Minocin (Minocycline)

Minocycline hydrochloride

Minocycline is a semisynthetic tetracycline antibiotic derived from tetracycline.

Dosage and administration

Reconstitution and administration

Minocycline hydrochloride is usually taken by mouth. If oral treatment is not possible, it may be given by IV infusion; however, oral treatment should replace IV treatment as soon as possible. If minocycline is given IV, the risk of thrombophlebitis should be taken into account.

Minocycline hydrochloride capsules, pellet-filled capsules, or oral suspension may be taken with or without food. To reduce the risk of oesophageal irritation and ulceration, minocycline hydrochloride capsules or pellet-filled capsules should be taken with plenty of fluid and should not be taken at bedtime or by patients with oesophageal obstruction or compression.

Minocycline hydrochloride sterile powder is reconstituted by adding 5 mL of sterile water for injection to the vial labelled as containing 100 mg of minocycline to provide a solution containing 20 mg/mL. Each 100 mg of minocycline must then be diluted before administration with 500 mL to 1 litre of compatible IV infusion fluid to provide solutions containing 100-200 mcg/mL. Diluted IV solutions should be given immediately after preparation and are usually infused over 6 hours.

Dosage

The dosage of minocycline hydrochloride is expressed in terms of minocycline and is the same for either route of administration. The usual adult oral or IV dose of minocycline is 200 mg initially, followed by 100 mg every 12 hours.

Alternatively, if more frequent dosing is preferred, the manufacturer states that adults may receive 100-200 mg of minocycline initially, followed by 50 mg 4 times daily. The usual oral or IV dose of minocycline for children older than 8 years is 4 mg/kg initially, followed by 2 mg/kg every 12 hours.

Asymptomatic meningococcus carriers

To eliminate meningococci from the nasopharynx of asymptomatic Neisseria meningitidis carriers when the risk of meningococcal disease is high, the manufacturer states that 100 mg of oral minocycline should be given every 12 hours for 5 days; however, in the UK, public health guidance generally recommends other agents (for example, rifampicin, ceftriaxone, ciprofloxacin) for chemoprophylaxis in close contacts of people with invasive meningococcal disease.

Leprosy

For the treatment of multibacillary leprosy in adults who cannot receive rifampicin because of side effects, intercurrent disease (for example, chronic hepatitis), or infection with rifampicin-resistant Mycobacterium leprae, the World Health Organization (WHO) recommends supervised treatment with a regimen of clofazimine (50 mg daily), ofloxacin (400 mg daily), and minocycline (100 mg daily) for 6 months, followed by clofazimine (50 mg daily) and minocycline (100 mg daily) for at least a further 18 months.

For the treatment of multibacillary leprosy in adults who will not accept or cannot tolerate clofazimine, the WHO recommends supervised treatment with a once-monthly rifampicin-based multidrug regimen (ROM) that includes rifampicin (600 mg once monthly), ofloxacin (400 mg once monthly), and minocycline (100 mg once monthly) for 24 months.

For single-lesion paucibacillary leprosy in certain patient groups, the WHO currently states that adults may receive a single-dose rifampicin-based multidrug regimen (ROM) consisting of a single 600-mg dose of rifampicin, a single 400-mg dose of ofloxacin, and a single 100-mg dose of minocycline. For paediatric patients, children 5-14 years of age may receive a single 300-mg dose of rifampicin, a single 200-mg dose of ofloxacin, and a single 50-mg dose of minocycline; children younger than 5 years should receive an appropriately adjusted dose of each drug.

Other mycobacterial infections

Although the manufacturer states that the optimum dosage has not been established, granulomas of the skin caused by Mycobacterium marinum have been successfully treated with 100 mg of oral minocycline every 12 hours for 6-8 weeks. In UK practice, oral minocycline 100 mg twice daily may be used for at least 3 months for cutaneous M. marinum infections, and a minimum of 4-6 weeks of treatment is generally needed to assess whether the infection is responding.

Gonorrhoea and associated infections

The manufacturer states that uncomplicated gonorrhoea (other than urethritis and anorectal infections in men) may be treated with 200 mg of oral minocycline initially, followed by 100 mg every 12 hours for a minimum of 4 days; follow-up cultures should be done within 2-3 days after completion of treatment. For uncomplicated gonococcal urethritis in adult males, the manufacturer states that oral minocycline 100 mg every 12 hours for 5 days may be used. However, tetracyclines are not included in current UK guidance for the treatment of gonorrhoea, and doxycycline is the preferred tetracycline for presumptive treatment of coexisting chlamydial infection when indicated.

Syphilis

The manufacturer states that the usual oral minocycline dose may be given for 10-15 days for the treatment of syphilis; close follow-up and laboratory tests are recommended. However, parenteral penicillin G is the treatment of choice for all stages of syphilis, and in UK practice doxycycline is generally the preferred tetracycline-based alternative for non-pregnant patients who are allergic to penicillin.

Chlamydial and mycoplasmal infections

For nongonococcal urethritis caused by Chlamydia trachomatis or Ureaplasma urealyticum, the manufacturer states that adults may receive oral minocycline 100 mg every 12 hours for at least 7 days. However, in the UK, doxycycline is generally the preferred tetracycline for the treatment of nongonococcal urethritis.

