Perfocyn Plus

Uses

Chloramphenicol is used for Ocular infections, Bacterial meningitis, Anaerobic bacterial infections, Anthrax, Brain abscess, Ehrlichiosis, Gas gangrene, Granuloma inguinale, Infections caused by H. influenzae, Listeriosis, Plague, Psittacosis, Q fever, Severe gastroenteritis, Severe melioidosis, Severe systemic infections with Camphylobacter fetus, Tularaemia, Whipple's disease, Otitis externa

The confirmed indication for Clotrimazole include:

• All dermatomycoses due to dermatophytes (e.g. Trichophyton species).
• All dermatomycoses due to yeasts (Candida species).
• Dermatomycoses due to moulds and other fungi.
• Skin diseases showing superinfections with these fungi.

To the dermatomycoses listed under 1-4 belong for example, interdigital myocoses (e.g. athlete’s foot), paronychias (associated with nail mycoses), myocoses in skin folds, Candida vulvitis, Candida balanitis, Pityriasis versicolor, erythrasma.

Clotrimazole rectal preparation is used for vaginal itching, burning and discharge associated with recurrent vaginal yeast infections (Vaginal candidiasis) and also in viginitis due to Candida species as well as Mycotic infections complicated by other microorganisms sensitive to the drug.

Clotrimazole Sterile Eye Ointment is used for the treatment of fungal keratitis due to filamentous fungi and Candida species.

Clotrimazole Ear Drop is used for the treatment of fungal infections of the ear.

Lidocaine is a topical anesthetic used for the following purposes-

• To help prevent pain associated with minor surgical procedures in the ear, nose and throat
• To help prevent pain and or discomfort during dental procedures (e.g., prior to an injection)
• During general anesthesia to prevent coughing
• To help prevent pain during the final stages of childbirth, before the cutting or stitching of the perineum (skin between the vagina and anus)

Perfocyn Plus is also used to associated treatment for these conditions: Acne, Bacterial Conjunctivitis, Bacterial Conjunctivitis caused by susceptible bacteria, Bacterial Infections, Bacterial dacryocystitis, Bacterial diarrhoea, Conjunctivitis allergic, Corneal Inflammation, Eye swelling, Keratitis bacterial, Ocular Inflammation, Trachoma, Anterior eye segment inflammation, Bacterial blepharitis, Bacterial corneal ulcers, Non-purulent ophthalmic infections caused by susceptible bacteria, Superficial ocular infections, Skin disinfectionBalanitis candida, Candidiasis, Dermatitis, Dermatomycoses, Ear infection fungal, Erythrasma, Fungal Vaginal Infections, Fungal skin infection, Genital candidiasis, Inflammation, Mixed Vaginal Infections, Oropharyngeal Candidiasis, Pityriasis versicolor, Pyoderma, Ringworm, Skin Infections, Skin candida, Tinea Corporis, Tinea Cruris, Tinea Pedis, Tinea inguinalis, Trichophytosis, Vaginal Candidiasis, Vaginal Mycosis, Vulvitis, Cutaneous candidiasis, Infection mycotic, Susceptible Bacterial Infections, Symptomatic Tinea Corporis caused by Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum, Symptomatic Tinea Cruris caused by Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum, Symptomatic Tinea Pedis caused by Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum, Tinea versicolor caused by Malassezia infectionAcute 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 Perfocyn Plus works

Chloramphenicol is lipid-soluble, allowing it to diffuse through the bacterial cell membrane. It then reversibly binds to the L16 protein of the 50S subunit of bacterial ribosomes, where transfer of amino acids to growing peptide chains is prevented (perhaps by suppression of peptidyl transferase activity), thus inhibiting peptide bond formation and subsequent protein synthesis.

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane ,. Because ergosterol directly promotes the growth of fungal cells in a hormone‐like fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth .

Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as CYP51) is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca2+‐ATPase, depletion of intracellular calcium, and blocking of calcium‐dependent potassium channels and voltage‐dependent calcium channels . The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities .

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

Perfocyn Plus dosage

For Eye: Adults, children and infants (all age groups): One or two drops 4 to 6 times a day should be placed in the infected eyes. If necessary the frequency of dose can be increased. Treatment should be continued for approximately 7 days but should not be continued for more than three weeks without re-evaluation by the prescribing physician.

For Ear: 2 to 3 drops into ear canal thrice or four times daily.

Otic/Aural: Otitis externa:Instill 2-3 drops of a 5% solution into the ear bid-tid.

