Summary of Product Characteristics (SmPC) - Demeclocycline Hydrochloride Dawa 150 mg capsules
1 NAME OF THE MEDICINAL PRODUCT
Demeclocycline Hydrochloride DAWA 150 mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 150 mg of demeclocycline hydrochloride
3 PHARMACEUTICAL FORM
Capsule, hard gelatin
Light brown cap with dirty yellow body hard gelatin size ‘2’ capsule filled with yellow granular powder.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of infections caused by tetracycline-sensitive organisms. For example, Demeclocycline is highly effective in the treatment of infections caused by Borrelia recurrentis (relapsing fever), Calymmatobacterium granulinatis (granuloma inguinale), Chlamydia species (psittacosis, lymphogranuloma vereneum, trachoma, inclusion conjunctivitis), Francisella tularensis (tularaemia), Haemophilus ducreyi (chancroid), Leptospira (meningitis, jaundice), Mycoplasma pneumoniae (non-gonococcal urethritis), Pseumomonas mallei and pseudomallei (glanders and melioidosis), Rickettsiae (typhus fever, Q fever, rocky mountain spotted fever), Vibrio species (cholera). It is also highly effective, alone or in combination with streptomycin, in the treatment of infections due to Brucella species (brucellosis) and Yersinia pestis (bubonic plague). Severe acne vulgaris.
Other sensitive organisms include: Actinomyces israelii, Bacillus anthracis (pneumonia), Clostridium species (gas gangrene, tetanus), Entamoeba histolytica (dysentery), Neisseria gonorrhoeae and anaerobic species, Treponema pallidum and pertenue (syphilis and yaws).
For the treatment of chronic hyponatraemia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) secondary to malignant disease, where water restriction is ineffective and the patient does not have concomitant cirrhosis.
4.2 Posology and method of administration
Posology
For Antibiotic Use:
Adults
(Capsules) - 600mg daily in 2 or 4 divided doses. For primary atypical pneumonia, the average daily dose is 900mg in 3 divided doses for 6 days.
Elderly
Use with caution in elderly patients. (See Section 4.3 Contraindications and Section 4.4 Special warnings and special precautions for use)
Paediatric population
Not recommended for children under 12 years of age.
For the treatment of Chronic Hyponatraemia due to SIADH:
Adults only
Initially: 900mg-l200mg daily in divided doses
Maintenance dose: 600-900mg daily in divided doses
Demeclocycline hydrochloride capsule should be swallowed whole with plenty of fluid while sitting or standing. Doses should be taken an hour before or 2 hours after meals as absorption of demeclocycline hydrochloride capsule is impaired by milk and food. Antibiotic therapy should be continued for one to three days after characteristic symptoms of fever have subsided. The incidence of rheumatic fever or glomerulonephritis following streptococcal infections suggests that therapy of a streptococcal infection should be continued for 8 full days even though symptoms have subsided.
Demeclocycline hydrochloride capsule therapy in the treatment of chronic hyponatraemia due to SIADH should not be withdrawn without commencing other methods of control.
Method of administration
Oral administration.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
The use of Demeclocycline is contraindicated in patients with acute porphyria, patients who are pregnant or breast-feeding, children under 12 years of age, patients with a history of hypersensitivity to tetracyclines and patients with renal impairment.
4.4 Special warnings and precautions for use
Demeclocycline hydrochloride capsule should be used with caution in patients with renal or hepatic dysfunction, or in conjunction with other potentially hepatotoxic or nephrotoxic drugs. Concurrent use with the anaesthetic methoxyflurane increases the risk of kidney failure. The anti-anabolic action of the tetracyclines may cause an increase in BUN. The treatment of chronic hyponatraemia may necessitate the administration of high doses of demeclocycline hydrochloride capsule for prolonged periods, so increasing the potential for nephrotoxicity (manifested by rises in plasma urea and creatinine) and photoallergic reactions. Cross-resistance between tetracyclines may develop in micro-organisms and cross sensitisation in patients. Demeclocycline hydrochloride capsule should be discontinued if there are signs/symptoms of overgrowth of resistant organisms including candida, enteritis, glossitis, stomatitis, vaginitis, pruritis ani or staphylococcal enterocolitis.
Lower doses are indicated in cases of renal impairment to avoid excessive systemic accumulation and if therapy is prolonged, serum level determinations are advisable. Patients who have known liver disease should not receive more than 1g daily. In long term therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies should be performed.
Demeclocycline hydrochloride capsule has the greatest potential of the tetracycline analogues for causing photo-allergic reactions in hypersensitive persons. Such patients should be warned to avoid direct exposure to natural or artificial sunlight and to discontinue therapy at the first sign of skin discomfort. Exacerbation of pre-existing SLE has been reported with tetracyclines.
Demeclocycline hydrochloride capsule may increase muscle weakness in patients with myasthenia gravis.
4.5 Interaction with other medicinal products and other forms of interaction
Demeclocycline hydrochloride capsule should not be used with penicillins.
Tetracyclines depress plasma prothrombin activity and reduced doses of concomitant anti-coagulants such as Coumarins and phenindione may be required.
Absorption of demeclocycline hydrochloride capsule is impaired by the concomitant administration of milk and dairy products, food, iron, calcium, zinc, magnesium and particularly aluminium salts commonly used as antacids.
Absorption of tetracyclines is possibly reduced by kaolin, quinapril tablets (quinapril tablets contain magnesium carbonate), strontium ranelate, sucralfate, tripotassium dicitratobismuthate.
