Naropin

ropivacaine hydrochloride

Dosage Form: injection, solution
Naropin® (ropivacaine HCl) Injection

Rx only

Naropin Description

Naropin® Injection contains ropivacaine HCl which is a member of the amino amide class of local anesthetics.  Naropin Injection is a sterile, isotonic solution that contains the enantiomerically pure drug substance, sodium chloride for isotonicity and Water for Injection.  Sodium hydroxide and/or hydrochloric acid may be used for pH adjustment.  It is administered parenterally.

Ropivacaine HCl is chemically described as S-(-)-1-propyl-2',6'-pipecoloxylidide hydrochloride monohydrate.  The drug substance is a white crystalline powder, with the following structural formula:

C17H26N2O•HCl•H2O               M.W. 328.89

At 25°C ropivacaine HCl has a solubility of 53.8 mg/mL in water, a distribution ratio between n-octanol and phosphate buffer at pH 7.4 of 14:1 and a pKa of 8.07 in 0.1 M KCl solution.  The pKa of ropivacaine is approximately the same as bupivacaine (8.1) and is similar to that of mepivacaine (7.7).  However, ropivacaine has an intermediate degree of lipid solubility compared to bupivacaine and mepivacaine.

Naropin Injection is preservative-free and is available in single dose containers in 2 (0.2%), 5 (0.5%), 7.5 (0.75%) and 10 mg/mL (1%) concentrations.  The specific gravity of Naropin Injection solutions range from 1.002 to 1.005 at 25°C.

Naropin - Clinical Pharmacology

Mechanism of Action

Ropivacaine is a member of the amino amide class of local anesthetics and is supplied as the pure S-(-)-enantiomer.  Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential.  In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.  Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.

PHARMACOKINETICS

Absorption

The systemic concentration of ropivacaine is dependent on the total dose and concentration of drug administered, the route of administration, the patient's hemodynamic/circulatory condition, and the vascularity of the administration site.

From the epidural space, ropivacaine shows complete and biphasic absorption.  The half-lives of the 2 phases, (mean ± SD) are 14 ± 7 minutes and 4.2 ± 0.9 h, respectively.  The slow absorption is the rate limiting factor in the elimination of ropivacaine that explains why the terminal half-life is longer after epidural than after intravenous administration.  Ropivacaine shows dose-proportionality up to the highest intravenous dose studied, 80 mg, corresponding to a mean ± SD peak plasma concentration of 1.9 ± 0.3 mcg/mL.

                                                                        Table 1

                      Pharmacokinetic (plasma concentration-time) data from clinical trials

Route	Epidural Infusion*		Epidural Infusion*	Epidural Block†	Epidural Block†	Plexus Block‡	IV Infusion§
Dose (mg)	1493 ± 10	2075 ± 206	1217 ± 277	150	187.5	300	40
N	12	12	11	8	8	10	12
Cmax (mg/L)	2.4 ± 1¶	2.8 ± 0.5¶	2.3 ± 1.1¶	1.1 ± 0.2	1.6 ± 0.6	2.3 ± 0.8	1.2 ± 0.2#
Tmax (min)	n/a♠	n/a	n/a	43 ± 14	34 ± 9	54 ± 22	n/a
AUC0- (mg.h/L)	135.5 ± 50	145 ± 34	161 ± 90	7.2 ± 2	11.3 ± 4	13 ± 3.3	1.8 ± 0.6
CL (L/h)	11.03	13.7	n/a	5.5 ± 2	5 ± 2.6	n/a	21.2 ± 7
t1/2 (hr) ♥	5 ± 2.5	5.7 ± 3	6 ± 3	5.7 ± 2	7.1 ± 3	6.8 ± 3.2	1.9 ± 0.5

*  Continuous 72 hour epidural infusion after an epidural block with 5 or 10 mg/mL.

†  Epidural anesthesia with 7.5 mg/mL (0.75%) for cesarean delivery.

‡  Brachial plexus block with 7.5 mg/mL (0.75%) ropivacaine.

§  20 minute IV infusion to volunteers (40 mg).

¶  Cmax measured at the end of infusion (ie, at 72 hr).

#  Cmax measured at the end of infusion (ie, at 20 minutes).

♠  n/a=not applicable

♥  t½ is the true terminal elimination half-life.  On the other hand, t½ follows absorption‑dependent elimination (flip-flop) after non-intravenous administration.

 

In some patients after a 300 mg dose for brachial plexus block, free plasma concentrations of ropivacaine may approach the threshold for CNS toxicity (see PRECAUTIONS).  At a dose of greater than 300 mg, for local infiltration, the terminal half-life may be longer (>30 hours).

Distribution

After intravascular infusion, ropivacaine has a steady-state volume of distribution of 41 ± 7 liters.  Ropivacaine is 94% protein bound, mainly to α1-acid glycoprotein.  An increase in total plasma concentrations during continuous epidural infusion has been observed, related to a postoperative increase of α1-acid glycoprotein.  Variations in unbound, ie, pharmacologically active, concentrations have been less than in total plasma concentration.  Ropivacaine readily crosses the placenta and equilibrium in regard to unbound concentration will be rapidly reached (see PRECAUTIONS , Labor and Delivery).

Metabolism

Ropivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxy ropivacaine.  After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine.  Low concentrations of 3-hydroxy ropivacaine have been found in the plasma.  Urinary excretion of the 4-hydroxy ropivacaine, and both the 3-hydroxy N-de-alkylated (3-OH-PPX) and 4-hydroxy N-de-alkylated (4-OH-PPX) metabolites account for less than 3% of the dose.  An additional metabolite, 2-hydroxy-methyl-ropivacaine, has been identified but not quantified in the urine.  The N-de-alkylated metabolite of ropivacaine (PPX) and 3-OH-ropivacaine are the major metabolites excreted in the urine during epidural infusion.  Total PPX concentration in the plasma was about half as that of total ropivacaine; however, mean unbound concentrations of PPX were about 7 to 9 times higher than that of unbound ropivacaine following continuous epidural infusion up to 72 hours.  Unbound PPX, 3-hydroxy and 4-hydroxy ropivacaine, have a pharmacological activity in animal models less than that of ropivacaine.  There is no evidence of in vivo racemization in urine of ropivacaine.

Elimination

The kidney is the main excretory organ for most local anesthetic metabolites.  In total, 86% of the ropivacaine dose is excreted in the urine after intravenous administration of which only 1% relates to unchanged drug.  After intravenous administration ropivacaine has a mean ± SD total plasma clearance of 387 ± 107 mL/min, an unbound plasma clearance of 7.2 ± 1.6 L/min, and a renal clearance of 1 mL/min.  The mean ± SD terminal half-life is 1.8 ± 0.7 h after intravascular administration and 4.2 ± 1 h after epidural administration (see Absorption).

Pharmacodynamics

Studies in humans have demonstrated that, unlike most other local anesthetics, the presence of epinephrine has no major effect on either the time of onset or the duration of action of ropivacaine.  Likewise, addition of epinephrine to ropivacaine has no effect on limiting systemic absorption of ropivacaine.

Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems.  At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance have been reported.  Toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities.  In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.

Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.  Apparent central stimulation is usually manifested as restlessness, tremors and shivering, progressing to convulsions, followed by depression and coma, progressing ultimately to respiratory arrest.  However, the local anesthetics have a primary depressant effect on the medulla and on higher centers.  The depressed stage may occur without a prior excited stage.

In 2 clinical pharmacology studies (total n=24) ropivacaine and bupivacaine were infused (10 mg/min) in human volunteers until the appearance of CNS symptoms, eg, visual or hearing disturbances, perioral numbness, tingling and others.  Similar symptoms were seen with both drugs. In 1 study, the mean ± SD maximum tolerated intravenous dose of ropivacaine infused (124 ± 38 mg) was significantly higher than that of bupivacaine (99 ± 30 mg) while in the other study the doses were not different (115 ± 29 mg of ropivacaine and 103 ± 30 mg of bupivacaine).  In the latter study, the number of subjects reporting each symptom was similar for both drugs with the exception of muscle twitching which was reported by more subjects with bupivacaine than ropivacaine at comparable intravenous doses.  At the end of the infusion, ropivacaine in both studies caused significantly less depression of cardiac conductivity (less QRS widening) than bupivacaine.  Ropivacaine and bupivacaine caused evidence of depression of cardiac contractility, but there were no changes in cardiac output.

Clinical data in one published article indicate that differences in various pharmacodynamic measures were observed with increasing age.  In one study, the upper level of analgesia increased with age, the maximum decrease of mean arterial pressure (MAP) declined with age during the first hour after epidural administration, and the intensity of motor blockade increased with age.  However, no pharmacokinetic differences were observed between elderly and younger patients.

In non-clinical pharmacology studies comparing ropivacaine and bupivacaine in several animal species, the cardiac toxicity of ropivacaine was less than that of bupivacaine, although both were considerably more toxic than lidocaine.  Arrhythmogenic and cardio-depressant effects were seen in animals at significantly higher doses of ropivacaine than bupivacaine.  The incidence of successful resuscitation was not significantly different between the ropivacaine and bupivacaine groups.

