 DESCRIPTION:
Ocupress® (carteolol hydrochloride) Ophthalmic Solution, 1%, is a
nonselective beta-adrenoceptor blocking agent for ophthalmic use.
The chemical name for carteolol hydrochloride is
(±)-5-[3-[(1,1-dimethylethyl) amino]-2 hydroxypropoxy]ð3,
4ðdihydroð2(1H)ðquinolinone monohydrochloride. The structural formula
is as shown above:
Each mL contains 10 mg carteolol HCl and the inactive ingredients ð
Benzalkonium chloride 0.05 mg (0.005%) as a preservative; sodium
chloride; sodium phosphate, dibasic; sodium phosphate, monobasic; and
water for injection, USP. The product has a pH of 6.2 to 7.2
CLINICAL PHARMACOLOGY: Carteolol HCl is a nonselective beta-adrenergic
blocking agent with associated intrinsic sympathomimetic activity and
without significant membrane-stabilizing activity. Ocupress (carteolol
HCl) reduces normal and elevated intraocular pressure (IOP) whether or
not accompanied by glaucoma. The exact mechanism of the ocular
hypotensive effect of beta-blockers has not been definitely
demonstrated. In general, beta-adrenergic blockers reduce cardiac
output in patients in good and poor cardiovascular health. In patients
with severe impairment of myocardial function, beta-blockers may
inhibit the sympathetic stimulation necessary to maintain adequate
cardiac function. Beta-adrenergic blockers may also increase airway
resistance in the bronchi and bronchioles due to unopposed
parasympathetic activity. Given topically twice daily in controlled
domestic clinical trials ranging from 1.5 to 3 months, Ocupress
produced a median percent reduction of IOP 22% to 25%. No significant
effects were noted on corneal sensitivity, tear secretion, or pupil
size.
INDICATIONS AND USAGE: Ocupress Ophthalmic Solution, 1%, has
been shown to be effective in lowering intraocular pressure and may be
used in patients with chronic open-angle glaucoma and intraocular
hypertension. It may be used alone or in combination with other
intraocular pressure lowering medications.
CONTRAINDICATIONS: Ocupress Ophthalmic Solution is
contraindicated in those individuals with bronchial asthma or with a
history of bronchial asthma, or severe chronic obstructive pulmonary
disease (see WARNINGS); sinus bradycardia; second- and third-degree
atrioventricular block; overt cardiac failure (see WARNINGS);
cardiogenic shock; or hypersensitivity to any component of this
product.
WARNINGS: Ocupress Ophthalmic Solution has not been detected in
plasma following ocular instillation. However, as with other topically
applied ophthalmic preparations, Ocupress may be absorbed
systemically. The same adverse reactions found with systemic
administration of beta-adrenergic blocking agents may occur with
topical administration. For example, severe respiratory reactions and
cardiac reactions, including death due to bronchospasm in patients
with asthma, and rarely death in association with cardiac failure,
have been reported with topical application of beta-adrenergic
blocking agents (see CONTRAINDICATIONS).
Cardiac Failure: Sympathetic stimulation may be essential for
support of the circulation in individuals with diminished myocardial
contractility, and its inhibition by beta-adrenergic receptor blockade
may precipitate more severe failure.
In Patients Without a History of Cardiac Failure: Continued
depression of the myocardium with beta-blocking agents over a period
of time can, in some cases, lead to cardiac failure. At the first sign
or symptom of cardiac failure, Ocupress should be discontinued.
Non-allergic Bronchospasm: In patients with non-allergic
bronchospasm or with a history of non-allergic bronchospasm (e.g.,
chronic bronchitis, emphysema), Ocupress should be administered with
caution since it may block bronchodilation produced by endogenous and
exogenous catecholamine stimulation of beta2 receptors.
