Phesgo^® (Solution) Instructions for Use

Marketing Authorization Holder

F. Hoffmann-La Roche, Ltd (Switzerland)

ATC Code

L01FY01 (Pertuzumab and Trastuzumab)

Active Substances

Trastuzumab (Rec.INN registered by WHO)

Pertuzumab (Rec.INN registered by WHO)

Dosage Forms

	Phesgo®	Solution for subcutaneous administration 600 mg+600 mg/10 ml: vial 1 pc.
		Solution for subcutaneous administration 1200 mg+600 mg/15 ml: vial 1 pc.

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration as a clear or opalescent colorless to slightly brownish liquid.

Excipients: recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine hydrochloride monohydrate, α,α-trehalose dihydrate, sucrose, polysorbate 20, L-methionine, water for injection.

10 ml – vials (1) – cardboard packs.

A protective holographic sticker is applied to the packaging to control the first opening.

Solution for subcutaneous administration as a clear or opalescent colorless to slightly brownish liquid.

Excipients: recombinant human hyaluronidase (rHuPH20), L-histidine, L-histidine hydrochloride monohydrate, α,α-trehalose dihydrate, sucrose, polysorbate 20, L-methionine, water for injection.

15 ml – colorless glass vials (1) – cardboard packs.

A protective holographic sticker is applied to the packaging to control the first opening.

Clinical-Pharmacological Group

Antitumor drug. Monoclonal antibodies

Pharmacotherapeutic Group

Antineoplastic agents; other antineoplastic agents; combinations of antineoplastic agents

Pharmacological Action

Pertuzumab and Trastuzumab are recombinant humanized monoclonal antibodies IgG1κ (immunoglobulin G, subclass 1, light chain κ), which interact with the human epidermal growth factor receptor type 2 (HER2, also known as c-erbB-2), a transmembrane glycoprotein with intrinsic tyrosine kinase activity.

Pertuzumab and Trastuzumab, without competing with each other, bind to specific HER2 epitopes, subdomains II and IV, and have complementary mechanisms for disrupting HER2 signaling. The use of pertuzumab and trastuzumab in combination leads to enhanced antiproliferative activity in vitro and in vivo.

Furthermore, part of the crystallizing fragment (Fc) of the IgG1 scaffolds of pertuzumab and trastuzumab contributes to potent activation of antibody-dependent cellular cytotoxicity (ADCC). In vitro ADCC of pertuzumab and trastuzumab is more directed towards tumor cells with HER2 overexpression than towards tumor cells without HER2 overexpression.

Pharmacokinetics

Pharmacokinetic analysis using the described population pharmacokinetic model showed no effect of pertuzumab as part of the combination on the pharmacokinetics of trastuzumab as part of the combination, since the pharmacokinetics of trastuzumab as part of the combination and the pharmacokinetics of subcutaneous trastuzumab were similar.

The mean C_max in blood serum and the time to reach maximum concentration (T_max) for pertuzumab as part of the Phesgo^® preparation were 157 µg/ml and 3.82 days, respectively. Based on population pharmacokinetic analysis, the absolute bioavailability was 0.712, and the first-order absorption rate (Ka) was 0.348 1/day.

The mean C_max in blood serum and T_max for trastuzumab as part of this combination were 114 µg/ml and 3.84 days, respectively. Based on population pharmacokinetic analysis, the absolute bioavailability was 0.771, and Ka was 0.404 1/day.

According to population pharmacokinetic analysis data, the volume of distribution of pertuzumab as part of this combination in the central compartment (Vc) is 2.77 L in an average patient. According to population pharmacokinetic analysis data, the Vc of subcutaneous trastuzumab is 2.91 L in an average patient.

The metabolism of this combination has not been specifically studied. Antibodies are eliminated primarily by catabolism.

Based on population pharmacokinetic analysis, the clearance of pertuzumab as part of this combination was 0.163 L/day, T_1/2 – approximately 24.3 days.

Based on population pharmacokinetic analysis, the linear clearance of subcutaneous trastuzumab was 0.111 L/day.

It has been established that Trastuzumab reaches concentrations <1 µg/ml 7 months after the last dose administration in ≥95% of patients. This constitutes about 3% of the population-calculated minimum steady-state concentration (Cmin,ss) or corresponds to the elimination of ~97% of this combination.

Indications

Early HER2-positive breast cancer – in combination with chemotherapy.

Metastatic HER2-positive breast cancer.

ICD codes

Dosage Regimen

For subcutaneous administration.

Administration should be performed by healthcare professionals proficient in managing patients with anaphylaxis in settings where immediate initiation of a full range of resuscitation measures is possible.

Used according to a specific regimen.

The loading dose is 1200 mg of pertuzumab/600 mg of trastuzumab, the maintenance dose is 600 mg of pertuzumab/600 mg of trastuzumab.

Adverse Reactions

Infections and infestations very common – nasopharyngitis; common – paronychia, upper respiratory tract infections.

Blood and lymphatic system disorders very common – febrile neutropenia, neutropenia, leukopenia, anemia.

Immune system disorders very common – infusion reactions; common – hypersensitivity reactions, drug hypersensitivity; uncommon – anaphylactic reactions; rare – cytokine release syndrome.

Metabolism and nutrition disorders very common – decreased appetite; rare – tumor lysis syndrome.

Psychiatric disorders very common – insomnia.

Nervous system disorders very common – peripheral neuropathy, headache, dysgeusia, peripheral sensory neuropathy, dizziness, paresthesia.

Eye disorders very common – lacrimation increased.

Cardiac disorders common – left ventricular dysfunction; uncommon – congestive heart failure; rare – flushing.

Respiratory, thoracic and mediastinal disorders very common – cough, epistaxis, dyspnea; uncommon – interstitial lung disease, pleural effusion.

Gastrointestinal disorders very common – intestinal disorders, diarrhea, vomiting, stomatitis, nausea, constipation, dyspepsia, abdominal pain.

Skin and subcutaneous tissue disorders very common – alopecia, rash, nail pathology, pruritus, dry skin.

Musculoskeletal and connective tissue disorders very common – myalgia, arthralgia, pain in extremity.

General disorders and administration site conditions very common – mucosal inflammation, peripheral edema, pyrexia, increased fatigue, asthenia, injection site reactions; common – chills, pain, edema.

Contraindications

Hypersensitivity to pertuzumab, trastuzumab; pregnancy, breastfeeding period, children and adolescents under 18 years of age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Women of childbearing potential, as well as women who are sexual partners of patients receiving this drug, should use effective methods of contraception during the use of this combination and for 7 months after the last dose administration.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Drug Interactions

Results from the study of the pharmacokinetics of capecitabine and cisplatin when used in combination with trastuzumab or without it suggest that the exposure of biologically active metabolites of capecitabine (e.g., fluorouracil) did not change with the simultaneous use of cisplatin or cisplatin and trastuzumab. However, higher concentrations of capecitabine and a longer T_1/2 were recorded when combined with trastuzumab. The data also indicate that the pharmacokinetics of cisplatin did not change with the simultaneous use of capecitabine or capecitabine in combination with trastuzumab.

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.