Doxycycline Capsules 100mg
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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 gram-positive
and gram-negative bacteria and certain other micro-organisms.
1. 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.
2. Urinary Tract Infections: caused by susceptible strains of Klebsiella species, Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.
3. 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:
4. 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).
5. Rickettsial Infections: Rocky Mountain spotted fever, typhus group, Q fever, Coxiella endocarditis and tick fevers.
6. 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 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.
4.2 Posology and method of administration
For oral administration
Adults: 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 more severe infections (particularly chronic infections of urinary tract), a daily dose of 200 mg can be used.
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.
Paediatric population: Doxycycline capsules are contraindicated in children under 12 years of age (see section 4.3).
In severe infections, a daily dose of 200 mg can be used in children and adolescents 12 years and over.
Use in patients with impaired hepatic function: See section 4.4.
Use in patients with renal impairment: Dosage restriction is not normally required in cases of renal impairment.
Studies to date have indicated that administration of doxcycyline at the usual recommended doses does not lead to accumulation of the antibiotic in patients with renal impairment (see section 4.4).
Administration of adequate amounts of fluid along with capsule forms of drugs in the tetracycline class is recommended to reduce the risk of oesophageal irritation and ulceration. Intake of fluids is recommended in the upright position and well before retiring for the night.
If gastric irritation occurs it is recommended that doxycycline be given with food or milk. Studies indicate that the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food and 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 ten days to prevent the development of rheumatic fever or glomerulonephritis.
Specific infections:
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: Have been successfully treated with a single oral dose of 100 to 200 mg according to severity.
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 (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 (No information available to support prophylactic therapy beyond 21 days).
4.3 Contraindications
Hypersensitivity to doxycycline or any other tetracycline, or any of the excipients listed in section 6.1.
The use of drugs of the tetracycline class during tooth development (pregnancy, infancy and childhood to the age of 12 years) may cause permanent discolouration of the teeth (yellow-grey-brown). This adverse reaction is more common during longterm use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Doxycycline is therefore contraindicated in these groups of patients.
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 above about use during tooth development).
Nursing mothers
Tetracyclines are excreted into milk and are therefore contraindicated in nursing mothers. (See above about use during tooth development).
Children
Doxycycline is contraindicated in children under the age of 12 years. As with other tetracyclines, doxycycline forms a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracyclines in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. (See above about use during tooth development).
4.4. Special warnings and precautions for use
Microbial overgrowth
The use of antibiotics may occasionally result in over-growth of non-susceptible organisms including Candida. Constant observation of the patient is essential. 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 life-threatening. 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.
Bulging fontanelles
Bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported in individuals receiving full therapeutic dosages. These conditions disappeared rapidly when the drug was discontinued.
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.
Skeletal development
Doxycycline can cause a retardation of skeletal development since animal studies indicate that tetracyclines cross the placenta, are found in foetal tissues and have toxic effects on the developing foetus.
Beta-haemolytic streptococci infections
Infections due to group A beta-haemolytic streptococci should be treated for at least ten days.
Photosensitivity
Patients likely to be exposed to direct sunlight or ultraviolet light should be advised that photosensitivity leading to exaggerated sunburn can occur with tetracyclines, and treatment should be discontinued at the first sign of skin erythema.
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 halflife of doxycycline in individuals with normal and severely impaired renal function. 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.
Haemodialysis has no effect on the serum half-life of doxycycline.
Use in patients with hepatic impairment
Doxycycline should be administered with caution in patients with hepatic impairment, acute porphyria or in patients taking hepatotoxic drugs. Abnormal hepatic function has been reported rarely and has been caused by both oral and parenteral administration of tetracyclines including doxycycline.
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.
Myasthenia gravis
Care should be taken in the treatment of patients with myasthenia gravis who may be at risk of a weak neuromuscular blockade.
Systemic lupus erythematosus
Tetracyclines can cause the exacerbation of SLE.
4.5. Interaction with other medicinal products and other forms of interaction
Absorption of doxycycline may be impaired by antacids containing aluminium, calcium, magnesium, bismuth, iron-containing products, sucralfate and zinc sulphate. Doses should be maximally separated.
Barbiturates, carbamazepine and phenytoin cause reduced plasma concentrations. Increase in daily dosage of doxycycline should be considered.
Alcohol may decrease the half-life of doxycycline.
