Minocycline (Minocin) is available orally and as an injection formulation that is used mainly to treat patients with inflammatory, non-nodular acne. It is also used to treat patients with purulent skin infections, respiratory, and gastrointestinal infections. It belongs to the class of antibiotics called tetracyclines. It acts by inhibiting bacterial protein synthesis.

Minocycline Uses:

• Acute intestinal amebiasis:

  • In the treatment of acute intestinal amebiasis, it serves as an adjuvant therapy to amebicides.

• Acne:

  • Combined use of oral (immediate release) and intravenous medications for severe acne
  • Oral (extended-release): It is exclusively used to treat inflammatory lesions in people with non-nodular, moderate-to-severe acne vulgaris who are at least 12 years old.

• Actinomycosis:

  • When penicillin cannot be administered, it is used to treat actinomycosis caused by Actinomyces israelii.

• Anthrax:

  • When penicillin cannot be used to treat anthrax caused by Bacillus anthracis, it is used instead.

• Asymptomatic carriers of Neisseria meningitidis:

  • Meningococci are removed from the nasopharynx of asymptomatic carriers of N. meningitidis using an oral (immediate-release) medication.

• Campylobacter:

  • It is prescribed to treat infections caused by Campylobacter foetus.

• Cholera:

  • It is prescribed to treat cholera caused by Vibrio cholerae.

• Clostridium:

  • When penicillin cannot be administered, it is recommended for the treatment of infections caused by Clostridium spp.

• Gram-negative infections:

  • It is prescribed to treat infections brought on by Acinetobacter species, Escherichia coli, Enterobacter aerogenes, and Shigella species.

• Listeriosis:

  • When penicillin is not appropriate, it is used to treat Listeria monocytogenes-related listeriosis.

• Meningitis:

  • When penicillin is not appropriate, it is used to treat meningitis caused by Neisseria meningitidis.

• Ophthalmic infections:

  • It is used to treat trachoma brought on by Chlamydia trachomatis as well as inclusion conjunctivitis.

• Relapsing fever:

  • It is utilised to treat Borrelia recurrentis-related relapsing fever.

• Respiratory tract infections:

  • It is utilised in the treatment of respiratory tract infections (RTIs) brought by by Mycoplasma pneumonia, Klebsiella spp., or Haemophilus influenzae. for the treatment of Streptococcus pneumoniae-related upper respiratory tract infections.

• Rickettsial infections:

  • Rocky Mountain spotted fever, typhus and the typhus group, Q fever, rickettsialpox, and tick-borne Rickettsiae fevers are all treated with it.

• Sexually transmitted infections:

  • it is used for the treatment of following STI when penicillin is contraindicated
    • lymphogranuloma venereum caused by C. trachomatis
    • Nongonococcal urethritis
    • Endocervical, or rectal infections in adults caused by Ureaplasma urealyticum or C. trachomatis
    • Donovanosis (granuloma inguinale) caused by Klebsiella granulomatis
    • Syphilis caused by Treponema pallidum subspecies pallidum

• Skin and skin structure infections:

  • Staphylococcus aureus-related skin and skin structure infections are treated with it (not considered a first-line agent for any staphylococcal infection)

• Urinary tract infections:

  • Urinary tract infections brought on by Klebsiella species are treated with it.

• Vincent infection:

  • When penicillin is not appropriate, it is used to treat Vincent infection brought on by Fusobacterium fusiforme.

• Yaws:

  • When T. pallidum subspecies pertenue causes yaws, it is utilised to cure them.

• Zoonotic infections:

  • It is used for following zoonotic infections
    • Psittacosis (ornithosis) due to Chlamydia psittaci
    • Plague due to Yersinia pestis
    • Tularemia due to Francisella tularensis
    • Brucellosis due to Brucella spp (in conjunction with streptomycin)
    • Bartonellosis due to Bartonella bacilliformis

• Off Label Use of Minocycline in Adults:

  • Cellulitis (purulent) due to community-acquired MRSA
  • Leprosy
  • Nocardiosis
  • Prosthetic Joint Infection
  • Rheumatoid arthritis

Minocycline Dose in Adults:

Usual dosage range:

• IV: Initial dose of 200 mg; maintenance dose of 100 mg twice daily (maximum: 400 mg a day)
• Oral: Initial: 200 mg for a single dosage; Maintenance: 100 mg twice daily; longer intervals between doses are also possible (100 - 200 mg initially, followed by 50 mg 4 times a day)

Minocycline (Minocin) Dose in the treatment of Acne:

• 50–100 mg twice daily by capsule or immediate-release tablet. Note: To prevent the emergence of bacterial resistance, treatments should be kept as brief as possible. After three to four months, they should be reviewed.

