Dimetindene
Drug group: Antihistamine
Dimetindene (Fenistil) is an antihistamine/anticholinergic used orally and locally as an antipruritic
Mechanism of effect
Dimethindene is a competitive inhibitor of histamine at H1 receptors. In low concentrations it stimulates histamine methyltransferase resulting in histamine deactivation. It possesses a strong H1-receptor affinity and is a strong mast cell
stabilizer. It also has local anesthetic activity. It has no action on H2 receptors. Dimethindene also acts as an antagonist to bradykinin, serotonin, andacetylcholine. It is a racemic mixture with R-(-)-dimethindene having greater H1-antihistaminic activity
stabilizer. It also has local anesthetic activity. It has no action on H2 receptors. Dimethindene also acts as an antagonist to bradykinin, serotonin, andacetylcholine. It is a racemic mixture with R-(-)-dimethindene having greater H1-antihistaminic activity
Pharmacodynamic
Dimethindene is a selective histamine H1 antagonist and binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine
Pharmacokinetics
Absorption
A) Bioavailability
1) Oral, drops: 70%
a) The mean bioavailability ranges between 37% to 150%, with a mean of 74%, following oral administration
Distribution
A) Distribution Sites
1) Protein Binding
a) 90%
B) Distribution Kinetics
1) Volume of Distribution
a) 1.3 to 4.3 L/kg
Metabolism
A) Metabolism Sites and Kinetics
1) LIVER
B) Metabolites
1) 6-hydroxy-dimethindene
a) Reported to be the primary metabolite
2) N-desmethyldimethindene
a) Reported to be the primary metabolite
Excretion
A) Kidney
1) Renal Excretion (%)
a) 5% to 9%
2) Of an intravenous dose, 9% is excreted unchanged in the urine; the amount varies with urinary pH
3) Of an oral dose, 5% is excreted unchanged in the urine within 3 days (DeGraeve et al, 1989); 29 hours after a 4 mg oral dose, 0.98% was excreted unchanged and 1.43% as metabolites in the urine in healthy subjects
Elimination Half-life
A) Parent Compound
1) ELIMINATION HALF-LIFE
a) 6.3 hours
1) Oral, immediate-release tablet: 5.89 to 6.3 hours
2) Oral, sustained-release tablet: 11 hours
3) Oral, drops: 5.4 hours (range 5 to 7.6 hours)
4) Intravenous, injection: 4.9 hours (range 2.99 to 12.4 hours)
2) Oral, sustained-release tablet: 11 hours
3) Oral, drops: 5.4 hours (range 5 to 7.6 hours)
4) Intravenous, injection: 4.9 hours (range 2.99 to 12.4 hours)
Extracorporeal Elimination
A) Hemodialysis
1) Dialyzable: Yes
a) Mean clearance: 38 mL/min/m(2); the average plasma dimethindene concentration decreased from 16.6 to 12.6 ng/mL after 1 hour of dialysis
Drug indications
Indicated as symptomatic treatment of allergic reactions: urticaria, allergies of the upper respiratory tract such as hey fever and perennial rhinitis, food and drug allergies; pruritus of various origins, except pruritus due to cholestasis; insect bites. Dimethindene is also indicated for pruritus in eruptive skin diseases such as chicken-pox. Dimethindene can also be used as an adjuvant in eczema and other pruriginous dermatoses of allergic origin.
