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Phenylephrine Hydrochloride
Sub-sections
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Introduction
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Uses
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Dosage and Administration
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Cautions
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Drug Interactions
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Pharmacology

Pharmacokinetics

Chemistry and Stability

Preparations
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References
Drug Nomenclature
Generic Name: Phenylephrine Hydrochloride
CAS Number: 61-76-7
Introduction
Phenylephrine is a sympathomimetic amine that predominantly acts by a
direct effect on α-adrenergic receptors.
Uses
Hypotension and Shock
Phenylephrine is administered parenterally to produce vasoconstriction as an
adjunct to correct hemodynamic imbalances in the treatment of shock that
persists after adequate fluid volume replacement. (See Cautions:
Precautions and Contraindications.) Individual hemodynamic abnormalities
must be identified and monitored so that therapy can be adjusted as
necessary. If severe peripheral vasoconstriction exists, the drug may be
ineffective and may have a deleterious effect by causing further reductions
in plasma volume and blood flow to vital organs.
The value of pressor therapy in shock, especially when caused by
septicemia, burns, trauma, or drug overdosage, is questionable, either
because the effectiveness has not been proved or because vasoconstriction
caused by the drug may adversely affect the patient. Although a vasopressor
may be indicated if the patient fails to respond to administration of fluids, a
change in position or other measures directed to the specific cause of shock,
drugs that also stimulate the myocardium (e.g., norepinephrine,
metaraminol) usually are preferred to phenylephrine, especially in shock
caused by myocardial infarction, septicemia, or surgical complications. Some
clinicians believe that phenylephrine should not be used in the management
of shock, especially when caused by myocardial infarction, because it greatly
increases arterial resistance and the workload on the heart. However,
phenylephrine may be useful when cardiac stimulation is undesirable (as in
the treatment of hypotension occurring during general anesthesia with
cyclopropane, halothane, or other agents that sensitize the myocardium to
arrhythmias).
Vasopressor therapy in overdosage of barbiturates or other sedatives is
especially controversial; some clinicians have stated that the incidence of
mortality actually may be increased when a vasopressor is given. The
manufacturer states that phenylephrine may be used to treat hypotension or
shock resulting from overdosage of or idiosyncratic reactions to certain
drugs (e.g., adrenergic and ganglionic blocking agents, rauwolfia and
veratrum alkaloids, phenothiazines).
Although the manufacturer states phenylephrine may be useful to control
shock following pheochromocytomectomy, shock generally can be prevented
by maintenance of adequate blood volume and/or preoperative
administration of an α-adrenergic blocking agent.
Hypotension during Spinal Anesthesia
Although phenylephrine has been used both for the prevention and
treatment of hypotension resulting from spinal anesthesia, some clinicians
state that pure α-adrenergic agonists should not be used because they may
further reduce cardiac output. In addition, routine prophylactic use of any
vasopressor in spinal anesthesia has been questioned because hypotension
does not always occur during spinal anesthesia and treatment can readily be
instituted if necessary. It has been suggested that vasopressors be
administered prophylactically only in those cases in which a substantial
decrease in blood pressure is expected.
The use of vasopressors to correct hypotension occurring during anesthesia
in obstetrical patients is controversial. Hypotension usually can be minimized
by adequate hydration and changing the position of the patient so that the
uterus does not compress the inferior vena cava. If a vasopressor is
required, ephedrine usually is preferred.
Prolongation of Spinal Anesthesia
Phenylephrine may be added to solutions of some local anesthetics to
decrease the rate of vascular absorption of the anesthetic, thereby localizing
anesthesia and prolonging the duration of anesthesia. The risk of systemic
toxicity due to the local anesthetic is also decreased. (See Local Anesthetics,
Parenteral, General Statement 72:00.) Phenylephrine is not as effective as
epinephrine in prolonging local anesthesia but may be preferred when
cardiostimulation is undesirable.
Paroxysmal Supraventricular Tachycardia
Phenylephrine is administered IV to raise blood pressure in order to
terminate some attacks of paroxysmal supraventricular tachycardia,
especially in patients who are also hypotensive or in shock. Administration of
an anticholinesterase drug having a short duration of action (e.g.,
edrophonium chloride) may be safer, however.
Nasal Congestion
Phenylephrine hydrochloride is administered orally for self-medication as a
nasal decongestant for temporary relief of nasal congestion associated with
upper respiratory allergy (e.g., hay fever) or the common cold; the drug also
is used to provide temporary relief of sinus congestion and pressure.114 123 124
Preparations containing phenylephrine in fixed combination with other
agents (e.g., acetaminophen, chlorpheniramine, dextromethorphan,
diphenhydramine, guaifenesin, pheniramine) are used for temporary relief of
nasal/sinus congestion and/or other symptoms (e.g., rhinorrhea, sneezing,
lacrimation, itching eyes, oronasopharyngeal itching, cough) associated with
seasonal or perennial allergic rhinitis, other upper respiratory allergies, or
the common cold.133 134 135 136 137 138 139 Because of recent state and federal actions
restricting the sale and purchase of nonprescription preparations containing
decongestants such as pseudoephedrine, ephedrine, or phenylpropanolamine
(no longer commercially available in the US),109 110 111 112 some manufacturers
have begun to reformulate various existing nonprescription
pseudoephedrine-containing preparations by substituting phenylephrine for
pseudoephedrine.113 116 (See Uses: Misuse and Abuse, in Pseudoephedrine
12:12.12.) However, few studies evaluating the efficacy of oral
phenylephrine in the treatment of nasal congestion have been published,
and efficacy of the drug at currently recommended oral dosages has been
questioned by some clinicians.115 125 126 127
Nasal decongestants, including phenylephrine, are labeled and have been
used for self-medication for the temporary relief of nasal congestion
associated with sinusitis.114 117 However, prospective studies of nasal
decongestants for this use are lacking,118 and data on their use as adjunctive
therapy in the management of sinusitis are limited and controversial.117 119
Furthermore, evidence from an animal study indicates that topical nasal
decongestants (i.e., oxymetazoline) may increase the degree of sinus
inflammation,120 potentially delaying resolution of sinusitis.117 Because current
labeling for nonprescription (over-the-counter, OTC) nasal decongestant
preparations includes use for sinusitis, there are concerns that consumers
will assume that nasal decongestants are effective in the treatment of
sinusitis, thereby choosing self-medication over medical evaluation and
definitive treatment by a clinician; such delay in medical evaluation could
result in a lost opportunity for early diagnosis of another serious medical
condition (e.g., bacterial sinusitis).117 As a result, the US Food and Drug
Administration (FDA) no longer considers oral or topical nasal decongestants
appropriate for self-medication of sinusitis.117 In October 2005, the agency
issued a final rule amending the final monograph for OTC nasal decongestant
preparations to remove the indication for relief of nasal congestion
associated with sinusitis from labeling and prohibiting use of the term
“sinusitis” elsewhere in labeling.117 The compliance date for preparations with
annual sales less than $25,000 is October 11, 2007; the compliance date for
all other preparations is April 11, 2007.117
Phenylephrine also is applied topically to the nasal mucosa as a
vasoconstrictor to relieve nasal congestion. (See Phenylephrine 52:32.)
