Ketomax Wrap

Uses

For the relief of occasional constipation

Treatment of superficial and deep mycoses:

• Infections of the skin, hair and nails by dermatophytes and/or yeasts (dermatomycosis, onychomycosis, perionyxis, pityriasis versicolor, chronic mucocutaneous candidiasis etc.) especially when topical treatment is difficult or not very effective, owing to involvement of large skin surfaces or to lesions affecting deeper dermal layers, nails and hairs
• Yeast infection of the mouth (oral thrush, perleche) and the gastrointestinal tract
• Vaginal candidiasis, especially chronic recurrent cases or cases responding poorly to topcial treatment
• Systemic mycotic infections such as systemic candidiasis, paracoccidioidomycosis, histoplasmosis, coccidioidomycosis etc.

Maintenance treatment to prevent recurrence in systemic mycotic infections and in chronic mucocutaneous candidiasis.Prophylactic treatment to prevent mycotic infection in patients with reduced host defenses, e.g., patients with cancer, organ transplant and burns.

Ketomax Wrap is also used to associated treatment for these conditions: Cold Sore, Constipation, Dry Mouth, Dry Skin, Dry throat, Edema of the cerebrum, Hypertension Intracranial, Occasional Constipation, Ocular Discomfort, Ocular Hypertension, Ocular Irritation, Skin Infections, Sore Throat, Mouth soreness, Ocular burning, Bowel preparation therapy, Topical Antisepsis, Skin protectionBacterial Vaginosis (BV), Blastomycosis, Candidiasis, Systemic, Chromomycosis, Chronic Mucocutaneous Candidiasis (CMC), Coccidioidomycosis, Dandruff, Endogenous Cushing's Syndrome, Histoplasmosis, Infections, Fungal, Paracoccidioidomycosis, Seborrheic Dermatitis, Tinea Corporis caused by Epidermophyton floccosumin, Tinea Corporis caused by Trichophyton mentagrophytes, Tinea Corporis caused by Trichophyton rubrum, Tinea Cruris caused by Epidermophyton floccosumin, Tinea Cruris caused by Trichophyton mentagrophytes, Tinea Cruris caused by Trichophyton rubrum, Tinea Pedis caused by Epidermophyton floccosumin, Tinea Pedis caused by Trichophyton mentagrophytes, Tinea Pedis caused by Trichophyton rubrum, Vaginal Candidiasis, Vulvovaginal Candidiasis, Cutaneous candidiasis, Recalcitrant Dermatophytosis, Tinea versicolor caused by Malassezia infection

How Ketomax Wrap works

When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream.

Ketoconazole interacts with 14-α-sterol demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability due to reduced amounts of ergosterol present in the fungal cell membrane. This metabolic inhibition also results in accumulation of 14α-methyl-3,6-diol, a toxic metabolite. The increase in membrane fluidity is also thought to produce impairment of membrane-bound enzyme systems as components become less closely packed.

Dosage

Ketomax Wrap dosage

Children under 2 years: Consult a physician.

Children (2 to 6 years): only 1 Glycerin 1.15 suppository per 24 hours or as directed by a physician.

Adults and Children (From 6 years): only 1 Glycerin 2.30 suppository per 24 hours or as directed by a physician

Insert suppository well up into rectum. Suppository need to melt completely to produce laxative action.

Oral-

Fungal infections:

• Adult: 200 mg once daily; may increase to 400 mg once daily if clinical response is insufficient. Continue treatment until symptoms have cleared and cultures have become negative.
• Child: ≥2 yr 3.3-6.6 mg/kg once daily. Treatment duration: 1-2 wk for candidiasis; at least 4 wk in recalcitrant dermatophyte infections and up to 6 mth for other systemic mycoses.
• Elderly: No dosage adjustment needed.

Topical (Adult)-

Pityriasis versicolor, Skin fungal infections:

• As 2% cream: Apply 1-2 times daily to cover affected and surrounding area until at least a few days after disappearance of symptoms.
• As 2% shampoo: Apply on scalp once daily for up to 5 days. For prophylaxis: As 2% shampoo, use once daily for a max of 3 days before exposure to sunlight.

Seborrhoeic dermatitis:

• As 2% foam: Apply to the affected area bid for 4 wk.
• As 1 or 2% shampoo: Apply on the scalp twice wkly for 2-4 wk. For prophylaxis: As 2% shampoo, use once every 1-2 wk.

