DOXYCYCLINE CAPSULES 100 MG - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Doxycycline Capsules 100mg.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Doxycycline hyclate equivalent to 100mg of doxycycline.

For the full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM

Capsule, hard

Hard gelatin, No 3, opaque green capsules, containing yellow powder. Overprinted “DE 100” with “G”.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

The treatment of a variety of infections caused by susceptible strains of grampositive and gram-negative bacteria and certain other micro-organisms.

Respiratory Tract Infections: Pneumonia and other lower respiratory tract infections including those caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and other organisms. Mycoplasma pneumoniae pneumonia. Treatment of chronic bronchitis and sinusitis.

Urinary Tract Infections: caused by susceptible strains of Klebsiella species, Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.

Sexually Transmitted Diseases: infections caused by Chlamydia trachomatis including uncomplicated urethral, endocervical or rectal infections. Non-gonococcal urethritis caused by Ureaplasma urealyticum (T-mycoplasma). Doxycycline is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum. Doxycycline is an alternative drug in the treatments of gonorrhoea and syphilis.

As doxycycline is a member of the tetracycline family it may be useful in treating infections which respond to other tetracyclines such as:

Ophthalmic Infections: Caused by susceptible strains of gonococci, staphylococci, and Haemophilus influenzae. Trachoma, although the infectious agent, as judged by immunofluorescence, is not always eliminated. Inclusion conjunctivitis. (Doxycycline may be used in conjunction with topical agents).

Rickettsial Infections: Rocky Mountain spotted fever, typhus group, Q fever, Coxiella endocarditis and tick fevers.

Other Infections: Psittacosis, brucellosis (in combination with streptomycin), colera, bubonic plague, louse and tick-borne relapsing fever, tularaemia glanders, melioidosis, chloroquine- resistant falciparum malaria and acute intestinal amoebiasis (as an adjunct to amoebicides).

Doxycycline is an alternative drug in the treatment of leptospirosis, gas gangrene and tetanus.

Doxycycline is also indicated for the prophylaxis of: Scrub typhus, travellers’ diarrhoea (caused by entero-toxigenic Escherichia coli), leptospirosis and malaria. Prophylaxis of malaria should be used in accordance with current guidelines, as resistance is an ever changing problem.

Consideration should be given to official guidance on the appropriate use of antibacterial a­gent.

4.2 Posology and method of administration

Posology

Adults and children aged 12 years to less than 18 years

The usual dose of Doxycycline capsules for the treatment of acute infections in adults and children aged 12 years to less than 18 years is 200 mg on first day (as a single dose or divided in two 100 mg doses with a 12-hour interval), followed by a maintenance dose of 100 mg daily. In the management of more severe infections, 200 mg daily should be given throughout treatment.

Children aged 8 years to less than 12 years (Section 4.4)

The use of doxycycline for the treatment of acute infections in children aged 8 years to less than 12 years should be carefully justified in situations where other drugs are not available, are not likely to be effective or are contraindicated.

In such circumstance, the doses for the treatment of acute infections are:

For children 45 kg or less- Initial dose: 4.4 mg/kg (in single or 2 divided doses) with maintenance dose: 2.2 mg/kg (in single or 2 divided dosed). In the management of more severe infections, up to 4.4 mg/kg should be given throughout treatment.

For children, over 45 kg – Dose administered for adults should be used.

Children aged from birth to less than 8 years

Doxycycline should not be used in children aged younger than 8 years due to the risk of teeth discolouration. (Section 4.4 and 4.8)

Sexually Transmitted Diseases: Recommended dose is 100 mg twice daily for 7 days for the following infections: Uncomplicated gonococcal infections (except anorectal infections in men); uncomplicated urethral, endocervical or rectal infection caused by Chlamydia trachomatis; non-gonococcal urethritis caused by Ureaplasma urealyticum.

Acute Epididymo-Orchitis: Caused by Chlamydia trachomatis or Neisseria gonorrhoeae 100 mg twice daily for 10 days.

Primary and Secondary Syphilis: Non-pregnant penicillin-allergic patients who have primary or secondary syphilis can be treated with the following regimen: doxycycline 200 mg orally twice daily for two weeks as an alternative to penicillin.

Louse and Tick-Borne Relapsing Fevers: A single oral dose of 100 to 200 mg according to severity.

Treatment of chloroquine-resistant falciparum malaria: 200 mg daily for at least 7 days. Due to the potential severity of the infection, a fast-acting schizonticide such as quinine should also be given. Quinine dosage recommendations vary in different areas.

Prophylaxis of malaria: 100 mg daily in adults and children over the age of 12 years. Prophylaxis can begin 1–2 days before travel to malarial areas. It should be continued daily during travel in the malarial areas and for 4 weeks after the traveller leaves the malarial area. For current advice on geographical resistance patterns and appropriate chemoprophylaxis, current guidelines or the Malaria Reference Laboratory should be consulted, details of which can be found in the British National Formulary (BNF).

