DOXYCIN CAP 100MG

Main information

  • Trade name:
  • DOXYCIN CAP 100MG CAPSULE
  • Dosage:
  • 100MG
  • Pharmaceutical form:
  • CAPSULE
  • Composition:
  • DOXYCYCLINE (DOXYCYCLINE HYCLATE) 100MG
  • Administration route:
  • ORAL
  • Units in package:
  • 100/300
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOXYCIN CAP 100MG CAPSULE
    Canada
  • Language:
  • English

Therapeutic information

  • Therapeutic area:
  • TETRACYCLINES
  • Product summary:
  • Active ingredient group (AIG) number: 0105569001; AHFS: 08:12.24

Other information

Status

  • Source:
  • Health Canada
  • Authorization status:
  • MARKETED
  • Authorization number:
  • 00817120
  • Authorization date:
  • 31-12-1989
  • Last update:
  • 27-11-2018

Summary of Product characteristics: dosage,interactions,side effects

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 1 of 25

Prescribing Information and Patient Medication Information

Pr

DOXYCIN CAPSULES

100mg

Doxycycline Hyclate Capsules, USP

100 mg doxycycline (as hyclate)

Pr

DOXYCIN TABLETS

100mg

Doxycycline Hyclate Tablets, USP

100 mg doxycycline (as hyclate)

Antibiotic

LABORATOIRE RIVA INC.

660 Industriel Blvd.

Blainville, Canada

J7C 3V4

www.labriva.com

Date of Revision:

April 5, 2018

Control #: 211564

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 2 of 25

NAME OF DRUGS

Pr

DOXYCIN CAPSULES

Doxycycline Hyclate Capsules, USP

100mg doxycycline (as hyclate)

Pr

DOXYCIN TABLETS

Doxycycline Hyclate Tablets, USP

100mg doxycycline (as hyclate)

THERAPEUTIC CLASSIFICATION

Antibiotic

ACTION

Doxycycline hyclate is a broad-spectrum antibiotic and is active against a wide range of Gram-

negative and Gram-positive organisms. Doxycycline exerts its bacteriostatic effect by the inhibition of

protein synthesis.

INDICATIONS AND CLINICAL USE

DOXYCIN CAPSULES AND DOXYCIN TABLETS

(doxycycline hyclate) may be indicated for

the treatment of:

Pneumonia:

Single and multilobe pneumonia and bronchopneumonia due to susceptible strains of

Streptococcus

pneunomiae

and other

Streptococcus

spp.,

Staphylococcus

spp.,

H. influenzae

Klebsiella

pneumoniae

Other Respiratory Tract Infections:

Pharyngitis, tonsillitis, sinusitis, otitis media, bronchitis caused by susceptible strains of β-hemolytic

Streptococcus

Staphylococcus

spp.,

Streptococcus pneunomiae

H.

influenzae

Genitourinary Tract Infections:

Pyelonephritis, cystitis, urethritis caused by susceptible strains of

Klebsiella

spp.,

Enterobacter

aerogenes, E. coli

Enterococcus

spp.,

Staphylococcus

spp.,

Streptococcus

spp. and gonococcal

urethritis caused by

Neisseria gonorrhoeae.

In adult patients with urethritis, cervicitis and vaginitis with a positive test for

Chlamydia trachomatis

and/or

Ureaplasma urealyticum

, clinical resolution and absence of detectable organisms have only

been observed at completion of ORAL therapy with doxycycline hyclate

.

Relapses or reinfection can

occur. In these cases, limited data suggest that some patients may derive clinical benefit from an

alternative therapy. The effect on long term morbidity has not been established.

Skin and Soft Tissue Infections:

Impetigo, furunculosis, cellulitis, abscess, wound infections, paronychia, caused by susceptible strains

Staphylococcus aureus

epidermidis

Streptococcus

spp.,

E. coli

Klebsiella

spp. and

Enterobacter aerogenes.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 3 of 25

Gastro-intestinal Infections:

Caused by susceptible strains of

Shigella

spp.,

Salmonella

spp. and

E. coli

Up to 44 percent of strains of

Streptococcus pyogenes

and 74 percent of

Streptococcus faecalis

have

been found to be resistant to tetracycline drugs.

Appropriate culture and susceptibility studies should be carried out prior to initiation of therapy with

DOXYCIN CAPSULES AND DOXYCIN TABLETS

and if clinically indicated during treatment.

Consideration may be given to the initiation of therapy before obtaining results of these tests, however

modification of such treatment may be required once the results become available.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

and other antibacterial drugs,

DOXYCIN CAPSULES

AND DOXYCIN TABLETS

should be used only to treat infections that are proven or strongly suspected

to be caused by bacteria susceptible to doxycycline. When culture and susceptibility information are

available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such

data, local epidemiology data, susceptibility patterns, and local official antibiotic prescribing guidelines,

may contribute to the empiric selection of therapy.

CONTRAINDICATIONS

DOXYCIN CAPSULES AND DOXYCIN TABLETS

are contraindicated in individuals who have

shown hypersensitivity to doxycycline hyclate, and to any of the non-medicinal ingredients or to any

other tetracyclines, and in patients with myasthenia gravis.

DOXYCIN CAPSULES AND DOXYCIN TABLETS

is contraindicated in patients taking

isotretinoin (see

PRECAUTIONS AND DRUG INTERACTIONS

WARNINGS

General

Doxycycline hyclate like other tetracyclines, may form a stable calcium complex in any bone-forming

tissue, though

in vitro

it binds calcium less strongly than other tetracyclines. It should be anticipated

that the use of doxycycline hyclate

during tooth development (last trimester of pregnancy, during

lactation, neonatal period and early childhood to the age of 8 years) may cause permanent

discoloration of the teeth (yellow-gray-brown). Though more commonly associated with long term use

of tetracyclines, this effect has also been known to occur after short courses. Enamel hypoplasia has

also been reported.

DOXYCIN CAPSULES AND DOXYCIN TABLETS

should, therefore, not be used in these age

groups unless other drugs are unlikely to be effective or are contraindicated.

Carcinogenesis and Mutagenesis

Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been

conducted. However, there has been evidence of oncogenic activity in rats in studies with the related

antibiotics, oxytetracycline (adrenal and pituitary tumors) and minocycline (thyroid tumors).

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 4 of 25

Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in

in-vitro mammalian cell assays have been reported for related antibiotics (tetracycline).

Gastrointestinal

Instances of esophageal lesions (esophagitis and ulcerations), sometimes severe, have been reported in

patients receiving doxycycline. The patients must be instructed to take

DOXYCIN

CAPSULES AND

DOXYCIN TABLETS

with a full glass of water, to keep in orthostatic position after the

administration and not to go to bed within 1-2 hours after the intake. If symptoms such as dysphagia

and retrosternal pain occur,

DOXYCIN CAPSULES AND DOXYCIN TABLETS

should be

discontinued and an esophagic lesion must be investigated (see

PRECAUTIONS, ADVERSE

REACTIONS and DOSAGE AND ADMINISTRATION)

DOXYCIN CAPSULES AND

DOXYCIN TABLETS

should not be prescribed to patients with obstructive esophagic pathology,

such as stenosis and achalasia.

