Anacaine HC

Uses

Hydrocortisone plus Lidocaine cream is used for the anti-inflammatory and anesthetic relief of itching, pain, soreness and discomfort due to hemorrhoids, anal fissures, pruritus ani and similar conditions of the anal area.

Anacaine HC is also used to associated treatment for these conditions: Acute Gouty Arthritis, Acute Otitis Externa, Adrenal Insufficiency, Allergic Rhinitis (AR), Allergic corneal marginal ulcers, Anal Fissures, Ankylosing Spondylitis (AS), Anterior Segment Inflammation, Aspiration Pneumonitis, Asthma, Atopic Dermatitis (AD), Berylliosis, Bullous dermatitis herpetiformis, Chorioretinitis, Choroiditis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Corneal Inflammation, Crohn's Disease (CD), Dermatitis, Dermatitis exfoliative generalised, Dermatitis, Contact, Dermatomyositis, Dermatosis, Drug hypersensitivity reaction, Epicondylitis, Erythroblastopenia, Hemorrhoids, Herpes Labialis, Hypercalcemia of Malignancy, Idiopathic Thrombocytopenic Purpura, Infection of the Fenestration Cavity, Infection of the Mastoidectomy Cavity, Iridocyclitis, Iritis, Itching caused by Hemorrhoids, Itching of the Anus, Leukemia, Acute, Leukemias, Loeffler's syndrome, Lymphomas NEC, Malignant Lymphomas, Mycosis Fungoides (MF), Ophthalmia, Sympathetic, Optic Neuritis, Pain caused by Hemorrhoids, Pemphigus, Post-traumatic Osteoarthritis, Primary adrenocortical insufficiency, Proctitis, Proteinuria, Psoriatic Arthritis, Rectal inflammations NEC, Rheumatic heart disease, unspecified, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Seasonal Allergic Conjunctivitis, Secondary adrenocortical insufficiency, Secondary thrombocytopenia, Serum Sickness, Severe Seborrheic Dermatitis, Skin Diseases, Stevens-Johnson Syndrome, Synovitis, Systemic Lupus Erythematosus (SLE), Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Acquired immune hemolytic anemia, Acute Bursitis, Acute Tenosynovitis, Acute rheumatic carditis, Cryptitis, Disseminated Pulmonary Tuberculosis, Fulminating Pulmonary Tuberculosis, Itching skin, Non-suppurative Thyroiditis, Severe Erythema multiforme, Severe Psoriasis, Subacute Bursitis, Superficial infection of the external auditory canal with inflammation, Symptomatic Sarcoidosis, Systemic Dermatomyositis, Varicella-zoster virus acute retinal necrosis, PalliativeAcute Otitis Media, Anal Fissures, Anorectal discomfort, Arrhythmia, Back Pain Lower Back, Bacterial Vaginosis (BV), Burns, Cervical Syndrome, Earache, Hemorrhoids, Infection, Inflammatory Reaction caused by ear infection-not otherwise specified, Insect Bites, Joint Pain, Mixed Vaginal Infections, Multiple Myeloma (MM), Myringitis, Neuritis, Osteolysis caused by Bone Tumors, Osteoporosis, Otitis Externa, Pain caused by ear infection-not otherwise specified, Pain, Inflammatory, Post-Herpetic Neuralgia (PHN), Postherpetic Neuralgia, Primary Hyperparathyroidism, Rheumatic Diseases, Rheumatic Joint Disease, Sciatica, Skin Irritation, Soft Tissue Inflammation, Sore Throat, Sunburn, Susceptible infections, Trichomonas Vaginitis, Ulcers, Leg, Urethral Strictures, Vulvovaginal Candidiasis, Abrasions, Anal discomfort, Arrhythmia of ventricular origin, Cutaneous lesions, Gum pain, Minor burns, Superficial Wounds, Susceptible Bacterial Infections, Ulceration of the mouth, Viral infections of the external ear canal, Post Myocardial Infarction Treatment, Regional Anesthesia, Local anesthesia therapy

How Anacaine HC works

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.[A187463] Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.[A187463]

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.[A187463]

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.[A187463] High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.[A187463]

Lidocaine is a local anesthetic of the amide type . It is used to provide local anesthesia by nerve blockade at various sites in the body . It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action . In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes . At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions . The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization . As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential . This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place .

In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system . After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction .

Dosage

Anacaine HC dosage

Apply twice daily around the anal opening in a thin layer using an applicator.

Side Effects

Side effects like Rectal bleeding, Swelling of the skin, Adrenal suppression, Anaphylaxis, Angioedema, Cushing syndrome, Hirsutism, Acne, Cutaneous and subcutaneous atrophy, Dry scaly skin, Urticaria.