Minocycline (Minocin) Dose in the treatment of moderate to severe non-nodular inflammatory acne vulgaris:

Note: It should be given for 12 weeks. Safety of use for more than 12 weeks has not been established.

• Extended-release capsule (Ximino):

  • Oral: 1 mg/kg (rounded to the nearest capsule) once a day

• Extended-release tablet: Oral:

  • Minolira:
    • 45 - 59 kg:5 mg (one-half of the 105 mg tablet) once a day
    • 60 - 89 kg:5 mg (one-half of the 135 mg tablet) once a day
    • 90 - 125 kg: 105 mg once a day
    • 126 - 136 kg: 135 mg once a day
  • CoreMino, Solodyn:
    • 45 - 49 kg: 45 mg once a day
    • 50 - 59 kg: 55 mg once a day
    • 60 - 71 kg: 65 mg once a day
    • 72 - 84 kg: 80 mg once a day
    • 85 - 96 kg: 90 mg once a day
    • 97 - 110 kg: 105 mg once a day
    • 111 - 125 kg: 115 mg once a day
    • 126 - 136 kg: 135 mg once a day

Dose for treating Purulent Cellulitis due to community-acquired MRSA (off-label): Oral:

• Initial dosage is 200 mg; maintenance is 100 mg twice daily for five to ten days.

Dose for treating uncomplicated Chlamydial or Ureaplasma urealyticum infection:

• Oral, IV: 100 mg twice daily for at least 7 days in the urethral, endocervical, or rectal

Dose for treating uncomplicated Gonococcal infection in males: Oral, IV:

• Without urethritis or anorectal infection:

  • Initial dose: 200 mg; ongoing dose: 100 mg twice daily for at least 4 days (cultures 2 - 3 days post-therapy)

• Urethritis:

  • Five days at 100 mg twice every day

Minocycline (Minocin) Dose as an alternative agent in the treatment of Leprosy (off-label): Oral:

• Lepromatous (multibacillary):

  • Combining 100 mg once day for 24 months with clofazimine and rifampin

• Tuberculoid (paucibacillary):

  • In addition to rifampin, 100 mg once daily for 12 months.

Dose for treating Meningococcal carrier state (manufacturer's labeling):

• 100 mg orally twice day for five days.

Note: Minocycline is not recommended by the CDC for eliminating meningococcal carriage in the nasopharynx.

Dose for treating Mycobacterium marinum:

• Oral, twice daily for 6–8 weeks at 100 mg.

Dose for treating Nocardiosis (off-label):

• Oral: 100–200 mg twice daily, with or without other concurrent antimicrobials. To more clearly identify the function of minocycline in this scenario, more information could be required.

Dose for treating prosthetic joint infection:

• Treatment for Staphylococci (oxacillin-sensitive or -resistant) in the oral phase following a one-stage exchange (after completion of pathogen-specific IV therapy).:

  • Total ankle, elbow, hip, or shoulder replacement: 100 mg twice daily for three months; take note that rifampin must also be taken.
  • Total knee replacement: 100 mg twice daily for six months; rifampin must also be administered in conjunction.

Dose for chronic oral antimicrobial suppression (off-label): Oral:

• Cutibacterium spp (alternative to penicillin or amoxicillin):

  • 100 mg two per day.

• Staphylococci (oxacillin-resistant):

  • 100 mg two per day.

Dose for treating Rheumatoid arthritis (off-label):

• Oral: 100 mg two per day

Minocycline (Minocin) Dose in the treatment of Syphilis:

• Oral, IV: Initial dose of 200 mg; maintenance dose of 100 mg twice daily for 10–15 days.

