Table 1.
The 10 drugs singled out for an authorised “off-label” use in PPC
| Drug | On-label use | Authorized l. 648/96 off-label use | Advised dosage |
|---|---|---|---|
| HYOSCINA BUTYLBROMIDE | Pill in child > 14 years, supp in child > 6 years: spastic– painful events of urinary and genital tract. | 1. Iv administration for intestinal obstruction due to peritonitis in pediatric patients with cancer. 2. Iv administration for reduction of secretions and rattle in terminally ill patient. |
Iv: Child 1 month-4 years: 300–500 micrograms/Kg 3–4 times a day (max. Per dose 5 mg) Child 5–11 years: 5–10 mg 3–4 times a day Child 12–17 years:10–20 mg 3–4 times a day [24] |
| DEXMEDETOMIDINE | Procedural analgo-sedation outside the operating room (Not Operating Room Anesthesia - NORA) in children with difficult airway management and child with seizure disorders who must undergo diagnostic studies for locating epileptogenic foci Analgo-sedation of critical infant and child in ICU, mechanically ventilated and poorly responsive to conventional analgo-sedation treatment. |
1. Control of stressful symptoms from disease or procedure and fix sleep outside the ICU in patients in palliative care, not responsive to conventional therapies. 2. Intranasal route of administration. |
Iv: 1 mcg/kg in a 10-min bolus, increased up to a maximum of 3 mcg/kg, and followed by a 1 mcg/kg/h infusion [25] In: 1 to 4 mcg/kg, eventually re-administered at 1 mcg/Kg [25] |
| FENTANYL | Premedication for any type of anesthesia (also local) both in the postoperative period as during surgery. | 1. Transdermal, iv use for acute and/or chronic pain management from cancer and not, in children in PPC. 2. Transmucosal use for procedural/acute/breakthrough pain in PPC. |
Transdermal: based on oral morphine dose equivalent (given at 24-h totals). Product monograph: oral morphine 45 mg = 12 mcg/h patch oral morphine < 90 mg = 25 mcg/h patch oral morphine 135–189 mg = 50 mcg/h patch oral morphine 225–314 mg = 75 mcg/h patch [26] Iv: Child > 6 months and < 50 Kg: bolus 0,5–1 mcg/Kg every 1–2 h, dose to be administered over at least 30 s; infusion 0,5–2 mcg/Kg/h Child > 50 Kg: bolus 25–50 mcg every 1–2 h, dose to be administered over at least 30 s; infusion 25–200 mcg/h [27] Transmucosal: Child 2–18 years and weiting > 10 Kg: 15–20 mcg/Kg as a single dose, titrated to a maximum dose of 400 mcg [26] |
| GABAPENTIN | Pill in child > 6 years: adjunctive therapy in the treatment of partial seizures in the presence or absence of secondary generalization. > 12 years: monotherapy in the treatment of partial seizures in the presence or absence of secondary generalization |
Neuropathic or mixed pain in children older than 2 years in palliative care. | By mouth: Child > 2 years: Day 1: 10 mg/Kg (maximum single dose 300 mg) Day 2: 10 mg/Kg twice daily Day 3 onwards: 10 mg/Kg 3 times daily Increase further if necessary to a maximum of 20 mg/Kg/dose (maximum single dose 600 g) Child > 12 years: The maximum daily dose can be increased according to responde, up to e a maximum of 3600 mg/day [26] |
| KETAMINE | Im, iv and continuous infusion administering Use for induction and maintenance of general anesthesia from neonatal and premedication in children older than1 month. |
1.Use in patients in PPC for managing procedural or mixed/neuropathic pain that does not respond to other therapy, alone or in combination/replacement for opioid analgesics. 2. Intranasal administration |
Im: Neonate: 4 mg/Kg, adjusted according to response, a dose of 4 mg/Kg usually produces 15 min of surgical anaesthesia Child: 4–13 mg/Kg, adjusted according to response, a dose of 4 mg/Kg sufficient for some diagnostic procedures, a dose of 10 mg/Kg usually produces 12–25 min of surgical anaesthesia [24] Iv for short procedures: Neonate: 1–2 mg/Kg, adjusted according to response, to be given over at least 60 s, a dose of 1–2 mg/Kg produces 5-1o minutes of surgical anaesthesia Child 1 month-11 years: 1–2 mg/Kg, adjusted according to response, to be given over at least 60 s, a dose of 1–2 mg/Kg produces 5-1o minutes of surgical Child 12–17 years: 1–4,5 mg/Kg, adjusted according to response, to be given over at least 60 s, a dose of 2 mg/Kg usually produces 5-1o minutes of surgical [24] Continuous Iv Infusion: Child 1 month-17 years: starting dose 40 mcg/Kg/h., increase according to response, usual maximum dose is 100 mcg/Kg/h [26] Intranasal: Child 1 month-17 years: 0,5–10 mg/kg/dose, start with lower dose and increase according to response [28–31] |
