Preparation H

DRUG IMAGES

PREPARATION H SUPPOSITORY

The following indications for PREPARATION H (hydrocortisone) have been approved by the FDA:

Indications:
Allergic dermatitis
Atopic dermatitis
Contact dermatitis
Cutaneous T-cell lymphoma
Discoid lupus erythematosus
Genital organ pruritus
Granuloma annulare
Hemorrhoids
Lichen simplex chronicus
Plaque psoriasis
Proctitis
Pruritus ani
Pruritus of skin
Pyoderma gangrenosum
Rectal pain
Scalp psoriasis
Seborrheic dermatitis
Skin inflammation

Professional Synonyms:
Atopic eczema
Circumscribed neurodermatitis
Dermatitis seborrheica
Dermatitis venenata
Dermatitis
Disseminated neurodermatitis
Dyssebacea
Dyssebacia
Genital pruritus
Itchy skin eruption
Lichen annularis
Primary cutaneous T-cell lymphoma
Proctalgia
Pruritic dermatitis
Rectitis
Seborrhea corporis
Seborrheic eczema
Small cerebriform cell lymphoma
Unna's disease
Vidal's disease

The following dosing information is available for PREPARATION H (hydrocortisone):

Dosing
Administration
PREPARATION H
HYDROCORTISONE

Hydrocortisone and its acetate, buteprate, butyrate, and valerate esters are applied topically. Dermatologic preparations of the drugs are applied sparingly in thin films and are rubbed gently into the affected area 1-4 times daily. Rectal creams and ointments of the drugs are applied externally to the anal area.

Some commercially available creams may be applied externally to the anogenital areas. Nonprescription preparations of the drugs should not be used for self-medication for longer than 7 days; if the condition worsens or symptoms persist, the drug should be discontinued and a physician consulted. Nonprescription preparations of the drugs should not be used in children younger than 2 years of age unless directed and supervised by a physician.

For dermatoses of the scalp, the hair may be parted and a small amount of lotion applied directly to the affected area and rubbed gently into the scalp. Usual hair care should be maintained, but the lotion should not be washed out immediately after application. Alternatively, for dermatoses of the scalp, hydrocortisone aerosol is applied to the dry scalp after shampooing.

When the aerosol is used for other dermatoses, each 10-cm2 of affected area is sprayed for 1-2 seconds from a distance of about 15 cm 2 or 3 times daily.

Occlusive dressings may be used for severe or resistant dermatoses.

For use in the mouth, a small amount of 0.5% hydrocortisone acetate paste is pressed to the lesion without rubbing until a thin film develops. The paste is applied 2 or 3 times daily after meals and at bedtime.

If substantial regeneration or repair of the oral tissues does not occur after 7 days of treatment, further investigation of the etiology of the oral lesions should be undertaken.

Hydrocortisone is administered rectally as a retention enema, and hydrocortisone acetate is given rectally as a suppository or an aerosol foam suspension according to the manufacturers' instructions. Patients should be advised that hydrocortisone acetate suppositories may stain fabric so that they can take appropriate precautionary measures. For the adjunctive treatment of ulcerative colitis, 100 mg of hydrocortisone is administered nightly as a retention enema.

The patient should lie on his left side during and for 30 minutes after administration of the retention enema so that the drug will distribute throughout the left colon; the enema should be retained for at least 1 hour and preferably all night. Some clinicians administer 100 mg as a retention enema twice daily followed by 100 mg nightly when improvement occurs. The drug is usually given for 21 days or until clinical and proctologic remissions are achieved.

Clinical symptoms may improve in 3-5 days, followed by proctologic improvement; in some cases, 2-3 months of therapy may be required to attain a proctologic remission. Therapy with hydrocortisone retention enema should be discontinued if clinical or proctologic improvement does not occur within 2-3 weeks. Following treatment for longer than 21 days, therapy with hydrocortisone enema should be withdrawn gradually by giving the drug every other night for 2-3 weeks and then discontinuing it.