Clostridium difficile

-associated disease (CDAD) has been reported with use of many antibacterial

agents, including doxycycline hyclate. CDAD may range in severity from mild diarrhea to fatal colitis.

It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis,

pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration

of any antibacterial agent. CDAD has been reported to occur over 2 months after the administration of

antibacterial agents.

Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth

Clostridium difficile

C. difficile

produces toxins A and B, which contribute to the development of

CDAD. CDAD may cause significant morbidity and mortality. CDAD can be refractory to

antimicrobial therapy.

If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be

initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed

against

Clostridium difficile

. In moderate to severe cases, consideration should be given to

management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial

agent clinically effective against

Clostridium difficile

. Surgical evaluation should be instituted as

clinically indicated, as surgical intervention may be required in certain severe cases (see

ADVERSE

REACTIONS

Skin

Photosensitivity reaction manifested by an exaggerated sunburn reaction has been observed in some

individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should

be advised that this reaction can occur with doxycycline hyclate

,

and treatment should be discontinued

at the first evidence of skin erythema (see

PRECAUTIONS and ADVERSE REACTIONS

). The use

of sunscreen or sunblock prior to sun or UV light exposure should be considered in patients taking

DOXYCIN CAPSULES AND DOXYCIN TABLETS

Hypersensitivity

Hypersensitivity adverse drug reactions that included, but not limited to anaphylactic reaction,

angioedema, dyspnea, tachycardia, hypotension, pericarditis, urticaria, rash, erythema multiforme,

Stevens-Johnson and toxic epidermal necrolysis have been reported with doxycycline hyclate

use.

Some of these reactions were serious. If an allergic reaction occurs, administration of

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

should be discontinued and appropriate therapy should be

initiated.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 5 of 25

Doxycycline hyclate

has been associated with the development of autoimmune adverse drug reactions

including exacerbation of systemic lupus erythematous, rash, peripheral edema, arthralgia, myalgia,

serum sickness. If patients with autoimmune reactions are suspected, administration of

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

should be discontinued and liver function tests, ANA,

CBC, and other appropriate tests should be performed to evaluate the patients.

Renal

The anti-anabolic action of tetracyclines may cause an increase in BUN. Studies to date indicate that

this anti-anabolic effect does not occur with the use of doxycycline in patients with impaired renal

function.

Antimicrobial Susceptibility/Resistance

Prescribing

DOXYCIN CAPSULES AND DOXYCIN TABLETS

in the absence of a proven or

strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development

of drug-resistant bacteria.

Usage in Pregnancy

DOXYCIN CAPSULES AND DOXYCIN TABLETS

should not be administered to pregnant

women, unless in the judgment of the physician the potential benefit to the mother outweighs the risk

to the fetus (see above

WARNINGS

section about use during tooth development).

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and

can have toxic effects on the developing fetus (often related to retardation of skeletal development).

Evidence of embryotoxicity has also been noted in animals treated early in pregnancy.

Usage During Lactation

Tetracyclines are excreted in the milk of lactating women. Accordingly, the use of

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

is not recommended in women while they are breast

feeding (see above

WARNINGS

section about use during tooth development).

Use in Newborns, Infants and Children

The use of

DOXYCIN CAPSULES AND DOXYCIN TABLETS

in children under 8 years is not

recommended because safe conditions for its use have not been established (see above

WARNINGS

section about use during tooth development).

Doxycycline hyclate like other tetracyclines forms a stable calcium complex in any bone-forming

tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in

doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was

discontinued.

PRECAUTIONS

In clinical studies to date, administration of doxycycline hyclate did not lead to increased serum levels

nor to an increase in the serum half-life of doxycycline in patients with impaired renal function.

Modification of doxycycline hyclate dosage for these patients is not necessary. Although no evidence

of increased toxicity has been observed in such patients, the potential for increased hepatic or other

toxicity should be considered until further data on the metabolic fate of doxycycline under these

conditions become available.

Concurrent administration of doxycycline hyclate with agents known to be hepatotoxic should be

avoided.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 6 of 25

The use of antibiotics may occasionally result in overgrowth of non-susceptible organisms including

fungi; thus, observation of the patient is essential.

Patients should be advised that the use of doxycycline might increase the incidence of vaginal

candidiasis (see

ADVERSE REACTIONS

Benign intracranial hypertension (pseudotumor cerebri) has been associated with the use of

tetracyclines including doxycycline. Benign intracranial hypertension (pseudotumor cerebri) is usually

transient, however cases of permanent visual loss secondary to benign intracranial hypertension

(pseudotumor cerebri) have been reported with tetracyclines including doxycycline. If visual

disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since

intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored

until they stabilize. Concomitant use of isotretinoin and doxycycline should be avoided because

isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri) (see

ADVERSE REACTIONS

Cases of esophageal injury consisting of esophagitis and esophageal ulceration have been reported in

patients receiving doxycycline hyclate orally. Most of these patients took medication immediately

before going to bed and/or without adequate amount of fluid (see

DOSAGE AND

ADMINISTRATION

). If this should occur, doxycycline hyclate should be discontinued until healing

occurs. Administration of antacids and/or cimetidine has provided relief in the treatment of such cases.

TO REDUCE THE RISK OF ESOPHAGEAL INJURY, PATIENTS SHOULD BE ADVISED TO

TAKE

DOXYCIN CAPSULES OR DOXYCIN TABLETS

WITH AN ADEQUATE AMOUNT OF

FLUID WHILE STANDING OR SITTING UPRIGHT.

DOXYCIN CAPSULES AND DOXYCIN

TABLETS

should not be given at bedtime.

In long term therapy with

DOXYCIN CAPSULES AND DOXYCIN TABLETS,

periodic laboratory

evaluation of organ systems, including hematopoietic, renal and hepatic studies should be performed.

Liver function tests should be carried out at regular intervals on patients receiving high doses for

prolonged periods of time.

Drug interactions

Doxycycline hyclate

should be given with caution to patients receiving oral anticoagulants. Because

the tetracyclines have been shown to depress plasma prothrombin activity, patients who are on

anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Antacids containing aluminum, calcium or magnesium impair absorption and should not be given to

patients taking doxycycline hyclate.

The concurrent use of doxycycline hyclate with alcohol, barbiturates, phenytoin and carbamazepine

(hepatic enzyme inducers) has been reported to result in a reduction of plasma half-life of doxycycline,

thereby reducing the antimicrobial effectiveness of doxycycline hyclate. This effect may last for

several days after discontinuation of therapy with the interacting agent. Therefore, consideration

should be given to re-adjustment of the daily dose of doxycycline hyclate

when administered

concomitantly with alcohol and with drugs known to be enzyme inducers.

It has been reported that concurrent administration of ferrous sulphate (iron) lowered serum

concentrations of doxycycline given orally and shortened the serum half-life after a single intravenous

injection. In the event that iron and iron-containing products have to be given during treatment with

doxycycline hyclate,

the interval between administration of each drug should be as wide as possible.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 7 of 25

It has been reported that when subsalicylate bismuth was given simultaneously and as a multiple-dose

regimen before oral doxycycline hyclate

there was a reduced bioavailability of doxycycline. Also peak

serum concentrations of doxycycline were significantly decreased when subsalicylate bismuth was

given 2 hours before oral doxycycline

but not when given 2 hours after oral doxycycline hyclate.

