Teplizumab inj

Indications

Teplizumab inj is used for: Type 1 Diabetes Mellitus

Adult Dose

IV infusion Type 1 Diabetes Mellitus Indicated to delay the onset of stage 3 type 1 diabetes mellitus (T1DM) in adults who currently have stage 2 type 1 diabetes. Administer by IV infusion over 30 min once daily for 14 consecutive days. 2 mg per 2 mL (1 mg/mL) single-dose vial Premedicate with NSAID or paracetamol, an antihistamine, and/or an antiemetic, for the first 5 days of dosing. Hepatic impairment: No recommendations listed in prescribing information

Child Dose

IV infusion Type 1 Diabetes Mellitus Indicated to delay the onset of stage 3 type 1 diabetes mellitus (T1DM) in children aged >8 years who currently have stage 2 type 1 diabetes Administer by IV infusion over 30 min once daily for 14 consecutive days. 2 mg per 2 mL (1 mg/mL) single-dose vial Premedicate with NSAID or paracetamol, an antihistamine, and/or an antiemetic, for the first 5 days of dosing.

Renal Dose

Renal impairment:No recommendations listed in prescribing information

Administration

IV Preparation Inspect visually before use (supplied solution is clear and colorless); discard if particulate matter or coloration observed Preparation of diluted 10 mcg/mL solution Prepare using aseptic technique; each vial is for single dose only Prepare a sterile glass vial or PVC infusion bag with 18 mL of 0.9% NaCl, and slowly add 2 mg (2 mL) of teplizumab Mix gently by slowly inverting vial or rocking infusion bag Resulting 20 mL diluted solution contains 100 mcg/mL Preparation of infusion bag using diluted solution Using an appropriately sized syringe (eg, 5 mL), withdraw volume of diluted teplizumab solution required for that day’s calculated dose from 100 mcg/mL solution Slowly add contents of the syringe containing the dose to 25 mL 0.9% NaCl PVC infusion bag Gently rock infusion bag to ensure the solution mixes sufficiently; do not shake Discard unused portion of remaining diluted teplizumab solution in the sterile glass vial or PVC infusion bag Start infusion within 2 hr of preparation If not used immediately, store at room temperature (15-30ºC [59-86ºF]) and complete infusion within 4 hr of the start of preparation Discard infusion solution if not administered within 4 hr of preparation IV Administration Infuse over 30 minutes Premedicate with NSAID or paracetamol, an antihistamine, and/or an antiemetic for the first 5 days of dosing

Contra Indications

Precautions

Bacterial and viral infections (eg, gastroenteritis, cellulitis, pneumonia, abscess, sepsis) reported; not recommended with active, serious infection or chronic infection other than localized skin infections; monitor for signs and symptoms during and after treatment; if serious infection develops, treat appropriately and discontinue drug Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting, and bronchospasm reported; if severe hypersensitivity reactions occur, discontinue use and treat promptly Lymphopenia commonly occurs during treatment In most patients who experienced lymphopenia, lymphocyte levels began to recover after day 5 of treatment and returned to pretreatment values within 2 weeks after completion and without dose interruption Monitor WBC counts during treatment period CRS observed in clinical trials during treatment through 28 days after the last dose CRS manifestations included fever, nausea, fatigue, headache, myalgia, arthralgia, increased ALT/AST, and increased total bilirubin These manifestations typically occurred during the first 5 days of treatment

Pregnancy-Lactation

Pregnancy Available case reports from clinical trials are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes Although there are no data on teplizumab, monoclonal antibodies can be actively transported across the placenta, and teplizumab may cause immunosuppression in the utero-exposed infant Minimize fetal exposure by avoiding use during pregnancy and at least 30 days (6 half-lives) before planned pregnancy Clinical considerations Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses, and peaks during the third trimester Because teplizumab may interfere with immune response to infections, consider risks and benefits before administering live vaccines to infants exposed to in utero Data are insufficient regarding infant serum levels of teplizumab at birth and the duration of persistence in infant serum after birth to identify a specific time frame to delay live virus immunizations in infants exposed in utero Animal studies Mice were given a surrogate anti-mouse CD3 antibody SC during organogenesis through lactation Pups born to dams who were administered the murine surrogate antibody during pregnancy showed a reduction in the adaptive immune response consistent with the expected pharmacology Lactation No data are available regarding presence of teplizumab in either human or animal milk, effects on breastfed children, or effects on milk production Endogenous maternal IgG and monoclonal antibodies are transferred into human milk A lactating woman may interrupt breastfeeding and pump and discard breast milk during treatment and for 20 days after administration to minimize drug exposure to a breastfed child

Interactions

Vaccinations Administer all age-appropriate vaccinations prior to starting teplizumab Live-attenuated vaccines: Not recommended within 8 weeks before teplizumab treatment, during treatment, or up to 52 weeks after treatment Inactivated or mRNA vaccines: Not recommended within 2 weeks before teplizumab treatment, during treatment, or 6 weeks after completion of treatment Safety of immunization with live-attenuated vaccines in treated patients has not been studied Additionally, teplizumab may interfere with immune response to vaccination and decrease vaccine efficacy

Side Effects

Side effects of Teplizumab inj : >10% Lymphopenia (73%) Rash (36-48%) Anemia (27%) Leukopenia (21%) Headache (11%) 1-10% Serious infections (9%) Increased ALT (5%) Nausea (5%) Diarrhea (5%) Nasopharyngitis (5%) Cytokine release syndrome (2%) Urticaria (1.9%) Peripheral and generalized edema (1.6%) <1% Hypersensitivity Angioedema

Mode of Action

Humanized monoclonal antibody (mAb) that targets the cluster of differentiation 3 (CD3) antigen, which is coexpressed with the T-cell receptor (TCR) on the surface of T lymphocytes The Fc region of the mAb has been engineered to have Fc receptor nonbinding (FNB) properties to avoid adverse effects (eg, cytokine release) associated with intact Fc Mechanism may involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes, leading to an increase in the proportion of regulatory T cells and of exhausted CD8+ T cells in peripheral blood