Trigaine

Uses

Azelaic acid is used for acne vulgaris, rosacea.

Minoxidil is used for the treatment of androgenic alopecia in males and females and stabilisation of hair loss in patients with androgenic alopecia, and also of alopecia areata.

• For the treatment of acne vulgaris in which comedones, papules and pustules predominate.
• For the treatment of hyperpigmentation, roughness and fine wrinkling of photodamaged skin due to chronic sun exposure.
• For the treatment of Acute promyelocytic leukaemia

Trigaine is also used to associated treatment for these conditions: Acne Vulgaris, Inflammatory lesions caused by rosacea, Susceptible Bacterial Infections, Nutritional supplementationAndrogenetic Alopecia, Severe, symptomatic HypertensionAcne Vulgaris, Alopecia, Cornification and dystrophic skin disorders, FAB classification M3 Acute promyelocytic leukemia, Skin hyperpigmentation, Solar Lentigines, Facial fine wrinkling, Keratinization disorders of the feet, Keratinization disorders of the hand, Moderate Melasma, Mottled hyperpigmentation, Severe Melasma, Severe, recalcitrant Cystic acne, Tactile roughness of facial skin

How Trigaine works

The exact mechanism of action of azelaic acid is not known. It is thought that azelaic acid manifests its antibacterial effects by inhibiting the synthesis of cellular protein in anaerobic and aerobic bacteria, especially Staphylococcus epidermidis and Propionibacterium acnes. In aerobic bacteria, azelaic acid reversibly inhibits several oxidoreductive enzymes including tyrosinase, mitochondrial enzymes of the respiratory chain, thioredoxin reductase, 5-alpha-reductase, and DNA polymerases. In anaerobic bacteria, azelaic acid impedes glycolysis. Along with these actions, azelaic acid also improves acne vulgaris by normalizing the keratin process and decreasing microcomedo formation. Azelaic acid may be effective against both inflamed and noninflamed lesions. Specifically, azelaic acid reduces the thickness of the stratum corneum, shrinks keratohyalin granules by reducing the amount and distribution of filaggrin (a component of keratohyalin) in epidermal layers, and lowers the number of keratohyalin granules.

Minoxidil is thought to promote the survival of human dermal papillary cells (DPCs) or hair cells by activating both extracellular signal-regulated kinase (ERK) and Akt and by preventing cell death by increasing the ratio of BCl^-2/Bax. Minoxidil may stimulate the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs. Minoxidil, when used as a vasodilator, acts by opening adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells. This vasodilation may also improve the viability of hair cells or hair follicles.

Tretinoin binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone. Although the exact mechanism of action of tretinoin is unknown, current evidence suggests that the effectiveness of tretinoin in acne is due primarily to its ability to modify abnormal follicular keratinization. Comedones form in follicles with an excess of keratinized epithelial cells. Tretinoin promotes detachment of cornified cells and the enhanced shedding of corneocytes from the follicle. By increasing the mitotic activity of follicular epithelia, tretinoin also increases the turnover rate of thin, loosely-adherent corneocytes. Through these actions, the comedo contents are extruded and the formation of the microcomedo, the precursor lesion of acne vulgaris, is reduced. Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. When Tretinoin is given systemically to APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.

Dosage

Trigaine dosage

Acne vulgaris:

• Adult: As 20% cream or 15% gel: Apply thinly into the affected areas bid (morning and evening) after cleansing. Improvement may be detectable w/n 4 wk. Duration of treatment: Up to 6 mth.
• Child: ≥12 yr Same as adult dose.

Rosacea:

• Adult: As 15% gel: Apply thinly into the affected areas bid (morning and evening). Improvement occurs in 4-8 wk.
• Child: ≥12 yr Same as adult dose.

Minoxidil topical solution is for external use only and should be applied when the hair and scalp are clean and dry. Apply 1 ml (7 sprays) of Minoxidil topical solution twice daily at 12-hour intervals to the scalp, beginning at the centre of the affected area and spreading the solution out to cover the entire affected area. The total daily application dose should not exceed 2 ml.