Therefore subsalicylate bismuth should not be taken during therapy with oral doxycycline hyclate.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to

avoid giving doxycycline hyclate,

or any other tetracycline, in conjunction with penicillin.

There have been anecdotal reports that concurrent use of tetracyclines may render oral contraceptives

less effective.

The concurrent use of tetracycline and Penthrane (methoxyflurane) has been reported to result in fatal

renal toxicity.

Concomitant use of isotretinoin and doxycycline should be avoided because isotretinoin is also known

to cause benign intracranial hypertension (pseudotumor cerebri) (

see PRECAUTIONS

Drug Laboratory Test Interactions

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence

test.

ADVERSE REACTIONS

GASTROINTESTINAL:

with

other

broad

spectrum

antibiotics

administered

orally

parenterally,

gastro-intestinal

disturbances such as decreased appetite, nausea, vomiting, diarrhea, glossitis, dysphagia, stomatitis,

proctitis and enterocolitis, may occur, but have rarely been sufficiently troublesome to warrant

discontinuation of therapy with

DOXYCIN CAPSULES AND DOXYCIN TABLETS

. Abdominal

pain,

dyspepsia

(heartburn/gastritis),

pseudomembranous

colitis,

Clostridium

difficile

colitis

inflammatory lesions (with monilial overgrowth) in the anogenital region have also been reported. Due

to oral doxycycline’s virtually complete absorption, side effects of the lower bowel, particularly

diarrhea, have been infrequent.

Cases of esophagitis and esophageal ulcer, sometimes severe, in patients receiving capsule and tablet

form of doxycycline have been reported (see

WARNINGS, PRECAUTIONS and DOSAGE AND

ADMINISTRATION

AUTONOMIC NERVOUS SYSTEM:

Flushing.

HYPERSENSITIVITY

Hypersensitivity reactions consisting of urticaria, angioedema, anaphylactic reaction, anaphylactoid

reaction, Henoch-Schonlein Purpura, dyspnea, hypotension, pericarditis, peripheral edema, serum

sickness, tachycardia and exacerbation of systemic lupus erythematosus have been reported.

SKIN

Maculopapular

erythematous

rashes,

photosensitivity

reaction,

photo-onycholysis,

erythema

multiforme,

Stevens-Johnson

syndrome

Toxic

Epidermal

Necrolysis

have

been

reported.

Exfoliative dermatitis

has also been reported but is uncommon (see

WARNINGS

, skin).

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 8 of 25

MUSCULO-SKELETAL

Arthralgia and myalgia.

CENTRAL NERVOUS SYSTEM

Headache, fontanelle bulging in infants and benign intracranial hypertension (pseudotumor cerebri) in

adults.

relation

benign

intracranial

hypertension,

symptoms

included

blurring

vision,

scotomata and diplopia. Permanent visual loss has been reported (see

PRECAUTIONS

LIVER/BILIARY

There have been reports of hepatotoxicity (including hepatic failure, autoimmune hepatitis and

cholestasis) and hepatic function abnormal. As with other tetracyclines, hepatitis, elevation of SGOT

or SGPT values have been reported, the significance of which is not known.

HAEMATOLOGIC

Hemolytic anemia, thrombocytopenia, neutropenia, eosinophilia, leukopenia.

IMMUNE SYSTEM DISORDERS

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

HEARING/VESTIBULAR

Tinnitus.

INVESTIGATIONS (Renal Function Analyses)

Blood urea increased (apparently dose related) has been reported.

UROGENITAL:

Vaginal candidiasis (see

PRECAUTIONS

OTHERS:

When

given

over

prolonged

periods

tetracyclines

have

been

reported

produce

brown-black

microscopic discolouration of the thyroid gland. Abnormalities of thyroid function have not been

shown to date (see

TOXICOLOGY

, Subacute Toxicity).

SYMPTOMS AND TREATMENT OF OVERDOSAGE

Specific information on symptoms or treatment of overdosage with doxycycline hyclate

is not

available. In case of overdosage, discontinue medication. Treatment, therefore, should be symptomatic

and gastric lavage may be considered for overdosage with the oral preparation. Dialysis does not alter

serum half-life and thus would not be of benefit in treating cases of overdosage.

management

suspected

drug

overdose

contact

your

regional

Poison

Control

Centreimmediately.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 9 of 25

DOSAGE AND ADMINISTRATION

DOSAGE

EXCEEDING

RECOMMENDED

DOSAGE

RESULT

INCREASED

INCIDENCE OF SIDE EFFECTS.

Adults

The recommended dosage of

DOXYCIN CAPSULES AND DOXYCIN TABLETS

for the majority

of susceptible infections is a single loading dose of 200 mg on the first day of treatment followed by a

maintenance dosage of 100 mg once daily at the same time each day thereafter.

In the management of more severe infections (particularly chronic infections of the urinary tract), 200

mg should be given daily throughout the treatment period.

Therapy should be continued for at least 24-48 hours after symptoms and fever have subsided. It

should be noted, however, that effective antibacterial levels are usually present 24 to 36 hours

following discontinuance of doxycycline hyclate

therapy.

When used in streptococcal infections, therapy should be continued for 10 days to prevent the

development of rheumatic fever or glomerulonephritis.

For treatment of uncomplicated acute gonococcal infections, the recommended dosage is 200 mg

starting and 100 mg in the evening, the first day, followed by 100 mg b.i.d. for 3 days.

For treatment of uncomplicated urethral, endocervical, or vaginal infections in adults associated with

Chlamydia trachomatis

Ureaplasma urealyticum

: 100 mg, by mouth, twice a day for at least 10

days.

No alteration in recommended dosage schedule need be made when treating patients with impaired

renal function.

ADMINISTRATION

DOXYCIN CAPSULES AND DOXYCIN TABLETS

should be given with or after a meal in order

to minimize the possibility of gastric upset. Antacids and iron preparations impair absorption and

should not be given concomitantly to patients taking oral doxycycline hyclate.

Patients should be advised to take

DOXYCIN CAPSULES AND DOXYCIN TABLETS

with a full

glass of water, to keep in orthostatic position after the administration and not to go to bed within 1-2

hours after the intake.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 10 of 25

PHARMACEUTICAL INFORMATION

CHEMISTRY

Proper Name:

doxycycline hyclate

Chemical Name:

2-Naphthacenecarboxamide,

4-(dimethyIamino)-1,4,4a,5,5a,6,11,12a

octahydro-3,5,10,12,12a-pentahydroxy-6- methyl-1,11-dioxo-

monohydrochloride, compd. with ethanol (2:1), monohydrate,

|4S-(4α,4a α,5 α,5a α,6 α,12 α) | -or α -6-deoxy-5-oxytetracycline

Structural Formula:

Molecular Formula:

HCl)

C

OH

Molecular Weight:

1025.89 g/mol

Description:

Doxycycline hyclate is a yellow crystalline powder with a slight ethanolic odour and a bitter taste. The

melting point is about 200°C with decomposition. It is soluble in a 1 in 3 dilution with water, 1 in 60

with alcohol and 1 in 4 with methyl alcohol; slightly soluble in chloroform and ether; soluble in

solutions of alkali hydroxides and carbonates.

