation; however, a causal relationship has not been established.

5.11 Laboratory Tests

In most instances, treatment of women with Neogentin 75 (Urofollitropin)^® will result only in follicular growth and maturation. In the absence of an endogenous LH surge, hCG is given when monitoring of the woman indicates that sufficient follicular development has occurred. This may be estimated by ultrasound alone or in combination with measurement of serum estradiol levels. The combination of both ultrasound and serum estradiol measurement are useful for monitoring follicular growth and maturation, timing of the ovulatory trigger, detecting ovarian enlargement and minimizing the risk of the Ovarian Hyperstimulation Syndrome and multiple gestation.

The clinical confirmation of ovulation is obtained by direct or indirect indices of progesterone production as well as sonographic evidence of ovulation.

Direct or indirect indices of progesterone production:

• Urinary or serum luteinizing hormone (LH) rise
• A rise in basal body temperature
• Increase in serum progesterone
• Menstruation following the shift in basal body temperature

Sonographic evidence of ovulation:

• Collapsed follicle
• Fluid in the cul-de-sac
• Features consistent with corpus luteum formation
• Secretory endometrium

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed elsewhere in the labeling:

• Hypersensitivity and Anaphylactic Reactions
• Abnormal Ovarian Enlargement
• Ovarian Hyperstimulation Syndrome
• Thromboembolic events
• Ovarian Torsion
• Multi-fetal Gestation and Birth
• Congenital Malformations
• Ectopic Pregnancy
• Spontaneous Abortion
• Ovarian Neoplasms

• The most common adverse reactions (≥5% incidence) in ovulation induction include: headache, hot flashes, OHSS, pain, and respiratory disorder (6.1)
• The most common adverse reactions (≥2% incidence) in ART include: abdominal cramps, abdominal fullness/enlargement, headache, nausea, OHSS, pain, pelvic pain, and post retrieval pain (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

The safety of Neogentin 75 (Urofollitropin)^® was examined in four clinical studies that enrolled a total of 222 women who received Neogentin 75 (Urofollitropin)^®.

Ovulation Induction

In a randomized, multi-center, active controlled study, a total of 72 women received Neogentin 75 (Urofollitropin)^® (35 in a subcutaneous administration arm and 37 in an intramuscular administration arm) for induction of ovulation. Adverse reactions occurring at an incidence of ≥2% incidence in women receiving Neogentin 75 (Urofollitropin)^® are shown in Table 1.

Assisted Reproductive Technology

Three studies examined the safety profile of Neogentin 75 (Urofollitropin)^® in ART. A total of 150 women received treatment with Neogentin 75 (Urofollitropin)^® in these studies. Adverse reactions occurring at an incidence of ≥2% incidence for this integrative assessment are presented in Table 2.

6.2 Postmarketing Experience

The following adverse reactions have been reported during postmarketing use of gonadotropins. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to Neogentin 75 (Urofollitropin)^® cannot be reliably determined.

• Gastrointestinal disorders: Abdominal pain, Nausea, Vomiting, Abdominal distension, Abdominal discomfort, Diarrhea, Constipation
• General disorders and administration site conditions: Pain, Injection site reactions (redness, bruising, swelling and/or pruritus)
• Infections and infestations: Urinary tract infection, Nasopharyngitis
• Musculoskeletal and connective tissue disorders: Muscle spasm
• Nervous system disorders: Headache
• Reproductive system disorders: Vaginal hemorrhage, OHSS , Pelvic pain, Breast tenderness, Vaginal discharge. Ovarian enlargement, Multiple pregnancies
• Skin and subcutaneous tissue disorders: Rash
• Vascular disorders: Hot flushes

7 DRUG INTERACTIONS

No drug/drug interaction studies in humans have been conducted for Neogentin 75 (Urofollitropin)^®.

No drug/drug interaction studies have been conducted for Neogentin 75 (Urofollitropin)^® in humans (7)

8 USE IN SPECIFIC POPULATIONS

• Pregnancy Category X. Do not use Neogentin 75 ^® in pregnant women. (4, 8.1)
• Nursing Mothers: It is not known whether Neogentin 75 (Urofollitropin)^® is excreted in human milk. (8.3)
• Pediatric Use: Safety and efficacy not established. (8.4)
• Renal and Hepatic Insufficiency: Safety, efficacy, and pharmacokinetics of Neogentin 75 (Urofollitropin)^® in women with renal or hepatic insufficiency have not been established. (8.6)

8.1 Pregnancy

Teratogenic effects

Pregnancy Category X .