Minocycline Dose in Children:

Minocycline (Minocin) general dosing for susceptible infections:

• Children >8 years and Adolescents:

  • Oral:
    • Immediate-release formulations: At first, a dose of 4 mg/kg once (maximum: 200 mg), followed by 2 mg/kg twice day (maximum: 100 mg/dose).
  • IV: Initial: Maximum daily dose: 400 mg, given as 4 mg/kg once (maximum dose: 200 mg) and 2 mg/kg twice (maximum dose: 100 mg/dose).

Dose for treating moderate to severe non-nodular inflammatory acne:

Note: Higher doses can cause immediate vestibular adverse effects but do not increase efficacy. It shouldn't be used as a monotherapy for acne vulgaris due to increasing resistance patterns. Formulations for immediate release:

• Children ≥8 years and Adolescents:
  • Oral: 50–100 mg once or twice daily along with topical therapy (eg, benzoyl peroxide)
  • Therapy must last for 4 to 8 weeks to determine the patient's initial clinical response; longer therapy sessions are needed for the greatest impact (3 - 6 months).

• Extended-release formulations:

  • Children ≥12 years and Adolescents: Oral: ~1 mg/kg/dose once a day for 12 weeks.

Minocycline product-specific dosing:

• Extended-release capsule: Ximino: Oral:

  • 45 - 59 kg: 45 mg per day.
  • 60 - 90 kg: 90 mg per day.
  • 91 - 136 kg: 135 mg per day.

• Extended-release tablet:

  • Minolira: Oral:
    • 45 - 59 kg:5 mg (one-half of the 105 mg tablet) per day.
    • 60 - 89 kg: 5 mg (one-half of the 135 mg tablet) per day.
    • 90 - 125 kg: 105 mg per day.
    • 126 - 136 kg: 135 mg per day.
  • CoreMino, Solodyn: Oral:
    • 45 - 49 kg: 45 mg per day.
    • 50 - 59 kg: 55 mg per day.
    • 60 - 71 kg: 65 mg per day.
    • 72 - 84 kg: 80 mg per day.
    • 85 - 96 kg: 90 mg per day.
    • 97 - 110 kg: 105 mg per day.
    • 111 - 125 kg: 115 mg per day.
    • 126 - 136 kg: 135 mg per day.

Minocycline (Minocin) dose in the treatment of Skin and soft tissue infection (ie, purulent cellulitis), community-acquired MRSA:

Note: It should be administered for the time determined by the clinical response; the typical duration for outpatient cellulitis is 5 to 10 days.

• Children >8 years and Adolescents:

  • Immediate-release formulations: Oral: Initial: 2 mg/kg/dose (maximum dose: 100 mg/dose) twice daily, followed by 4 mg/kg (highest dose: 200 mg).

Pregnancy Risk Category: D

• The placenta is exposed to minocycline.
• Tetracyclines, such as minocycline, can build up in the long tubular bone tissue and the fetus's growing teeth.
• It can result in infants' limb delay, deformity, and persistent tooth yellowing, greying, or browning after maternal exposure in gestation.
• Tetracyclines are second-line antibiotics and should be avoided in pregnancy.
• Minocycline should not be used to treat Rocky Mountain Spotted Fever or Q fever in pregnant women.
• For acne during pregnancy use alternate agents
• Seminal fluid contains minocycline. Minocycline was not intended to be used by males or women trying to conceive.

Use during breastfeeding:

• Breast milk contains minocycline
• Oral absorption doesn't change with the use of dairy products. Therefore, oral absorption for minocycline is not affected by calcium in maternal milk.
• The decision to continue nursing during therapy should take into account both the advantages for the mother and the risks to the baby, according to the product's maker.
• Tetracyclines, as a class, are not recommended for nursing mothers because they can permanently stain infant's teeth.
• Sources note that breastfeeding can be continued during tetracycline therapy, but they recommend using alternative medications whenever possible.
• Others note that some short-term exposure is acceptable. However, breast-feeding mothers should avoid long-term use (e.g., to treat acne).
• Breast milk antibiotics can cause non-dose-related changes in the bowel flora.
• Monitor infants for GI disorders.