Composition:

DOXYCIN TABLETS

contain Doxycycline Hyclate equivalent to 100 mg of doxycycline.

Non-medicinal ingredients: Allura Red AC (FD&C Red No. 40), Carnauba wax, Hypromellose, Indigo

carmine (FD&C Blue No. 2), Magnesium stearate, Microcrystalline cellulose, Polyethylene glycol,

Polysorbate 80, Ouinoline Yellow WS (D&C Yellow No. 10), Silicon dioxide colloidal, Sodium starch

glycolate, Starch, Stearic acid, Sunset Yellow FCF (FD&C Yellow No. 6) and Titanium dioxide.

DOXYCIN CAPSULES

contain Doxycycline Hyclate equivalent to 100 mg of doxycycline. Non-

medicinal ingredients: Allura Red AC (FDC Red No. 40), Brilliant Blue FCF sodium salt (FD & C

Blue No. 1), Gelatin, Indigo Carmine (FDC Blue No. 2), Iron oxide, Lactose, Magnesium stearate,

Microcrystalline cellulose, Propylene glycol, Ouinoline Yellow WS (DC Yellow NO.1 0), Shellac,

Silicon dioxide colloidal, Stearic acid and Titanium dioxide.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 11 of 25

DOSAGE FORMS

AVAILABILITY

DOXYCIN

TABLETS:

Orange,

round,

biconvex

film-coated

tablets,

having

imprint

DOXYCIN/100 on one side and scored on the other side. Available in bottles of 100 and 300 tablets.

DOXYCIN CAPSULES:

Aqua colored hard gelatin capsules, having an imprint in black “H” or

“539”on the body and “H” or “539”on the head. Available in bottles of 100 capsules.

STORAGE

Bottles of

DOXYCIN TABLETS AND DOXYCYIN CAPSULES

(doxycycline hyclate) 100 mg

should be stored at controlled room temperature (15-30°C), protected from light and excessive

humidity.

MICROBIOLOGY

Doxycycline is a broad spectrum antibiotic and has been shown to be active

in vitro

against the

following Gram-negative, Gram-positive and other micro-organisms:

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 12 of 25

Staphylococcus aureus

Staphylococcus epidermidis (albus)

Streptococcus pyogenes

Streptococcus faecalis

Streptococcus pneumoniae

Streptococcus viridans

Listeria monocytogenes

Klebsiella pneumoniae

Salmonella typhi

Salmonella typhimurium

Salmonella enteriditis

Shigella sonnei

Shigella flexneri

Corynebacterium diphtheriae

Bacillus anthracis

Bacillus subtilis

Neisseria gonorrhoeae

Neisseria catarrhalis

Escherichia coli

Enterobacter aerogenes

Pseudomonas aeruginosa

Haemophilus influenzae

Serratia

spp.

Brucella

spp.

Proteus

spp.

Pasteurella

spp.

Mycoplasma pneumoniae

Chlamydia trachomatis

Ureaplasma urealyticum

The drugs in the tetracycline class have closely similar antimicrobial spectra, and cross-resistance

among them is common.

SUSCEPTIBILITY TESTING

The Kirby-Bauer method of disc susceptibility testing (using the 30 mcg doxycycline disc) and

dilution susceptibility should be interpreted according to the criteria in

TABLE 1

TABLE 1

SUSCEPTIBILITY TEST

ZONE DIAMETER

(30 mcg doxycycline disc) mm

M.I.C.

mg/L

Susceptible

Intermediate

Resistant

≥ 16

13-15

≤ 12

≤ 4

≥16

PHARMACOLOGY

Serum levels of doxycycline administered orally follow a similar pattern to those obtained with

equivalent dosages administered intravenously as shown in

TABLE 2

. Peak serum levels were slightly

higher and occurred earlier following intravenous administration than for oral administration (see

TABLE 2

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 13 of 25

TABLE 2

Serum levels (mg/L) after oral and I.V. infusion over 60 minutes (0.5 mg/mL) of a total daily dose of

200 mg of doxycycline hyclate on the first day (100 mg every 12 hours) and a dose of 100 mg on the

second and third day of administration (22 Male Volunteers/Group).

Time

(hr:min)

Mean Serum Level

I.V.

Mean Serum Level

Capsules

____

0:05

1:00

2:00

3:00

16:00

11:00

____

13:00

15:00

24:00

____

35:00

48:00

____

48:05

49:00

50:00

51:00

54:00

59:00

72:00

83:00

96:00

107:00

AUC (mgh/L)

0-107 hr

_____

2.455

1.608

1.551

1.421

1.131

0.800

____

2.397

2.130

1.468

____

1.734

1.159

____

3.658

2.945

2.848

2.760

2.150

1.665

1.021

0.700

0.426

0.247

mean area

I.V.

____

0.000

1.206

1.643

1.482

1.124

0.815

____

1.107

2.000

1.663

____

1.725

1.078

____

1.124

2.147

2.406

2.436

1.989

1.516

0.945

0.709

0.399

0.234

mean area

capsules

<.001

<.01

<.001

.088

<.001

<.001

.056

Where no p is stated, p>.10

____ time of dosing

Doxycycline

rapidly

almost

completely

absorbed

following

oral

administration.

absorption of doxycycline was not significantly influenced by ingestion of food or milk

(see

TABLE 3

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 14 of 25

TABLE 3

Effect of Food or Milk on Absorption of a Single Oral Dose of Doxycycline 100 mg as Hyclate

(5 Male Volunteers/Group).

AVERAGE SERUM LEVELS (mg/L)

Hours

Breakfast

Fasting

6 oz. milk

0.966

1.004

1.081

1.188

1.377

1.325

1.269

1.296

1.244

1.036

1.133

1.046

0.973

0.936

0.885

0.738

0.801

0.686

0.498

0.528

0.475

Doxycyline is approximately 93% protein bound. The serum half-life of doxycycline is 18 hours.

Doxycycline is excreted in the urine (approximately 35-40% of the administered dose) and in the bile.

The volume of distribution is approximately 0.7 L/kg. Hemodialysis does not alter the serum half-live.

Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal renal

function (creatinine clearance about 75 mL/min.). This percentage excretion may fall to a range as low

1-5%/72

hours

individuals

with

severe

renal

insufficiency

(creatinine

clearance

below

10mL/min.). The serum half-life of doxycycline is not increased, nor does it accumulate in the blood

of patients with impaired renal function.

TOXICOLOGY

Doxycycline Hyclate

Acute Toxicity

The acute oral and parenteral toxicity of doxycycline in mice, rats and dogs are as follows:

TABLE 4

(95% Confidence Limits) mg/kg

ORAL

I.V.

Mice

1,900 (1696-2128)

241 (230-253)

Rats

>2,000

228 (202-258)

Dogs

> 500

>100

The intraperitoneal LD

's of doxycycline in weanling and newborn rats are 262 (222-309) and 300

(275-327) mg/kg, respectively.

Subacute Toxicity

One to 2 1/2-month subacute toxicity studies were conducted in rats, hamsters, dogs and monkeys.

