Overdose
Accidental ingestion of at least 50 mg of MINIPRESS in a
two year old child resulted in profound drowsiness and depressed reflexes. No
decrease in blood pressure was noted. Recovery was uneventful.
Should overdosage lead to hypotension, support of the
cardiovascular system is of first importance. Restoration of blood pressure and
normalization of heart rate may be accomplished by keeping the patient in the
supine position. If this measure is inadequate, shock should first be treated
with volume expanders. If necessary, vasopressors should then be used. Renal
function should be monitored and supported as needed. Laboratory data indicate
MINIPRESS is not dialysable because it is protein bound.
Contraindications
MINIPRESS is contraindicated in patients with known sensitivity
to quinazolines, prazosin, or any of the inert ingredients.
Undesirable effects
Clinical trials were conducted on more than 900 patients.
During these trials and subsequent marketing experience, the most frequent
reactions associated with MINIPRESS therapy are: dizziness 10.3%, headache
7.8%, drowsiness 7.6%, lack of energy 6.9%, weakness 6.5%, palpitations 5.3%,
and nausea 4.9%. In most instances, side effects have disappeared with
continued therapy or have been tolerated with no decrease in dose of drug.
Less frequent adverse reactions which are reported to
occur in 1-4% of patients are:
Gastrointestinal: vomiting, diarrhea,
constipation.
Cardiovascular: edema, orthostatic hypotension,
dyspnea, syncope.
Central Nervous System: vertigo, depression,
nervousness.
Dermatologic: rash.
Genitourinary: urinary frequency.
EENT: blurred vision, reddened sclera, epistaxis,
dry mouth, nasal congestion.
In addition, fewer than 1% of patients have reported the
following (in some instances, exact causal relationships have not been
established):
Gastrointestinal: abdominal discomfort and/or
pain, liver function abnormalities, pancreatitis.
Cardiovascular: tachycardia.
Central Nervous System: paresthesia,
hallucinations.
Dermatologic: pruritus, alopecia, lichen planus.
Genitourinary: incontinence, impotence, priapism.
EENT: tinnitus.
Other: diaphoresis, fever, positive ANA titer,
arthralgia.
Single reports of pigmentary mottling and serous
retinopathy, and a few reports of cataract development or disappearance have
been reported. In these instances, the exact causal relationship has not been established
because the baseline observations were frequently inadequate.
In more specific slit-lamp and funduscopic studies, which
included adequate baseline examinations, no drug-related abnormal
ophthalmological findings have been reported.
Literature reports exist associating MINIPRESS therapy
with a worsening of pre-existing narcolepsy. A causal relationship is uncertain
in these cases.
In post-marketing experience, the following adverse
events have been reported:
Autonomic Nervous System: flushing.
Body As A Whole: allergic reaction, asthenia,
malaise, pain.
Cardiovascular, General: angina pectoris,
hypotension.
Endocrine: gynecomastia.
Heart Rate/Rhythm: bradycardia.
Psychiatric: insomnia.
Skin/Appendages: urticaria.
Vascular (Extracardiac): vasculitis.
Vision: eye pain.
Special Senses: During cataract surgery, a variant
of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has
been reported in association with alpha-1 blocker therapy (see PRECAUTIONS).
Therapeutic indications
MINIPRESS is indicated for the treatment of hypertension,
to lower blood pressure. Lowering blood pressure reduces the risk of fatal and
nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
These benefits have been seen in controlled trials of antihypertensive drugs
from a wide variety of pharmacologic classes, including this drug.
