Physical And Pharmaceutical Properties
Synonyms: Dossiciclina Iclato; Doxycycline
Hyclate (BANM, rINNM); Doxycyclini Hyclas.
Chemical Name: Doxycycline
hydrochloride hemiethanolate hemihydrate.
C22H24N2O8,HCl,1/2C2H -5OH, -1/2H2O
Molecular Weight: 512.9
A yellow hygroscopic crystalline powder.
Doxycycline hydrochloride 115 mg is approximately equivalent to 100 mg of
doxycycline. Ph. Eur. solubilities are: freely soluble in water and in methyl
alcohol; sparingly soluble in alcohol; practically insoluble in ether; dissolves
in solutions of alkali hydroxides and carbonates. USP solubilities are: soluble
in water; slightly soluble in alcohol; practically insoluble in chloroform and
in ether; soluble in solutions of alkali hydroxides and carbonates. A 1%
solution in water has a pH of 2 to 3.
Store in airtight containers. Protect from light.
Preparations of doxycycline hydrochloride have an
acid pH and incompatibility may reasonably be expected with alkaline
preparations or with drugs unstable at low pH. Reduced antimicrobial activity
has been reported in vitro when doxycycline hydrochloride was mixed with
Adverse Effects And Precautions
As for Tetracycline Hydrochloride.
Gastrointestinal disturbances are reported to be less frequent than with
tetracycline and doxycycline may also cause less tooth discoloration.
Oesophageal ulceration may be a particular
problem if capsules or tablets are taken with insufficient fluid or in a
recumbent posture: doxycycline should be taken with at least half a glass of
water, in an upright position, and one hour or more before retiring to bed.
There is some evidence from studies in animals that preparations of the base,
which have a higher pH, cause less oesophageal damage than those of the more
acid hydrochloride. Dispersible tablets or liquid formulations should be used in
elderly patients, who may be at greater risk of oesophageal injury.
Unlike many tetracyclines, doxycycline does not
appear to accumulate in patients with impaired renal function, and aggravation
of renal impairment may be less likely.
Anosmia or dysosmia (absent or impaired sense of
smell) have occasionally been reported in patients receiving doxycycline,
although the association has not been definitely established.
For the suggestion that doxycycline might be
As for Tetracycline Hydrochloride. Doxycycline
has a lower affinity for binding with calcium than many tetracycline's. In
consequence its absorption is less likely to be affected by milk or food,
although it is still affected by antacids and iron preparations.
The metabolism of doxycycline may be accelerated
by drugs that induce hepatic enzymes such as alcohol (chronic use);
antiepileptics including carbamazepine, phenobarbitone, and phenytoin; and
rifampicin. It has been suggested that doxycycline could increase cyclosporin
concentrations, but evidence for this seems to be scant.
As for Tetracycline Hydrochloride. Doxycycline is
more active than tetracycline against many bacterial species including the
enterococci and various anaerobes. Cross-resistance is common although some
tetracycline-resistant Staphylococcus aureus respond to doxycycline. Doxycycline
is also reported to be more active against protozoa, particularly Plasmodium spp.
For the general pharmacokinetics of the
tetracycline's, see Tetracycline Hydrochloride. Doxycycline hydrochloride is
readily and almost completely absorbed from the gastrointestinal tract and
absorption is not significantly affected by the presence of food in the stomach
or duodenum. Mean peak plasma concentrations of 2.6 micrograms per mL have been
reported 2 hours after a 200-mg dose by mouth, falling to 1.45 micrograms per mL
at 24 hours. After intravenous infusion of the same dose peak plasma
concentrations are briefly somewhat higher, but become very similar to those
after oral administration following equilibration into the tissues.
From 80 to 95% of doxycycline in the circulation
is reported to be bound to plasma proteins. Its biological half-life varies from
about 12 to 24 hours. Doxycycline is more lipid-soluble than tetracycline. It is
widely distributed in body tissues and fluids.
In patients with normal renal function about 40%
of a dose is slowly excreted in the urine although more is excreted by this
route if urine is made alkaline. However, the majority of a dose of doxycycline
is excreted in the faeces following chelation in the intestines. Although
doxycycline has been reported to undergo some inactivation in the liver, some
sources consider this doubtful; however, the kinetics of doxycycline have been
reportedly altered in patients receiving drugs which induce hepatic metabolism.
Doxycycline is stated not to accumulate
significantly in patients with renal impairment although excretion in the urine
is reduced; increased amounts of doxycycline are excreted in the faeces in these
patients. Nevertheless there have been reports of some accumulation in renal
failure. Removal of doxycycline by haemodialysis is insignificant.
Concentrations of doxycycline in CSF of patients
with neurological manifestations of Lyme disease receiving doxycycline 200 mg
daily by mouth ranged from 0.4 to 2.5 micrograms per mL at 4 hours after a dose.
(1) This represented 3 to 36% of the serum concentration at that time and was
reported to be adequate for the treatment of the infection
Uses And Administration
Doxycycline is a tetracycline derivative with
uses similar to those of tetracycline. It may sometimes be preferred to other
tetracycline's in the treatment of sensitive infections because of its fairly
reliable absorption and its long half-life which permits less frequent (often
once daily) dosage. It also has the advantage that it can be given (with care)
to patients with renal insufficiency. However, relatively high doses may need to
be given for urinary-tract infections because of its low renal excretion.
Doxycycline is normally administered by mouth as
doxycycline or its various derivatives. Doses are expressed in terms of
doxycycline. The usual dose is 200 mg of doxycycline on the first day (as a
single dose or 100 mg repeated after 12 hours), followed by 100 mg daily.
Older children weighing 45 kg or less may be
given 4 mg per kg body-weight initially and thereafter 2 mg per kg daily but the
effect of tetracycline’s on teeth and bones should be considered. In severe
infections the initial dosage is maintained throughout the course of treatment.
In patients with sensitive gonococcal infections doxycycline has occasionally
been given in a single dose of 300 mg, alone or followed by a second similar
dose one hour later.
For syphilis, doxycycline 200 or 300 mg is given
daily for at least 15 or 10 days, respectively. In the treatment of acne a dose
of 50 mg daily may be adequate. For relapsing fever and louse-borne typhus,
doxycycline 100 or 200 mg may be given as a single dose. For prophylaxis of
scrub typhus, 200 mg may be taken as a single dose.
Doxycycline capsules and tablets should be given
with plenty of fluid, with the patient in an upright position, and well before
retiring for the night. It may be given with food or milk if gastric irritation
occurs. Dispersible tablets or liquid formulations are advisable in elderly
In patients in whom oral therapy is not feasible
doxycycline may be given, as the hydrochloride, by slow intravenous infusion of
a solution containing 0.1 to 1 mg per mL, in doses equivalent to those by mouth.
Infusions should be given over 1 to 4 hours.
Doxycycline is used in some areas for the
treatment of chloroquine-resistant falciparum malaria in a dose of 200 mg daily
for at least 7 days in combination with quinine. Doxycycline 100 mg daily has
been used for prophylaxis in areas of high risk where other drugs are likely to
be ineffective, but it is not suitable for extended prophylactic use.