Name of the medicinal product

Phenobarbital Tablets USP 15mg Taj Pharma
Phenobarbital Tablets USP 30mg Taj Pharma
Phenobarbital Tablets USP 60mg Taj Pharma

2. Qualitative and quantitative composition

a) Each tablet contains:
Phenobarbital USP………….15mg
Excipients……………………q.s

b) Each tablet contains:
Phenobarbital USP………….30mg
Excipients……………………q.s

c) Each tablet contains:
Phenobarbital USP………….60mg
Excipients……………………q.s

Pharmaceutical form

Tablet.

Clinical particulars

4.1 Therapeutic indications

The treatment and control of all forms of epilepsy, except absence seizures. Phenobarbital should only be used in the treatment of febrile convulsions in exceptional circumstances.

4.2 Posology and method of administration

Adults: 60-180mg at night

Child: 5-8mg/kg daily

Elderly: Phenobarbital clearance diminishes in the elderly. Therefore the dose of phenobarbital is usually lower in elderly patients.

The dose of phenobarbital should be adjusted to meet the needs of individual patients. This usually requires plasma concentration of 15 to 40 micrograms/ml (65 to 170 micromoles/litre).

Method of Administration

For oral administration

4.3 Contraindications

Phenobarbital should not be given to patients with:

Known hypersensitivity to phenobarbital, other barbiturates or other ingredients in the tablet
Acute intermittent porphyia
Severe respiratory depression
Severe renal or hepatic impairment

4.4 Special warnings and precautions for use

Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomized placebo-controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for phenobarbital.

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 behavior emerge.

Steven-Johnson syndrome and toxic epidermal necrolysis

Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of phenobarbital. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment.

If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, Phenobarbital treatment should be discontinued. The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis.

If the patient has developed SJS or TEN with the use of phenobarbital, phenobarbital must not be re-started in this patient at any time.

Care should be used in the following situations:

Patients with the rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose – galactose malabsorption should not take this medicine
Respiratory depression (avoid if severe)
Young, debilitated or senile patients
Renal impairment
Existing liver disease
Sudden withdrawal should be avoided as severe withdrawal syndrome (rebound insomnia, anxiety, tremor, dizziness, nausea, fits and delirium) may be precipitated
Acute chronic pain – paradoxical excitement may be induced or important symptoms masked.
Prolonged use may result in dependence of the alcohol-barbiturate type. Care should be taken in treating patients with a history of drug abuse or alcoholism.

4.5 Interaction with other medicinal products and other forms of interaction

Effects on Phenobarbital

Effects of phenobarbital on other medicines

• Alcohol – concurrent administration with alcohol may lead to an additive CNS depressant effect. This is likely with concurrent administration with other CNS depressants.

• Antidepressants – including MAOIs, SSRIs and tricyclics may antagonise the antiepileptic activity of phenobarbital by lowering the convulsive threshold

• Antiepileptics – phenobarbital plasma concentrations increased by oxcarbazepine, phenytoin and sodium valproate. Vigabatrin possibly decreases phenobarbital plasma concentrations.

• Antipsychotics – concurrent use of chlorpromazine and thioridazine with phenobarbital can reduce the serum levels of either drug.

• Folic acid – if folic acid supplements are given to treat folate deficiency, which can be caused by the use of phenobarbital, the serum phenobarbital levels may fall, leading to decreased seizure control in some patients. (see section 4.6).

• Memantine – the effect of Phenobarbital is possibly reduced.

• Methylphenidate – plasma concentration of Phenobarbital is possibly increased.

• St John’s wort (Hypericum perforatum) – the effect of phenobarbital can be reduced by concomitant use of the herbal remedy St John’s wort.

Phenobarbital increases the rate of metabolism reducing serum concentrations of the following drugs:

• Anti-arrhythmics – disopyramide and quinidine loss of arrhythmia control is possible. Plasma levels of antiarrhymics should be monitored, if phenobarbital is added or withdrawn. Changes in dosage may be necessary.

• Antibacterials – chloramphenicol, doxycycline, metronidazole and rifampicin. Avoid concomitant use of telithromycin during and for 2 weeks after Phenobarbital.

