Drugs List

Therapeutic Indications

Uses

Treatment to reduce papulopustular lesions in adult patients with facial rosacea.

Administration

For oral administration.

Capsules should be swallowed whole with water whilst sitting upright or standing to reduce the risk of oesophageal ulceration and irritation.

Contraindications

Children under 12 years
Pregnancy (see Pregnancy)
Patients that have, or suspected to have achlorhydria
Duodenectomy
Duodenal bypass
Hereditary fructose intolerance

Precautions and Warnings

Doxycycline in this formulation is designed to yield plasma levels below the antimicrobial threshold. Doxycycline 40mg modified release capsules must not be used to treat infections caused by organisms susceptible (or suspected to be susceptible) to doxycycline.

Capsules should be swallowed whole with water whilst sitting upright or standing to reduce the risk of oesophageal ulceration and irritation.

Dooxycycline should be taken with adequate amounts of water in order to reduce the risk of oesophageal irritation and ulceration.

Breastfeeding (see Lactation).

Treatment with higher doses, may result in the overgrowth of opportunistic organisms, including candida. If a superinfection occurs, discontinue doxycycline and institute appropriate therapy.
Use with caution in patients with a history of predisposition to candidiasis overgrowth.

Treatment with higher doses of tetracyclines is associated with emergence of resistant intestinal bacteria, such as enterococci and enterobacteria.

There is a risk of the development of pseudomembranous colitis with doxycycline treatment. In the event of the development of diarrhoea during treatment during treatment with doxycycline, the possibility of pseudomembranous colitis should be considered and appropriate therapy instituted. This may include the discontinuation of therapy.

Advise patients that photosensitivity is possible and to avoid prolonged exposure to sunlight and UV rays during treatment. The use of sunscreen or sunblock should be considered.
Discontinue treatment immediately if photosensitivity or phototoxicity (e.g. skin eruption) occurs.

Bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported. Treatment should be withdrawn if raised intracranial pressure develops.

Use with caution in patients with myasthenia gravis as there is potential for worsening of the condition.

Alcohol dependence or chronic alcohol abuse may result in sub-therapeutic doxycycline concentrations due to liver enzyme induction and accelerated metabolism of doxycycline.

Doxycycline may cause permanent discolouration of the teeth (yellow/grey/brown) in patients during tooth development. This more commonly occurs during long term use but has also been observed with repeated short courses. Enamel hypoplasia has also been reported.
A decrease in fibula growth has been observed in premature infants given oral tetracycline in doses of 25mg/kg every 6 hours.

Oesophagitis and oesophageal ulceration have been reported in patients receiving doxycycline. The incidence of these effects can be minimised by taking the dose while sitting or standing upright and with an adequate amount of water.

The Faculty of Sexual and Reproductive Health has issued revised guidance concerning additional contraceptive cover when antibiotics are prescribed to patients taking combined oral contraceptives. With the exception of the enzyme-inducing antibiotics rifampicin and rifabutin, it is no longer necessary to advise the patient to take additional contraceptive precautions while also taking an antibiotic.

Advise the patient that if vomiting occurs, she should follow the guidance for the oral contraceptive in respect of additional doses or contraceptive precautions.

Tetracyclines used concurrently with oral contraceptives have in a few cases resulted in either breakthrough bleeding or pregnancy.

Food and other medicinal products should be taken 2-3 hours after doxycycline ingestion to prevent lower absorption of doxycycline in the gastrointestinal tract.

Porphyria (see Precautions and Warnings - Porphyria ).

Hepatic impairment (see Dosage- Hepatic Impairment ).

There is limited efficacy and safety data in patients with ocular manifestations of rosacea, such as ocular rosacea, blepharitis or meibomianitis. If symptoms of ocular rosacea develop, treatment with modified release doxycycline should be discontinued and the patient should be referred to an ophthalmologist.

