atezolizumab (Rx)

Brand and Other Names:Tecentriq
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 60mg/mL (1200mg/20mL)

Urothelial Carcinoma

Indicated for locally advanced or metastatic urothelial carcinoma in patients who are ineligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained infiltrating immune cells [IC] covering ≥5% of the tumor area) as defined by a FDA-approved test, in patients who are ineligible for any platinum-containing therapy regardless of PD-L1 status, or in patients who have disease progression during or following any platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy

840 mg IV q2Weeks or

1200 mg IV q3Weeks or

1680 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Non-Small Cell Lung Cancer

Single agent for disease progression

  • Indicated for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab
  • 840 mg IV q2Weeks or
  • 1200 mg IV q3Weeks or
  • 1680 mg IV q4Weeks

Combination therapy for first-line treatment

  • Indicated in combination with bevacizumab, paclitaxel, and carboplatin for first-line treatment of patients with metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations
  • 1200 mg IV on Day 1 q3Weeks for maximum of 4-6 cycles, followed by bevacizumab, paclitaxel, and carboplatin
  • Refer to prescribing information for bevacizumab, paclitaxel, and carboplatin for recommended dosing information
  • After completion of chemotherapy cycles 4-6 with bevacizumab
    • After completion of chemotherapy cycles 4-6: 1200 mg IV, followed by bevacizumab on Day 1 q3Weeks; continue until disease progression or unacceptable toxicity
  • Following completion of 4-6 cycles, and if bevacizumab is discontinued
    • 840 mg IV q2Weeks or
    • 1200 mg IV q3Weeks or
    • 1680 mg IV q4Weeks
    • Continue until disease progression or unacceptable toxicity

Triple-Negative Breast Cancer

Indicated in combination with paclitaxel protein-bound for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating IC of any intensity covering ≥1% of the tumor area), as defined by an FDA-approved test

Atezolizumab 840 mg IV on Days 1 and 15 for each 28-day cycle PLUS

Paclitaxel protein-bound 100 mg/m² on Days 1, 8, and 15 for each 28-day cycle

Continue until disease progression or unacceptable toxicity

Small Cell Lung Cancer

Indication in combination with carboplatin and etoposide for first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC)

1200 mg IV on Day 1 q3Weeks

Continue until disease progression or unacceptable toxicity

Refer to prescribing information for chemotherapy agents administered in combination for recommended dosing information

Following completion of 4 cycles of carboplatin and etoposide

  • 840 mg IV q2Weeks or
  • 1200 mg IV q3Weeks or
  • 1680 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity

Dosage Modifications

No dose reductions are recommended

Interrupt or slow infusion rate

  • Grade 1 or 2 infusion rate reactions

Withhold dose until Grade 1 or resolved and corticosteroid dose ≤prednisone 10 mg/day (or equivalent)

  • Grade 2 pneumonitis
  • AST or ALT >3 and <8x ULN or total bilirubin >1.5 and <3x ULN
  • Grade 2 or 3 diarrhea or colitis
  • Grade 3 other immune-mediated adverse reactions involving a major organ

Withhold dose until Grade 1 or resolved and clinically stable on hormone replacement therapy

  • Grade 2-4 endocrinopathies (including but not limited to hypophysitis, adrenal insufficiency, hyperthyroidism, and type 1 diabetes mellitus)
  • Grade 3 or 4 infection

Withhold dose until Grade 1 or resolved

  • Grade 3 or 4 infection

Permanently discontinue

  • Grade 3 or 4 pneumonitis
  • AST or ALT >8x ULN or total bilirubin >3x ULN
  • Grade 4 diarrhea or colitis
  • Grade 4 other immune-mediated adverse reactions involving a major organ
  • Grade 3 or 4 infusion-related reactions
  • Grade 2 or 3 adverse reaction that does not recover to Grade 0 or 1 within 12 weeks after last atezolizumab dose
  • Inability to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks after last atezolizumab dose
  • Recurrent Grade 3 or 4 (severe or life-threatening) adverse reaction

Renal impairment

  • Mild or moderate (eGFR 30-89 mL/min/1.73 m²): No dose adjustment is recommended
  • Severe (eGFR <20 mL/min/1.73 m²): Not studied