Hemorrhoids
Anorectal preparations (e.g., creams, gels, ointments, suppositories)
containing phenylephrine hydrochloride are used topically or rectally to
provide temporary symptomatic relief of external or internal hemorrhoids.101
102 103 104 105 106 107 108
When applied topically or rectally to the anorectal area,
vasoconstrictors such as phenylephrine stimulate α-adrenergic receptors in
the vascular beds102 with a resultant temporary constriction of arterioles and
a modest and transient reduction in congestion (swelling) of hemorrhoidal
tissues.101 102 108 Vasoconstrictors also may relieve anorectal pruritus,
discomfort, and irritation, possibly in part secondary to some weak local
anesthetic action; the mechanism of this local anesthetic effect is
unknown.102 108 Phenylephrine also may relieve pruritus associated with
histamine release.102 108 However, vasoconstrictors are expected to provide
only partial relief of pruritus associated with hemorrhoids, and there are
more effective agents for relief of anorectal itching.108 The presence of other
ingredients in the formulation (e.g., protectants, local anesthetics,
astringents, antipruritics, analgesics) may provide additional relief of these
and other anorectal symptoms (e.g., discomfort, pain, burning) associated
with hemorrhoids.101 102 103 104 105 106 107 Although locally applied vasoconstrictors
have been shown to alter mucosal blood flow, safety and efficacy for selfmedication control of minor hemorrhoidal bleeding have not been
established.102 108 If minor bleeding is present, a clinician should be consulted
promptly for advice because anorectal bleeding may be a sign of conditions
ranging in seriousness from simple abrasions to cancer.108
Effectiveness of topical or intrarectal therapy with phenylephrine for relief of
symptoms secondary to swollen hemorrhoidal tissues is based on a predicted
effect of the drug's vasoconstrictive activity in reducing capillary and
arteriovenous congestion in the anorectal area rather than on specific
efficacy studies.108 Effective dosage of anorectal therapy with the drug was
based on predictions from established efficacy of local therapy for nasal
congestion.108
Other Uses
IV phenylephrine has been used to increase blood pressure as an aid in the
diagnosis of heart murmurs†.
For the use of phenylephrine as a mydriatic, see Phenylephrine
Hydrochloride 52:24. For the use of phenylephrine as a
vasoconstrictor in the eye or mucosa, see Phenylephrine
Hydrochloride 52:32.
Dosage and Administration
Administration
Parenteral
As a vasopressor, phenylephrine hydrochloride is administered by IM,
subcutaneous, or slow IV injection, or IV infusion. The route of
administration should be determined by the needs of the individual patient;
patients who are in shock may require IV administration to ensure
absorption of the drug. For treating hypotension or shock, phenylephrine
usually is administered by IV infusion as a dilute solution; however, direct IV
injections are administered in treating paroxysmal atrial or nodal tachycardia
or in emergencies requiring a strong, immediate pressor effect.
In emergencies, phenylephrine may be administered by direct IV injection.
For convenience in administration by direct IV injection, 1 mL of the
commercially available phenylephrine hydrochloride injection containing 10
mg/mL may be diluted with 9 mL of sterile water for injection to prepare a
solution containing 1 mg/mL.
For IV infusion, phenylephrine may be diluted with 5% dextrose or 0.9%
sodium chloride injection. The concentration of phenylephrine and the
infusion rate depend on the drug and fluid requirements of the individual
patient. Infusion solutions usually are prepared by adding 10 mg of
phenylephrine hydrochloride to 500 mL of diluent.
During therapy with a vasopressor, blood pressure should be elevated to
slightly less than the patient's normal blood pressure. In previously
normotensive patients, systolic blood pressure should be maintained at 80–
100 mm Hg; in previously hypertensive patients, systolic blood pressure
should be maintained at 30–40 mm Hg below their usual blood pressure. In
some patients with very severe hypotension, maintenance of even lower
blood pressure may be desirable if blood or fluid volume replacement has
not been completed. Patients receiving the drug by IV infusion should not be
left unattended and the infusion flow rate must be closely monitored. Blood
pressure should be checked frequently, especially when the drug is
administered IV.
Phenylephrine therapy should be continued until adequate blood pressure
and tissue perfusion are maintained. When IV infusions are discontinued, the
infusion rate should be slowed gradually and abrupt withdrawal avoided. The
patient should be observed carefully so that therapy may be resumed if the
blood pressure falls too rapidly. Pressor therapy should not be reinstated
until the systolic blood pressure falls to 70–80 mm Hg. In some patients,
additional administration of IV fluids may be necessary before phenylephrine
can be discontinued.
Oral
As a vasoconstrictor for the management of nasal congestion, phenylephrine
is administered orally alone or as a fixed-combination decongestant
preparation.
For self-medication in children receiving phenylephrine orally dissolving
strips, the caregiver should be instructed to place the strip on the patient's
tongue, where it rapidly dissolves and then can be swallowed.123 124
Topical and Rectal
As a vasoconstrictor for the management of hemorrhoidal symptoms,
phenylephrine hydrochloride topical preparations are administered externally
to the affected perianal area and rectal preparations are administered
externally to the affected perianal area and/or intrarectally.101 102 103 104 105 106 107 108
Topical preparations of phenylephrine hydrochloride that are labeled for
external use only should be applied externally to the affected area and
should not be administered inside the rectum by either using fingers or any
mechanical device or applicator.101 102 103 105 107
Rectal preparations of phenylephrine hydrochloride are labeled either for
rectal use only (e.g., suppositories) or for external and/or intrarectal use
only.101 102 104 106 107 When a special applicator such as a pile pipe or other
mechanical device is used to administer the drug intrarectally, the applicator
should be attached to the tube of drug and then the applicator should be
lubricated well and gently inserted into the rectum;101 102 104 the applicator
should be cleansed thoroughly after each use and stored according to the
manufacturer's instructions.104 Such preparations should not be used if
introduction of the applicator or device into the rectum causes additional
pain; patients should be advised to consult a clinician promptly in such
cases.101 102 104 107 The wrapper should be removed from suppositories prior to
insertion into the rectum.101 102 106 107
Patients receiving phenylephrine hydrochloride for the local management of
hemorrhoids should be advised to cleanse the affected perianal area by
patting with warm water and mild soap and rinsing thoroughly or with an
appropriate cleansing wipe whenever practical.101 102 103 104 105 106 107 The area then
should be dried by patting or blotting with toilet tissue or a soft cloth before
application of the drug.101 102 103 104 105 106 107
Dosage
Phenylephrine should be administered in the lowest effective dosage for the
shortest possible time. When possible, small doses should be injected
initially and subsequent doses determined by pressor response.