Dose in Kidney Disease:

• IV:

  • CrCl ≥80 mL/minute: No change in dose is necessary.
  • CrCl <80 mL/minute:  Never go beyond 200 mg per day.

• Oral:

  • Immediate release:

    • CrCl ≥80 mL/minute: No change in dose is necessary.
    • CrCl <80 mL/minute: Never go beyond 200 mg per day.
  • Extended-release: No dose change has been mentioned in the labelling by the manufacturer. It is possible to think about decreasing the dose or lengthening the gap.

Dose in Liver disease:

The manufacturer has not provided any dose adjustment in labeling; however, hepatotoxicity has been reported. Use cautiously

Side Effects of Minocycline (Minocin):

• Central nervous system:

  • Dizziness
  • Fatigue
  • Malaise
  • Drowsiness

• Dermatologic:

  • Pruritus
  • Urticaria

• Neuromuscular & skeletal:

  • Arthralgia

• Otic:

  • Tinnitus

Less common side effects:

• Cardiovascular:

  • Myocarditis
  • Vasculitis

• Central nervous system:

  • Intracranial hypertension
  • Vertigo

• Dermatologic:

  • Skin photosensitivity
  • Skin rash

• Gastrointestinal:

  • Diarrhea
  • Discoloration of permanent tooth
  • Enamel hypoplasia

• Hematologic & oncologic:

  • Lymphadenopathy

• Renal:

  • Nephritis

• Miscellaneous:

  • Fever

Contraindications to Minocycline (Minocin):

• severe allergic reaction to one or more of the tetracyclines or to any component of this combination

Canadian labeling: Additional contraindications not in the US labeling

• Grave liver disease
• Failure of the renal system
• Myasthenia gravis
• Children under 13 years old
• Pregnancy
• Breastfeeding

Warnings and precautions

• Autoimmune syndromes:

  • Autoimmune disorders such as lupus-like, liver disease, and vasculitis, which can include serum sickness, may be present
  • If autoimmune symptoms occur, discontinue use
  • Examine liver functions, ANA and complete blood count.

• Intracrânal hypertension benign (eg pseudotumor cerebri [PTC]).

  • It may cause headaches, diplopia, blurred or lost vision, papilledema, and/or intracranial hypertension (Pseudotumor Cerebri).
  • The most vulnerable groups to pseudotumor cerebri are those who use oral contraceptives, are fat or pregnant, have a history of cerebral hypertension, or who are pregnant.
  • It is best to avoid the simultaneous use of isotretinoin and tetracycline, which are known to cause pseudotumor cebri [PTC]).
  • If the drug is not stopped promptly, permanent vision loss is possible.
  • It is important to seek prompt medical attention if you experience visual symptoms.
  • Patients should be monitored until intracranial pressure stabilizes.

• CNS effects

  • Use of it can cause dizziness, lightheadedness, vertigo, and other symptoms. Patients should be cautious about driving or engaging in activities that require high mental alertness.
  • With discontinuation, symptoms can be relieved.

• Hepatotoxicity:

  • Use of acne treatment can lead to hepatotoxicity in varying degrees, including irreversible drug-induced liver damage and fatal fulminant heart failure.

• Hyperpigmentation

  • Hyperpigmentation may result from its use. This includes nails, bones, skin (including scar or injury sites), eyes and sclerae.
  • Dose and duration do not affect skin or oral hyperpigmentation.

• Hypersensitivity

  • Anaphylaxis has reportedly occurred. Take quick action to stop using the medication, then support yourself.

• Increased BUN

  • Patients with impaired renal function should be cautious when using it as it can raise serum BUN levels due to its anti-anabolic properties.
  • Tetracyclines can cause acidosis, hyperphosphatemia, azotemia, acidosis, drug accumulation, and possible hepatotoxicity.

• Photosensitivity

  • Photosensitivity patients who experience skin erythema or photosensitivity should stop using it.
  • Avoid using tanning equipment.
  • Avoid prolonged sun exposure and use sunscreen to protect your skin.