• Anticoagulants.

• Antidepressants – paroxetine, mianserin and tricyclic antidepressants.

• Antiepileptics – carbamazepine, lamotrigine, tiagabine, zonisamide, primidone and possibly ethosuxamide.

• Antifungals – the antifungal effects of griseofulvin can be reduced or even abolished by concurrent use. Phenobarbital possibly reduces plasma concentrations of itraconazole or posaconazole. Avoid concomitant use of voriconazole.

• Antipsychotics – phenobarbital possibly reduces concentration of aripiprazole.

• Antivirals – phenobarbital possibly reduces plasma levels of abacavir, amprenavir, darunavir, lopinavir, indinavir, nelfinavir, saquinavir.

• Anxiolytics and Hypnotics – clonazepam.

• Aprepitant – phenobarbital possibly reduces plasma concentration of aprepitant.

• Beta-blockers – metoprolol, timolol and possibly propranolol.

• Calcium channel blockers – phenobarbital causes reduced levels of felodipine, isradipine, diltiazem, verapamil, nimodipine and nifedipine and an increase in dosage may be required.

• Cardiac Glycosides – blood levels of digitoxin can be halved by concurrent use.

• Ciclosporin or tacrolimus.

• Corticosteroids.

• Cytotoxics – phenobarbital possibly reduces the plasma levels of etoposide or irinotecan.

• Diuretics – concomitant use with eplerenone should be avoided.

• Haloperidol- serum levels are approximately halved by concurrent used with phenobarbital.

• Hormone Antagonists – gestrinone and possibly toremifene.

• Methadone – levels can be reduced by concurrent use of phenobarbital and withdrawal symptoms have been reported in patients maintained on methadone when phenobarbital has been added. Increases in the methadone dosage may be necessary.

• Montelukast.

• Oestrogens – reduced contraceptive effect.

• Progestogens – reduced contraceptive effect.

• Sodium oxybate – enhanced effects, avoid concomitant use.

• Theophylline – may require an increase in theophylline dose.

• Thyroid hormones-may increase requirements for thyroid hormones in hypothyroidism.

• Tibolone

• Tropisetron

• Vitamins – barbiturates possibly increase requirements for vitamin D

Phenobarbital may interfere with some laboratory tests including metyrapone test, phenlolamine tests and serum bilirubin estimation.

4.6 Fertility, pregnancy and lactation

Phenobarbital therapy in epileptic pregnant women presents a risk to the fetus in terms of major and minor congenital defects such as congenital craniofacial, digital abnormalities and, less commonly, cleft lip and palate. The risk of teratogenic effects developing appears to be greater if more than one antiepileptic drug is administered. The risk to the mother, however is greater if phenobarbital is withheld and seizure control is lost. The risk: benefit balance, in this case, favours continued use of the drug during pregnancy at the lowest possible level to control seizures.

Patients taking Phenobarbital should be adequately supplemented with folic acid before conception and during pregnancy (see section 4.5). Folic acid supplementation during pregnancy can help to reduce the risk of neural defects to the infant.

Phenobarbital readily crosses the placenta following oral administration and is distributed throughout fetal tissue, the highest concentrations being found in the placenta, fetal liver and brain. Adverse effects on neurobehavioral development have also been reported.

Haemorrhage at birth and addiction are also a risk. Prophylactic treatment with vitamin K¹for the mother before delivery (as well as the neonate) is recommended, the neonate should be monitored for signs of bleeding.

Phenobarbital is excreted into breast milk and there is a small risk of neonatal sedation. Breast feeding is therefore not advisable.

4.7 Effects on ability to drive and use machines

Phenobarbital may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Patients should be advised to make sure they are not affected before undertaking any potentially hazardous tasks.

4.8 Undesirable effects

Blood and the lymphatic system disorders:megaloblastic anaemia (due to folate deficiency), agranulocytosis, thrombocytopenia.
Musculoskeletal and connective tissue disorders:Dupuytren’s contracture, frozen shoulder, arthralgia, osteomalacia, rickets.

There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with phenobarbital. The mechanism by which phenobarbital affects bone metabolism has not been identified.