Mild or Moderate Hypotension
In treating mild to moderate hypotension in adults, subcutaneous or IM
doses range from 1–10 mg; 2–5 mg is most frequently used. The initial
adult IM or subcutaneous dose should not exceed 5 mg. Children may
receive 0.1 mg/kg or 3 mg/m2 IM or subcutaneously. Additional IM or
subcutaneous doses may be given in 1–2 hours if needed. For the treatment
of mild to moderate hypotension in adults, the drug may also be
administered by slow IV injection in a dose ranging from 0.1–0.5 mg; 0.2
mg is the usual dose. The initial adult IV dose should not exceed 0.5 mg. IV
doses may be given no more frequently than every 10–15 minutes.
Severe Hypotension or Shock
When used as an adjunct in the treatment of severe hypotension or shock,
phenylephrine is administered by IV infusion as a dilute solution. (See
Dosage and Administration: Administration.) The rate of infusion is adjusted
to maintain the blood pressure at the desired level. The drug is usually
administered at an initial rate of 0.1–0.18 mg/minute. After the blood
pressure stabilizes, 0.04–0.06 mg/minute usually is adequate. If necessary
to produce the desired pressor response, additional phenylephrine in
increments of 10 mg or more may be added to the infusion solution and the
rate of flow adjusted according to the response of the patient.
Hypotension during Spinal Anesthesia
If phenylephrine is administered prophylactically to prevent hypotension
during spinal anesthesia, it should be administered IM or subcutaneously 3–
4 minutes prior to the spinal anesthetic. A dose of 2 mg usually is adequate
with low spinal anesthesia in adults, but 3 mg may be necessary with high
spinal anesthesia. For hypotensive emergencies during spinal anesthesia in
adults, the drug may be given IV in an initial dose of 0.2 mg; any
subsequent dose should not exceed the previous dose by 0.1–0.2 mg and a
single dose should not exceed 0.5 mg. The manufacturer recommends that
0.044–0.088 mg/kg be administered IM or subcutaneously to treat
hypotension during spinal anesthesia in children.
Prolongation of Spinal Anesthesia
To prolong spinal anesthesia, 2–5 mg of phenylephrine hydrochloride may
be added to the anesthetic solution.
Vasoconstriction for Regional Anesthesia
To produce vasoconstriction in regional anesthesia, the manufacturer states
that the optimum concentration of phenylephrine hydrochloride is 0.05
mg/mL (1:20,000). Solutions may be prepared for regional anesthesia by
adding 1 mg of phenylephrine hydrochloride to each 20 mL of local
anesthetic solution. Some pressor response can be expected when at least 2
mg is injected.
Paroxysmal Supraventricular Tachycardia
To terminate attacks of paroxysmal supraventricular tachycardia,
phenylephrine is administered rapidly (within 20–30 seconds) by direct IV
injection. The manufacturer recommends that the initial dose should not
exceed 0.5 mg and that subsequent doses may be increased in increments
of 0.1–0.2 mg, depending on the blood pressure response of the patient.
Systolic blood pressure should not be raised above 160 mm Hg. The
maximum single dose of phenylephrine hydrochloride recommended by the
manufacturer is 1 mg. Some clinicians, however, have recommended that
0.5–1 mg be administered rapidly initially and that an additional 2 mg may
be given slowly IV if cardiac rhythm fails to revert within 60–90 seconds.
Nasal Congestion
Phenylephrine is administered orally as a nasal decongestant alone or in
fixed combination with other drugs.133 134 135 136 137 138 139 The usual oral
decongestant dosage of phenylephrine hydrochloride for self-medication in
adults and children 12 years of age or older is 10 mg every 4 hours.114
Children 6–11 years of age may receive 5 mg of phenylephrine
hydrochloride every 4 hours, and children 2–5 years of age may receive 2.5
mg every 4 hours.123 124 (See Cautions: Pediatric Precautions.) The
manufacturer states that no more than 6 doses should be administered in a
24-hour period.114 123 124 For self-medication, the manufacturer recommends
that patients discontinue the drug and consult a clinician if symptoms persist
more than 7 days or are accompanied by fever, or if nervousness, dizziness,
or insomnia occurs.114 123 124
Hemorrhoids
When used topically or rectally as a vasoconstrictor for temporary relief of
hemorrhoidal symptoms in adults and children 12 years of age and older,
phenylephrine hydrochloride is used for self-medication as a cream, gel,
ointment, or suppository containing 0.25% of the drug alone or in
combination with other anorectal agents (e.g., protectants, local anesthetics,
astringents, antipruritics, analgesics).101 102 103 104 105 106 107 108 Anorectal
preparations of the drug usually are administered at bedtime, in the
morning, and after bowel movements102 103 104 105 106 up to 4 times daily.101 102 103 104
105 106 107 108
Patients should be advised not to exceed the recommended dosage of
phenylephrine hydrochloride unless otherwise directed by a clinician.101 102 103
104 105 106 107 108
Although the systemic bioavailability of phenylephrine
hydrochloride following local application to the anorectal area is not known,
it is recommended that anorectal dosage for self-medication of hemorrhoids
not exceed 2 mg daily (i.e., 0.5 mg 4 times daily) in order to minimize
adverse systemic effects.108 It currently is not known whether higher dosages
would provide additional benefit.108
Patients should be advised to consult a clinician if the anorectal condition
worsens or does not improve within 7 days or if bleeding occurs.101 102 103 104 105
106 107
Cautions
Adverse Effects
Systemic Use
Phenylephrine may cause restlessness, anxiety, nervousness, weakness,
dizziness, precordial pain or discomfort, tremor, respiratory distress, pallor
or blanching of the skin, or a pilomotor response. Injections of the drug may
be followed by paresthesia in the extremities or a feeling of coolness in the
skin. When 2 mg or more of phenylephrine hydrochloride is injected during
regional local anesthesia, a pressor response may occur.