| KETOROLAC | The safety and efficacy in children has not been established. The use of the drug is therefore contraindicated below 16 years. Pill and drop: used to treat short term (max 5 days) of moderate postoperative pain. Iv/im: indicated in the short term treatment (maximum two days) for moderate-severe postoperative pain. By mouth/im use for treatment of acute pain starting from 16 years of life, iv from 6 months. |
By mouth and sublingual use for chidlren 4–15 years old, for a maximum period of 5 days, in patients receiving PPC without vascular access, for management of moderate/severe acute episodic nociceptive pain, which integrate other analgesia if not effective, in the course of pathology eligible to PPC or in terminall illness. | Iv: Child 6 months-15 years: initially 0,5–1 mg/Kg (max. Per dose 15 mg), than 500 mcg/Kg every 6 h (max. Per dose 15 mg) as required for maximum duration of treatment 2 days; maximum 60 mg per day [24] Im e Iv: Child 16–17 years (body-weight up to 50 Kg): initially 10 mg, than 10–30 mg every 4–6 h as required for maximum duration of treatment 2 days, maximum 60 mg per day Child 16–17 years (body-weight 50 Kg and above): initially 10 mg, than 10–30 mg every 4–6 h as required for maximum duration of treatment 2 days, maximum 90 mg per day [24] By mouth/sublingual: Child 4–15 years: 0,5 mg/Kg/ dose, maximum 3 doses/day for maximum duration of treatment 5 days [32] |
| LIDOCAINE | Peripheral and regional anesthesia, surgical stomatology. | 1.Nebulized use for the treatment of cough refractory to other therapies, if pulmonary metastases 2. Intravenous use to treat neuropathic pain in patients in PPC not responsive to conventional therapies. |
Nebulized: 5 ml of 0,2% solution every 8 h [33] Iv: 10–15 mcg/Kg/min [34] |
| MIDAZOLAM | Iv: conscious sedation before and during diagnostic or therapeutic procedures with or without local anaesthesia; Anesthesia: Premedication before induction of anesthesia; Sedation in ICU. Children 3 months-18 years: treatment of acute prolonged seizures Children > 1 month: treatment of status epilepticus or following crises |
1. Intranasal use due to less invasiveness and high speed of administration in the absence of venous access, even in urgent cases in patients aged over 1 month in PPC. 2. Intravenous use to manage non-painful distress symptoms during end of life. |
Intranasal: 0,2–0,5 mg/Kg/dose [35, 36] Iv: Child 1 month-17 years: 0,05–0,3 mg/Kg/h [26] |
| ONDANSETRON | Pill, syrup, vial in children ≥6 months to control chemotherapy-induced nausea and vomiting (CINV). Vial in children ≥1 month for prevention and treatment of post-operative nausea and vomiting (PONV). |
Control of nausea and vomiting during opioid therapy in patients aged > 6 months in palliative care | Iv: Child 1–12 years: 5 mg/m2 (maximum single dose 8 mg) every 8–12 h Child 12–17 years: 8 mg every 8–12 h [26] By mouth Child 6 months-17 years (BSA up to 0.6 m2): 2 mg every 12 h for up to 5 days (dose can be started 12 h after iv administration); maximum 32 mg per day. Child 6 months-17 years (BSA 0.6–1.2 m2): 4 mg every 12 h for up to 5 days (dose can be started 12 h after iv administration); maximum 32 mg per day. Child 6 months-17 years (BSA 1.3 m2 and above): 8 mg every 12 h for up to 5 days (dose can be started 12 h after iv administration); maximum 32 mg per day [24] |
| SCOPOLAMINE | Not marketed in Italy | Treatment of hypersalivation in patients in palliative care and end of life by transdermal route. | Neonate: quarter of a patch every 72 h Child 1 month to 3 years: quarter of a patch every 72 h Child 3–10 years: half a patch every 72 h Child 11–17 years: one patch every 72 h [26] |
Abbreviation: Iv Intravenous, In Intranasal, Im Intramuscular, BSA Body surface area, ICU Intensive Care Unit, PPC Pediatric Palliative Care