Major Surgery: The necessity or desirability of withdrawal of
beta-adrenergic blocking agents prior to major surgery is
controversial. Beta-adrenergic receptor blockade impairs the ability
of the heart to respond to beta-adrenergically mediated reflex
stimuli. This may augment the risk of general anesthesia in surgical
procedures. Some patients receiving beta-adrenergic receptor blocking
agents have been subject to protracted severe hypotension during
anesthesia. For these reasons, in patients undergoing elective
surgery, gradual withdrawal of beta-adrenergic receptor blocking
agents may be appropriate. If necessary during surgery, the effects of
beta-adrenergic blocking agents may be reversed by sufficient doses of
such agonists as isoproterenol, dopamine, dobutamine or levarterenol
(see OVERDOSAGE).
Diabetes Mellitus: Beta-adrenergic blocking agents should be
administered with caution in patients subject to spontaneous
hypoglycemia or to diabetic patients (especially those with labile
diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic
receptor blocking agents may mask the signs and symptoms of acute
hypoglycemia.
Thyrotoxicosis: Beta-adrenergic blocking agents may mask
certain clinical signs (e.g., tachycardia) of hyperthyroidism.
Patients suspected of developing thyrotoxicosis should be managed
carefully to avoid abrupt withdrawal of beta-adrenergic blocking
agents which might precipitate a thyroid storm.
PRECAUTIONS:
General: Ocupress Ophthalmic Solution should be used with caution in
patients with known hypersensitivity to other beta-adrenoceptor
blocking agents.
Use with caution in patients with known diminished pulmonary function.
In patients with angle-closure glaucoma, the immediate objective of
treatment is to reopen the angle. This requires constricting the pupil
with a miotic. Ocupress has little or no effect on the pupil. When
Ocupress is used to reduce elevated intraocular pressure in
angle-closure glaucoma, it should be used with a miotic and not alone.
Information to the Patient: For topical use only. To prevent
contaminating the dropper tip and solution, care should be taken not
to touch the eyelids or surrounding areas with the dropper tip of the
bottle. Keep bottle tightly closed when not in use. Protect from
light.
Risk from Anaphylactic Reaction: While taking beta-blockers, patients
with a history of atopy or a history of severe anaphylactic reaction
to a variety of allergens may be more reactive to repeated accidental,
diagnostic, or therapeutic challenge with such allergens. Such
patients may be unresponsive to the usual doses of epinephrine used to
treat anaphylactic reactions.
Muscle Weakness: Beta-adrenergic blockade has been reported to
potentiate muscle weakness consistent with certain myasthenic symptoms
(e.g., diplopia, ptosis and generalized weakness).
Drug Interactions: Ocupress should be used with caution in
patients who are receiving a beta-adrenergic blocking agent orally,
because of the potential for additive effects on systemic
beta-blockade.
Close observation of the patient is recommended when a beta-blocker is
administered to patients receiving catecholamine-depleting drugs such
as reserpine, because of possible additive effects and the production
of hypotension and/or marked bradycardia, which may produce vertigo,
syncope, or postural hypotension.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carteolol
hydrochloride did not produce carcinogenic effects at doses up to 40
mg/kg/day in two-year oral rat and mouse studies. Tests of
mutagenicity, including the Ames Test, recombinant (rec)-assay, in
vivo cytogenetics and dominant lethal assay demonstrated no evidence
for mutagenic potential. Fertility of male and female rats and male
and female mice was unaffected by administration of carteolol
hydrochloride dosages up to 150 mg/kg/day.
Pregnancy: Teratogenic Effects: Pregnancy Category C: Carteolol
hydrochloride increased resorptions and decreased fetal weights in
rabbits and rats at maternally toxic doses approximately 1052 and 5264
times the maximum recommended human oral dose (10 mg/70 kg/day),
respectively. A dose-related increase in wavy ribs was noted in the
developing rat fetus when pregnant females received daily doses of
approximately 212 times the maximum recommended human oral dose. No
such effects were noted in pregnant mice subjected to up to 1052 times
the maximum recommended human oral dose. There are no adequate and
well-controlled studies in pregnant women. Ocupress (carteolol
hydrochloride) should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
Nursing Mothers: It is not known whether this drug is excreted
in human milk, although in animal studies carteolol has been shown to
be excreted in breast milk. Caution should be exercised when Ocupress
is administered to nursing mothers.