Dosage
1) DROPS
a) For the treatment of itching due to urticaria, dermatitis, eczema, diabetes, liver disease, leukemia, lymphogranulomatosis, insect bites, allergies, hay fever, the recommended dose is 1 to 2 milligrams (20 to 40 drops of a 1 milligram/milliliter solution) three times daily
2) IMMEDIATE RELEASE TABLET
a) For the treatment of itching due to urticaria, dermatitis, eczema, diabetes, liver disease, leukemia, lymphogranulomatosis, insect bites, allergies, hay fever, the recommended dose is 1 to 2 milligrams three times daily
3) SUSTAINED-RELEASE TABLET
a) For the treatment of ITCHING due to URTICARIA, DERMATITIS, ECZEMA, diabetes, liver disease, leukemia, lymphogranulomatosis, insect bites, ALLERGIES, or HAY FEVER, the recommended dose is 2.5 milligrams twice daily in the morning and evening
4) SYRUP
a) For the treatment of itching due to urticaria, dermatitis, eczema, diabetes, liver disease, leukemia, lymphogranulomatosis, insect bites, allergies, hay fever, the recommended dose is 1 teaspoonful (5 milliliters) of a 0.123-milligram/milliliter syrup up to 9 times daily
Parenteral route
1) For the treatment of itching due to urticaria, dermatitis, eczema, diabetes, liver disease, leukemia, lymphogranulomatosis, insect bites, allergies, or hay fever, the recommended dose is 4 milligrams (4 milliliters) intravenously once or twice daily. The maximum recommended length of therapy is 7 days
2) For PREMEDICATION with H2-receptor antagonists before general anesthesia, parenteral contrast agents or plasma substitutes, the recommended dose is 1 milligram (1 milliliter) per 10 kilograms of body weight by slow intravenous injection (2 milliliters/minute)
Topical application route
1) For pruritus due to skin disorders such as eczema, urticaria, INSECT BITES, SUNBURN, or FIRST DEGREE BURNS the 0.1% gel should be applied thinly to the affected skin and massaged in gently several times daily. If dressings or bandages are used, they should not be occlusive. Do not use the gel on large areas or broken or inflamed skin, especially in infants, toddlers or pregnant women. Nursing mothers should not apply the gel to the nipples
Drug contraindications
A) Hypersensitivity
B) Premature infants and neonates
C) Lactation
D) Prostate hypertrophy
E) Bladder obstruction
F) Hypersensitivity to parabens (contained in the topical gel, oral drops and oral syrup)
G) Cardiac arrhythmias
H)Alcohol abuse
Side effects
Cardiovascular Effects
Cardiovascular finding
1) Dimethindene may cause PALPITATIONS
Dermatologic Effects
Skin finding
1) Rare cases of RASH, periorbital and FACIAL EDEMA, increased ITCHING, and MORBILLIFORM ERUPTION have been reported after oral administration of dimethindene
Gastrointestinal Effects
Gastrointestinal tract finding
1) Dimethindene may cause NAUSEA, GASTRALGIA, ANOREXIA, DIARRHEA or DRY MOUTH. TASTE CHANGES have been reported after the IV injection
Immunologic Effects
Hypersensitivity reaction
1) Individual cases of hypersensitivity reactions, mostly of an anaphylactoid nature, have been reported with dimethindene. Dimethindene is associated with a relatively high risk of skin sensitization, leading to contact dermatitis or eczematous eruptions
Musculoskeletal Effects
Musculoskeletal finding
1) Intravenous dimethindene has been associated with MUSCLE TREMORS
Neurologic Effects
Central nervous system finding
1) Dimethindene may cause paradoxical EXCITEMENT in children, DROWSINESS, impaired reaction time, VERTIGO, HEADACHE, and NERVOUSNESS. Tolerance develops to the sedative effects of dimethindene within one to two days. IV injections may produce feelings of warmth or CHILLS
2) Dimethindene reportedly produces less CNS sedation than diphenhydramine and does not produce CNS irritability in high doses . Dimethindene reduces sleep latency as measured by EEG
Ophthalmic Effects
Eye / vision finding
1) Dimethindene may cause BLURRED VISION
Respiratory Effects
Respiratory finding
1) Rarely, DRY NOSE and SHORTNESS OF BREATH have been reported after dimethindene administration
Donepezil
Procarbazine
Procarbazine
Alerts
A) Peptic ulcer
B) Pyloroduodenal obstruction
C) Cardiovascular disease
D) Severe hypertension
E) Hyperthyroidism
F) Narrow-angle glaucoma
G)Asthma
Pregnancy level
There are no adequate studies in women for determining risk when using Fenistil® during pregnancy or while breastfeeding. Please always consult with your doctor to weigh the potential benefits and risks before taking Fenistil®. Fenistil® is pregnancy risk category C, according to the US Food and Drug Administration
Breast feeding warning
Avoid breastfeeding if you are applying Fenistil® gel or cream onto the breast.
User's questions
No comments yet.
Ask a Pharmacist