8.3 Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant from Neogentin 75 ^®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.6 Renal and Hepatic Insufficiency

Safety and effectiveness in women with renal and hepatic sufficiency have not been established.

10 OVERDOSAGE

Aside from possible ovarian hyperstimulation and multiple gestations , little is known concerning the consequences of acute overdosage with Neogentin 75 (Urofollitropin)^®.

11 DESCRIPTION

Neogentin 75 (Urofollitropin)^® is a product containing a highly purified preparation of human follicle stimulating hormone (hFSH) extracted from the urine of postmenopausal women. Human FSH is a gonadotropin and consists of two non-covalently linked glycoproteins designated as the α and β subunits. The α subunit has 92 amino acids of which two are modified by attachment of carbohydrates. The β subunit has 111 amino acids of which two are modified by attachment of carbohydrates.

Neogentin 75 (Urofollitropin)^® is a sterile, lyophilized powder intended for subcutaneous or intramuscular injection after reconstitution with sterile 0.9% Sodium Chloride Injection, USP. Each vial of Neogentin 75 (Urofollitropin)^® contains 82.5 International Units (IU) of Follicle Stimulating Hormone (FSH) activity, 23 mg Lactose Monohydrate, 0.005 mg Polysorbate 20, and Sodium Phosphate buffer (Sodium Phosphate dibasic, Heptahydrate and Phosphoric acid) for pH adjustments, which, when reconstituted with diluent, will deliver 75 International Units of FSH. Neogentin 75 (Urofollitropin)^® contains up to 2% luteinizing hormone (LH) activity based on bioassay. Human Chorionic Gonadotropin (hCG) is not detected in Neogentin 75 (Urofollitropin)^®. When stored at 3° to 25°C, up to 40% of the α-subunits may be oxidized.

The in vivo biological activity of Neogentin 75 (Urofollitropin) for injection, purified is determined by using reference standards calibrated against the First International Standard for follicle-stimulating hormone, (FSH, Neogentin 75 (Urofollitropin)), Urinary, Human for Bioassay, National Institute for Biological Standards and Control (NIBSC) at its 46th meeting in 1995.

FSH is a glycoprotein that is acidic and water-soluble.

Neogentin 75 (Urofollitropin)^® has been mixed in vitro with MENOPUR^® with no evidence of aggregation.

Therapeutic class: Infertility

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Neogentin 75 ^® administered for 7 to 12 days produces ovarian follicular growth in women who do not have primary ovarian failure. Treatment with Neogentin 75 (Urofollitropin)^® in most instances results only in follicular growth and maturation. When sufficient follicular maturation has occurred, hCG must be given to induce ovulation.

12.3 Pharmacokinetics

Single doses of 225 International Units and multiple daily doses (7 days) of 150 International Units of Neogentin 75 (Urofollitropin)^® were administered to healthy volunteer female subjects while their endogenous FSH was suppressed. Sixteen subjects received Neogentin 75 (Urofollitropin)^® subcutaneously and 12 received the drug intramuscularly. Serum FSH concentrations were determined. Based on the steady state ratio of FSH C_max and AUC, subcutaneous and intramuscular administration of Neogentin 75 (Urofollitropin)^® were not bioequivalent. Multiple doses of Neogentin 75 (Urofollitropin)^® intramuscular resulted in C_max and AUC of 77.7% and 81.8% compared to multiple doses of Neogentin 75 (Urofollitropin)^® subcutaneous. The FSH pharmacokinetic parameters for single and multiple dose Neogentin 75 (Urofollitropin)^®, administered subcutaneously and intramuscularly are in Table 3.

Absorption

The subcutaneous route of administration trends toward greater bioavailability than the IM route for single and multiple doses of Neogentin 75 (Urofollitropin)^®.

Distribution

Human tissue or organ distribution of FSH has not been studied for Neogentin 75 (Urofollitropin)^®.