Reproductive and breast disorders:Peyronie’s disease.
Psychiatric disorders:paradoxical reaction (unusual excitement), hallucinations, restlessness and confusion in the elderly, mental depression, memory and cognitive impairment, drowsiness, lethargy.
Nervous system disorders:hyperactivity, behavioural disturbances in children, ataxia, nystagmus.
Cardiac disorders: hypotension.
Respiratory disorders: respiratory depression.
Hepato-bilary: hepatitis, cholestasis.
Skin and subcutaneous tissue disorders:allergic skin reactions (maculopapular morbilliform or scarlatiniform rashes), other skin reactions such as exfoliative dermatitis, erythema multiforme.

Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (see section 4.4).

Frequency: very rare

General disorders and administration site conditions: antiepileptic hypersensitivity syndrome (features include fever, rash, lymphadenopathy, lymphocytosis, eosinophilia, haematological abnormalities, hepatic and other organ involvement including renal and pulmonary systems which may become life threatening).

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.

4.9 Overdose

Toxicity varies between patients; tolerance will develop with chronic use. Features of poisoning are to be expected after ingestion of 1g in adults.

Features:

Drowsiness, dysarthria, ataxia, nystagmus and disinhibition. There may also be coma, cardiovascular collapse, cardiac arrest, hypotension, hypotonia, hyporeflexia, hypothermia, hypotension and respiratory depression.

Barbiturates decrease gut motility, which may lead to slow onset and worsening of symptoms or cyclical improvement and worsening of symptoms.

Management:

Consider activated charcoal (50g for an adult, 10-15g for a child under 5 years) if more than 10mg/kg body weight of phenobarbital has been ingested within 1 hour, provided the airway can be protected. Repeat dose activated charcoal is the best method of enhancing elimination of phenobarbital in symptomatic patients. In severe hypotension dopamine or dobutamine can be used. Treat rhabdomyolysis with urinary alkalinistion. Haemodialysis or haemofiltration may be required for cases of acute renal or severe hyperkalaemia.

Charcoal haemoperfusion is the treatment of choice for the majority of patients with severe barbiturate poisoning who fail to improve, or who deteriorate despite good supportive care.

Pharmacological properties

5.1 Pharmacodynamic properties

Phenobarbital is a long-acting barbiturate, which because of its depressant effect on the motor cortex, is used in the treatment of epilepsy.

Phenobarbital has a widespread depressant action on cerebral function. It has sedative effects and has some protective action against all varieties of human partial and generalised epilepsy, with the exception of absence seizures. Phenobarbital is also effective in preventing seizures in the corresponding experimental animal models of epilepsy. In different studies phenobarbital appears to have had inconsistent effects in suppressing experimental epileptic foci, and epileptic after-discharges, but it inhibits synaptic transmission, at least in the spinal cord. The drug’s probable biochemical mechanism of action is through prolonging the opening time of Cl^– ion channels in postsynaptic neuronal membranes. This effect causes membrane hyperpolarisation and thus impairs nerve impulse propagation. Phenobarbital also decreases intraneuronal Na⁺ concentrations, and inhibits Ca²⁺influx into depolarised synaptosomes. It raises brain serotonin levels, and inhibits noradrenaline (norepinephrine) reuptake into synaptosomes. These additional biochemical actions may contribute towards the anticonvulsant effects of the drug.

5.2 Pharmacokinetic properties

Absorption – phenobarbital is readily absorbed from the gastrointestinal tract, although it is relatively lipid – insoluble; peak concentrations are reached in about 2 hours after oral administration.

Distribution – phenobarbital is about 45 to 60% bound to plasma proteins. Phenobarbital crosses the placental barrier and is distributed into breast milk.

Metabolism – the plasma half-life is about 75 to 120 hours in adults but is greatly prolonged in neonates, and shorter (about 21 to 75 hours) in children. There is considerable interindividual variation in phenobarbital kinetics. Phenobarbital in only partly metabolised in the liver.

Elimination – about 25% of a dose is excreted in the urine unchanged at normal urinary pH.

5.3 Preclinical safety data

There is no preclinical safety data of relevance to a prescriber which is additional to that already included in other sections of the SPC.

