TALTZ^® (Solution) Instructions for Use

Marketing Authorization Holder

Swix Healthcare LLC (Russia)

Manufactured By

Eli Lilly and Company (USA)

Packaging and Quality Control Release

ELI LILLY and Company (USA)

Or

PHARMSTANDARD-UfaVITA, JSC (Russia)

ATC Code

L04AC13 (Ixekizumab)

Active Substance

Ixekizumab (Rec.INN registered by WHO)

Dosage Form

TALTZ®

Solution for subcutaneous injection 80 mg/ml: syringes 1, 2, or 3 pcs.

Dosage Form, Packaging, and Composition

Solution for subcutaneous injection from clear to opalescent, from colorless to slightly yellow, to slightly brown.

Excipients: sodium citrate dihydrate – 5.11 mg, anhydrous citric acid – 0.51 mg, sodium chloride – 11.69 mg, polysorbate 80 – 0.3 mg, water for injection – q.s. to 1 ml.

1 ml – autoinjectors* (1) – cardboard packs.
1 ml – autoinjectors* (2) – cardboard packs.
1 ml – autoinjectors* (3) – cardboard packs.

* 1 ml of the drug in a colorless glass syringe type I with a 27G injection needle with a protective cap; the syringe is built into the autoinjector.

Clinical-Pharmacological Group

Immunosuppressive drug – monoclonal antibodies

Pharmacotherapeutic Group

Immunosuppressants, interleukin inhibitors

Pharmacological Action

Agent for the treatment of psoriasis. It is a humanized monoclonal antibody to the cytokine interleukin 17A (IL-17A and IL-17A/F) from the immunoglobulin G4 (IgG4) subclass.

An increase in the concentration of IL-17A stimulates the proliferation and activation of keratinocytes and thus plays a key role in the pathogenesis of psoriasis and psoriatic arthritis. Ixekizumab selectively binds to IL-17A and suppresses its action by neutralizing activity, as a result of which no interaction occurs between IL-17A and its receptor. Ixekizumab does not bind to IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F ligands.

In vitro studies have proven that Ixekizumab does not bind to human Fcγ receptors I, IIa, and IIIa or the C1q complement component.

Ixekizumab modulates biological responses that are induced or regulated via IL-17A. Ixekizumab therapy reduces redness, thickening, and scaling of the skin in areas affected by plaque psoriasis.

Within the first week of using ixekizumab, a decrease in the level of C-reactive protein, which is a marker of inflammation, is noted.

Antibodies to ixekizumab were detected in 9-17% of patients with plaque psoriasis receiving ixekizumab therapy according to the recommended dosage regimen. The titer of most antibodies was low, and no decrease in clinical activity was observed with therapy duration up to 60 weeks. At the same time, 1% of patients were found to have neutralizing antibodies to ixekizumab, which was associated with lower ixekizumab concentration and reduced clinical response.

Antibodies to ixekizumab were detected in 11% of patients with psoriatic arthritis receiving ixekizumab therapy according to the recommended dosage regimen with therapy duration up to 52 weeks. The titer of most antibodies was low, while 8% of patients were found to have neutralizing antibodies to ixekizumab. No obvious relationship was found between the presence of neutralizing antibodies and the effect on ixekizumab concentration or efficacy.

No obvious relationship was found between immunogenicity and the occurrence of adverse events.

Pharmacokinetics

After a single subcutaneous administration of ixekizumab to patients with psoriasis in the dose range from 5 to 160 mg, the mean C_max was reached between days 4 and 7 after the start of therapy. The mean C_max of ixekizumab in blood plasma after administration of the initial dose of 160 mg was 19.9 µg/ml. After administration of the initial dose of 160 mg, steady state was reached by week 8 with a regimen of 80 mg once every 2 weeks. The mean values of C_max at steady state (C_{max, ss}) and minimum concentration at steady state (C_{through, ss}) were 21.5 µg/ml and 5.23 µg/ml, respectively.

After switching from the ixekizumab administration regimen of 80 mg once every 2 weeks for 12 weeks to a regimen of 80 mg once every 4 weeks, steady state was reached in approximately 10 weeks. The mean values of C_{max, ss} and C_{through, ss} were 14.6 µg/ml and 1.87 µg/ml, respectively.

The bioavailability of ixekizumab with subcutaneous administration averaged from 54 to 90%.

According to population pharmacokinetic analysis, the mean total V_d at steady state was 7.11 L.

Since Ixekizumab is a monoclonal antibody, it is assumed that, like endogenous immunoglobulins, it will be broken down into small peptides and amino acids via a catabolic pathway.

According to population pharmacokinetic analysis, the mean serum clearance was 0.0161 L/h. Clearance is dose-independent. In patients with plaque psoriasis, the mean T_1/2, calculated using population pharmacokinetic analysis, is 13 days.