Toxicity

Data regarding acute overdoses of glucocorticoids are rare. Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency. Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.

Symptoms of overdose and/or acute systemic toxicity involves central nervous system toxicity that presents with symptoms of increasing severity . Patients may present initially with circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis, and tinnitus . Visual disturbance and muscular tremors or muscle twitching are more serious and precede the onset of generalized convulsions . These signs must not be mistaken for neurotic behavior . Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes . Hypoxia and hypercapnia occur rapidly following convulsions due to increased muscular activity, together with the interference with normal respiration and loss of the airway . In severe cases, apnoea may occur. Acidosis increases the toxic effects of local anesthetics . Effects on the cardiovascular system may be seen in severe cases . Hypotension, bradycardia, arrhythmia and cardiac arrest may occur as a result of high systemic concentrations, with potentially fatal outcome .

Pregnancy Category B has been established for the use of lidocaine in pregnancy, although there are no formal, adequate, and well-controlled studies in pregnant women . General consideration should be given to this fact before administering lidocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place . Ultimately, although animal studies have revealed no evidence of harm to the fetus, lidocaine should not be administered during early pregnancy unless the benefits are considered to outweigh the risks . Lidocaine readily crosses the placental barrier after epidural or intravenous administration to the mother . The ratio of umbilical to maternal venous concentration is 0.5 to 0.6 . The fetus appears to be capable of metabolizing lidocaine at term . The elimination half-life in the newborn of the drug received in utero is about three hours, compared with 100 minutes in the adult . Elevated lidocaine levels may persist in the newborn for at least 48 hours after delivery . Fetal bradycardia or tachycardia, neonatal bradycardia, hypotonia or respiratory depression may occur .

Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity . The potential for toxicity depends 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 . 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, spinal, paracervical, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts . In one study, paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation . However, spinal and epidural anesthesia have also been reported to prolong the second stage of labor by removing the parturient’s reflex urge to bear down or by interfering with motor function . The use of obstetrical anesthesia may increase the need for forceps assistance .

The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life . The long-term significance of these observations is unknown . Fetal bradycardia may occur in 20 to 30 percent of patients receiving paracervical nerve block anesthesia with the amide-type local anesthetics and may be associated with fetal acidosis . Fetal heart rate should always be monitored during paracervical anesthesia . The physician should weigh the possible advantages against risks when considering a paracervical block in prematurity, toxemia of pregnancy, and fetal distress . Careful adherence to the recommended dosage is of the utmost importance in obstetrical paracervical block . Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection . Cases compatible with unintended fetal intracranial injection of local anesthetic solution have been reported following intended paracervical or pudendal block or both. Babies so affected present with unexplained neonatal depression at birth, which correlates with high local anesthetic serum levels, and often manifest seizures within six hours . Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication .

It is not known whether this drug is excreted in human milk . Because many drugs are excreted in human milk, caution should be exercised when lidocaine is administered to a nursing woman .

Dosages in children should be reduced, commensurate with age, body weight and physical condition .

The oral LD 50 of lidocaine HCl in non-fasted female rats is 459 (346-773) mg/kg (as the salt) and 214 (159-324) mg/kg (as the salt) in fasted female rats .

Precaution

If extensive areas are treated, the possibility of systemic absorption exists. Systemic absorption of topical steroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glycosuria in some patients. If irritation or sensitivity occurs or infection appears, discontinue use and institute appropriate therapy.

Interaction

This cream should be used with caution together with dental injection anaesthesia, other local anaesthetics or agents structurally related to local anaesthetics of amide type eg, antiarrhythmic drugs (eg, mexiletine), as the toxic effects of these drugs are additive.

Patients treated with class III antiarrhythmic drugs (eg, amiodarone) should be closely observed and ECG monitoring should be considered, as the cardiac effects of lidocaine and class III antiarrhythmic drugs can be additive.

Drugs that inhibit the metabolism of lidocaine (eg, cimetidine or ?-blockers) may cause potentially toxic plasma concentrations when lidocaine is given in repeated high doses over a long time period. Such interactions are of no clinical importance following short-term treatment with lidocaine at recommended doses.

Volume of Distribution

Total hydrocortisone has a volume of distribution of 39.82L, while the free fraction has a volume of distribution of 474.38L.

The volume of distribution determined for lidocaine is 0.7 to 1.5 L/kg .