Duration of Treatment

• Pityriasis versicolor: 1 to 6 weeks
• Dermatomycoses: 2 to 8 weeks
• Onychomycoses: 1 to 12 months
• Mycoses of hair and scalp: 1 to 2 months
• Chronic mucocutaneous candidiasis : 1 to 12 months
• Oral mycoses: 5 to 10 days
• Systemic candidiasis: 1 to 2 months
• Paracoccidioidomycosis,histoplasmosis
• and other systemic mycosis: 1 month to 2 years

Side Effects

Glycerin when used rectally may cause rectal discomfort or a burning sensation

Ketoconazole is very well tolerated. Nausea and itching may occasionally occur. In some patients, an idosyncratic liver reaction may occur (incidence 1 : 10,000).

Toxicity

Glycerol has very low toxicity when ingested ; Rat LD50 (oral)-12600mg/kg Mice LD50 (oral )-4090mg/kg Human TDLo (oral) - 1428mg/kg

Symptoms of overdose include acute liver injury, which may include both hepatocellular and cholestatic injury, accompanied by anorexia, fatigue, nausea, and jaundice. In case of overdose, gastric lavage with activated charcoal may be used if within one hour of ketoconazole ingestion otherwise provide supportive care. If the patient shows signs of adrenal insufficiency, administer 100 mg hydrocortisone once together with saline and glucose infusion and monitor the patient closely. Blood pressure and fluid and electrolyte balance should be monitored over the next few days.

Precaution

Predisposition to adrenocortical insufficiency. Admin with acidic drink in patients with achlorhydria. Pregnancy and lactation.

Interaction

Reduced absorption with antimuscarinics, antacids, H2-blockers, PPIs and sucralfate. Reduced plasma concentrations with rifampicin, isoniazid, efavirenz, nevirapine, phenytoin. May also reduce concentrations of isoniazid and rifampicin. May reduce efficacy of oral contraceptives. May increase serum levels of CYP3A4 substrates e.g. digoxin, oral anticoagulants, sildenafil, tacrolimus.

Volume of Distribution

Glycerin is distributed throughout the blood. Although glycerin generally does not appear in ocular fluids, it may enter the orbital sac when the eye is inflamed, with a consequent decrease in osmotic effect.

Ketoconazole has an estimated volume of distribution of 25.41 L or 0.36 L/kg. It distributes widely among the tissues, reaching effective concentrations in the skin, tendons, tears, and saliva. Distribution to vaginal tissue produces concentrations 2.4 times lower than plasma. Penetration into the CNS, bone, and seminal fluid are minimal. Ketoconazole has been found to enter the breast milk and cross the placenta in animal studies.

Elimination Route

Well absorbed orally, poorly absorbed rectally. Studies in humans and animals indicate glycerol is rapidly absorbed in the intestine and the stomach

Ketoconazole requires an acidic environment to become soluble in water. At pH values above 3 it becomes increasingly insoluble with about 10% entering solution in 1 h. At pH less than 3 dissolution is 85% complete in 5 min and entirely complete within 30 min. A single 200 mg oral dose produces a Cmax of 2.5-3 mcg/mL with a Tmax of 1-4 h. Administering ketoconazole with food consistently increases Cmax and delays Tmax but literature is contradictory regarding the effect on AUC, which may experience a small decrease. A bioavailablity of 76% has been reported for ketoconazole.

Half Life

30 - 45 minutes

Ketoconazole experiences biphasic elimination with the first phase having a half-life of 2 hours and a terminal half life of 8 hours.

Clearance

Ketoconazole has an estimated clearance of 8.66 L/h.

Elimination Route

Approx 7-14% of dose is excreted unchanged in the urine within 2.5 hr.

Only 2-4% of the ketoconazole dose is eliminated unchanged in the urine. Over 95% is eliminated through hepatic metabolism.

Pregnancy & Breastfeeding use

Pregnancy category C. There are no controlled data in human pregnancy

Category C: Either studies in animals have revealed adverse effects on the foetus (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 foetus.

Contraindication

Sensitivity to the ingredients. Do not use unless the patient to be treated is, in fact, constipated.

Hypersensitivity; preexisting liver disease. Concurrent use with CYP3A4 substrates e.g. HMG-CoA reductase inhibitors (e.g. lovastatin, simvastatin), midazolam, triazolam, cisapride, dofetilide, eplerenone, nisoldipine, pimozide, quinidine, terfenadine, astemizole, ergot alkaloids (e.g. ergotamine, dihydroergotamine).

Special Warning

Renal Impairment: Oral: No dosage adjustment needed.

Hepatic Impairment: Oral: Contraindicated.

Storage Condition

Store below 25° C. Protect from moisture.

Store between 15-25° C. Protect from moisture and light.

Innovators Monograph

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