Cleeravue-M

Minocycline is a prescription antibiotic used to treat a variety of bacterial infections such as pneumonia, urinary tract infections, gonorrhea, chlamydia, Rocky Mountain spotted fever, and acne.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the other medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Minocycline may affect the way other medicines work, and other medicines may affect how minocycline works.

Especially tell your doctor if you take:

• birth control pills. Minocycline may make your birth control pills less effective. You could become pregnant. You should use a second form of birth control while taking minocycline.
• a blood thinner medicine.
• a penicillin antibiotic medicine. Minocycline and penicillins should not be used together.
• antacids that contain aluminum, calcium, or magnesium or iron-containing products.
• an acne medicine that contains isotretinoin (Amnesteem, Claravis, Sotret). Minocycline and isotretinoin should not be used together.

Ask your doctor or pharmacist if you are not sure if your medicine is one that is listed above.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of minocycline there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are breastfeeding or plan to breastfeed. Minocycline passes into your milk and may harm your baby. You and your doctor should decide if you will take minocycline or breastfeed. You should not do both.

• Store minocycline at room temperature between 59°F to 86°F (15°C to 30°C).
• Keep minocycline and all medicines out of the reach of children.

Minocycline is used to treat pimples and red bumps (non-nodular inflammatory lesions) that occur with moderate to severe acne vulgaris in patients 12 years of age and older.

Minocycline capsules are used to treat bacterial infections in many different parts of the body. It is also used to treat anthrax infection and other infections in patients who cannot receive penicillins.

Minocycline belongs to the class of medicines known as tetracycline antibiotics. It works by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections.

This medicine is available only with your doctor's prescription.

This section provides information on the proper use of a number of products that contain minocycline. It may not be specific to Cleeravue-M. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects. This medicine is not for long-term use.

This medicine comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Swallow the capsule, extended-release capsule, or tablet whole with water. Do not, crush, break, or chew it.

You may take this medicine with or without food. Taking this medicine with food may lower your chances of irritation or ulcers in your esophagus (tube that connects mouth to the stomach).

To help clear up your infection completely, keep taking this medicine for the full time of treatment, even if you begin to feel better after a few days. If you stop taking this medicine too soon, your symptoms may return.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For infections:
    • Adults—At first, 200 milligrams (mg) followed by 100 mg every 12 hours. Some patients may start at 2 or 4 capsules of 50 mg followed by one 50 mg capsule 4 times a day.
    • Children 8 years of age and older—Dose is based on body weight and must be determined by your doctor. The initial dose is usually 4 milligram (mg) per kilogram (kg) of body weight followed by 2 mg per kg of body weight every 12 hours. However, the dose should not be more than the usual adult dose.
    • Children younger than 8 years of age—Use is not recommended.
• For oral dosage forms (extended-release capsules or tablets):
  • For treatment of acne vulgaris:
    • Adults and children 12 years of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 1 milligram (mg) per kilogram (kg) of body weight per day for 12 weeks.
    • Children 8 to 12 years of age—Use and dose must be determined by your doctor.
    • Children younger than 8 years of age—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• blistering, peeling, or loosening of the skin
• blood in the urine or stools
• blurred or double vision
• bulging soft spot on the head of an infant
• chest pain, possibly moving to the left arm, neck, or shoulder
• confusion
• diarrhea
• dizziness or lightheadedness
• eye pain
• fast heartbeat
• general feeling of discomfort or illness
• general tiredness and weakness
• hives, itching, or skin rash
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• nausea or vomiting
• red skin lesions, often with a purple center
• severe headache
• severe stomach pain
• sores, ulcers, or white spots on the lips or in the mouth
• troubled breathing
• unusual bleeding or bruising
• upper right abdominal or stomach pain
• yellow eyes and skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Continuing ringing or buzzing or other unexplained noise in the ears
• difficulty with moving
• hearing loss
• hives or welts
• muscle stiffness
• redness of the skin
• sleepiness or unusual drowsiness