Overdosage of phenylephrine may cause hypertension, headache, seizures,
cerebral hemorrhage, palpitation, paresthesia, or vomiting. Headache may
be a symptom of hypertension. Hypertension may be relieved by
administration of an α-adrenergic blocking agent (e.g., phentolamine). If
phenylephrine is administered by rapid IV injection in the treatment of
paroxysmal supraventricular tachycardia, overdosage may result in short
paroxysms of ventricular tachycardia, ventricular extrasystoles, or a
sensation of fullness in the head.
Phenylephrine can cause severe peripheral and visceral vasoconstriction,
reduced blood flow to vital organs, decreased renal perfusion, and probably
reduced urine output and metabolic acidosis. Severe vasoconstrictive effects
may be most likely to occur in hypovolemic patients. In addition, prolonged
use of the drug may result in plasma volume depletion that may result in
perpetuation of the shock state or the recurrence of hypotension when
phenylephrine is discontinued.
Phenylephrine can cause severe bradycardia and decreased cardiac output.
Decreased cardiac output may be especially harmful to elderly patients
and/or those with initially poor cerebral or coronary circulation. Bradycardia
may be treated by administration of atropine. The drug also increases
cardiac work by increasing peripheral arterial resistance and may possibly
induce or exacerbate heart failure associated with a diseased myocardium.
Some clinicians believe that phenylephrine is contraindicated in shock
caused by myocardial infarction. In addition, phenylephrine may increase
pulmonary arterial pressure.
Phenylephrine may cause necrosis or sloughing of tissue if extravasation
occurs during IV administration or following subcutaneous administration.
Anorectal Use
When used in recommended dosages for local effect in anorectal disorders
(e.g., hemorrhoids), adverse systemic effects of vasoconstrictors such as
phenylephrine generally are minimal.108 Such effects, although unlikely, can
include blood pressure elevation, cardiac arrhythmia or irregular heart rate,
CNS disturbance or nervousness, tremor, sleeplessness, and aggravation of
hyperthyroid symptoms.108
Based on observations with local use for nasal congestion, prolonged local
use of excessive anorectal dosages of vasoconstrictors will likely lead to
rebound vasodilation and congestion.108 Less commonly, prolonged local use
of excessive anorectal dosages of vasoconstrictors can lead to anxiety and
paranoia.108
Phenylephrine reportedly is less likely than other topical vasoconstrictors
(e.g., ephedrine, epinephrine) to cause local irritation.108 Contact dermatitis
has been reported following topical application of certain formulations of
vasoconstrictors.108
The possibility that topical anorectal application of vasoconstrictors if
absorbed systemically in adequate amounts could interact with monoamine
oxidase (MAO) inhibitors resulting in potentiated hypertensive effects should
be considered.108 Such hypertensive potentiation could result in serious,
potentially fatal effects such as cerebral hemorrhage or stroke.108 (See
Anorectal Precautions and Contraindications under Cautions: Precautions and
Contraindications.)
Precautions and Contraindications
In patients with shock, pressor therapy is not a substitute for replacement of
blood, plasma, fluids, and/or electrolytes. Blood volume depletion should be
corrected as fully as possible before phenylephrine is administered. In an
emergency, the drug may be used as an adjunct to fluid volume replacement
or as a temporary supportive measure to maintain coronary and cerebral
artery perfusion until volume replacement therapy can be completed, but
phenylephrine must not be used as sole therapy in hypovolemic patients.
Additional volume replacement also may be required during or after therapy
with the drug, especially if hypotension recurs. Monitoring of central venous
pressure or left ventricular filling pressure may be helpful in detecting and
treating hypovolemia; in addition, monitoring of central venous or
pulmonary arterial diastolic pressure is necessary to avoid overloading the
cardiovascular system and precipitating congestive heart failure. Hypoxia
and acidosis, which also may reduce the effectiveness of phenylephrine,
must be identified and corrected prior to or concurrently with administration
of the drug.
Prolonged administration of vasopressors has caused edema, hemorrhage,
focal myocarditis, subpericardial hemorrhage, necrosis of the intestine, or
hepatic and renal necrosis; these effects have generally occurred in patients
with severe shock and it is not clear if the drug or the shock state itself was
the cause.
As with other sympathomimetic drugs, phenylephrine hydrochloride should
not be used for self-medication of nasal congestion in patients with thyroid
disease, diabetes mellitus, hypertension, or heart disease without consulting
a clinician.114 123 124 In addition, the drug should not be used for selfmedication of nasal congestion in patients with difficulty urinating because of
prostatic hypertrophy without consulting a clinician.114 Patients should be
advised to discontinue the drug and consult a clinician if symptoms persist
more than 7 days or are accompanied by fever, or if nervousness, dizziness,
or insomnia develops during therapy.114 In addition, patients should be
advised to avoid phenylephrine if they are currently receiving or have
recently received (i.e., within 2 weeks) a monoamine oxidase (MAO)
inhibitor.114
When phenylephrine is used in combination with other drugs, the cautions
applicable to all ingredients in the formulations should be kept in mind.133 134
135 136 137 138 139
Commercially available formulations of phenylephrine hydrochloride injection
may contain sodium metabisulfite, a sulfite that may cause allergic-type
reactions, including anaphylaxis and life-threatening or less severe asthmatic
episodes, in certain susceptible individuals. The overall prevalence of sulfite
sensitivity in the general population is unknown but probably low; such
sensitivity appears to occur more frequently in asthmatic than in
nonasthmatic individuals.
The drug should be administered with extreme caution to geriatric or
hyperthyroid patients or those with bradycardia, partial heart block,
myocardial disease, or severe arteriosclerosis. Some clinicians, however,
consider severe coronary disease or cardiovascular disease (including
myocardial infarction) to be contraindications to use of phenylephrine.
Phenylephrine should be administered parenterally with extreme caution if at
all to hypertensive patients. Phenylephrine is contraindicated in patients with
severe hypertension or ventricular tachycardia and in patients who are
hypersensitive to the drug. If administered to patients with acute
pancreatitis or hepatitis, the drug may increase ischemia in the liver or
pancreas. Phenylephrine should not be used in patients with peripheral or
mesenteric vascular thrombosis, because ischemia may be increased and the
area of infarction extended. In conjunction with local anesthetics,
phenylephrine is contraindicated for use in fingers, toes, ears, nose, or
genitalia.