Pharmaceutical particulars

6.1 List of excipients

Lactose, Starch, Talc, Stearic Acid

6.2 Incompatibilities

None known.

6.3 Shelf life

18 months.

6.4 Special precautions for storage

Store below 25°C. Keep the blister in the outer carton in order to protect from light.

6.5 Nature and contents of container

The product may be supplied in blister packs.

(i) 250µm white rigid PVC.

(ii) 20µm aluminium foil.

Pack size: 28 tablets.

6.6 Special precautions for disposal and other handling

No specific instructions. All medicines should be stored out of the reach of children.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Phenobarbital Tablets USP 15mg/30mg/60mg Taj Pharma

Read all of this leaflet carefully before you start taking this medicine.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

Index

1 What Phenobarbital tablets are and what they are used for

2 Before you take

3 How to take

4 Possible side effects

5 How to store

6 Further information

1 What Phenobarbital tablets are and what they are used for

Phenobarbital tablets belong to a group of medicines called

barbiturates. These medicines reduce brain activity which would otherwise cause fits or seizures in epilepsy, except absence seizures (day dreaming).

2 Before you take

Do not take Phenobarbital tablets and tell your doctor if you have:

an allergy (hypersensitivity) to phenobarbital, other barbiturates or any of the other ingredients (see section 6)
porphyria (a genetic or inherited disorder of the red blood pigment haemoglobin)
severe breathing difficulties
severe kidney or liver

If you develop a rash or the following skin symptoms, seek immediate advice from a doctor and tell that you are taking this medicine:

potentially life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported with the use of Phenobarbital tablets appearing initially as reddish target-like spots or circular patches often with central blisters on the trunk. Additional signs to look for include ulcers in the

mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes). These potentially life-threatening skin rashes are often accompanied by flu-like symptoms. The rash may progress to widespread blistering or peeling of the skin. The highest risk for occurrence of serious skin reactions is within the first weeks of treatment.

If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis with the use of Phenobarbital tablets you must not be re-started on Phenobarbital tablets at any time.

Check with your doctor or pharmacist before taking Phenobarbital tablets if you:

or the person taking these tablets are young, run down, senile

or have a history of drug abuse or alcoholism

have kidney or liver problems
have breathing difficulties
have severe or long term pain.

A small number of people being treated with anti-epileptics such as Phenobarbital have had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Especially:

disopyramide and quinidine (to treat irregular heartbeats)
chloramphenicol, doxycycline, metronidazole, rifampicin, telithromycin, griseofluvin, itraconazole, posaconazole, voriconazole. abacavir, amprenavir, lopinavir, indinavir, darunavir, nelfinavir and saquinavir (to treat infections)
medicines used to thin the blood such as warfarin
mianserin, paroxetine, MAOI or tricyclic antidepressants or St Johns’s wort (Hypericum perforatum) a herbal remedy (to treat depression)
oxcarbazepine, primidone, phenytoin, sodium valproate, carbamazepine, lamotrigine, tiagabine, zonisamide, ethosuxamide and vigabatrin (to treat epilepsy)
chlorpromazine, thioridazine, haloperidol, aripiprazole and clonazepam (to treat mental illness)
felodipine, verapamil, diltiazem, nimodipine, nifedipine, metoprolol, timolol and propranolol (to treat high blood pressure)
digitoxin or eplerenone (to treat certain heart conditions)
ciclosporin or tacrolimus (to prevent organ transplant rejection)
steroids such as hydrocortisone or prednisolone
folic acid or vitamin D (supplements)
toremifene, gestrinone, irinotecan or etoposide (to treat some cancers)
methadone (used in severe pain or drug addiction)
oral contraceptives (talk to your doctor about the best method of contraception for you) or tibolone (female hormone)
levothyroxine (thyroid hormone)
montelukast or theophylline (to treat asthma)
tropisetron and aprepitant (to treat nausea and vomiting)
memantine (to treat dementia)
methylphenidate (to treat attention deficit disorder)
sodium oxybate (to treat narcolepsy).

Pregnancy and breast-feeding

Your doctor should discuss the possible effects of Phenobarbital tablets on the unborn child and the risks and benefits of treatment should be considered carefully.