• Bloating
• discoloration of the tooth
• increased sensitivity of the skin to sunlight
• indigestion
• severe sunburn

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Applies to minocycline: oral capsule, oral capsule extended release, oral suspension, oral tablet, oral tablet extended release

Other dosage forms:

• intravenous powder for solution

Along with its needed effects, minocycline (the active ingredient contained in Cleeravue-M) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking minocycline:

• Black, tarry stools
• blistering, peeling, or loosening of the skin
• blood in the urine or stools
• blurred or double vision
• bulging soft spot on the head of an infant
• chest pain, possibly moving to the left arm, neck, or shoulder
• confusion
• diarrhea
• dizziness or lightheadedness
• eye pain
• fast heartbeat
• general feeling of discomfort or illness
• general tiredness and weakness
• hives, itching, or skin rash
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• nausea or vomiting
• red skin lesions, often with a purple center
• severe headache
• severe stomach pain
• sores, ulcers, or white spots on the lips or in the mouth
• troubled breathing
• unusual bleeding or bruising
• upper right abdominal or stomach pain
• yellow eyes and skin

Some side effects of minocycline may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Continuing ringing or buzzing or other unexplained noise in the ears
• difficulty with moving
• hearing loss
• hives or welts
• muscle stiffness
• redness of the skin
• sleepiness or unusual drowsiness

• Bloating
• discoloration of the tooth
• increased sensitivity of the skin to sunlight
• indigestion
• severe sunburn

Applies to minocycline: intravenous powder for injection, oral capsule, oral suspension, oral tablet, oral tablet extended release, oral and topical kit

Nervous system

Headache, dizziness, vertigo. and ataxia have been reported. These side effects were reversible within 3 to 48 hours of stopping therapy and occurred less often with low doses.

Pseudotumor cerebri, bulging fontanels (infants), and decreased hearing have also been reported during postmarketing experience.[Ref]

Very common (10% or more): Headache (up to 23%)
Common (1% to 10%): Dizziness (lightheadedness), somnolence, tinnitus, vertigo
Rare (0.01% to 0.1%): Hypoesthesia, paresthesia, intracranial hypertension, impaired/decreased hearing
Very rare (less than 0.01%): Bulging fontanels (in infants)
Frequency not reported: Convulsions, sedation, ataxia, benign intracranial hypertension (pseudotumor cerebri), vestibular reactions[Ref]

Dermatologic

Hyperpigmentation of various body sites (including the skin, nails, teeth, oral mucosa, bones, thyroid, eyes [including sclera, conjunctiva], breast milk, lacrimal secretions, perspiration) has been reported. This blue/black/grey or muddy-brown discoloration was localized or diffuse. The most common site was the skin. Pigmentation often reversed when the drug was discontinued; however, resolution took several months or persisted in some cases. The generalized muddy-brown skin pigmentation sometimes persisted, especially in areas exposed to sun.

Biopsies of pigmented tissue have shown granules within the cells which stained positive for iron. This pigmentation faded over time after drug discontinuation.

DRESS syndrome (including fatal cases) has been reported. DRESS syndrome with persistent myocarditis has been reported in at least 3 cases.

Fixed drug eruptions, erythema multiforme, Stevens-Johnson syndrome, and photosensitivity have also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Pruritus, urticaria
Rare (0.01% to 0.1%): Alopecia, erythema multiforme, erythema nodosum, fixed drug eruptions, hyperpigmentation (brownish or bluish-black pigmentation) of skin, photosensitivity, rash, vasculitis
Very rare (less than 0.01%): Angioedema, exfoliative dermatitis, hyperpigmentation of nails/nail beds, Stevens-Johnson syndrome, toxic epidermal necrolysis
Frequency not reported: Hyperpigmentation of various body sites (including bones, mucous membranes, teeth, oral mucosa, tongue, thyroid, eyes [including sclera, conjunctiva], breast milk, lacrimal secretions, structures of inner organs), maculopapular rash, erythematous rash, discolored perspiration, Sweet's syndrome (acute febrile neutrophilic dermatosis)
Postmarketing reports: Anaphylactoid purpura, pigmentation of skin and mucous membranes, angioneurotic edema, drug rash with eosinophilia and systemic symptoms (DRESS)[Ref]

