Acute overdosage with antibiotics is rare. In the event of overdosage discontinue medication. Gastric lavage plus appropriate supportive treatment is indicated.
Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.
Acute overdosage with antibiotics is rare. In the event of overdosage discontinue medication. Gastric lavage plus appropriate supportive treatment is indicated.
Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.
In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.
To date no significant acute toxicity has been described in the case of a single oral intake of a multiple of therapeutic doses of doxycycline. In case of overdosage there is, however, a risk of parenchymatous hepatic and renal damage and of pancreatitis.
The usual dose of Mondoxyne NL is low when compared with the usual doses for doxycycline when used for antimicrobial therapy. Therefore clinicians should bear in mind that a significant proportion of overdoses are likely to produce blood concentrations of doxycycline within the therapeutic range of antimicrobial treatment, for which there is a large quantity of data supporting the safety of the drug. In these cases observation is recommended. In cases of significant overdosage, doxycycline therapy should be stopped immediately; and symptomatic measures undertaken as required. Intestinal absorption of unabsorbed doxycycline should be minimised by producing non-absorbable chelate complexes by the administration of magnesium or calcium salt containing antacids. Gastric lavage should be considered.
Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.
Pregnancy Mondoxyne NL is contraindicated 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..
Nursing mothers Tetracyclines are excreted into milk and are therefore contraindicated in nursing mothers..
Paediatric population Mondoxyne NL is contraindicated in children under the age of 12 years. As with other tetracyclines, Mondoxyne NL 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..
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 long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Mondoxyne NL is therefore contraindicated in these groups of patients.
Pregnancy
Mondoxyne NL 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).
Paediatric population
Mondoxyne NL is contraindicated in children under the age of 12 years. As with other tetracyclines, Mondoxyne NL 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).
Mondoxyne NL MPC is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.
In common with other drugs of the tetracycline class, Mondoxyne NL is contra-indicated in infants and children up to 12 years of age.
Doxycycline should not be administered to patients who have shown hypersensitivity to doxycycline hyclate, other tetracyclines or to any of the excipients.
Patients known to have, or suspected to have, achlorhydria should not be prescribed doxycycline.
Use of doxycycline is contra-indicated during pregnancy and lactation (See 4.6 Pregnancy and lactation).
Not applicable.
None known
Not applicable.
The following adverse reactions have been observed in patients receiving tetracyclines, including doxycycline.
| System Organ Class | Common >1/100 to <1/10 | Uncommon >1/1000 to <1/100 | Rare >1/10,000 to <1/1000 | Not known Cannot be estimated from the available data. |
| Infections and infestations | Vaginal infection | Candida Infection | ||
| Blood and lymphatic system disorders | Haemolytic anaemia, neutropenia, thrombocytopenia, eosinophilia | |||
| Immune system disorders | Hypersensitivity (including anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, angioedema, exacerbation of systemic lupus erythematosus, pericarditis, serum sickness, Henoch-Schonlein purpura, hypotension, dyspnoea, tachycardia, peripheral oedema and urticaria) | Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) | Jarisch-Herxheimer reaction | |
| Endocrine disorders | Brown-black microscopic discoloration of thyroid glands | |||
| Metabolism and nutrition disorders | Porphyria, decreased appetite | |||
| Nervous system disorders | Headache | Anxiety, benign intracranial hypertension (pseudotumor cerebri)*, fontanelle bulging | ||
| Ear and labyrinth disorders | Tinnitus | |||
| Vascular disorders | Flushing | |||
| Gastrointestinal disorders | Nausea/vomiting | Dyspepsia (Heartburn/gastritis) | Pancreatitis, pseudomembranous colitis, Clostridium difficile colitis, oesophageal ulcer, oesophagitis, enterocolitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, dysphagia, abdominal pain, diarrhoea, glossitis, stomatitis, tooth discolourationa | |
| Hepatobiliary disorders | Hepatic failure, hepatitis, hepatotoxicity, jaundice, hepatic function abnormal | |||
| Skin and subcutaneous tissue disorders | Photosensitivity reaction, rash including maculopapular and erythematous rashes | Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, dermatitis exfoliative, photoonycholysis | ||
| Musculoskeletal, connective tissue and bone disorders | Arthralgia, myalgia | |||
| Renal and urinary disorders | Blood urea increased |
* Symptoms included blurring of vision, scotomata and diplopia. Permanent visual loss has been reported.
a Reversible and superficial discolouration of permanent teeth has been reported with the use of doxycycline.
