- Generic name : Minocycline hydrochloride
- Brand names: Dynacin, Minocin, Solodyn
- Therapeutic class: Antibiotic
- Pharmacologic class: Tetracycline
- FDA Approved: June 30, 1971
- Pregnancy Category: D
- Originally discovered: 1960s, Lederle Laboratories, USA
Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch
Minocycline is a highly lipophilic semisynthetic second-generation tetracycline antibiotic. Its antimicrobial spectrum is very similar to that of doxycycline with one important addition: minocycline has much more antistaphylococcal activity.
The first tetracycline, chlortetracycline, was discovered in 1948 during systematic screening of soil specimens for antibiotic-producing microorganisms. Chlortetracycline and oxytetracycline come from Streptomyces aureofaciens and Streptomyces rimosus, respectively. Tetracycline is produced semisynthetically from chlortetracycline. Minocycline is a semisynthetic derivative of tetracycline.
Minocycline was synthesized by Lederle Laboratories in 1967 and became widely available under the brand name Minocin in 197216.
Lederle Laboratories, founded in 1902, is a pharmaceutical division of Cyanamid, a large diversified American chemical manufacturer.
FDA approved uses
- Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox and tick fevers
- Respiratory tract infections: laryngotracheitis, tracheobronchitis, bronchitis, bronchiolitis, bronchiectasis, bronchopneumonia, pneumonia (single lobe and multilobe), lung abscess.
- Psittacosis (Ornithosis)
- Inclusion conjunctivitis
- Nongonococcal urethritis, endocervical, or rectal infections in adults
- Relapsing fever
- Campylobacter fetus infections
- Granuloma inguinale
- Urinary tract infections: cystitis, pyelonephritis
- Skin and skin structure infections: abscess, acne, cellulitis, infected dermatitis, folliculitis, furunculosis, impetigo, lymphadenitis, suppurative hydradenitis, paronychia, infected wounds.
- Gonococcal infections
- Vincentís infection
- Infections caused by Clostridium species
- Intestinal amebiasis: Minocycline may be a useful adjunct to amebicides
Off-label & Investigational uses
Minocycline is used as a disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis. Rheumatoid arthritis is a chronic inflammatory disease affecting about 1% of the adult population.
Although rheumatoid arthritis is not an infection, minocycline may improve the signs and symptoms of this disease. It may slow the progression of joint damage in arthritis and prevent disability. There is evidence that, besides its antibiotic effects, minocycline can reduce body's inflammatory responses. It decreases the production of substances causing inflammation, such as prostaglandins and leukotrienes, while increasing production of interleukin-10, a substance that reduces inflammation.
Minocycline has a slow onset - it may take 1-3 months after the start of therapy to observe an improvement. And the most benefits are seen when minocycline is used in early disease.
Results of a 48-week multicenter clinical study20 of 219 adults with rheumatoid arthritis show that minocycline reduces joint pain and swelling and is safe in mild to moderate disease. Minocycline may slow down the progression of disease and provide relief from swollen, tender joints.
According to the American College of Rheumatology, "Minocycline is prescribed for patients with symptoms of mild rheumatoid arthritis. It is sometimes combined with other medications to treat patients with persistent symptoms of this form of arthritis."
Minocycline has been shown to increase bone mineral density, improve bone strength and formation, and slow bone resorption in old laboratory animals with surgically-induced menopause21.
- Lyme disease
Lyme disease, or borreliosis, is an emerging infectious disease caused by the bacterium Borrelia burgdorferi and is transmitted to humans by the bite of infected blacklegged ticks. Minocycline may be useful for the treatment of Lyme disease19.
Sarcoidosis is a disease that results from a specific type of inflammation of tissues of the body.
Studies24 indicate that minocycline may be beneficial for the treatment of cutaneous sarcoidosis.
- Cystic fibrosis22-23
Cystic fibrosis (also known as CF, mucoviscoidosis, or mucoviscidosis) is a hereditary disease that affects mainly the exocrine (mucus) glands of the lungs, liver, pancreas, and intestines, causing progressive disability due to multisystem failure.
Periodontitis is a dental disorder that results from progression of gingivitis, involving inflammation and infection of the ligaments and bones that support the teeth. Minocycline is used to control bacteria and reduce the size of periodontal pockets. The periodontist puts the minocycline micro-spheres into the pockets after scaling and root planing. The particles release minocycline slowly over time.
- Gougerot-Carteaud Syndrome 17, an uncommon dermatosis of unknown etiology.
- Autistic disorder, as adjunctive treatment to risperidone 35
Minocycline "pros" and "cons"
- Less photosensitizing. Photosensitivity is least likely than with other tetracyclines25-26.
- High concentrations in the tissues. Minocycline is widely distributed in body tissues27, with higher concentrations being found in cerebrospinal fluid and sputum than with other tetracyclines. As in blood, the concentration in tissues is generally 2 to 4 times higher with minocycline than with tetracycline. Equivalent blood and tissue levels achieved whether administered intravenously or orally.
