dostarlimab (Rx)

Brand and Other Names:Jemperli, dostarlimab-gxly
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 50mg/mL (10 mL, single-dose vials)

Endometrial Cancer

Indicated for adults with mismatch repair–deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen

Doses 1-4: 500 mg IV q3Weeks, THEN

Dose 5 and thereafter (start 3 weeks after Dose 4): 1,000 mg IV q6Weeks until disease progression or unacceptable toxicity

Dosage Modifications

No dose reductions are recommended

Pneumonitis

  • Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
  • Grade 3 or 4 or recurrent Grade 2: Permanently discontinue

Colitis

  • Grade 2 or 3: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
  • Grade 4: Permanently discontinue

Hepatitis with no tumor involvement of the liver

  • AST or ALT increases to >3 and ≤8x ULN or total bilirubin increases to >1.5 and <3x ULN: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
  • AST or ALT increases to >8x ULN or total bilirubin increases to >3x ULN: Permanently discontinue

Hepatitis with tumor involvement of liver

  • Withhold therapy
    • Baseline AST or ALT >1 and ≤3x ULN and increases to >5 and ≤10x ULN
    • Baseline AST or ALT >3 and ≤5x ULN and increases to >8 and ≤10x ULN
    • Resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
    • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
  • Permanently discontinue
    • AST or ALT increases >10x ULN or total bilirubin increases to >3x ULN

Endocrinopathies

  • Grade 2, 3, or 4: Withhold until clinically stable or permanently discontinue depending on severity
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids

Nephritis with renal dysfunction

  • Grade 2 or 3 increased blood creatinine: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
  • Grade 4 increased blood creatinine: Permanently discontinue

Exfoliative dermatologic conditions

  • Suspected Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS) syndrome: Withhold therapy

  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids

  • Confirmed SJS, TEN, or DRESS syndrome: Permanently discontinue

Myocarditis

  • Grade 2, 3, or 4: Permanently discontinue

Neurologic toxicities

  • Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
  • Grade 3 or 4: Permanently discontinue

Infusion-related reactions

  • Grade 1 or 2: Interrupt or slow infusion rate
  • Grade 3 or 4: Permanently discontinue

Renal or hepatic impairment

  • Mild-severe and end-stage renal disease: No dosage adjustment necessary

Hepatic impairment

  • Mild-to-moderate (total bilirubin ≤3x ULN and any AST): No dose adjustment is recommended
  • Severe: Not studied

Dosing Considerations

Females of reproductive potential: Verify pregnancy status before initiation

Patient selection

Safety and efficacy not established

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Interactions

Interaction Checker

and dostarlimab

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      Serious - Use Alternative

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            Adverse Effects

            >10%

            All grades

            • Fatigue (48%)
            • Lymphopenia (37%)
            • Hypoalbuminemia (30%)
            • Nausea (30%)
            • Increased creatinine (27%)
            • Hyponatremia (26%)
            • Diarrhea (26%)
            • Increased alkaline phosphatase (25%)
            • Anemia (24%)
            • Leukopenia (21%)
            • Constipation (20%)
            • Vomiting (18%)
            • Increased AST (16%)
            • Hypercalcemia (15%)
            • Increased ALT (15%)
            • Hypokalemia (15%)
            • Decreased appetite (14%)
            • Cough (14%)
            • Pruritus (14%)
            • Urinary tract infection (13%)
            • Myalgia (12%)

            Grade 3 or 4

            • Anemia (13%)

            1-10%

            All grades

            • Sepsis (2.9%)
            • Acute kidney injury (2.9%)
            • Urinary tract infection (2.9%)
            • Abdominal pain (2.9%)
            • Pyrexia (2.9%)

            Grade 3 or 4

            • Lymphopenia (9%)
            • Hyponatremia (4.8%)
            • Increased ALT (2.9%)
            • Leukopenia (2.9%)
            • Hypoalbuminemia (2.9%)
            • Increased alkaline phosphatase (2.9%)
            • Increased creatinine (2.9%)
            • Hypercalcemia (1.9%)
            • Hypokalemia (1.9%)
            • Increased AST (1.9%)
            • Urinary tract infection (1.9%)
            • Diarrhea (1.9%)
            • Pruritus (1%)
            • Fatigue (1%)

            <1%

            Constipation (0.9%)

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            Warnings

            Contraindications

            None

            Cautions

            May cause severe or life-threatening infusion-related reactions; monitor for signs and symptoms of infusion-related reactions

            Severe infections (eg, sepsis, herpes encephalitis, mycobacterial infection) leading to retroperitoneal hemorrhage reported; most common infection was upper respiratory tract infection; monitor for signs and symptoms of infection