Metabolism

Metabolism of FSH has not been studied for Neogentin 75 (Urofollitropin)^® in humans.

Elimination

The mean elimination half-lives of FSH for subcutaneous and intramuscular single dosing are 31.8 and 37 hours, respectively. However, following multiple dosing (× 7 days) they are 20.6 and 15.2 hours for SC and IM, respectively.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term toxicity studies in animals and in vitro mutagenicity tests have not been performed to evaluate the carcinogenic potential of Neogentin 75 (Urofollitropin) for injection, purified.

14 CLINICAL STUDIES

The efficacy of Neogentin 75 ^® was examined in two clinical studies, one for in-vitro fertilization (IVF) and one for ovulation induction (OI).

14.1 Ovulation Induction

In the randomized, multi-center, active-controlled, ovulation induction study, women underwent pituitary suppression with a GnRH agonist before being randomized to subcutaneously administered Neogentin 75 (Urofollitropin)^® , intramuscularly-administered Neogentin 75 (Urofollitropin)^®, or a subcutaneously administered commercial recombinant FSH product. A total of 111 oligo-anovulatory women were randomized to both treatment arms, of which 72 received Neogentin 75 (Urofollitropin)^®, starting at a dose of 150 International Units daily for 5 days. Subsequently each woman received individual titration of the Neogentin 75 (Urofollitropin)^® dose from 75 to 450 International Units daily based on ultrasound and estradiol (E₂) levels. The total duration of dosing did not exceed 12 days. Results for the Intent-To-Treat Population are summarized in Table 4.

14.2 Assisted Reproductive Technologies [ART]

In the randomized, multi-center, active-controlled, IVF study, women underwent pituitary suppression with a GnRH agonist before being randomized to subcutaneously administered Neogentin 75 (Urofollitropin)^® or a subcutaneously administered commercial recombinant FSH product. A total of 120 patients were randomized to both treatment arms, of which 60 received Neogentin 75 (Urofollitropin)^®, starting at a dose of 225 International Units daily for 5 days. Subsequently each woman received individual titration of the dose from 75 to 450 International Units daily based on ultrasound and estradiol (E₂) levels. The total duration of dosing did not exceed 12 days. Results are summarized in Table 5 for the Intent-To-Treat population.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Neogentin 75 ^® (urofollitropin for injection, purified) is supplied in a sterile, lyophilized, single dose vial containing 82.5 International Units of FSH, to deliver 75 International Units FSH after reconstituting with the diluent.

Each vial is available with an accompanying vial of sterile diluent containing 2 mL of 0.9% Sodium Chloride Injection, USP.

75 International Units FSH activity, supplied as:

NDC 55566-8505-6: Box of 5 vials + 5 vials diluent + 5 Q-Cap^® vial adaptors.

16.2 Storage and Handling

Lyophilized powder may be stored refrigerated or at room temperature (3° to 25° C/37° to 77°F). Protect from light. Use immediately after reconstitution. Discard unused material.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling

17.1 Dosing and Use

Instruct women on the correct usage and dosing of MENOPUR^® . Caution women not to change the dosage or the schedule of administration unless she is told to do so by her healthcare provider.

17.2 Duration and Monitoring Required

Prior to beginning therapy with Neogentin 75 ^®, inform women about the time commitment and monitoring procedures necessary for treatment.

17.3 Instructions Regarding a Missed Dose

Inform the woman that if she misses or forgets to take a dose of Neogentin 75 (Urofollitropin)^®, the next dose should not be doubled and she should call her healthcare provider for further dosing instructions.

17.4 Ovarian Hyperstimulation Syndrome

Inform women regarding the risks of OHSS and OHSS-associated symptoms including lung and blood vessel problems and ovarian torsion with the use of Neogentin 75 (Urofollitropin)^®.

17.5 Multi-fetal Gestation and Birth

Inform women regarding the risk of multi-fetal gestation and birth with the use of Neogentin 75 (Urofollitropin)^® .

Vials of sterile diluent of 0.9% Sodium Chloride Injection, USP, manufactured for Ferring Pharmaceuticals Inc.

MANUFACTURED FOR:

Step 1. Preparing your Neogentin 75 (Urofollitropin)^® or Neogentin 75 (Urofollitropin)^® mixed with MENOPUR^®.

