APX-DOXYCYCLINE

What it is

APX-DOXYCYCLINE is a broad spectrum antibiotic synthetically derived from oxytetracycline. APX-DOXYCYCLINE tablets contain doxycycline 50 mg or 100 mg as doxycycline hyclate. The 50 mg tablets are white film-coated circular biconvex tablets with a diameter of 6.3 mm, while the 100 mg tablets are white film-coated biconvex tablets with a breakline on one face.

Approved indications

— Infections caused by Mycoplasma pneumoniae (primary atypical pneumonia) — Infections caused by Rickettsiae (Queensland tick typhus, epidemic typhus fever, Q fever, murine endemic typhus fever, Australo-Pacific endemic scrub typhus) — Infections caused by Chlamydia psittaci (psittacosis) — Infections caused by Chlamydia trachomatis (lymphogranuloma venereum, trachoma, inclusion conjunctivitis) — Infections caused by Borreliae (relapsing fever) — Infections caused by Calymmatobacterium (Donovania) granulomatis (granuloma inguinale) — Infections caused by Vibrio sp. (cholera) — Infections caused by Brucella sp. (Brucellosis; in conjunction with streptomycin) — Infections caused by Haemophilus ducreyi (chancroid) — Infections caused by Yersinia pestis (plague) — Infections caused by Francisella tularensis (tularaemia) — Infections caused by Bartonella bacilliformis (Bartonellosis) — Alternative treatment for syphilis when penicillin is contraindicated — Alternative treatment for yaws when penicillin is contraindicated — Alternative treatment for gonococcal infections when penicillin is contraindicated — Acute intestinal amoebiasis, as a useful adjunct to amoebicides — Severe acne, as useful adjunctive therapy — Chemoprophylaxis for malaria caused by Plasmodium falciparum in adults and children older than 10 years — Chemoprophylaxis in combination with other antimalarial agents for malaria caused by Plasmodium vivax in adults and children older than 10 years

Dosing overview

For adults and children over 8 years weighing above 50 kg, the usual dose is 200 mg on the first day of treatment (administered as 100 mg every twelve hours) followed by a maintenance dose of 100 mg per day, which may be administered as a single dose or as 50 mg every twelve hours. For more severe infections, particularly chronic infections of the urinary tract, 100 mg every twelve hours is recommended. For acute uncomplicated gonococcal infections, the dose is 100 mg twice daily for 5 to 7 days. For primary and secondary syphilis, the dose is 300 mg a day in divided doses for at least 10 days. Louse-borne typhus has been successfully treated with a single oral dose of 100 or 200 mg according to severity. For the prevention of scrub typhus, the dose is 200 mg as a single dose. For children above 8 years of age without skeletal growth retardation but weighing less than 50 kg, the adult dose of 100 mg should be recalculated on a weight basis as 2 mg/kg. For severe acne, some efficacy has been demonstrated at a dose of 50 mg per day over a period of 12 weeks. For malaria chemoprophylaxis, the dose is 100 mg once a day; commencing two days prior to entering malarious areas, while in the malarious area and for two weeks after leaving the malarious area.

Key safety warnings

Intracranial hypertension has been associated with the use of tetracyclines including doxycycline, and women of childbearing age who are overweight or have a history of intracranial hypertension are at greater risk for developing tetracycline-associated intracranial hypertension. Clinical manifestations include headache, blurred vision, diplopia and vision loss, and although intracranial hypertension typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Clostridium difficile-associated diarrhoea and antibiotic-associated pseudomembranous colitis have been reported with doxycycline and may range in severity from mild diarrhoea to fatal colitis; hypertoxin-producing strains of C. difficile cause increased morbidity and mortality as these infections can be refractory to antimicrobial therapy and may require colectomy. Clostridium difficile-associated diarrhoea must be considered in all patients who present with diarrhoea following antibiotic use, and careful medical history is necessary since it has been reported to occur over two months after the administration of antibacterial agents. The use of doxycycline during tooth development (latter half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discolouration of the teeth and enamel hypoplasia; doxycycline should not be used in this age group unless other drugs are not likely to be effective or are contraindicated. Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracycline; patients likely to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur and treatment should be discontinued at the first evidence of skin erythema. Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms have been reported; fixed drug eruptions have occurred and have been associated with worsening severity upon subsequent administrations; if severe skin reactions occur, doxycycline should be discontinued immediately.

Contraindications

Hypersensitivity to any of the tetracyclines or any of the excipients is contraindicated. Rare cases of benign intracranial hypertension have been reported after tetracyclines and after vitamin A or oral retinoids such as isotretinoin or etretinate; concomitant treatment is contraindicated. Use in pregnancy (16 weeks post conception) and lactation is contraindicated. The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.

Regulatory history

APX-DOXYCYCLINE was first registered on the Australian Register of Therapeutic Goods on 5 May 2020, with two registered variants: doxycycline 100 mg tablets (ARTG 333669) and doxycycline 50 mg tablets (ARTG 333670).