Clinical Trials

Ropivacaine was studied as a local anesthetic both for surgical anesthesia and for acute pain management (see DOSAGE AND ADMINISTRATION).

The onset, depth and duration of sensory block are, in general, similar to bupivacaine.  However, the depth and duration of motor block, in general, are less than that with bupivacaine.

Epidural Administration In Surgery

There were 25 clinical studies performed in 900 patients to evaluate Naropin epidural injection for general surgery.  Naropin was used in doses ranging from 75 to 250 mg.  In doses of 100 to 200 mg, the median (1st to 3rd quartile) onset time to achieve a T10 sensory block was 10 (5 to 13) minutes and the median (1st to 3rd quartile) duration at the T10 level was 4 (3 to 5) hours (see DOSAGE AND ADMINISTRATION).  Higher doses produced a more profound block with a greater duration of effect.

Epidural Administration In Cesarean Section

A total of 12 studies were performed with epidural administration of Naropin for cesarean section.  Eight of these studies involved 218 patients using the concentration of 5 mg/mL (0.5%) in doses up to 150 mg.  Median onset measured at T6 ranged from 11 to 26 minutes.  Median duration of sensory block at T6 ranged from 1.7 to 3.2 h, and duration of motor block ranged from 1.4 to 2.9 h.  Naropin provided adequate muscle relaxation for surgery in all cases.

In addition, 4 active controlled studies for cesarean section were performed in 264 patients at a concentration of 7.5 mg/mL (0.75%) in doses up to 187.5 mg.  Median onset measured at T6 ranged from 4 to 15 minutes.  Seventy‑seven to 96% of Naropin-exposed patients reported no pain at delivery.  Some patients received other anesthetic, analgesic, or sedative modalities during the course of the operative procedure.

Epidural Administration In Labor And Delivery

A total of 9 double-blind clinical studies, involving 240 patients were performed to evaluate Naropin for epidural block for management of labor pain.  When administered in doses up to 278 mg as intermittent injections or as a continuous infusion, Naropin produced adequate pain relief.

A prospective meta-analysis on 6 of these studies provided detailed evaluation of the delivered newborns and showed no difference in clinical outcomes compared to bupivacaine.  There were significantly fewer instrumental deliveries in mothers receiving ropivacaine as compared to bupivacaine.

                             Table 2

            LABOR AND DELIVERY  

META-ANALYSIS: MODE OF DELIVERY

Delivery Mode	Naropin n=199		Bupivacaine n=188
	n	%	n	%
Spontaneous Vertex	116	58	92	49
Vacuum Extractor	26		33
		}27*		}40
Forceps	28		42
Cesarean Section	29	15	21	11

* p=0.004 versus bupivacaine   

 

Epidural Administration In Postoperative Pain Management

There were 8 clinical studies performed in 382 patients to evaluate Naropin 2 mg/mL (0.2%) for postoperative pain management after upper and lower abdominal surgery and after orthopedic surgery.  The studies utilized intravascular morphine via PCA as a rescue medication and quantified as an efficacy variable.

Epidural anesthesia with Naropin 5 mg/mL, (0.5%) was used intraoperatively for each of these procedures prior to initiation of postoperative Naropin.  The incidence and intensity of the motor block were dependent on the dose rate of Naropin and the site of injection.  Cumulative doses of up to 770 mg of ropivacaine were administered over 24 hours (intraoperative block plus postoperative continuous infusion).  The overall quality of pain relief, as judged by the patients, in the ropivacaine groups was rated as good or excellent (73% to 100%).  The frequency of motor block was greatest at 4 hours and decreased during the infusion period in all groups.  At least 80% of patients in the upper and lower abdominal studies and 42% in the orthopedic studies had no motor block at the end of the 21-hour infusion period.  Sensory block was also dose rate-dependent and a decrease in spread was observed during the infusion period.

A double-blind, randomized, clinical trial compared lumbar epidural infusion of Naropin (n=26) and bupivacaine (n=26) at 2 mg/mL (8 mL/h), for 24 hours after knee replacement.  In this study, the pain scores were higher in the Naropin group, but the incidence and the intensity of motor block were lower.

Continuous epidural infusion of Naropin 2 mg/mL (0.2%) during up to 72 hours for postoperative pain management after major abdominal surgery was studied in 2 multicenter, double-blind studies.  A total of 391 patients received a low thoracic epidural catheter, and Naropin 7.5 mg/L (0.75%) was given for surgery, in combination with GA.  Postoperatively, Naropin 2 mg/mL (0.2%), 4 to 14 mL/h, alone or with fentanyl 1, 2, or 4 mcg/mL was infused through the epidural catheter and adjusted according to the patient’s needs.  These studies support the use of Naropin 2 mg/mL (0.2%) for epidural infusion at 6 to 14 mL/h (12 to 28 mg) for up to 72 hours and demonstrated adequate analgesia with only slight and nonprogressive motor block in cases of moderate to severe postoperative pain.

Clinical studies with 2 mg/mL (0.2%) Naropin have demonstrated that infusion rates of 6 to 14 mL (12 to 28 mg) per hour provide adequate analgesia with nonprogressive motor block in cases of moderate to severe postoperative pain.  In these studies, this technique resulted in a significant reduction in patients’ morphine rescue dose requirement.  Clinical experience supports the use of Naropin epidural infusions for up to 72 hours.

Peripheral Nerve Block

Naropin, 5 mg/mL (0.5%), was evaluated for its ability to provide anesthesia for surgery using the techniques of Peripheral Nerve Block.  There were 13 studies performed including a series of 4 pharmacodynamic and pharmacokinetic studies performed on minor nerve blocks.  From these, 235 Naropin-treated patients were evaluable for efficacy.  Naropin was used in doses up to 275 mg.  When used for brachial plexus block, onset depended on technique used.  Supraclavicular blocks were consistently more successful than axillary blocks.  The median onset of sensory block (anesthesia) produced by ropivacaine 0.5% via axillary block ranged from 10 minutes (medial brachial cutaneous nerve) to 45 minutes (musculocutaneous nerve).  Median duration ranged from 3.7 hours (medial brachial cutaneous nerve) to 8.7 hours (ulnar nerve).  The 5 mg/mL (0.5%) Naropin solution gave success rates from 56% to 86% for axillary blocks, compared with 92% for supraclavicular blocks.

In addition, Naropin, 7.5 mg/mL (0.75%), was evaluated in 99 Naropin-treated patients, in 2 double-blind studies, performed to provide anesthesia for surgery using the techniques of Brachial Plexus Block.  Naropin 7.5 mg/mL was compared to bupivacaine 5 mg/mL.  In 1 study, patients underwent axillary brachial plexus block using injections of 40 mL (300 mg) of Naropin, 7.5 mg/mL (0.75%) or 40 mL injections of bupivacaine, 5 mg/mL (200 mg).  In a second study, patients underwent subclavian perivascular brachial plexus block using 30 mL (225 mg) of Naropin, 7.5 mg/mL (0.75%) or 30 mL of bupivacaine 5 mg/mL (150 mg).  There was no significant difference between the Naropin and bupivacaine groups in either study with regard to onset of anesthesia, duration of sensory blockade, or duration of anesthesia.

The median duration of anesthesia varied between 11.4 and 14.4 hours with both techniques.  In one study, using the axillary technique, the quality of analgesia and muscle relaxation in the Naropin group was judged to be significantly superior to bupivacaine by both investigator and surgeon.  However, using the subclavian perivascular technique, no statistically significant difference was found in the quality of analgesia and muscle relaxation as judged by both the investigator and surgeon.  The use of Naropin 7.5 mg/mL for block of the brachial plexus via either the subclavian perivascular approach using 30 mL (225 mg) or via the axillary approach using 40 mL (300 mg) both provided effective and reliable anesthesia.

Local Infiltration

A total of 7 clinical studies were performed to evaluate the local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management.  In these studies 297 patients who received Naropin in doses up to 200 mg (concentrations up to 5 mg/mL, 0.5%) were evaluable for efficacy.  With infiltration of 100 to 200 mg Naropin, the time to first request for analgesic was 2 to 6 hours.  When compared to placebo, Naropin produced lower pain scores and a reduction of analgesic consumption.

Indications and Usage for Naropin

Naropin is indicated for the production of local or regional anesthesia for surgery and for acute pain management.

Surgical Anesthesia: epidural block for surgery including cesarean section; major nerve block; local infiltration

Acute Pain Management: epidural continuous infusion or intermittent bolus, eg, postoperative or labor; local infiltration

Contraindications

Naropin is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type.

Warnings

In performing Naropin blocks, unintended intravenous injection is possible and may result in cardiac arrhythmia or cardiac arrest.  The potential for successful resuscitation has not been studied in humans.  There have been rare reports of cardiac arrest during the use of Naropin for epidural anesthesia or peripheral nerve blockade, the majority of which occurred after unintentional accidental intravascular administration in elderly patients and in patients with concomitant heart disease.  In some instances, resuscitation has been difficult.  Should cardiac arrest occur, prolonged resuscitative efforts may be required to improve the probability of a successful outcome.

