Dose Modification

Where dose modification is necessary for the treatment of cervical dystonia, uncontrolled open-label studies suggest that dose adjustment can be made in 250 Unit steps according to the individual patient's response, with re-treatment every 12 weeks or longer, as necessary, based on return of clinical symptoms. Uncontrolled, open-label studies also suggest that the total dose administered in a single treatment should be between 250 Units and 1000 Units. Re-treatment, if needed, should not occur in intervals of less than 12 weeks. Doses above 1000 Units have not been systematically evaluated.

Injection Technique

Glabellar facial lines arise from the activity of the lateral corrugator and vertical procerus muscles. These can be readily identified by palpating the tensed muscle mass while having the patient frown. The corrugator depresses the skin creating a "furrowed" vertical line surrounded by tensed muscle (i.e., frown lines). The location, size, and use of the muscles vary markedly among individuals. Physicians administering DYSPORT must understand the relevant neuromuscular and/or orbital anatomy of the area involved and any alterations to the anatomy due to prior surgical procedures.

Risk of ptosis can be mitigated by careful examination of the upper lid for separation or weakness of the levator palpebrae muscle (true ptosis), identification of lash ptosis, and evaluation of the range of lid excursion while manually depressing the frontalis to assess compensation.

In order to reduce the complication of ptosis, the following steps should be taken:

• Avoid injection near the levator palpebrae superioris, particularly in patients with larger brow depressor complexes.
• Medial corrugator injections should be placed at least 1 centimeter above the bony supraorbital ridge.
• Ensure the injected volume/dose is accurate and where feasible kept to a minimum.
• Do not inject toxin closer than 1 centimeter above the central eyebrow.

To inject DYSPORT, advance the needle through the skin into the underlying muscle while applying finger pressure on the superior medial orbital rim. Inject patients with a total of 50 Units in five equally divided aliquots. Using an appropriately sized needle, inject 10 Units of DYSPORT into each of five sites, two in each corrugator muscle, and one in the procerus muscle (see Figure 1).

Figure 1

Upper Limb Spasticity

In the clinical trial that assessed the efficacy and safety of DYSPORT for treatment of upper limb spasticity in adults [see Clinical Studies (14.3)], doses of 500 Units and 1000 Units were divided among selected muscles at a given treatment session (see Table 3 and Figure 2).

Figure 2: Muscles for Injection for Upper Limb Spasticity in Adults

Repeat DYSPORT treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection. A majority of patients in clinical studies were retreated between 12-16 weeks; however some patients had a longer duration of response (i.e., 20 weeks). The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose of DYSPORT and muscles to be injected. Clinical improvement may be expected one week after administration of DYSPORT.

Lower Limb Spasticity

In the clinical trial that assessed the efficacy and safety of DYSPORT for treatment of lower limb spasticity in adults [see Clinical Studies (14.3)], doses of 1000 Units and 1500 Units were divided among selected muscles at a given treatment session (see Table 4 and Figure 3).

Figure 3: Muscles for Injection for Lower Limb Spasticity in Adults

Repeat DYSPORT treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection. A majority of patients in clinical studies were retreated between 12-16 weeks. The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose of DYSPORT and muscles to be injected.

​Upper Limb Spasticity in Pediatric Patients 2 Years of Age and Older

​In the clinical trial that assessed the efficacy and safety of DYSPORT for treatment of upper limb spasticity in pediatric patients 2 years of age or older with a weight of at least 10 kg [see Clinical Studies (14.4)], doses of 8 Units/kg or 16 Units/kg were divided among selected muscles of the target upper limb at a given treatment session (see Table 5 and Figure 4).

​Table 5 describes the recommended Units/kg dose of DYSPORT per muscle. The maximum recommended total dose of DYSPORT administered for treatment of upper limb spasticity must not exceed 16 Units/kg or 640 Units, whichever is lower.

​Figure 4: Muscles for Injection for Upper Limb Spasticity in Pediatric Patients

​

​Repeat DYSPORT treatment should be administered when the effect of a previous injection has diminished but no sooner than 16 weeks after the previous injection. A majority of patients in the clinical study were retreated between 16-28 weeks; however, some patients had a longer duration of response (i.e., 34 weeks or more). The degree and pattern of muscle spasticity at the time of re-injection may necessitate alterations in the dose of DYSPORT and muscles to be injected.

Lower Limb Spasticity in Pediatric Patients 2 Years of Age and Older In the clinical trial that assessed the efficacy and safety of DYSPORT for treatment of lower limb spasticity in pediatric patients 2 years of age or older [see Clinical Studies (14.4)], doses of 10 Units/kg to 15 Units/kg were divided among selected muscles of the target lower limb at a given treatment session (see Table 6 and Figure 5).

Table 6 describes the recommended Units/kg dose of DYSPORT per muscle of the Gastrocnemius-Soleus Complex (GSC). The recommended total DYSPORT dose per treatment session is 10 Units/kg to 15 Units/kg for unilateral lower limb injections or 20 Units/kg to 30 Units/kg for bilateral lower limb injections. However, the total dose of DYSPORT administered in a 3-month interval must not exceed 15 Units/kg for unilateral lower limb injections, 30 Units/kg for bilateral lower limb injections, or 1000 units, whichever is lower. The total dose administered should be divided between the affected spastic muscles of the lower limb(s). When possible, the dose should be distributed across more than 1 injection site in any single muscle (see Table 6).

Figure 5: Muscles for Injection for Lower Limb Spasticity in Pediatric Patients

Although actual location of the injection sites can be determined by palpation, the use of injection guiding technique (e.g., electromyography or electrical stimulation, or ultrasound) is recommended to target the injection sites.

Repeat DYSPORT treatment should be administered when the effect of a previous injection has diminished but no sooner than 12 weeks after the previous injection. A majority of patients in the clinical studies were retreated between 16-22 weeks, however; some had a longer duration of response. The degree and pattern of muscle spasticity and overall clinical benefit at the time of re-injection may necessitate alterations in the dose of DYSPORT and muscles to be injected.

The safety and effectiveness of DYSPORT injected into proximal muscles of the lower limb for the treatment of spasticity in pediatric patients has not been established.