Medically reviewed by Fedorchenko Olga Valeryevna, PharmD. Last updated on 2020-04-09
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Tetrana is a bacteriostatic broad-spectrum antibiotic, active against a wide variety of Gram-positive and Gram-negative organisms.
Infections caused by Tetrana-sensitive organisms include:
1) Respiratory tract infections: Pneumonia and other lower respiratory tract infections due to susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and other organisms. Mycoplasma pneumoniae pneumonia. Treatment of chronic bronchitis (including the prophylaxis of acute exacerbations) and whooping cough.
2) Urinary tract infections: Caused by susceptible strains of the Klebsiella species. Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.
3) Sexually transmitted diseases: Infections due to Chlamydia trachomatis including uncomplicated urethral, endocervical or rectal infections. Non-gonococcal urethritis caused by Ureaplasma urealyticum. Tetrana is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum.
Tetrana is an alternative drug in the treatment of penicillin resistant gonorrhoea and syphilis.
4) Skin Infections: Acne vulgaris when antibiotic therapy is considered necessary and severe rosacea.
5) Ophthalmic infections: Trachoma, although the infectious agent, as judged by immunofluorescence, is not always eliminated. Inclusion conjunctivitis may be treated with oral Tetrana alone or in combination with topical agents.
6) Rickettsial infections: Rocky Mountain spotted fever, typhus group, Q fever and Coxiella endocarditis and tick fevers.
7) Other infections: Stagnant loop syndrome. Psittacosis, brucellosis (in combination with streptomycin), cholera, bubonic plague, louse and tick-borne relapsing fever, tularaemia, glanders, melioidosis and acute intestinal amoebiasis (as an adjunct to amoebicides).
Tetrana is an alternative drug in the treatment of leptospirosis, gas-gangrene and tetanus.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tetrana '250' and Tetrana '500' Tablets (Tetracycline Hydrochloride Tablets) and other antibacterial drugs, Sum- ycin '250' and Tetrana '500' Tablets (Tetracycline Hydrochloride Tablets) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. 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 and susceptibility patterns may contribute to the empiric selection of therapy.
Tetracycline hydrochloride is indicated for the treatment of the following infections:
Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox and tick fever caused by Rickettsiae.
Respiratory tract infections caused by Mycoplasma pneumoniae
Lymphogranuloma venereum caused by Chlamydia trachomatis
Psittacosis and ornithosis due to Chlamydia psittaci
Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immuno- fluorescence
Inclusion conjunctivitis caused by Chlamydia trachomatis
Tetracycline hydrochloride is indicated for the treatment of uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydia trachomatis
Nongonococcal urethritis caused by Ureaplasma urealyticum Relapsing fever due to Borrelia recurrentis
Tetracycline hydrochloride is also indicated for the treatment of infections caused by the following gram-negative microorganisms:
Chancroid caused by Haemophilus ducreyi
Plague due to Yersinia pestis (formerly Pasteurella pestis)
Tularemia due to Francisella tularensis (formerly Pasteurella tularensis)
Cholera caused by Vibrio cholerae (formerly Vibrio comma)
Campylobacter fetus infections caused by Campylobacter fetus (formerly Vibrio fetus)
Brucellosis due to Brucella species (in conjunction with streptomycin)
Bartonellosis due to Bartonella bacilliformis
Granuloma inguinale caused by Calymmatobacterium granulomatis
Because many strains of the following groups of microorganisms have been shown to be resistant to tetracycline hydrochloride, culture and susceptibility testing are recommended.
Tetracycline hydrochloride is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:
Enterobacter aerogenes (formerly Aerobacter aerogenes)
Acinetobacter species [formerly Mima species and Herellea species]
Respiratory tract infections caused by Haemophilus influenzae
Respiratory tract and urinary tract infections caused by Klebsiella species
Tetracycline hydrochloride is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicated appropriate susceptibility to the drug:
For upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae)
Skin and skin structure infections caused by Staphylococcus aureus. Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infections
When penicillin is contraindicated, tetracycline hydrochloride is an alternative drug in the treatment of the following infections:
Uncomplicated gonorrhea caused by Neisseria gonorrhoeae
Syphilis caused by Treponema pallidum
Yaws caused by Treponema pertenue
Listeriosis due to Listeria monocytogenes
Anthrax due to Bacillus anthracis
Vincent's infection caused by Fusobacterium fusiforme
Actinomycosis caused by Actinomyces israelii
Infections caused by Clostridia species
In acute intestinal amebiasis, the tetracycline hydrochlorides may be a useful adjunctive therapy to amebicides.
