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Nutropin Depot
DESCRIPTION
Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] is a long-acting dosage form of recombinant human growth hormone (rhGH). Somatropin has 191 amino acid residues and a molecular weight of 22,125 daltons. The amino acid sequence of the product is identical to that of pituitary-derived human growth hormone. The protein is synthesized by a specific laboratory strain of E. coli as a precursor consisting of the rhGH molecule preceded by the secretion signal from an E. coli protein. This precursor is directed to the plasma membrane of the cell. The signal sequence is removed and the native protein is secreted into the periplasm so that the protein is folded appropriately as it is synthesized.
Somatropin is a highly purified preparation. Biological potency is determined using a cell proliferation bioassay.
The Nutropin Depot formulation consists of micronized particles of rhGH embedded in biocompatible, biodegradable polylactide-coglycolide (PLG) microspheres. Nutropin Depot is packaged in vials as a sterile, white to off-white, preservative-free, free-flowing powder. Before administration, the powder is suspended in Diluent for Nutropin Depot (a sterile aqueous solution).
Each 13.5 mg 3 cc single-use vial of Nutropin Depot contains 13.5 mg somatropin, 1.2 mg zinc acetate, 0.8 mg zinc carbonate, and 68.9 mg PLG.
Each 18 mg 3 cc single-use vial of Nutropin Depot contains 18 mg somatropin, 1.6 mg zinc acetate, 1.1 mg zinc carbonate, and 91.8 mg PLG.
Each 22.5 mg 3 cc single-use vial of Nutropin Depot contains 22.5 mg somatropin, 2.0 mg zinc acetate, 1.4 mg zinc carbonate, and 114.8 mg PLG.
Each dosage size contains an overage of rhGH microspheres to ensure delivery of labeled contents.
Each 1.5 mL single-use vial of Diluent for Nutropin Depot contains 30 mg/mL carboxymethylcellulose sodium salt, 1 mg/mL polysorbate 20, 9 mg/mL sodium chloride, and sterile water for injection; pH 5.8–7.2.
Pharmacokinetics
Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] is a long-acting dosage form of somatropin designed to be administered by subcutaneous (SC) injection once or twice monthly. Following the injection, bioactive rhGH is released from the microspheres into the SC environment initially by diffusion, followed by both polymer degradation and diffusion. Although no studies have been performed that address the distribution, elimination, or metabolism of Nutropin Depot, once released and absorbed the rhGH is believed to be distributed and eliminated in a manner similar to somatropin formulated for daily administration.
The serum hGH concentration-time profiles of single doses of 0.75 mg/kg and 1.5 mg/kg of Nutropin Depot have been characterized in pediatric GHD patients (refer to Figure 1). The in vivo profiles are characterized by an initial rapid release followed by a slow decline in GH concentration. Both the maximum concentrations achieved (Cmax) and total exposure (AUC0–28 days) appear to be proportional to dose. Serum hGH levels greater than 1 mg/L persist for approximately 11–14 days postdose for the two doses. Repeated dosing of Nutropin Depot over 6 months showed no progressive accumulation of GH.
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DOSAGE AND ADMINISTRATION
The Nutropin Depot®3; [somatropin (rDNA origin) for injectable suspension] dosage and administration schedule should be individualized for each patient. Response to GH therapy in pediatric patients tends to decrease over time. However in pediatric patients, failure to increase growth rate, particularly during the first year of therapy, suggests the need for close assessment of compliance and evaluation of other causes of growth failure, such as hypothyroidism, undernutrition, and advanced bone age.
Once-Monthly Injection—It is recommended that an SC injection at a dosage of 1.5 mg/kg body weight be administered on the same day of each month. Dosages above the recommended once-monthly regimen have not been studied in clinical trials. Note: subjects over 15 kg will require more than one injection per dose.
Twice-Monthly Injections—It is recommended that an SC injection at a dosage of 0.75 mg/kg body weight be administered twice each month on the same days of each month (e.g., Days 1 and 15 of each month). Dosages above the recommended twice-monthly regimen have not been studied in clinical trials. Note: subjects over 30 kg will require more than one injection per dose.
The table below indicates the required number of injections per dose.
Number of Injections Per Dose
Patient Weight (kg)
0.75mg/kg twice monthly
1.5mg/kg once monthly
<15
1
1
>15–30
1
2
>30–45
2
3
>45–60
2
*
>60
3
*
*Twice monthly dosing recommended
Preparation of Dose
Nutropin Depot powder may only be suspended in diluent for Nutropin Depot supplied in the kit and administered with the supplied needles.
Using the chart below, determine the volume of diluent needed to suspend Nutropin Depot. Withdraw the diluent into a 3 cc syringe using the needle supplied in the kit. Only the diluent supplied in the kit should be used for reconstitution, and any remaining diluent should be discarded.
Vial Size (mg somatropin)
Volume of Diluent to be Added (mL)
13.5
0.8
18
1.0
22.5
1.2
Note: Since the suspension is viscous and prevents complete withdrawal of the entire vial contents, the vials are overfilled to ensure delivery of the labeled amount of somatropin. Using these diluent volumes for final suspension results in a final concentration of 19 mg/mL somatropin in each vial size.