Doxycycline induced a yellow fluorescence (under ultraviolet light) of bone, teeth, kidney and/or liver,

in all animal species tested. In rats, doxycycline produced no toxic effects in doses of up to 500

mg/kg/day for 30 days. In hamsters, doxycycline in dosages of 500 or 250 mg/kg/day produced weight

loss and early death, but the 50 mg/kg level (for 30 days) was nontoxic. In dogs, doxycycline in

dosages of 250 mg/kg/day for one month produced discoloration of the thyroid gland with the presence

of intracytoplasmic granules in follicular acini and occasional amorphous body formation within

follicular colloid.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 15 of 25

Certain biochemical, functional and histological changes of the liver occurred in the dogs (but not in

the rats, hamsters, or monkeys) receiving doxycycline for 30 days at dosage levels of 250 and 50

mg/kg/day, but not at the 25 mg/kg/day level. The biochemical changes in the blood were elevations of

alkaline phosphatase, SGPT and/or BSP retention. Histologic changes were confined to bile ductular

proliferation and hepatocellular intracytoplasmic inclusion bodies and Kupffer cells swollen with PAS-

positive granular material. These changes in the dog were reversible upon drug withdrawal.

Monkeys which received doxycycline at dosages of 25 and 50 mg/kg/day for 1 1/2 to 2 1/2 months

showed mild yellow ultraviolet fluorescence of liver, kidney and bone, and the presence of small

amounts of intracytoplasmic granular material in the thyroid gland.

Chronic Toxicity

In an 18-month chronic toxicity study, rats were fed diets containing doxycycline at levels to provide

daily drug intake of 500, 250, 50 and 0 mg/kg. Slight depression of weight gains in some rats receiving

the 500 mg/kg/day dose occurred during the middle third of the study. The usual yellow ultraviolet

fluorescence of bone, teeth and/or kidneys was seen in rats receiving all levels of doxycycline for 6, 12

or 18 months. Dark to light brown discoloration of the thyroid gland was also noted in rats receiving

doxycycline for 12 months at levels of 500 and 250 mg/kg/day, and at 18 months at all levels. The

only other change noted was depletion of hepatic glycogen in four rats receiving the highest dose level

for 12 months.

Beagle dogs received doxycycline at levels of 10 and 100 mg/kg, six days per week. Moderate to

marked elevations of alkaline phosphatase and SGPT (occasionally SGOT) were observed in animals

receiving doxycycline, 100 mg/kg/day. One of two dogs receiving doxycycline, 100 mg/kg/day,

displayed mild bile ductular proliferation and hepatocellular inclusion bodies after 5 months (biopsy

sample) and 12 months (necropsy sample). Administration of doxycycline for 5 and 12 months at a

level of 100 mg/kg/day and for 12 months at a level of 10 mg/kg caused black and brownish

discoloration

thyroid

gland,

respectively,

with

intracytoplasmic

granules.

Other

changes

included vasodilatation and focal areas of necrosis of the mucosa of the pyloric and fundic stomach of

dogs, and yellow ultraviolet fluorescence of teeth and bones of animals at 100 mg/kg/day dose levels

of doxycycline.

Additional groups of 4 beagles each received doxycycline in dosages of 5, 1 and 0 mg/kg/day for 6

months. The only abnormal findings were slight elevations of SGPT values in 3 dogs at the 5 mg/kg

level at 180 days.

In a one year chronic toxicity study, groups of four rhesus monkeys each received doxycycline in oral

doses of 0, 5, 25 and 50 mg/kg/day, respectively. Oral dosage of 100 mg/kg produced severe

gastrointestinal symptoms, e.g., vomiting and diarrhea. In one out of 4 monkeys receiving the 50

mg/kg/day dose, occasional anorexia and diarrhea were observed during the first six months.

Significant pathologic changes noted in monkeys sacrificed after receiving doxycycline for 1 year at

dose levels of 50 mg/kg/day were: 1) grossly, very light brown discoloration of the thyroid gland in

one of the four monkeys, and 2) microscopically, brownish intracytoplasmic inclusions in the acinar

cells of thyroid follicles of three out of four monkeys. Bone and dentin exhibited slight to moderate

ultraviolet fluorescence.

Two monkeys, in another study, receiving the 25 mg/kg/day dosage, were sacrificed after 6 and 8

months

test,

respectively.

Significant

gross

histopathologic

findings

were

slight

yellow

ultraviolet fluorescence of the endosteum and periosteum of bone, and microscopic appearance of

small amounts of granular intracytoplasmic material in the acinar cells of thyroid follicles.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 16 of 25

The highlights of the chronic toxicity studies can be summarized as follows:

1) Discoloration of the thyroid gland, with deposition of intracytoplasmic granules in the acinar cells

of the follicle. Thyroid function, however, did not seem to be affected. This phenomenon appears to be

a result of the interaction of the antibiotic with the active iodinating system of the gland.

2) Yellow staining of bones and teeth, which is thought to be due to formation of a tetracycline-

calcium-phosphate complex.

Otherwise doxycycline was well tolerated by the rat and monkey at doses up to and including 500 and

50 mg/kg/day for 18 and 12 months, respectively. In dogs, however, repeated daily oral administration

of large doses of doxycycline resulted in certain hepatic functional and histopathologic changes which

are reversible after drug withdrawal. No adverse hepatic effects were noted in the hamster (1 month),

rats (18 months) or monkeys (12 months) for doses up to and including 500, 500 and 50 mg/kg/day,

respectively. In view of this and in view of the lack of notable toxicity in our wide human clinical

program, it is our opinion that this is a species specific phenomenon, for the dog only.

Reproduction and Teratogenic Studies

Doxycycline has no teratologic effects in rats, rabbits or monkeys.

Breeding rats received doxycycline by gavage in doses of 50 and 250 mg/kg/day prior to and

throughout two consecutive litters. There was no evidence that doxycycline interfered with the

reproductive process in rats.

Pregnant female white New Zealand rabbits received doxycycline orally in doses of 8 and 40

mg/kg/day, respectively, from day 8 to day 16 of pregnancy. Spina bifida and partial anencephaly in

one pup each in the control and the 8 mg/kg group, respectively, are believed to be spontaneous and

drug-induced.

In teratogenic studies using a limited number of monkeys, doxycycline, in doses ranging from 1 to 50

mg/kg/day, did not produce any teratologic effects.

Doxycycline Monohydrate

With bulk doxycycline monohydrate administered in a 10% aqueous suspension, the oral LD

albino male mice was greater than 5000 mg/kg.

Doxycycline Hyclate with Ascorbic Acid

Studies in mice and rats showed the LD

of Doxycycline I.V.

to be 75 mg/kg in mice and 88 mg/kg in

rats of doxycycline (using a preparation of doxycycline hyclate equivalent to 100 mg of doxycycline

with 480 mg of ascorbic acid as a sterile powder).

No signs of drug toxicity were seen in dogs receiving 20 to 21 daily doses of Doxycycline I.V.

at a

dose level of 5 mg/kg when administered as a 0.5% solution at a rate of 1 mg/kg/min. Dogs receiving

14, 16 or 17 daily intravenous doses of 10 mg Doxycycline I.V.

per kg of bodyweight, or 4 daily 60

minute infusions of 300 mg Doxycycline I.V.,

or 300 mg degraded Doxycycline I.V.

evidenced serum

alkaline phosphatase and serum glutamic pyruvic transaminase elevations. No morphological basis for

these enzyme elevations was established although moderate bile ductular proliferation was seen in 1 of

2 dogs receiving 4 daily intravenous infusions of degraded Doxycycline I.V.

