Minocycline

Minocycline is a lipophilic tetracycline with good tissue and CNS penetration, used for acne, MRSA skin infection, Nocardia and other less common infections, leprosy, nontuberculous mycobacterial infection and, in some regions, Acinetobacter or Stenotrophomonas infection. Vestibular, pigmentary and autoimmune adverse effects limit its use.

Classification. Tetracycline, second generation.

Mechanism. Binds the 30S ribosomal subunit and blocks aminoacyl-tRNA attachment; bacteriostatic.

Spectrum. MRSA, MSSA, streptococci (resistance common), Nocardia, Stenotrophomonas maltophilia, Acinetobacter (variable), Chlamydia, Mycoplasma, Rickettsia, Mycobacterium leprae and Mycobacterium marinum. Not reliable against Pseudomonas or Enterobacterales.

Pharmacokinetics. Oral bioavailability about 90%. Half-life 11 to 22 hours. Protein binding about 75%. Extensive hepatic metabolism; excellent CSF penetration. Little renal excretion.

Maximum 200 mg daily in adults.

Adults.

• Loading dose 200 mg orally or IV, then 100 mg every 12 hours.
• Skin and soft tissue infection with MRSA: 100 mg every 12 hours for 5 to 10 days.
• Acne: 50 to 100 mg every 12 hours, or modified release 1 mg/kg once daily, for 12 weeks, reviewed before extending beyond 6 months.
• Nocardia infection (alternative): 100 mg every 12 hours as part of a multidrug regimen.
• Stenotrophomonas maltophilia and Acinetobacter (IV, specialist): 200 mg loading dose then 100 mg every 12 hours, usually in combination.
• Mycobacterium marinum: 100 mg every 12 hours for at least 3 months.
• Leprosy (alternative in multidrug regimens): 100 mg once daily.

Children 8 years and over. 4 mg/kg loading dose (maximum 200 mg), then 2 mg/kg every 12 hours (maximum 100 mg a dose).

Alternatives. Doxycycline, trimethoprim sulfamethoxazole, linezolid.

Contraindications. Tetracycline hypersensitivity; pregnancy; children under 8 years.

Adverse effects. Dizziness, vertigo, ataxia and tinnitus (vestibular toxicity, more frequent in women), nausea, headache, photosensitivity. Serious: skin, nail, scleral, thyroid and dental hyperpigmentation with prolonged use, drug-induced lupus, autoimmune hepatitis, hypersensitivity syndrome or DRESS (usually within 8 weeks), serum sickness, eosinophilic pneumonia, benign intracranial hypertension, Stevens-Johnson syndrome.

Interactions. Aluminium, magnesium, calcium, iron and zinc products reduce absorption; isotretinoin and other retinoids (intracranial hypertension); warfarin (INR rise); penicillins (antagonism); methoxyflurane (nephrotoxicity); oral typhoid vaccine.

Common prescribing errors. Prolonged acne courses without liver tests and antinuclear antibody review, ignoring dizziness, and giving to pregnant women or young children.

Special groups. - Pregnancy: contraindicated. Breastfeeding: avoid (may stain infant teeth). - Older adults: increased vestibular effects. - Kidney impairment: limit to 200 mg daily total; usual doses otherwise. - Liver impairment: use with caution and monitor.

Administration. Oral with a full glass of water, upright; separate from cations by 2 to 3 hours. IV: dilute to 1 mg/mL or less and infuse over 60 minutes (limited availability).

Baseline and monitoring. - Baseline: pregnancy test, liver tests, medication review. - During treatment: liver tests, antinuclear antibody and skin and nail pigment checks every 3 to 6 months in long-term use; ask about dizziness.

Stop rules. Stop for rash with fever or organ involvement, jaundice, lupus-like symptoms or severe vertigo.

Referral and escalation. Refer for hepatitis, DRESS, lupus-like syndrome and for specialist indications such as Nocardia or Acinetobacter.