In particular, lidocaine is distributed throughout the total body water . Its rate of disappearance from the blood can be described by a two or possibly even three-compartment model . There is a rapid disappearance (alpha phase) which is believed to be related to uptake by rapidly equilibrating tissues (tissues with high vascular perfusion, for example) . The slower phase is related to distribution to slowly equilibrating tissues (beta phase) and to its metabolism and excretion (gamma phase) .

Lidocaine's distribution is ultimately throughout all body tissues . In general, the more highly perfused organs will show higher concentrations of the agent . The highest percentage of this drug will be found in skeletal muscle, mainly due to the mass of muscle rather than an affinity .

Elimination Route

Oral hydrocortisone at a dose of 0.2-0.3mg/kg/day reached a mean C_max of 32.69nmol/L with a mean AUC of 90.63h*nmol/L A 0.4-0.6mg/kg/day dose reached a mean C_max of 70.81nmol/L with a mean AUC of 199.11h*nmol/L. However, the pharmacokinetics of hydrocortisone can vary by 10 times from patient to patient.

Topical hydrocortisone cream is 4-19% bioavailable[8546995] with a T_max of 24h.

Hydrocortisone retention enemas are have a bioavailability of 0.810 for slow absorbers and 0.502 in rapid absorbers. Slow absorbers take up hydrocortisone at a rate of 0.361±0.255/h while fast absorbers take up hydrocortisone at a rate of 1.05±0.255/h.

A 20mg IV dose of hydrocortisone has an AUC of 1163±277ng*h/mL.

In general, lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin . The agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream . And although lidocaine is also well absorbed across the gastrointestinal tract the oral bioavailability is only about 35% as a result of a high degree of first-pass metabolism . After injection into tissues, lidocaine is also rapidly absorbed and the absorption rate is affected by both vascularity and the presence of tissue and fat capable of binding lidocaine in the particular tissues .

The concentration of lidocaine in the blood is subsequently affected by a variety of aspects, including its rate of absorption from the site of injection, the rate of tissue distribution, and the rate of metabolism and excretion . Subsequently, the systemic absorption of lidocaine is determined by the site of injection, the dosage given, and its pharmacological profile . The maximum blood concentration occurs following intercostal nerve blockade followed in order of decreasing concentration, the lumbar epidural space, brachial plexus site, and subcutaneous tissue . The total dose injected regardless of the site is the primary determinant of the absorption rate and blood levels achieved . There is a linear relationship between the amount of lidocaine injected and the resultant peak anesthetic blood levels .

Nevertheless, it has been observed that lidocaine hydrochloride is completely absorbed following parenteral administration, its rate of absorption depending also on lipid solubility and the presence or absence of a vasoconstrictor agent . Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration .

Additionally, lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion .

Half Life

Total hydrocortisone via the oral route has a half life of 2.15h while the free fraction has a half life of 1.39h. A 20mg IV dose of hydrocortisone has a terminal half life of 1.9±0.4h.

The elimination half-life of lidocaine hydrochloride following an intravenous bolus injection is typically 1.5 to 2.0 hours . Because of the rapid rate at which lidocaine hydrochloride is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics . The half-life may be prolonged two-fold or more in patients with liver dysfunction .

Clearance

Total hydrocortisone by the oral route has a mean clearance of 12.85L/h, while the free fraction has a mean clearance of 235.78L/h. A 20mg IV dose of hydrocortisone has a clearance of 18.2±4.2L/h.

The mean systemic clearance observed for intravenously administered lidocaine in a study of 15 adults was approximately 0.64 +/- 0.18 L/min .

Elimination Route

Corticosteroids are eliminated predominantly in the urine.[A187436] However, data regarding the exact proportion is not readily available.

The excretion of unchanged lidocaine and its metabolites occurs predominantly via the kidney with less than 5% in the unchanged form appearing in the urine . The renal clearance is inversely related to its protein binding affinity and the pH of the urine . This suggests by the latter that excretion of lidocaine occurs by non-ionic diffusion .

Pregnancy & Breastfeeding use

Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Lactation: Unknown if distributed in breast milk; exercise caution

Contraindication

Patients with a history of hypersensitivity to any of its ingredients.

Special Warning

Use in elderly patients: Clinical studies were not done in patients’ aged 65 and above. In general dose selection for an elderly patients should be cautious, usually starting at the low end of the dosing range.

Hepatic Impairment Parenteral: Dosage reduction may be needed.

Acute Overdose

Symptoms: Severe hypotension, asystole, bradycardia, apnoea, seizures, coma, cardiac arrest, resp arrest and death.

Management: Maintain oxygenation, stop convulsion and support the circulation.

Storage Condition

Store at 15-30°C.

Store below 25°C.

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