In patients with ulcerative proctitis of the distal rectum who cannot retain corticosteroid enemas, 90 mg of hydrocortisone acetate (1 applicatorful of a 10% aerosol foam suspension) may be given rectally 1 or 2 times daily for 2-3 weeks and then, if necessary, every other day until clinical and proctologic improvements occur; symptoms may improve within 5-7 days. For the adjunctive treatment of ulcerative colitis of the rectum and other inflammatory conditions of the anorectum, 25 mg of hydrocortisone acetate as a suppository may be administered rectally in the morning and at night for 2 weeks; in severe proctitis, 25 mg may be given 3 times daily or 50 mg may be given twice daily. For the adjunctive treatment of postirradiation or factitial proctitis, therapy is generally continued for 6-8 weeks or less if an adequate response is attained.

Alternatively, for the symptomatic treatment of internal hemorrhoids and the adjunctive treatment of other inflammatory conditions of the anorectum, 10 mg of hydrocortisone acetate as a suppository may be administered rectally in the morning and at night for 2-6 days.

For self-medication for the temporary relief of pain and itching associated with lip or skin irritations in adults and children 2 years of age and older, pramoxine hydrochloride 1% gel, lotion, ointment, or solution is applied topically to the affected area up to 3 or 4 times daily. For use in children younger than 2 years of age, a pediatrician should be consulted.

For self-medication for the temporary relief of pain, soreness, burning, itching, or discomfort caused by hemorrhoids or other anorectal disorders in adults and children 12 years of age and older, pramoxine hydrochloride 1% aerosol foam, cream, ointment, or pledget is applied topically to the affected area up to 4 or 5 times daily or after each bowel movement. The manufacturers state that this dosage should not be exceeded unless directed by a clinician. For use in children younger than 12 years of age, a clinician should be consulted.

For self-medication for the management of anogenital pruritus, pramoxine hydrochloride 1% pledget is applied to the external vaginal area up to 3-4 times daily. For use in children younger than 12 years of age, a clinician should be consulted.

To produce decongestion of the conjunctiva, 1 or 2 drops of a 0.12-0.25% ophthalmic solution of phenylephrine hydrochloride may be applied topically to the conjunctiva every 3-4 hours (up to 4 times daily for self-medication) as needed.

Vasoconstriction for diagnosis of ocular congestion or to improve visualization of ocular blood vessels in sickle-cell disease may be achieved by application of 1 or 2 drops of a 2.5% solution. In the ''blanching test'', congestion probably is caused by conjunctivitis rather than iridocyclitis if the drug produces perilimbal blanching in the congested eye.

A 2.5 or 10% solution of the drug may also be administered prior to surgery to produce mydriasis and aid in controlling hemorrhage. (See Phenylephrine Hydrochloride 52:24.)

To produce nasal decongestion in adults and children 12 years of age or older, the usual dosage is 2 or 3 drops, 1-3 sprays, or 1-3 metered sprays instilled in each nostril. In cases of extreme nasal congestion in adults, a 1% solution may be used initially. To produce nasal decongestion in children 6-12 years of age, 2 or 3 drops or 1 or 2 sprays of a 0.25%

solution may be instilled in each nostril. Doses of the drug as drops or spray may be repeated in 4 hours if needed. Phenylephrine nasal solutions should not be used for self-medication for longer than 3 days; if symptoms persist, the drug should be discontinued and a physician consulted.

Intranasal application of phenylephrine should generally be used for no longer than 3-5 days.

For use with local anesthetics, phenylephrine hydrochloride may be used in concentrations of 1:2500 to 1:20,000.

Preparations containing pramoxine hydrochloride are applied topically. These preparations may be applied to the lip in the form of an ointment (''lip balm''); to the skin in the form of a gel, lotion, ointment, or solution; to the external vaginal area in the form of pledgets (pads); or to the external anorectal area in the form of an aerosol foam, cream, ointment, or pledgets. The lotion containing pramoxine hydrochloride should be shaken well prior to use.

The aerosol foam should be shaken well and dispersed onto a clean tissue before applying to the affected area. Pledgets should be applied gently by patting or wiping the affected area; pledgets should be used only once and then discarded. Patients receiving pramoxine-containing preparations for the management of hemorrhoids or other anorectal disorders should be advised to cleanse the affected perianal area with mild soap and warm water and rinsing thoroughly whenever practical; the area then should be dried by patting or blotting with toilet tissue or a soft cloth before application of the drug.

Phenylephrine hydrochloride ophthalmic solutions are applied topically to the conjunctiva. Digital pressure should be applied on the lacrimal sac for 1-2 minutes following topical instillation of ophthalmic solutions to minimize drainage into the nose and throat and reduce the risk of absorption and systemic reactions. Excess solution around the eye should be removed with a tissue.

