Section 4.2: Posology and method of administration Rev. 1 SmPC training presentation Note: for full information refer to the European Commission’s Guideline on summary of product characteristics (SmPC) SmPC Advisory Group An agency of the European Union Index I. General objectives II. Key principles II.1 Conditions for use II.2 Posology II.3 Other posology requirements II.4 Special population II.5 Paediatric population II.6 Method of administration III. FAQs* 2 Section 4.2: Posology and method of administration I. General objectives of section 4.2 This section should include all the relevant information to guide the posology recommendation taking into account patient and product specificities 3 Section 4.2: Posology and method of administration Section index II.1 Conditions for use In case of restricted medical prescription, this SmPC examples section should be started by specifying the 1 restricted prescription conditions 2 restricted prescription In case of specific safety need, any recommended restriction to a particular setting 3 specific safety need should also be stated e.g. 4 specific safety need “restricted to hospital use only” or “appropriate resuscitation equipment should be available” 4 Section 4.2: Posology and method of administration Section index Example 1–restricted medical prescription Example 1 – restricted medical prescription In case of restricted medical prescription, this section should be started by specifying the conditions Active substance XY 150 mg/300 mg film-coated tablets Therapy should be initiated by a physician experienced in the management of HIV infection. 5 Section 4.2: Posology and method of administration Conditions for use Section index Example 2–restricted medical prescription Example 1 – restricted medical prescription In case of restricted medical prescription, this section should be started by specifying the conditions Active substance X 6 mg solution for injection Active substance X therapy should be initiated and supervised by physicians experienced in oncology and/or haematology. 6 Section 4.2: Posology and method of administration Conditions for use Section index Example 3–specific safety need Example 1 – restricted medical prescription In case of specific safety need, any recommended restriction to a particular setting should also be stated Active substance X 40 micrograms per dose iontophoretic transdermal Active substance X should be restricted to hospital use only. 7 Section 4.2: Posology and method of administration Conditions for use Section index Example 4–specific safety need Example 1 – restricted medical prescription In case of specific safety need, any recommended restriction to a particular setting should also be stated Active substance X 30 MU/0.5 ml solution for injection or infusion in pre-filled syringe The mobilisation and apheresis procedures should be performed in collaboration with an oncology-haematology centre with acceptable experience in this field and where the monitoring of haematopoietic progenitor cells can be correctly performed. 8 Section 4.2: Posology and method of administration Conditions for use Section index II.2 Posology Dosage for each indication, each method/route of administration SmPC examples as appropriate: 5 dosage 6 dosage 2 Dose recommendations e.g. mg, mg/kg, mg/m 7 dosage Frequency of dosing e.g. once or twice daily or every 6 hours Where appropriate, a reference to official recommendation should be made e.g. for primary vaccination and antibiotics as well as for booster dose) 9 Section 4.2: Posology and method of administration Section index Example 5-dosage Example 5 - dosage Dosage should be clearly specified for each method/route of administration and for each indication. Dose recommendations Frequency of dosing Active substance X 250 mg capsules Use in renal transplant: Adults: oral active substance X should be initiated within 72 hours following transplantation. The recommended dose in renal transplant patients is 1.0 g administered twice daily (2 g daily dose). 10 Section 4.2: Posology and method of administration Posology Section index Example 6-dosage Example 5 - dosage Dosage should be clearly specified for each method/route of administration and for each indication. Dose recommendations –mg/kg Frequency of dosing Active substance X 25 mg/ml concentrate for solution for infusion Metastatic breast cancer (mBC) The recommended dose of active substance X is 10 mg/kg of body weight given once every 2 weeks or 15mg/kg of body weight given once every 3 weeks as an intravenous infusion. 