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.
The following adverse reactions have been observed in patients receiving tetracyclines, including Mondoxyne NL.
Adverse Reactions Table
| System Organ Class | Common > 1/100 to < 1/10 | Uncommon > 1/1000 to < 1/100 | Rare > 1/10000 to < 1/1000 |
| Infections and infestations | Vaginal infection | Candida infection | |
| Blood and lymphatic system disorders | Haemolytic anaemia Neutropenia Thrombocytopaenia Eosinophilia | ||
| Immune system disorders | Anaphylactic Reaction (including angioedema, exacerbation of systemic lupus erythematosus, pericarditis, hypersensitivity, serum sickness Henoch- Schonlein Purpura, hypotension, dyspnoea, tachycardia peripheral oedema and urticaria) | Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) | |
| endocrine disorders | Brown-black microscopic discoloration of thyroid glands | ||
| Metabolism and nutrition disorders | Porphyria, decreased appetite | ||
| Nervous system disorders | Headache | Benign intracranial Hypertension (pseudotumor cerebri)* fontanelle bulging | |
| Ear and labyrinth disorders | Tinnitus | ||
| Vascular disorders | Flushing | ||
| Gastrointestinal disorders | Nausea/vomiting | Dyspepsia (Heartburn/ gastritis) | Pancreatitis, pseudomembranous colitis Clostridium.difficile colitis, oesophageal ulcer, oesophagitis, enterocolitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, dysphagia, abdominal pain, diarrhoea, glossitis, stomatitis |
| Hepatobiliary disorders | Hepatic failure, hepatitis, hepatotoxicity, jaundice, hepatic function abnormal | ||
| Skin and subcutaneous tissue disorders | Photosensitivity reaction, rash including maculopapular and erythematous rashes | Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, dermatitis exfoliative, photoonycholysis | |
| Musculoskeletal, connective tissue and bone disorders | Arthralgia, myalgia | ||
| Renal and urinary disorders | Blood urea increased |
* Symptoms included blurring of vision, scotomata and diplopia. Permanent visual loss has been reported.
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.
The following adverse reactions have been identified during post-approval use of doxycycline. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Due to oral doxycycline’s virtually complete absorption, side effects to the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines:
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, and pancreatitis. Hepatotoxicity has been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline-class. Most of these patients took medications immediately before going to bed.
Skin: Maculopapular and erythematous rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, and erythema multiforme have been reported. Photosensitivity is discussed above.
Renal: Rise in BUN has been reported and is apparently dose-related.
Hypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus.
Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.
Intracranial Hypertension: Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracycline
Thyroid Gland Changes: 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.
The most commonly reported adverse reactions in Phase III trials were headache (26%) and common cold (22%). The following table lists those adverse reactions occurring in four Phase III trials conducted in 213 patients.
| Organ System | Undesirable Effect | Very Common (>1/10) | Common (>1/100, <1/10) | Uncommon (>1/1000,<1/100) | Rare (>1/10000,<1/1000) |
| Infections & Infestations | Infection Periodontal Abscess |
| 4 8 |
|
|
| Respiratory | Common Cold Flu Symptoms Sinusitis Coughing Bronchitis | 47 24
|
18 9 7 |
|
|
| Gastrointestinal | Dyspepsia Diarrhoea Acid Indigestion |
| 13 12 8 |
|
|
| Skin Disorders | Rash |
| 8 |
|
|
| Musculoskeletal | Toothache Joint Pain Back Pain Pain Muscle Pain Gum Pain |
| 14 12 11 8
|
2 1 |
|
| Reproductive | Menstrual Cramps |
| 9 |
|
|
| General | Headache Nausea Tooth Disorder Sore Throat Sinus Headache | 55 |
17 13 11 8 |
|
|
| Injury | Accidental Injury |
| 11 |
|
|
The following adverse reactions have been observed in patients receiving tetracyclines, including doxycycline:-
Gastrointestinal: Anorexia, nausea, vomiting, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions with monilial overgrowth in the anogenital region. Hepatotoxity has been reported rarely. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Oesophagitis and oesophageal ulceration have been reported, most often in patients administered the hyclate salt in capsule form. Most of these patients took medication just prior to going to bed.
