Posology : מינונים

4.2 Posology and method of administration
Dosage with single and daily doses:
An ECG (50 mm/s) should be recorded before and 1 and 3 weeks after commencing treatment and the Bazett frequency-corrected QT time (QTc) determined manually. Such an ECG should also be recorded before and 2 weeks after any subsequent increase in dose. Further ECG check-ups should then take place at least once a year. Treatment must be avoided or discontinued in patients who show baseline QTc values above 420 ms, an increase of more than 60 ms during treatment with PK-Merz infusion, or a QTc time in excess of 480 ms during treatment with PK-Merz infusion, and in patients who show discernible U waves.
By following the above precautions and taking the contraindications listed in section 4.3 into account, the very rare, but life-threatening the undesirable effect of Torsades-de-Pointes can be prevented.


Parkinson’s syndromes:
In the event of an acute exacerbation in parkinsonian symptoms in the sense of an akinetic crisis, intravenous doses of 200 mg amantadine sulphate in 500 ml of solution should be administered 1-3 times a day.

The rate of infusion should not exceed 55 drops/min, equivalent to an infusion time of approximately 3 hours.

Decreased vigilance:


To improve vigilance in post-comatose states of varying aetiology, a therapy with a daily dose of 200 mg amantadine sulphate given as a slow infusion (> 3 hours) can be tried for an initial period of 3-5 days. Depending on the clinical course, treatment can then be continued – if possible with oral dosage forms - for up to 4 weeks at a dose of 200 mg amantadine sulphate per day.


Dosage in patients with renal impairment:
In patients with renal impairment the dosage must be tailored according to the extent of the decrease in renal clearance (measured as the glomerular filtration rate: GFR), as shown in the following table: GFR                                                 Dosage                                        Dosing interval [ml/min]                                            (amantadine sulfate 200 mg/500 ml)
80-60                                               100 mg                                        every 12 hours 60-50                                               200 mg and 100 mg                             on alternate days 50-30                                               100 mg                                        once daily 30-20                                               200 mg                                        twice a week 20-10                                               100 mg                                        three times a week
< 10 and haemodialysis                              200 mg and 100 mg                             once a week or once every two weeks


The glomerular filtration rate (GFR) can be estimated according to the following approximation: 

(140 – age)  weight
Clcr =
72  creatinine where:
Clcr = creatinine clearance in ml/min and creatinine = serum creatinine in mg/100 ml.
The creatinine clearance calculated according to this expression applies to men only, the corresponding value in women is approximately 85% of this value and can be equated to the inulin clearance for determination of the GFR (120 ml/min in adults).
Amantadine is dialyzed only slightly (approx. 5%).


Method and duration of administration:
Intravenous use:
Abrupt discontinuation of PK-Merz infusion must be avoided, as Parkinson patients may otherwise experience a severe intensification in extrapyramidal symptoms sometimes including akinetic crisis, and duration effects sometimes including delirium can occur.
The duration of use when continuing treatment with oral dosage forms, in patients with decreased vigilance, (See section 4.1 and 4.2) should not exceed 4 weeks.
Children:
There has been insufficient experience in children.