Autologous chondrocytes

Locally applied antibiotics or disinfectants may have potential toxicity on articular cartilage and it is not recommended that autologous chondrocytes suspension comes into direct contact with those substances.

Autologous chondrocyte implantation in obese patients is not recommended.

No clinical data on exposed pregnancies are available for autologous chondrocytes or spheroids from autologous chondrocytes.

As autologous chondrocyte implantation is used to repair cartilage defects of the joint and is therefore implanted during a surgical procedure, it is not recommended for use in pregnant women.

As autologous chondrocyte implantation is used to repair cartilage defects of the joint and is therefore implanted during a surgical procedure, it is not recommended for use in breast-feeding women.

Fertility

There are no data on possible effects of autologous chondrocytes treatment on fertility.

The surgical procedure of autologous chondrocyte implantation will have a major influence on the ability to drive and use machines. Also, during the rehabilitation period, the ability to drive and use machines may be restricted due to reduced mobility. Therefore, patients should consult their treating physician and follow his/her advice strictly.

Summary of safety profile

Information on adverse reactions from clinical trials and a non-interventional study in adolescents as well as from post-marketing experience are available. During treatment with spheroids of human autologous matrix-associated chondrocytes for implantation, surgery-related (implantation) or autologous chondrocyte-related adverse reactions may occur.

Paediatric population

In general, the adverse reactions in paediatric patients were similar in frequency and type to those seen in adult patients.

Tabulated list of adverse reactions

The adverse reactions related to autologous chondrocytes are displayed by system organ class and frequency in the table below: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Undesirable Effects related to autologous chondrocytes:

Description of selected adverse reactions

Graft delamination

Graft delamination describes the partial or complete detachment of the formed tissue from the subchondral bone and the surrounding cartilage. A complete graft delamination is a serious complication which can be accompanied by pain. Risk factors are in particular non-treatment of concomitant diseases, such as joint instability or to renege on the rehabilitation protocol.

Hypertrophy

A symptomatic implant site hypertrophy may occur during treatment with autologous chondrocytes resulting in pain.

Adverse reactions related to the surgical procedure

The following adverse reactions considered surgery-related have been reported during the course of the clinical trials and/or from spontaneous sources:

• SOC Infections and infestations: pneumonia (not known)
• SOC Vascular disorders: lymphoedema (uncommon), thrombophlebitis(rare), deep vein thrombosis (uncommon), haematoma (rare)
• SOC Respiratory, thoracic and mediastinal disorders: pulmonary embolism (uncommon)
• SOC Skin and subcutaneous tissue disorders: scar pain (uncommon)
• SOC Musculoskeletal and connective tissue disorders: joint effusion (common), arthralgia (common), joint swelling (common), tendonitis (uncommon), muscular weakness (uncommon), patellofemoral pain syndrome (uncommon), osteonecrosis(rare), synovitis (uncommon), loose body in the joint (uncommon)
• SOC General disorders and administration site conditions: pain (common), gait disturbance (uncommon), discomfort (very rare)
• SOC Injury, poisoning and procedural complications: ligament sprain (uncommon), suture-related complication (rare), wound dehiscence (rare)