11 Section 4.2: Posology and method of administration Posology Section index Example 7-dosage Example 5 - dosage Dosage should be clearly specified for each method/route of administration and for each indication. Dose recommendations –mg/m2 Frequency of dosing Active substance X 2 mg/ml concentrate for solution for infusion Breast cancer/Ovarian cancer: Active substance X is administered intravenously at a dose of 50 mg/m2 once every 4 weeks for as long as the disease does not progress and the patient continues to tolerate treatment. AIDS-related KS: Active substance X is administered intravenously at 20 mg/m2 every two-to-three weeks. Avoid intervals shorter than 10 days as medicinal product accumulation and increased toxicity cannot be ruled out. Treatment of patients for two-to-three months is recommended to achieve a therapeutic response. Continue treatment as needed to maintain a therapeutic response. The dose of active substance X is diluted in 250 ml 5 % (50 mg/ml) glucose solution for infusion and administered by intravenous infusion over 30 minutes. 12 Section 4.2: Posology and method of administration Posology Section index II.3 Other posology requirements (illustrated by SmPC examples) Normal duration of use. e.g. 8 Preventative measures for adverse reactions. e.g. 18 Recommendation related to non-serious adverse Maximum recommended dose. reaction that are frequent but transient or e.g. 9 single 10 single 11 daily 12 total manageable with dose-titration. e.g. 19 Dose titration. e.g. 13 Intake in relation to food and drink. e.g. 20 Advice on discontinuation. e.g. 14 Interactions requiring dose adjustments. e.g. 21 Advice if dose(s) missed. e.g. 15 16 vomiting Advice regarding repeat use. e.g. 22 Advice relevant for dose adjustment e.g. from monitoring of clinical signs and symptoms +/- lab investigations. e.g. 17 13 Section 4.2: Posology and method of administration Section index Example 8–normal duration of use Normal duration of use and any restrictions on duration Active substance X 2 mg/ml concentrate for solution for infusion Active substance X is administered intravenously at a dose of 50 mg/m2 once every 4 weeks for as long as the disease does not progress and the patient continues to tolerate treatment. 14 Section 4.2: Posology and method of administration Other posology requirements Section index Example 9-maximum dose-single Maximum recommended dose (single) Active substance X 25 micrograms/ml solution for infusion Dosing of active substance X should be initiated at 2.4 μg/day and titrated on an individual patient basis according to the patient’s analgesic response and adverse reactions. Patients should be titrated in dose increments of ≤ 2.4 μg/day, up to a maximum dose of 21.6 μg/day. The minimal interval between dose increases is 24 hours; the recommended interval, for safety reasons, is 48 hours or more. If necessary the dose can be decreased by any amount (including stopping the infusion) for the management of adverse reactions. Approximately 75% of patients who respond satisfactorily to treatment require a dose of ≤ 9.6 μg/day. 15 Section 4.2: Posology and method of administration Other posology requirements Section index Example 10-maximum dose-single Maximum recommended dose (single) Active substance X 6,000 units. Powder and solvent for solution for injection Active substance X should be administered on the basis of body weight, with a maximum dose of 10,000 units (50 mg active substance X). 16 Section 4.2: Posology and method of administration Other posology requirements Section index Example 11-maximum dose-daily Maximum recommended dose (daily) Active substance X 20 mg powder for solution for injection The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. 17 Section 4.2: Posology and method of administration Other posology requirements Section index Example 12-maximum dose-total Maximum recommended dose (total) Active substance X Squamous cell carcinoma Intramuscular or intravenous injection of 10-15 x 103 IU/m2 once or twice a week. Treatment can be continued in the weeks following this or, which is more common, with intervals of 3-4 weeks, up to a total cumulative dose of 400 x 103 IU. 18 Section 4.2: Posology and method of administration Other posology requirements Section index Example 13-dose titration Dose titration Active substance X 100 micrograms buccal tablets Dose titration Active substance X should be individually titrated to an “effective” dose that provides adequate analgesia and minimises undesirable effects. In clinical studies, the effective dose of active substance X for breakthrough pain was not predictable from the daily maintenance dose of opioid. Patients should be carefully monitored until an effective dose is reached. Titration in patients not switching from other fentanyl containing products The initial dose of active substance X should be 100 micrograms, titrating upwards as necessary through the range of available tablets strengths (100, 200, 400, 600, 800 micrograms). Titration in patients switching from other fentanyl containing products Due to different absorption profiles, switching must not be done at a 1:1 ratio. If switching from another oral fentanyl citrate product, independent dose titration with active substance X is required as bioavailability between products differs significantly. However, in these patients, a starting dose higher than 100 micrograms may be considered.