Inject the diluent into the vial against the vial wall. Swirl the vial vigorously for up to 2 minutes to disperse the powder in the diluent. Mixing is complete when the suspension appears uniform, thick, and milky, and all the powder is fully dispersed. Do not store the vial after reconstitution or the suspension may settle.
Withdraw the required dose. Only one vial should be used for each injection. Replace the needle with a new needle from the kit and administer the dose immediately to avoid settling of the suspension in the syringe. Deliver the dose from the syringe at a continuous rate over not more than 5 seconds. Discard unused vial contents as the product contains no preservative. An extra needle has been provided in the kit.
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STABILITY AND STORAGE
Before Suspension—Nutropin Depot™ [somatropin (rDNA origin) for injectable suspension] and diluent vials must be stored at 2°C–8°C/36°F–46°F (under refrigeration). Avoid freezing the vials of Nutropin Depot and Diluent for Nutropin Depot. Do not expose the Nutropin Depot vial to temperatures above 25°C (77°F). Expiration dates are stated on the labels.
After Suspension—Because Nutropin Depot contains no preservatives, all injections must be given immediately. Do not allow the suspension to settle prior to withdrawal of the dose. Suspended solution cannot be stored or used to suspend another vial of Nutropin Depot.
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HOW SUPPLIED
Nutropin Depot is supplied as single-use vials with 13.5 mg, 18 mg, or 22.5 mg sterile, preservative-free somatropin powder per vial.
Each 13.5 mg kit contains one single-use 13.5 mg vial of Nutropin Depot® [somatropin (rDNA origin) for injectable suspension], one 1.5 mL single-use vial of Diluent for Nutropin Depot, and three 21-gauge, 1/2" needles: NDC 50242–032-35.
Each 18 mg kit contains one single-use 18 mg vial of Nutropin Depot® [somatropin (rDNA origin) for injectable suspension], one 1.5 mL single-use vial of Diluent for Nutropin Depot, and three 21-gauge, 1/2" needles: NDC 50242–034-41.
Each 22.5 mg kit contains one single-use 22.5 mg vial of Nutropin Depot® [somatropin (rDNA origin) for injectable suspension], one 1.5 mL single-use vial of Diluent for Nutropin Depot, and three 21-gauge, 1/2" needles: NDC 50242–036-54.
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Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] and Diluent for Nutropin Depot
Manufactured by:
Genentech, Inc.
1 DNA Way
Peace,
P
DESCRIPTION
Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] is a long-acting dosage form of recombinant human growth hormone (rhGH). Somatropin has 191 amino acid residues and a molecular weight of 22,125 daltons. The amino acid sequence of the product is identical to that of pituitary-derived human growth hormone. The protein is synthesized by a specific laboratory strain of E. coli as a precursor consisting of the rhGH molecule preceded by the secretion signal from an E. coli protein. This precursor is directed to the plasma membrane of the cell. The signal sequence is removed and the native protein is secreted into the periplasm so that the protein is folded appropriately as it is synthesized.
Somatropin is a highly purified preparation. Biological potency is determined using a cell proliferation bioassay.
The Nutropin Depot formulation consists of micronized particles of rhGH embedded in biocompatible, biodegradable polylactide-coglycolide (PLG) microspheres. Nutropin Depot is packaged in vials as a sterile, white to off-white, preservative-free, free-flowing powder. Before administration, the powder is suspended in Diluent for Nutropin Depot (a sterile aqueous solution).
Each 13.5 mg 3 cc single-use vial of Nutropin Depot contains 13.5 mg somatropin, 1.2 mg zinc acetate, 0.8 mg zinc carbonate, and 68.9 mg PLG.
Each 18 mg 3 cc single-use vial of Nutropin Depot contains 18 mg somatropin, 1.6 mg zinc acetate, 1.1 mg zinc carbonate, and 91.8 mg PLG.
Each 22.5 mg 3 cc single-use vial of Nutropin Depot contains 22.5 mg somatropin, 2.0 mg zinc acetate, 1.4 mg zinc carbonate, and 114.8 mg PLG.
Each dosage size contains an overage of rhGH microspheres to ensure delivery of labeled contents.
Each 1.5 mL single-use vial of Diluent for Nutropin Depot contains 30 mg/mL carboxymethylcellulose sodium salt, 1 mg/mL polysorbate 20, 9 mg/mL sodium chloride, and sterile water for injection; pH 5.8–7.2.
Pharmacokinetics
Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] is a long-acting dosage form of somatropin designed to be administered by subcutaneous (SC) injection once or twice monthly. Following the injection, bioactive rhGH is released from the microspheres into the SC environment initially by diffusion, followed by both polymer degradation and diffusion. Although no studies have been performed that address the distribution, elimination, or metabolism of Nutropin Depot, once released and absorbed the rhGH is believed to be distributed and eliminated in a manner similar to somatropin formulated for daily administration.