.

In 8 dogs receiving daily intravenous doses of 10 mg Doxycycline I.V./kg/day (0.5% solution), 5 of 24

vessels used for injections evidenced degrees of thrombosis with recanalization.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 17 of 25

Thrombosis in 3 of 6 sites occurred in 2 dogs receiving infusions of degraded Doxycycline I.V.

mg/kg-0.5% solution). Injection site thrombosis did not occur in 6 dogs (18 sites) receiving daily doses

of 5 mg Doxycycline I.V.

/

kg bodyweight administered as a 0.5% solution at a rate of 1 mg/kg/min

(approximately 1 mL/min).

Studies to date indicate that the maximum tolerated intravenous daily dose of Doxycycline I.V.

in dogs

for 21 consecutive days is 5 mg/kg/day when administered as a 0.5% solution at a rate of 1 mg/kg/min.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 18 of 25

BIBILIOGRAPHY

DOXYCYCLINE - GENERAL

Aitchison WRC, Grant IWB, Gould JC. Treatment of acute exacerbations in chronic bronchitis.

Brit J Clin Pract 1968; 22:343-45.

Barteaux JW. Clinical experience with doxycycline, a new tetracycline. Intl J Clin Pharmacol Ther

Toxicol 1968; 1:404-405.

Clinical Research Reports, Medical Division, Pfizer Co. Ltd.

Montreal

Colemore JP, Braden B, Wilkerson R. Effectiveness of doxycycline treatment in chronic urinary

tract infections. Antimicrob Agents Chemother 1966; 118-120.

Domescik

McLone

Scotti

Mackey

single

dose

doxycycline

monohydrate for treating gonorrheal urethritis in men. Public Health Reports 1969; 84:182-83.

Gallai Z, Sylvestre L, Breault JP. Doxycycline in the treatment of acute gonorrhea in couples.

Presented at the 6th International Congress of Chemotherapy. Aug. 11-14 1969, Tokyo, Japan.

Gallai Z, Sylvestre L, Breault JP. Instant treatment of acute gonococcal urethritis with doxycycline.

Presented at the second world congress of the Int. Soc. of Tropical Dermatology. Aug. 16-18 1969,

Kyoto, Japan.

Grossan M. Management of infections of the ear, nose and throat with a new tetracycline

antibiotic: doxycycline. EENT Month 1968; 47:321-24.

Hany A, Petite J, Robert M, Fabre J. La doxycycline en clinique (fre). Chemotherapy 1968;

13(Suppl):59-63.

Hinton NA. The effect of oral tetracycline HCI and doxycycline on the intestinal flora. Curr Ther

Res 1970; 12:341-52.

Huang NN, Shang K, Basavanand N. Doxycycline treatment of children with cystic fibrosis of

pancreas. Antimicrob Agents Chemother 1966; 127-133.

Isenberg D.

In Vitro

activity of doxycycline against bacteria from clinical material. Appl Microbiol

1967; 15(5):1074-78.

Kalfopoulos P at al. Absorption digestive de la doxycycline chez l'homme comparee a celle des

autres tetracyclines. Policlinique de medecine (Pr. J. Fabre) et Clinique Medicale Therapeutique

(Pr. R.S. Mach) de l'universite de Geneve.

Lassus A. The treatment of gonorrhea with doxycycline as a single dose. Chemotherapy 1968;

13(6):366-68.

Lundberg C, Gullers K, MaImborg AS. Antibiotics in sinus secretions. Lancet 1968; 2:107-108.

Migliardi JR, Schach von Wittenau M. Pharmacokinetic properties of doxycycline in man. In:

Proceedings of the 5th Intl Cong of Chemother, Vienna, pp. 167-172, 1967.

Monnier J, Bourse R, Onfray J. Doxycycline:

In Vitro

bacteriostatic activity and serum levels in

man. Antibiotica 1966; 4:268-82.

Neuvonen PJ, Gothoni G, Hackman R, Bjorksten KAF. Interference of iron with the absorption of

tetracyclines in man, Brit Med J 1970; 4:532-34.

Pankey GA. Sinusitis. Current Therapy 1971, edited by Howard F. Conn. M.D., W.B. Saunders

Co. Toronto, pp. 125-27.

Roberge R, Lauchance W. Etude de la doxycycline en clinique et en laboratoire. Saguenay Med

1968; 15:101-107.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 19 of 25

Rosenblatt JE, Barrett JE, Brodie JL, Kirhy WM. Comparison of

In Vitro

Activity and Clin.

Pharm. of Doxycycline and other tetracyclines. Antimicrobial Agents Chemother 1966; 6:134-41.

Schach von Wittenau M. Some pharmacokinetic aspects of doxycycline metabolism in man.

Chemotherapy 1968; 13(Suppl):41-50.

Steigbigel NH, Reed CW, Finland M. Susceptibility of common pathogenic bacteria to seven

tetracycline antibiotics

in vitro

. Amer J Med Sci 1968; 255:179-95.

Sylvestre

Gallai

Traitement

minute

gonorrhee

nouveau

derive

l'oxytetracycline: la doxycycline. Union Med Can 1968; 97:639-40.

Sylvestre L, Gallai Z. Instant treatment of gonorrhea with a new oxytetracycline derivative:

doxycycline (preliminary report), Intl Clin Pharm Ther Toxicol 1968; 1:401-403.

Williamson GM. Laboratory studies of Vibramycin (doxycycline) International Symposium. New

resource in antibiotic therapy: doxycycline, Buenos Aires, June 14-15, 1967.

Williamson

in

vitro

activity

Vibramycin

(doxycycline).

Chemotherapy

1968;

13(Suppl):1-6.

DOXYCYCLINE RENAL INSUFFICIENCY

Edel. Doxycycline in renal insufficiency. VI Intern Congress of Chemotherapy. Tokyo, August

1969.

Fabre J, Pitton JS, Kunz JP. Distribution and excretion of doxycycline in man. Chemotherapy

1966; 11:73-85.

Fabre J Pitton JS, Virieux C, Laurencet FL, Bernhardt JP, Godel JC. Doxycycline absorption,

distribution

broad-spectrum

antibiotic

man.

Schweiz

Wochenschr

1967;

97(28):915-24. (translation)

Fabre J. Medicaments et fonctions renales. HeIv Med Acta 1967; 47(34):24-41.

Fabre J, Kunz JP, Virieux C, Laurencet JL, Pitton JS. Le comportement de la doxycycline chez

I'homme. Chemotherapy 1968; 13(Suppl):2340.

Giromini M, Wasem R, Merier G, Fabre J. Influence de I'anurie et des hemodialyses sur le

comportement des antibiotiques. Praxis 1969; 38:1181-87.

Laurencet FL, Fabre J. Influence de l'insuffisance renale sur le comportement de la doxycycline. J

Urol Nephrol 1968; 74:1038-47.

Little PJ, Bailey FIR. Tetracyclines and renal failure. N Z Med J 1970; 72:183-84.

Mahon

Wittenberg

JVP,

Tuffnel

Studies

absorption

distribution

doxycycline in normal patients and in patients with severely impaired renal function. Can Med

Assoc J 1970; 103:1031-34.