Check with your doctor before taking folic acid supplements as they interact with Phenobarbital tablets, your doctor may need to adjust your dose.

If you are taking Phenobarbital tablets, do not breastfeed, as the medicine will pass into the breast milk and may harm the baby.

Driving and using machines

Phenobarbital tablets may make you feel less alert than normal. Make sure you are not affected before driving or operating machinery.

Sugar intolerance

If you have been told you have an intolerance to some sugars, contact your doctor before taking this medicine, as it contains a type of sugar called lactose.

Tests

If you see another doctor or go into hospital or need a blood or urine test, let them know what medicines you are taking as Phenobarbital tablets may interfere with the results.

3 How to take

Always take Phenobarbital tablets exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

You are advised not to drink alcohol, check with your doctor if you have any questions.

Swallow the tablets with water at the same time each day. Doses:

Adults: 60mg-180mg at night.
Children: 5mg-8mg per kg of bodyweight a day.
Elderly: your doctor may prescribe a lower dose.

If you take more than you should

If you (or someone else) swallow a lot of tablets at the same time, or you think a child may have swallowed any, contact your nearest hospital casualty department or tell your doctor immediately. Signs of an overdose include drowsiness, speech problems, jerky movements, jerky eye movements, loss of inhibition, reduced reflex response, low body temperature, low blood pressure and breathing problems.

If you forget to take the tablets

Do not take a double dose to make up for a forgotten dose. If you forget to take a dose take it as soon as you remember it and then take the next dose at the right time.

If you stop taking the tablets

If you stop taking the tablets you may develop withdrawal effects such as sleeplessness, anxiety, tremor, dizziness, feeling sick, fits and delirium.

4 Possible side effects

Like all medicines, Phenobarbital tablets can cause side effects, although not everybody gets them.

Tell your doctor if you notice any of the following side effects or notice any other effects not listed:

Allergic reaction: skin rash, fever, swelling of the face, lips, tongue or throat, or difficulty breathing or swallowing.

Blood: altered numbers and types of blood cells, if you notice increased bruising, nosebleeds, sore throats or infections, you should tell your doctor who may want to perform a blood test.

Muscle, bone and connective tissue: Problems with inflammation of tendons (e.g. Dupuytren’s contracture of the hand, frozen shoulder), joint pain (arthralgia), bone softening and bone disease. There have been reports of bone disorders including osteopenia and osteoporosis (thinning of the bone) and fractures. Check with your doctor or pharmacist if you are on long-term antiepileptic medication, have a history of osteoporosis, or take steroids.
Reproductive system: scar tissue formation in the penis that can cause various penis problems (Peyronie’s disease of the penis)
Mental health: restlessness and confusion in the elderly, unusual excitement, depression, memory impairment, hallucinations.
Nervous system: hyperactivity, behavioural disturbances in children, jerky movements, jerky eye movements, drowsiness, lethargy.
Heart: low blood pressure.
Lungs: difficulty breathing.
Liver: inflammation of the liver (hepatitis), damaged bile system (cholestasis). Seen as yellowing of skin and whites of eyes.
Kidneys: changes in the amount or need to pass water.
Skin: rashes, erythema multiforme (circular, irregular red patches), lumps in the armpits or groin area. Potentially life-threatening skin rashes (Stevens-Johnson syndrome – severe skin rash with flushing, fever, blisters or ulcers and toxic epidermal necrolysis – severe rash involving reddening, peeling and swelling of the skin that resembles severe burns) have been reported very rarely (see section 2).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

By reporting side affects you can help provide more information on the safety of this medicine.

5 How to store

Keep out of the sight and reach of children. Stored below 25°C in a dry place.

Do not use Phenobarbital tablets after the expiry date stated on the label/carton/bottle. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6 Further information

What Phenobarbital tablets contain

The active substance (the ingredient that makes the tablet work) is phenobarbital. Each tablet contains either 30mg or 60mg of the active substance.
The other ingredients are lactose, magnesium stearate, maize starch.

What Phenobarbital tablets look like and contents of the pack

Phenobarbital tablets are white, uncoated tablets.