MARCH 2001
Rivastigmine (ExelonÒ) 1.5 mg, 3 mg, 4.5 mg, 6 mg capsules 2 mg/2 mL solution Novartis
Pharmaceuticals
Rivastigmine, a selective, reversible, long-acting acetylcholinesterase inhibitor, is indicated for the treatment of mild-to-moderate dementia of the Alzheimer’s type. Rivastigmine
is associated with gastrointestinal side effects including nausea and
vomiting, anorexia, and weight loss. Cholinesterase inhibitors increase
gastric acid secretion due to increased cholinergic activity. Patients should be monitored for symptoms
of active or occult gastrointestinal bleeding, particularly patients with a
history of ulcer disease or those receiving concurrent NSAIDs. As a cholinesterase inhibitor, rivastigmine
is likely to exaggerate succinylcholine-type muscle relaxation during
anesthesia. Agents that increase
cholinergic activity may cause bradycardia.
Caution is recommended in patients with sick sinus syndrome or other
supraventricular conduction disorders.
Rivastigmine was not associated with an increased incidence of
cardiovascular adverse events, heart rate or blood pressure changes, or ECG
abnormalities in clinical trials.
Syncope occurred in 3% of rivastigmine-treated patients compared to 2%
of placebo-treated patients. Agents
that increase cholinergic activity may cause urinary obstruction, cause
seizures, or exacerbate asthma or chronic obstructive pulmonary disease. Rivastimine is classified in Pregnancy
Category B. FOOD-DRUG INTERACTION: Administration
with food is recommended to reduce gastrointestinal side effects. Rivastigmine
should be taken with food in divided doses in the morning and evening. The recommended starting dose is 1.5 mg
twice daily. If this dose is well
tolerated, the dose can be increased to 3 mg twice daily after a minimum of 2
weeks. Subsequent increases to 4.5 mg
twice daily and 6 mg twice daily should be attempted after 2 weeks at the
previous dose. If gastrointestinal
intolerance occurs, the patient should discontinue treatment for several
doses and then restart at the same or next lower dose level. If therapy has been interrupted for longer
than several days, treatment should be reinitiated at the lowest daily dose
and titrated back to maintenance dose to reduce the possibility of severe
vomiting. The maximum dose is 6 mg
twice daily (12 mg/day). The dosage of rivastigmine shown to be effective in
clinical trials is 6 to 12 mg/day, given as twice-daily dosing. Doses at the higher end of the range
appeared more effective. The oral
solution and capsules are interchangeable at equal doses. The syringe provided with the oral
solution should be used for measuring doses.
Each dose may be swallowed directly from the syringe or first mixed
with a small glass of water, cold fruit juice, or soda. When mixed with cold fruit juice or soda,
the mixture is stable at room temperature for up to 4 hours. Argatroban (AcovaÒ) 100 mg/mL sterile, nonpyrogenic
solution in 250 mg (2.5 mL) single-use amber vials Texas
Biotechnology Corporation/SmithKline Beecham
Argatroban, a synthetic, reversible direct thrombin inhibitor, is indicated for use as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). Additional uses include disseminated intravascular coagulation (DIC), as an adjunct to thrombolytic agents in the treatment of acute myocardial infarction, heparin-induced thrombosis syndrome, and stroke. For patients
with moderate hepatic impairment, an initial dose of 0.5 mcg/kg/min is
recommended, based on the approximately 4-fold decrease in argatroban
clearance compared to patients with normal hepatic function. The aPTT should be monitored closely and
the dosage adjusted as needed. Some sources have recommended argatroban
therapy be tapered rather than abruptly halted when it needs to be
discontinued. Prior to
initiating therapy, heparin therapy should be discontinued and a baseline
aPTT obtained. The recommended
initial dose for adult patients with HIT, and without hepatic impairment, is
2 mcg/kg/min, administered as a continuous infusion. The aPTT should be checked 2 hours after
initiation of therapy to confirm the aPTT is within the desired range, and
dosage adjustments made as necessary.
The dose can be adjusted as clinically indicated, but not to exceed 10
mcg/kg/min, until the steady-state aPTT is 1.5 to 3 times the initial
baseline (not to exceed 100 seconds). For patients
with moderate hepatic impairment, an initial dose of 0.5 mcg/kg/min is
recommended, based on the approximately 4-fold decrease in argatroban
clearance compared to patients with normal hepatic function. The aPTT should be monitored closely and
the dosage adjusted as needed. Some sources have recommended argatroban
therapy be tapered rather than abruptly halted when it needs to be
discontinued. Individuals
with a condition predisposing them to a bleed should also be assessed for the
benefit of therapy with argatroban and be closely monitored (e.g., duodenal
and gastric ulcers, history of a recent operative or invasive procedure, renal
insufficiency, sub-acute bacterial endocarditis, or thrombocytopenia). When argatroban therapy needs to be
discontinued, some sources have recommended tapering the dose instead of
abruptly discontinuing the drug.