• Wash your hands well with soap and water and dry them with a clean towel.
• Place all the supplies you need on the clean surface you already prepared.
• Check the vial(s) of Neogentin 75 (Urofollitropin) (and ^® MENOPUR^® if needed) to make sure there is powder or a pellet in the vial(s). If you do not see any powder in the vial(s) do not use the vial and call your pharmacist or healthcare provider.
• Check the 0.9% Sodium Chloride, USP vial to make sure that the liquid is clear and does not contain any particles. If you see any particles in the liquid or the liquid is discolored, do not use the vial and call your pharmacist or healthcare provider.
• Check the Q-Cap^® blister pack package to make sure it is intact. Do not use if the package is damaged.
• Remove the plastic cap(s) from the vial(s) of Neogentin 75 (Urofollitropin)^® (and MENOPUR^® if needed) and 0.9% Sodium Chloride, USP vial. See Figure B.
  

• Wipe the tops of the vials with alcohol and allow them to dry. Do not touch the tops of the vials after you have wiped them. See Figure C.
  

• Place the vial of 0.9% Sodium Chloride, USP on the table.
• Open the Q-Cap^® blister pack by peeling back the lidding. See Figure D . Do not take the Q-Cap^® out of the blister pack at this time. Do not touch the spike or connector (luer) ends of the Q-Cap^®.
  

• Hold the 0.9% Sodium Chloride, USP vial in 1 hand. With your other hand, hold the sides of the Q-Cap^® blister pack, turn the Q-Cap^® blister pack over, and place it on top of the vial. Push the Q-Cap^® straight down into the rubber stopper of the vial until it stops. See Figure E.
  • Do not use the Q-Cap^® if it falls out of the blister pack. Throw it away and get a new one.
  
  

• Remove the blister pack and throw it away in your household trash. Do not touch the connector end (luer) of the Q-Cap^®. See Figure F.
  

• Take the syringe and pull down on the syringe plunger rod until you have withdrawn the amount of 0.9% Sodium Chloride, USP from the vial that your healthcare provider told you to use.
  • The usual amount of 0.9% Sodium Chloride, USP used to mix your Neogentin 75 (Urofollitropin)^® is 1 mL, but you should use the amount that your healthcare provider tells you to use. See Figure G.
    

  • Be very careful not to touch the syringe plunger during this step.
• Place the tip of the syringe into the connector end (luer) of the Q-Cap^® then twist the syringe clockwise until it is tight. Be careful not to overtighten the syringe. See Figure H.
  

• Slowly push down on the syringe plunger to push the air from the syringe into the vial. See Figure I.
  

• Keeping the syringe and Q-Cap^® together, turn the vial upside down and pull down on the syringe plunger to withdraw the right amount of 0.9% Sodium Chloride, USP from the vial. Your healthcare provider should tell you the right amount of 0.9% Sodium Chloride, USP to use. See Figure J.
  

• Separate the Q-Cap^® and syringe from the vial by pulling up on the syringe barrel. Do not pull the plunger to remove the Q-Cap^®. Throw away 0.9% Sodium Chloride, USP vial in your household trash. See Figure K.
  

• Hold the vial of Neogentin 75 (Urofollitropin)^® powder in 1 hand. With your other hand, hold the sides of the syringe with the Q-Cap^® attached and place the tip of the Q-Cap^® over the top of the vial. Push the tip of the Q-Cap^® into the rubber stopper on the top of the vial until it stops and snaps into place. Be careful not to push down on the syringe plunger during this step. See Figure L.
  

• Slowly push down on the syringe plunger to push the 0.9% Sodium Chloride, USP into the vial with the Neogentin 75 (Urofollitropin)^® powder in it. Gently swirl the vial until the Neogentin 75 (Urofollitropin)^® powder is completely dissolved. Do not shake the vial as this will cause bubbles. See Figure M.
  

• As soon as the powdered medicine has completely dissolved, push the plunger down to empty any remaining air from the syringe, then turn the vial upside down and slowly pull down on the plunger to withdraw all of the Neogentin 75 (Urofollitropin)^® into the syringe. See Figure N.
  • Be careful not to pull the plunger stopper all the way out of the syringe barrel.
  