Hepatic impairment

  • Mild: No dose adjustment is recommended
  • Moderate-to-severe: Not studied

Dosing Considerations

Patient selection for treatment of urothelial carcinoma and triple-negative breast cancer

  • Select patients based on the PD-L1 expression on tumor infiltrating immune cells
  • Information on FDA-approved tests for the determination of PD-L1 expression in locally advanced or metastatic urothelial carcinoma or triple-negative breast cancer are available at: http://www.fda.gov/CompanionDiagnostics

Melanoma (Orphan)

Orphan designation (with or without cobimetinib) for treatment of stage IIb, IIc, III, and IV melanoma

Sponsor

  • Genentech, Inc; 1 DNA Way, MS 35-5E; South San Francisco, California 94080

Safety and efficacy not established

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Adverse Effects

All grades of severity are listed unless otherwise indicated

>10% (Urothelial carcinoma)

Fatigue (52%)

Decreased appetite (24-26%)

Nausea (22-25%)

Diarrhea (18-24%)

Urinary tract infection (17-22%)

Constipation (15-21%)

Pyrexia (14-21%)

Back/neck pain (15-18%)

Pruritus (13-18%)

Peripheral edema (17-18%)

Rash (15-17%)

Vomiting (16-17%)

Abdominal pain (15-17%)

Dyspnea (12-16%)

Cough (14%)

Hyponatremia, Grade 3 or 4 (15%)

Arthralgia (13-14%)

Hematuria (14%)

>10% (NSCLC, in combination with bevacizumab, paclitaxel, and carboplatin)

Anemia (67-83%)

Hyperglycemia (61%)

Neuropathy (56%)

Increased BUN (52%)

Neutropenia (52%)

Fatigue/asthenia (44-50%)

Lymphocytopenia (49%)

Alopecia (48%)

Lymphopenia (48%)

Hypoalbuminemia (40-48%)

Hyponatremia (38-42%)

Myalgia/pain (42%)

Hypomagnesemia (26-42%)

Increased AST (31-40%)

Nausea (18-39%)

Increased alkaline phosphatase (39%)

Increased ALT (27-37%)

Diarrhea (16-33%)

Neutropenia, Grade 3 or 4 (31%)

Increased TSH (30%)

Constipation (18-30%)

Decreased appetite (23-29%)

Hyperkalemia (28%)

Increased creatinine (23-28%)

Hypocalcemia (26%)

Arthralgia (26%)

Cough (20-26%)

Hypertension (25%)

Hyperphosphatemia (25%)

Hypophosphatemia (25%)

Hypokalemia (23%)

Rash (12-23%)

Dyspnea (22%)

Pyrexia (18-19%)

Vomiting (19%)

Epistaxis (17%)

Lymphopenia, Grade 3 or 4 (17%)

Proteinuria (16%)

Headache (16%)

Arthralgia (1-12%)

>10% (TNBC)

Alopecia (56%)

Fatigue (47%)

Peripheral neuropathies (47%)

Nausea (46%)

Diarrhea (33%)

Anemia (28%)

Constipation (25%)

Headache (23%)

Neutropenia (21%)

Vomiting (20%)

Decreased appetite (20%)

Pyrexia (19%)

Arthralgia (18%)

Rash (17%)

Peripheral edema (15%)

Back pain (15%)

Myalgia (14%)

Pruritus (14%)

Dizziness (14%)

Dysgeusia (14%)

Hypothyroidism (14%)

Decreased neutrophils (13%)

Urinary tract infection (12%)

Asthenia (12%)

Pain in extremity (11%)

Upper respiratory infection (11%)

Nasopharyngitis (11%)

>10% (SCLC)

Anemia (94%)

Neutropenia (73%)

Hyperglycemia (67%)

Thrombocytopenia (58%)

Lymphopenia (46%)

Neutropenia, Grade 3-4 (45%)

Increased alkaline phosphatase (38%)

Fatigue/asthenia (39%)

Nausea (38%)

Alopecia (37%)

Hyponatremia (34%)

Hypoalbuminemia (32%)