Abrupt discontinuation may lead to a hypercoagulable state since some
patients have shown an increase in concentration of thrombin-antithrombin III
complex within 2 hours of discontinuation of the argatroban infusion. In patients with hepatic impairment,
therapy should be initiated at a lower dose and carefully titrated. Upon discontinuation of therapy, full
reversal of anticoagulant effects may require longer than 4 hours due to
decreased clearance. The side
effects reported with argatroban include hypotension, fever, diarrhea,
ventricular tachycardia, vomiting, bleeding, hemorrhage, dizziness, headache,
injection site reactions, nausea, pain, rash, and rebound anginal
symptoms. In addition, increases in
serum transaminases have been reported. Hemorrhagic adverse events and
non-hemorrhagic adverse events occurred more frequently with argatroban than
placebo in premarketing studies. Allergic reactions were reported in 156
patients receiving argatroban in other studies. Approximately 95% of these reactions occurred in patients
receiving concomitant streptokinase and/or contrast media. Concomitant use of argatroban with
antiplatelet agents, thrombolytics, and other anticoagulants may increase the
risk of bleeding. When argatroban is initiated after cessation of
heparin therapy, sufficient time for heparin’s effect on the aPTT to decrease
should be allowed prior to initiation of argatroban therapy. Pharmacokinetic
interactions between argatroban and warfarin have not been observed; however,
concomitant administration does result in prolongation of the PT and
INR. The combination of argatroban
and warfarin does not result in further reduction in vitamin K dependent
factor Xa activity than that which is seen with warfarin alone. Argatroban is classified in Pregnancy
Category B and is not compatible with nursing. Entacapone (ComtanÒ) 200 mg tablets Novartis
Pharmaceuticals
Entacapone, a selective and
reversible catechol-O-methyltransferase (COMT) inhibitor, is used as an
adjunct to levodopa therapy in the treatment of Parkinson’s Disease. This product has been approved for the
treatment of idiopathic Parkinson’s Disease as an adjunct to
levodopa/carbidopa therapy in patients who experience end-of-dose “wearing
off”. According to prescribing information, the most common
adverse events reported in pre-marketing development included
dyskinesia/hyperkinesia, nausea, urine discoloration, diarrhea, and abdominal
pain. Other significant adverse reactions include orthostatic hypertension,
hallucinations, and purpura. Serious
side effects that have been associated with dopaminergic therapy include
rhabdomyolysis, hyperpyrexia, confusion, and fibrotic complications. Patients should be advised that
brownish-orange or dark yellow urine discoloration may occur. Three basic mechanisms contribute to the drug interactions
associated with entacapone therapy. Potential drug interactions and their
management are summarized in the following table:
According to prescribing information,
one 200 mg tablet should be administered with each levodopa/carbidopa
dose. The maximum recommended dose is
8 times daily (1600 mg daily).
Because entacapone exhibits no antiparkinsonian effect itself, it
should always be administered in conjunction with levodopa/carbidopa. Entacapone may be administered with either
immediate or sustained-release levodopa/carbidopa formulations. Reduction of levodopa dose or extending
levodopa dosing intervals may be necessary.
Caution should be exercised in patients with hepatic insufficiency. Abrupt reduction or withdrawal of
entacapone may lead to the emergence of signs and symptoms of Parkinson’s
Disease, as well as hyperpyrexia and confusion resembling neuroleptic
malignant syndrome. The manufacturer
recommends withdrawing patients from entacapone therapy slowly. Entacapone is classified in Pregnancy
Category C and should only be administered during pregnancy if the potential
benefit outweighs the potential risk to the fetus. Caution should be
exercised when entacapone is administered to nursing mothers. FOOD-DRUG
INTERACTION: Food has no
effect on entacapone pharmacokinetics. Budesonide
Inhalation Suspension (Pulmicort RespulesÒ) 0.25 mg and
0.5 mg single dose ampules Astra
Pharmaceuticals Budesonide is an anti-inflammatory corticosteroid. Pulmicort RespulesÒ is an inhalation suspension indicated for administration via jet nebulizer in asthmatic patients 12 months to 8 years of age. The
most common adverse reactions experienced in clinical trials included:
respiratory infection, rhinitis, coughing, otitis media, viral infection,
gastroenteritis, vomiting, diarrhea, abdominal pain, ear infection, epistaxis, conjunctivitis, and rash. Reactions observed in 1% to 3% of patients in
clinical trials included: allergic reaction, chest pain, fatigue, flu-like
disorder, stridor, Herpes simplex, external ear infection, dysphonia,
hyperkinesias, eczema, pustular rash, pruritus, earache, eye infection,
anorexia, emotional lability, fracture, myalgia, purpura, and cervical
lymphadenopathy. The
frequency of adverse events does not increase when budesonide is administered
with other drugs that are commonly used to treat asthma. Coadministration of ketoconazole may
increase plasma levels of budesonide, although the clinical significance of
this interaction is not known. Pulmicort
RespulesÒ
is contraindicated as the primary treatment of status asthmaticus or other
acute episodes of asthma where intensive measures are required. Inhaled corticosteroids may be associated
with growth suppression when administered to pediatric patients. Suppression
of HPA function may occur when dosage recommendations are exceeded. Patients
should be observed carefully for any evidence of systemic corticosteroid
effects. Symptom
improvement can occur within 2-8 days of initiation of inhaled budesonide
treatment. Maximum benefit may not be
observed until 4-6 weeks after initial treatment. Once stability of symptoms has been achieved, administration
should be titrated down to the lowest effective dose. Refer to the following table from product
prescribing information for recommended dosing based on prior asthma therapy:
A
starting dose of 0.25 mg once daily may be considered for symptomatic
children not responding to non-steroidal therapy. In all patients, the total daily dose should be increased
and/or administered as a divided dose if adequate control of symptoms is not
achieved with once daily treatment.
Patients receiving chronic oral corticosteroids should continue to
take the usual maintenance dose of oral corticosteroid for approximately one
week after the initiation of inhaled budesonide therapy. At that time, gradual withdrawal of the
systemic corticosteroid may be initiated.
The manufacturer strongly recommends a slow rate of withdrawal. Budesonide is classified in Pregnancy category C and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised if budesonide is administered to nursing women. |
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