There have been reports of prolonged prothrombin times in patients taking warfarin and doxycycline. Long term treatment with tetracyclines can depress plasma prothrombin activity. Patients receiving anticoagulants may require a reduction in their dose of anticoagulants.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, the combination of doxycycline and penicillin should be avoided.
The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.
As with other tetracyclines, doxycycline forms a stable calcium complex in any boneforming tissue. A decrease in fibula growth rate has been observed in prematures given oral tetracycline in doses of 25mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.
Although not reported with doxycycline, in a few cases concurrent use of tetracycline or oxytetracycline with oral contraceptives has led to pregnancy or breakthrough bleeding.
Doxycycline possibly increases plasma-ciclosporin concentration. Co-administration should only be undertaken with appropriate monitoring.
Laboratory test interactions. False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.
4.6 Fertility, pregnancy and lactation
Pregnancy
Doxycycline is contraindicated in pregnancy. Results of animal studies indicate that tetracyclines cross the placenta, are found in foetal tissues and can have toxic effects on the developing foetus (often related to retardation of skeletal development). Evidence of embryo toxicity has also been noted in animals treated early in pregnancy. (See section 4.3 for use on tooth development).
Breast-feeding
Tetracyclines can pass into breast milk and should therefore not be given to nursing mothers (see section 4.3 for use on tooth development).
4.7 Effects on ability to drive and use machines
Patients being treated with doxycycline may present with blurring of vision, they should be advised that the ability to drive or operate machinery may be impaired.
4.8 Undesirable effects
May cause permanent tooth discolouration and enamel hyperplasia if administered during tooth development, (i.e. pregnancy, infancy and in children up to 12 years old). This reaction is more common during long term use of the drug but has been observed following repeated short term courses.
Photosensitivity reactions following exposure to direct sunlight or UV light can occur and treatment should be discontinued.
Autonomic nervous system: Flushing
Since doxycycline is virtually completely absorbed, gastro-intestinal side effects are infrequent. However, the following adverse reactions have been observed in patients receiving doxycycline therapy.
Gastrointestinal: Abdominal pain, anorexia, nausea, diarrhoea, vomiting, glossitis, , dyspepsia, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region.
Pancreatitis and antibiotic-associated colitis have been reported.
There have also been reports for products in the tetracycline class of stomatitis.
Oesophagitis and Oesophageal Ulceration: Occurring more frequently in patients who took their medicine immediately before bedtime.
Skin: Maculopapular and erythematous rashes. Exfoliative dermatitis and erythema multiforme have been reported but is uncommon. Photosensitivity and photoonycholysis. Stevens-Johnson syndrome and toxic epidermal necrolysis.
Superinfection: As with all antibiotics, overgrowth of non-susceptible organisms may cause candidiasis, glossitis, staphylococcal enterocolitis, pseudomembranous colitis (with Clostridium difficile overgrowth) and inflammatory lesions (with candidal overgrowth) in the anogenital region. There have also been reports for products in the tetracycline class of vaginitis.
Renal toxicity: Rise in blood urea has been reported with tetracyclines and is apparently dose-related.
Hearing/Vestibular: Tinnitus.
Hypersensitivity reactions: Anaphylatic shock, anaphylaxis, anaphylactoid purpura, anaphylactoid reactions, hypotension, pericarditis, angioneurotic oedema, urticaria, dyspnoea, serum sickness, peripheral oedema, tachycardia and exacerbation of Systemic lupus erythematosus (SLE).
Central and Peripheral nervous system: Headache. Bulging fontanelles in infants and benign intracranial hypertension in adults have been reported in individuals receiving full therapeutic doses of tetracyclines. Treatment should be ceased if evidence of intracranial pressure develops, symptoms of which include blurring of vision, scotomata and diplopia. Permanent visual loss has been reported.
Blood: Thrombocytopenia, haemolytic anaemia, neutropenia, eosinophilia and porphyria have been reported.
Endocrine disorders
Given over prolonged periods, tetracyclines have been reported to produce a brown/black microscopic discolouration of the thyroid tissue. No abnormalities of thyroid function are known to occur.
Hepatobiliary disorders
Transient increases in liver function tests, hepatitis, jaundice and hepatic failure have been reported rarely.
Musculoskeletal: Arthralgia and myalgia
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.
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.
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 2hours decreasing to 1.45micrograms/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.
Haemodialysis does not alter the serum half-life of doxycycline.
6.2 Incompatibilities None known
6.3 Shelf life
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: Last renewal date: |
15th September 1983 3rd March 1999 |
10 DATE OF REVISION OF THE TEXT
11/03/2015