Anorectal Precautions and Contraindications
Unless otherwise directed by a clinician, patients should not receive external
or rectal preparations of vasoconstrictors such as phenylephrine
hydrochloride for self-medication of hemorrhoidal symptoms if they have
cardiac disease, high blood pressure, thyroid disease, diabetes mellitus, or
difficulty in urination secondary to prostatic hyperplasia.101 102 103 104 105 106 107 108
Patients also should be advised to consult a clinician before initiating selfmedication with an anorectal preparation of the drug if they currently are
receiving an antihypertensive agent or antidepressant (e.g., monoamine
oxidase inhibitor [MAO] inhibitor).101 102 103 104 105 106 107 108 For additional
precautions associated with anorectal phenylephrine therapy, see Dosage
and Administration.
Pediatric Precautions
Overdosage and toxicity (including death) have been reported in children
younger than 2 years of age receiving nonprescription (over-the-counter,
OTC) preparations containing antihistamines, cough suppressants,
expectorants, and nasal decongestants alone or in combination for relief of
symptoms of upper respiratory tract infection.128 129 There is limited evidence
of efficacy for these preparations in this age group, and appropriate dosages
(i.e., approved by the US Food and Drug Administration [FDA]) have not
been established.128 Therefore, FDA stated that nonprescription cough and
cold preparations should not be used in children younger than 2 years of
age;699 the agency continues to assess safety and efficacy of these
preparations in older children.702 704 Meanwhile, because children 2–3 years of
age also are at increased risk of overdosage and toxicity, some
manufacturers of oral nonprescription cough and cold preparations recently
have agreed to voluntarily revise the product labeling to state that such
preparations should not be used in children younger than 4 years of age.701 702
703 704
Because FDA does not typically request removal of products with
previous labeling from pharmacy shelves during a voluntary label change,
some preparations will have the new recommendation (“do not use in
children younger than 4 years of age”), while others will have the previous
recommendation (“do not use in children younger than 2 years of age”).702 704
FDA recommends that parents and caregivers adhere to the dosage
instructions and warnings on the product labeling that accompanies the
preparation if administering to children and consult with their clinician about
any concerns.701 702 703 Clinicians should ask caregivers about use of
nonprescription cough and cold preparations to avoid overdosage.693 For
additional information on precautions associated with the use of cough and
cold preparations in pediatric patients, see Cautions: Pediatric Precautions in
Pseudoephedrine 12:12.12.
Pregnancy and Lactation
Pregnancy
Administration of phenylephrine to patients in late pregnancy or labor may
cause fetal anoxia and bradycardia by increasing contractility of the uterus
and decreasing uterine blood flow.132 If a vasopressor is used in conjunction
with oxytocic drugs, the vasopressor effect is potentiated and may result in
potentially serious adverse effects. (See Drug Interactions: Oxytocic Drugs.)
Animal reproduction studies have not been performed with phenylephrine. It
is also not known whether the drug can cause fetal harm when administered
to pregnant women. Phenylephrine should be used during pregnancy only
when clearly needed. Other pressors (e.g., ephedrine) usually are
preferred.132
Lactation
Phenylephrine does not appear to be distributed to any great extent into
breast milk.121 However, the drug should be used with caution in nursing
women.
Drug Interactions
α- and β-Adrenergic Blocking Agents
The vasopressor response to phenylephrine is decreased by prior
administration of an α-adrenergic blocking agent such as phentolamine
mesylate. Phentolamine may be used to treat hypertension if it occurs
during administration of phenylephrine. Phenothiazine drugs have some αadrenergic blocking effects; therefore, prior administration of a
phenothiazine may reduce the pressor effect and duration of action of
phenylephrine. Larger doses than usual may be required when
phenylephrine is used to treat hypotension caused by overdosage of a
phenothiazine (e.g., chlorpromazine) or other drugs that block α-adrenergic
function.
The cardiostimulating effects of phenylephrine are blocked by prior
administration of β-adrenergic blocking drugs such as propranolol.
Propranolol may be used to treat cardiac arrhythmias occurring during
administration of phenylephrine.
Oxytocic Drugs
When a vasopressor (e.g., phenylephrine) is used in conjunction with
oxytocic drugs, the pressor effect is potentiated.132 If phenylephrine is used
during labor and delivery to correct hypotension or is added to a local
anesthetic solution, the obstetrician should be cautioned that some oxytocic
drugs may cause severe persistent hypertension and that rupture of a
cerebral blood vessel may occur during the postpartum period.132
Sympathomimetic Agents
Combination products containing phenylephrine and a bronchodilator
sympathomimetic agent should not be used concomitantly with epinephrine
or other sympathomimetic agents because tachycardia or other serious
arrhythmias may occur.
General Anesthetics
Rarely, administration of phenylephrine to patients who have received
cyclopropane or halogenated hydrocarbon general anesthetics that increase
cardiac irritability and seem to sensitize the myocardium to phenylephrine
may result in arrhythmias. The manufacturer states that vasopressors
should be used only with extreme caution or not at all with these general
anesthetics. However, in usual therapeutic doses, phenylephrine is much
less likely to produce arrhythmias than is norepinephrine or metaraminol.
Monoamine Oxidase Inhibitors and Drugs Affecting Norepinephrine
The cardiac and pressor effects of phenylephrine are potentiated by prior
administration of monoamine oxidase (MAO) inhibitors because the
metabolism of phenylephrine is reduced. The potentiation is greater
following oral administration of phenylephrine than after parenteral
administration of the drug because reduction of the metabolism of
phenylephrine in the intestine results in increased absorption of the drug.
Oral administration of phenylephrine to patients receiving a MAO inhibitor
should be avoided. Parenteral administration of phenylephrine to these
patients, if unavoidable, should be undertaken with extreme caution and
initial doses should be small. Patients should consult a clinician before
initiating anorectal phenylephrine therapy if they are receiving an MAO
inhibitor. (See Anorectal Precautions and Contraindications under Cautions:
Precautions and Contraindications.)
Tricyclic antidepressants (e.g., imipramine) or guanethidine may also
potentiate the vasopressor effects of phenylephrine.
Other Drugs
Atropine sulfate blocks the reflex bradycardia caused by phenylephrine and
enhances the pressor response to phenylephrine.