Oral:Bacterial meningitis, Anaerobic bacterial infections, Anthrax, Brain abscess, Ehrlichiosis, Gas gangrene, Granuloma inguinale, Infections caused by H. influenzae, Listeriosis, Plague, Psittacosis, Q fever, Severe gastroenteritis, Severe melioidosis, Severe systemic infections with Camphylobacter fetus, Tularaemia, Whipple's disease:

• Adult:50 mg/kg/day in 4 divided doses increased to 100 mg/kg/day for meningitis or severe infections due to moderately resistant organisms. Continue treatment after the patient's temperature has normalised for a further 4 days in rickettsial disease and 8-10 days in typhoid fever.
• Child:Premature and full-term neonates: 25 mg/kg/day in 4 divided doses. Full-term infants >2 wk: 50 mg/kg/day in 4 divided doses. Children: 50 mg/kg/day in 4 divided doses increased to 100 mg/kg/day for meningitis or severe infections.

Topical

Wash skin with soap and water and dry thoroughly. Apply a thin layer of the cream or solution 2-3 times daily and gently massage over affected area as directed by the doctor. For Athlete’s foot, pay special attention to the spaces between the toes. Best results in Athlete's foot and ringworm are usually obtained with 4 weeks use of this product. The cream should be applied two or three times daily for one month or for at least two weeks after the disappearance of all signs of infection. If satisfactory results have not occurred within these times consultation with doctor is essential. For best results, follow directions and continue treatment for length of time indicated. The duration of treatment varies; it depends among other factors on the extent and localization of the disease.

Recommended duration of treatment :

• Dermatomycoses: 3-4 weeks
• Candida vulvitis and candida balanitis: 1-2 weeks
• Erythrasma and pityriasis versicolor (approx.): 3 weeks
• In fungal infection of the feet, to prevent relapses:Treatment should be continued for about 2 weeks beyond the disappearance of all signs of disease.

Clotrimazole cream is odourless, can be washed off and does not stain.

Rectal

First infections: In general, a 3-day treatment is sufficient for Candida vaginitis. On 3 consecutive nights, Clotrimazole 200 mg vaginal preparation is inserted as deeply as possible into the vagina. This is best achieved when lying on one's back with the knees slightly bent.

Re-infections: In general, a 6-day treatment is sufficient. This applies also to mixed infections with the above-mentioned causative organisms. On six consecutive nights, 1 Clotrimazole 100 mgvaginal preparation is inserted as deeply as possible into the vagina. If necessary, 2 Clotrimazole 100 mg(1 in the morning and 1 in the evening) or 1 Clotrimazole 200 mg daily can be used for 6-12 days. Treatment should be timed so as to avoid the menstrual period and be finished before the onset of menstruation. To avoid re-infection, the partner should undergo local treatment with Clotrimazole cream at the same time.

Clotrimazole 500 mg vaginal preparation: Single dose, complete treatment with one vaginal tablet. The tablet should be inserted as deeply as possible into the vagina. This is best achieved when lying on one's back with the knees slightly bent. It is recommended that the treatment should be timed so as to avoid the menstrual period. For prevention of re-infection the partner should be treated locally with Clotrimazole cream at the same time.

Clotrimazolevaginal preparation are colorless and do not stain the underwear.

Eye

Adult: It should be applied thinly and evenly to the conjunctival sac every 4 hours daily or as advised by a physician.

Children: Safety and effectiveness in children have been established for Clotrimazole when used as indicated and in the recommended dosage.

Ear

Instill 2-3 drops of Clarizol Ear Drops in the affected ear two or three times daily.The treatment should be continued for at least two weeks after the disappearance of all signs of infection to prevent re-infection.

Intramuscular:Emergency treatment of ventricular arrhythmias: 300 mg injected into the deltoid muscle, repeat after 60-90 min if necessary.

Intraspinal:Spinal anaesthesia: As hyperbaric soln of 1.5% or 5% lidocaine in 7.5% glucose soln. Normal vaginal delivery: Up to 50 mg (as 5% soln) or 9-15 mg (as 1.5% soln). Caesarian operation: Up to 75 mg (as 5% soln). Other surgical procedures: 75-100 mg.Intravenous:Pulseless ventricular fibrillation or ventricular tachycardia : 1-1.5 mg/kg repeated as necessary. Max: 3 mg/kg. For ventricular arrhythmias in more stable patients: Usual loading dose: 50-100 mg as an IV inj at 25-50 mg/min, may repeat once or twice up to a max of 200-300 mg in 1 hr, followed by 1-4 mg/min via continuous IV infusion. May need to reduce dose if the infusion is longer than 24 hr.

Intravenous:Intravenous regional anaesthesia: As 0.5% soln w/o epinephrine: 50-300 mg. Max: 4 mg/kg.

Parenteral:Percutaneous infiltration anaesthesia: As 0.5% or 1% soln: 5-300 mg.Sympathetic nerve block: As 1% soln: 50 mg for cervical block or 50-100 mg for lumbar block.Peripheral nerve block:

• As 1.5% soln: For brachial plexus block: 225-300 mg.
• As 2% soln: For dental nerve block: 20-100 mg.
• As 1% soln: For intercostal nerve block: 30 mg;
• For paracervical block: 100 mg on each side, repeated not more frequently than every 90 min;
• For paravertebral block: 30-50 mg;
• For pudendal block: 100 mg on each side.
• As 4% soln: For retrobulbar block: 120-200 mg.

Spray:

• The maximum dose is 200 mg (Approximately 20 spray).
• In dentistry, the normal dose is 1-5 sprays. Two sprays per quarter of the mouth is recommended, with a maximum of 3 sprays per quarter of the mouth over 30 minutes.
• In sinus procedures 3 sprays are used.
• In procedures of the throat and windpipe, up to 20 sprays may be necessary.
• Up to 20 sprays may be necessary in childbirth (cesarian procedure).
• Lower doses are used for children aged 3-12 years. Lidocaine 10% Spray is not recommended for children under 3 years.

Topical: Anaesthesia before e.g. venepuncture (not for infants), apply a thick layer under an occlusive dressing 1-5 hours before procedure; split skin grafting, apply a thick layer under an occlusive dressing 2-5 hours before procedure; genital warts (not for children), apply up to 10 gm 5-10 minutes before removal.

For the treatment to become a complete success, reliable and sufficiently long application of Clotrimazole cream is important. The duration of treatment varies; it depends among other factors on the extent and localisation of the disease.

Side Effects

Oral: GI symptoms; bleeding; peripheral and optic neuritis, visual impairment, blindness; encephalopathy, confusion, delirium, mental depression, headache. Haemolysis in patients with G6PD deficiency.

ophthalmic application: Hypersensitivity reactions including rashes, fever and angioedema.

Ear drops: Ototoxicity.

Clotrimazole is generally well tolerated after local application but the few side effects have been reported infrequently like erythema, stinging, blistering, peeling, oedema, pruritus, urticaria and general irritation.

Since there is practically no Clotrimazole absorption through the vaginal skin, no systemic effect is expected. The local tolerance of Clotrimazole vaginal tablet is generally good. Local irritation or burning sensation may occur in a very few cases but these symptoms are not considered harmful.

Rarely patients may experience burning or irritation immediately after applying the ointment.

Arrhythmia, bradycardia, arterial spasms, CV collapse, oedema, flushing, hert block, hypotension, sinus node suppression, agitation, anxiety, coma, confusion, drowsiness, hallucinations, euphoria, headache, hyperaesthesia, hypoaesthesia, lightheadedness, lethargy, nervousness, psychosis, seizure, slurred speech, unconsciousness, somnolence, nausea, vomiting, metallic taste, tinnitus, disorientation, dizziness, paraesthesia, resp depression and convulsions. Patch: Bruising, depigmentation, petechiae, irritation. Ophth: Conjunctival hyperaemia, corneal epithelial changes, diplopia,visual changes.

Toxicity

Oral, mouse: LD₅₀ = 1500 mg/kg; Oral, rat: LD₅₀ = 2500 mg/kg. Toxic reactions including fatalities have occurred in the premature and newborn; the signs and symptoms associated with these reactions have been referred to as the gray syndrome. Symptoms include (in order of appearance) abdominal distension with or without emesis, progressive pallid cyanosis, vasomotor collapse frequently accompanied by irregular respiration, and death within a few hours of onset of these symptoms.

Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps. As with all topical agents, skin sensitization may result .

Oral LD50 (rat): 708 mg/kg; Intraperitoneal LD50 (rat): 445 mg/kg; Subcutaneous LDLO (rat): 10 g/kg; Oral LD50 (mouse): 761 mg/kg; Subcutaneous LDLO (mouse): 10 g/kg; Intraperitoneal LD50 (mouse): 108 mg/kg;

Overdose

This drug poses no risk of acute intoxication, as it is unlikely to occur following a single vaginal or dermal application of an overdose (application over a large area under conditions favorable to absorption) or accidental oral ingestion. There is no specific antidote .

