Carbinib

DIAMOX Tablets are for oral administration.

Acteazolamide is an enzyme inhibitor which acts specifically on carbonic anhydrase. It is indicated in the treatment of:

i) Glaucoma: DIAMOX Tablets is useful in glaucoma (chronic simple (open angle) glaucoma, secondary glaucoma, and perioperatively in acute angle closure glaucoma where delay of surgery is desired in order to lower intraocular pressure) because it acts on inflow, decreasing the amount of aqueous secretion.

ii) Abnormal retention of fluids: DIAMOX Tablets is a diuretic whose effect is due to the effect on the reversible hydration of carbon dioxide and dehydration of carbonic acid reaction in the kidney. The result is renal loss of HC0^3- ion which carries out sodium, water and potassium. DIAMOX Tablets can be used in conjunction with other diuretics when effects on several segments of the nepbron are desirable in the treatment of fluid retaining states.

iii) Epilepsy: In conjunction with other anticonvulsants best results with DIAMOX Tablets have been seen in petit mal in children. Good results, however, have been seen in patients, both children and adults, with other types of seizures such as grand mal, mixed seizure patterns, myoclonic jerk patterns etc.

i) Glaucoma (simple acute congestive and secondary):

Adults: 250 - 1,000mg (1-4 tablets) per 24 hours, usually in divided doses for amounts over 250mg daily.

ii) Abnormal retention of fluid: Congestive heart failure, drug-induced oedema.

Adults: For diuresis, the starting dose is usually 250 - 375mg (1-1½ tablets) once daily in the morning. If, after an initial response, the patient fails to continue to lose oedema fluid, do not increase the dose but allow for kidney recovery by omitting a day. Best results are often obtained on a regime of 250 - 375mg (1-1½ tablets) daily for two days, rest a day, and repeat, or merely giving the DIAMOX tablets every other day. The use of DIAMOX tablets does not eliminate the need for other therapy, eg. digitalis, bed rest and salt restriction in congestive heart failure and proper supplementation with elements such as potassium in drug-induced oedema.

For cases of fluid retention associated with pre-menstrual tension, a daily dose (single) of 125 - 375mg is suggested.

iii) Epilepsy:

The change from other medication to DIAMOX tablets should be gradual.

Elderly: DIAMOX tablets should only be used with particular caution in elderly patients or those with potential obstruction in the urinary tract or with disorders rendering their electrolyte balance precarious or with liver dysfunction.

Carbinib is contra-indicated in situations in which sodium and/or potassium blood levels are depressed, in cases of marked kidney and liver disease or dysfunction, suprarenal gland failure, and hyperchloremic acidosis. DIAMOX tablets should not be used in patients with hepatic cirrhosis as this may increase the risk of hepatic encephalopathy.

Long-term administration of DIAMOX tablets is contra-indicated in patients with chronic non-congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.

DIAMOX tablets should not be used in patients hypersensitive to sulphonamides.

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also 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 Carbinib.

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.

Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paraesthesia.

Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.

When DIAMOX tablets is prescribed for long-term therapy, special precautions are advisable. The patient should be cautioned to report any unusual skin rash. Periodic blood cell counts and electrolyte levels are recommended. Fatalities have occurred, although rarely, due to severe reactions to sulphonamides. A precipitous drop in formed blood cell elements or the appearance of toxic skin manifestations should call for immediate cessation of DIAMOX tablets therapy.

In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, DIAMOX tablets may aggravate acidosis and should be used with caution.

In patients with a past history of renal calculi, benefit should be balanced against the risks of precipitating further calculi.

The occurrence at the treatment initiation of a feverish generalized erythema associated with pustula may be a symptom of acute generalised exanthematous pustulosis (AGEP). In case of AGEP diagnosis, Carbinib should be discontinued and any subsequent administration of Carbinib contraindicated.

Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paraesthesia. Less commonly, fatigue, dizziness and ataxia have been reported. Disorientation has been observed in a few patients with oedema due to hepatic cirrhosis. Such cases should be under close supervision. Transient myopia has been reported.

These conditions invariably subside upon diminution or discontinuance of the medication.

Adverse reactions during short-term therapy are usually non-serious. Those effects which have been noted include: paraesthesia, particularly a “tingling” feeling in the extremities; some loss of appetite; taste disturbance, polyuria, flushing, thirst, headache, dizziness, fatigue, irritability, depression, reduced libido and occasional instances of drowsiness and confusion. Rarely, photosensitivity has been reported.

During long-term therapy, metabolic acidosis and electrolyte imbalance may occasionally occur. This can usually be corrected by the administration of bicarbonate.

Transient myopia has been reported. This condition invariably subsides upon diminution or withdrawal of the medication.

Gastrointestinal disturbances such as nausea, vomiting and diarrhoea.

Carbinib is a sulphonamide derivative and therefore some side-effects similar to those caused by sulphonamides have occasionally been reported. These include fever, agranulocytosis, thrombocytopenia, thrombocytic purpura, leukopenia, and aplastic anaemia, bone marrow depression, pancytopenia, rash (including erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis), anaphylaxis, crystalluria, calculus formation, renal and ureteral colic, and renal lesions. Rarely, fulminant hepatic necrosis has been reported.

Other occasional adverse reactions include: urticaria, melaena, haematuria, glycosuria, impaired hearing and tinnitus, abnormal liver function, renal failure and rarely, hepatitis or cholestatic jaundice, flaccid paralysis, and convulsions.

Skin and subcutaneous tissue disorders

Not known: acute generalised exanthematous pustulosis (AGEP)

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

No specific antidote. Supportive measures with correction of electrolyte and fluid balance. Force fluids.

Pharmacotherapeutic group: Carbonic anhydrase inhibitors.

ATC Code: S01EC01

Carbinib is an inhibitor of carbonic anhydrase. By inhibiting the reaction catalysed by this enzyme in the renal tubules, Carbinib increases the excretion of bicarbonate and of cations, chiefly sodium and potassium, and so promotes alkaline diuresis.

Continuous administration of Carbinib is associated with metabolic acidosis and resultant loss of diuretic activity. Therefore, the effectiveness of Carbinib tablets in diuresis diminishes with continuous use.

By inhibiting carbonic anhydrase in the eye, Carbinib decreases intra-ocular pressure and is therefore useful in the treatment of glaucoma.

Carbinib is fairly rapidly absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 2 hours after administration by mouth. It has been estimated to have a plasma half-life of about 4 hours. It is tightly bound to carbonic anhydrase and accumulates in tissues containing this enzyme, particularly red blood cells and the renal cortex. It is also bound to plasma proteins. It is excreted unchanged in the urine; renal clearance being enhanced in alkaline urine.

Not applicable

None.

None.