Skin: Maculo papular, erythematous rashes and Stevens-Johnson syndrome. Skin photosensitivity can occur. Exfoliative dermatitis has been reported but is uncommon.
Renal: An apparently dose related increase in blood urea has been reported with tetracyclines.
Blood: Thrombocytopenia, neutropenia, haemolytic anaemia, eosinophilia and porphyria have been reported with tetracyclines.
Hypersensitivity reactions: Exacerbation of systemic lupus erythematosus, anaphylaxis, anaphylactoid purpura, pericarditis, urticaria and angioneurotic oedema.
Musculoskeletal: Arthralgia
Other: Bulging fontanelles in infants and benign intracranial hypertension in adults has been reported with the use of tetracyclines. Treatment should cease if evidence of raised intracranial pressure develops. These conditions disappeared rapidly when the drug was discontinued. Brown-black microscopic discolouration of thyroid tissue has been reported with long-term use of tetracyclines. Thyroid function is normal.
Adverse reactions typical of the tetracycline class of drugs are less likely to occur during medication with Mondoxyne NL, due to the reduced dosage and the relatively low serum levels involved. This assertion is supported by several clinical trials which suggest that no significant differences exist with regard to frequency of adverse events between active and placebo groupings. However, the clinician should always be aware of the possibility of adverse events occurring and should monitor patients accordingly.
The following adverse events have been reported during post-marketing:
(Frequency estimate: very common > 1 in 10; common >1 in 100 to <1 in 10; uncommon >1 in 1000 to <1 in 100; rare >1 in 10,000 to <1 in 1000; very rare <1 in 10,000) and not known : cannot be estimated from the available data
Infections
Rare: Vaginal moniliasis, Anogenital moniliasis
Immune system disorders
Rare: Mild allergic reactions
Not known: Jarisch-Herxheimer reaction
Nervous system disorders
Rare: Headache
Very rare: Dizziness
Gastrointestinal disorders
Rare: Nausea, diarrhoea, dyspepsia
Very rare: Abdominal pain, constipation, dry mouth, superficial tooth discolouration
There have been isolated case reports of bloody diarrhoea, colitis and pseudomembranous colitis.
Skin and subcutaneous tissue disorders
Rare: Rash
Very rare: Urticaria, pruritus, skin photosensitivity.
Unknown: Photo-onycholysis.
Musculoskeletal disorders
Very rare: Arthralgia
General disorders
Very rare: Asthenia
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. Tel: Freephone 0808 100 3352. Website: www.mhra.gov.uk/yellowcard.
None stated
Not applicable.
The carcinogenic potential of doxycycline has been investigated and no changes indicative of a direct carcinogenic effect were seen. Increases in benign tumours of the mammary gland (fibroadenoma), uterus (polyp) and thyroid (C-cell adenoma), which are consistent with a hormonal effect, were observed in treated females. Doxycycline has shown no mutagenic activity and no convincing evidence of clastogenic activity.
Effects on fertility and reproductive performance and on pre- and post-natal toxicity have been assessed in rats over the dose range 50 to 500 mg/kg/day. At 50 mg/kg/day (88 times the human dose) there was a decrease in the straight-line velocity of sperm, but there was no apparent effect on male or female fertility or on sperm morphology. Maternal toxicity at 500 mg/kg/day was shown by noisy breathing, loose faeces, and transient reductions in both body weight gain and food consumption after parturition with a slight increase in the duration of gestation. No maternal toxicity was apparent at or below 100 mg/kg/day and there was no effect on the F1 generation at 50 mg/kg/day during parturition, lactation or post-weaning. Developmental toxicity studies have not been conducted, but doxycycline is known to cross the placenta.
Hyperpigmentation of the thyroid following administration of members of the tetracycline class has been observed in rats, minipigs, dogs and monkeys and thyroid hyperplasia has occurred in rats, dogs, chickens and mice.
The anticipated human dose for doxycycline, 20 mg b.i.d. is equivalent to ~0.5 mg/kg/day for a 70 kg man. At this dose plasma Cmax and AUC0-24 were 780 ng/ml and 10954 ng*h/ml respectively.
