Imjudo (Concentrate) Instructions for Use

Marketing Authorization Holder

AstraZeneca AB (Sweden)

Manufactured By

Vetter Pharma-Fertigung, GmbH & Co. KG (Germany)

Packaging and Quality Control Release

ASTRAZENECA AB (Sweden)

ATC Code

L01FX20 (Tremelimumab)

Active Substance

Tremelimumab (Rec.INN registered by WHO)

Dosage Form

Imjudo

Concentrate for solution for infusion 20 mg/1 ml: vial 1.25 ml or 15 ml

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion

1.25 ml – vials – cardboard packs – Prescription only
15 ml – vials – cardboard packs – Prescription only

Clinical-Pharmacological Group

Antitumor drug. Monoclonal antibodies

Pharmacotherapeutic Group

Antineoplastic agents; monoclonal antibodies and their drug conjugates; other monoclonal antibodies and their drug conjugates

Pharmacological Action

Antitumor agent. A selective, fully human IgG2 antibody that blocks the interaction of CTLA-4 with CD80 and CD86, thereby enhancing T-cell activation and proliferation, leading to increased T-cell diversity and enhanced antitumor activity of the immune system.

The combination of durvalumab, a PD-L1 inhibitor, and tremelimumab enhances the activation and function of antitumor T-cells at multiple stages of the immune response, increasing antitumor immunity.

Pharmacokinetics

The pharmacokinetics of tremelimumab were evaluated when used as monotherapy, in combination with durvalumab, and in combination with durvalumab and platinum-based chemotherapy.

The pharmacokinetics of tremelimumab were studied in patients at doses ranging from 75 mg to 750 mg or 10 mg/kg, administered intravenously every 4 or 12 weeks as monotherapy, or as a single 300 mg dose. Exposure increased proportionally with dose (linear pharmacokinetics) at doses ≥75 mg. Steady state was reached approximately after 12 weeks.

Based on a population pharmacokinetic analysis that included patients receiving Tremelimumab as monotherapy or in combination with other drugs in the dose range ≥75 mg (or 1 mg/kg) every 3 or 4 weeks, the estimated clearance and V_d of tremelimumab were 0.309 L/day and 6.33 L, respectively. The terminal T_1/2 was approximately 14.2 days.

Indications

Unresectable hepatocellular carcinoma (uHCC) – in combination with durvalumab.

Metastatic non-small cell lung cancer (in the absence of activating mutations in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene fusion) – in combination with durvalumab and platinum-based chemotherapy.

ICD codes

Dosage Regimen

Administer as an intravenous infusion over 60 minutes through a sterile, non-pyrogenic, low-protein binding in-line filter (pore size 0.2-0.22 micrometer).

Do not administer as an intravenous push or bolus. Do not mix with other medicinal products.

For unresectable hepatocellular carcinoma (uHCC), use in combination with durvalumab. Administer tremelimumab 300 mg as a single one-time dose concurrently with durvalumab 1500 mg on the same day, followed by durvalumab 1500 mg every 4 weeks.

For metastatic non-small cell lung cancer (NSCLC), use in combination with durvalumab and platinum-based chemotherapy. Administer tremelimumab 75 mg concurrently with durvalumab 1500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by durvalumab 1500 mg every 4 weeks.

Withhold or permanently discontinue tremelimumab and durvalumab based on the severity of the adverse reaction. Refer to the durvalumab prescribing information for recommended dosage modifications.

Premedicate with antipyretics and/or antihistamines for prior infusion-related reactions. Monitor patients for signs and symptoms of an infusion-related reaction during and after the infusion.

For preparation, withdraw the required volume from the vial(s) and transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to prepare a final concentration between 1 mg/mL and 15 mg/mL.

Mix diluted solution by gentle inversion. Do not shake. The solution should be clear to opalescent, colorless to slightly yellow; discard if visible particles are present.

Administer the prepared infusion solution immediately at room temperature for no more than 24 hours from the time of preparation, or refrigerate at 2°C to 8°C for no more than 24 hours, followed by room temperature for no more than 4 hours (including infusion time). Do not freeze.

