Ibalizumab

Dosage Forms

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

Solution, Intravenous [preservative free]:

Trogarzo: ibalizumab-uiyk 150 mg/mL (1.33 mL) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Ibalizumab, a recombinant humanized monoclonal antibody, is a post-attachment inhibitor. It blocks HIV-1 from infecting CD4⁺ T cells by binding to domain 2 of CD4⁺ cell receptors leading to a conformational change that blocks the interaction of gp120 and HIV co-receptors; it is active against CCR5 and CXCR4 isolates. The selective binding to domain 2 of the CD4⁺ cells allows ibalizumab to block HIV entry without causing immunosuppression or depleting CD4⁺ cell counts (Iacob 2017).

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 4.8 L

Half-Life Elimination

3.1 to 3.3 days (Jacobson 2009)

Use: Labeled Indications

HIV-1 infection: Treatment of HIV-1 infection in combination with other antiretrovirals in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosage and Administration

Dosing: Adult

HIV-1 infection: IV: Initial: 2,000 mg as a single dose, followed by a maintenance dose of 800 mg every 14 days thereafter

Missed dose: If a maintenance dose (800 mg) is missed by ≥3 days beyond the originally scheduled dosing day, a loading dose (2,000 mg) should be given as soon as possible. Resume maintenance dosing every 14 days thereafter.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

IV: Withdraw 1.33 mL from each vial needed for a dose (10 vials for loading dose or 4 vials for maintenance dose) and transfer total volume withdrawn into a 250 mL bag of NS. Do not mix or dilute with other medications.

Administration

IV: For IV administration only. Do not administer IV push or bolus. Administer in the cephalic vein, or if not accessible, an appropriate vein elsewhere may be used.

Administer initial infusion (loading dose) over ≥30 minutes. Observe patient for 1 hour after completion of initial infusion. If no infusion-associated adverse reactions are observed, subsequent infusions (maintenance doses) may be administered over ≥15 minutes and post-infusion observation time may be reduced to 15 minutes. Flush with 30 mL NS after completion of each infusion.

Storage

Store intact vials under refrigeration at 2ºC to 8ºC (36ºF to 46ºF). Do not freeze; protect from light. Diluted solution may be stored at 20°C to 25°C (68°F to 77°F) for ≤4 hours or under refrigeration at 2°C to 8°C (36°F to 46°F) for ≤24 hours. If refrigerated, allow to stand at room temperature for ≥30 minutes but ≤4 hours prior to administration.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Reactions reported with combination therapy.

1% to 10%:

Central nervous system: Dizziness (8%)

Dermatologic: Skin rash (5%)

Endocrine & metabolic: Increased serum glucose (>250 mg/dL: 3%), increased uric acid (>12 mg/dL: 3%)

Gastrointestinal: Diarrhea (8%), increased serum lipase (>3 x ULN: 5%), nausea (5%)

Hematologic & oncologic: Decreased neutrophils (<0.6 x 10⁹ cells/L: 5%), leukopenia (<1.5 x 10⁹ cells/L: 5%), decreased hemoglobin (<8.5 g/dL: 3%), decreased platelet count (<50,000/mm³: 3%)

Hepatic: Increased serum bilirubin (≥2.6 x ULN: 5%), increased direct serum bilirubin (> ULN: 3%)

Renal: Increased serum creatinine (>1.8 x ULN or 1.5 x baseline: 10%)

<1%, postmarketing, and/or case reports: Antibody development, immune reconstitution syndrome

Warnings/Precautions

Concerns related to adverse effects:

• Immune reconstitution inflammatory syndrome: Patients may develop immune reconstitution inflammatory syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment; further evaluation and treatment may be required.
• Infusion-associated reactions: May occur; observe patients for 1 hour after completion of infusion for at least the first infusion. If no infusion-associated reactions are observed after the first infusion, may reduce post-infusion observation time to 15 minutes for subsequent infusions.

Disease-related concerns:

• Appropriate use: Use is not recommended in antiretroviral therapy-naïve patients.

Dosage form specific issues:

• Polysorbate 80: Contains polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Monitoring Parameters

CD4 count, HIV RNA plasma levels, infusion-related reactions

Pregnancy

Pregnancy Considerations

Monoclonal antibodies are known to cross the placenta and fetal exposure to ibalizumab may be expected.

The Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend ibalizumab for pregnant females living with HIV who are antiretroviral naive, who have had antiretroviral therapy (ART) therapy in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), who are not yet pregnant but are trying to conceive, or who become pregnant while taking ibalizumab. Available pharmacokinetic data are insufficient to make dosing recommendations.

In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.

Health care providers are encouraged to enroll pregnant females exposed to ibalizumab as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2019).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea, dizziness, nausea, or rash. Have patient report immediately to prescriber signs of infection (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.