Merier G, Laurencet FL, Rudhardt M, Chuit A, Fabre J. Behaviour of doxycycline in renal

insufficiency. Helv Med Acta 1969; 35:124-34.

Porpaczy P. Doxycycline (Vibramycin) in renal insufficiency. Wien Klin Wschr. 1970; 82:710-14.

Ritzerfeld W, Westerboer S, Geller R. Doxycyclin in serum, diallysate and urine in patients with

renal functional disease. Intl J Clin Pharmacol Ther Toxicol 1970; 3:325-29.

Schach

Wittenau

Twomey

disposition

doxycycline

dog.

Chemotherapy 1971; 16:217-28.

Schach von Wittenau, Twomey TM, Swindell AC. The disposition of doxycycline by the rat.

Chemotherapy. 1971; 17(l):26-39.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 20 of 25

Stein W, Schoog M, Franz HE. Doxycycline serum levels in patients with renal insufficiency

(Ger). Arzneim Forsch (Drug Research). 1969; 19:827-28.

Vibramycin. Pharmacology Actua September 1969; 1(8): 8.

Zech P, Traeger J. Tolerance de la doxycycline dans l'insuffisance renale severe. Lyon Med 1969;

999:943-45.

DOXYCYLINE IN GONORRHEA

Caldwell JG, Wessler S, Avioli LV. Current therapy of gonorrhea. JAMA 1971; 218:714-17.

Ketterer

Homosexuality

venereal

disease.

Medical

Aspects

Human

Sexuality.

December 1971; 1(4):43-50.

Neumann HH, Baecker JM. Treatment of gonorrhea. Penicillin or tetracyclines? JAMA 1972;

219:471-74.

Smart WH, Lighter AC. Gonorrhea, the silent epidemic. A Scientific Exhibit, 23rd Clinical

Convention of the A.M.A., Denver, Colorado. November 30-December 3, 1969.

DOXYCYCLINE CHLAMYDIA TRACHOMATIS AND UREAPLASMA UREALYTICUM

INFECTlONS

Cunha BA, Comer JB, Jonas M. Symposium on antimicrobial therapy: The tetracyclines. Med Clin

North Am 1982; 66 (l):293-302.

Health and Welfare Canada, Bureau of Epidemiology. Canada Diseases Weekly Report 1981;

7(21):101-108.

Jaffe HW. Nongonococcal urethritis: Treatment of men and their sexual partners. Rev Infect Dis

1982; 4(6 Suppl):S772-S777.

Johannisson G, Sernryd A, Lycke E. Susceptibility of Chlamydia trachomatis to antibiotics in vitro

and in vivo. Sex Trans Dis 1979; 6(2):50-57.

Lassus A, Perko RL, Stubb S, Mattila R, Jansson E. Doxycycline treatment of nongonococcal

urethritis with special reference to T-strain mycoplasmas. Br J Vener Dis 1971;47: 126-130.

McNeil PJ, Fiumara NJ, Caliando JJ, Benes S, McCormack WM. Evaluation of doxycycline

hyclate in the treatment of nongonococcal urethritis. Sex Transm Dis 1981;8(2 Suppl):127-131.

Root TE, Edwards LID, Spengler PJ. Nongonococcal urethritis: A survey of clinical and laboratory

features. Sex Transm Dis 1980; 7(2):59-65.

Siboulet A, Bohbot JM, Catalan F, Siboulet A, Henry-Suchet J. Les infections uretro-genitales a

Chlamydia trachomatis. Bull Mem Soc Med Paris 1982; (4):103-13.

Thompson SE, ed. Urogenital chlamydial infections: an international perspective with a focus on

doxycycline. Proceedings of a symposium held in conjunction with The Second World Congress of

Sexually Transmitted Diseases, Paris, June 1986. Clin Ther 1986; 9(Suppl A):1-39.

Prescription Information – Vibramycin Capsules and Vibra-Tabs Film Coated Tablets, Pfizer Canada

Inc.,

Date of Revision: December 22, 2015. Control number: 187868.

Prescription

Information

Teva-Doxycycline

Capsules/Teva-Doxycycline

Tablets,

Teva

Canada

Limited,

Date of Revision: March 28, 2017, Control number: 192207.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 21 of 25

READ THIS FOR SAFE AND EFFECTIVE USE OF YOUR MEDICINE

PATIENT MEDICATION INFORMATION

Pr

DOXYCIN CAPSULES

Doxycycline Hyclate Capsules, USP

100 mg doxycycline (as hyclate)

Pr

DOXYCIN TABLETS

Doxycycline Hyclate Tablets, USP

100 mg doxycycline (as hyclate)

Read this carefully before you start taking

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

each time you get a refill. This leaflet is a summary and will not tell you everything about this drug.

Talk to your healthcare professional about your medical condition and treatment and ask if there is any

new information about

DOXYCIN CAPSULES AND DOXYCIN TABLETS

Antibacterial drugs like

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

treat only bacterial

infections. They do not treat viral infections such as the common cold. Although you may feel better

early in treatment,

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

should be used exactly as

directed. Misuse or overuse of

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

could lead to

growth

bacteria

that

will

killed

DOXYCIN

CAPSULES

AND

DOXYCIN

TABLETS

(resistance). This means that

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

not work for you in the future. Do not share your medicine.

What are DOXYCIN CAPSULES AND DOXYCIN TABLETS

used for?

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

are used to treat infections caused by

germs (bacteria).

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

NOT

used to treat viral infections

(e.g. the common cold).

How does DOXYCIN CAPSULES AND DOXYCIN TABLETS

work?

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

are an antibiotic. It stops the bacteria’s ability

to make what it needs to grow new cells. This helps get rid of the infection.

What are the ingredients in DOXYCIN CAPSULES AND DOXYCIN TABLETS?

Medicinal ingredients:

DOXYCIN CAPSULES AND DOXYCIN TABLETS

: doxycycline hyclate.

Non-medicinal ingredients:

DOXYCIN CAPSULES:

Allura Red AC (FDC Red No. 40), Brilliant Blue FCF sodium salt (FD & C

Blue No. 1), Gelatin, Indigo Carmine (FDC Blue No. 2), Iron oxide, Lactose, Magnesium stearate,

Microcrystalline cellulose, Propylene glycol, Ouinoline Yellow WS (DC Yellow NO.1 0), Shellac,

Silicon dioxide colloidal, Stearic acid and Titanium dioxide.

DOXYCIN

TABLETS

:

Allura Red AC (FD&C Red No. 40), Carnauba wax, Hypromellose, Indigo

carmine (FD&C Blue No. 2), Magnesium stearate, Microcrystalline cellulose, Polyethylene glycol,

Polysorbate 80, Ouinoline Yellow WS (D&C Yellow No. 10), Silicon dioxide colloidal, Sodium starch

glycolate, Starch, Stearic acid, Sunset Yellow FCF (FD&C Yellow No. 6) and Titanium dioxide.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 22 of 25

DOXYCIN CAPSULES AND DOXYCIN TABLETS

come in the following dosage forms:

DOXYCIN CAPSULES

: Aqua colored hard gelatin capsules, having an imprint in black “H” or

“539”on the body and “H” or “539”on the head.