            Can cause fetal harm

            Immune-mediated adverse reactions

            • Severe or fatal immune-mediated adverse reactions can occur in any organ system or tissue
            • May start at any time after initiating a programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1)–blocking antibody; may manifest during treatment and after discontinuation
            • Immune-mediated pneumonitis, colitis, hepatitis, hypophysitis, thyroid disorders, thyroiditis, hypothyroidism, nephritis, or hyperthyroidism may occur
            • Can cause primary or secondary adrenal insufficiency
            • Type 1 diabetes mellitus reported, which can present with diabetic ketoacidosis; monitor for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated; withhold or permanently discontinue depending on severity
            • Immune-mediated rash or dermatitis (bullous and exfoliative dermatitis, SJS, TEN, DRESS syndrome) has occurred
            • Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions
            • If immune-mediated adverse reactions are suspected, initiate appropriate workup to exclude alternative etiologies, including infection; institute medical management promptly, including specialty consultation as appropriate
            • Other immune-mediated adverse reactions are the following
              • Nervous system: Meningitis, encephalitis, myelitis, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy
              • Cardiac/vascular: Myocarditis, pericarditis, vasculitis
              • Ocular: Uveitis, iritis, other ocular inflammatory toxicities; some cases can be associated with retinal detachment; various grades of visual impairment to include blindness can occur; if uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss
              • Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis
              • Musculoskeletal and connective tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica
              • Endocrine: Hypoparathyroidism
              • Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection

            Complications of allogeneic hematopoietic stem cell transplantation

            • Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody
            • Transplantation-related complications include hyperacute graft versus host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced-intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
            • These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
            • Closely monitor for evidence of transplantation-related complications and intervene promptly; consider benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT
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            Pregnancy & Lactation

            Pregnancy

            Based on its mechanism of action, can cause fetal harm when administered during pregnancy

            No available data on use in pregnant females

            Verify pregnancy status in females of reproductive potential before initiation

            Animal data

            • Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus, resulting in fetal death

            Contraception

            Females of reproductive potential: Use effective contraception during treatment and for at least 4 months following the last dose

            Lactation

            No data are available on presence in human milk, effects on breastfed children, or on milk production

            Advise lactating females not to breastfeed during treatment and for at least 4 months after the last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Humanized monoclonal antibody of the IgG4 isotype binds to PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway–mediated inhibition of the immune response, including antitumor immune response

            Binding of PD-1 ligands, PD-L1 and PD-L2, to PD-1 receptor found on T-cells; inhibits T-cell proliferation and cytokine production

            Up-regulation of PF-1 ligands occurs in some tumors; signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors

            Absorption

            Peak plasma concentration

            • 500-mg dose: 171 mcg/mL
            • 1,000-mg dose: 309 mcg/mL

            AUC

            • 500-mg dose: 35,730 mcg·hr/mL
            • 1,000-mg dose: 95,820 mcg·hr/mL

            Distribution

            Vd (steady-state): 5.3 L

            Metabolism

            Metabolized into small peptides and amino acids by catabolic pathways

            Elimination

            Half-life: 25.4 days

            Clearance (steady-state): 0.007 L/hr

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            Administration

            IV Incompatibilities

            Do not coadminister other drugs through same infusion line

            IV Compatibilities

            0.9% NaCl

            Dextrose 5% (D5W)

            IV Preparation

            Visually inspect vials for particulate matter and discoloration; solution is clear to slightly opalescent, colorless to yellow; discard if visible particles are observed

            Do not shake

            500-mg dose

            • Withdraw 10 mL (from 1 vial) using disposable polypropylene sterile syringe

            • Dilute into IV infusion bag (not to exceed 250 mL) containing 0.9% NaCl or D5W; resulting final concentration is 2-10 mg/mL

            1,000-mg dose

            • Withdraw 20 mL (from 2 vials) using a disposable polypropylene sterile syringe
            • Dilute into IV infusion bag (not to exceed 250 mL) containing 0.9% NaCl or D5W; resulting final concentration is 4-10 mg/mL

            Gently invert to mix diluted solution; do NOT shake

            Discard any unused portion left in vial(s)

            IV Administration

            Infuse over 30 minutes through IV line using tubing made of polyvinyl chloride or platinum-cured silicon; fittings made of polyvinyl chloride or polycarbonate; and a sterile, nonpyrogenic, low-protein–binding, 0.2-micron, inline or add-on filter

            Do not administered as IV push or bolus injection

            Do not coadminister other drugs through same infusion line

            Storage

            Unopened vials

            • Refrigerate at 2-8°C (36-46°F)
            • Protect from light

            Diluted solutions

            From time of preparation until end of infusion
            • Store at room temperature for ≤6 hr, OR
            • Refrigerate at 2-8°C (36-46°F) for ≤24 hr
            • Discard after 6 hr at room temperature or after 24 hr under refrigeration; do not freeze
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.