Hypomagnesemia (31%)

Decreased TSH (28%)

Decreased appetite (27%)

Constipation (26%)

Hypocalcemia (26%)

Increased ALT (26%)

Increased AST (22%)

Increased blood creatinine (22%)

Neutropenia (22%)

Hyperphosphatemia (21%)

Increased TSH (21%)

Thrombocytopenia, Grade 3-4 (20%)

Vomiting (20%)

Anemia, Grade 3-4 (17%)

Hyponatremia, Grade 3-4 (15%)

Lymphopenia, Grade 3-4 (14%)

Hyperglycemia, Grade 3-4 (10%)

1-10% (Urothelial carcinoma)

Hyperglycemia, Grade 3 or 4 (10%)

Lymphopenia, Grade 3 or 4 (9%)

Fatigue, Grade 3 or 4 (8%)

Increased alkaline phosphatase, Grade 3 or 4 (7%)

Anemia, Grade 3 or 4 (7%)

Increased creatinine, Grade 3 or 4 (5%)

Diarrhea, Grade 3 or 4 (5%)

Urinary tract infection, Grade 3 or 4 (5%)

Hypophosphatemia, Grade 3 or 4 (4%)

Increased ALT/AST, Grade 3 or 4 (4%)

Decreased appetite, Grade 3 or 4 (1-3%)

Hyperkalemia, Grade 3 or 4 (3%)

Hypermagnesemia, Grade 3 or 4 (3%)

Hyperbilirubinemia, Grade 3 or 4 (3%)

Back/neck pain (2-3%)

Hematuria, Grade 3 or 4 (3%)

Nausea, Grade 3 or 4 (2%)

Peripheral edema, Grade 3 or 4 (2%)

Constipation, Grade 3 or 4 (2%)

Arthralgia, Grade 3 or 4 (1%)

1-10% (NSCLC, in combination with bevacizumab paclitaxel, and carboplatin)

Hyponatremia, Grade 3 or 4 (10%)

Anemia, Grade 3 or 4 (10%)

Hypertension, Grade 3 or 4 (9%)

Hypokalemia, Grade 3 or 4 (7%)

Fatigue/asthenia, Grade 3 or 4 (6%)

Diarrhea, Grade 3 or 4 (6%)

Increased ALT, Grade 3 or 4 (6%)

Nausea, Grade 3 or 4 (4%)

Decrease appetite, Grade 3 or 4 (4%)

Increased AST, Grade 3 or 4 (4%)

Hypophosphatemia, Grade 3 or 4 (4%)

Hyperkalemia, Grade 3 or 4 (3%)

Neuropathy, Grade 3 or 4 (3%)

Myalgia/pain, Grade 3 or 4 (1.3-3%)

Proteinuria, Grade 3 or 4 (3%)

Hypoalbuminemia, Grade 3 or 4 (3%)

Hypocalcemia, Grade 3 or 4 (3%)

Dyspnea, Grade 3 or 4 (2.8%)

Rash, Grade 3 or 4 (2%)

Hypomagnesemia, Grade 3 or 4 (2%)

Increased alkaline phosphatase, Grade 3 or 4 (2%)

Vomiting, Grade 3 or 4 (1%)

Epistaxis, Grade 3 or 4 (1%)

Increased creatinine (1%)

1-10% (TNBC)

Increased ALT (10%)

Abdominal pain (10%)

Neutropenia, Grade 3 or 4 (8%)

Decreased neutrophils, Grade 3 or 4 (4.6%)

Anemia, Grade 3 or 4 (2.9%)

Diarrhea, Grade 3 or 4 (1.3%)

Nausea, Grade 3 or 4 (1.1%)

1-10% (SCLC)

Fatigue/asthenia, Grade 3-4 (5%)

Hypomagnesemia, Grade 3-4 (5%)

Pneumonia (4.5%)

Increased blood creatinine, Grade 3-4 (4%)

Neutropenia, Grade 3 or 4 (3.5%)

Hypocalcemia, Grade 3-4 (3%)

Increased ALT, Grade 3-4 (3%)

Febrile neutropenia (2.5%)

Thrombocytopenia (2.5%)

