AMGEVITA pre-filled pen

Section 4.4 Warnings and Precautions

Dry natural rubber

The needle cover of the pre-filled syringe or pen is made from dry natural rubber (a derivative of latex), which may cause allergic reactions.

Section 6.5 Nature and contents of container

AMGEVITA 20 mg solution for injection in pre-filled syringe

0.4 mL solution in pre-filled syringe (type I glass) with a plunger stopper (bromobutyl rubber) and a stainless steel needle with a needle shield (thermoplastic elastomer). The needle cover of the pre-filled syringe is made from dry natural rubber (a derivative of latex) (see section 4.4).

Pack size of one pre-filled syringe.

AMGEVITA 40 mg solution for injection in pre-filled syringe

0.8 mL solution in pre-filled syringe (type I glass) with a plunger stopper (bromobutyl rubber) and a stainless steel needle with a needle shield (thermoplastic elastomer). The needle cover of the pre-filled syringe is made from dry natural rubber (a derivative of latex) (see section 4.4).

Pack sizes of one, two, four or multipack of six (3x2) pre-filled syringes.

Not all pack sizes may be marketed.

Section 10 Date of revision of the text

June 2019

Section 4.1 Therapeutic indications

Hidradenitis suppurativa (HS)

AMGEVITA is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adults and adolescents from 12 years of age with an inadequate response to conventional systemic HS therapy (see sections 5.1 and 5.2).

Paediatric uveitis

AMGEVITA is indicated for the treatment of paediatric chronic non-infectious anterior uveitis in patients from 2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in whom conventional therapy is inappropriate.

Section 4.2 Posology

“Special alert card” is now called the “Patient Reminder Card”

Adolescent hidradenitis suppurativa (from 12 years of age, weighing at least 30 kg)

There are no clinical trials with adalimumab in adolescent patients with HS. The posology of AMGEVITA in these patients has been determined from pharmacokinetic modelling and simulation (see section 5.2).

The recommended AMGEVITA dose is 80 mg at Week 0 followed by 40 mg every other week starting at Week 1 via subcutaneous injection.

In adolescent patients with inadequate response to AMGEVITA 40 mg every other week, an increase in dosage to 40 mg every week or 80 mg every other week may be considered.

Antibiotics may be continued during treatment with AMGEVITA if necessary. It is recommended that the patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment with AMGEVITA.

Continued therapy beyond 12 weeks should be carefully reconsidered in a patient with no improvement within this time period.

Should treatment be interrupted, AMGEVITA may be re-introduced as appropriate.

The benefit and risk of continued long-term treatment should be periodically evaluated (see adult data in section 5.1).

There is no relevant use of AMGEVITA in children aged less than 12 years in this indication.

Paediatric uveitis

The recommended dose of AMGEVITA for paediatric patients with uveitis from 2 years of age is based on body weight (table 5). AMGEVITA is administered via subcutaneous injection.

In paediatric uveitis, there is no experience in the treatment with AMGEVITA without concomitant treatment with methotrexate.

When AMGEVITA therapy is initiated, a loading dose of 40 mg for patients < 30 kg or 80 mg for patients ≥ 30 kg may be administered one week prior to the start of maintenance therapy. No clinical data are available on the use of a AMGEVITA loading dose in children < 6 years of age (see section 5.2).

There is no relevant use of AMGEVITA in children aged less than 2 years in this indication.

It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a yearly basis (see section 5.1).

Section 4.4 Warnings and Precautions

BCG provided as an example of a live vaccine:

Vaccinations

Patients on AMGEVITA may receive concurrent vaccinations, except for live vaccines.

Administration of live vaccines (e.g., BCG vaccine) to infants exposed to AMGEVITA in utero is not recommended for 5 months following the mother’s last AMGEVITA injection during pregnancy.

Section 4.6 Fertility, pregnancy and lactation

Women of child bearing potential

Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy and continue its use for at least five months after the last AMGEVITA treatment.

Pregnancy

A large number (approximately 2100) of prospectively collected pregnancies exposed to adalimumab resulting in live birth with known outcomes, including more than 1500 exposed during the first trimester, does not indicate an increase in the rate of malformation in the newborn.

In a prospective cohort registry, 257 women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab at least during the first trimester and 120 women with RA or CD not treated with adalimumab were enrolled. The primary endpoint was the birth prevalence of major birth defects. The rate of pregnancies ending with at least one live born infant with a major birth defect was 6/69

(8.7%) in the adalimumab-treated women with RA and 5/74 (6.8%) in the untreated women with RA (unadjusted OR 1.31, 95% CI 0.38-4.52) and 16/152 (10.5%) in the adalimumab-treated women with CD and 3/32 (9.4%) in the untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR (accounting for baseline differences) was 1.10 (95% CI 0.45-2.73) with RA and CD combined. There were no distinct differences between adalimumab-treated and untreated women for the secondary endpoints spontaneous abortions, minor birth defects, preterm delivery, birth size and serious or opportunistic infections and no stillbirths or malignancies were reported. The interpretation of data may be impacted due to methodological limitations of the study, including small sample size

and non-randomised design.

In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available (see section 5.3).

Due to its inhibition of TNFα, adalimumab administered during pregnancy could affect normal immune responses in the new born. AMGEVITA should only be used during pregnancy if clearly needed.

Adalimumab may cross the placenta into the serum of infants born to women treated with adalimumab during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months following the mother’s last adalimumab injection during pregnancy.

Breast-feeding

Limited information from the published literature indicates that adalimumab is excreted in breast milk at very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1% to 1% of the maternal serum level. Given orally, immunoglobulin G proteins undergo intestinal proteolysis and have poor bioavailability. No effects on the breastfed newborns/infants are anticipated.

Consequently, AMGEVITA can be used during breastfeeding.

Fertility

Preclinical data on fertility effects of adalimumab are not available.

4.8 Undesirable effects

Lichenoid skin reaction added as a rare adverse reaction

5.1 Pharmacodynamic properties

New subsections for adolescent HS and paediatric uveitis

5.2 Pharmacokinetic properties

New subsections for adolescent HS and paediatric uveitis

Section 10 Date of revision of the text

March 2019

Section 4.2 Posology

Rheumatoid arthirtis – addition of option for dosing every other week for patients who require an increase in dosage

Psoriasis - addition of option for dosing every other week for patients who require an increase in dosage

Hidradenitis suppurativa – addition of option for dosing every other week

Crohn’s disease - addition of option for dosing every other week for patients who require an increase in dosage

Ulcerative colitis - addition of option for dosing every other week for patients who require an increase in dosage

Polyarticular juvenile idiopathic arthritis from 2 years of age  – addition of weight-based fixed dosing

Enthesitis-related arthritis – addition of weight-based fixed dosing

Paediatric plaque psoriasis - addition of weight-based fixed dosing

Paediatric Crohn’s disease – addition of weight-based fixed dosing

Section 4.4 Warnings and Precautions

Addition of excipients information:

Excipients with known effects

This medicinal product contains less than 1 mmol of sodium (23 mg) per 0.8 ml dose, i.e. essentially

‘sodium-free’.

Section 5 Pharmacological Properties

Addition of  information on non-radiographic axial spondyloarthritis following final results from originator remission-withdrawal-retreatment study (M13-375).

Section 10 Date of revision of the text

October 2018