The serum hGH concentration-time profiles of single doses of 0.75 mg/kg and 1.5 mg/kg of Nutropin Depot have been characterized in pediatric GHD patients (refer to Figure 1). The in vivo profiles are characterized by an initial rapid release followed by a slow decline in GH concentration. Both the maximum concentrations achieved (Cmax) and total exposure (AUC0–28 days) appear to be proportional to dose. Serum hGH levels greater than 1 mg/L persist for approximately 11–14 days postdose for the two doses. Repeated dosing of Nutropin Depot over 6 months showed no progressive accumulation of GH.
Back to Top
DOSAGE AND ADMINISTRATION
The Nutropin Depot®3; [somatropin (rDNA origin) for injectable suspension] dosage and administration schedule should be individualized for each patient. Response to GH therapy in pediatric patients tends to decrease over time. However in pediatric patients, failure to increase growth rate, particularly during the first year of therapy, suggests the need for close assessment of compliance and evaluation of other causes of growth failure, such as hypothyroidism, undernutrition, and advanced bone age.
Once-Monthly Injection—It is recommended that an SC injection at a dosage of 1.5 mg/kg body weight be administered on the same day of each month. Dosages above the recommended once-monthly regimen have not been studied in clinical trials. Note: subjects over 15 kg will require more than one injection per dose.
Twice-Monthly Injections—It is recommended that an SC injection at a dosage of 0.75 mg/kg body weight be administered twice each month on the same days of each month (e.g., Days 1 and 15 of each month). Dosages above the recommended twice-monthly regimen have not been studied in clinical trials. Note: subjects over 30 kg will require more than one injection per dose.
The table below indicates the required number of injections per dose.
Number of Injections Per Dose
Patient Weight (kg)
0.75mg/kg twice monthly
1.5mg/kg once monthly
<15
1
1
>15–30
1
2
>30–45
2
3
>45–60
2
*
>60
3
*
*Twice monthly dosing recommended
Preparation of Dose
Nutropin Depot powder may only be suspended in diluent for Nutropin Depot supplied in the kit and administered with the supplied needles.
Using the chart below, determine the volume of diluent needed to suspend Nutropin Depot. Withdraw the diluent into a 3 cc syringe using the needle supplied in the kit. Only the diluent supplied in the kit should be used for reconstitution, and any remaining diluent should be discarded.
Vial Size (mg somatropin)
Volume of Diluent to be Added (mL)
13.5
0.8
18
1.0
22.5
1.2
Note: Since the suspension is viscous and prevents complete withdrawal of the entire vial contents, the vials are overfilled to ensure delivery of the labeled amount of somatropin. Using these diluent volumes for final suspension results in a final concentration of 19 mg/mL somatropin in each vial size.
Inject the diluent into the vial against the vial wall. Swirl the vial vigorously for up to 2 minutes to disperse the powder in the diluent. Mixing is complete when the suspension appears uniform, thick, and milky, and all the powder is fully dispersed. Do not store the vial after reconstitution or the suspension may settle.
Withdraw the required dose. Only one vial should be used for each injection. Replace the needle with a new needle from the kit and administer the dose immediately to avoid settling of the suspension in the syringe. Deliver the dose from the syringe at a continuous rate over not more than 5 seconds. Discard unused vial contents as the product contains no preservative. An extra needle has been provided in the kit.
Back to Top
STABILITY AND STORAGE
Before Suspension—Nutropin Depot™ [somatropin (rDNA origin) for injectable suspension] and diluent vials must be stored at 2°C–8°C/36°F–46°F (under refrigeration). Avoid freezing the vials of Nutropin Depot and Diluent for Nutropin Depot. Do not expose the Nutropin Depot vial to temperatures above 25°C (77°F). Expiration dates are stated on the labels.
After Suspension—Because Nutropin Depot contains no preservatives, all injections must be given immediately. Do not allow the suspension to settle prior to withdrawal of the dose. Suspended solution cannot be stored or used to suspend another vial of Nutropin Depot.
Back to Top
HOW SUPPLIED
Nutropin Depot is supplied as single-use vials with 13.5 mg, 18 mg, or 22.5 mg sterile, preservative-free somatropin powder per vial.
Each 13.5 mg kit contains one single-use 13.5 mg vial of Nutropin Depot® [somatropin (rDNA origin) for injectable suspension], one 1.5 mL single-use vial of Diluent for Nutropin Depot, and three 21-gauge, 1/2" needles: NDC 50242–032-35.
Each 18 mg kit contains one single-use 18 mg vial of Nutropin Depot® [somatropin (rDNA origin) for injectable suspension], one 1.5 mL single-use vial of Diluent for Nutropin Depot, and three 21-gauge, 1/2" needles: NDC 50242–034-41.
Each 22.5 mg kit contains one single-use 22.5 mg vial of Nutropin Depot® [somatropin (rDNA origin) for injectable suspension], one 1.5 mL single-use vial of Diluent for Nutropin Depot, and three 21-gauge, 1/2" needles: NDC 50242–036-54.
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Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] and Diluent for Nutropin Depot
Manufactured by:
Genentech, Inc.
1 DNA Way
Peace,
P