Vomiting, Grade 3-4 (2%)

Increased AST, Grade 3-4 (1%)

Nausea, Grade 3-4 (1%)

Constipation, Grade 3-4 (1%)

Decreased appetite, Grade 3-4 (1%)

Increased alkaline phosphatase, Grade 3-4 (1%)

Hypoalbuminemia, Grade 3-4 (1%)

<1% (Urothelial carcinoma)

Pyrexia, Grade 3 or 4

Vomiting, Grade 3 or 4

Abdominal pain, Grade 3 or 4

Pruritus, Grade 3 or 4

Rash, Grade 3 or 4

<1% (NSCLC, in combination with bevacizumab paclitaxel, and carboplatin)

Headache, Grade 3 or 4

Pyrexia, Grade 3 or 4

Constipation, Grade 3 or 4

Cough, Grade 3 or 4

<1% (TNBC)

Alopecia, Grade 3 or 4

Rash, Grade 3 or 4

Pyrexia, Grade 3 or 4

Peripheral edema, Grade 3 or 4

Asthenia, Grade 3 or 4

Constipation, Grade 3 or 4

Vomiting, Grade 3 or 4

Abdominal pain, Grade 3 or 4

Headache, Grade 3 or 4

Dyspnea, Grade 3 or 4

Decreased appetite, Grade 3 or 4

Arthralgia, Grade 3 or 4

Myalgia, Grade 3 or 4

Pain in extremity, Grade 3 or 4

Urinary tract infection, Grade 3 or 4

Postmarketing Reports

Cardiac: Myocarditis

Dermatologic: Bullous dermatitis, pemphigoid, erythema multiforme, Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN)

Gastrointestinal: Pancreatitis, including increases in serum amylase or lipase levels

General: Systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis

Hematological: Autoimmune hemolytic anemia, immune thrombocytopenic purpura

Musculoskeletal: Myositis, rhabdomyolysis

Neurological: Guillain-Barre syndrome, myasthenia syndrome/myasthenia gravis, demyelination, immune-related meningoencephalitis, aseptic meningitis, encephalitis, facial and abducens nerve paresis, polymyalgia rheumatica, autoimmune neuropathy, and Vogt-Koyanagi- Harada syndrome

Ophthalmological: Uveitis, iritis

Renal: Nephrotic syndrome, nephritis

Vascular: Vasculitis

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Warnings

Contraindications

None

Cautions

Immune-mediated pneumonitis or interstitial lung disease occurred; monitor for signs and symptoms of pneumonitis; administer steroids at a dose of 1-2 mg/kg/day prednisone equivalents for Grade ≥2 pneumonitis, followed by corticosteroid taper

May cause liver test abnormalities and immune-mediated hepatitis; fatal cases reported; monitor for signs and symptoms of hepatitis, during and after discontinuation of therapy, including clinical chemistry monitoring; administer corticosteroids, prednisone 1-2 mg/kg/day or equivalents, followed by a taper for Grade 2 or higher elevations of ALT, AST, and/or total bilirubin (see Dosage Modifications)

Immune-mediated colitis or diarrhea reported; if symptoms persist for >5 days or recur, administer 1-2 mg/kg prednisone or equivalent per day; withhold treatment for Grade 3 diarrhea or colitis; treat with IV methylprednisolone 1-2 mg/kg per day and convert to oral steroids once patient improves (see Dosage Modifications)

Therapy can cause severe or life-threatening infusion-related reactions; monitor for signs and symptoms of infusion-related reactions; interrupt, slow rate of, or permanently discontinue therapy based on severity; for Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses

Severe infections (eg, sepsis, herpes encephalitis, mycobacterial infection) leading to retroperitoneal hemorrhage reported; monitor for signs and symptoms of infection

Can cause fetal harm; advise females of reproductive potential of potential risk to a fetus and use of effective contraception (see Pregnancy)