An excessive rise in blood pressure may occur if phenylephrine is
administered to patients receiving a parenteral injection of an ergot alkaloid
such as ergonovine maleate.132
The possibility that digitalis can sensitize the myocardium to the effects of
sympathomimetic drugs should be considered.
Administration of furosemide or other diuretics may decrease arterial
responsiveness to vasopressors such as phenylephrine.
Pharmacology
Phenylephrine acts predominantly by a direct effect on α-adrenergic
receptors. In therapeutic doses, the drug has no substantial stimulant effect
on the β-adrenergic receptors of the heart (β1-adrenergic receptors) but
substantial activation of these receptors may occur when larger doses are
given. Phenylephrine does not stimulate β-adrenergic receptors of the
bronchi or peripheral blood vessels (β2-adrenergic receptors). It is believed
that α-adrenergic effects result from the inhibition of the production of cyclic
adenosine-3′,5′-monophosphate (cAMP) by inhibition of the enzyme adenyl
cyclase, whereas β-adrenergic effects result from stimulation of adenyl
cyclase activity. Phenylephrine also has an indirect effect by releasing
norepinephrine from its storage sites. Although the manufacturer reports
that there is no decrease in effectiveness with repeated injections of
phenylephrine, some investigators have reported that tachyphylaxis may
develop. The main effect of therapeutic doses of phenylephrine is
vasoconstriction.
Cardiovascular Effects
Phenylephrine constricts resistance and, to a lesser degree, capacitance
blood vessels by its effects on α-adrenergic receptors. Total peripheral
resistance is increased, resulting in increased systolic and diastolic blood
pressure. Venous return to the heart may be decreased; however,
phenylephrine increases venous pressure slightly. Blood flow to vital organs,
skin, and probably skeletal muscle is reduced. Phenylephrine may reduce
circulating plasma volume (especially with prolonged use) as a result of loss
of fluid into the extracellular spaces caused by postcapillary vasoconstriction.
In contrast to methoxamine, phenylephrine constricts coronary and
pulmonary blood vessels. Pulmonary arterial pressure usually is increased;
however, a decrease in pulmonary arterial pressure has occurred in some
patients, probably because of decreased cardiac output secondary to reflex
bradycardia.
Constriction of renal blood vessels by phenylephrine decreases renal blood
flow. In hypotensive patients, phenylephrine may initially decrease urine
flow and excretion of sodium and potassium. If the patient is not
hypovolemic, renal blood flow and glomerular filtration rate increase as the
systemic blood pressure is raised toward normal levels; however, renal
blood flow and glomerular filtration rate again decrease if blood pressure is
further increased toward hypertensive levels.
Local vasoconstriction and hemostasis also occur following topical application
or infiltration of phenylephrine into tissues. Like epinephrine, phenylephrine
probably produces hemostasis in cases of small vessel bleeding but does not
control bleeding from larger vessels. When administered by oral inhalation
(preparations for oral inhalation no longer are commercially available in the
US), phenylephrine reduces bronchiolar blood flow and shrinks swollen
membranes, thereby reducing edema and congestion. When used in
conjunction with a bronchodilator by oral inhalation, phenylephrine-induced
vasoconstriction slows the absorption of the bronchodilator and prolongs its
duration of action. Following oral administration or topical application of
phenylephrine to the mucosa, constriction of blood vessels in the nasal
mucosa may relieve nasal congestion.
The main effect of phenylephrine on the heart is bradycardia, which results
from increased vagal activity occurring as a reflex to increased arterial blood
pressure. Bradycardia occurs after parenteral administration of usual
therapeutic doses and also may result from overdosage via oral inhalation.
Attacks of paroxysmal atrial or nodal tachycardia may be ended by the
decrease in sympathetic cardioaccelerator tone and increase in
parasympathomimetic cardiodecelerator tone. Bradycardia is blocked by
atropine; if phenylephrine is administered after atropine, a slight increase in
heart rate may occur. In some patients, phenylephrine has caused a
paradoxical increase in heart rate when administered to treat hypotension
occurring after spinal anesthesia. Phenylephrine acts on β1-adrenergic
receptors in the heart, producing a positive inotropic effect on the
myocardium only at doses greater than those usually used therapeutically.
Cardiac output is decreased slightly, probably as a result of the reflex
bradycardia. Phenylephrine constricts coronary blood vessels but increases
coronary blood flow, probably as a result of increased systemic blood
pressure. An increase in myocardial oxygen uptake has been demonstrated
following administration of phenylephrine in animals, and the drug increases
the work of the heart by increasing peripheral arterial resistance. However,
phenylephrine does not appear to decrease cardiac efficiency. Rarely, the
drug may increase the irritability of the heart, causing arrhythmias such as
atrioventricular nodal rhythm, premature ventricular beats, ventricular
tachycardia, or ventricular extrasystoles.
Phenylephrine constricts cerebral blood vessels but increases cerebral blood
flow in hypotensive patients, probably secondary to increased systemic blood
pressure.
Other Effects
In therapeutic doses, phenylephrine causes little if any CNS stimulation but
may cause nervousness, restlessness, anxiety, dizziness, and tremor in
some patients, especially after overdosage.
As a result of its effects on α-adrenergic receptors, phenylephrine may cause
contraction of the pregnant uterus and constriction of uterine blood vessels;
however, the vasoconstrictor effect may be overcome by an increase in
maternal blood pressure.
Pharmacokinetics
Absorption
Phenylephrine is completely absorbed following oral administration and
undergoes extensive first-pass metabolism in the intestinal wall.121 122 The
bioavailability of phenylephrine following oral administration is
approximately 38% relative to IV administration.121 122 Because of extensive
first-pass metabolism, there is considerable interindividual and possibly
intraindividual variation in oral bioavailability of the drug.121 Following oral
administration of phenylephrine (1 or 7.8 mg), peak serum concentrations
occur at 0.75–2 hours.121 122
To achieve cardiovascular effects, phenylephrine should be given
parenterally. After IV administration, a pressor effect occurs almost
immediately and persists for 15–20 minutes. After IM administration, a
pressor effect occurs within 10–15 minutes and persists for 30 minutes to 1
or 2 hours. Occasionally, enough phenylephrine may be absorbed after oral
inhalation to produce systemic effects. Following oral administration, nasal
decongestion may occur within 15 or 20 minutes and may persist for 2–4
hours.
