Interaction with other medicinal products and other forms of interaction
There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline.Tetracyclines depress plasma prothrombin activity and reduced doses of concomitant anticoagulants may be necessary.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving doxycycline in conjunction with penicillin.
Absorption of doxycycline may be impaired by concurrently administered antacids containing aluminium, calcium, magnesium or other drugs containing these cations; oral zinc, iron salts or bismuth preparations. Dosages should be maximally separated.
Barbiturates, carbamazepine, primidone and phenytoin may increase the metabolism of doxycycline (reduced half-life). An increase in the daily dosage of doxycycline should be considered.
Alcohol may decrease the half-life of doxycycline.
The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity. See section 4.4.
Doxycycline may increase the plasma concentration of ciclosporin. Co-administration should only be undertaken with appropriate monitoring.
Drugs that induce hepatic enzymes such as rifampicin may accelerate the decomposition of doxycycline, thereby decreasing its half-life. Sub-therapeutic doxycycline concentrations may result. Monitoring concurrent use is advised and an increase in doxycycline dose may be required.
Ergotamine and methysergide
There is an increased risk of ergotism when doxycycline is co-administered with ergotamine and methysergide.
Doxycycline increases the risk of methotrexate toxicity; prescribe with caution to patients on methotrexate.
Kaolin and sucralfate may reduce the absorption of doxycycline.
Quinapril contains magnesium carbonate and may interfere with the absorption of doxycycline.
A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracycline antibiotics with oral contraceptives.
There is a possible increased risk of benign intra-cranial hypertension when doxycycline given with retinoids. Concomitant use should be avoided.
Antibacterials inactivate oral typhoid vaccines. Avoid administration of vaccine during treatment with doxycycline.
Laboratory test interactions
False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.
4.6 Fertility, pregnancy and lactation
See “Contra-indications”, section 4.3.
4.7 Effects on ability to drive and use machines
Visual disturbances such as blurring of vision may occur during treatment with doxycycline and in such cases; patients must be informed to refrain from driving or operating machinery.
4.8 Undesirable effects
The following adverse reactions have been observed in patients receiving tetracyclines, including doxycycline.
Hypersensitivity reactions, including anaphylactic shock, anaphylaxis, anaphylactoid reactions, anaphylactoid purpura, hypotension, pericarditis, angioneurotic oedema, exacerbation of systemic lupus erythematosus, dyspnoea, serum sickness, peripheral oedema, tachycardia and urticaria.
Infections and infestations: As with all antibiotics, overgrowth of non-susceptible organisms may cause candidiasis, glossitis, staphylococcal enterocolitis, pseudomembranous colitis (with Clostridium difficile overgrowth) and inflammatory lesions (with candidal overgrowth) in the anogenital region.
Blood and lymphatic system disorders: Haemolytic anaemia, thrombocytopenia, neutropenia, porphyria and eosinophilia have been reported with tetracyclines.
Immune system diosorders: Jarisch-Herxheimer reaction (frequency not known) (see section 4.4).
Endocrine disorders: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid tissue. No abnormalities of thyroid function are known to occur.
Nervous system disorders: Headache. Bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported in some individuals receiving full therapeutic dosages of tetracyclines. These are reversible on stopping the drug. Symptoms include blurring of vision, scotomata and diplopia. Permanent visual loss has been reported.