Toxicity following repeated oral administration has been evaluated in rats and cynomolgus monkeys. Discolouration of the thyroid was a finding common to rats exposed at 25 mg/kg/day for 13 weeks or 20 mg/kg/day for 26 weeks, and to cynomolgus monkeys at 30 mg/kg/day for 1 year. Cmax and AUC0-24 following a single oral dose of 25 mg/kg were 2.2 and 1.6 times respectively the values recorded in man. Dose-related increases in both the incidence and severity of tubular degeneration/regeneration in the kidney were seen following administration to cynomolgus monkeys for 28 days or 52 weeks. At 5 mg/kg/day, focal lesions were present after 28 days, but no lesions were present in monkeys treated for 52 weeks. Mean plasma Cmax and AUC0-24 values at 28 days in monkeys receiving 5 mg/kg/day were 1235 ng/ml and 11600 ng*h/ml respectively and there was no evidence of accumulation.
In humans the use of tetracyclines during tooth development may cause permanent discolouration of the teeth (yellow-grey-brown). This reaction is more common during long-term use of the drug but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. As for other tetracyclines, doxycycline forms a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.
Mondoxyne NL has been found clinically effective in the treatment of a variety of infections caused by susceptible strains of Gram-positive and Gram-negative bacteria and certain other micro-organisms.
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. Treatment of chronic bronchitis, sinusitis.
Urinary tract infections caused by susceptible strains of Klebsiella species, Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.
Sexually transmitted diseases Infections due to Chlamydia trachomatis including uncomplicated urethral, endocervical or rectal infections. Non-gonococcal urethritis caused by Ureaplasma urealyticum (T-mycoplasma). Mondoxyne NL is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum. Mondoxyne NL is an alternative drug in the treatment of gonorrhoea and syphilis.
Skin infections Acne vulgaris, when antibiotic therapy is considered necessary.
Since Mondoxyne NL is a member of the tetracycline series of antibiotics, it may be expected to be useful in the treatment of infections which respond to other tetracyclines, such as:
Ophthalmic infections Due to susceptible strains of gonococci, staphylococci and Haemophilus influenzae. Trachoma, although the infectious agent, as judged by immunofluorescence, is not always eliminated. Inclusion conjunctivitis may be treated with oral Mondoxyne NL alone or in combination 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), cholera, bubonic plague, louse and tick-borne relapsing fever, tularaemia glanders, melioidosis, chloroquine-resistant falciparum malaria and acute intestinal amoebiasis (as an adjunct to amoebicides).
Mondoxyne NL is an alternative drug in the treatment of leptospirosis, gas gangrene and tetanus.
Mondoxyne NL is indicated for prophylaxis in the following conditions: Scrub typhus, travellers' diarrhoea (enterotoxigenic Escherichia coli), leptospirosis and malaria. Prophylaxis of malaria should be used in accordance to current guidelines, as resistance is an ever changing problem.
The treatment of a variety of infections caused by susceptible strains of gram-positive 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). Mondoxyne NL is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum. Mondoxyne NL is an alternative drug in the treatments of gonorrhoea and syphilis.
As Mondoxyne NL 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. (Mondoxyne NL 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).
Mondoxyne NL is an alternative drug in the treatment of leptospirosis, gas gangrene and tetanus.
Mondoxyne NL 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.
Rickettsial InfectionsMondoxyne NL MPC is indicated for treatment of Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.
Sexually Transmitted InfectionsMondoxyne NL MPC is indicated for treatment of the following sexually transmitted infections:
Mondoxyne NL MPC is indicated for treatment of the following respiratory tract infections:
Mondoxyne NL MPC is indicated for treatment of the following specific bacterial infections:
Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended.
Mondoxyne NL MPC is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug:
Mondoxyne NL MPC is indicated for treatment of the following ophthalmic infections:
Mondoxyne NL MPC is indicated for treatment of Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.
Alternative Treatment For Selected Infections When Penicillin Is ContraindicatedMondoxyne NL MPC is indicated as an alternative treatment for the following selected infections when penicillin is contraindicated:
In acute intestinal amebiasis, Mondoxyne NL MPC may be a useful adjunct to amebicides. In severe acne, Mondoxyne NL MPC may be useful adjunctive therapy.
Prophylaxis Of MalariaMondoxyne NL MPC is indicated for the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains.
UsageTo reduce the development of drug-resistant bacteria and maintain the effectiveness of Mondoxyne NL MPC and other antibacterial drugs, Mondoxyne NL MPC 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.