Naropin should be administered in incremental doses.  It is not recommended for emergency situations, where a fast onset of surgical anesthesia is necessary.  Historically, pregnant patients were reported to have a high risk for cardiac arrhythmias, cardiac/circulatory arrest and death when 0.75% bupivacaine (another member of the amino amide class of local anesthetics) was inadvertently rapidly injected intravenously.

Prior to receiving major blocks the general condition of the patient should be optimized and the patient should have an IV line inserted.  All necessary precautions should be taken to avoid intravascular injection.  Local anesthetics should only be administered by clinicians who are well versed in the diagnosis and management of dose-related toxicity and other acute emergencies that may arise from the block to be employed, and then only after ensuring the immediate (without delay) availability of oxygen, other resuscitative drugs, cardiopulmonary resuscitative equipment, and the personnel resources needed for proper management of toxic reactions and related emergencies (see also ADVERSE REACTIONS, PRECAUTIONS and MANAGEMENT OF LOCAL ANESTHETIC EMERGENCIES).  Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death.  Solutions of Naropin should not be used for the production of obstetrical paracervical block anesthesia, retrobulbar block, or spinal anesthesia (subarachnoid block) due to insufficient data to support such use.  Intravenous regional anesthesia (bier block) should not be performed due to a lack of clinical experience and the risk of attaining toxic blood levels of ropivacaine.

Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions.  The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours.  There is insufficient information to determine whether shorter infusion periods are not associated with these findings.  The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery.  Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.

It is essential that aspiration for blood, or cerebrospinal fluid (where applicable), be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection.  However, a negative aspiration does not ensure against an intravascular or subarachnoid injection.

A well-known risk of epidural anesthesia may be an unintentional subarachnoid injection of local anesthetic.  Two clinical studies have been performed to verify the safety of Naropin at a volume of 3 mL injected into the subarachnoid space since this dose represents an incremental epidural volume that could be unintentionally injected.  The 15 and 22.5 mg doses injected resulted in sensory levels as high as T5 and T4, respectively.  Anesthesia to pinprick started in the sacral dermatomes in 2 to 3 minutes, extended to the T10 level in 10 to 13 minutes and lasted for approximately 2 hours.  The results of these two clinical studies showed that a 3 mL dose did not produce any serious adverse events when spinal anesthesia blockade was achieved.

Naropin should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics, since the toxic effects of these drugs are additive.

Patients treated with class III antiarrhythmic drugs (eg, amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive.

Precautions

General

The safe and effective use of local anesthetics depends on proper dosage, correct technique, adequate precautions and readiness for emergencies.

Resuscitative equipment, oxygen and other resuscitative drugs should be available for immediate use (see WARNINGS and ADVERSE REACTIONS).  The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse events.  Injections should be made slowly and incrementally, with frequent aspirations before and during the injection to avoid intravascular injection.  When a continuous catheter technique is used, syringe aspirations should also be performed before and during each supplemental injection.  During the administration of epidural anesthesia, it is recommended that a test dose of a local anesthetic with a fast onset be administered initially and that the patient be monitored for central nervous system and cardiovascular toxicity, as well as for signs of unintended intrathecal administration before proceeding.  When clinical conditions permit, consideration should be given to employing local anesthetic solutions, which contain epinephrine for the test dose because circulatory changes compatible with epinephrine may also serve as a warning sign of unintended intravascular injection.  An intravascular injection is still possible even if aspirations for blood are negative.  Administration of higher than recommended doses of Naropin to achieve greater motor blockade or increased duration of sensory blockade may result in cardiovascular depression, particularly in the event of inadvertent intravascular injection.  Tolerance to elevated blood levels varies with the physical condition of the patient.  Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical condition.  Local anesthetics should also be used with caution in patients with hypotension, hypovolemia or heart block.

Careful and constant monitoring of cardiovascular and respiratory vital signs (adequacy of ventilation) and the patient's state of consciousness should be performed after each local anesthetic injection.  It should be kept in mind at such times that restlessness, anxiety, incoherent speech, light-headedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, depression, or drowsiness may be early warning signs of central nervous system toxicity.  Because amide-type local anesthetics such as ropivacaine are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease.  Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations.  Local anesthetics should also be used with caution in patients with impaired cardiovascular function because they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs.

Many drugs used during the conduct of anesthesia are considered potential triggering agents for malignant hyperthermia (MH).  Amide-type local anesthetics are not known to trigger this reaction.  However, since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for MH management should be available.

Epidural Anesthesia

During epidural administration, Naropin should be administered in incremental doses of 3 to 5 mL with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.  Syringe aspirations should also be performed before and during each supplemental injection in continuous (intermittent) catheter techniques.  An intravascular injection is still possible even if aspirations for blood are negative.  During the administration of epidural anesthesia, it is recommended that a test dose be administered initially and the effects monitored before the full dose is given.  When clinical conditions permit, the test dose should contain an appropriate dose of epinephrine to serve as a warning of unintentional intravascular injection.  If injected into a blood vessel, this amount of epinephrine is likely to produce a transient "epinephrine response" within 45 seconds, consisting of an increase in heart rate and systolic blood pressure, circumoral pallor, palpitations and nervousness in the unsedated patient.  The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds.  Therefore, following the test dose, the heart should be continuously monitored for a heart rate increase.  Patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect a rise in systolic blood pressure.  A test dose of a short-acting amide anesthetic such as lidocaine is recommended to detect an unintentional intrathecal administration.  This will be manifested within a few minutes by signs of spinal block (eg, decreased sensation of the buttocks, paresis of the legs, or, in the sedated patient, absent knee jerk).  An intravascular or subarachnoid injection is still possible even if results of the test dose are negative.  The test dose itself may produce a systemic toxic reaction, high spinal or epinephrine-induced cardiovascular effects.

Use in Brachial Plexus Block

Ropivacaine plasma concentrations may approach the threshold for central nervous system toxicity after the administration of 300 mg of ropivacaine for brachial plexus block.  Caution should be exercised when using the 300 mg dose (see OVERDOSAGE).

The dose for a major nerve block must be adjusted according to the site of administration and patient status.  Supraclavicular brachial plexus blocks may be associated with a higher frequency of serious adverse reactions, regardless of the local anesthetic used.

Use in Peripheral Nerve Block

Major peripheral nerve blocks may result in the administration of a large volume of local anesthetic in highly vascularized areas, often close to large vessels where there is an increased risk of intravascular injection and/or rapid systemic absorption, which can lead to high plasma concentrations.

Use in Head and Neck Area

Small doses of local anesthetics injected into the head and neck area may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses.  The injection procedures require the utmost care.  Confusion, convulsions, respiratory depression, and/or respiratory arrest, and cardiovascular stimulation or depression have been reported.  These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation.  Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed.  Resuscitative equipment and personnel for treating adverse reactions should be immediately available.  Dosage recommendations should not be exceeded (see DOSAGE AND ADMINISTRATION).

Use in Ophthalmic Surgery

The use of Naropin in retrobulbar blocks for ophthalmic surgery has not been studied.  Until appropriate experience is gained, the use of Naropin for such surgery is not recommended.

Information for Patients

When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity in the anesthetized part of the body following proper administration of lumbar epidural anesthesia.  Also, when appropriate, the physician should discuss other information including adverse reactions in the Naropin package insert.

Drug Interactions

Specific trials studying the interaction between ropivacaine and class III antiarrhythmic drugs (eg, amiodarone) have not been performed, but caution is advised (see WARNINGS).

Naropin should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics, since the toxic effects of these drugs are additive.  Cytochrome P4501A2 is involved in the formation of 3-hydroxy ropivacaine, the major metabolite.  In vivo, the plasma clearance of ropivacaine was reduced by 70% during coadministration of fluvoxamine (25 mg bid for 2 days), a selective and potent CYP1A2 inhibitor.  Thus strong inhibitors of cytochrome P4501A2, such as fluvoxamine, given concomitantly during administration of Naropin, can interact with Naropin leading to increased ropivacaine plasma levels.  Caution should be exercised when CYP1A2 inhibitors are coadministered.  Possible interactions with drugs known to be metabolized by CYP1A2 via competitive inhibition such as theophylline and imipramine may also occur.  Coadministration of a selective and potent inhibitor of CYP3A4, ketoconazole (100 mg bid for 2 days with ropivacaine infusion administered 1 hour after ketoconazole) caused a 15% reduction in in vivo plasma clearance of ropivacaine.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals of most local anesthetics, including ropivacaine, to evaluate the carcinogenic potential have not been conducted.

Weak mutagenic activity was seen in the mouse lymphoma test.  Mutagenicity was not noted in the other assays, demonstrating that the weak signs of in vitro activity in the mouse lymphoma test were not manifest under diverse in vivo conditions.