Control of high blood pressure should be part of
comprehensive cardiovascular risk management, including, as appropriate, lipid
control, diabetes management, antithrombotic therapy, smoking cessation, exercise,
and limited sodium intake. Many patients will require more than one drug to
achieve blood pressure goals. For specific advice on goals and management, see
published guidelines, such as those of the National High Blood Pressure
Education Program's Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of
pharmacologic classes and with different mechanisms of action, have been shown
in randomized controlled trials to reduce cardiovascular morbidity and
mortality, and it can be concluded that it is blood pressure reduction, and not
some other pharmacologic property of the drugs, that is largely responsible for
those benefits. The largest and most consistent cardiovascular outcome benefit
has been a reduction in the risk of stroke, but reductions in myocardial
infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased
cardiovascular risk, and the absolute risk increase per mmHg is greater at
higher blood pressures, so that even modest reductions of severe hypertension
can provide substantial benefit. Relative risk reduction from blood pressure
reduction is similar across populations with varying absolute risk, so the
absolute benefit is greater in patients who are at higher risk independent of
their hypertension (for example, patients with diabetes or hyperlipidemia), and
such patients would be expected to benefit from more aggressive treatment to a lower
blood pressure goal.
Some antihypertensive drugs have smaller blood pressure
effects (as monotherapy) in black patients, and many antihypertensive drugs
have additional approved indications and effects (e.g., on angina, heart failure,
or diabetic kidney disease). These considerations may guide selection of
therapy.
MINIPRESS can be used alone or in combination with other
antihypertensive drugs such as diuretics or beta-adrenergic blocking agents.
Date of revision of the text
Feb 2015
Name of the medicinal product
Minipress
Qualitative and quantitative composition
| Strength |
Capsule Color |
Capsule Code |
NDC |
Package Size |
| MINIPRESS® 1 mg |
White |
431 |
0069-4310-71 |
250's |
| MINIPRESS® 2 mg |
Pink and White |
437 |
0069-4370-71 |
250's |
| MINIPRESS® 5 mg |
Blue and White |
438 |
0069-4380-71 |
250's |
Distributed by: Pfizer Labs, Divsion of Pfizer Inc., NY,
NY 10017. Revised: Feb 2015
Special warnings and precautions for use
WARNINGS
As with all alpha-blockers, MINIPRESS may cause
syncope with sudden loss of consciousness. In most cases, this is believed to
be due to an excessive postural hypotensive effect, although occasionally the syncopalepis
ode has been preceded by a bout of severe tachycardia with heart rates of 120-160
beats per minute. Syncopalepis odes have usually occurred within 30 to 90 minutes
of the initial dos e of the drug; occasionally, they have been reported in
association with rapid dos age increases or the introduction of another
antihypertensive drug into the regimen of a patient taking high doses of
MINIPRESS. The incidence of syncopalepis odes is approximately 1% in patients
given an initial dose of 2 mg or greater. Clinical trials conducted during the investigational
phase of this drug suggest that syncopal episodes can be minimized by limiting
the initial dos e of the drug to 1 mg, by subs equently increasing the dos age
slowly, and by introducing any additional antihypertensive drugs into the
patient's regimen with caution (see DOSAGE AND ADMINISTRATION). Hypotension may
develop in patients given MINIPRESS who are also receiving a beta-blocker such
as propranolol.
If syncope occurs, the patient should be placed in the
recumbent position and treated supportively as necessary. This adverse effect
is self-limiting and in most cases does not recur after the initial period of
therapy or during subsequent dose titration.
Patients should always be started on the 1 mg capsules of
MINIPRESS. The 2 and 5 mg capsules are not indicated for initial therapy.
More common than loss of consciousness are the symptoms
often associated with lowering of the blood pressure, namely, dizziness and
lightheadedness. The patient should be cautioned about these possible adverse
effects and advised what measures to take should they develop. The patient
should also be cautioned to avoid situations where injury could result should
syncope occur during the initiation of MINIPRESS therapy.
Priapism
Prolonged erections and priapism have been reported with
alpha-1 blockers including prazosin in post marketing experience. In the event
of an erection that persists longer than 4 hours, seek immediate medical
assistance. If priapism is not treated immediately, penile tissue damage and
permanent loss of potency could result.
PRECAUTIONS
General
Intraoperative Floppy Iris Syndrome (IFIS) has been
observed during cataract surgery in some patients treated with alpha-1 blockers.