Distribution
Phenylephrine undergoes rapid distribution into peripheral tissues; there is
some evidence that the drug may be stored in certain organ
compartments.121 The pharmacologic effects of phenylephrine are terminated
at least partially by uptake of the drug into tissues. Penetration of
phenylephrine into the brain appears to be minimal.121
Phenylephrine does not appear to be distributed to any great extent into
breast milk.121
Elimination
Phenylephrine undergoes extensive metabolism in the intestinal wall (firstpass) and in the liver.121 122 The principal routes of metabolism involve sulfate
conjugation (primarily in the intestinal wall) and oxidative deamination (by
monoamine oxidase [MAO]); glucuronidation also occurs to a lesser
extent.121 122
Phenylephrine and its metabolites are excreted mainly in urine.121 122
Following oral or IV administration, approximately 80 or 86% of the dose,
respectively, is excreted in urine within 48 hours, principally as metabolites;
approximately 2.6% of an oral dose or 16% of an IV dose is excreted in
urine as unchanged drug.121 122 The elimination half-life of phenylephrine
averages 2–3 hours following oral or IV administration.121 122
Clinical data regarding effects of renal or hepatic impairment on the
pharmacokinetics of phenylephrine are limited.121 Because the majority of an
oral dose is metabolized in the intestinal wall and a lower fraction in the
liver, hepatic impairment is unlikely to result in major changes following oral
administration; however, phenylephrine pharmacokinetics may be
substantially altered following IV administration of the drug.121
Chemistry and Stability
Chemistry
Phenylephrine is a sympathomimetic amine that is pharmacologically similar
to methoxamine hydrochloride. Phenylephrine is commercially available as
the hydrochloride. Phenylephrine hydrochloride occurs as odorless, white or
practically white crystals having a bitter taste and is freely soluble in water
and in alcohol. Phenylephrine hydrochloride injection has a pH of 3.0–6.5.
Phenylephrine bitartrate occurs as a white, crystalline powder and is soluble
in water and insoluble in alcohol. Commercially available phenylephrine
hydrochloride injections may contain the antioxidant, sodium metabisulfite,
and the air in the ampuls has been replaced by nitrogen to prevent
oxidation.
Stability
Phenylephrine hydrochloride and solutions containing the drug are subject to
oxidation and should be stored in tight, light-resistant containers. Solutions
of the drug must not be used if they are brown or contain a precipitate.
However, oxidation of the drug resulting in loss of activity may occur without
a color change being evident.
Solutions of phenylephrine hydrochloride that have been diluted in 5%
dextrose injection are stable for at least 48 hours at pH 3.5–7.5. Although
phenylephrine has been reported to be incompatible with alkalies, the drug
is stable for at least 48 hours when diluted to 0.02 mg/mL with 5% sodium
bicarbonate injection. Phenylephrine is incompatible with ferric salts,
oxidizing agents, or metals.
Phenylephrine hydrochloride oral tablets should be stored at 15–25°C in a
dry place;114 orally dissolving strips should be stored at 20–25°C.123 124
Phenylephrine hydrochloride injections should be stored at room
temperature up to 30°C and protected from light.
Preparations
Excipients in commercially available drug preparations may have clinically
important effects in some individuals; consult specific product labeling for
details.
Many prescription cough, cold, and allergy preparations commercially
available in the US have not been approved by the US Food and Drug
Administration (FDA).500 Because of the potentially serious health risks
associated with unapproved preparations, FDA announced on March 3, 2011,
that it would take enforcement action (e.g., seizure, injunction, other judicial
or administrative proceeding) against any currently marketed and listed
unapproved cough, cold, and allergy preparation manufactured on or after
June 1, 2011 or shipped on or after August 30, 2011.500 For additional
information and for a complete list of unapproved cough, cold, and allergy
preparations affected by this FDA notice, see FDA website ([Web]).
Phenylephrine Hydrochloride
Routes
Dosage
Forms
Brand
Strengths Names
Manufacturer
Oral
Tablets
10 mg
Sudafed PE®
Congestion
McNeil
Parenteral Injection
10
mg/mL*
Generic
Name:
Phenylephrine
Hydrochloride
Injection
Topical
Cream
0.25%
Preparation
with
H®
Glycerin
14.4%,
Petrolatum
15%, and
Pramokine
1%
Pfizer
Gel
0.25%
Preparation
with Witch H®
Pfizer
Routes
Dosage
Forms
Brand
Strengths Names
Manufacturer
Hazel 50%
Ointment
0.25%
Preparation
with
H®
Mineral Oil
14%,
Petrolatum
71.9%
Suppository 0.25%
with
Cocoa
Butter
85.39%
Preparation
H®
Pfizer
Pfizer
* available from one or more manufacturer, distributor, and/or repackager
by generic (nonproprietary) name
Phenylephrine Hydrochloride Combinations
Dosage
Routes Forms
Oral
Strengths
Brand
Names
Manufacturer
Capsules, 5 mg with
(liquidAcetaminophen
filled)
325 mg and
Dextromethorphan
Hydrobromide 10
mg
Vicks®
Procter &
®
DayQuil
Gamble
Cold & Flu
Relief
LiquiCaps
For
Solution
10 mg/packet with
Acetaminophen
325 mg/packet
and Pheniramine
Maleate 20
mg/packet
Theraflu®
Cold &
Sore
Throat
Novartis
10 mg/packet with
Acetaminophen
650 mg/packet
and
Dextromethorphan
Theraflu®
Daytime