Studies performed with ropivacaine in rats did not demonstrate an effect on fertility or general reproductive performance over 2 generations.

Pregnancy Category B

Reproduction toxicity studies have been performed in pregnant New Zealand white rabbits and Sprague-Dawley rats.  During gestation days 6 to 18, rabbits received 1.3, 4.2, or 13 mg/kg/day subcutaneously.  In rats, subcutaneous doses of 5.3, 11 and 26 mg/kg/day were administered during gestation days 6 to 15.  No teratogenic effects were observed in rats and rabbits at the highest doses tested.  The highest doses of 13 mg/kg/day (rabbits) and 26 mg/kg/day (rats) are approximately 1/3 of the maximum recommended human dose (epidural, 770 mg/24 hours) based on a mg/m2 basis.  In 2 prenatal and postnatal studies, the female rats were dosed daily from day 15 of gestation to day 20 postpartum.  The doses were 5.3, 11 and 26 mg/kg/day subcutaneously.  There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring.

In another study with rats, the males were dosed daily for 9 weeks before mating and during mating.  The females were dosed daily for 2 weeks before mating and then during the mating, pregnancy, and lactation, up to day 42 post coitus.  At 23 mg/kg/day, an increased loss of pups was observed during the first 3 days postpartum.  The effect was considered secondary to impaired maternal care due to maternal toxicity.

There are no adequate or well-controlled studies in pregnant women of the effects of Naropin on the developing fetus.  Naropin should only be used during pregnancy if the benefits outweigh the risk.

Teratogenicity studies in rats and rabbits did not show evidence of any adverse effects on organogenesis or early fetal development in rats (26 mg/kg sc) or rabbits (13 mg/kg).  The doses used were approximately equal to total daily dose based on body surface area.  There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring in 2 perinatal and postnatal studies in rats, at dose levels equivalent to the maximum recommended human dose based on body surface area.  In another study at 23 mg/kg, an increased pup loss was seen during the first 3 days postpartum, which was considered secondary to impaired maternal care due to maternal toxicity.

Labor and Delivery

Local anesthetics, including ropivacaine, rapidly cross the placenta, and when used for epidural block can cause varying degrees of maternal, fetal and neonatal toxicity (see CLINICAL PHARMACOLOGY and PHARMACOKINETICS).  The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration.  Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone and cardiac function.

Maternal hypotension has resulted from regional anesthesia with Naropin for obstetrical pain relief.  Local anesthetics produce vasodilation by blocking sympathetic nerves.  Elevating the patient's legs and positioning her on her left side will help prevent decreases in blood pressure.  The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.  Epidural anesthesia has been reported to prolong the second stage of labor by removing the patient's reflex urge to bear down or by interfering with motor function.  Spontaneous vertex delivery occurred more frequently in patients receiving Naropin than in those receiving bupivacaine.

Nursing Mothers

Some local anesthetic drugs are excreted in human milk and caution should be exercised when they are administered to a nursing woman.  The excretion of ropivacaine or its metabolites in human milk has not been studied.  Based on the milk/plasma concentration ratio in rats, the estimated daily dose to a pup will be about 4% of the dose given to the mother.  Assuming that the milk/plasma concentration in humans is of the same order, the total Naropin dose to which the baby is exposed by breast-feeding is far lower than by exposure in utero in pregnant women at term (see PRECAUTIONS).

Pediatric Use

The safety and efficacy of Naropin in pediatric patients have not been established.

Geriatric Use

Of the 2,978 subjects that were administered Naropin Injection in 71 controlled and uncontrolled clinical studies, 803 patients (27%) were 65 years of age or older which includes 127 patients (4%) 75 years of age and over.  Naropin Injection was found to be safe and effective in the patients in these studies.  Clinical data in one published article indicate that differences in various pharmacodynamic measures were observed with increasing age.  In one study, the upper level of analgesia increased with age, the maximum decrease of mean arterial pressure (MAP) declined with age during the first hour after epidural administration, and the intensity of motor blockade increased with age.

This drug and its metabolites are known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.  Elderly patients are more likely to have decreased hepatic, renal, or cardiac function, as well as concomitant disease.  Therefore, care should be taken in dose selection, starting at the low end of the dosage range, and it may be useful to monitor renal function (see PHARMACOKINETICS , Elimination).

Adverse Reactions

Reactions to ropivacaine are characteristic of those associated with other amide-type local anesthetics.  A major cause of adverse reactions to this group of drugs may be associated with excessive plasma levels, which may be due to overdosage, unintentional intravascular injection or slow metabolic degradation.

The reported adverse events are derived from clinical studies conducted in the U.S. and other countries.  The reference drug was usually bupivacaine.  The studies used a variety of premedications, sed

Pinewood Cold Sore Cream

1. Name Of The Medicinal Product

Pinewood Cold Sore Cream

Galpharm Cold Sore Cream

Superdrug Cold Sore Cream

Numark Cold Sore Cream

Lypsyl Aciclovir 5% Cold Sore Cream

Lloyds Pharmacy Cold Sore Cream

Asda Cold Sore Cream

Morrisons Cold Sore Cream

2. Qualitative And Quantitative Composition

Each g contains 50 mg of Aciclovir

Excipients:

Cetyl alcohol	15mg/g
Propylene Glycol	150mg/g

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Cream.

White to off-white cream.

4. Clinical Particulars

4.1 Therapeutic Indications

For the treatment of Herpes Simplex virus infections of the lips and face (Herpes labialis).

4.2 Posology And Method Of Administration

Adults and children

Treatment should be initiated as soon as possible after the start of the infection, ideally during the prodromal period or when the lesions first appear.

A thin film of cream should be applied to the infected and immediately adjacent skin areas 5 times daily at 4-hour intervals during the day.

Treatment should be continued for 5 days, following by a further 5 days treatment if healing has not occurred.

Patients should wash their hands before and after applying the cream and avoid unnecessary rubbing of the lesions or touching with a towel, to avoid aggravating or transferring the infection.

Elderly

No special requirements

4.3 Contraindications

Hypersensitivity to Aciclovir or any other ingredients of the preparation.

4.4 Special Warnings And Precautions For Use

Only recommended for use on cold sores on the lips and face.

People with particularly severe Herpes labialis should be encouraged to seek medical advice.

Not to be applied to mucous membranes such as inside the mouth or vagina, or on the eye. Particular care should be taken to avoid contact with the eye.

Not for use for the treatment of genital herpes or ocular herpes infections.

Not recommended for use by patients who know they are immunocompromised e.g. by HIV infection, bone marrow transplant or cancer treatment, except on the advice of a doctor.

Cold sore sufferers should be advised to avoid transmitting the virus, particularly when active lesions are present.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Probenecid increases the mean half-life and area under the plasma concentration curve of systemically administered Aciclovir. Other drugs affecting renal physiology could potentially influence the pharmacokinetics of Aciclovir. However this is likely to be of little relevance to the cutaneous application of Aciclovir.

No interactions with other drugs have been described for topical Acyclovir.

4.6 Pregnancy And Lactation

No specific studies of topical Aciclovir have been carried out in pregnant women or nursing mothers.

So far, no relevant plasma levels have been measured and no systemic effects have been observed.

However, use of the cream should be considered only when the potential benefit outweighs the possibility of unknown risks.

In internationally accepted standard tests the systemic administration of Aciclovir did not produce embryotoxic or teratogenic effects in rabbits, rats or mice.

Foetal abnormalities were observed in non-standard tests in rats, but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.

Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses greatly in excess of those employed therapeutically. Two generation studies in mice did not reveal any effect of orally administered Aciclovir on fertility.

There is no experience of the effect of Aciclovir tablets on human female fertility. Aciclovir tablets have been shown to have no definite effect upon sperm count, morphology or motility in man.

Following oral administration of 200 mg Aciclovir five times a day, Aciclovir has been detected in breast milk at concentrations ranging from 0.6 to 4.1 times the corresponding plasma levels. These levels would potentially expose breast fed infants to Aciclovir doses of up to 0.3 mg/kg/day.

4.7 Effects On Ability To Drive And Use Machines

The medicinal product has no influence on the ability to drive or operate machinery.

4.8 Undesirable Effects

The following convention has been used for the classification of undesirable effects in terms of frequency:-

Very common

Skin and subcutaneous tissue disorders

Common

- Mild drying or flaking of the skin

Uncommon

- Itching

Rare

- Erythema

- Contact dermatitis following application. Where sensitivity tests have been conducted, the reactive substances have most often been shown to be components of the cream base rather than aciclovir.

Immune system disorders

Very rare

- Immediate hypersensitivity reactions including angioedema.

After application of the cream, transient burning or stinging of the treated skin areas may occur.

4.9 Overdose

Overdose is unlikely to occur, if the cream is applied locally and as indicated. There are no reports concerning an overdose of Aciclovir cream.