For intranasal applications, phenylephrine may be administered in solution as drops or spray. Vicks Sinex(R) (with mist spray nozzle) nasal solution is administered by nasal inhalation using a special nasal inhaler that produces metered droplet sprays. Care must be taken to avoid contamination of the dropper, inhaler, or spray.

Except in young children in whom sprays are difficult to use, nasal sprays may be preferable to drops because of the lesser risk of swallowing the drug and resultant systemic absorption. Drops should be applied to the dependent (lower) nostril, with the patient in a lateral head-low position. The patient should remain in the same position for 5 minutes, then the solution should be applied to the other nostril in a similar manner.

Alternatively, drops may be instilled when the patient is reclining with the head tilted back as far as possible. Sprays should be delivered or pumped (Vicks Sinex(R) metered spray) into each nostril with the patient's head erect so that excess solution is not released. The nose should be blown thoroughly 3-5 minutes later.

Prior to initial use of the metered sprays, the nasal inhaler must be primed by depressing the pump firmly several times. To minimize the risk of spreading infections, droppers, inhalers, and spray dispensers should not be used by more than one person, and tips of the dispensers, inhalers, or droppers should be rinsed with hot water following use. Phenylephrine nasal solutions also may be applied to a tampon or nasal pack for insertion into nasal passages. However, this method of application should be restricted to use in diagnostic or surgical procedures performed under medical supervision because mechanical injury may occur.

Dosing information for PREPARATION H
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
PREPARATION H HC 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day

Generic dosing information for HYDROCORTISONE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day
RA HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day
KRO HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day
EQ HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day
CVS HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day
HM HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day
QC HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day
GNP HYDROCORTISONE 1% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route 2 times per day

The following drug interaction information is available for PREPARATION H (hydrocortisone):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Sympathomimetics (Indirect & Mixed Acting)/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine). CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Fatalities have occurred. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of monoamine oxidase inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic. DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact. Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors. Since procarbazine, an antineoplastic agent, is a weak monoamine oxidase inhibitor, hypertensive reactions may result from its concurrent use with indirect and mixed acting sympathomimetics. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics. Linezolid is another antibacterial with monoamine oxidase inhibitor properties. Metaxalone is a weak inhibitor of MAO. Foods containing large amounts of tyramine have also been implicated in this interaction. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. At recommended dosages, rasagiline, oral selegiline, and transdermal selegiline up to 6mg/day are selective for MAO-B; however, at higher dosages they have been shown to lose their selectivity. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.	EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE

Drug Interaction

Drug Names

Sympathomimetics (Indirect & Mixed Acting)/MAOIs

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine).

CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Fatalities have occurred.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of monoamine oxidase inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic.

DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact.

Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors. Since procarbazine, an antineoplastic agent, is a weak monoamine oxidase inhibitor, hypertensive reactions may result from its concurrent use with indirect and mixed acting sympathomimetics. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics.

Linezolid is another antibacterial with monoamine oxidase inhibitor properties. Metaxalone is a weak inhibitor of MAO. Foods containing large amounts of tyramine have also been implicated in this interaction.

Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. At recommended dosages, rasagiline, oral selegiline, and transdermal selegiline up to 6mg/day are selective for MAO-B; however, at higher dosages they have been shown to lose their selectivity. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems.

This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.

EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE

There are 4 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Mixed;Indirect Sympathomimetics/Selected MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine). CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Fatalities have occurred with combinations of sympathomimetics and MAO-A inhibitors. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of MAO-A inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic. Patients receiving direct or indirect acting sympathomimetics should not receive linezolid unless they are monitored for potential increases in blood pressure. Initial dosages of dopamine and epinephrine should be reduced. At recommended dosages, oral selegiline and transdermal selegiline up to 6mg/day are selective for MAO-B; however, at higher dosages they have been shown to lose their selectivity. Patients receiving higher dosages of selegiline should be considered susceptive to this interaction. DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact. Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics. Foods containing large amounts of tyramine have also been implicated in this interaction. A significant pressor response was observed in normal subjects receiving linezolid and tyramine doses of more than 100 mg. Administration of linezolid (600 mg BID for 3 days) with pseudoephedrine (60 mg q 4 hours for 2 doses) increased blood pressure by 32 mmHg. Administration of linezolid (600 mg BID for 3 days) with phenylpropanolamine (25 mg q 4 hours for 2 doses) increased blood pressure by 38 mmHg. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.	EMSAM, LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, SELEGILINE HCL, XADAGO, ZELAPAR, ZYVOX
Iobenguane I 123/Agents that Affect Catecholamines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1) CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1) DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine)	ADREVIEW
Long-acting Bupivacaine/Local Anesthetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1) CLINICAL EFFECTS: Concurrent or use of local anesthetics with 96 hours of use of long-acting bupivacaine may result in neurologic and cardiovascular toxicity. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also result in methemoglobinemia.(1,2) Non-liposomal bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally.(1) PREDISPOSING FACTORS: Use of additional agents that are associated with methemoglobinemia may further increase the risk of methemoglobinemia.(1) Patients who are at increased risk of developing methemoglobinemia include those with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.(1) PATIENT MANAGEMENT: Avoid the use of other local anesthetics within 96 hours following the administration of long-acting bupivacaine. In patients for whom use is required, monitor for neurologic and cardiovascular effects. Also monitor for methemoglobinemia with use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine.(1,2) Non-liposomal bupivacaine may be administered in the same syringe as bupivacaine liposomal or injected immediately before bupivacaine liposomal as long as the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1) DISCUSSION: Concurrent use of other local anesthetics or use of other local anesthetics within 96 hours following long-acting bupivacaine may result in additive neurologic and cardiovascular effects. Use of articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, and tetracaine may also increase the risk of methemoglobinemia.(1,2) Non-liposome bupivacaine may impact the pharmacokinetic and/or physicochemical properties of the liposomal formulation when administered in the same syringe or used simultaneously unless the ratio of mg of non-liposomal bupivacaine to mg of bupivacaine liposomal does not exceed 1:2.(1) Local anesthetics other than bupivacaine may trigger the immediate release of bupivacaine from the liposomal formulation when administered together locally. Lidocaine may be administered 20 minutes or more prior to bupivacaine. It is unknown if other local anesthetics may be used without compromising the release characteristic of bupivacaine liposomal.(1)	BUPIVACAINE LIPOSOME, EXPAREL, XARACOLL, ZYNRELEF
Mixed;Indirect Sympathomimetics/Rasagiline SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine). CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Hypertensive crisis has been reported in patients taking recommended doses of rasagiline with sympathomimetic agents. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: At recommended dosages, rasagiline is selective for MAO-B; however, at higher dosages it has been shown to lose its selectivity. Patients receiving higher dosages of rasagiline should be considered susceptive to this interaction. Concurrent use should be approached with caution. DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact. Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors.	AZILECT, RASAGILINE MESYLATE

There are 2 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Sympathomimetics/Rauwolfia Alkaloids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Reserpine depletes catecholamine stores within the peripheral vascular adrenergic nerve endings, thus indirect acting sympathomimetics are unable to trigger the release of catecholamines. The reserpine-induced catecholamine release increases sensitivity to the effects of direct acting sympathomimetics. CLINICAL EFFECTS: Increased effects of direct acting sympathomimetics. Decreased effects of indirect acting sympathomimetics. Mixed acting sympathomimetics will show effects based on the predominance of either direct or indirect activity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If these agents are administered concurrently, monitor blood pressure. The dose of the sympathomimetic may need to be adjusted. DISCUSSION: This interaction has been well documented in animal studies and human case reports have confirmed the interaction. Reserpine has been shown to decrease the response to epinephrine administered for hypotension. Reserpine has also been shown to decrease the effectiveness of ophthalmic epinephrine, a direct acting sympathomimetic. Ophthalmic phenylephrine has been shown to decrease the hypotensive effects of reserpine.	RESERPINE
Sympathomimetics (Direct, Mixed-Acting)/Methyldopa SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa. DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported.	METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE, METHYLDOPATE HCL

Drug Interaction

Drug Names

Sympathomimetics/Rauwolfia Alkaloids

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Reserpine depletes catecholamine stores within the peripheral vascular adrenergic nerve endings, thus indirect acting sympathomimetics are unable to trigger the release of catecholamines. The reserpine-induced catecholamine release increases sensitivity to the effects of direct acting sympathomimetics.

