PHENOBARBITAL COLONIS

Posology It may take more than two weeks for the medicine to reach sufficient levels in the bloodstream in order to control seizures. This also applies when the dose is adjusted. When therapeutic drug monitoring is justified, current clinical practice guidelines for phenobarbital blood level monitoring should be followed.

Adults 2 to 3 mg/kg per day, taken once daily at bedtime. Paediatric population (by weight) -Less than 20 kg: 5 mg/kg per day, as one or two divided doses, -Between 20 and 30 kg: 3 to 4 mg/kg per day, as one or two divided doses, -Above 30 kg: 2 to 3 mg/kg per day, as one or two divided doses.

Method of administration For oral use. 2 ml and a “Press- In” Bottle Adapter (PIBA) are provided with the product. 1. Shake the bottle well, before use. 2. Open the bottle and at first use insert the “Press-In” Bottle Adapter (PIBA). 3. Insert the syringe into the PIBA and draw out the required volume from the inverted bottle.

4. Remove the filled syringe from the bottle in the upright position. 5. Discharge the syringe contents into the mouth. Repeat steps 3 to 5 as needed to achieve the required dose. 6. Replace the cap on the bottle (PIBA remains in place).

7. Rinse the syringe with water and allow to air dry. If you are giving Phenobarbital oral suspension to a child: - Make sure that the child is sitting up or standing. - Put the syringe into the child’s mouth, placing the barrel-opening in the area between the gums and the inside of the cheek.

- Push the plunger slowly, giving the child time to swallow the medicine as it squirts out. Do not push the plunger too quickly as the medicine may come out too quickly and the child may choke. - Give the child some water to drink in order to ensure that all the medicine is washed down.

Note If necessary, Phenobarbital oral suspension can be administered via intragastric feeding tubes (nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) tubes). Tubes should be rinsed with 2 ml of water immediately after administration.

6.

The following adverse effects have been associated with use of phenobarbital. The most frequent adverse effect is sedation. The classification of adverse events according to their frequency is based on the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

System organ class 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) Not known Blood and lymphatic system disorders pancytopenia, aplastic anaemia, folate deficiency anaemia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia, hypoprothrombinaemia, methaemoglobinaemia (in infants nursed by mothers receiving phenobarbital) Endocrine disorders reduced thyroid hormones serum concentration Metabolism and nutrition disorders folate deficiency, hypocalcaemia, hypophosphataemia, abnormal Vitamin D metabolism, vitamin K deficiency Psychiatric disorders abnormal behaviour, agitation, aggression (particularly in children) mood altered, sleep disorders/ insomnia dependence, delirium, depression, hallucination, paradoxical excitement, restlessness, suicidal ideation, withdrawal syndrome, hyperactivity (particularly in children) Nervous system disorders drowsiness, cognitive impairment, memory impairment ataxia, dizziness, headache attention deficit dyskinesia, Grand Mal convulsion, irritability, lethargy, nystagmus, sedation, behavioural disturbances in children Vascular disorders hypotension Respiratory, thoracic and mediastinal disorders respiratory depression Gastrointestinal disorders nausea, vomiting Hepato-biliary disorders increased GGT, increased transaminases and/or alkaline phosphatases hepatitis, cholestasis Skin and subcutaneous tissue disorders allergic dermatitis (morbiliform or scarlatiniform maculo- papular rashes) fixed pigmented erythema, erythema multiforme, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), exfoliative dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized System organ class 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) Not known exanthematous pustulosis (AGEP), photosensitivity, purpura Musculoskeletal and connective tissue disorders Dupuytren's disease arthralgia (shoulder- hand syndrome or rheumatism) Ledderhose’s syndrome, Peyronie’s disease, decreased bone mineral density, osteopenia, osteoporosis, osteomalacia, fractures, rickets, frozen shoulder, fibromas, general joint pain Pregnancy, puerperium and perinatal conditions neonatal sedation, neonatal drug dependence and withdrawal syndrome, neonatal bleeding due to vitamin K deficiency Congenital, familial and genetic disorders cleft lip and palate, congenital malformations, other developmental abnormalities General disorders and administration site conditions antiepileptic hypersensitivity syndrome (including fever, rash, lymphadenopathy, lymphocytosis, eosinophilia, liver and other organ involvement) Serious effects affecting the hepatic and/or cutaneous systems as well as hypersensitivity reactions require discontinuation of treatment.

