A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Tasmar Indications, Dosage, Storage, Stability - Tolcapone
Tasmar Indications, Dosage, Storage, Stability - Tolcapone
INDICATIONS
TASMAR is indicated as an adjunct to levodopa and carbidopa for the treatment
of the signs and symptoms of idiopathic Parkinson’s disease. Because of
the risk of potentially fatal, acute fulminant liver failure, TASMAR (tolcapone)
should ordinarily be used in patients with Parkinson’s disease on levodopa/carbidopa
who are experiencing symptom fluctuations and are not responding satisfactorily
to or are not appropriate candidates for other adjunctive therapies. Because
of the risk of liver injury and because TASMAR, when it is effective,
provides an observable symptomatic benefit, the patient who fails to wshow
substantial clinical benefit within 3 weeks of initiation of treatment,
should be withdrawn from TASMAR.
The effectiveness of TASMAR was demonstrated in randomized controlled
trials in patients receiving concomitant levodopa therapy with carbidopa
or another aromatic amino acid decarboxylase inhibitor who experienced
end of dose wearing-off phenomena as well as in patients who did not experience
such phenomena (see CLINICAL PHARMACOLOGY:
Clinical Studies).
DOSAGE AND ADMINISTRATION
Because of the risk of potentially fatal, acute fulminant liver failure,
TASMAR (tolcapone) should ordinarily be used in patients with Parkinson’s
disease on levodopa/carbidopa who are experiencing symptom fluctuations
and are not responding satisfactorily to or are not appropriate candidates
for other adjunctive therapies (see INDICATIONS
section).
Because of the risk of liver injury and because TASMAR when it is effective
provides an observable symptomatic benefit, the patient who fails to wshow
substantial clinical benefit within 3 weeks of initiation of treatment,
should be withdrawn from TASMAR.
TASMAR therapy should not be initiated if the patient exhibits clinical
evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than
the upper limit of normal. Patients with severe dyskinesia or dystonia
should be treated with caution (see PRECAUTIONS:
Rhabdomyolysis).
Patients who develop evidence of hepatocellular injury while on TASMAR
and are withdrawn from the drug for any reason may be at increased risk
for liver injury if TASMAR is reintroduced. Accordingly, such patients
should not ordinarily be considered for retreatment.
Treatment with TASMAR should always be initiated at a dose of 100 mg
t.i.d., always as an adjunct to levodopa/carbidopa therapy. The recommended
daily dose of TASMAR is also 100 mg t.i.d. In clinical trials, elevations
in ALT occurred more frequently at the dose of 200 mg t.i.d. While it
is unknown whether the risk of acute fulminant liver failure is increased
at the 200-mg dose, it would be prudent to use 200 mg only if the anticipated
incremental clinical benefit is justified (see BOXED
WARNING, WARNINGS, PRECAUTIONS:
Laboratory Tests). If a patient fails to wshow the expected
incremental benefit on the 200-mg dose after a total of 3-weeks of treatment
(regardless of dose), TASMAR should be discontinued.
In clinical trials, the first dose of the day of TASMAR was always taken
together with the first dose of the day of levodopa/carbidopa, and the
subsequent doses of TASMAR were given approximately 6 and 12 hours later.
In clinical trials, the majority of patients required a decrease in their
daily levodopa dose if their daily dose of levodopa was > 600 mg or if
patients had moderate or severe dyskinesias before beginning treatment.
To optimize an individual patient’s response, reductions in daily levodopa
dose may be necessary. In clinical trials, the average reduction in daily
levodopa dose was about 30% in those patients requiring a levodopa dose
reduction.(Greater than 70% of patients with levodopa doses above 600
mg daily required such a reduction.)
TASMAR can be combined with both the immediate and sustained release
formulations of levodopa/carbidopa.
TASMAR may be taken with or without food(see CLINICAL
PHARMACOLOGY).
Patients With impaired Hepatic Function: TASMAR therapy
should not be initiated if any patient with liver disease or two SGPT/ALT
or SGOT/AST values greater than the upper limit of normal.(See BOXED
WARNING, WARNINGS, and
CLINICAL PHARMACOLOGY).
Patients With Impaired Renal Function: No dose adjustment
of TASMAR is recommended for patients with mild to moderate renal impairment.
However, patients with severe renal impairment should be treated with
caution. The safety of tolcapone has not been examined in subjects who
had creatinine clearance less than 25 mL/min (see CLINICAL
PHARMACOLOGY).
Withdrawing Patients From TASMAR: As with any dopaminergic
drug, withdrawal or abrupt reduction in the TASMAR dose may lead to emergence
of signs and symptoms of Parkinson’s disease or Hyperpyrexia and Confusion,
a syndrome complex resembling the neuroleptic malignant syndrome (see
PRECAUTIONS: Events Reported With
Dopaminergic Therapy). If a decision is made to discontinue treatment
with TASMAR, then it is recommended to closely monitor the patient and
adjust other dopaminergic treatments as needed. This syndrome should be
considered in the differential diagnosis for any patient who develops
a high fever or severe rigidity. Tapering TASMAR has not been systematically
evaluated. As the duration of COMT inhibition with TASMAR is generally
5 to 6 hours on average, decreasing the frequency of dosage to twice or
once a day may not in itself prevent withdrawal effects.
HOW SUPPLIED
TASMAR is supplied as film-coated tablets containing 100 mg or 200 mg
tolcapone. The 100 mg beige tablet and the 200 mg reddish-brown tablet
are hexagonal and biconvex. Imprinted with black ink on one side of the
tablet is TASMAR and the tablet strength (100 or 200), on the other side
is ROCHE.
TASMAR 100 mg Tablets: bottles of 90 (NDC 0004-5920-01).
TASMAR 200 mg Tablets: bottles of 90 (NDC 0004-5921-01).
Storage: Store at controlled room temperature 20° to 25°C
(68° to 77°F) in tight containers as defined in USP/NF
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