In severe acne the tetracycline hydrochlorides may be useful ad- junctive therapy.
Tetrana should be given one hour before or two hours after meals, since food and some dairy products interfere with absorption. Therapy should be continued for up to three days after symptoms have subsided.
All infections due to Group A beta-haemolytic streptococci should be treated for at least 10 days.
Adults (including the elderly) and children over 12 years: The minimum recommended dosage is 250mg every six hours. Therapeutic levels are attained more rapidly by the administration of 500mg initially, followed by 250mg every six hours. For severe infections, the dosage may be increased to 500mg every six hours.
Children under 12 years: Contraindicated in this age group.
Elderly: Usual adult dose. Caution should be observed as subclinical renal insufficiency may lead to drug accumulation.
Renal impairment: In general Tetranas are contraindicated in renal impairment and the dosing recommendations only apply if use of this class of drug is deemed absolutely essential. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.
Dosage recommendations in specific infections:
Skin infections: 250-500mg daily in single or divided doses should be administered for at least three months in the treatment of acne vulgaris and severe rosacea.
Streptococcal infections: A therapeutic dose of Tetrana should be administered for at least 10 days.
Brucellosis: 500mg Tetrana four times daily accompanied by streptomycin.
Sexually transmitted diseases: 500mg four times daily for seven days is recommended in the following infections: Uncomplicated gonococcal infections (except anorectal infections in man); 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 gonorrhoea, 500mg four times daily for 10 days. Primary and secondary syphilis: 500mg four times daily for 15 days. Syphilis of more than one year's duration, (latent syphilis of uncertain or more than one year's duration, cardiovascular or late benign syphilis) except neurosyphilis, should be treated with 500mg, four times daily for 30 days. Patient compliance with this regimen may be difficult so care should be taken to encourage optimal compliance. Close follow-up including laboratory tests, is recommended.
Method of Administration
For oral administration.
Adults: usual daily dose is 1 to 2 g: for mild to moderate infections: 500 mg bid or 250 mg qid; higher dosages such as 500 mg qid may be required for severe infections.
For children above eight years of age: usual daily dose is 10 to 20 mg/lb (25 to 50 mg/kg) body weight divided in four equal doses.
Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.
The treatment of brucellosis, 500 mg tetracycline four times daily for three weeks should be accompanied by streptomycin, 1 g intramuscularly twice daily the first week and once daily the second week.
For treatment of uncomplicated gonorrhea, 500 mg every six hours for seven days.
For treatment of syphilis, a total of 30 to 40 g in equally divided doses over a period of 10 to 15 days should be given. Close follow up, including laboratory tests, is recommended.
Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 500 mg by mouth, four times a day for at least seven days.
In cases of severe acne which in the judgment of the clinician, requires long-term treatment, the recommended initial dosage is 1 g daily in divided doses. When improvement is noted, usually within one week, dosage should be gradually reduced to maintenance levels ranging from 125 to 500 mg daily. In some patients it may be possible to maintain adequate remission of lesions with alternateday or intermittent therapy. Tetracycline therapy of acne should augment the other standard measures known to be of value.
In patients with renal impairment (see WARNINGS) total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.
In the treatment of streptococcal infections, a therapeutic dose of tetracycline should be administered for at least 10 days.
Concomitant therapy: Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron containing preparations.
Food and some dairy products also interfere with absorption.
Administration of adequate amounts of fluid with the tablet and especially capsule formulations of tetracycline is recommended to wash down the drug and reduce the risk of esophageal irrita- tion and ulceration (see ADVERSE REACTIONS)
- Chronic renal/hepatic dysfunction;
- Renal impairment, particularly if severe;
- Systemic lupus erythematosus;
- Children under 12 years ;
- Pregnancy and breastfeeding women.