Severe
Cold &
Cough
Novartis
Dosage
Routes Forms
Strengths
Brand
Names
Manufacturer
Hydrobromide 20
mg
10 mg/packet with Theraflu® Novartis
Acetaminophen
Flu & Sore
650 mg/packet
Throat
and Pheniramine
Maleate 20
mg/packet
10mg/packet with
Acetaminophen
650 mg/packet
and
Diphenhydramine
Hydrochloride 25
mg
Solution
Theraflu®
Nighttime
Severe
Cold &
Cough
Novartis
10 mg/packet with Theraflu®
Dextromethorphan Cold &
Hydrobromide 20 Cough
mg/packet and
Pheniramine
Maleate 20
mg/packet
Novartis
5 mg/15 mL with
Acetaminophen
325 mg/15 mL
and
Dextromethorphan
Hydrobromide 10
mg/15 mL
Novartis
Theraflu
Warming
Relief®
Daytime
Severe
Cold &
Cough
Tylenol®
McNeil
Cold MultiSymptom
Daytime
Citrus
Burst®
Liquid
Vicks®
DayQuil®
Procter &
Gamble
Dosage
Routes Forms
Strengths
Brand
Names
Manufacturer
Cold & Flu
Relief
5 mg/15 mL with
Acetaminophen
325 mg/15 mL
and
Diphenhydramine
Hydrochloride
12.5 mg/15 mL
Theraflu® Novartis
Warming
Relief® Flu
& Sore
Throat
Theraflu®
Warming
Relief®
Nighttime
Severe
Cold &
Cough
2.5 mg/5 mL with Children's
Acetaminophen
Tylenol®
160 mg/5 mL and Plus Cold
Chlorpheniramine
Maleate 1 mg/5
mL
Novartis
McNeil
2.5 mg/5 mL with
Acetaminophen
160 mg/5 mL and
Chlorpheniramine
Maleate 1 mg/5
mL, and
Dextromethorphan
Hydrobromide 5
mg/5mL
Children's McNeil
Tylenol®
Plus MultiSymptom
Cold
2.5 mg/5 mL with
Acetaminophen
160 mg/5 mL and
Diphenhydramine
Hydrochloride
12.5 mg/5 mL
Children's
Tylenol®
Plus Cold
& Allergy
2.5 mg/5 mL with Triaminic®
McNeil
Novartis
Dosage
Routes Forms
Strengths
Brand
Names
Manufacturer
Chlorpheniramine
Maleate 1 mg/5
mL
Cold &
Allergy
2.5 mg/5 mL with
Dextromethorphan
Hydrobromide 5
mg/5mL
Children's McNeil
Sudafed
PE® Cold &
Cough
Triaminic®
Day Time
Cold &
Cough
2.5 mg/5mL with
Diphenhydramine
Hydrochloride
6.25 mg/5 mL
Novartis
Triaminic® Novartis
Night Time
Cold &
Cough
2.5 mg/5 mL with Triaminic® Novartis
Guaifenesin 50
Chest &
mg/5mL
Nasal
Congestion
Strips,
2.5 mg with
orally
Dextromethorphan
dissolving 3.67 mg
(equivalent to
Dextromethorphan
Hydrobromide 5
mg)
Tablets
Triaminic
Thin
Strips®
Day Time
Cold &
Cough
Novartis
5 mg with
Diphenhydramine
Hydrochloride
12.5 mg
Triaminic
Novartis
Thin
Strips®
Night Time
Cold &
Cough
5 mg with
Acetaminophen
325 mg,
Chlorpheniramine
Maleate 2 mg, and
Theraflu®
Warming
Relief
Caplets®
Nighttime
Novartis
Dosage
Routes Forms
Strengths
Brand
Names
Manufacturer
Dextromethorphan MultiHydrobromide 10 Symptom
mg
Cold
Tablets,
filmcoated
5 mg with
Acetaminophen
325 mg and
Dextromethorphan
Hydrobromide 10
mg
Theraflu
Warming
Relief
Caplets ®
Daytime
MultiSymptom
Cold
Novartis
10 mg with
Chlorpheniramine
Maleate 4 mg
Sudafed
PE® Sinus
+ Allergy
McNeil
5 mg with
Acetaminophen
325 mg
Excedrin®
Sinus
Headache
Novartis
Sudafed
McNeil
®
PE
Pressure +
Pain
Caplets
5 mg with
Acetaminophen
325 mg,
Chlorpheniramine
Maleate 2 mg, and
Dextromethorphan
Hydrobromide 10
mg
Tylenol®
McNeil
Cold Head
Congestion
Nighttime
Cool
Burst®
Caplets
5 mg with
Acetaminophen
325 mg and
Dextromethorphan
Hydrobromide 10
mg
Tylenol®
McNeil
Cold Head
Congestion
Daytime
Cool
Burst®
Caplets
Dosage
Routes Forms
Strengths
Brand
Names
Manufacturer
5 mg with
Acetaminophen
325 mg,
Dextromethorphan
Hydrobromide 10
mg, and
Guaifenesin 100
mg
Sudafed
McNeil
PE® Cold +
Cough
Caplets
5 mg with
Acetaminophen
325 mg,
Dextromethorphan
Hydrobromide 10
mg, and
Guaifenesin 200
mg
Tylenol®
McNeil
Cold Head
Congestion
Severe
Cool
Burst®
Caplets
5 mg with
Acetaminophen
325 mg and
Diphenhydramine
Hydrochloride
12.5 mg
Sudafed
McNeil
®
PE Severe
Cold
Caplets
5 mg with
Guaifenesin 200
mg
Sudafed
PE® NonDrying
Sinus
Caplets
McNeil
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS
Pharmacy. This pricing information was updated 02/2013. For the most
current and up-to-date pricing information, please visit www.drugstore.com.
Actual costs to patients will vary depending on the use of specific retail or
mail-order locations and health insurance copays.
Donatussin 10-2-15-100MG/5ML Syrup (LASER PHARMACEUTICALS):
473/$36.25 or 1419/$108.75
Duraphen Forte 30-30-1200MG 12-hr Tablets (KOWA PHARMACEUTICALS
AMERICA): 100/$135.98 or 300/$375.97
Duratuss AC 12 15-12.5-15MG/5ML Suspension (VICTORY PHARMA):
473/$215.99 or 1419/$609.96
Promethazine VC Plain 6.25-5MG/5ML Syrup (QUALITEST): 473/$39.99 or
1419/$109.97
R-Tanna 9-25MG Tablets (PRASCO LABORATORIES): 30/$39.99 or
90/$109.97
Rynatan 9-25MG Tablets (MEDA PHARMACEUTICALS): 30/$122.99 or
90/$349.97
Rynatan Pediatric 4.5-5MG/5ML Suspension (MEDA PHARMACEUTICALS):
120/$105.99 or 360/$299.96
AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions
November 4, 2011. American Society of Health-System Pharmacists, Inc.,
7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and
Drug Administration.
References
Only references cited for selected revisions after 1984 are available
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Burst® caplets (acetaminophen, chlorpheniramine maleate,
dextromethorphan hydrobromide, and phenylephrine hydrochloride) patient
information. From McNeil website. Accessed 2008 Feb 25.
40.
500. Food and Drug Administration. Drugs for human use; unapproved
and misbranded oral drugs labeled for prescription use and offered for relief
of symptoms of cold, cough, or allergy, enforcement action dates. Notice.
[Docket No. FDA-2011-N-0100] Fed Regist. 2011; 76:11794-8.
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