4.1. Therapeutic indications

For contrast enhancement in direct magnetic resonance arthrography.

This medicinal product is for diagnostic use by intraarticular administration only.

Magnevist 2 mmol/l should be used only when diagnostic information is essential and not available with unenhanced magnetic resonance imaging (MRI) and when another authorised product cannot be used.

4.2. Posology and method of administration

The usual precautions for MRI (e.g. exclusion of cardiac pacemakers and other ferro-magnetic objects including vascular clips etc) must be observed.

Posology

The recommendations for the use of Magnevist 2 mmol/l apply to a field strength between 0.2 Tesla and 1.5 Tesla.

Intraarticular administrations of contrast agents are to be given with the patient lying or sitting. After the end of the injection, the patient should be kept under supervision for at least half an hour.

The lowest dose that provides sufficient enhancement for diagnostic purposes should be used.

Adults:

In general, for all joints the administration of up to 20 ml (knee joint up to 50 ml) Magnevist 2 mmol/l is sufficient for good opacification and to answer all the relevant clinical questions. A volume leading to a slight distension of the joint capsule should be injected. Only so much contrast medium should be injected until discrete resistance is felt and/or the patient experiences a mild feeling of pressure.

Guidelines on volumes to be administered:

Joint

Volume required

Shoulder

15-20 ml

Elbow

~ 10 ml

Wrist

4 ml

Finger joint

1-2 ml

Hip

10-20 ml

Knee

25-50 ml

Ankle

12-20 ml

Paediatric population:

The safety and efficacy of Magnevist 2 mmol/l in children aged up to 18 years has not yet been established. No data are available. Magnevist 2 mmol/l is not recommended in the paediatric age group until further data become available.

Method of administration

The dose required is administered via intraarticular injection under strict aseptic technique and according to the instructions provided in section 6.6. Contrast-enhanced MRI can be commenced immediately afterwards.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Gadopentetic acid must not be used intrathecally. Serious, life-threatening and fatal cases, primarily with neurological reactions (e.g. coma, encephalopathy, seizures), have been reported with intrathecal use.

Strict aseptic technique is required to prevent infection.

Fluoroscopic control should be used to ensure proper needle placement and prevent extracapsular injection. Undue pressure should not be exerted during injection.

Intraarticular injections of Magnevist 2 mmol/l should be avoided in infected joints.

• Hypersensitivity

Severe systemic hypersensitivity reactions cannot be totally excluded (see section 4.8).

Mild angioedema, conjunctivitis, coughing, pruritus, rhinitis, sneezing and urticaria, which can occur irrespective of the amount administered and the mode of administration, may be the first signs of incipient state of shock.

As with other contrast agents, delayed reactions may occur (hours later or up to several days).

As with other contrast enhanced diagnostic procedures, post-procedure observation of the patient is recommended.

Medication for the treatment of hypersensitivity reactions as well as readiness for institution of emergency measures are necessary. Appropriate drugs and instruments (e.g. endotracheal tube and ventilator) must be readily available.

The risk of hypersensitivity reactions is higher in case of:

- previous reaction to contrast media,

- history of bronchial asthma,

- history of allergic disorders

The decision to use Magnevist 2 mmol/l must be made after particularly careful evaluation of the risk-benefit-ratio in patients with an allergic disposition.

After intravenous administration of gadopentetic acid, dimeglumine salt, gadolinium can be retained in the brain and in other tissues of the body (bones, liver, kidneys, skin) and can cause dose-dependent increases in T1-weighted signal intensity in the brain, particularly in the dentate nucleus, globus pallidus, and thalamus. Clinical consequences are unknown. Retention of gadolinium in the brain has not been identified for intra-articular administration. The possible diagnostic advantages of using gadopentetic acid, dimeglumine salt in patients who will require repeated scans should be weighed against the potential for deposition of gadolinium in the brain and other tissues.

• Magnevist 2 mmol/l contains sodium

This medicinal product contains 67.6 mg sodium per pre-filled syringe, equivalent to 3.38 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5. Interaction with other medicinal products and other forms of interaction

As for all other gadolinium containing contrast media, no interactions with other medicaments have been observed. Formal drug interaction studies have not been carried out. See also section 6.2.

Magnevist should be administered without the addition of iodinated contrast media as iodinated contrast media reduce the level of contrast achievable with Magnevist (see section 6.6).

4.6. Fertility, pregnancy and lactation

• Pregnancy

Data on the use of gadolinium-based contrast agents including gadopentetic acid in pregnant women is limited. Gadolinium can cross the placenta. It is unknown whether exposure to gadolinium is associated with adverse effects in the foetus. Animal studies do not indicate direct or indirect harmful effects with respect to embryonal / foetal development (see section 5.3).

Caution should be exercised using Magnevist 2 mmol/l in pregnant women.

• Breast-feeding

No data exist concerning intra-articular administration in lactating women. After intravascular use minimal amounts of gadopentetic acid, dimeglumine salt (a maximum of 0.04%) of the intravenously administered dose enters the breast milk. From experience gained so far, harm to the breast-fed infant is considered unlikely.

4.7. Effects on ability to drive and use machines

No effects of Magnevist 2 mmol/l on driving ability and use of machinery can be expected. However, joint effusion may affect the ability to drive due to a limited joint mobility.

4.8. Undesirable effects

Frequency of adverse reactions from clinical trial data

Based on experience in more than 4,900 patients, the undesirable effects listed below have been observed and classified by investigators as drug-related.

Adverse reactions with the use of Magnevist 2 mmol/l are usually of mild to moderate intensity.

The most frequently reported reactions were local injection site reactions, i.e. injection site pain and joint pressure sensations which are mainly related to the procedure itself.

The table below reports adverse reactions by MedDRA system organ classes (MedDRA SOCs).

System Organ Class

Common

(≥1/100 to <1/10)

Uncommon

(≥1/1,000 to <1/100)

Rare

(≥1/10,000 to <1/1,000)

Nervous system disorders

Headache

Dizziness

Vascular disorders

Vasovagal reaction

Gastrointestinal disorders

Nausea

Vomiting

General disorders and administration site conditions

Injection site pain/ Injection site (joint) pressure sensation

The most appropriate MedDRA term is used to describe a reaction and its synonyms and related conditions.

• Immune system disorders/Hypersensitivity/Allergic reaction

Systemic hypersensitivity may occur rarely in the form of skin reactions. The possibility of a severe hypersensitivity reaction cannot be totally excluded (see section 4.4).

• General disorders and administration site conditions

Injection of Magnevist 2 mmol/l into the joint is commonly associated with transient discomfort, e.g. pressure and pain due to the injected volume. Severe pain may often result from undue use of pressure or the injection of large volumes.

Other adverse reactions commonly known from intravenous injection of gadolinium chelates were so far not observed with Magnevist 2 mmol/l, due to the low dose and the topical administration.

Reporting of suspected adverse reactions

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

No signs of intoxication secondary to an overdose have so far been observed or reported on clinical use.