No unwanted effects would be expected if the entire contents of a 2.0g tube of the cream were ingested. Doses of 800 mg five times daily (4 g per day), have administered without adverse effects. Single intravenous doses of up to 80 mg/kg have been inadvertently administered without adverse effects. Aciclovir is dialysable.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Aciclovir is a pharmacologically inactive substance. After penetration into cells which are infected with herpes simplex virus types I and (HSV I & HSV II) or varicella-zoster virus (VSV), Aciclovir is converted into a virostatic agent. The conversion of Aciclovir is catalysed by viral HSV- or VZV- thymidine kinase. Human thymidine kinase does not use Aciclovir effectively as a substrate, hence the toxicity to mammalian host cells is low.

In the infected cell, Aciclovir is phosphorylated by viral thymidine kinase to Aciclovir monophosphate, which is further converted by cellular enzymes to Aciclovir triphosphate. Aciclovir triphosphate has a greater affinity for viral DNA polymerase than host cell DNA polymerase and therefore selectively interferes with the viral enzyme causing inhibition of viral DNA replication. Aciclovir is also incorporated into viral DNA by viral DNA polymerase, which results in chain termination, as Aciclovir lacks a 3'-hydroxyl group, preventing addition of nucleotides by 3',5'-linkage.

In severely immunocompromised patients a longer or repeated treatment with Aciclovir can lead to a selection of viral strains with reduced sensitivity. As a result, these patients no longer respond to treatment with Aciclovir. Most of the clinical isolates with reduced sensitivity showed a relative lack of virus thymidine kinase. However, strains with changed/different virus thymidine kinase or DNS polymerase were also reported. The in vitro exposition of HSV-isolates can also lead to the development of less sensitive strains. The connection between the in vitro determined sensitivity of HSV-isolates and the clinical response to the treatment with Aciclovir is not clear.

5.2 Pharmacokinetic Properties

Absorption and plasma concentrations

Aciclovir penetrates into the skin. The intracutaneous concentration levels are higher than the minimal inhibitory concentration (MIC) in tissue at steady state.

After topical application of Aciclovir, no Aciclovir plasma concentration could be determined.

As the Aciclovir plasma concentrations following topical application are below the limit of detection, no pharmacokinetic studies are available on topical Aciclovir. Therefore, the following data is based on the data after oral or intravenous administration.

Plasma protein binding is reported to range between 9 and 33% as a function of dose. The volume of distribution at steady state in adults is 50± 8.7ν1.73 m², or 0.7 I/kg.

Two metabolites could be identified in the urine of patients with normal renal function after single dosing with ¹⁴C-Aciclovir: 9-carboxymethoxymethylguanine (2-14% of an administered dose) and 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine(<0.2% of a dose). Subjects with normal renal function eliminate 62-91% of an Aciclovir dose unchanged and 9-14% as 9-carboxymethoxymethylguanine via the kidneys.

Aciclovir is predominantly eliminated via the kidneys, primarily by glomerular filtration and to a lesser extent by tubular secretion.

In vitro and in vivo studies of Aciclovir cream and Aciclovir ointment versus oral Aciclovir were carried out to determine the bioavailability of Aciclovir in human skin. The in vitro studies used human skin biopsates, whilst the bioassays either used human skin grafts on mice or were carried out in the human eye (3 patients).

The following dermal drug concentration gradient emerged for both topical and oral Aciclovir: stratum corneum> epidermis>dermis. There was no difference in concentration between cream and ointment.

The upper layer of the epidermis on average showed a 48-fold higher concentration following topical application of Aciclovir ointment or cream 5% than after oral dosing, but the drug concentration in the basal epidermis – the site of herpes virus infection – was 2 to 3 times lower following topical application than after oral dosing.

On the basis of continuous absorption the concentration increased as a function of time (higher drug concentrations being found 48 hours post-topical dose than 24 hours post-topical dose). Thus short dosing intervals appear rational for the special treatment of herpes simplex virus (HSV) infections.

5.3 Preclinical Safety Data

For 24 days, PEG-based Aciclovir Cream 5 or 10% was applied to the shaved (intact and grazed) skin of guinea-pigs. The treated area corresponded to 10% of the body surface. There were neither systemic nor local toxic symptoms. This is also confirmed by histologic studies and autopsy. According to the test carried out by Draize, who evaluated the allergic sensitising potential of a substance, there were no pathogenic findings.

Studies carried out in swine showed that 5% Aciclovir cream in a PEG vehicle caused an only minimal (quantitative) delay in epidermal wound healing.

Rabbits had 1, 3 or 6% Aciclovir cream in a white petrolatum vehicle introduced directly into both eyes 5 times daily at 90-minute intervals for 3 weeks. Neither autopsy nor inspection nor histological examination revealed any pathological changes in the rabbit eyes.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Arlatone 983S

Dimeticone

Cetyl alcohol

Liquid paraffin

White soft paraffin

Propylene glycol

Purified water

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years (unopened)

6 weeks (open)

6.4 Special Precautions For Storage

Do not store above 25°C. Do not refrigerate.

6.5 Nature And Contents Of Container

Aluminium tube with polyethylene screw cap.

Pack size: 2g

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Pinewood Laboratories Limited

Ballymacarbry

Clonmel

Co Tipperary

Ireland

8. Marketing Authorisation Number(S)

PL 04917/0066

9. Date Of First Authorisation/Renewal Of The Authorisation

22^nd December 2004

10. Date Of Revision Of The Text

24/04/2010

Hydrocortisone Butyrate topical

Class: Anti-inflammatory Agents
Note: This monograph also contains information on Hydrocortisone, Hydrocortisone Acetate, Hydrocortisone Buteprate, Hydrocortisone Valerate
ATC Class: D07BB04
VA Class: OR900
CAS Number: 50-23-7
Brands: Ala-Cort, Ala-Scalpt, Analpram-HC, Anucort-HC, Anu-Med HC, Anusert HC, Anusol-HC, Aquanil HC, Caldecort Anti-Itch, Carmol HC, Cetacort, CortaGel Extra Strength, Cortaid Intensive Therapy, Cortaid Maximum Strength, Cortaid Sensitive Skin Formula, Cortenema, Corticaine, Cortifoam, Cortisporin, Cortizone for Kids, Cortizone, Cortizone External Anal Itch Relief, Cortizone Scalp Itch Formula, Dermacort, Dermarest, DriCort, DermiCort, Dermtex HC, Enzone, Epifoam, Gynecort, Hemorrhoidal-HC, Hemril-HC, HydroSKIN, Hytone, LactiCare-HC, Lanacort, Lazersporin-C, Locoid, Mantadil, Massengill Medicated Soft Cloth Towelette, Nupercainal Hydrocortisone Anti-Itch, Nutracort, Orabase HCA, Pandel, Penecort, Pramosone, Preparation H Hydrocortisone, Proctocort, proctoCream-HC, proctoFoam-HC, Sarnol HC, Scalp-Aid, Scalpcort Maximum Strength, Texacort, Westcort, Zone-A Cream, Zone-A Forte Lotion

Introduction

Corticosteroid secreted by the adrenal cortex; topical anti-inflammatory agent.^a

Uses for Hydrocortisone Butyrate

Corticosteroid-responsive Dermatoses

Relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.^b

Nonprescription preparations used for temporary relief of minor skin irritations, itching, and rash caused by eczema, dermatitis, insect bites, poison ivy, poison oak, poison sumac, soaps, detergents, cosmetics, or jewelry.^a

Nonprescription preparations used for temporary relief of itchy anal and/or genital areas.^a

Nonprescription preparations used for temporary relief of itching and minor scalp irritation caused by scalp dermatitis.^a

Generally most effective in acute or chronic dermatoses (e.g., seborrheic or atopic dermatitis, localized neurodermatitis, anogenital pruritus, psoriasis, late phase of allergic contact dermatitis, inflammatory phase of xerosis).^b

Topical therapy generally preferred over systemic therapy; fewer associated adverse systemic effects.^b

Topical therapy generally only controls manifestations of dermatoses; eliminate cause if possible.^b

Topical efficacy may be increased by using a higher concentration or occlusive dressing therapy. (See Administration with Occlusive Dressing under Dosage and Administration.)^b

Response may vary from one topical corticosteroid preparation to another.^b

Anti-inflammatory activity may vary considerably depending on the vehicle, drug concentration, site of application, disease, and individual patient.^b

Infected Dermatoses

Topical treatment of infected dermatoses in combination with topical anti-infectives (e.g., neomycin, polymyxin B) or antifungals.^b

If a topical corticosteroid is used in combination with a topical anti-infective, weigh benefits against risks.^b (See Skin Infection under Cautions.)^b

Oral Lesions

Hydrocortisone acetate paste used as an adjunct for temporary symptomatic relief of oral inflammatory or ulcerative lesions resulting from trauma.^a

Ulcerative Colitis and Anorectal Disorders

Used rectally as a retention enema for adjunctive treatment of mild or moderate acute ulcerative colitis limited to the rectosigmoid or left colon.^b

Used rectally as a retention enema for mild acute ulcerative colitis of the transverse or descending colon.^b