- Long half-life (from 11 to 23 hours).
- Broader spectrum of antimicrobial activity. Against certain pathogens, minocycline is more potent than the other tetracyclines. Minocycline has excellent in vitro inhibitory activity against both Staphylococcus aureus and coagulase-negative staphylococci, particularly methicillin-resistant S. aureus and methicillin-resistant S. epidermidis strains3-5.
- Can be used in renal impairment. Most tetracyclines should be avoided in patients with renal insufficiency. However, minocycline can be used in patients with malfunction of the kidneys. It is eliminated through the hepatobiliary and gastrointestinal tracts.
- Low rate of bacterial resistance. Minocycline produces less antibiotic resistance than tetracycline.28-29 Bacterial cell membranes contain a lipid layer. One mechanism of building up a resistance to an antibiotic is to produce a thicker lipid layer. This layer makes it difficult for an antibiotic to penetrate. Minocycline chemical structure makes it the most lipid soluble of all the tetracyclines.
- Minocycline can be taken with food, including dairy products.
- Expensive. Minocycline is considerably more expensive than the other generic tetracyclines.
- Contraindicated in children. May cause enamel hypoplasia and permanent teeth discoloration.
- Lupus-like syndrome. Minocycline is more likely than other tetracyclines to produce a lupus-like syndrome. Minocycline-induced lupus is characterized by the development of non-specific symptoms after long-term consumption of the drug, and the patient usually continues to take minocycline despite their illness as the association is not immediately obvious1. These abnormalities tend to occur after prolonged therapy (often longer than 12 months).
- Serum sickness-like reaction. Minocycline induced serum sickness like reaction (SSLR) was first reported in 199030. This is a type of delayed allergic reaction, in which the immune system interprets the antibiotic as a foreign threat. A serum sickness-like reaction (SSLR) to drug usually consists of cutaneous rash, arthralgia/arthritis, and, often, fever.
- Vasculitis, usually resembling cutaneous polyarteritis nodosa, may occur in association with minocycline use.
- Intracranial hypertension (pseudotumor cerebri) is an accumulation of fluid around the brain. Minocycline can cause the rare condition of secondary intracranial hypertension31 which has initial symptoms of headache, visual disturbances, and confusion.
- Vestibular side effects, that not generally shared by other tetracyclines. Minocycline can cause quite severe dizziness, nausea, vertigo, ataxia, and vomiting32. Vertigo has been reported in as many as 86% of individuals in some series33.
- Hyperpigmentation. Unlike other tetracyclines, minocycline
can cause a potentially irreversible slate-grey hyperpigmentation
of the skin. Blue or blue-black oral pigmentation was seen in 10%
of patients taking minocycline for at least 1 year; the rate increased
to 20% after 4 years of continuous use2.
Minocycline-induced hyperpigmentation does not appear to be dose dependent. Sites of previous tissue trauma or inflammation are more vulnerable to the development of pigmentation36.
Large daily doses of ascorbic acid (vitamin C) may prevent this phenomenon34.
Mode of action
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis.
Minocycline is a semisynthetic derivative of tetracycline and is active against many tetracycline resistant strains of organisms such as staphylococci, streptococci and E. coli. Thus the combined results of many studies show its activity against approximately 87% of tetracycline resistant staphylococci. Minocycline is also active against many strains of staphylococci which are resistant to penicillin G and certain semisynthetic penicillins.
Minocycline and other tetracycline derivatives have neuroprotective effects unrelated to their antimicrobial properties. Minocycline has the greatest permeability of all tetracyclines through the blood-brain barrier and is well suited for treatment of CNS disorders.
Minocycline can reduce neuronal death after excitotoxicity and ionizing radiation in culture6-7 and in animal models of stroke7-9, Parkinson's disease10-11, Huntington's disease12, and amyotrophic lateral sclerosis13. The neuroprotective effects of minocycline have been attributed both to reduced inflammation and a direct effect on neuronal survival.
Minocycline induces anti-inflammatory and antinociceptive effects unrelated to its antimicrobial activitiy15. Although the exact mechanisms of minocycline anti-inflammatory effects are still poorly understood, they may include the inhibition of matrix metalloproteinase-2 activity, the inhibition of inducible nitric oxide synthase14, prostaglandin E2, caspase-1, caspase-3, and COX-2 expressions and the impairment of cytokine production.
Time to clear out of the system
Minocycline half-life is 16 hours (range: 11-23 hours).
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Published: July 01, 2008
Last updated: January 28, 2017
- Minocycline is the least frequently prescribed of the three tetracyclines, but it has the largest fraction of repeat prescriptions.
- Minocycline may cause rare but very serious side effects, including hypersensitivity syndrome, autoimmune hepatitis, and lupus.
- Aside from its antimicrobial properties, minocycline has been found to have beneficial effects on inflammation, microglial activation, matrix metalloproteinases, nitric oxide production, and apoptotic cell death.