AUC with subcutaneous administration increased proportionally to the dose in the range from 5 to 160 mg.

The pharmacokinetic parameters of ixekizumab in patients with psoriatic arthritis and plaque psoriasis were similar. According to population pharmacokinetic analysis, the bioavailability of ixekizumab in patients with psoriatic arthritis ranged from 61-84%.

Indications

Treatment of moderate to severe plaque psoriasis when systemic therapy is required; treatment of active psoriatic arthritis – as monotherapy or in combination with methotrexate in case of insufficient response to previous therapy with one or more disease-modifying antirheumatic drugs (DMARDs) or its intolerance.

ICD codes

Dosage Regimen

Administer TALTZ^® by subcutaneous injection only.

For moderate to severe plaque psoriasis, the recommended dose is 160 mg (two 80 mg injections) at Week 0. Follow with 80 mg at Weeks 2, 4, 6, 8, 10, and 12. For maintenance, administer 80 mg every 4 weeks.

For active psoriatic arthritis, the recommended dose is 160 mg (two 80 mg injections) at Week 0. Follow with 80 mg every 4 weeks. For concomitant moderate to severe plaque psoriasis, administer an additional 80 mg dose at Week 12.

Rotate injection sites with each dose. Do not inject into areas of psoriasis or skin that is tender, bruised, red, hard, thick, scaly, or scarred.

Inspect the solution visually before use. The solution should appear clear to opalescent and colorless to slightly yellow or brown. Do not use if the liquid is cloudy, discolored, or contains visible particles.

Allow the pre-filled syringe or autoinjector to reach room temperature (approximately 30 minutes) before injection. Do not warm in any other way.

If a dose is missed, administer the injection as soon as possible. Then, resume the regular scheduled dosing regimen.

No dose adjustment is required for elderly patients (65 years and older) or for patients with renal or hepatic impairment.

Adverse Reactions

Infections very common: upper respiratory tract infections (including nasopharyngitis); common – infections caused by Herpes Simplex virus types 1 and 2; uncommon – influenza-like reactions (more common in patients with psoriatic arthritis), rhinitis, oral candidiasis (or oral fungal infection), conjunctivitis (more common in patients with psoriatic arthritis), cellulitis.

From the hematopoietic system: uncommon – neutropenia, thrombocytopenia.

From the immune system: uncommon – angioedema; rare – anaphylactic shock.

From the respiratory system: common – oropharyngeal pain.

From the digestive system: common – nausea.

From the skin and subcutaneous tissues: uncommon – urticaria, rash, eczema.

Local reactions very common – erythema, pain at the injection site.

Contraindications

Hypersensitivity to the components of the agent; pregnancy, breastfeeding period; serious infectious diseases in the acute phase, including tuberculosis; children under 18 years of age.

With caution chronic and recurrent infectious diseases of viral, fungal or bacterial nature, history of malignant tumors, patients with inflammatory bowel disease.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Women of childbearing potential must use effective methods of contraception during therapy with ixekizumab and for at least 10 weeks after its last dose.

Pediatric Use

Contraindicated for use in children under 18 years of age.

Geriatric Use

Dose adjustment in patients aged 65 years and older is not required.

Special Precautions

Ixekizumab should be prescribed with caution to patients with clinically significant, chronic infections. If signs of infection appear, careful monitoring of the patient’s condition is necessary. In case of no response to standard therapy or in case of complication of the course of infection, it is necessary to stop treatment with ixekizumab until the infection is eliminated.

Patients with latent tuberculosis are recommended to undergo a standard course of anti-tuberculosis therapy before starting treatment with ixekizumab. During therapy, as well as after it, careful monitoring for signs of active tuberculosis is necessary.

Cases of serious hypersensitivity reactions have been reported, including anaphylactic shock, angioedema, urticaria, and, rarely, delayed, developing on days 10-14 after injection, serious hypersensitivity reactions (including extensive urticaria, dyspnea, high antibody titers). If serious hypersensitivity reactions occur, treatment with ixekizumab should be immediately discontinued and appropriate therapy initiated.

Cases of development or exacerbation of Crohn’s disease and ulcerative colitis have been reported. Caution should be exercised when prescribing ixekizumab to patients with inflammatory bowel disease, and careful monitoring of the condition of such patients is necessary.

Immunization with live and inactivated vaccines should not be carried out simultaneously with ixekizumab therapy. There are no data on the adequacy of the immune response to live and inactivated vaccines in patients receiving Ixekizumab.

Drug Interactions

A clinically significant effect on drugs with a narrow therapeutic index, which are substrates of cytochrome system enzymes, and the dose of which is selected individually (for example, warfarin), cannot be excluded. The possibility of clinical monitoring should be considered when initiating ixekizumab therapy in patients receiving treatment with drugs of the above groups.

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.