Dose modifications for tremelimumab are not recommended for patients with mild or moderate hepatic impairment or for patients with mild or moderate renal impairment. The safety in patients with severe hepatic or severe renal impairment has not been established.

Adverse Reactions

Adverse reactions for the combination of tremelimumab with durvalumab

Very common: diarrhea, hypothyroidism, abdominal pain, peripheral edema, fever, increased ALT, increased AST, cough.

Common: pneumonia, colitis, hepatitis, upper respiratory tract infections, influenza-like illness, dental and oral soft tissue infections, hyperthyroidism, thyroiditis, adrenal insufficiency, pneumonitis, increased lipase, increased amylase, pancreatitis, dermatitis, night sweats, myalgia, increased blood creatinine, dysuria, infusion reaction (fever, or redness).

Uncommon: oral fungal infection, pituitary hypofunction, pituitary inflammation, myasthenia gravis, meningitis, myocarditis, dysphonia, interstitial lung disease, pemphigoid, myositis, polymyositis, nephritis (which may cause decreased urine output), immune-mediated arthritis.

Unknown: immune thrombocytopenia, diabetes insipidus, type 1 diabetes mellitus, Guillain-Barré syndrome, encephalitis, intestinal perforation, cystitis, uveitis.

It is necessary to monitor for the appearance of clinical signs and symptoms of hypophysitis or hypopituitarism.

Renal function parameters should be monitored in patients before starting therapy with tremelimumab in combination with durvalumab and periodically during therapy.

It is necessary to monitor for the appearance of clinical signs and symptoms of rash and dermatitis.

It is necessary to monitor for the appearance of clinical signs and symptoms of immune-mediated myocarditis.

It is necessary to monitor for the appearance of clinical signs and symptoms of other immune-mediated reactions.

There are limited data on elderly patients (≥75 years) receiving Tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic NSCLC. The potential benefit/risk of this regimen should be carefully considered on an individual basis.

Contraindications

Hypersensitivity to tremelimumab, children and adolescents under 18 years of age, pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Tremelimumab should not be used during pregnancy and in women of childbearing potential not using effective contraception during treatment and for at least 3 months after the last dose of this drug.

Tremelimumab should not be used during breastfeeding and for at least 3 months after the last dose of this drug.

Use in Hepatic Impairment

According to population pharmacokinetic analysis, no dose adjustment is required for patients with mild or moderate hepatic impairment. Use in patients with severe hepatic impairment has not been studied.

Use in Renal Impairment

According to population pharmacokinetic analysis, no dose adjustment is required for patients with mild and moderate renal impairment. Use in patients with severe renal impairment has not been studied.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

For elderly patients (≥65 years), no dose adjustment is required.

Data on patients aged 75 years and older with metastatic NSCLC are limited.

Special Precautions

It is necessary to monitor for signs and symptoms of pneumonitis. If pneumonitis is suspected, a radiological examination should be performed to confirm the diagnosis and to exclude other causes, including infectious and those related to the underlying disease.

Liver function tests should be monitored in patients before starting therapy with tremelimumab in combination with durvalumab and before each subsequent infusion.

It is necessary to monitor for signs and symptoms of colitis, diarrhea, or intestinal perforation.

Thyroid function tests should be monitored in patients before starting therapy and periodically during therapy.

It is necessary to monitor for clinical signs and symptoms of adrenal insufficiency.

It is necessary to monitor for clinical signs and symptoms of type 1 diabetes mellitus.

Effect on ability to drive vehicles and operate machinery

If patients experience adverse reactions affecting their ability to concentrate and react, they are advised to exercise caution when driving vehicles or operating machinery.

Drug Interactions

The use of systemic corticosteroids or immunosuppressants prior to starting tremelimumab therapy, with the exception of systemic corticosteroids at physiological doses (≤10 mg prednisone per day or equivalent), is not recommended due to the potential impact on the pharmacodynamic activity and efficacy of tremelimumab. However, systemic corticosteroids or other immunosuppressants may be used after starting tremelimumab therapy to treat immune-mediated adverse reactions.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.