- Benign intracranial hypertension has been reported following the concomitant use of Tetranas and Vitamin A or retinoids and therefore concurrent use should be contraindicated.
This drug is contraindicated in persons who have shown hyper- sensitivity to any of the tetracyclines.
- Tetrana drugs may cause permanent tooth discolouration (yellow-grey-brown), if administered during tooth development, in the last half of pregnancy and in infancy up to twelve years of age. Enamel hypoplasia has also been reported. This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses.
- The anti-anabolic action of Tetranas may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired renal function, higher serum levels of Tetrana may lead to azotaemia, hyperphosphataemia and acidosis.
- When treating venereal disease, where co-existent syphilis is suspected, proper diagnostic procedures should be utilised. In all such cases, monthly serological tests should be made for at least four months.
- The use of antibiotics may occasionally result in the overgrowth of nonsusceptible organisms including Candida. Constant observation of the patients is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.
- Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment (including several weeks after treatment) with Tetrana tablets, may be symptomatic of Clostridium difficile- associated disease (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of which is pseudomembranous colitis. It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with Tetrana tablets. If CDAD is suspected or confirmed Tetrana tablets should be stopped immediately and appropriate therapy initiated without delay. Anti-peristaltic drugs are contraindicated in this clinical situation.
- In longterm therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies should be performed.
- High doses of Tetranas have been associated with a syndrome involving fatty liver degeneration and pancreatitis.
- The use of Tetrana in general is contraindicated in renal impairment due to excessive systemic accumulation and used with caution in patients with hepatic impairment or those receiving drugs which may have hepatotoxic effects; high doses should be avoided.
- Photosensitivity reactions may occur in hypersensitive persons and 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.
- SLE (systemic lupus erythematosus) can be exacerbated by the use of Tetranas.
- Care is advised when administered to patients with myasthenia gravis.
Tetrana tablets contain sunset yellow (E110), which can cause allergic - type reactions.
TETRACYCLINE-CLASS ANTIBIOTICS CAN CAUSE FETAL HARM WHEN ADMINISTERED TO A PREGNANT WOMAN. IF ANY TETRACYCLINE IS USED DURING PREGNANCY, OR IF THE PATIENT BECOMES PREGNANT WHILE TAKING THESE DRUGS, THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS.
THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY AND CHILDHOOD TO AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (YELLOWISH-GRAY-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. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED DURING TOOTH DEVELOPMENT UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.
All tetracyclines form a stable calcium complex in any bone forming tissues. A decrease in fibula growth rate has been observed in young animals (rats and rabbits) given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.
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.
The antianabolic action of tetracycline may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, even usual oral or parenteral dose may lead to excessive systemic accumulation of the drug and possible liver toxicity. Under such conditions, lower than usual doses are indicated and, if therapy is prolonged, serum level determinations of the drug may be advisable.
Photosensitivity, manifested by an exaggerated sunburn reaction, has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultra-violet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.
NOTE: Photosensitization reactions have occurred most frequently with demeclocycline, less with chlortetracycline, and very rarely with oxytetracycline and tetracycline.
Prescribing Tetrana '250' and Tetrana '500' Tablets (Tetracycline Hydrochloride Tablets) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
As with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted. NOTE: Superinfection of the bowel by staphylococci may be life-threatening.
Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Bulging fon- tanels have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve after discontinuation of the tetracycline, the possibility for permanent sequelae exists.
Since sensitivity reactions are more likely to occur in persons with a history of allergy, asthma, hay fever, or urticaria, the preparation should be used with caution in such individuals.
Cross-sensitization among the various tetracyclines is extremely common.
Incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy, when indicated.
Under no circumstances should outdated tetracyclines be administered, as the degradation of tetracyclines are highly nephrotoxic and have, on occasion, produced a Fanconi-like syndrome.
During long-term therapy, periodic laboratory evaluation of organ system function, including renal, hepatic, and hematopoietic systems, should be performed.