Effects on Fertility

No human studies of the effects of clotrimazole on fertility have been conducted; however, animal studies have not shown any effects on the drug on fertility .

Use in Pregnancy

There are limited data regarding the use of clotrimazole in pregnant women. Animal studies do not show direct or indirect harmful effects on reproduction. Although the topical application of clotrimazole may result in very low serum and tissue levels, the use of clotrimazole topical cream by pregnant women is not recommended unless it is advised by the prescribing physician. Clotrimazole topical cream should not be used in the first trimester of pregnancy unless it is considered by the physician to be essential to patient well-being .

Use in Breastfeeding

Available pharmacodynamic/toxicological studies in animals have shown excretion of clotrimazole/metabolites in breastmilk. Clotrimazole should not be administered during breastfeeding. Although the topical application of clotrimazole has resulted in very low serum and tissue levels, the use of clotrimazole topical cream by lactating women is not recommended unless it recommended by the prescribing physician .

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

Impaired renal or hepatic function; premature and full-term neonates. Monitor plasma concentrations to avoid toxicity.

If local intolerance develops, consider withdrawal of the medicine and institution of appropriate therapy. Clotrimazole solution is not intended for ophthalmic use. Avoid contact with eyes upon topical application. Children 3 yrs. Pregnancy, lactation. If irritation or sensitivity develops with the use of Clotrimazole ointment, treatment should be discontinued.

Patient with pseudocholinesterase deficiency, resp depression. Hepatic and renal impairment. Elderly or debilitated patients. Pregnancy and lactation.

Interaction

Decreased effects of iron and vitamin B12 in anaemic patients. Phenobarbitone and rifampin reduce efficacy of chloramphenicol. Impairs the action of oral contraceptives.

There have been reports of a heat reaction when this medication used concomitantly with Sofradex drops in the ear.

Antagonism with polyene antibiotics.

May increase serum levels with cimetidine and propranolol. Increased risk of cardiac depression with β-blockers and other antiarrhythmics. Additive cardiac effects with IV phenytoin. Hypokalaemia caused by acetazolamide, loop diuretics and thiazides may antagonise effect of lidocaine. Dose requirements may be increased with long-term use of phenytoin and other enzyme-inducers.

Volume of Distribution

The topical form is minimally absorbed in the serum and tissues . Clotrimazole is a lipophilic drug , and has been shown to be secreted in breastmilk in animal studies . There are limited data available regarding the volume of distribution following oral troche administration.

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

Rapidly and completely absorbed from gastrointestinal tract following oral administration (bioavailability 80%). Well absorbed following intramuscular administration (bioavailability 70%). Intraocular and some systemic absorption also occurs after topical application to the eye.

Because clotrimazole is generally not significantly absorbed, drug interactions are not a major issue with its use .

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

Half-life in adults with normal hepatic and renal function is 1.5 - 3.5 hours. In patients with impaired renal function half-life is 3 - 4 hours. In patients with severely impaired hepatic function half-life is 4.6 - 11.6 hours. Half-life in children 1 month to 16 years old is 3 - 6.5 hours, while half-life in infants 1 to 2 days old is 24 hours or longer and is highly variable, especially in low birth-weight infants.

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

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

Mainly hepatic .

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. Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Pregnancy:Clotrimazole is recommended during pregnancy only after first consulting a doctor.

Lactation:Because systemic absorption of clotrimazole following topical application is marginal, there should be no risk for the infant during lactation.

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

History of hypersensitivity or toxic reaction to the drug; pregnancy, lactation; porphyria; parenteral admin for minor infections or as prophylaxis; preexisting bone marrow depression or blood dyscrasias.

Hypersensitivity to clotrimazole.

Hypovolaemia, complete heart block, Adam-Stokes syndrome, Wolff-Parkinson-White syndrome. Must not be applied to inflamed or injured skin.

Special Warning

Hepatic Impairment Parenteral: Dosage reduction may be needed.

Acute Overdose

Supportive measures should be taken incase of accidental oral ingestion.

In case of accidental oral ingestion, supportive measures should be taken.

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

Cap/susp: Store at temp not exceeding 30°C.

Ophth/otic preparation: Store between 2-8°C. Do not freeze. Protect from light.

Store at a cool and dry place. Protect from light. Do not freeze.

Store below 25°C.

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