Retention enema usually is effective in mild or moderate acute rectosigmoid ulcerative colitis when response to sulfasalazine (generally considered the maintenance drug of choice) is inadequate or when sulfasalazine cannot be given.^b

Systemic corticosteroids and/or corticosteroid enemas are more effective than sulfasalazine in acute ulcerative colitis attacks, but if surgery is required, it should not be delayed in favor of corticosteroid therapy.^b

Hydrocortisone acetate rectal suppositories or suspension (foam), may be effective as adjunctive treatment of rectal ulcerative colitis.^b

Hydrocortisone acetate rectal suppositories also are used in the treatment of other anorectal inflammatory conditions (e.g., inflamed hemorrhoids, postirradiation or factitial proctitis, cryptitis, pruritus ani).^b

Fixed-combination preparations of a corticosteroid and local anesthetic may be useful for symptomatic relief of anorectal conditions (e.g., hemorrhoids), but combinations with antihistamines, astringents, keratolytics, and/or vasoconstrictors are of questionable efficacy.^b

Hydrocortisone Butyrate Dosage and Administration

General

• 
  

  Consider location of the lesion and the condition being treated when choosing a dosage form.^b

  
  


• 
  

  Creams are suitable for most dermatoses,^b but ointments may also provide some occlusion and are usually used for the treatment of dry, scaly lesions.^b

  
  


• 
  

  Lotions are probably best for treatment of weeping eruptions, especially in areas subject to chafing (e.g., axilla, foot, groin).^b Lotions, gels, and aerosols may be used on hairy areas, particularly the scalp.^b

  
  


• 
  

  Formulation affects percutaneous penetration and subsequent activity; extemporaneous preparation or dilution of commercial preparations with another vehicle may decrease effectiveness.^b

  
  


• 
  

  Patients applying a topical corticosteroid to a large surface area and/or to areas under occlusion should be evaluated periodically for evidence of hypothalamic-pituitary-adrenal (HPA)-axis suppression by appropriate endocrine testing (e.g., ACTH stimulation, plasma cortisol, urinary free cortisol).^b (See Hypothalamic-Pituitary-Adrenal Axis Suppresion and also Systemic Effects, under Cautions.)

  
  

Administration

Topical Administration

For dermatologic use only; avoid contact with eyes.^{d e}

Apply creams, lotions, ointments, solutions, and aerosol foams topically to the skin or scalp.^a

Apply paste topically inside the oral cavity.^a

Apply rectal creams and ointments externally to the anal area; some commercially available creams also may be applied externally to the anogenital areas.^a

The area of skin to be treated may be thoroughly cleansed before topical application to reduce the risk of infection; however, some clinicians believe that, unless an occlusive dressing is used, cleansing of the treated area is unnecessary and may be irritating.^b

Apply cream, lotion, ointment, or solution sparingly in a thin film and rub gently into affected area.^a

For scalp dermatoses, part the hair and apply small amount of lotion or solution directly to the affected area; rub gently into scalp.^a Maintain usual hair care, but do not wash out lotion immediately after application.^a Alternatively, for scalp dermatoses, apply aerosol to dry scalp after shampooing.^a

To dispense foam, shake container well (for 5–10 seconds) immediately prior to use.^f Hold container upright and press down on container cap until foam appears.^f Apply a small amount to affected area.^f

For use in the mouth, press a small amount of paste to the lesion without rubbing until a thin film develops.^a

After a favorable response is achieved, frequency of application or concentration (strength) may be decreased to the minimum necessary to maintain control and to avoid relapse; discontinue if possible.^b

Administration with Occlusive Dressing

Occlusive dressings may be used for severe or resistant dermatoses (e.g., psoriasis).^a (See Occlusive Dressings under Cautions.)

Soak or wash the affected area to remove scales; apply a thin film of cream, lotion, or ointment; rub gently into the lesion; and apply another thin film.^b Cover affected area with a thin, pliable plastic film and seal it to adjacent normal skin with adhesive tape or hold in place with a gauze or elastic bandage.^b

If affected area is moist, incompletely seal the edges of the plastic film or puncture the film to allow excess moisture to escape.^b For added moisture in dry lesions, apply cream, ointment, or lotion and cover with a dampened cloth before the plastic film is applied or briefly soak the affected area in water before application of the drug and plastic film.^b

Thin polyethylene gloves may be used on the hands and fingers, plastic garment bags may be used on the trunk or buttocks, a tight shower cap may be used for the scalp, or whole-body suits may be used instead of plastic film to provide occlusion.^b

Frequency of occlusive dressing changes depends on the condition being treated; cleansing of the skin and reapplication of the corticosteroid are essential at each dressing change.^b

Occlusive dressing is usually left in place for 12–24 hours and therapy is repeated as needed.^b Although occlusive dressing may be left in place for 3–4 days at a time in resistant conditions, most clinicians recommend intermittent use of occlusive dressings for 12 hours daily to reduce the risk of adverse effects (particularly infection) and systemic absorption and for greater convenience.^b

The drug and an occlusive dressing may be used at night, and the drug or a bland emollient may be used without an occlusive dressing during the day.^b

In patients with extensive lesions, sequential occlusion of only one portion of the body at a time may be preferable to whole-body occlusion.^b (See Occlusive Dressings under Cautions.)

Rectal Administration

Administer rectally as a retention enema, suppository, or aerosol foam.^a

Administer retention enema, suppository, or foam carefully according to manufacturer’s instructions.^a

Dosage

Available as hydrocortisone (dosage expressed in terms of the base) and as hydrocortisone acetate, buteprate, butyrate, and valerate (dosage expressed in terms of the salt).^a

Pediatric Patients

Administer the least amount of topical preparations that provides effective therapy.^b (See Pediatric Use under Cautions.)

Corticosteroid-responsive Dermatoses

Topical

Nonprescription hydrocortisone preparations should not be used in children <2 years of age unless directed and supervised by a clinician.^b

Children ≥2 years of age: Apply appropriate cream, lotion, ointment, or solution sparingly 1–4 times daily.^a

Adults

Corticosteroid-responsive Dermatoses

Topical

Apply appropriate cream, lotion, ointment, or solution sparingly 1–4 times daily.^a

Apply aerosol foam to affected area 2–4 times daily.^{a f}

Nonprescription preparations should not be used for self-medication for >7 days.^a

If the condition worsens or symptoms persist, discontinue and consult a clinician.^a

Oral Lesions

Topical

Apply a small amount of paste to the lesion 2 or 3 times daily after meals and at bedtime.^a

If substantial regeneration or repair of oral tissues does not occur after 7 days, further investigate etiology of the lesions.^a

Ulcerative Colitis and Anorectal Disorders

Rectal (as Retention Enema)

Adjunctive treatment of ulcerative colitis: 100 mg nightly.^a Some clinicians recommend 100 mg twice daily followed by 100 mg nightly when improvement occurs.^a

Usually given for 21 days or until clinical and proctologic remissions are achieved.^a

Lay on left side during and for 30 minutes after administration to distribute drug throughout the left colon.^a Retain for ≥1 hour, preferably all night.^a

Symptoms may improve in 3–5 days, followed by proctologic improvement.^a Discontinue if clinical or proctologic improvement does not occur within 2–3 weeks.^a

Protologic remission may require 2–3 months of therapy.^a

Following treatment for >21 days, gradually withdraw use; give every other night for 2–3 weeks, then discontinue.^a

Rectal (as Foam)

Ulcerative proctitis of the distal rectum: 90 mg (1 applicatorful of a 10% aerosol foam suspension) 1 or 2 times daily for 2–3 weeks.^{a g} Then, if necessary, every other day until clinical and proctologic improvement.^{a g}

Symptoms may improve within 5–7 days.^{a g}

Rectal (as Suppository)

Adjunctive treatment of ulcerative colitis of the rectum and other inflammatory conditions of the anorectum: 25 mg in the morning and at night for 2 weeks.^a

Severe proctitis: 25 mg 3 times daily or 50 mg twice daily.^a

Adjunctive treatment of postirradiation or factitial proctitis: 25 mg in the morning and at night for 6–8 weeks (or less if an adequate response is attained).^a

For internal hemorrhoid symptoms and adjunctive treatment of other anorectal inflammatory conditions: 10 mg in the morning and at night for 2–6 days.^a

Prescribing Limits

Pediatric Patients

Corticosteroid-responsive Dermatoses

Self-medication

Topical

Maximum 7 days.^a

Adults

Corticosteroid-responsive Dermatoses

Self-medication

Topical

Maximum 7 days.^a

Cautions for Hydrocortisone Butyrate

Contraindications

• 
  

  Known hypersensitivity to hydrocortisone or any ingredient in the formulation.^{b d e}

  
  


• 
  

  Rectal corticosteroid therapy in patients with intestinal obstruction, abscess, impending perforation, peritonitis, extensive fistulas, and fresh intestinal anastomoses or sinus tracts.^b

  
  

Warnings/Precautions

Sensitivity Reactions

Allergic contact dermatitis may manifest as failure to heal rather than irritation as occurs with other topical preparations that do not contain corticosteroids; confirm with diagnostic patch testing.^e

General Precautions

Hypothalamic-Pituitary-Adrenal Axis Suppression.