For the best results, Minoxidil topical solution should be allowed to remain on the scalp for about 4 hours before washing. The night-time application should be done 2-4 hours before going to bed to allow the solution to dry out. Minoxidil topical solution should not be massaged into the scalp, but applied lightly. A hair dryer should not be used to speed up the drying of the solution as it may decrease the effectiveness. Minoxidil topical solution should not be mixed with any hair oil. The drug should not be used more than two times a day, or be taken orally or applied to any other part of the body to avoid the risk of adverse effects and unwanted hair growth. More frequent use or longer application time have no effect on hair growth. In case of missing any daily applications of Minoxidil topical solution, the patient should continue with the next application.

Hands should be washed immediately if Minoxidil topical solution is applied with the fingertips. Clinical experience with Minoxidil indicates that twice-daily applications for 4 months or more may be required before there is evidence of hair growth. To arresthair fall, Minoxidil topical solution should be used for not less than 45 days. Depending upon the severity of hair loss or type and extent of baldness, particular strength of Minoxidil topical solution may be selected.

Tretinoin cream: Tretinoin cream should be applied sparingly to the whole affected area once or twice daily. The skin should be thoroughly cleaned and dried before application. Patient should be advised that 6 to 8 weeks of treatment may be required before a therapeutic effect is observed. Moisturisers and cosmetics may be used during treatment with Cosmotrin cream but should not be applied to the skin at the same time. Astringent toiletries should be avoided.

Tretinoin gel: Tretinoin gel should be applied once or twice a day, before retiring, to the skin where lesions appear, using enough to cover the entire affected area lightly. The frequency of application can be adjusted to obtain maximum clinical efficacy with minimal erythema and scaling.

If Tretinoin gel is applied excessively, no more rapid or better results will be obtained and marked redness, peeling or discomfort may occur. Should this occur accidentally or through over-enthusiastic use, application should be discontinued for few days.

Patience is needed in this treatment, since the therapeutic effects will not usually be observed until after 6-8 weeks of treatment. During the early weeks of treatment, an apparent exacerbation of inflammatory lesions may occur. This is due to the action of the medication on deep, previously unseen comedones and papules. Once the acne lesions have responded satisfactorily, it should be possible to maintain the improvement with less frequent applications.

Moisturizers and cosmetics may be used during treatment with Tretinoin gel but should not be applied to the skin at the same time. The skin should be thoroughly washed before application of Tretinoin gel. Astringent toiletries should be avoided.

Capsule: The recommended dose is 45 mg/m2/day administered as two evenly divided doses until complete remission is documented. Therapy should be discontinued 30 days after achievement of complete remission or after 90 days of treatment, whichever occurs first.

If after initiation of treatment of Tretinoin the presence of the translocation is not confirmed by cytogenetics and/or by polymerase chain reaction studies and the patient has not responded to Tretinoin, alternative therapy appropriate for acute myelogenous leukemia should be considered.

Side Effects

Burning, erythema, stinging, pruritus, dryness and scaling, peeling, irritation, dermatitis, hypopigmentation, rash, and photosensitivity. Rarely, exacerbation of asthma.

Commonly encountered side effects in clinical trials with Minoxidil topical solution were minor dermatological reactions. Dermatitis or hypertrichosis may occur. These incidences may occur in 0.1–5% of patients.

True allergic contact dermatitis is rare but a primary irritant dermatitis, manifesting itself as irritation, erythema, peeling and sensation of warmth, is common. Slight stinging is common as a mild reaction in many people but usually settles with continuous use and/or reduction in the frequency of application of the drug.

Toxicity

Oral LD50 in rat: >5 g/kg

Oral LD₅₀ in rats has ranged from 1321-3492 mg/kg; in mice, 2456-2648 mg/kg. Side effects include cardiovascular effects associated with hypotension such as sudden weight gain, rapid heart beat, faintness or dizziness.