This variant of small pupil syndrome is characterized by the combination of a
flaccid iris that billows in response to intraoperative irrigation currents,
progressive intraoperative miosis despite preoperative dilation with standard
mydriatic drugs, and potential prolapse of the iris toward the
phacoemulsification incisions. The patient's ophthalmologist should be prepared
for possible modifications to the surgical technique, such as the utilization
of iris hooks, iris dilator rings, or viscoelastic substances. There does not
appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract
surgery.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No carcinogenic potential was demonstrated in an 18 month
study in rats with MINIPRESS at dose levels more than 225 times the usual
maximum recommended human dose of 20 mg per day. MINIPRESS was not mutagenic in
in vivo genetic toxicology studies. In a fertility and general reproductive performance
study in rats, both males and females, treated with 75 mg/kg (225 times the
usual maximum recommended human dose), demonstrated decreased fertility, while
those treated with 25 mg/kg (75 times the usual maximum recommended human dose)
did not.
In chronic studies (one year or more) of MINIPRESS in
rats and dogs, testicular changes consisting of atrophy and necrosis occurred
at 25 mg/kg/day (75 times the usual maximum recommended human dose). No
testicular changes were seen in rats or dogs at 10 mg/kg/day (30 times the
usual maximum recommended human dose). In view of the testicular changes
observed in animals, 105 patients on long term MINIPRESS therapy were monitored
for 17-ketosteroid excretion and no changes indicating a drug effect were
observed. In addition, 27 males on MINIPRESS for up to 51 months did not have
changes in sperm morphology suggestive of drug effect.
Usage In Pregnancy
Pregnancy Category C. MINIPRESS has been shown to
be associated with decreased litter size at birth, 1, 4, and 21 days of age in
rats when given doses more than 225 times the usual maximum recommended human
dose. No evidence of drug-related external, visceral, or skeletal fetal
abnormalities were observed. No drug-related external, visceral, or skeletal
abnormalities were observed in fetuses of pregnant rabbits and pregnant monkeys
at doses more than 225 times and 12 times the usual maximum recommended human
dose, respectively.
The use of prazosin and a beta-blocker for the control of
severe hypertension in 44 pregnant women revealed no drug-related fetal
abnormalities or adverse effects. Therapy with prazosin was continued for as
long as 14 weeks.1
Prazosin has also been used alone or in combination with
other hypotensive agents in severe hypertension of pregnancy by other
investigators. No fetal or neonatal abnormalities have been reported with the
use of prazosin.2
There are no adequate and well controlled studies which
establish the safety of MINIPRESS in pregnant women. MINIPRESS should be used
during pregnancy only if the potential benefit justifies the potential risk to
the mother and fetus.
Nursing Mothers
MINIPRESS has been shown to be excreted in small amounts
in human milk. Caution should be exercised when MINIPRESS is administered to a
nursing woman.
Usage In Children
Safety and effectiveness in children have not been
established.
REFERENCES
1. Lubbe, WF, and Hodge, JV: New Zealand Med J, 94 (691)
169-172, 1981.
2. Davey, DA, and Dommisse, J: S.A. Med J, Oct. 4, 1980
(551-556).
Dosage (Posology) and method of administration
The dose of MINIPRESS should be adjusted according to the
patient's individual blood pressure response. The following is a guide to its
administration:
Initial Dose
1 mg two or three times a day (see WARNINGS.)
Maintenance Dose
Dosage may be slowly increased to a total daily dose of
20 mg given in divided doses. The therapeutic dosages most commonly employed
have ranged from 6 mg to 15 mg daily given in divided doses. Doses higher than
20 mg usually do not increase efficacy, however a few patients may benefit from
further increases up to a daily dose of 40 mg given in divided doses. After
initial titration some patients can be maintained adequately on a twice daily
dosage regimen.
Use With Other Drugs
When adding a diuretic or other antihypertensive agent,
the dose of MINIPRESS should be reduced to 1 mg or 2 mg three times a day and retitration
then carried out.
Concomitant administration of MINIPRESS with a PDE-5
inhibitor can result in additive blood pressure lowering effects and
symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated
at the lowest dose in patients taking MINIPRESS.
Interaction with other medicinal products and other forms of interaction
SIDE EFFECTS
Clinical trials were conducted on more than 900 patients.