Immune-related endocrinopathies

  • Immune-related myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, or meningoencephalitis reported; permanently discontinue for any grade
  • Monitor for clinical signs and symptoms of meningitis or encephalitis; permanently discontinue treatment for any grade of meningitis or encephalitis; treat with IV steroids (1-2 mg/kg/day methylprednisolone or equivalent) and convert to oral steroids (prednisone 60 mg/day or equivalent) once patient improves; when symptoms improve to Grade ≤1, taper steroids over ≥1 month
  • Monitor for symptoms of motor and sensory neuropathy; permanently discontinue treatment for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome; consider initiation of systemic corticosteroids at a dose of 1-2 mg/kg/day prednisone
  • Symptomatic pancreatitis without an alternative etiology occurred in 0.1% of patients across clinical trials; monitor for signs and symptoms of acute pancreatitis
  • Monitor for signs and symptoms of myocarditis
  • Thyroid disorders may occur; monitor thyroid function prior to and periodically during treatment; initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated; continue therapy for hypothyroidism and interrupt for hyperthyroidism based on severity
  • Adrenal insufficiency may occur; monitor patients for clinical signs and symptoms of adrenal insufficiency; for Grade 2 or higher adrenal insufficiency, initiate prednisone 1-2 mg/kg/day or equivalents, followed by a taper and hormone replacement as clinically indicated; interrupt treatment based on severity
  • Type 1 diabetes mellitus reported; monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated; interrupt treatment based on severity
  • Hypophysitis/hypopituitarism may occur; for Grade 2 or higher hypophysitis, initiate prednisone 1-2 mg/kg/day or equivalents, followed by a taper and hormone replacement therapy as clinically indicated
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Pregnancy

Pregnancy

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

No available data on use in pregnant women

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

  • Advise females of reproductive potential to use effective contraception during treatment and for at least 5 months following the last dose

Infertility

  • Based on animal studies, atezolizumab may impair fertility in females of reproductive potential while receiving treatment

Lactation

Unknown if distributed in human breast milk

As human IgG is excreted in human milk, potential for absorption and harm to the infant is unknown

Advise lactating woman not to breastfeed during treatment and for at least 5 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

Monoclonal antibody to programmed cell death ligand-1 protein (PDL1); binding PDL1 blocks the interaction between PDL-1 and its ligands (including B7.1 receptors)

PDL-1

  • PDL1 is expressed on the surface of activated T cells under normal conditions; binding PDL1 inhibits immune activation and reduces T-cell cytotoxic activity when bound
  • This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation
  • Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PDL1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells

Absorption

Systemic accumulation over 2-3 cycles of repeated dosing

  • Peak plasma concentration: 1.91-fold
  • Minimum plasma concentration: 1.46-fold
  • AUC: 2.75-fold

Steady state: 6-9 weeks

Distribution

Vd: 6.9 L

Elimination

Half-life: 27 days

Clearance: 0.2 L/day

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Administration

IV Compatibilities

0.9% NaCl

IV Preparation

Visually inspect solution for particulate matter and discoloration prior to administration

Solution should appear colorless to slightly yellow; discard if cloudy, discolored, or particles observed

Do NOT shake vial

Dilution

  • Withdraw required amount from vial
  • Dilute into a 250-mL polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag containing 0.9% NaCl
  • Dilute with 0.9% NaCl only
  • Gently invert diluted solution; do not shake
  • Discard partially used or empty vial

IV Administration

For IV infusion only; do not give as IV bolus or IV push

Administer through an IV line with or without a sterile, nonpyrogenic, low-protein binding in-line filter (pore size of 0.2-0.22 micron)

First IV infusion: Infuse over 60 min

Subsequent IV infusions: If first infusion is tolerated, may administer subsequent doses over 30 min

When administering in combination with chemotherapy, administer atezolizumab before chemotherapy when given on the same day

Do not coadminister with other drugs through the same IV line

Storage

Contains no preservatives

Do not freeze

Do not shake

Unopened vials

  • Refrigerate at 2-8°C (36-46°F) in original carton to protect from light

Diluted infusion solution

  • Administer immediately once prepared
  • If not used immediately, it can be stored by either:
    • At room temperature for no more than 6 hr from time of preparation (includes infusion time) OR
    • Refrigerate at 2-8°C (36-46°F) for no more than 24 hr
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Formulary

FormularyPatient Discounts

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

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • 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.