In the event of a severe acute hypersensitivity reaction (e.g. anaphylaxis), treatment with doxycycline must be stopped at once and the standard emergency measures taken (administration of antihistamines and corticosteroids).

Capsules contain sucrose so they should be administered with caution in patients with glucose-galactose malabsorption syndrome.

Use in Porphyria

The drug database for acute porphyria states use doxycycline with caution in porphyria as its possibly porphyrogenic.

Pregnancy and Lactation

Pregnancy

Doxycycline is contraindicated in pregnancy.

Tetracyclines cross the placenta and causes a permanent brown discolouration of deciduous teeth and inhibition of bone growth in infants exposed in utero. Inadvertent early pregnancy exposure to tetracyclines occurs frequently and has not been associated with an increased risk of other congenital malformations (Briggs, 2011). Inadvertent use of doxycycline is not considered an indication for termination of pregnancy or for invasive prenatal diagnostic procedures (Schaefer, 2007).

Maternal tetracycline-induced severe hepatotoxicity, especially following high doses or via intravenous administration, in the second half of pregnancy has been reported.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - Contraindicated

Crosses placenta? - Yes

Effects on foetus - Permanent staining of bone and deciduous teeth in infants exposed to tetracyclines in utero.

Adverse effects on the mother - Tetracycline use in pregnancy has also been linked to the rare but often fatal syndrome in the mother of acute fatty metamorphosis of the liver.

Lactation

Doxycycline should be used with caution in breastfeeding.

Doxycycline is excreted in breast milk and in low levels. Long-term use or repeated courses of doxycycline while breastfeeding may result in significant absorption of doxycycline by the suckling infant and is not recommended. Theoretically, dental staining and inhibition of bone growth could occur in breastfed infants whose mothers were being treated with doxycycline on a long term basis.

However, short term use (defined as up to 3-4 weeks by Hale) is acceptable. As a precaution, infants should be monitored for rash, diarrhoea or candidiasis as doxycycline may alter gastrointestinal flora.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - On a short term basis. Long term use of doxycycline is not recommended because of theoretical risk of dental discolouration and decreased bone growth of the suckling child.

Side Effects

Anorexia
Nausea
Vomiting
Diarrhoea
Glossitis
Dysphagia
Hepatotoxicity
Oesophagitis
Oesophageal ulceration
Erythema
Maculopapular rash
Photosensitivity
Exfoliative dermatitis
Blood urea increased
Thrombocytopenia
Neutropenia
Haemolytic anaemia
Eosinophilia
Exacerbation of systemic lupus erythematosus
Anaphylaxis
Anaphylactoid purpura
Pericarditis
Urticaria
Bulging fontanelles in infants
Benign intracranial hypertension
Brown-black microscopic discolouration of thyroid tissue
Yellowish-brown discolouration of teeth
Vaginitis
Rash
Hypersensitivity reactions
Headache
Pseudomembranous colitis
Abnormal liver function tests
Hepatic failure
Abdominal pain
Enamel hypoplasia
Nasopharyngitis
Sinusitis
Fungal infection
Anxiety
Sinus headache
Dry mouth
Back pain
Enterocolitis
Angioneurotic oedema
Hypertension
Increase in serum glucose
Raised intracranial pressure

Presentation

Modified release capsules containing 40mg of doxycycline (as doxycycline monohydrate).

Drugs List

Therapeutic Indications

Uses

Treatment to reduce papulopustular lesions in adult patients with facial rosacea.

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration.

Capsules should be swallowed whole with water whilst sitting upright or standing to reduce the risk of oesophageal ulceration and irritation.

Contraindications

Children under 12 years
Pregnancy (see Pregnancy)
Patients that have, or suspected to have achlorhydria
Duodenectomy
Duodenal bypass
Hereditary fructose intolerance

Precautions and Warnings

Doxycycline in this formulation is designed to yield plasma levels below the antimicrobial threshold. Doxycycline 40mg modified release capsules must not be used to treat infections caused by organisms susceptible (or suspected to be susceptible) to doxycycline.