All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with tetracycline should have a follow-up serologic test for syphilis after 3 months.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies conducted in rats and mice to determine whether tetracycline hydrochloride has carcinogenic potential were negative. Some related antibiotics (oxytetracycline, minocycline) have shown evidence of oncogenic activity in rats. In twoin vitro mammalian cell assay systems (L51784y mouse lymphoma and Chinese hamster lung cells), there was evidence of mutagenicity at tetracycline hydro- chloride concentrations of 60 and 10µg/mL, respectively.
Tetracycline hydrochloride had no effect on fertility when administered in the diet to male and female rats at a daily intake of 25 times the human dose.
Pregnancy: Teratogenic effects: Pregnancy Category D (see WARNINGS.)
Pregnancy: Nonteratogenic effects: (see WARNINGS.)
Labor and Delivery
The effect of tetracyclines on labor and delivery is unknown.
Tetracyclines are present in the milk of lactating women who are taking a drug in this class. Because of the potential for serious adverse reactions in nursing infants from tetracyclines, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see WARNINGS.)
See WARNINGS and DOSAGE AND ADMINISTRATION.
The following convention has been utilised for the classification of frequency. Very common (> 1/10); common( > 1/100 and < 1/10); uncommon (> 1/1000 and < 1/100); rare (> 1/10,000 and < 1/1000); very rare (< 1/10,000); Frequency not known (cannot be estimated from the available data).
Infections and infestations:
Frequency not known: overgrowth of resistant organisms (Candida albicans, in particular); this may cause glossitis, stomatitis, pseudomembranous colitis (Clostridium difficile overgrowth), enterocolitis (caused by resistant staphylococci), rectal and vaginal irritation, inflammatory lesions (with candidial overgrowth) in the anogenital regions
Blood and lymphatic system disorders:
Rare: haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia, agranulocytosis, aplastic anaemia.
Immune system disorders:
Frequency not known: hypersensitivity reactions including Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis, urticaria, anaphylaxis, anaphylactoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus , fixed drug eruptions, exfoliative dermatitis.
Frequency not known: brown-black microscopic discolouration of thyroid tissue. No abnormalities of thyroid function are known to occur.
Nervous system disorders:
Frequency not known: headache.
Frequency not known: visual disturbances, permanent visual loss.
Frequency not known: bulging fontanelles in infants; benign intracranial hypertension in juveniles and adults. Presenting features were headache, dizziness, tinnitus and visual disturbances including blurring of vision, scotomata and diplopia. Treatment should cease if evidence of raised intracranial pressure develops.
Rare: dysphagia, oesophagitis and oesophageal ulceration (most of these patients took medication immediately before going to bed)
Frequency not known: gastrointestinal irritations, nausea, abdominal discomfort, vomiting, diarrhoea, anorexia, pancreatitis, permanent tooth discolouration and enamel hypoplasia in children. Tooth discolouration has also been seen in adults. If gastric irritation occurs, tablets should be taken with food.
Rare: transient increases in liver function tests, hepatitis, jaundice, hepatic failure.
Frequency not known: hepatotoxicity associated with fatty liver.
Skin and subcutaneous tissue disorders:
Frequency not known: erythematous and maculo-papular rashes, photosensitivity (Patients exposed to direct sunlight or ultraviolet light should be advised to discontinue treatment if any skin reaction occurs), pruritis, bullous dermatoses, skin discolouration.
Musculoskeletal, connective tissue and bone disorders:
Frequency not known: increased muscle weakness in patients with myasthenia gravis.
Renal & urinary disorders:
Rare: acute renal failure, nephritis.
Frequency not known: raised serum urea, renal dysfunction, especially in patients with pre-existing renal impairment.
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; website: www.mhra.gov.uk/yellowcard
Gastrointestinal: anorexia, epigastric distress, nausea, vomiting, diarrhea, bulky loose stools, stomatitis, sore throat, glossitis, black hairy tongue, dysphagia, hoarseness, enterocolitis, and inflammatory lesions (with candidal overgrowth) in the anogenital region, including proctitis and pruritus ani. Rare instances of esophagitis and esophageal ulceration have been reported in patients receiving particularly the capsule and also the tablet forms of tetracyclines. Most of the patients were reported to have medication immediately before going to bed (see DOSAGE AND ADMINISTRATION). These reactions have been caused by both the oral and parenteral administration of tetracyclines but are less frequent after parenteral use.
