Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: CO.DON AG, Warthestraße 21, 14513 Teltow, Germany
Spherox is an autologous medicinal product and must not be given to any other patient than the donor.
Prior to use, it must be verified if patient name matches the information of the patient/donor provided on the shipping documents and the product label. Also it needs to be checked if the correct order number (lot number) is on the primary package. If the primary or secondary packaging is damaged and therefore unsterile, Spherox must not be applied.
The application of Spherox in patients with cartilage defects outside the knee joint is not recommended. The safety and efficacy of Spherox in patients with cartilage defects outside the femoral condyle and the patella of the knee have not been established. No data are available.
Patients with local inflammations or acute as well as recent bone or joint infections should be temporarily deferred until the recovery from the infection is documented.
In the pivotal studies of Spherox, patients were excluded if they had signs of chronic inflammatory diseases.
Concomitant joint problems like early osteoarthritis, subchondral bone defects, instability of the joint, lesions of ligaments or of the meniscus, abnormal weight distribution in the joint, varus or valgus malalignment, patellar malalignment or instability, and metabolic, inflammatory, immunological or neoplastic diseases of the affected joint are potential complicating factors. Untreated bone oedema corresponding with the cartilage defect to be treated may adversely affect the success of the procedure. If possible, concomitant joint problems should be corrected prior to or at the latest at the time of Spherox implantation.
For decision on treatment of facing defects (“kissing lesions” larger than ICRS grade II) the degree of overlap and location of the defects in the joint have to be taken into consideration. Post-operative haemarthrosis occurs mainly in patients with a predisposition to haemorrhage or poor surgical haemorrhage control. The patient’s haemostatic functions should be screened prior to surgery. Thromboprophylaxis should be administered according to local guidelines.
Application of Spherox in obese patients is not recommended.
After implantation, the patient should follow an appropriate rehabilitation schedule. Physical activity should be resumed as recommended by the physician. Too early and vigorous activity may compromise the grafting and the durability of clinical benefit from Spherox.
Compliance with an adequate rehabilitation programme after implantation (especially for patients with mental disorders or addiction) should be warranted.
If the manufacturing of spheroids has failed or if the release criteria are not fulfilled, e.g. due to insufficient biopsy quality, the medicinal product cannot be delivered. The physician will be informed immediately.
No interaction studies have been performed.
Locally applied antibiotics or disinfectants may have potential toxicity on articular cartilage and it is not recommended that Spherox comes into direct contact with those substances.
In the pivotal studies of Spherox, patients were excluded if they were under medical treatment with corticosteroids.
No clinical data on exposed pregnancies are available for autologous chondrocytes or spheroids from autologous chondrocytes.
As Spherox 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 or breast-feeding women.
There are no data on possible effects of Spherox treatment on fertility.
The surgical procedure 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.
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 Spherox surgery-related (implantation) or Spherox-related adverse reactions may occur.
In general, the adverse reactions in paediatric patients were similar in frequency and type to those seen in adult patients.
The adverse reactions related to Spherox are displayed by system organ class and frequency in Table 1 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.
Table 1. Undesirable Effects related to Spherox:
| System Organ Class (SOC) | Frequency | Adverse Reaction |
|---|---|---|
| Infections and infestations | Rare | Cellulitis, Osteomyelitis |
| Immune system disorders | Rare | Hypersensitivity |
| Musculoskeletal and connective tissue disorders | Common | Bone marrow oedema, Joint effusion, Arthralgia, Joint swelling |
| Uncommon | Chondromalacia, Joint noise, Joint lock, Synovial cyst, Chondropathy, Synovitis, Loose body in the joint | |
| Rare | Osteochondrosis, Osteonecrosis, Osteophyte formation, Arthritis infective | |
| Not known | Arthrofibrosis | |
| General disorders and administration site conditions | Common | Pain |
| Uncommon | Gait disturbance | |
| Injury, poisoning and procedural complications | Uncommon | Hypertrophy, Graft loss |
| Rare | Graft delamination, Implant site infection, Infrapatellar fat pad inflammation |
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.
A symptomatic implant site hypertrophy may occur during treatment with Spherox resulting in pain.
The following adverse reactions considered surgery-related have been reported during the course of the clinical trials and/or from spontaneous sources:
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In absence of compatibility studies, this medicinal product should not be mixed with other medicinal products.
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