During these trials and subsequent marketing experience, the most frequent
reactions associated with MINIPRESS therapy are: dizziness 10.3%, headache
7.8%, drowsiness 7.6%, lack of energy 6.9%, weakness 6.5%, palpitations 5.3%,
and nausea 4.9%. In most instances, side effects have disappeared with
continued therapy or have been tolerated with no decrease in dose of drug.
Less frequent adverse reactions which are reported to
occur in 1-4% of patients are:
Gastrointestinal: vomiting, diarrhea,
constipation.
Cardiovascular: edema, orthostatic hypotension,
dyspnea, syncope.
Central Nervous System: vertigo, depression,
nervousness.
Dermatologic: rash.
Genitourinary: urinary frequency.
EENT: blurred vision, reddened sclera, epistaxis,
dry mouth, nasal congestion.
In addition, fewer than 1% of patients have reported the
following (in some instances, exact causal relationships have not been
established):
Gastrointestinal: abdominal discomfort and/or
pain, liver function abnormalities, pancreatitis.
Cardiovascular: tachycardia.
Central Nervous System: paresthesia,
hallucinations.
Dermatologic: pruritus, alopecia, lichen planus.
Genitourinary: incontinence, impotence, priapism.
EENT: tinnitus.
Other: diaphoresis, fever, positive ANA titer,
arthralgia.
Single reports of pigmentary mottling and serous
retinopathy, and a few reports of cataract development or disappearance have
been reported. In these instances, the exact causal relationship has not been established
because the baseline observations were frequently inadequate.
In more specific slit-lamp and funduscopic studies, which
included adequate baseline examinations, no drug-related abnormal
ophthalmological findings have been reported.
Literature reports exist associating MINIPRESS therapy
with a worsening of pre-existing narcolepsy. A causal relationship is uncertain
in these cases.
In post-marketing experience, the following adverse
events have been reported:
Autonomic Nervous System: flushing.
Body As A Whole: allergic reaction, asthenia,
malaise, pain.
Cardiovascular, General: angina pectoris,
hypotension.
Endocrine: gynecomastia.
Heart Rate/Rhythm: bradycardia.
Psychiatric: insomnia.
Skin/Appendages: urticaria.
Vascular (Extracardiac): vasculitis.
Vision: eye pain.
Special Senses: During cataract surgery, a variant
of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has
been reported in association with alpha-1 blocker therapy (see PRECAUTIONS).
DRUG INTERACTIONS
MINIPRESS has been administered without any adverse drug
interaction in limited clinical experience to date with the following: (1)
cardiac glycosides-digitalis and digoxin; (2) hypoglycemics-insulin, chlorpropamide,
phenformin, tolazamide, and tolbutamide; (3) tranquilizers and sedatives- chlordiazepoxide,
diazepam, and phenobarbital; (4) antigout-allopurinol, colchicine, and
probenecid; (5) antiarrhythmics-procainamide, propranolol (see WARNINGS
however), and quinidine; and (6) analgesics, antipyretics and
anti-inflammatories-propoxyphene, aspirin, indomethacin, and phenylbutazone.
Addition of a diuretic or other antihypertensive agent to
MINIPRESS has been shown to cause an additive hypotensive effect. This effect
can be minimized by reducing the MINIPRESS dose to 1 to 2 mg three times a day,
by introducing additional antihypertensive drugs cautiously, and then by
retitrating MINIPRESS based on clinical response. Concomitant administration of
MINIPRESS with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive
blood pressure lowering effects and symptomatic hypotension (see DOSAGE AND ADMINISTRATION).
Drug/Laboratory Test Interactions
In a study on five patients given from 12 to 24 mg of
prazosin per day for 10 to 14 days, there was an average increase of 42% in the
urinary metabolite of norepinephrine and an average increase in urinary VMA of
17%. Therefore, false positive results may occur in screening tests for
pheochromocytoma in patients who are being treated with prazosin. If an
elevated VMA is found, prazosin should be discontinued and the patient retested
after a month.
Laboratory Tests
In clinical studies in which lipid profiles were
followed, there were generally no adverse changes noted between pre- and
post-treatment lipid levels.