Capsules should be swallowed whole with water whilst sitting upright or standing to reduce the risk of oesophageal ulceration and irritation.

Dooxycycline should be taken with adequate amounts of water in order to reduce the risk of oesophageal irritation and ulceration.

Breastfeeding (see Lactation).

Treatment with higher doses, may result in the overgrowth of opportunistic organisms, including candida. If a superinfection occurs, discontinue doxycycline and institute appropriate therapy.
Use with caution in patients with a history of predisposition to candidiasis overgrowth.

Treatment with higher doses of tetracyclines is associated with emergence of resistant intestinal bacteria, such as enterococci and enterobacteria.

There is a risk of the development of pseudomembranous colitis with doxycycline treatment. In the event of the development of diarrhoea during treatment during treatment with doxycycline, the possibility of pseudomembranous colitis should be considered and appropriate therapy instituted. This may include the discontinuation of therapy.

Advise patients that photosensitivity is possible and to avoid prolonged exposure to sunlight and UV rays during treatment. The use of sunscreen or sunblock should be considered.
Discontinue treatment immediately if photosensitivity or phototoxicity (e.g. skin eruption) occurs.

Bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported. Treatment should be withdrawn if raised intracranial pressure develops.

Use with caution in patients with myasthenia gravis as there is potential for worsening of the condition.

Alcohol dependence or chronic alcohol abuse may result in sub-therapeutic doxycycline concentrations due to liver enzyme induction and accelerated metabolism of doxycycline.

Doxycycline may cause permanent discolouration of the teeth (yellow/grey/brown) in patients during tooth development. This more commonly occurs during long term use but has also been observed with repeated short courses. Enamel hypoplasia has also been reported.
A decrease in fibula growth has been observed in premature infants given oral tetracycline in doses of 25mg/kg every 6 hours.

Oesophagitis and oesophageal ulceration have been reported in patients receiving doxycycline. The incidence of these effects can be minimised by taking the dose while sitting or standing upright and with an adequate amount of water.

The Faculty of Sexual and Reproductive Health has issued revised guidance concerning additional contraceptive cover when antibiotics are prescribed to patients taking combined oral contraceptives. With the exception of the enzyme-inducing antibiotics rifampicin and rifabutin, it is no longer necessary to advise the patient to take additional contraceptive precautions while also taking an antibiotic.

Advise the patient that if vomiting occurs, she should follow the guidance for the oral contraceptive in respect of additional doses or contraceptive precautions.

Tetracyclines used concurrently with oral contraceptives have in a few cases resulted in either breakthrough bleeding or pregnancy.

Food and other medicinal products should be taken 2-3 hours after doxycycline ingestion to prevent lower absorption of doxycycline in the gastrointestinal tract.

Porphyria (see Precautions and Warnings - Porphyria ).

Hepatic impairment (see Dosage- Hepatic Impairment ).

There is limited efficacy and safety data in patients with ocular manifestations of rosacea, such as ocular rosacea, blepharitis or meibomianitis. If symptoms of ocular rosacea develop, treatment with modified release doxycycline should be discontinued and the patient should be referred to an ophthalmologist.

In the event of a severe acute hypersensitivity reaction (e.g. anaphylaxis), treatment with doxycycline must be stopped at once and the standard emergency measures taken (administration of antihistamines and corticosteroids).

Capsules contain sucrose so they should be administered with caution in patients with glucose-galactose malabsorption syndrome.

Use in Porphyria

The drug database for acute porphyria states use doxycycline with caution in porphyria as its possibly porphyrogenic.

Pregnancy and Lactation

Pregnancy

Doxycycline is contraindicated in pregnancy.