CLINICAL EFFECTS: Increased effects of direct acting sympathomimetics. Decreased effects of indirect acting sympathomimetics. Mixed acting sympathomimetics will show effects based on the predominance of either direct or indirect activity.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If these agents are administered concurrently, monitor blood pressure. The dose of the sympathomimetic may need to be adjusted.

DISCUSSION: This interaction has been well documented in animal studies and human case reports have confirmed the interaction. Reserpine has been shown to decrease the response to epinephrine administered for hypotension. Reserpine has also been shown to decrease the effectiveness of ophthalmic epinephrine, a direct acting sympathomimetic. Ophthalmic phenylephrine has been shown to decrease the hypotensive effects of reserpine.

RESERPINE

Sympathomimetics (Direct, Mixed-Acting)/Methyldopa

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unknown.

CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa.

DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported.

METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE, METHYLDOPATE HCL

The following contraindication information is available for PREPARATION H (hydrocortisone):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 0 contraindications.

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Large open wound

There are 7 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Benign prostatic hyperplasia
Cardiac arrhythmia
Coronary artery disease
Hypertension
Hyperthyroidism
Hypothalamic-pituitary insufficiency
Nervousness

The following adverse reaction information is available for PREPARATION H (hydrocortisone):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 38 severe adverse reactions.

More Frequent	Less Frequent
None.	Dermatitis due to topical drug Folliculitis Purpura Skin and skin structure infection Skin atrophy

Rare/Very Rare
Acute respiratory failure Adrenocortical insufficiency Anaphylaxis Angioedema Bradycardia Bronchospastic pulmonary disease Bullous dermatitis Cardiac arrhythmia Cataracts Central serous chorioretinopathy CNS toxicity Cyanosis Dizziness Eyelid edema Glaucoma Headache disorder Hyperhidrosis Hypotension Hypothalamic-pituitary insufficiency Insomnia Methemoglobinemia Nervousness Ocular hypertension Pallor Respiratory depression Seizure disorder Skin hypopigmentation Skin striae Skin ulcer Tachycardia Tremor Unconsciousness Urticaria

Rare/Very Rare

Acute respiratory failure
Adrenocortical insufficiency
Anaphylaxis
Angioedema
Bradycardia
Bronchospastic pulmonary disease
Bullous dermatitis
Cardiac arrhythmia
Cataracts
Central serous chorioretinopathy
CNS toxicity
Cyanosis
Dizziness
Eyelid edema
Glaucoma
Headache disorder
Hyperhidrosis
Hypotension
Hypothalamic-pituitary insufficiency
Insomnia
Methemoglobinemia
Nervousness
Ocular hypertension
Pallor
Respiratory depression
Seizure disorder
Skin hypopigmentation
Skin striae
Skin ulcer
Tachycardia
Tremor
Unconsciousness
Urticaria

There are 43 less severe adverse reactions.

More Frequent	Less Frequent
Erythema Stinging of skin	Acute pain at drug application site Blanching of skin Blurred vision Edema Erythema Headache disorder Paresthesia Pruritus of skin Skin rash Stinging of skin Telangiectasia Treatment site sequelae Urticaria

Rare/Very Rare
Acneiform eruption Acute cognitive impairment Alopecia Apprehension Blistering skin Blurred vision Contact dermatitis Dizziness Drowsy Dry skin Dyschromia Euphoria Glycosuria Hirsutism Hypercortisolism Hyperesthesia Hyperglycemia Miliaria Muscle fasciculation Nervousness Perioral dermatitis Rectal irritation Sensation of cold Sensation of warmth Skin irritation Tinnitus Tremor Vomiting

The following precautions are available for PREPARATION H (hydrocortisone):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Women who are pregnant should consult a clinician before initiating therapy with pramoxine-containing preparations. Animal reproduction studies have not been performed with phenylephrine. It is not known whether topically applied phenylephrine can cause fetal harm when administered to pregnant women.

Parenterally administered phenylephrine in late pregnancy or labor may cause fetal anoxia. (See Cautions: Pregnancy and Lactation, in Phenylephrine Hydrochloride 12:12.04.) Topically applied phenylephrine should be used during pregnancy only when clearly needed.

Women who are breast-feeding should consult a clinician before initiating therapy with pramoxine-containing preparations. Since it is not known whether phenylephrine is distributed into milk, the drug should be used with caution in nursing women.