Prevention of Scrub Typhus: 200 mg as a single dose.

Prevention of Travellers’ Diarrhoea in Adults: 200 mg on the first day of travel (administered as a single dose or as 100 mg every 12 hours) followed by 100 mg daily throughout a three week stay in the area (No information available to support prophylactic therapy beyond 21 days).

Prevention of Leptospirosis: 200 mg once each week throughout the stay in the area and 200 mg at the completion of the trip (Data on the use of the drug prophylactically are not available beyond 21 days).

Paediatric population: See section 4.3.

Older People: Doxycycline may be prescribed in the usual dose with no special precautions. No dosage adjustment is necessary in the presence of renal impairment.

Patients with renal impairment: Studies to date have indicated that administration of Doxycycline at the usual recommended doses does not lead to accumulation of the antibiotic in patients with renal impairment see section 4.4.

Method of administration

The capsules should be swallowed with plenty of fluid in either the sitting or standing position and well before going to bed for the night to reduce the risk of oesophageal irritation and ulceration. If gastric irritation occurs, it is recommended that Doxycycline Capsules be given with food or milk. Studies indicate that the absorption of doxycycline is not notably influenced by simultaneous ingestion of food or milk.

Exceeding the recommended dosage may result in an increased incidence of side-effects.

Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided. When used in streptococcal infections, therapy should be continued for 10 days to prevent the development of rheumatic fever or glomerulonephritis.

4.3 Contraindications

Hypersensitivity to the active substance, any other tetracycline, or to any of the excipients listed in section 6.1.

Pregnancy

Doxycycline is contra-indicated in pregnancy. It appears that the risks associated with the use of tetracyclines during pregnancy are predominantly due to effects on teeth and skeletal development. (See Section 4.4 regarding use during tooth development).

Nursing mothers

Tetracyclines are excreted into milk and are therefore contraindicated in nursing mothers. (See Section 4.4 regarding use during tooth development).

4.4 Special warnings and precautions for use

Paediatric population

The use of drugs of the tetracycline class during tooth development (last half of pregnancy; infancy and childhood to the age of 8 years) may cause permanent discolouration of the teeth (yellow-grey-brown). The adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use doxycycline in paediatric patients aged younger than 8 years only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g. Rocky Mountain spotted fever), only when there are no adequate alternative therapies.

Although the risk of permanent teeth staining is rare in children aged 8 years to less than 12 years, the use of doxycycline should be carefully justified in situations where other drugs are not available, are not likely to be effective or are contraindicated.

Use in patients with impaired hepatic function

Doxycycline should be administered with caution in patients with hepatic impairment or those receiving potentially hepatotoxic drugs. Abnormal hepatic function has been reported rarely and has been caused by both oral and parenteral administration of tetracyclines including doxycycline.

Use in patients with renal impairment

Excretion of doxycycline by the kidney is about 40%/72 hours in patients with normal renal function. This percentage excretion may fall to a range as low as 1–5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10ml/min). Studies have shown no significant difference in the serum half-life of doxycycline in individuals with normal and severely impaired renal function. Haemodialysis does not alter the serum half-life of doxycycline. The anti-anabolic action of the tetracyclines may cause an increase in blood urea. Studies to date indicate that this anti-anabolic effect does not occur with the use of doxycycline in patients with impaired renal function.

Photosensitivity

Photosensitivity manifested by exaggerated sunburn reaction has been observed in

some individuals taking tetracyclines, including doxycycline. Patients likely to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs and treatment should be discontinued at the first sign of skin erythema.

Benign intracranial hypertension

Bulging fontanelles in infants have been reported in individuals receiving tetracyclines. 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 disturbances occur 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 or other systemic retinoids and doxycycline should be avoided because isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri). (see section 4.5).

Microbial overgrowth

The use of antibiotics may occasionally result in over-growth of non-susceptible organisms including Candida. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including doxycycline, and has ranged in severity from mild to lifethreatening. It is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of the antibacterial agents.

Clostridium difficile

Associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD.

Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Oesophagitis

Instances of oesophagitis and oesophageal ulcerations have been reported in patients receiving the capsule and tablet form of the drugs in the tetracycline class, including doxycycline. Most of the patients took medications immediately before going to bed or with inadequate amounts of fluid.

Porphyria

There have been rare reports of porphyria in patients receiving tetracyclines.

Venereal disease

When treating venereal disease when co-existent syphilis is suspected, proper diagnostic procedures, including dark-field examinations, should be utilised. In all such cases, monthly serological tests should be made for at least four months.

Beta-haemolytic streptococci infections

Infections due to group A beta-haemolytic streptococci should be treated for at least ten days.

