TEGRETOL

What it is

Tegretol contains carbamazepine and is available as tablets containing 100 mg or 200 mg of carbamazepine. Tegretol controlled release (CR) tablets contain 200 mg or 400 mg of carbamazepine, and Tegretol liquid contains 100 mg of carbamazepine per 5 mL.

Approved indications

— Complex or simple partial seizures (with or without loss of consciousness) with or without secondary generalisation. — Generalised tonic-clonic seizures. — Mixed seizure patterns incorporating partial and generalised tonic-clonic seizures. — Relief of pain in idiopathic trigeminal neuralgia and trigeminal neuralgia due to multiple sclerosis, and in idiopathic glossopharyngeal neuralgia. — Treatment of mania and maintenance treatment of bipolar affective disorders to prevent or attenuate recurrence.

Dosing overview

**Epilepsy:** For adults and children over 15 years, the initial dose is 100 to 200 mg once or twice daily, slowly raised until an optimum response is obtained, generally at 400 mg 2 or 3 times daily. In some patients, 1600 mg or even 2000 mg daily may be required in rare instances. Children aged 6 to 12 years should commence treatment with 100 mg daily in 2 divided doses, increasing by 100 mg per day at weekly intervals until optimal control is obtained, with dosage generally not exceeding 1000 mg daily. **Trigeminal neuralgia:** The recommended initial dose is 200 to 400 mg daily in 2 divided doses, increasing by 200 mg each day until pain relief is obtained, usually achieved with doses up to 800 mg daily. The maximum dose should not exceed 1200 mg daily. **Mania and bipolar affective disorder:** The dosage range is 400–1600 mg daily. When used alone in mania the starting dose should be 200–400 mg daily in 2 divided doses, increased to 800–1000 mg during the first week and up to 1600 mg if no response is found after a second week.

Key safety warnings

Serious dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported very rarely with Tegretol. Patients with these reactions may require hospitalisation, as these conditions may be life-threatening and fatal. Most SJS/TEN cases appear in the first few months of treatment. Testing for the presence of HLA-A*3101 allele should be considered in patients with ancestry in genetically at-risk populations prior to initiating treatment with Tegretol. The use of Tegretol should be avoided in patients found to be positive for HLA-A*3101 unless the benefits clearly outweigh the risks. A strong correlation exists between SJS/TEN skin reactions and the presence of the HLA-B*1502 allele in patients of Han Chinese and Thai origin. Testing should be considered in patients with ancestry in genetically at-risk populations, and the use of Tegretol should be avoided in tested patients who are positive for HLA-B*1502 unless benefits clearly outweigh the risks. Aplastic anaemia and agranulocytosis (in some cases fatal) have been reported in association with the use of Tegretol, although due to the very low incidence of these conditions, meaningful risk estimates are difficult to obtain. Complete blood counts, including platelets, should be obtained before treatment and periodically thereafter. If definitely low or decreased white blood cell or platelet counts are observed, the patient and the complete blood count should be monitored closely, and Tegretol should be discontinued if any evidence of significant bone-marrow depression appears. Antiepileptic drugs, including carbamazepine, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication. Patients treated with any antiepileptic drug for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and any unusual changes in mood or behaviour. Hyponatraemia is known to occur with carbamazepine. In patients with pre-existing renal conditions associated with low sodium or in patients treated concomitantly with sodium-lowering medicinal products, serum sodium levels should be measured prior to initiating carbamazepine therapy and after approximately two weeks and then at monthly intervals for the first three months during therapy.

Contraindications

Tegretol is contraindicated in patients with known hypersensitivity to carbamazepine or structurally related drugs (such as tricyclic antidepressants), atrioventricular block, systemic lupus erythematosus, history of hepatic porphyrias, and history of bone marrow depression. Because it is structurally related to tricyclic antidepressants, the use of Tegretol is contraindicated in combination with monoamine-oxidase inhibitors. Before administering Tegretol, MAOIs should be discontinued for a minimum of 2 weeks. Tegretol is contraindicated in hepatic failure as metabolism occurs in the liver. Tegretol is contraindicated in neonates below 4 weeks of age.

PBS listing

Tegretol tablet 100 mg is listed on the PBS with 3 items, restriction type restricted/unrestricted, at an ex-manufacturer price of A$6.98. Tegretol tablet 200 mg is listed with 3 items, restriction type restricted/unrestricted, at an ex-manufacturer price of A$10.24. Tegretol CR tablet 200 mg is listed with 3 items, restriction type unrestricted/restricted, at an ex-manufacturer price of A$8.27. Tegretol CR tablet 400 mg is listed with 3 items, restriction type unrestricted/restricted, at an ex-manufacturer price of A$15.71. Tegretol oral suspension 100 mg per 5 mL (300 mL) is listed with 3 items, restriction type restricted/unrestricted, at an ex-manufacturer price of A$12.07.

Regulatory history

Tegretol 200 mg tablet in bottle form was first listed on the ARTG on 2 August 1991. Tegretol 200 mg and 100 mg tablets in blister pack form, and Tegretol CR 200 mg and 400 mg tablets, were first listed on the ARTG in 1992 and 1993 respectively. Tegretol liquid (carbamazepine 20 mg/mL) was first listed on the ARTG on 26 March 1997.