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for PREPARATION H (hydrocortisone)'s list of indications:

Allergic dermatitis
L20	Atopic dermatitis
L20.0	Besnier's prurigo
L20.8	Other atopic dermatitis
L20.81	Atopic neurodermatitis
L20.82	Flexural eczema
L20.83	Infantile (acute) (chronic) eczema
L20.84	Intrinsic (allergic) eczema
L20.89	Other atopic dermatitis
L20.9	Atopic dermatitis, unspecified
L23	Allergic contact dermatitis
L23.0	Allergic contact dermatitis due to metals
L23.1	Allergic contact dermatitis due to adhesives
L23.2	Allergic contact dermatitis due to cosmetics
L23.3	Allergic contact dermatitis due to drugs in contact with skin
L23.4	Allergic contact dermatitis due to dyes
L23.5	Allergic contact dermatitis due to other chemical products
L23.6	Allergic contact dermatitis due to food in contact with the skin
L23.7	Allergic contact dermatitis due to plants, except food
L23.8	Allergic contact dermatitis due to other agents
L23.81	Allergic contact dermatitis due to animal (cat) (dog) dander
L23.89	Allergic contact dermatitis due to other agents
L23.9	Allergic contact dermatitis, unspecified cause
Atopic dermatitis
L20	Atopic dermatitis
L20.0	Besnier's prurigo
L20.8	Other atopic dermatitis
L20.81	Atopic neurodermatitis
L20.82	Flexural eczema
L20.84	Intrinsic (allergic) eczema
L20.89	Other atopic dermatitis
L20.9	Atopic dermatitis, unspecified
Contact dermatitis
L23	Allergic contact dermatitis
L23.0	Allergic contact dermatitis due to metals
L23.1	Allergic contact dermatitis due to adhesives
L23.2	Allergic contact dermatitis due to cosmetics
L23.3	Allergic contact dermatitis due to drugs in contact with skin
L23.4	Allergic contact dermatitis due to dyes
L23.5	Allergic contact dermatitis due to other chemical products
L23.6	Allergic contact dermatitis due to food in contact with the skin
L23.7	Allergic contact dermatitis due to plants, except food
L23.8	Allergic contact dermatitis due to other agents
L23.81	Allergic contact dermatitis due to animal (cat) (dog) dander
L23.89	Allergic contact dermatitis due to other agents
L23.9	Allergic contact dermatitis, unspecified cause
L24	Irritant contact dermatitis
L24.0	Irritant contact dermatitis due to detergents
L24.1	Irritant contact dermatitis due to oils and greases
L24.2	Irritant contact dermatitis due to solvents
L24.3	Irritant contact dermatitis due to cosmetics
L24.4	Irritant contact dermatitis due to drugs in contact with skin
L24.5	Irritant contact dermatitis due to other chemical products
L24.6	Irritant contact dermatitis due to food in contact with skin
L24.7	Irritant contact dermatitis due to plants, except food
L24.8	Irritant contact dermatitis due to other agents
L24.81	Irritant contact dermatitis due to metals
L24.89	Irritant contact dermatitis due to other agents
L24.9	Irritant contact dermatitis, unspecified cause
L24.A0	Irritant contact dermatitis due to friction or contact with body fluids, unspecified
L24.A1	Irritant contact dermatitis due to saliva
L24.A2	Irritant contact dermatitis due to fecal, urinary or dual incontinence
L24.A9	Irritant contact dermatitis due friction or contact with other specified body fluids
L24.B	Irritant contact dermatitis related to stoma or fistula
L24.B0	Irritant contact dermatitis related to unspecified stoma or fistula
L24.B1	Irritant contact dermatitis related to digestive stoma or fistula
L24.B2	Irritant contact dermatitis related to respiratory stoma or fistula
L24.B3	Irritant contact dermatitis related to fecal or urinary stoma or fistula
L25	Unspecified contact dermatitis
L25.0	Unspecified contact dermatitis due to cosmetics