Precaution

Patient with sensitive skin. Not intended for application to broken, sunburnt or eczematous skin. Avoid use of occlusive dressing or wrappings. Pregnancy and lactation.

Minoxidil topical solution is more likely to cause scalp irritation. If scalp irritation continues or worsen, use of Minoxidil topical solution should be stopped.

Interaction

Avoid spicy foods, alcoholic beverages and hot drinks that might provoke erythema, flushing and blushing during treatment of rosacea.

Minoxidil topical solution should not be used along with other topical agents known to alter the stratum corneum barrier such as tretinoin or dithranol, due to the enhanced absorption of Minoxidil. Although there is no clinical evidence, there exists the theoretical possibility of absorbed Minoxidil potentiating orthostatic hypotension caused by peripheral vasodilators.

Particular caution should be exercised in using preparations containing peeling agents (i.e. sulfur, resorcinol, benzoyl peroxide or salicylic acid). Use of topical preparations with high concentrations of alcohol, menthol, spices or lime- such as shaving lotions, astringents and perfume- should be avoided, especially during initial therapy.

Elimination Route

Approximately 4% of the topically applied azelaic acid is systemically absorbed.

Minoxidil is at least 90% absorbed from the GI tract in experimental animals and man.

1-31% (topical)

Half Life

The observed half-lives in healthy subjects are approximately 45 minutes after oral dosing and 12 hours after topical dosing, indicating percutaneous absorption rate-limited kinetics.

4.2 hours

0.5-2 hours

Elimination Route

Azelaic acid is mainly excreted unchanged in the urine, but undergoes some ß-oxidation to shorter chain dicarboxylic acids.

Pregnancy & Breastfeeding use

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a fetal 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).

Minoxidil topical solution should not be used during pregnancy and lactation.

Tretinoin is contraindicated in pregnancy or suspected pregnancy. The drug should be avoided by breast feeding mothers.

Contraindication

azelaic acid cream is contraindicated in individuals who have shown hypersensitivity to any of its components.

• Patients with cardiac abnormalities
• Children below 18 years of age
• Patients using occlusive dressings or other medicines on the scalp
• Patients with red, inflamed infection, or irritated or painful scalp (including psoriasis & sunburn)

Tretinoin is contraindicated in patients who are allergic to this drug. It is contraindicated in pregnancy or suspected pregnancy. It is also contraindicated in personal or familial history of cutaneous epithelioma.

Local irritation: The presence of cutaneous irritative signs (e.g. erythema, peeling, pruritus, sunburn, etc.) should prohibit initiation or recommencement of treatment with Tretinoin until the symptoms resolve. Tretinoin has been reported to cause severe irritation on eczematous skin and should be used with caution in patients with this condition.

Exposure to sunlight: Exposure to sunlight, including ultraviolet sun-lamps, should be avoided or minimised during the use of Tretinoin.

General precaution: Before application of Tretinoin, areas to be treated should be cleansed thoroughly. Abstain from washing the treated area frequently; twice daily is sufficient. Use of mild soap is recommended. Dry the skin without rubbing.

Avoid contact with eyes, eyelids, nostrils, mouth and mucous membranes. If contact in these areas occurs, careful washing with water is recommended.

Acute Overdose

Increased systemic absorption of Minoxidil may potentially occur if higher-than-recommended doses of Minoxidil are applied to larger surface areas of the body or areas other than the scalp. There are no known cases of Minoxidil overdosage resulting from topical administration of Minoxidil.

Signs and symptoms of Minoxidil overdosage would primarily be cardiovascular effects associated with sodium and water retention, and tachycardia. Fluid retention can be managed with appropriate diuretic therapy. Clinically significant tachycardia can be controlled by administration of a beta-adrenergic blocking agent.

Storage Condition

Store between 15-30° C.

Store at a cool and dry place, protected from light. Keep out of the reach of the children.

Store in a cool and dry place, away from light. Keep out of reach of children.

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