For patients with adult periodontitis. Mondoxyne NL is indicated as an adjunct to supra-gingival and sub-gingival scaling and root planing, with oral hygiene instruction, carried out by a dental practitioner or hygienist as appropriate.
Pharmacotherapeutic group: Tetracyclines, ATC code: J01 AA02.
Mondoxyne NL is primarily bacteriostatic and is believed to exert its antimicrobial effect by the inhibition of protein synthesis. Mondoxyne NL is active against a wide range of Gram-positive and Gram-negative bacteria and certain other micro-organisms.
Pharmacotherapeutic group: Tetracyclines, ATC code: J01 AA02
Mondoxyne NL is primarily bacteriostatic and is believed to exert its antimicrobial effect by the inhibition of protein synthesis. Mondoxyne NL is active against a wide range of Gram-positive and Gram-negative bacteria and certain other micro-organisms.
Pharmacotherapeutic group: Tetracyclines
ATC code: J01A A02
The active ingredient of Mondoxyne NL, doxycycline, is synthetically derived from oxytetracycline, with a molecular formula of C22H24N2O8-HCl-½ C2H5OH-½ H2O.
Mondoxyne NL is an inhibitor of collagenase activity. Studies have shown that at the proposed 20 mg b.i.d. dose level, Mondoxyne NL reduces the elevated collagenase activity in the gingival crevicular fluid of patients with chronic adult periodontitis, whilst not demonstrating any clinical evidence of anti-microbial activity.
Susceptibility
The dosage achieved with this product during administration is well below the concentration required to inhibit microorganisms commonly associated with adult periodontitis. Clinical studies with this product demonstrated no effect on total anaerobic and facultative bacteria in plaque samples from patients administered this dose regimen for 9 to 18 months. This product SHOULD NOT be used for reducing the numbers of, or eliminating, those microorganisms associated with periodontitis.
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and faeces at high concentrations 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 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 micrograms/ml of doxycycline at 2 hours decreasing to 1.45 micrograms/ml at 24 hours. Doxycycline has a high degree of lipid solubility and a low affinity for calcium. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.
Absorption
Tetracyclines are readily absorbed and are bound to proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and faeces at high concentration and in a biologically active form. Mondoxyne NL is virtually completely absorbed after oral administration. Studies reported to date indicate that the absorption of Mondoxyne NL 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. Mondoxyne NL has a high degree of lipid solubility and a low affinity for calcium. It is highly stable in normal human serum. Mondoxyne NL will not degrade into an epianhydro form.
AbsorptionFollowing administration of a single dose of Mondoxyne NL MPC under fasting conditions, the AUCinf and Cmax were 26.7 mcg-h/mL and 1.6 mcg/mL, respectively. The Tmax was 2.8 hours. In a single-dose study to evaluate the relative bioavailability in healthy adult subjects under fasted conditions, Mondoxyne NL MPC 120 mg Tablets were found to be bioequivalent to Mondoxyne NL 100 mg Tablets. When a single dose of Mondoxyne NL MPC 120 mg Tablet was administered with a standardized high-fat high-calorie meal, (937kcal consisting of approximately 55% fat, 30% carbohydrate and 15% protein), the Cmax was approximately 30% lower, but there was no significant difference in the AUCinf compared to administration under fasting conditions.
ExcretionTetracyclines are concentrated in bile by the liver and excreted in the urine and feces at high concentrations and in a biologically active form. Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with a creatinine clearance of about 75 mL/min. This percentage may fall as low as 1-5%/72 hours in individuals with a creatinine clearance below 10 mL/min.
Studies have shown no significant difference in the 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.
Absorption:
Doxycycline is almost completely absorbed after oral administration. Following ingestion of 20 mg doxycycline twice daily, mean maximum plasma concentrations were 0.79 µg/ml. Peak levels were generally achieved 2 hours after administration. Food intake reduced the extent of absorption by 10% and decreased and delayed the peak plasma levels.
Distribution:
Doxycycline is greater than 90% bound to plasma proteins and has an apparent volume of distribution of 50L.
Metabolism:
Major metabolic pathways of doxycycline have not been identified, however, enzyme inducers decrease the half-life of doxycycline.