  

If your healthcare provider tells you to use more than 1 vial of Neogentin 75 (Urofollitropin)^® or tells you to mix your Neogentin 75 (Urofollitropin)^® with MENOPUR^® in the same syringe:

• Mix your first vial of Neogentin 75 (Urofollitropin)^® powder or MENOPUR^® powder with 0.9% Sodium Chloride, USP. Do not inject your dose yet.
• Use the liquid in the syringe you have just mixed to mix the next vial of Neogentin 75 (Urofollitropin)^® or MENOPUR^®. See Figures L through N.
• You can use the liquid in the syringe to mix up to 5 more vials of medicine.
• Your healthcare provider will tell you how many vials of Neogentin 75 (Urofollitropin)^® and MENOPUR^® to use.

Step 2. Removing the Q-Cap^® and adding your needle for injection.

• When you have finished mixing the last vial needed for your injection and have withdrawn all the medicine into the syringe, remove the syringe from the Q-Cap^® by twisting the syringe counter-clockwise while holding the Q-Cap^® steady. See Figure O. Throw away the Q-Cap^® with the attached vial into your household trash.
  

• You are now ready to attach the needle to the syringe for your injection.
  

  Your healthcare provider will tell you what needle you should use for your injection.

• While holding the syringe with the syringe tip pointing up, place the needle on the top of the syringe. Gently push down on the needle and twist the needle onto the syringe in a clockwise direction until it is tight. See Figure P.
  

• Do not remove the needle cap until you are ready for your injection.(See Step 4 )
  • Carefully set the syringe with the needle down on the table. See Figure Q.
    

Step 3. Prepare Injection site for Neogentin 75 (Urofollitropin)^® or with Neogentin 75 (Urofollitropin)^® mixed with MENOPUR^®.

• Select a site to inject Neogentin 75 (Urofollitropin)^® or with Neogentin 75 (Urofollitropin)^® mixed with MENOPUR^® on your stomach area (abdomen).
  • Pick a site on your lower abdomen, 1-2 inches below the navel, alternating between left and right sides.
  • Each day, inject in a different site to help reduce soreness and skin problems. For example, on day 1, inject yourself on the right side of your abdomen. The next day, inject yourself on the left side of your abdomen. Changing your injection sites every day will help reduce soreness and skin problems. See Figure R.
    

• Clean your injection site with an alcohol pad. Let the alcohol dry. See Figure S.
  

• Carefully remove the needle cap from the syringe. See Figure T .
  

• Hold the syringe with the needle pointing straight up. Pull down slightly on the plunger and tap the barrel of the syringe so that any air bubbles rise to the top. Slowly press the plunger up until all the air is out of the syringe and a small drop of liquid is seen at the tip of the needle. See Figure U.
  

• Tap the syringe to remove the small drop of liquid at the tip of the needle. Do not let the needle touch anything to keep it sterile. See Figure V.
  

• The medicine is now ready for you to inject. See Figure V .

• Hold the syringe in 1 hand. Use your other hand to gently pinch a fold of cleaned skin where you will insert your needle. Hold the skin between your thumb and index finger. See Figure W.
  

• Hold your syringe at a right angle to your skin. Quickly insert the needle all the way into your skin fold. See Figure X.
  

• Push down the plunger of the syringe with a steady motion. Keep pushing until all the fluid is injected into your skin. See Figure Y.
  

• Let go of your skin fold and pull the needle straight out of your skin. See Figure Z.
  

• If there is any bleeding at your injection site, place a gauze pad over your injection site. Apply gentle pressure to stop the bleeding. Do not rub the site. See Figure AA.
  

• If your injection site becomes sore or red, you may put ice on your injection site for 1 minute and then take it off for 3 minutes. If needed, you may repeat this 3 or 4 times.

• Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away loose needles and syringes in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that:
  • is made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • remains upright and stable during use,
  • is leak-resistant, and
  • is properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

MANUFACTURED FOR:

FERRING PHARMACEUTICALS INC.

PARSIPPANY, NJ 07054

Revised: July 2015

Figure A Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M Figure N Figure O Figure P Figure Q Figure R Figure S Figure T Figure U Figure V Figure W Figure X Figure Y Figure Z Figure AA Logo