DOXYCIN

TABLETS

Orange,

round,

biconvex

film-coated

tablets,

having

imprint

DOXYCIN/100 on one side and scored on the other side.

Do not use DOXYCIN CAPSULES AND DOXYCIN TABLETS

if you:

are allergic to this drug.

are allergic to any of the ingredients in these products. See also “What are the ingredients in

DOXYCIN CAPSULES AND DOXYCIN TABLETS

” above.

are allergic to tetracycline drugs (a class of antibiotics).

have myasthenia gravis (a muscle disease).

are taking isotretinoin (e.g. Accutane). See the next section, “To help avoid side effects and ensure

proper use”.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you

take DOXYCIN CAPSULES AND DOXYCIN TABLETS. Talk about any health conditions or

problems you may have, including if you:

are pregnant or plan to become pregnant.

are breastfeeding or planning to breastfeed. Some of this drug may pass to your baby.

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

are not recommended for women who are

breastfeeding.

have trouble swallowing.

have health problems that affect or block the tube that carries food from your mouth to your

stomach (esophagus).

DOXYCIN CAPSULES AND DOXYCIN TABLETS

should not be used in children under 8 years

of age.

Tetracyclines such as

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

may cause a serious

side effect, benign intracranial hypertension (pressure around the brain) with symptoms such as

headache, nausea, vomiting and vision loss. If this occurs, contact your doctor immediately. Do not use

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

and isotretinoin together as they both can

cause this effect.

Tell

your

healthcare

professional

about

all

the

medicines

you

take,

including

any

drugs,

vitamins, minerals, natural supplements or alternative medicines.

Do not take

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

with:

alcohol.

barbiturates (drugs that help you sleep).

phenytoin (a drug that controls epilepsy).

carbamazepine (a drug that controls epilepsy).

methoxyflurane (an anaesthetic).

Some drugs can make

DOXYCIN

CAPSULES AND DOXYCIN TABLETS

not work as well as

they should. These include:

drugs to thin the blood (oral anticoagulants).

penicillin, a drug to treat infections.

drugs to treat upset stomach that contain bismuth subsalicylate.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 23 of 25

drugs to treat heartburn that contain aluminum, calcium or magnesium.

products that contain iron.

Do not take these drugs at the same time of day as

DOXYCIN CAPSULES AND DOXYCIN

TABLETS

Birth control pills may not work if you are on them while taking DOXYCIN CAPSULES AND

DOXYCIN TABLETS

. You should use other birth control while taking these products and for 7 days

after stopping.

How to take DOXYCIN CAPSULES AND DOXYCIN TABLETS:

Take this medicine exactly as your doctor has told you to.

Do not skip doses.

Stop taking

DOXYCIN CAPSULES AND DOXYCIN TABLETS

right away if you become

pregnant.

Tell your doctor if you become pregnant.

Do not use

DOXYCIN CAPSULES AND DOXYCIN TABLETS

to treat any other medical

problems unless your doctor tells you to.

This medicine has been prescribed for you only. Do not share it with others. It may harm them,

even if their symptoms are the same as yours.

Do not stop taking this medicine until you have taken all of it, even if you feel better.

Stopping this medicine early may:

- increase the risk that bacteria will become resistant to it.

- make this product not work as well in the future.

Usual dose:

Take your medicine when your doctor tells you.

Take the amount of medicine your doctor tells you.

Take your medicine with or after a meal.

Take your medicine with a glass of water.

Take your medicine while standing or sitting.

After taking your medicine, wait at least 1 to 2 hours before lying down.

Overdose:

If you think you have taken too much

DOXYCIN

CAPSULES OR DOXYCIN TABLETS

, call your

doctor, pharmacist, hospital, or Poison Control Centre right away. Do this even if there are no symptoms.

Missed Dose:

If you forget to take

DOXYCIN CAPSULES AND DOXYCIN TABLETS

take them as soon as

you remember unless it is time to take the next dose.

Continue taking the rest of the doses as your doctor has told you to.

Do not take more than one dose at a time.

What are possible side effects from using DOXYCIN CAPSULES AND DOXYCIN TABLETS?

These are not all the possible side effects you may feel when taking

DOXYCIN CAPSULES AND

DOXYCIN TABLETS

. If you experience any side effects not listed here, contact your healthcare

professional. Please also see Warnings and Precautions.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 24 of 25

If you experience symptoms such as severe diarrhea (bloody or watery) with or without fever,

abdominal pain, or tenderness, you may have

Clostridium difficile

colitis (bowel inflammation). If this

occurs,

stop

taking

DOXYCIN

CAPSULES

AND

DOXYCIN

TABLETS

contact

your

healthcare professional immediately.

Other side effects that may occur while using

DOXYCIN CAPSULES AND DOXYCIN TABLETS

change in tooth colour.

diarrhea.

loss of appetite.

nausea.

stomach pain.

vomiting.

If these become bothersome, contact your doctor.

You may be sensitive to the sun when taking

DOXYCIN CAPSULES AND DOXYCIN TABLETS

You could get a sunburn.

If you will be in direct sunlight protect your skin, use sunscreen.

Avoid excessive sunlight.

Avoid tanning beds.

Stop using

DOXYCIN CAPSULES AND DOXYCIN TABLETS

if you become sensitive to the

sun. Symptoms of sun sensitivity include rash, blisters or skin break outs.

Serious side effects and what to do about them

Symptom / effect

Talk to your healthcare professional

Stop

taking

drug

get immediate medical

help

Only if severe

In all cases

UNKNOWN

Pain or difficulty swallowing

Rash

Yeast infection

Hypersensitivity (allergic) reaction.

Symptoms are:

- difficuly breathing.

- fast heartbeat.

- dizziness.

- itching.

- rash.

- skin blistering.

Autoimmune adverse drug reactions.

Symptoms are:

- swelling of hands and feet.

- muscle and joint pain.

- rash.

Benign intracranial hypertension

(high blood pressure in the brain).

Symptoms are:

- headache.

- nausea.

- vomiting.

- visual disturbances (e.g. blurred

vision, double vision, blank spots).

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to

interfere with your daily activities, talk to your healthcare professional.

Prescribing Information – DOXYCIN CAPSULES AND DOXYCIN TABLETS

Page 25 of 25

Reporting Side Effects

You can report any suspected side effects associated with the use of health products to Health Canada

Visiting the Web page on Adverse Reaction Reporting (http://www.hc-sc.gc.ca/dhp-

mps/medeff/report-declaration/index-eng.php) for information on how to report online,

by mail or by fax; or

Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need information about how to manage your side

effects. The Canada Vigilance Program does not provide medical advice.

Storage:

Store at controlled room temperature (15-30°C) protect from light and humidity.

Keep out of reach and sight of children.

You should not use your medication after the expiration date printed on the carton and label.

If you want more information about DOXYCIN CAPSULES AND DOXYCIN TABLETS:

- Please contact your doctor, pharmacist or other healthcare professional.

- This leaflet plus the full product monograph, prepared for health professionals, can be obtained by

contacting Laboratoire Riva Inc. at: 1-800-363-7988.

- This leaflet can also be found at: www.labriva.com

This leaflet was prepared by Laboratoire Riva Inc., Blainville, Québec, J7C 3V4.

Date of Revision: April 5, 2018