Elimination:
Doxycycline is excreted in the urine and faeces as unchanged drug. Between 40% and 60% of an administered dose can be accounted for in the urine by 92 hours, and approximately 30% in the faeces. The terminal half-life after a single 20 mg doxycycline dose averaged 18h.
Special populations:
The half-life is not significantly altered in patients with severely impaired renal function. Doxycycline is not eliminated to any great extent during haemodialysis.
Use in children 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 long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use of doxycycline is contraindicated in pediatric patients under the age of 12 years..
Use in patients with impaired hepatic function Mondoxyne NL should be administered with caution to patients with hepatic impairment or those receiving potentially hepatotoxic drugs.
Abnormal hepatic function has been reported rarely and has been caused by both the 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 individuals 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 Mondoxyne NL in patients with impaired renal function.
Serious skin reactions Serious skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline. If serious skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted.
Photosensitivity Photosensitivity manifested by an 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 evidence of skin erythema.
Photoonycholysis has also been reported in patients receiving doxycycline.
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 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 or other systemic retinoids and doxycycline should be avoided because isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri)..
Microbiological overgrowth The use of antibiotics may occasionally result in the overgrowth 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 life-threatening. It is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of 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 capsule and tablet forms of drugs in the tetracycline class, including doxycycline. Most of these 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, where 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 10 days.
Myasthenia gravis Due to a potential for weak neuromuscular blockade, care should be taken in administering tetracyclines to patients with myasthenia gravis.
Systemic lupus erythematosus Tetracyclines can cause exacerbation of SLE.
Methoxyflurane Caution is advised in administering tetracyclines with methoxyflurane.
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.
Use in patients with impaired hepatic function
Mondoxyne NL 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 Mondoxyne NL.
Use in patients with renal impairment
Excretion of Mondoxyne NL 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 Mondoxyne NL in individuals with normal and severely impaired renal function. Haemodialysis does not alter the serum half-life of Mondoxyne NL. 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 Mondoxyne NL in patients with impaired renal function.
Photosensitivity
Photosensitivity manifested by exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including Mondoxyne NL. 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 Mondoxyne NL. 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 Mondoxyne NL. 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 Mondoxyne NL should be avoided because isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri)..
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 Mondoxyne NL, 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 Mondoxyne NL, 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 Mondoxyne NL. 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.
WARNINGSIncluded as part of the "PRECAUTIONS" Section
PRECAUTIONS Tooth DevelopmentThe 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 discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drugs but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use Mondoxyne NL MPC in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies.
Clostridium Difficile Associated DiarrheaClostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Mondoxyne NL MPC Tablets, and may range in severity from mild diarrhea 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 diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
PhotosensitivityPhotosensitivity 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 tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.
Potential For Microbial OvergrowthMondoxyne NL MPC may result in overgrowth of non-susceptible organisms, including fungi. If such infections occur, discontinue use and institute appropriate therapy.
Intracranial HypertensionIntracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracycline including Mondoxyne NL MPC. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Avoid concomitant use of isotretinoin and Mondoxyne NL MPC because isotretinoin is also known to cause pseudotumor cerebri.
Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. 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.
Skeletal DevelopmentAll tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in 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..
Antianabolic ActionThe antianabolic action of the tetracyclines may cause an increase in BUN. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.
MalariaDoxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains.
Doxycycline does not suppress P. falciparum’s sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.
Development Of Drug-Resistant BacteriaPrescribing Mondoxyne NL MPC 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.
Laboratory Monitoring For Long-Term TherapyIn long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies should be performed.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of FertilityLong-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been ev idence of oncogenic activity in rats in studies with the related antibiotics, oxytetracycline (adrenal and pituitary tumors) a nd minocycline (thyroid tumors). Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro mammalian cell assays have been reported for related antibacterials (tetracycline, oxytetracycline).
Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.
Use In Specific Populations Pregnancy Risk SummaryThere are no adequate studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women such as that proposed for the treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS -the Teratogen Information System -concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk.1 In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively [see Data].
Clinical ConsiderationsEmbryo/Fetal Risk
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 also has been noted in animals treated early in pregnancy. 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..
