COMPOSITION
Each capsule contains
Calcium Dobesilate 500mg
MECHANISM OF ACTION
Calcium dobesilate has a
comprehensive mode of action. It increases endothelial nitric oxide levels by
enhancing the activity of nitric-oxide synthase, there by decreasing capillary
hyper-permeability.
Calcium dobesilate shows
anti-platelete and fibrinolytic activities by inhibiting platelet activation factor
(PAF) and enhancing the release of tissue plasminogen activator (tPA), thereby
improving the local blood flow to tissue, otherwise inhibited due to
thrombosis.
Calcium dobesilate also
inhibits the two pathophysiological reactions in diabetes viz. polyol pathway
and glycation of proteins due to its inhibitory effects on aldose reductase.
·
Calcium dobesilate
acts on the endothelial layer and basement membrane o the capillaries. It
reduces histamine and bradykinin-induced hyperpermeability. It increases red
blood cell membrane flexibility and reduces capillary fragility.
Calcium dobesilate can reduce
the platelet aggregation stimulated by collagen and thrombin, but not by
arachidonic acid.
·
Calcium dobesilate
may also inhibit the formation of sorbitol, thus providing another possible
mechanism for its usefulness in diabetic retinopathy.
·
Glucose inhibits
the formation of both type I and type II collagen formation. Calcium dobesilate
does not affect type l inhibition by glucose but accelerates type II collagen
fibrillogenesis, a major structural component of the arterial wall.
·
Calcium dobesilate
has angioprotective action by reducing the permeability and fragility of
microvessels, which should restrict fluid extravasation into the cardiac
interstitium. Its antiplatelets effects should counteract thrombosis and its
reduction of plasma viscosity should prevent stasis.
PHARMACOKINETICS
«
Drug concentration
levels: Therapeutic
«
Time to peak
concentration : 1. Oral: 6 hours
Maximum plasma levels
of 8 mcg/ml
ADULT DOSAGE – ORAL
1.
Doses of 1000mg
twice daily have demonstrated efficacy in the treatment of CHRONIC VENOUS
INSUFFICIENCY. A starting dose of calcium dobesilate of 500mg twice daily for 1
to 3 weeks, followed by 500mg once daily is recommended.
2.
For the treatment
of DIABETIC RETINOPATHY, 1500mg daily has demonstrated efficacy. Some recommended
a dose of calcium dobesilate of 500 to 1000mg daily for 4 to 6 months, 500mg
once daily.
For
advanced retinopathy, the dose is 500mg three times daily for one month, 500mg
twice daily for the second month, and 500mg once or twice daily for the third
month.
Calcium
dobesilate 500mg three times daily for two years did not produce significant
progression of pre- existing diabetic retinopathy compared to placebo in a
studying of 74 patients.
3.
In a placebo-
controlled dose-response study of 52 patients with increased platelet
aggregation, calcium dobesilate 1500mg/ day for four days produced a 22%
decrease in platelet aggregation, a 96.4% increase in reaction time and a 75%
decrease in the platelet aggregation/ reaction time quotient as compared to
placebo.
Doses
of 500mg and 1000mg daily did not produce significant changes.
ADVERSE
REACTIONS
Drug induced fever, epigastric
pain, gastric irritation, pruritus, skin rashes and agranulocytosis( rare).
INDICATIONS
a) Diabetic
Retinopathy and Glaucoma
·
Reduces blood hyperviscosity,
retinal hemorrhages, visual field defects, and intraocular pressure
·
Enhances outflow
facility
·
Inhibits the
formation of sorbitol
Calcium
dobesilate has been shown to decrease blood hyperviscosity and intraocular
pressure in patients with diabetic retinopathy and
GLAUCOMA. In a randomized
double blind trial, 79 non-insulin dependent diabetics with early retinopathy
or OPEN-ANGLE GLAUCOMA received 1500 milligrams daily for 6 months, or placebo.
The treatment group experienced statistically significant decreases in
intraocular pressure, visual field defects, surface area of retinal hemorrhage
and blood viscosity. There were also significant decrease in albumin,
prothrombin time, and platelet counts after 6 months of treatment.
b) Diabetic
Microangiopathy
500
milligrams orally 3 times daily for six months to 1 year.
·
Increases collagen
formation there by reducing vascular permeability
·
Reduces histaminic
and brandykinin induced hyper- permeability of capillaries
·
Maintains
flexibility of erythrocytes
·
Inhibits polyol
pathway and sorbitol formation in diabetes
·
Enhances Tissue
Plasminogen Activator ( TPA) activity and potentiates fibrinolysis
·
Exhibits direct
antioxidant properties and thereby maintains endothelial function
·
Inhibits Platelet
activating Factor ( PAF) and reduces platelet aggregation
c)
Chronic Venous Insufficiency
·
Effective in the
treatment of chronic venous insufficiency
·
Reduces volume in
the foot and lower legs
·
Reduces ankle and
calf circumferences
·
Decreases venous
distensibility index
·
Decreases maximum
venous outflow and capillary filtration index
·
Reduces ankle
edema
500 milligrams orally 3 times
daily for 28 days was highly effective and well tolerated in an open,
multicenter study of 373 patients with chronic VENOUS INSUFFICIENCY.
d) Haemorrhoids
·
Improves capillary
function
·
Reduces venous
engorgement
·
Reduces the anal
pain
·
Reduces blood loss
·
Improvement in the
vascular tensile strength
e)
Myocardial Infarction
Acute
Myocardial Infarction
·
Reduces infarct
size following acute myocardial infarction
·
Has a protective
effect on the myocardium in early acute myocardial infarction.
CONTRAINDICATIONS
Hypersensitivity to calcium
dobesilate.
PRECAUTIONS
Duodenal or peptic ulcer,
recurrent gastritis. In case of severe renal insufficiency requiring dialysis,
the dose should be reduced.
PREGNANCY
Calcium dobesilate shows no
teratogenic effects as it does not cross the placental barrier. Hence, it may
be used during pregnancy, however experience with same in clinical practice is
limited.
LACTATION
Exercise caution since safety
for use in the nursing mothers has not been established.