Topically applied corticosteroids can be absorbed in sufficient amounts to reversibly suppress the HPA axis.^b

Perform periodic HPA-axis evaluation by appropriate testing (e.g., ACTH stimulation, morning plasma cortisol, urinary free cortisol), especially in patients applying a topical corticosteroid to a large surface area or to areas under occlusion.^b

If HPA-axis suppression occurs, withdraw the drug, reduce the frequency of application, and/or substitute a less potent corticosteroid.^b

HPA-axis function recovery generally is prompt and complete following drug discontinuance.^b

Rarely, glucocorticosteroid insufficiency may require systemic corticosteroid therapy.^b

Systemic Effects

Systemic absorption following topical administration may result in manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.^b

Adverse systemic effects may occur when corticosteroids are used on large areas of the body, for prolonged periods of time, with an occlusive dressing, and/or concurrently with other corticosteroid-containing preparations.^b

Infants and children may be more susceptible to adverse systemic effects.^a (See Pediatric Use under Cautions.)

Local Effects

Possible adverse local reactions (e.g., irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, miliaria); may occur more frequently with the use of occlusive dressings, especially with prolonged therapy.^b

Prolonged use of topical corticosteroids may cause atrophy of the epidermis and subcutaneous tissue;^b these effects are most likely to occur (even with short-term use) in intertriginous (e.g., axilla, groin), flexor, and facial areas.^b

If irritation occurs, discontinue drug and initiate appropriate therapy.^b

Skin Infection

If concurrent skin infection is present or develops, initiate appropriate anti-infective therapy.^b If infection does not respond promptly, discontinue topical corticosteroid therapy until the infection has been controlled.^b

When topical corticosteroids and topical anti-infectives are used concomitantly, consider that the corticosteroid may mask clinical signs of bacterial, fungal, or viral infections; prevent recognition of ineffectiveness of the anti-infective; or suppress hypersensitivity reactions to ingredients in the formulation.^{b h} In addition, consider the cautions, precautions, and contraindications associated with the anti-infective.^{b h}

Do not use occlusive dressings in patients with primary skin infection.^b

Some manufacturers state that topical corticosteroids are contraindicated in patients with tuberculosis of the skin, dermatologic fungal infections, and cutaneous or systemic viral infection (including vaccinia and varicella and herpes simplex of the eye or adjacent skin); however, most clinicians believe topical corticosteroids may be used with caution if the infection is treated.^b

Severe Ulcerative Colorectal Disease

Use rectally with caution in severe ulcerative disease and only after adequate proctologic examination; risk of intestinal perforation.^b

Occlusive Dressings

Adverse systemic corticosteroid effects may occur with use of occlusive dressings on large areas of the body and for prolonged periods of time; monitor accordingly.^b (See Hypothalamic-Pituitary-Adrenal Axis Suppression and also Systemic Effects, under Cautions.)

Adverse local reactions may occur more frequently with the use of occlusive dressings, especially with prolonged therapy.^b (See Local Effects under Cautions.)

Do not use occlusive dressings on weeping or exudative lesions.^b

Do not use occlusive dressings in patients with primary skin infection.^b

Remove occlusive dressings covering large areas if body temperature increases; thermal homeostasis may be impaired.^b

Use plastic occlusive material with care to avoid the risk of suffocation.^b

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C.^c

Lactation

Not known whether topical hydrocortisone is distributed into milk.^b Caution advised if topical hydrocortisone is used.^b

Pediatric Use

Nonprescription hydrocortisone preparations should not be used in children <2 years of age unless directed and supervised by a clinician.^b

Tight-fitting diapers or plastic pants should not be used on a child being treated in the diaper area, since such garments may constitute occlusive dressings.^b

Children are more susceptible to topical corticosteroid-induced HPA-axis suppression and Cushing’s syndrome than mature individuals because of a greater skin surface area-to-body weight ratio,^b especially when topical corticosteroids are applied to >20% of body surface area.^b The risk of adrenal suppression appears to increase with decreasing age.^b (See Systemic Effects under Cautions.)

Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol concentrations, and lack of response to corticotropin (ACTH) stimulation.^b

Children also are at greater risk of glucocorticoid insufficiency during and/or after withdrawal of treatment.^b

Intracranial hypertension has occurred in children; manifestations include bulging fontanelles, headaches, and bilateral papilledema.^b

Striae has been reported in children treated inappropriately with topical corticosteroids.^b

Topical corticosteroid therapy in children should be limited to the minimum amount necessary for therapeutic efficacy; chronic topical corticosteroid therapy may interfere with growth and development.^b

Common Adverse Effects

Burning, stinging, itching, irritation, dry skin, erythema, folliculitis, hypopigmentation, allergic contact dermatitis, secondary infection.^b

Interactions for Hydrocortisone Butyrate

Specific Drugs and Laboratory Tests

Drug or Test	Interaction
Corticosteroids	Potential pharmacologic interaction with other corticosteroid-containing preparationsb
Nitroblue-tetrazolium test for bacterial infection	Concurrent use of corticosteroids reportedly may result in false-negative resultsb

Hydrocortisone Butyrate Pharmacokinetics

Absorption

Bioavailability

Percutaneous penetration of corticosteroids following topical application to the skin varies among individuals and may be increased by occlusive dressings, high corticosteroid concentrations, and certain vehicles.^b

Only minimal amounts of topical corticosteroid reach the dermis and subsequently the systemic circulation after application to most normal skin areas; more absorption occurs from the scrotum, axilla, eyelid, face, and scalp than from the forearm, knee, elbow, palm, and sole.^b

Absorption is markedly increased by loss of the skin’s keratin layer and by inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema).^b

Occlusive dressings used with hydrocortisone for 96 hours substantially enhance percutaneous penetration;^b occlusive dressings used for up to 24 hours do not appear to alter penetration.^b

In healthy individuals, up to 30–90% of hydrocortisone administered rectally as a retention enema may be absorbed.^b Greater amounts of hydrocortisone may be absorbed if the intestinal mucosa is inflamed.^b

Distribution

Extent

Not known whether topical hydrocortisone is distributed into milk.^b

Elimination

Metabolism

Once absorbed through the skin, topically applied corticosteroids are metabolized primarily in the liver.^b

Elimination Route

Topical corticosteroids and metabolites are excreted by the kidneys and, to a lesser extent, in the bile.^b

Stability

Storage

Topical

Creams, Lotions, Ointments, Solutions, Aerosol Foams

Room temperature; consult product information for specific recommendations.

Rectal

Creams, Suspensions for Retention Enemas, Aerosol Foams, Suppositories

Room temperature; consult product information for specific recommendations.

ActionsActions

• 
  

  Produces anti-inflammatory, antipruritic, and vasoconstrictor actions, possibly resulting in part from steroid receptor binding.^b

  
  


• 
  

  Precise mechanism of action for topical anti-inflammatory activity is unknown; therapeutic benefit in the management of corticosteroid-responsive dermatoses mediated primarily through anti-inflammatory, antipruritic, and vasoconstrictive actions.^{b d e}

  
  


• 
  

  Anti-inflammatory effects may occur through induction of phospholipase A₂ inhibitory proteins (lipocortins); decreased arachidonic acid release from membrane phospholipids.^e Decreased arachidionic acid precursors may downregulate biosynthesis of potent inflammatory mediators (e.g., prostaglandins, leukotrienes).^e

  
  


• 
  

  Decreases inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown.^b

  
  

Advice to Patients

• 
  

  Importance of using only as directed, only for the disorder for which it was prescribed, and for no longer than prescribed;^b avoid contact with the eyes.^{d e} (See Topical Administration under Dosage and Administration.)