Pleural effusions

When used intrapleurally as a sclerosing agent to control pleural effusions associated with metastatic tumours, 300 mg of minocycline has reportedly been diluted with 40-50 mL of 0.9% sodium chloride injection and instilled into the pleural space through a thoracostomy tube, followed by clamping of the tube and subsequent removal of the fluid.

Cholera

For the treatment of cholera together with fluid and electrolyte replacement, an initial 200-mg oral dose of minocycline has been given followed by 100-mg oral doses every 12 hours for 48-72 hours.

Nocardiosis

For the treatment of nocardiosis, the usual oral minocycline dose has been given together with a sulfonamide for 12-18 months.

Acne

As an additional treatment for inflammatory acne vulgaris that has not responded to oral tetracycline hydrochloride or oral erythromycin, 50 mg of minocycline has been given by mouth 1-3 times daily.

Rheumatoid arthritis

When used in the management of rheumatoid arthritis, adults have received oral minocycline 100 mg twice daily. A benefit may be seen 1-3 months after starting minocycline treatment.

Dosage in renal impairment

In patients with renal impairment, doses and/or frequency should be reduced according to the degree of impairment. One manufacturer states that the total daily oral dose should not exceed 200 mg in patients with impaired renal function.

Cautions

Side effects affecting the central nervous system (for example, vestibular reactions) occur more often with minocycline than with other tetracyclines. The true incidence has not been determined. Previously, vestibular symptoms were reported in up to 21% of patients treated with minocycline. However, some studies indicate these reactions may occur in 30-90% of patients treated with usual doses of minocycline.

Pharmacokinetics

In all studies described below, minocycline was administered as the hydrochloride salt.

Absorption

Approximately 90-100% of an oral dose of minocycline hydrochloride is absorbed from the gastrointestinal tract in fasting adults. Following oral administration in fasting adults with normal renal function, peak serum concentrations are reached within 1-4 hours and average 2-3.5 mcg/mL following a single 200-mg dose. In one study, after an initial 200-mg oral dose followed by 100-mg doses every 12 hours, steady-state serum concentrations averaged 2.3-3.5 mcg/mL.

When given as pellet-filled capsules to healthy adults immediately after a standardised meal containing dairy products, peak plasma concentrations were slightly lower (11%) and delayed by about 1 hour compared with fasting adults; however, the extent of absorption (AUC) was similar in fed and fasting individuals.

Gastrointestinal absorption from oral dosage forms other than pellet-filled capsules may be reduced by up to 20% by food and/or milk; however, this effect is usually not clinically important. Because tetracyclines chelate divalent or trivalent cations (for example, aluminium, calcium, iron, magnesium), taking antacids or other products containing these cations by mouth at the same time may decrease absorption.

Following IV infusion over 1 hour of 200 mg of minocycline in adults with normal renal function, serum concentrations averaged 4.2 mcg/mL immediately after the infusion, 2 mcg/mL at 6 hours, and 1.4 mcg/mL at 12 hours.

Elimination

The serum half-life of minocycline is 11-26 hours in adults with normal renal function. In one study, the half-life was about 17 hours after a single dose and 21 hours after multiple doses. In a limited number of patients with hepatic dysfunction, the serum half-life reportedly ranged from 11-16 hours.

Although study results are conflicting, most data indicate that serum half-life is not significantly affected by renal function. In severe renal impairment, the half-life is generally reported to be 12-30 hours following single or multiple doses.

In patients with normal renal function, approximately 4-19% of a single oral or IV dose is excreted in urine and 20-34% is excreted in faeces within 72 hours as active drug. Some studies indicate that minocycline, unlike other tetracyclines, is partially metabolised to at least 6 metabolites.

Chemistry and stability

Chemistry

Minocycline is a semisynthetic tetracycline antibiotic derived from tetracycline. It is commercially available as the hydrochloride salt in oral powder- or pellet-filled capsules, an oral suspension, or sterile powder. Minocycline hydrochloride occurs as a yellow, crystalline powder and is soluble in water and slightly soluble in alcohol. After reconstitution with sterile water for injection, solutions have a pH of 2-2.8.

Stability

Minocycline hydrochloride capsules should be stored at 15-30°C (59-86°F) and pellet-filled capsules at 20-25°C (68-77°F). These preparations should be protected from light, moisture, and excessive heat. Minocycline hydrochloride oral suspension should be stored at 20-25°C (68-77°F) and should not be frozen.

Minocycline hydrochloride for injection should be stored at 15-30°C (59-86°F) and protected from light. After reconstitution, solutions containing 20 mg/mL are stable for 24 hours at room temperature. Minocycline hydrochloride is compatible with the following IV fluids: 0.9% sodium chloride, 5% dextrose, 5% dextrose and 0.9% sodium chloride, Ringer's, or lactated Ringer's. Although minocycline is compatible with Ringer's and lactated Ringer's, it should not be mixed with other IV fluids containing calcium because precipitation may occur.