DataHuman Data
A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. Sixty-three (0.19%) of the controls and 56 (0.30%) of the cases were treated with doxycycline. This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation), with the exception of a marginal relationship with neural tube defect based on only two-exposed cases.2
A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age.3
Lactation Risk SummaryTetracyclines are excreted in human milk, however, the extent of absorption of tetracyclines including doxycycline, by the breastfed infant is not known. Short-term use by lactating women is not contraindicated. The effects of prolonged exposure to doxycycline on breast milk production and breast fed neonates, infants and children are unknown.4 The developmental and health benefits of breast feeding should be considered along with the mother’s clinical need for Mondoxyne NL MPC and any potential adverse effects on the breast fed child from Mondoxyne NL MPC or from the underlying maternal condition.
Pediatric UseBecause of the effects of drugs of the tetracycline-class on tooth development and growth, use Mondoxyne NL MPC in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies.
Geriatric UseClinical studies of Mondoxyne NL MPC did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Mondoxyne NL MPC Tablets each contain less than 10 mg of sodium.
REFERENCES
1. Friedman JM, Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins University Press: 2000: 149-195. The TERIS (Teratogen Information System) is available at: http://www.micromedexsolutions.com/ (cited: 2016 Jan).
2. Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997; 89: 524-528.
3. Horne HW Jr. and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil 1980; 25: 315-317.
4. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); [Last Revision Date 2015 March 10; cited 2016 Jan]. Doxycycline; LactMed Record Number: 100; [about 3 screens]. Available from: http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm
).Mondoxyne NL is indicated for treatment periods of 3 months. Mondoxyne NL should not be administered for more than 3 consecutive three month periods.
No dosage modification is necessary in elderly patients.
Renal Impairment:
No dosage adjustment is necessary in the presence of renal impairment.
Children:
For use in children, see 'Contraindications'.
4.3 ContraindicationsIn common with other drugs of the tetracycline class, Mondoxyne NL is contra-indicated in infants and children up to 12 years of age.
Doxycycline should not be administered to patients who have shown hypersensitivity to doxycycline hyclate, other tetracyclines or to any of the excipients.
Patients known to have, or suspected to have, achlorhydria should not be prescribed doxycycline.
Use of doxycycline is contra-indicated during pregnancy and lactation (See 4.6 Pregnancy and lactation).
4.4 Special warnings and precautions for useTablet forms of the tetracycline class of drugs may cause oesophageal irritation and ulceration. To avoid oesophageal irritation and ulceration, adequate fluids should be taken with this medication. Mondoxyne NL should be swallowed whilst in an upright sitting or standing posture. Tablets taken in the evening should be taken well in advance of retiring (see 4.2: Posology and Method of Administration).
Whilst no overgrowth by opportunistic microorganisms such as yeast were noted during clinical studies, Mondoxyne NL therapy may result in overgrowth of non-susceptible microorganisms including fungi (with clinical symptoms of persistent bad breath, reddening of the gums, etc.). Periodic observation of the patient is essential. Mondoxyne NL therapy has been associated with diarrhoea, colitis and vaginal moniliasis which may suggest overgrowth of non-susceptible micro-organisms. If overgrowth by resistant organisms appears, Mondoxyne NL therapy should be discontinued and an appropriate treatment instituted.
Mondoxyne NL should be used with caution in patients with a history of or predisposition to oral candidosis. The safety and effectiveness of Mondoxyne NL has not been established for the treatment of periodontitis in patients with coexistent oral candidosis. Whilst not observed during clinical trials with Mondoxyne NL, the use of tetracyclines may increase the incidence of vaginal candidosis.
The blood doxycycline levels in patients treated with Mondoxyne NL are lower than in those treated with conventional antimicrobial formulations of doxycycline. As, however, there are no data to support safety in hepatic impairment at this lower dose, Mondoxyne NL should be administered with caution to patients with hepatic impairment or to those receiving potentially hepatotoxic drugs.
Caution should be observed in the treatment of patients with myasthenia gravis who may be at risk of worsening of the condition.
All patients receiving doxycycline including Mondoxyne NL should be advised to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruption etc.) occurs. Sunscreen or sunblock should be considered. Treatment should cease at the first sign of skin erythema.
In common with the use of antimicrobial drugs in general, there is a risk of the development of pseudomembranous colitis with doxycycline treatment. In the event of the development of diarrhoea during treatment with Mondoxyne NL, the possibility of pseudomembranous colitis should be considered and appropriate therapy instituted. This may include the discontinuation of doxycycline and the institution of specific antibiotic therapy (e.g vancomycin). Agents inhibiting peristalsis should not be employed in this situation.