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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Special warnings Phenobarbital is not effective in absences and myoclonic seizures which can sometimes be aggravated. The introduction of an antiepileptic drug may, rarely, be followed by relapse of seizures or the onset of a new form of seizure in the patient, irrespectively of the fluctuations observed in certain epileptic forms.

With regard to phenobarbital, the origin of these aggravations can be due to inappropriate choice of medication with respect to the patient's seizure form, a modification of the concomitant antiepileptic treatment or a pharmacokinetic interaction with it, toxicity or overdose.

There may be no other explanation than a paradoxical reaction. Prolonged intake of phenobarbital (100 mg per day for 3 months) may result in the appearance of a dependence syndrome and particular care should be taken in treating patients with a history of drug abuse or alcoholism.

Avoid sudden withdrawal to prevent rebound seizures. Phenobarbital should be used with caution in the young, the elderly, in debilitated patients and in those with depressive disorders. Suicidal risk Suicidal ideation and behaviour have been reported in patients treated with anti- epileptic agents for several indications.

A meta-analysis of randomised placebo- controlled trials of antiepileptic drugs has shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known, and the available data do not exclude the possibility of an increased risk for Phenobarbital oral suspension.

Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Serious skin reactions Serious skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN or Lyell's syndrome), drug hypersensitivity syndrome with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with phenobarbital treatment.

Patients should be informed of the signs and symptoms of serious skin lesions and be closely monitored. The risk of occurrence of SJS or TEN is greater during the first weeks of treatment. Treatment should be discontinued at the first emergence of rash, mucosal lesions or any other manifestation of skin hypersensitivity.

Early diagnosis and immediate discontinuation of any suspect medication leads to better results in the management of SJS or TEN. Early cessation is associated with a better prognosis. If SJS or TEN is developed during phenobarbital treatment, the patient should never take phenobarbital again.

Precautions for use If hypersensitivity or hepatic disorders occur, treatment with phenobarbital should be discontinued. Reduce the dosage in renal insufficiency, hepatic insufficiency (biological monitoring is advised, because of the risk of hepatic encephalopathy), in the elderly and in alcoholics.

There is still some debate on the effects of antiepileptics, including Phenobarbital, on bone metabolism. It is therefore recommended that Vitamin D supplementation is considered in patients who are immobilised for long periods or who have inadequate sun exposure or dietary intake of Vitamin D or calcium.

In children subjected to long- term treatment with phenobarbital, the addition of a prophylactic treatment for rickets: vitamin D2 (1200 to 2000 IU/day) or 25-OH-vitamin D3 is recommended. Patients are advised to avoid alcohol while using this medicine.

5). Women of childbearing potential Phenobarbital may cause foetal harm when administered to a pregnant woman. 6). Phenobarbital should not be used in women of childbearing potential unless the potential benefit is judged to outweigh the risks following consideration of other suitable treatment options.

Women of childbearing potential should be fully informed of the potential risk to the foetus if they take phenobarbital during pregnancy. A pregnancy test to rule out pregnancy should be considered prior to commencing treatment with phenobarbital in women of childbearing potential.

Women of childbearing potential should use highly effective contraception during treatment and for 2 months after the last dose. Due to enzyme induction, phenobarbital may result in a failure of the therapeutic effect of oral contraceptive drugs containing oestrogen and/or progesterone.

6). Women planning a pregnancy should be advised to consult in advance with their physician so that adequate counselling can be provided and appropriate other treatment options can be discussed prior to conception and before contraception is discontinued.

Women of childbearing potential should be counselled to contact their doctor immediately if they become pregnant or think they might be pregnant while on treatment with phenobarbital. The risk-benefit ratio should be carefully reassessed at regular intervals during treatment, at puberty, and urgently in women of childbearing potential treated with phenobarbital, planning pregnancy or are pregnant.

Phenobarbital Colonis 50 mg/5 ml oral suspension contains sodium benzoate and sodium. 5 mg sodium benzoate in each 1 ml of suspension. Sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to four weeks old).

17 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

1. • Severe respiratory depression. • Severe hepatic or renal impairment. • Acute intermittent porphyria. 5). • In combination with St. John’s wort. • Hyperkinetic children.