L25.1	Unspecified contact dermatitis due to drugs in contact with skin
L25.2	Unspecified contact dermatitis due to dyes
L25.3	Unspecified contact dermatitis due to other chemical products
L25.4	Unspecified contact dermatitis due to food in contact with skin
L25.5	Unspecified contact dermatitis due to plants, except food
L25.8	Unspecified contact dermatitis due to other agents
L25.9	Unspecified contact dermatitis, unspecified cause
Cutaneous t-cell lymphoma
C84.0	Mycosis fungoides
C84.A	Cutaneous t-cell lymphoma, unspecified
C84.A0	Cutaneous t-cell lymphoma, unspecified, unspecified site
C84.A1	Cutaneous t-cell lymphoma, unspecified lymph nodes of head, face, and neck
C84.A2	Cutaneous t-cell lymphoma, unspecified, intrathoracic lymph nodes
C84.A3	Cutaneous t-cell lymphoma, unspecified, intra-abdominal lymph nodes
C84.A4	Cutaneous t-cell lymphoma, unspecified, lymph nodes of axilla and upper limb
C84.A5	Cutaneous t-cell lymphoma, unspecified, lymph nodes of inguinal region and lower limb
C84.A6	Cutaneous t-cell lymphoma, unspecified, intrapelvic lymph nodes
C84.A7	Cutaneous t-cell lymphoma, unspecified, spleen
C84.A8	Cutaneous t-cell lymphoma, unspecified, lymph nodes of multiple sites
C84.A9	Cutaneous t-cell lymphoma, unspecified, extranodal and solid organ sites
Discoid lupus erythematosus
H01.12	Discoid lupus erythematosus of eyelid
H01.121	Discoid lupus erythematosus of right upper eyelid
H01.122	Discoid lupus erythematosus of right lower eyelid
H01.123	Discoid lupus erythematosus of right eye, unspecified eyelid
H01.124	Discoid lupus erythematosus of left upper eyelid
H01.125	Discoid lupus erythematosus of left lower eyelid
H01.126	Discoid lupus erythematosus of left eye, unspecified eyelid
H01.129	Discoid lupus erythematosus of unspecified eye, unspecified eyelid
L93.0	Discoid lupus erythematosus
Genital organ pruritus
L29.2	Pruritus vulvae
L29.3	Anogenital pruritus, unspecified
Granuloma annulare
L92.0	Granuloma annulare
Hemorrhoids
K64.0	First degree hemorrhoids
K64.8	Other hemorrhoids
K64.9	Unspecified hemorrhoids
O22.4	Hemorrhoids in pregnancy
O22.40	Hemorrhoids in pregnancy, unspecified trimester
O22.41	Hemorrhoids in pregnancy, first trimester
O22.42	Hemorrhoids in pregnancy, second trimester
O22.43	Hemorrhoids in pregnancy, third trimester
O87.2	Hemorrhoids in the puerperium
Lichen simplex chronicus
L28.0	Lichen simplex chronicus
Plaque psoriasis
L40.0	Psoriasis vulgaris
L40.9	Psoriasis, unspecified
Proctitis
K62.7	Radiation proctitis
K62.89	Other specified diseases of anus and rectum
Pruritus ani
L29.0	Pruritus ani
L29.3	Anogenital pruritus, unspecified
Pruritus of skin
L29.8	Other pruritus
L29.81	Cholestatic pruritus
L29.89	Other pruritus
L29.9	Pruritus, unspecified
Pyoderma gangrenosum
L88	Pyoderma gangrenosum
Rectal pain
K62.89	Other specified diseases of anus and rectum
Scalp psoriasis
L40.0	Psoriasis vulgaris
L40.1	Generalized pustular psoriasis
L40.4	Guttate psoriasis
L40.8	Other psoriasis
L40.9	Psoriasis, unspecified
Seborrheic dermatitis
L21	Seborrheic dermatitis
L21.0	Seborrhea capitis
L21.1	Seborrheic infantile dermatitis
L21.8	Other seborrheic dermatitis
L21.9	Seborrheic dermatitis, unspecified
Skin inflammation
L20	Atopic dermatitis
L20.8	Other atopic dermatitis
L20.89	Other atopic dermatitis
L20.9	Atopic dermatitis, unspecified
L21	Seborrheic dermatitis
L21.8	Other seborrheic dermatitis
L21.9	Seborrheic dermatitis, unspecified
L25	Unspecified contact dermatitis
L30.8	Other specified dermatitis
L30.9	Dermatitis, unspecified
L40	Psoriasis
L40.1	Generalized pustular psoriasis
L40.8	Other psoriasis
L40.9	Psoriasis, unspecified
R21	Rash and other nonspecific skin eruption