Pediatric Use: Safety and effectiveness in pediatric patients
have not been established.
ADVERSE REACTIONS: The following adverse reactions have been
reported in clinical trials with Ocupress Ophthalmic Solution:
Ocular: Transient eye irritation, burning, tearing,
conjunctival hyperemia and edema occurred in about 1 of 4 patients.
Ocular symptoms including blurred and cloudy vision, photophobia,
decreased night vision, and ptosis and ocular signs including
blepharoconjunctivitis, abnormal corneal staining, and corneal
sensitivity occurred occasionally.
Systemic: As is characteristic of nonselective adrenergic
blocking agents, Ocupress may cause bradycardia and decreased blood
pressure (see WARNINGS). The following systemic events have
occasionally been reported with the use of Ocupress: cardiac
arrhythmia, heart palpitation, dyspnea, asthenia, headache, dizziness,
insomnia, sinusitis, and taste perversion. The following additional
adverse reactions have been reported with ophthalmic use of beta1 and
beta2 (nonselective) adrenergic receptor blocking agents:
Body As a Whole: Headache
Cardiovascular: Arrhythmia, syncope, heart block, cerebral
vascular accident, cerebral ischemia, congestive heart failure,
palpitation (see WARNINGS). Digestive: Nausea
Psychiatric: Depression
Skin: Hypersensitivity, including localized and generalized
rash
Respiratory: Bronchospasm (predominantly in patients with
pre-existing bronchospastic disease), respiratory failure (see
WARNINGS)
Endocrine: Masked symptoms of hypoglycemia in insulin-dependent
diabetics (see WARNINGS)
Special Senses: Signs and symptoms of keratitis, blepharoptosis,
visual disturbances including refractive changes (due to withdrawal of
miotic therapy in some cases), diplopia, ptosis. Other reactions
associated with the oral use of nonselective adrenergic receptor
blocking agents should be considered potential effects with ophthalmic
use of these agents.
OVERDOSAGE: No specific information on emergency treatment of
overdosage in humans is available. Should accidental ocular overdosage
occur, flush eye(s) with water or normal saline. The most common
effects expected with overdosage of a beta-adrenergic blocking agent
are bradycardia, bronchospasm, congestive heart failure and
hypotension. In case of ingestion, treatment with Ocupress should be
discontinued and gastric lavage considered. The patient should be
closely observed and vital signs carefully monitored. The prolonged
effects of carteolol must be considered when determining the duration
of corrective therapy. On the basis of the pharmacologic profile, the
following additional measures should be considered as appropriate:
Symptomatic Sinus Bradycardia or Heart Block: Administer atropine. If
there is no response to vagal blockade, administer isoproterenol
cautiously.
Bronchospasm: Administer a beta2-stimulating agent such as
isoproterenol and/or a theophylline derivative.
Congestive Heart Failure: Administer diuretics and digitalis
glycosides as necessary.
Hypotension: Administer vasopressors such as intravenous dopamine,
epinephrine or norepinephrine bitartrate.
DOSAGE AND ADMINISTRATION: The usual dose is one drop of
Ocupress Ophthalmic Solution, 1%, in the affected eye(s) twice a day.
If the patientÕs IOP is not at a satisfactory level on this regimen,
concomitant therapy with pilocarpine and other miotics, and/or
epinephrine or dipivefrin, and/or systemically administered carbonic
anhydrase inhibitors, such as acetazolamide, can be instituted.
HOW SUPPLIED: Ocupress Ophthalmic Solution, 1%, is supplied as
a sterile ophthalmic solution in plastic dispenser bottles of 5 mL (NDC
58768-001-01), 10 mL (NDC 58768-001-02) and 15 mL (NDC 58768-001-04).
Store at 15° to 25°C (59° to 77°F) (room temperature) and protect from
light.
Licensed under U.S. Patent Nos. 3910924 and 4309432.
Made in Canada by:
CIBA Vision Sterile Mfg.,
Mississauga, Ontario L5N 2X5
For: CIBA Vision
A Novartis Company
©1999 CIBA Vision Corporation, Duluth, GA 30097
COOC 2228/081175 |