  
  


• 
  

  Importance of informing patients that treated areas of the skin should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by a clinician.^b

  
  


• 
  

  Importance of informing parents of children receiving the drug that if hydrocortisone is applied in the diaper area, tight-fitting diapers or plastic pants should not be used since they may act as an occlusive dressing.^b

  
  


• 
  

  Importance of reporting any local adverse reactions, especially those occurring under occlusive dressings, to a clinician.^b

  
  


• 
  

  Potential for hydrocortisone acetate suppositories to stain fabric; take appropriate precautionary measures.^b

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs; other corticosteroid-containing preparations should not be used without first consulting with clinician.^c

  
  


• 
  

  Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.^b

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Hydrocortisone

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Bulk	Powder*
Rectal	Cream	1%	Proctocort (with benzyl alcohol and propylene glycol)	Monarch
	Suspension	100 mg/60 mL	Cortenema (with methylparaben)	Solvay
			Hydrocortisone Enema	Copley
Topical	Cream	0.5%*	Cortizone-5 (with aloe and parabens)	Pfizer
			Cortizone for Kids (with aloe and parabens)	Pfizer
		1%*	Ala-Cort	Del-Ray
			Cortaid Intensive Therapy (with parabens and propylene glycol)	Pfizer
			Cortizone-10 (with aloe and parabens)	Pfizer
			Cortizone-10 External Anal Itch Relief Creme (with aloe and parabens)	Pfizer
			Dermacort	Solvay
			DermiCort	Republic
			HydroSKIN	Rugby
			Hytone (with propylene glycol)	Dermik
			Penecort (with benzyl alcohol and propylene glycol)	Allergan
			Preparation H Hydrocortisone (with parabens and propylene glycol)	Wyeth
		2.5%*	Anusol-HC (with benzyl alcohol and propylene glycol)	Pfizer
			Hytone (with propylene glycol)	Dermik
	Gel	1%	CortaGel Extra Strength	Norstar
	Lotion	0.5%*	HydroSKIN	Rugby
		1%*	Ala-Cort	Del-Ray
			Aquanil HC (with benzyl alcohol)	Person & Covey
			Cetacort (with parabens)	Healthpoint
			Dermacort (with benzyl alcohol)	Solvay
			HydroSKIN	Rugby
			LactiCare-HC	Stiefel
			Nutracort (with parabens)	Healthpoint
			Sarnol HC	Stiefel
		2%	Ala-Scalpt	Del-Ray
		2.5%	Hydrocortisone Lotion	Glades, Major
			Hytone (with propylene glycol)	Dermik
			LactiCare-HC	Stiefel
			Nutracort (with parabens)	Healthpoint
			ProctoCream-HC (with benzyl alcohol)	Physicians Total Care
	Ointment	0.5%*	Cortizone-5	Pfizer
		1%*	Cortizone-10	Pfizer
			HydroSKIN	Rugby
		2.5%*	Hytone	Dermik
	Pledgets (saturated with solution)	0.5%	Massengill Medicated Soft Cloth Towelette (with parabens and propylene glycol)	GlaxoSmithKline
	Solution	1%	Cortaid FastStick Maximum Strength (with alcohol and methylparaben)	Pfizer
			Cortaid Spray Maximum Strength (with alcohol and methylparaben)	Pfizer
			Cortizone-10 Scalp Itch Formula Liquid (with alcohol SD 40-2 60% v/v, benzyl alcohol, and propylene glycol)	Pfizer
			Penecort (with alcohol SD 40-2 57%, benzyl alcohol, and propylene glycol)	Allergan
			Texacort (with SD alcohol 33% and propylene glycol)	Sirius
		2.5%	Texacort	Sirius

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Hydrocortisone Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Ointment	1% with Bacitracin Zinc 400 units (of bacitracin) per g, Neomycin Sulfate 0.5% (0.35% of neomycin), and Polymyxin B Sulfate 5000 units (of polymyxin B) per g	Cortisporin	Monarch
		1% with Neomycin Sulfate 0.5% (0.35% of neomycin)*
	Solution	1% with Neomycin Sulfate 0.5% (0.35% of neomycin), and Polymyxin B Sulfate 10,000 units (of polymyxin B) per g	Lazersporin-C (with propylene glycol)	Pedinol

Hydrocortisone is also commercially available in combination with antihistamines, astringents, keratolytics, local anesthetics, and vasoconstrictors.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Hydrocortisone Acetate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Bulk	Powder*
Rectal	Aerosol, foam suspension	10%	Cortifoam (with parabens, propylene glycol, and chlorofluorohydrocarbon propellants)	Schwarz
	Suppositories	25 mg	Anucort-HC	G&W
			Anu-Med HC	Major
			Anusol-HC	Pfizer
			Hemorrhoidal-HC	Alpharma, CMC, Sandoz, Rugby, UDL
			Hemril-HC Uniserts	Upsher-Smith
			Hydrocortisone Acetate Suppositories	IVAX, Paddock, UDL, United Research
		30 mg	Proctocort	Monarch
Topical	Cream	0.5%	Corticaine (with parabens)	UCB
		0.5% (of hydrocortisone)*	Cortaid Sensitive Skin Formula (with aloe and parabens)	Pfizer
		1% (of hydrocortisone)	Caldecort Anti-Itch (with propylene glycol)	Novartis
			Cortaid Maximum Strength (with aloe and methylparaben)	Pfizer
			Dermarest DriCort	Del
			Dermtex HC (with menthol 1%)	Pfeiffer
			Nupercainal Hydrocortisone Anti-Itch Cream (with propylene glycol)	Novartis
	Lotion	0.5% (of hydrocortisone)*
	Ointment	0.5% (of hydrocortisone)	Cortaid Sensitive Skin Formula (with aloe and parabens)	Pfizer
		1%	Anusert HC-1	G&W
			Gynecort 10	Combe
			Lanacort 10	Combe
		1% (of hydrocortisone)	Anusol-HC-1	Pfizer
			Cortaid Maximum Strength (with aloe and methylparaben)	Pfizer
	Paste	0.5%	Orabase HCA	Colgate
	Solution	1%	Scalp-Aid	Major
			Scalpcort Maximum Strength	Clay-Park
		1% (of hydrocortisone)	Dermtex HC Spray	Pfeiffer

Hydrocortisone Acetate Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Rectal	Aerosol, foam suspension	1% with Pramoxine Hydrochloride 1%	proctoFoam-HC (with parabens, propylene glycol, and chlorofluorohydrocarbon propellants)	Schwarz
Topical	Aerosol, foam suspension	1% with Pramoxine Hydrochloride 1%	Epifoam (with parabens, propylene glycol, and hydrocarbon propellants)	Schwarz
	Cream	0.5% with Chlorcyclizine Hydrochloride 2%	Mantadil (with methylparaben)	GlaxoSmithKline
		0.5% with Neomycin Sulfate 0.5% (0.35% of neomycin) and Polymyxin B Sulfate 10,000 units (of polymyxin B) per g	Cortisporin (with methylparaben and propylene glycol)	Monarch
		1% with Pramoxine Hydrochloride 1%	Analpram-HC (with propylene glycol)	Ferndale
			Enzone (with propylene glycol)	Forest
			Pramosone (with propylene glycol)	Ferndale
			proctoCream-HC (with propylene glycol)	Schwarz
			Zone-A Cream (with propylene glycol)	Forest
		1% with Urea 10%	Carmol HC (with propylene glycol and sodium metabisulfite)	Doak
		2.5% with Pramoxine Hydrochloride 1%	Analpram-HC (with propylene glycol)	Ferndale
			Pramosone (with propylene glycol)	Ferndale
	Lotion	1% with Pramoxine Hydrochloride 1%	Pramosone (with povidone)	Ferndale
			Zone-A Lotion (with povidone)	Forest
		2.5% with Pramoxine Hydrochloride 1%	Pramosone (with povidone)	Ferndale
			Zone-A Forte Lotion (with povidone)	Forest
	Ointment	1% with Pramoxine Hydrochloride 1%	Pramosone	Ferndale
		2.5% with Pramoxine Hydrochloride 1%	Pramosone	Ferndale

Hydrocortisone acetate is also commercially available in combination with antihistamines, astringents, keratolytics, local anesthetics, and vasoconstrictors.

Hydrocortisone Buteprate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Cream	0.1%	Pandel (with parabens and propylene glycol)	Savage

Hydrocortisone Butyrate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Cream	0.1%	Locoid (with methylparaben)	Ferndale
	Ointment	0.1%	Locoid	Ferndale
	Solution	0.1%	Locoid (with isopropyl alcohol 50% and povidone)	Ferndale

Hydrocortisone Valerate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Cream	0.2%	Westcort (with propylene glycol)	Westwood-Squibb
	Ointment	0.2%	Westcort (with propylene glycol)	Westwood-Squibb

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 05/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Analpram-HC 1-1% Cream (FERNDALE LAB): 30/$91.99 or 90/$255.96

Analpram-HC 1-2.5% Cream (FERNDALE LAB): 30/$91.41 or 90/$261

Analpram-HC 1-2.5% Lotion (FERNDALE LAB): 59/$105.99 or 177/$295.98

Analpram-HC Singles 1-2.5% Cream (FERNDALE LAB): 120/$219 or 360/$615.98

Carmol-HC 1-10% Cream (PHARMADERM): 85/$210 or 255/$605.78

Cortisporin 0.5-0.5-10000 Cream (MONARCH PHARMACEUTICALS): 7/$54.99 or 22/$164.97

Hydrocortisone 0.5% Cream (FOUGERA): 28/$13.99 or 85/$19.97

Hydrocortisone 1% Cream (FOUGERA): 28/$16.99 or 85/$35.97

Hydrocortisone 1% Lotion (FOUGERA): 118/$13.99 or 236/$22.98

Hydrocortisone 1% Lotion (PERRIGO): 118/$15.99 or 236/$22.98

Hydrocortisone 2.5% Cream (FOUGERA): 30/$13.99 or 90/$41.97

Hydrocortisone 2.5% Lotion (PERRIGO PHARMACEUTICALS): 59/$39.99 or 177/$109.96

Hydrocortisone 2.5% Ointment (FOUGERA): 28/$14.99