• Skin rash

  • There are many possible causes of skin rash, including Stevens-Johnson syndrome, erythema multiforme and eosinophilia.
  • After discontinuing the drug, symptoms may persist for several weeks.
  • In up to 10% of cases, it can be fatal
  • If you suspect DRESS syndrome, discontinue use immediately.

• Superinfection

  • Long-term use of the drug can lead to super-infections, especially fungal or bacterial.
  • Pseudomembranous collitis and bacterial superinfection, such as clostridioides difficile-associated diarrhoea (CDAD), are potential side effects.
  • Clostridioides difficile -associated diarrhea (CDAD), can occur up to 2 months after the end of antibiotics.

• Hepatic impairment

  • Patients who already have kidney or liver illness are more likely to acquire hepatic impairment.
  • Avoid taking hepatotoxic drugs with you.

• Renal impairment

  • Patients with impaired renal function need to use it with caution.
  • Recommendations for adjustment of the dose

Minocycline (systemic): Drug Interaction

Monitoring parameters:

• Liver functions
• Renal function including BUN
• Serum magnesium in patients with renal impairment;
• if any symptoms of the autoimmune disorder: ANA, CBC
• Ophthalmologic evaluation if visual disturbances occur
• If used for syphilis, repeat serologic tests 3 months after treatment.

How to administer Minocycline (Minocin)?

Intravenous:

• Do not infuse rapidly, should be given > 60 minutes.
• Use parenteral route if orally can not be taken or tolerated.
• Prolonged IV administration cause thrombophlebitis

Oral:

• Both with and without meal is acceptable. In order to reduce the danger of esophageal irritation and ulcers, should be taken with plenty of fluid.
• Do not chew, crush, or break extended-release tablets or capsules; instead, swallow them whole.
• Splitting the 105 mg and 135 mg extended-release tablets of minolira is permitted.

Mechanism of action of Minocycline (Minocin):

Through attaching to the 30S or 50S ribosomal ribosome units of sensitive bacterium organisms, this tetracycline antibiotic prevents protein synthesis. It has no impact on how cell walls are made.

Absorption:

• Oral: Well absorbed

Distribution:

• Widely distributed to most body fluids, bile, and tissues
• Poor CNS penetration
• Deposits in fat for extended periods; V : 0.14 - 0.7 L/kg

Protein binding:

• 55% - 96%

Metabolism:

• Hepatic to inactive metabolites

Bioavailability:

• 90% - 100%

Half-life elimination:

• IV: 15 - 23 hours; 11 - 16 hours (hepatic impairment); 18 - 69 hours (renal impairment)
• Oral: 16 hours (range: 11 - 17 hours)

Time to peak:

• Capsule, pellet filled: 1 - 4 hours;
• Tablet: 1 - 3 hours;
• Extended release tablet: 3.5 - 4 hours

Excretion:

• Urine (5% - 12% excreted unchanged)
• feces (20% to 34%).

International Brand Names of Minocycline:

• CoreMino
• Minocin
• Minolira
• Solodyn
• Ximino
• CO Minocycline
• DOM-Minocycline
• Minocycline-100
• Minocycline-50
• MYLANMinocycline
• PHL-Minocycline
• PMS-Minocycline
• SANDOZ MInocycline
• SANDOZ Minocycline
• TEVA-Minocycline
• Acneclin
• Akamin
• Antinocil
• Bagomicina
• Borymycin
• Cyclimycin
• Cynomycin
• Delnil
• Dentomycin
• Haicin
• Klinomycin
• Klinotab
• Lederderm
• Melicin
• Mestacine
• Micromycin
• Minaxen
• Mino-50
• Minocin
• Minocin Akne
• Minocin MR
• Minoclin
• Minocyclin
• Minocyclin 50 Stada
• Minogran
• Minolin
• Minoline
• Minolox
• Minomycin
• Minosil
• Minostad
• Minot
• Minotab
• Minotab 50
• Minox
• Minoz MR
• Mirosin
• Mynocine
• Parocline
• Periocline
• Ximino

Minocycline Brand Names in Pakistan: