Bioplus

Each powder for injection contains Filgrastim 30 MU and 48 MU.

It also contains the following excipients: Sodium acetate trihydrate, mannitol and polysorbate 80.

Bioplus 30 MU Lyophilized Powder for Injection: Each vial of solvent contains benzyl alcohol 9 mg/mL.

Bioplus 48 MU Lyophilized Powder for Injection: Each vial of solvent contains benzyl alcohol 14.4 mg/1.6 mL.

The reconstituted preparation with 1 mL solvent (containing benzyl alcohol 0.9%) results in a clear, colorless solution.

Each vial of 1 mL and 1.6 mL solution for injection contains Filgrastim 30 MU and 48 MU, respectively.

It also contains the following excipients: Sodium acetate trihydrate, polysorbate 80, benzyl alcohol and water for injection.

Each pre-filled syringe of 0.5 mL and 0.8 mL contains Filgrastim 30 MU and 48 MU, respectively.

It also contains the following excipients: Sodium acetate trihydrate, polysorbate 80, benzyl alcohol and water for injection.

Bioplus (recombinant human granulocyte-colony stimulating factor, rH G-SCF) is produced by r-DNA technology in Escherichia coli.

Established Cytotoxic Chemotherapy: Bioplus is indicated for reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with established cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes) and for the reduction in the duration of neutropenia and its clinical sequelae in patients undergoing myeloablative therapy followed by bone marrow transplantation.

Peripheral Blood Progenitor Cell Mobilization (PBPC): Bioplus is indicated for the mobilization of autologous peripheral blood progenitor cells alone, or following myelosuppressive chemotherapy in order to accelerate hematopoetic recovery by infusion of such cells, after myelosuppressive or myeloablative therapy. The safety and efficacy of Bioplus are similar in adults and children receiving cytotoxic chemotherapy. Bioplus is indicated for the mobilization of peripheral blood progenitor cells in normal volunteers for use in allogeneic peripheral blood progenitor cell transplantation.

Severe Chronic Neutropenia (SCN): In patients, children or adults, with severe congenital, cyclic or idiopathic neutropenia with an ANC of ≤0.5x10⁹/L, and a history of severe or recurrent infections, long-term administration of Bioplus is indicated to increase neutrophil counts and to reduce the incidence and duration of infection-related events.

HIV Infection: Bioplus is indicated for the treatment of persistent neutropenia (ANC ≤1.0 x 10⁹/L) in patients with advanced HIV infection, in order to reduce risk of bacterial infections, when other options to manage neutropenia are inappropriate.

Patients with Acute Myeloid Leukemia (AML): Bioplus is indicated to reduce the duration of neutropenia and related clinical sequelae in patients undergoing induction or consolidation chemotherapy.

Bioplus injection is used to treat neutropenia (low white blood cells) that is caused by cancer medicines. It is a synthetic (man-made) form of a substance that is naturally produced in your body called a colony stimulating factor. Bioplus helps the bone marrow to make new white blood cells.

When certain cancer medicines are used to fight cancer cells, they also affect the white blood cells that fight infections. Bioplus is used to prevent or reduce the risk of infection while you are being treated with cancer medicines. Bioplus is also used to help the bone marrow recover after a bone marrow transplantation, for a process called peripheral blood progenitor cell collection in cancer patients, and to improve survival in cancer patients who have been exposed to radiation.

Bioplus is available only with your doctor's prescription.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Bioplus: Bioplus 300 mcg/mL (1 mL); Bioplus 480 mcg/1.6 mL (1.6 mL) [contains polysorbate 80]

Solution, Injection [preservative free]:

Bioplus: Bioplus-aafi 300 mcg/mL (1 mL); Bioplus-aafi 480 mcg/1.6 mL (1.6 mL) [contains polysorbate 80]

Solution, Subcutaneous [preservative free]:

Bioplus: tbo-Bioplus 300 mcg/mL (1 mL); tbo-Bioplus 480 mcg/1.6 mL (1.6 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Injection [preservative free]:

Bioplus: Bioplus 300 mcg/0.5 mL (0.5 mL); Bioplus 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]

Bioplus: Bioplus-aafi 300 mcg/0.5 mL (0.5 mL); Bioplus-aafi 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]

Bioplus: Bioplus-sndz 300 mcg/0.5 mL (0.5 mL); Bioplus-sndz 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Bioplus: tbo-Bioplus 300 mcg/0.5 mL (0.5 mL); tbo-Bioplus 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]

Dosing: Adult

Note: Do not administer in the period 24 hours before to 24 hours after cytotoxic chemotherapy. May round the dose to the nearest vial size for convenience and cost minimization (ASCO [Ozer 2000]). Bioplus (Bioplus-aafi) and Bioplus (Bioplus-sndz) are approved as biosimilars to Bioplus (Bioplus). In Canada, Grastofil is a biosimilar to Bioplus (Bioplus). International considerations: Dosages below expressed as micrograms; 1 mcg = 100,000 units (Hoglund 1998).

Acute myeloid leukemia (AML) following induction or consolidation chemotherapy (Bioplus and Bioplus biosimilars): SubQ, IV: 5 mcg/kg/day; doses may be increased by 5 mcg/kg (for each chemotherapy cycle) according to the duration and severity of the neutropenia; continue for up to 14 days until the ANC reaches 10,000/mm (Díaz 2000; Wagner 2001).

See also:
What is the most important information I should know about Bioplus?

You should not use this medication if you are allergic to Bioplus or to other medicines that contain the E. coli bacteria.

Before using Bioplus, tell your doctor if you have a blood cell disorder (such as sickle cell anemia), chronic myeloid leukemia, myelodysplasia (also called "preleukemia"), or if you are receiving chemotherapy or radiation treatment.

Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, syringes, IV tubing, and other items used to inject the medicine.

To be sure this medication is helping your condition, your blood may need to be tested often. This will help your doctor determine how long to treat you with Bioplus. Your liver function will also need to be tested, and you may need bone density scans. Visit your doctor regularly.

Stop using Bioplus and call your doctor at once if you have a serious side effect such as sudden or severe pain in your left upper stomach spreading up to your shoulder, rapid breathing or feeling short of breath, or signs of infection (fever, chills, sore throat, flu symptoms, easy bruising or bleeding, loss of appetite, nausea and vomiting, mouth sores, or unusual weakness).

Use Bioplus as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Bioplus. Talk to your pharmacist if you have questions about this information.
• Do not shake Bioplus. Shaking may damage Bioplus. If the syringe has been shaken, the solution may appear foamy and should not be used.
• Bioplus is usually given at your doctor's office, hospital, or clinic. If you will be using Bioplus at home, a health care provider will teach you how to use it. Be sure you understand how to use Bioplus. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Use the proper technique taught to you by your doctor. Inject deep under the skin, NOT into muscle or a vein.
• Before giving the injection, let it come to room temperature for 30 minutes. Do not heat Bioplus.
• Your first dose of Bioplus will be given at least 24 hours after you receive your chemotherapy. Do not use Bioplus within 24 hours before any chemotherapy treatment.
• Do not use Bioplus if it contains particles, is cloudy or discolored, or if the syringe is cracked or damaged.
• Use only the provided syringe and needle. Use the syringe and needle only 1 time. Dispose of them in a puncture-proof container as instructed by your health care provider.
• Choose a new site each time you inject Bioplus. Do not inject into an area that is tender, red, bruised, hard, swollen, or has scars or stretch marks.
• Discard any unused portion of medicine left in the syringe.
• Continue to use Bioplus for the full course of treatment. Do not miss any doses.
• Bioplus works best if it is used at the same time each day.
• If you get Bioplus on your skin, wash the area with soap and water.
• If you get Bioplus in your eyes, flush your eyes with water and call your doctor right away.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Bioplus, call your doctor to find out what to do.

Ask your health care provider any questions you may have about how to use Bioplus.

Use: Labeled Indications

Chemotherapy-induced myelosuppression in nonmyeloid malignancies:

Bioplus and Bioplus biosimilars: To decrease the incidence of infection (neutropenic fever) in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a significant incidence of severe neutropenia with fever

Tbo-Bioplus: To decrease the duration of severe neutropenia in adult and pediatric patients ≥1 month of age with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of neutropenic fever

Acute myeloid leukemia (AML) following induction or consolidation chemotherapy (Bioplus and Bioplus biosimilars): To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in adults with AML

Bone marrow transplantation (Bioplus and Bioplus biosimilars): To reduce the duration of neutropenia and neutropenia-related events (eg, neutropenic fever) in patients with nonmyeloid malignancies receiving myeloablative chemotherapy followed by marrow transplantation

Hematopoietic radiation injury syndrome, acute (Bioplus only): To increase survival in patients acutely exposed to myelosuppressive doses of radiation

Peripheral blood progenitor cell collection and therapy (Bioplus and Bioplus biosimilars): Mobilization of autologous hematopoietic progenitor cells into the peripheral blood for apheresis collection

Severe chronic neutropenia (Bioplus and Bioplus biosimilars): Long-term administration to reduce the incidence and duration of neutropenic complications (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital, cyclic, or idiopathic neutropenia

Note: Bioplus (Bioplus-aafi) and Bioplus (Bioplus-sndz) are approved as biosimilars to Bioplus (Bioplus). In Canada, Grastofil is a biosimilar to Bioplus (Bioplus).

Off Label Uses

Alcoholic hepatitis (severe)

Data from a small randomized, non-blinded pilot study suggest Bioplus may be safe and effective therapy and may improve liver function as well as survival in patients with severe alcoholic hepatitis.

See also:
What other drugs will affect Bioplus?

The safety and efficacy of Bioplus given on the same day as myelosuppressive cytotoxic chemotherapy have not been definitively established. In view of the sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, the use of Bioplus is not recommended in the period from 24 hrs before to 24 hrs after chemotherapy. Preliminary evidence from a small number of patients treated concomitantly with Bioplus and 5-fluorouracil indicate that the severity of neutropenia may be exacerbated. Possible interactions with other haematopoietic growth factors and cytokines have not yet been investigated in clinical trials.

Since lithium promotes the release of neutrophils, lithium is likely to potentiate the effect of Bioplus. Although this interaction has not been formally investigated, there is no evidence that such an interaction is harmful.

Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes. This should be considered when interpreting bone-imaging results.

Incompatibilities: Bioplus should not be diluted with saline solutions. If required, Bioplus may be diluted in 5% glucose.

Diluted Bioplus may be adsorbed to glass and plastic materials. However, when diluted in 5% glucose solution, Bioplus is compatible with glass and a variety of plastic including PVC, polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.

See also:
What are the possible side effects of Bioplus?

During clinical studies 183 cancer patients and 96 healthy volunteers were exposed to Bioplus.

The safety profile of Bioplus observed in these clinical studies was consistent with that reported with the reference product used in these studies.

The following undesirable effects and their frequencies have been observed under treatment with Bioplus based on published information.

The assessment of undesirable effects is based on the following frequency data: Very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to <1/1,000; very rare: <1/10,000; not known: cannot be estimated from the available data.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

In Cancer Patients: In clinical trials, the most frequent undesirable effects attributable to Bioplus at the recommended dose were mild or moderate musculoskeletal pain, occurring in 10%, and severe musculoskeletal pain in 3% of patients. Musculoskeletal pain is usually controlled with standard analgesics. Less frequent undesirable effects include urinary abnormalities predominantly mild or moderate dysuria.

In randomised, placebo-controlled clinical trials, Bioplus did not increase the incidence of undesirable effects associated with cytotoxic chemotherapy. Undesirable effects reported with equal frequency in patients treated with Bioplus chemotherapy and placebo/chemotherapy included nausea and vomiting, alopecia, diarrhoea, fatigue, anorexia, mucositis, headache, cough, skin rash, chest pain, generalised weakness, sore throat, constipation and unspecified pain.

Reversible, dose-dependent and usually mild or moderate elevations of lactate dehydrogenase, alkaline phosphatase, serum uric acid, and gamma-glutamyl transpeptidase occurred with Bioplus in approximately 50%, 35%, 25%, and 10% of patients, respectively at recommended doses.

Transient decreases in blood pressure, not requiring clinical treatment, have been reported occasionally.

There have been reports of GvHD and fatalities in patients receiving G-CSF after allogeneic bone marrow transplantation.

Vascular disorders, including veno-occlusive disease and fluid volume disturbances, have been reported occasionally in patients undergoing high dose chemotherapy followed by autologous bone marrow transplantation. The causal association with Bioplus has not been established.

Very rare events of cutaneous vasculitis have been reported in patients treated with Bioplus. The mechanism of vasculitis in patients receiving Bioplus is unknown.

Cases of capillary leak syndrome have been reported in the post marketing setting with granulocyte colony-stimulating factor use. These have generally occurred in patients with advanced malignant diseases, sepsis, taking multiple chemotherapy medications or undergoing apheresis. Capillary Leak Syndrome, which can be life-threatening if treatment is delayed, has been reported uncommonly (≥1/1,000 to <1/100) in cancer patients undergoing chemotherapy following administration of granulocyte colony-stimulating factors.

The occurrence of Sweet's syndrome (acute febrile dermatosis) has been reported occasionally. However, since a significant percentage of these patients were suffering from leukaemia, a condition known to be associated with Sweet's syndrome, a causal relationship with Bioplus has not been established.

Exacerbation of rheumatoid arthritis has been observed in individual cases.

Rare pulmonary adverse events including interstitial pneumonia, pulmonary oedema, and pulmonary infiltrates have been reported in some cases with an outcome of respiratory failure or adult respiratory distress syndrome (ARDS), which may be fatal.

Allergic Reactions: Allergic-type reactions, including anaphylaxis, skin rash, urticaria, angioedema, dyspnoea and hypotension, occurring on initial or subsequent treatment have been reported in patients receiving Bioplus. Overall, reports were more common after intravenous administration. In some cases, symptoms have recurred with rechallenge, suggesting a causal relationship.

Bioplus should be permanently discontinued in patients who experience a serious allergic reaction.

Isolated cases of sickle cells crises have been reported in patients with sickle cell disease.

Pseudogout has been reported in patients with cancer treated with Bioplus.

In Peripheral Blood Progenitor Cell Mobilisation in Normal Donors: The most commonly reported undesirable effect was mild to moderate transient musculo-skeletal pain. Leukocytosis [White Blood Cell (WBC) >50 x 10⁹/L] was observed in 41% of donors and transient thrombocytopenia (platelets <100 x 10⁹/L) following Bioplus and leukapheresis was observed in 35% of donors.

Transient, minor increases in alkaline phosphatase, LDH, SGOT and uric acid have been reported in normal donors receiving Bioplus; these were without clinical sequelae.

Exacerbation of arthritic symptoms has been observed very rarely.

Symptoms suggestive of severe allergic reactions have been reported very rarely.

Headaches, believed to be caused by Bioplus, have been reported in PBPC donor studies.

Common but generally asymptomatic cases of splenomegaly and very rare cases of splenic rupture have been reported in healthy donors and patients following administration of G-CSFs.

In normal donors, pulmonary adverse events (haemoptysis, pulmonary haemorrhage, pulmonary infiltrates, dyspnoea and hypoxia) have been reported very rarely in post marketing experience with other Bioplus-containing medicinal products.

In Severe Chronic Neutropenia (SCN) Patients: Undesirable effects related to Bioplus therapy in SCN patients have been reported and for some their frequency tend to decrease with time.

The most frequent undesirable effects attributable to Bioplus were bone pain, and general musculoskeletal pain.

Other undesirable effects seen include splenic enlargement, which may be progressive in a minority of cases and thrombocytopenia. Headache and diarrhoea have been reported shortly after starting Bioplus therapy, typically in less than 10% of patients. Anaemia and epistaxis have also been reported.

Transient increases with no clinical symptoms were observed in serum uric acid, lactic dehydrogenase, and alkaline phosphatase. Transient, moderate decreases in non-fasting blood glucose have also been seen.

Undesirable effects possibly related to Bioplus therapy and typically occurring in <2% of SCN patients were injection site reaction, headache, hepatomegaly, arthralgia, alopecia, osteoporosis, and rash.

During long term use cutaneous vasculitis has been reported in 2% of SCN patients. There have been very few instances of proteinuria/haematuria.

In Patients with HIV: In clinical studies, the only undesirable effects that were consistently considered to be related to Bioplus administration were musculoskeletal pain, predominantly mild to moderate bone pain and myalgia. The incidence of these events was similar to that reported in cancer patients.

Splenic enlargement was reported to be related to Bioplus therapy in <3% of patients. In all cases this was mild or moderate on physical examination and the clinical course was benign; no patients had a diagnosis of hypersplenism and no patients underwent splenectomy. As splenic enlargement is a common finding in patients with HIV infection and is present to varying degrees in most patients with AIDS, the relationship to Bioplus treatment is unclear.