In the event of a severe acute hypersensitivity reaction (e.g. anaphylaxis), treatment with Mondoxyne NL must be stopped at once and the usual emergency measures taken (e.g. administration of antihistamines, corticosteroids, sympathomimetics and if necessary artificial respiration instituted).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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.
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.
The effect of Mondoxyne NL on the ability to drive or operate heavy machinery has not been studied. There is no evidence to suggest that Mondoxyne NL may affect these abilities.
Mondoxyne NL therapy has been associated with nausea and dizziness. Those affected should not drive or operate machinery.
Posology
Adults
The usual dosage of Mondoxyne NL for the treatment of acute infections in adults is 200 mg on the first day (as a single dose or in divided doses) followed by a maintenance dose of 100 mg/day. In the management of more severe infections, 200 mg daily should be given throughout treatment.
Dosage recommendations in specific infections:
Acne vulgaris 50 mg daily with food or fluid for 6 to 12 weeks.
Sexually transmitted diseases 100 mg twice daily for 7 days is recommended in 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 gonorrhoea 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 therapy.
Louse and tick-borne relapsing fevers A single dose of 100 or 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 rapid-acting schizonticide such as quinine should always be given in conjunction with Mondoxyne NL; 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).
For the prevention of scrub typhus 200 mg as a single dose.
For the 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 the stay in the area. Data on the use of the drug prophylactically are not available beyond 21 days.
For the 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 Mondoxyne NL is contraindicated in children under the age of 12 years..
Use in the elderly Mondoxyne NL may be prescribed in the elderly in the usual dosages with no special precautions. No dosage adjustment is necessary in the presence of renal impairment. The Mondoxyne NL-D dispersible tablet may be preferred for the elderly since it is less likely to be associated with oesophageal irritation and ulceration.
Use in patients with impaired hepatic function
Use in patients with renal impairment
Method of administration
Dispersible Tablets are for oral administration only.
Mondoxyne NL-D tablets are administered by drinking a suspension of the tablets in a small amount of water. This should be done in the sitting or standing position and well before retiring at night to reduce the risk of oesophageal irritation and ulceration. If gastric irritation occurs, it is recommended that Mondoxyne NL be given with food or milk. Studies indicate that the absorption of Mondoxyne NL 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.
Posology
Adults
The usual dose of Mondoxyne NL capsules for the treatment of acute infections in adults 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.
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: Mondoxyne NL 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).
Older People: Mondoxyne NL may be prescribed in the usual dose with no special precautions. No dosage adjustment is necessary in the presence of renal impairment.
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 Mondoxyne NL Capsules be given with food or milk. Studies indicate that the absorption of Mondoxyne NL 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
Important Dosage And Administration InstructionsWhen switching from Mondoxyne NL to Mondoxyne NL MPC:
For adults, the recommended dose of Mondoxyne NL MPC is 120 mg daily.
For pediatric patients 8 years of age and older, the recommended dosage of Mondoxyne NL MPC is 2.4 mg per kg of body weight administered once daily. Pediatric patients weighing 45 kg or more should receive the adult dose.
Prophylaxis should begin 1 or 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.
Dosage For Inhalational Anthrax (Post-Exposure)For adults, the recommended dosage is 120 mg, of Mondoxyne NL MPC, by mouth, twice-a-day for 60 days.
For pediatric patients weighing less than 45 kg, the recommended dosage of Mondoxyne NL MPC is 2.6 mg per kg of body weight, by mouth, twice-a-day for 60 days. Pediatric patients weighing 45 kg or more should receive the adult dose.
Adults and the elderly:
Mondoxyne NL 20mg should be administered twice daily, at least one hour before meals or before bedtime. Tablets should be swallowed whole with adequate fluids (at least 100ml of water) and should be taken in an upright sitting or standing position (see 4.4: Special warnings and Precautions for Use).
Mondoxyne NL is indicated for treatment periods of 3 months. Mondoxyne NL should not be administered for more than 3 consecutive three month periods.
No dosage modification is necessary in elderly patients.
Renal Impairment:
No dosage adjustment is necessary in the presence of renal impairment.
Children:
For use in children, see 'Contraindications'.
No special requirements.