There is a possible increased risk of benign intracranial hypertension with concomitant use of tetracyclines and retinoids, e.g. acitretin, isotretinoin, tretinoin. There is increased risk of ergotism when tetracyclines given with ergotamine and methysergide.
Typhoid Vaccine (oral): Antibacterials inactivate oral typhoid vaccine and therefore Demeclocycline Hydrochloride Capsule should be avoided for 3 days before and after oral typhoid vaccine.
4.6 Fertility, pregnancy and lactation
Demeclocycline hydrochloride capsule is contra-indicated during pregnancy and lactation.
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 embryotoxicity has also been noted in animals treated early in pregnancy.
The use of tetracyclines during tooth development (last half of pregnancy and children to the age of 12 years) may cause permanent discoloration of the teeth (yellow-grey-brown). This 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.
Breast-feeding
Tetracyclines have been found in the milk of lactating women who are taking a drug in this class. Permanent tooth discoloration may occur in the developing infant and enamel hypoplasia has been reported. Therefore, demeclocycline hydrochloride capsule should not be administered to lactating women.
4.7 Effects on ability to drive and use machines
Headache, dizziness, visual disturbances and rarely impaired hearing have been reported with tetracyclines and patients should be warned about the possible hazards of driving or operating machinery during treatment.
4.8 Undesirable effects
The following undesirable effects have been reported for Demeclocycline hydrochloride.
The undesirable effects are listed according to their frequency:
Not known (cannot be estimated from the available data)
| System organ class | Frequency | Undesirable effects |
| Blood and lymphatic system disorders | Not Known | Haemolytic anaemia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and eosinophiliaa |
| Immune system disorders | Not Known | Hypersensitivity reactions including urticaria, Stevens-Johnson syndrome, angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis and exacerbation of systemic lupus erythematosus |
| Nervous system disorders | Not Known | Headache, dizziness, bulging fontanelles (in infants), benign intracranial hypertension (in juveniles and adults), raised intracranial pressure (such as severe or persistent headache or blurred vision) b, myasthenia |
| Eye disorders | Not Known | Visual disturbances |
| Ear and labyrinth disorders | Not Known | Impaired hearing |
| Gastrointestinal disorders | Not Known | Nausea, vomiting, diarrhoea, dysphagia, oesophagitis, oesphageal ulcerationc, candidiasis, pseudomembranous colitis (Clostridium difficile overgrowth) glossitis, stomatitis, vaginitis, or staphylococcal enterocolitis, pancreatitis |
| Skin and subcutaneous tissue disorders | Not Known | Photosensitivity, erythematous, maculo-papular rashes, pruritus, bullous dermatoses, exfoliative dermatitis, skin discolouration, serious skin reactions |
| Renal and urinary disorders | Not Known | Renal dysfunction, especially in patients with pre-existing renal impairment, acute renal failure or nephritis, reversible nephrogenic diabetes insipidus (prolonged and/or at high dosages) |
| Hepatobiliary disorders | Not Known | Hepatitis, jaundice, hepatic failure |
| Investigations | Not Known | Transient increases in liver function |
| test values |
a. When given over prolonged periods, tetracyclines have been reported to produce brown-black discoloration of the thyroid gland. No abnormalities of thyroid function are known to occur.
b. While the condition and related symptoms usually resolve soon after discontinuation of the tetracycline, the possibility of permanent sequelae exists.
c. In patients taking oral tetracyclines in solid dose form, usually where medication was taken immediately before retiring or with inadequate fluids.
Reporting of Adverse reactions
Reporting suspected adverse reactions after authorization 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
No specific antidote. Gastric lavage plus oral administration of milk or antacids. Maintain fluid and electrolyte balance.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterial for systemic use, Tetracyclines ATC code: J01AA01
Mechanism of action
Tetracyclines have a broad spectrum of anti-microbial activity and act by interfering with bacterial protein synthesis. They are active against a large number of gram positive and gram negative pathogenic bacteria, including some which are resistant to penicillin.
5.2 Pharmacokinetic properties
Absorption
Tetracyclines are incompletely and irregularly absorbed from the gastrointestinal tract. Absorption is affected by the soluble salts of divalent and trivalent metals, milk and food.
Distribution
Plasma concentrations of up to 2.4mg per ml have been reported 3 to 4 hours after an oral dose of 300mg, only falling to about 1mg per ml after 24 hours. 41-90% of circulating demeclocycline is bound to plasma proteins.
Tetracyclines are widely distributed throughout the body tissue and fluids, and are retained at sites of new bone formation and recent calcification. The biological half life of demeclocycline is 12 hours.
Elimination
Tetracyclines are excreted in the urine and faeces.
5.3 Preclinical safety data
There are no other preclinical safety data of relevance to the prescriber apart from those already detailed in the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline Cellulose
Colloidal Anhydrous Silica
Magnesium Stearate
Capsule body and cap: Iron oxide yellow (E172), iron oxide red (E172), titanium dioxide (E171), gelatin and purified water.
6.2 Incompatibilities
None
6.3 Shelf life
36 Months
6.4 Special precautions for storage
Store in original package in order to protect from light and moisture.
6.5 Nature and contents of container
Blister pack of Aluminium/Alu-Alu foil
Pack size: 28 capsules
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
DAWA Limited
5 Sandridge Close,
Harrow, Middlesex,
HA1 1XD,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 30684/0304
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
26/03/2021
10 DATE OF REVISION OF THE TEXT
18/11/2024