Myasthenia gravis

Due to potential for weak neuromuscular blockade, care should be taken in administering tetracyclines to patients with Myasthenia gravis.

Systemic lupus erythematosus

Tetracyclines can cause the exacerbation of SLE.

Methoxyflurane

Caution is advised in administering tetracyclines with methoxyflurane (see section 4.5).

Jarisch-Herxheimer reaction

Some patients with spirochete infections may experience a Jarisch-Herxheimer reaction shortly after doxycycline treatment is started. Patients should be reassured that this is a usually self-limiting consequence of antibiotic treatment of spirochete infections.

4.5 Interaction with other medicinal products and other forms of interaction

The absorption of doxycycline may be impaired by concurrently administered antacids containing aluminium, calcium, magnesium or other drugs containing these cations; oral zinc, iron salts or bismuth preparations. Dosages should be maximally separated.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving Vibramycin in conjunction with penicillin.

There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline. Tetracyclines depress plasma prothrombin activity and reduced doses of concomitant anticoagulants may be necessary.

The serum half-life of doxycycline may be shortened when patients are concurrently receiving barbiturates, carbamazepine or phenytoin. An increase in the daily dosage of Vibramycin should be considered.

Alcohol may decrease the half-life of doxycycline.

A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracycline antibiotics with oral contraceptives.

Doxycycline may increase the plasma concentration of ciclosporin. Co-administration should only be undertaken with appropriate monitoring.

The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity. See section 4.4.

Concomitant use of isotretinoin or other systemic retinoids and doxycycline should be avoided. Each of these agents used alone has been associated with benign intracranial hypertension (pseudotumor cerebri). (See section 4.4).

Laboratory test interactions

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

4.6 Fertility, pregnancy and lactation

Doxycycline is contraindicated in pregnancy and breast-feeding.

See “Contra-indications”.

4.7 Effects on ability to drive and use machines

The effect of doxycycline on the ability to drive or operate heavy machinery has not been studied. There is no evidence to suggest that doxycycline may affect these abilities.

4.8 Undesirable effects

The following adverse reactions have been observed in patients receiving tetracyclines, including doxycycline.

Adverse Reactions Table

* Symptoms included blurring of vision, scotomata and diplopia. Permanent visual loss has been reported.

Reversible and superficial discolouration of permanent teeth has been reported with the use of doxycycline but frequency cannot be estimated from available data Tetracyclines may cause discolouration of teeth and enamel hypoplasia, but usually only after long-term use.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Acute overdosage with antibiotics is rare. Gastric lavage and appropriate supportive measures are indicated should overdosage occur.

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Tetracyclines, ATC code: J01AA02

Doxycycline is primarily bacteriostatic and is believed to exert its anti microbial effect by the inhibition of protein synthesis. Doxycycline is active against a wide range of gram-positive and gram-negative bacteria and certain other microorganisms.

5.2 Pharmacokinetic properties

Tetracyclines are concentrated by the liver in the bile and excreted in the urine and faeces at high concentration and in a biologically active form.

Doxycycline is virtually completely absorbed after oral administration. Studies reported to date indicate that the absorption of doxycycline unlike certain other tetracyclines, is not notably influenced by the ingestion of food or milk.

Following a 200mg dose, normal adult volunteers averaged peak serum levels of 2.6 micrograms/ml at 24 hours. Studies have shown no significant difference in serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function.

Hemodialysis does not alter the serum half-life of doxycycline.

5.3 Preclinical safety data

There are no preclinical safety data of relevance to the prescriber, which are additional to those already included in other sections of the SPC.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

The capsule contains magnesium stearate, talc and maize starch.

The capsule shell contains gelatin, Patent Blue V (E131), yellow iron oxide (E172), black iron oxide (E172) and titanium dioxide (E171)

The printing ink contains shellac, titanium dioxide (E171), propylene glycol, and either ammonium hydroxide and simeticone, or sodium hydroxide and povidone

6.2 Incompatibilities

None known

6.3

36 months

6.4 Special precautions for storage

Store in the original package in order to protect from light and moisture. Store below 25°C

6.5 Nature and contents of container

Amber glass containers with moisture resistant screw caps, polypropylene containers with polyethylene caps (with optional polyethylene ullage filler), PVC Aluminium foil blisters and high density polyethylene (HDPE) containers with polyethylene snap closures in pack sizes of 5, 7, 8, 10, 14, 20, 21, 25, 28, 30, 50, 56, 60, 84, 90, 100 and 250.

Not all pack sizes may be marketed

6.6 Special precautions for disposal

No special requirements.

7.

MARKETING AUTHORISATION HOLDER

Generics [UK] Ltd t/a Mylan

Station Close

Potters Bar

Herts

EN6 1TL

8. MARKETING AUTHORISATION NUMBER

PL 0456 9/0035

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date MA granted:    15th September 1983

Last renewal date:    3rd March 1999