Purderal P 100 mg, 400 mg Tablets

PURDERAL P is indicated for the treatment of tuberculosis in combination with other antituberculosis medicines. Consideration should be given to the current local guidelines for treatment of tuberculosis.

Posology
In the treatment of tuberculosis, serum concentrations of 3 to 5 u03bcg per ml of ethambutol, as contained in PURDERAL P, are considered necessary and they are generally attained with a dose of 15 to 25 mg per kg body weight daily. A single dose of 25 mg per kg may be given for 2 months and thereafter reduced to 15 mg per kg. It has been suggested that tests of visual acuity should be regularly performed on patients being treated with ethambutol, as contained in PURDERAL P (see section 4.8).

Adult dose
The dosage must be adjusted according to the body mass of the patient - refer to the table of dosages.

For primary treatment
PURDERAL P should be administered in a single daily oral dose of 15 mg/kg with concomitant medicines being used at their recommended dosage levels.

For re-treatment
For the first 60 days of treatment, PURDERAL P should be administered in a single daily oral dose of 25 mg/kg. Thereafter the dosage should be reduced to 15 mg/kg with concomitant medicines being maintained at their recommended dosage levels.

Paediatric population
Daily doses for children above three months are 20 (15 to 25) mg/kg per body-weight daily. No dosing recommendation can be made in children less than three months due to the lack of specific data. PURDERAL P is not recommended for children under 13 years of age.

Method of administration
Examples of dosage and administration of PURDERAL P tablets are shown in the table below:

15 mg/kg schedule
25 mg/kg schedule
Mass range (kg) Total daily dosage (mg) Number of tablets 100mg 400mg Mass range (kg) Total daily dosage (mg) Number of tablets 100mg 400mg Under 37 500 1 1 Under 38 900 1 2 38 to 42,5 600 2 1 38 to 41,5 1 000 2 2 43 to 49,5 700 3 1 42 to 44,5 1 100 3 2 50 to 56,5 800 2 45 to 49,5 1 200 3 57 to 63,5 900 1 2 50 to 53,5 1 300 1 3 64 to 70,5 1 000 2 2 54 to 57,5 1 400 2 3 71 to 78,5 1 100 3 2 58 to 61,5 1 500 3 3 79 to 83,5 1 200 3 62 to 66,5 1 600 4 84 to 89,5 1 300 1 3 67 to 70,5 1 700 1 4 90 to 96,5 1 400 2 3 71 to 74,5 1 800 2 4 97 and over 1 500 3 3 75 to 78,5 1 900 3 4 79 to 82,5 2 000 5 83 to 86,5 2 100 1 5 87 to 90,5 2 200 2 5 91 to 94,5 2 300 3 5 95 to 98,5 2 400 6 99 and over 2 500 1 6

PURDERAL P is contraindicated in patients with:

• Hypersensitivity to ethambutol or to any of the excipients in PURDERAL P (see section 6.1).
• Severe renal impairment (creatinine clearance GFR < 30 mL/min).
• Optic neuritis and retrobulbar neuritis.

Consideration should be given to current local guidelines for the treatment of tuberculosis.

Optic neuritis
Ethambutol, as contained in PURDERAL P, can cause optic neuritis (ON), which may be unilateral or bilateral, and retrobulbar ON (normal appearing optic disc on presentation) is the most common form of ethambutol-induced optic neuritis (EON). EON is dose dependent with a prevalence ranging from < 1 % at u2264 15 mg/kg, to 5 % to 6 % at u2264 25 mg/kg. Other risk factors include patient on prolonged therapy, patients with renal impairment, the elderly and use with isoniazid. It is recommended that patients undergo a full ophthalmic examination before starting treatment. This should include visual acuity, colour vision, perimetry and ophthalmoscopy. Except for the high risk patients (see below), routine ophthalmological examination for adults is not thereafter necessary. Patients should be informed of the importance of reporting any change in vision and PURDERAL P should be withdrawn if vision deteriorates. For patients with risk factors for development of EON, frequent ophthalmologic examination is recommended. Each eye should be tested separately as ocular toxicity can be unilateral or bilateral. Ophthalmologic examination should include tests for black-white/chromatic visual acuity (e.g. Snellen eye chart and 65-test) and ophthalmoscopy. Routine ophthalmological examinations may be considered when treating young children.

Prognosis: The vision impairment (optic neuritis) is generally reversible when administration of ethambutol, as in PURDERAL P, is discontinued promptly. Studies have shown that the recovery of visual acuity took weeks to months after the ethambutol, as contained in PURDERAL P, was discontinued. Ethambutol, as contained in PURDERAL P, was restarted in some patients at lower doses without toxicity. Recovery may be delayed for up to one year or more or the effects may be irreversible.

Renal impairment and hyperuricemia
Renal function, including uric acid levels, should be checked before treatment with PURDERAL P and appropriate dosage adjustments made. PURDERAL P should preferably be avoided in patients with renal impairment and hyperuricemia, but if used the dose should be reduced. Toxic effects and hyperuricemia are more common if renal function is impaired. PURDERAL P therapy results in an increased concentration of urate in the blood in about 50 % of patients, due to decreased renal excretion of uric acid. The effects may be detectable as early as 24 hours after a single dose or as late as 90 days after treatment is started. This untoward effect is possibly enhanced by isoniazid and pyridoxine.

Excipients
Lactose
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take PURDERAL P.

Aluminum hydroxide
Aluminium hydroxide impairs the absorption of ethambutol. The results of a study of coadministration of ethambutol hydrochloride (50 mg/kg) with an aluminum hydroxide containing antacid to 13 patients with tuberculosis showed a reduction of mean serum concentrations and urinary excretion of ethambutol of approximately 20 % and 13 %, respectively, suggesting that the oral absorption of ethambutol may be reduced by these antacid products. It is recommended to avoid concurrent administration of PURDERAL P with aluminum hydroxide-containing antacids for at least 4 hours following PURDERAL P administration (see section 4.8).

Women of childbearing potential
There are no know adverse effects of ethambutol, as contained in PURDERAL P, on the reproductive potential of women of childbearing potential.

Pregnancy
The safety of PURDERAL P in pregnancy and lactation has not been established. The potential for risk in humans is unknown as there are no adequate and well controlled studies in pregnant women. Studies in animals have shown reproductive toxicity.

Breastfeeding
Ethambutol hydrochloride, as contained in PURDERAL P, is excreted into breast milk. Ethambutol/metabolites have been identified in breastfed newborns/ infants of treated women. Breastfeeding is not recommended during PURDERAL P treatment.

Fertility
No data available.

PURDERAL P has moderate influence on the ability to drive and operate machinery. Since adverse reactions such as visual disturbances have been reported in patients receiving PURDERAL P, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that PURDERAL P does not adversely affect their ability to do so (see section 4.4 and 4.8).

a) Summary of the safety profile
The most important side effect of ethambutol hydrochloride, as contained in PURDERAL P, is a dose dependant optic neuritis, resulting in decrease of visual acuity and loss of ability to perceive the colour green. This is quite uncommon (< 1 %) with a dose u2264 15 mg/kg per day, but increases to 5 % to 6 % with doses u2264 25 mg/kg per day.

b) Tabulated list of adverse reactions

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to: SAHPRA: https://www.sahpra.org.za/health-products-vigilance/ Aspen Pharmacare: E-mail: [email protected] Tel: 0800 118 088

Symptoms
The symptoms of overdosage are those stated under side effects above and in these cases the dosage should be reduced or the medicine discontinued.

Treatment
There is no specific antidote. Treatment is supportive and symptomatic.