Skin and Skin Structures: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Onycholysis and discoloration of the nails have been reported rarely. Photosensitivity has occurred. (See WARNINGS).
Renal Toxicity: increases in BUN have been reported and are apparently dose-related. (See WARNINGS.)
Hepatic Cholestasis: has been reported rarely, and is usually associated with high dosage levels of tetracycline.
Hypersensitivity Reactions: Anaphylaxis; serum sickness-like reactions, as fever, rash, and arthralgia; urticaria, angioneurotic edema, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus.
Hematological: Blood: anemia, hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, neutropenia and eosinophilia have been reported.
Miscellaneous: Dizziness and headache have been reported.
When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur. Bulging fontanels in infants and intracranial hypertension in adults have been reported. (See PRECAUTIONS-General.)
- There may be nausea and vomiting.
- Crystalluria and haematuria may occur following very large doses.
- Hypersensitivity reactions may occur.
There is no specific antidote.
- Gastric decontamination is not necessary.
- Give oral fluids for severe vomiting and diarrhoea if required.
- Manage anaphylaxis reactions conventionally.
- Single brief convulsions do not require treatment. If frequent or prolonged control with intravenous diazepam or lorazepam.
- General symptomatic therapy as indicated by the patient's clinical condition.
In case of overdosage, treat symptomatically and institute sup- portive measures.
Pharmacotherapeutic group: Tetrana hydrochloride is a broad-spectrum bacteriostatic antibiotic.
ATC code: D06AA04
Tetranas are taken up into sensitive bacterial cells by an active transport process. Once within the cell they bind reversibly to the 30S subunit of the ribosome, preventing the binding of aminoacyl transfer RNA and inhibiting protein synthesis and hence cell growth. Although Tetranas also inhibit protein synthesis in mammalian cells they are not actively taken up, permitting selective effects on the infecting organism.
Most Tetranas are incompletely absorbed from the gastrointestinal tract, about 60-80% of a dose of Tetrana usually being available. The degree of absorption is diminished by the presence of divalent and trivalent metal ions with which Tetranas form stable insoluble complexes and to a variable degree by milk or food. Formulation with phosphate may enhance the absorption of Tetrana.
Plasma concentrations will depend upon the degree of absorption. Administration of Tetrana 500mg every 6 hours generally produces steady-state concentrations of 4-5Âµg/ml. Peak plasma concentrations occur about 1-3 hours after ingestion. Higher concentrations can be achieved after intravenous administration; concentrations may be higher in women than in men.
In the circulation 20-65% of Tetrana is bound to plasma proteins.
They are widely distributed throughout the body tissues and fluids. Concentrations in cerebrospinal fluid are relatively low, but may be raised if the meninges are inflamed. Small amounts appear in saliva, and the fluids of the eye and lung. Tetranas appear in the milk of nursing mothers where concentrations may be 60% or more of those in the plasma. They diffuse across the placenta and appear in the foetal circulation in concentrations of about 25 to 75% of those in the maternal blood. Tetranas are retained at sites of new bone formation and recent calcification and in developing teeth.
The Tetranas have been classified in terms of their duration of action in the body, although the divisions appear to overlap somewhat.
The Tetranas are excreted in the urine and in the faeces. Renal clearance is by glomerular filtration. Up to 55% of a dose is eliminated unchanged in the urine; concentrations in the urine of up to 300Âµg/ml of Tetrana may be reached two hours after a usual dose is taken and be maintained for up to 12 hours. Urinary excretion is increased if urine is alkalinised. The Tetranas are excreted in the bile where concentrations 5-25 times those in plasma can occur. Since there is some enterohepatic reabsorption complete elimination is slow. Considerable quantities occur in the faeces after administration.
Not applicable.Administrative data
However, we will provide data for each active ingredient