Tetracyclines cross the placenta and causes a permanent brown discolouration of deciduous teeth and inhibition of bone growth in infants exposed in utero. Inadvertent early pregnancy exposure to tetracyclines occurs frequently and has not been associated with an increased risk of other congenital malformations (Briggs, 2011). Inadvertent use of doxycycline is not considered an indication for termination of pregnancy or for invasive prenatal diagnostic procedures (Schaefer, 2007).

Maternal tetracycline-induced severe hepatotoxicity, especially following high doses or via intravenous administration, in the second half of pregnancy has been reported.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - Contraindicated

Crosses placenta? - Yes

Effects on foetus - Permanent staining of bone and deciduous teeth in infants exposed to tetracyclines in utero.

Adverse effects on the mother - Tetracycline use in pregnancy has also been linked to the rare but often fatal syndrome in the mother of acute fatty metamorphosis of the liver.

Lactation

Doxycycline should be used with caution in breastfeeding.

Doxycycline is excreted in breast milk and in low levels. Long-term use or repeated courses of doxycycline while breastfeeding may result in significant absorption of doxycycline by the suckling infant and is not recommended. Theoretically, dental staining and inhibition of bone growth could occur in breastfed infants whose mothers were being treated with doxycycline on a long term basis.

However, short term use (defined as up to 3-4 weeks by Hale) is acceptable. As a precaution, infants should be monitored for rash, diarrhoea or candidiasis as doxycycline may alter gastrointestinal flora.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - On a short term basis. Long term use of doxycycline is not recommended because of theoretical risk of dental discolouration and decreased bone growth of the suckling child.

Effects on Ability to Drive and Operate Machinery

Doxycycline has no or negligible influence on the ability to drive and use machines.

Counselling

Advise patient to avoid milk, antacids and mineral supplements 2 hours before or after each doxycycline dose.

Advise patient to avoid taking St John's wort concurrently.

Advise patient that photosensitivity is possible and to avoid prolonged exposure to sunlight and UV rays during treatment. Also advise them to consult their physician immediately if skin erythema occurs.

Side Effects

Anorexia
Nausea
Vomiting
Diarrhoea
Glossitis
Dysphagia
Hepatotoxicity
Oesophagitis
Oesophageal ulceration
Erythema
Maculopapular rash
Photosensitivity
Exfoliative dermatitis
Blood urea increased
Thrombocytopenia
Neutropenia
Haemolytic anaemia
Eosinophilia
Exacerbation of systemic lupus erythematosus
Anaphylaxis
Anaphylactoid purpura
Pericarditis
Urticaria
Bulging fontanelles in infants
Benign intracranial hypertension
Brown-black microscopic discolouration of thyroid tissue
Yellowish-brown discolouration of teeth
Vaginitis
Rash
Hypersensitivity reactions
Headache
Pseudomembranous colitis
Abnormal liver function tests
Hepatic failure
Abdominal pain
Enamel hypoplasia
Nasopharyngitis
Sinusitis
Fungal infection
Anxiety
Sinus headache
Dry mouth
Back pain
Enterocolitis
Angioneurotic oedema
Hypertension
Increase in serum glucose
Raised intracranial pressure

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store original packaging in order to protect from light.

Further Information

Last Full Review Date: June 2012

Reference Sources

British National Formulary, 63rd Edition (2012) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Efracea 40mg Modified Release Capsules. Galderma (UK) Ltd. Revised March 2011.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

The Drug Database for acute Porphyria (NAPOS)
Available at: https://www.drugs-porphyria.org/languages/UnitedKingdom/s3.php?atc_code=J01AA02&l=gbr
Doxycycline Last revised: September 24, 2009
Last accessed: June 8, 2012

Faculty of Sexual and Reproductive Healthcare
https://www.ffprhc.org.uk/pdfs/CEUGuidanceDrugInteractionsHormonal.pdf
Last accessed: June 8, 2012

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Doxycycline. Last revised: March 1, 2012
Last accessed: June 8, 2012