Gastrointestinal

Pancreatitis has rarely been associated with use of this drug. In 2 case reports, cystic fibrosis patients experienced pancreatitis during treatment with this drug for acute bacterial exacerbations of respiratory disease. The authors suggested that cystic fibrosis patients, as a result of the disease process, may be more susceptible to drug-induced pancreatitis. Additionally, in at least 1 case, multiple concomitant medications were taken; therefore, a temporal relationship between this drug and pancreatitis could not be proven conclusively.

Esophagitis and esophageal ulcerations have been reported in patients taking the capsule or tablet formulations of tetracycline-class antibiotics. Most of these patients took the drug immediately before going to bed.

Enterocolitis, pancreatitis, glossitis, dysphagia, and tooth discoloration have also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Dry mouth
Rare (0.01% to 0.1%): Diarrhea, nausea, stomatitis, discoloration of teeth, vomiting
Very rare (less than 0.01%): Oral and anogenital candidiasis, dyspepsia, dysphagia, enamel hypoplasia, enterocolitis, esophagitis, esophageal ulcerations, glossitis, pancreatitis, pseudomembranous colitis
Frequency not reported: Antibiotic-associated colitis, oral cavity discoloration (including buccal mucosa, tongue, lip, gum), abdominal cramping, inflammatory lesions (with monilial overgrowth) in the oral and anogenital regions[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia, myalgia
Rare (0.01% to 0.1%): Lupus-like syndrome (consisting of positive antinuclear antibody [ANA], arthralgia, arthritis, joint stiffness/swelling, and at least 1 of the following: fever, myalgia, hepatitis, rash, vasculitis)
Very rare (less than 0.01%): Arthritis, bone discoloration, systemic lupus erythematosus (SLE), exacerbation of SLE, joint stiffness, joint swelling, joint discoloration, myopathy, hypersensitivity-associated rhabdomyolysis
Postmarketing reports: Polyarthralgia, exacerbation of systemic lupus, transient lupus-like syndrome[Ref]

Lupus-like reactions induced by this drug have commonly presented with arthralgia or arthritis, myalgia or malaise, and positive ANA titer. Patients with highly positive anti-double stranded DNA (anti-dsDNA) antibodies have rarely been reported. All patients recovered after the drug was discontinued; however, several required short courses of corticosteroids.

Severe acute myopathy associated with this drug (100 mg orally per day) occurred in a 17-year-old male after strenuous exercise. His laboratory values were as follows: ESR 33 mm/hr, CRP 0.84 mg/dL, creatine kinase 87,297 units/L, AST 1307 units/L, ALT 311 units/L, LDH 4935 units/L, aldolase 12.6 units/L, alkaline phosphatase 145 units/L, GGT 66 units/L. Muscle enzyme levels normalized and his symptoms resolved 1 month after this drug was discontinued.

IV minocycline plus quinupristin-dalfopristin were associated with myalgia and arthralgia in 36% of neutropenic cancer patients (n=56).[Ref]

Other

Common (1% to 10%): Fatigue, malaise
Uncommon (0.1% to 1%): Fever
Very rare (less than 0.01%): Discoloration of secretions

Injection:
-Frequency not reported: Magnesium intoxication (including flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and CNS depression, respiratory paralysis)[Ref]

Psychiatric

Common (1% to 10%): Mood alteration

Hypersensitivity

Death has been reported in some cases involving hypersensitivity syndrome, serum sickness-like syndrome, and lupus-like syndrome.

Pulmonary infiltrates, night sweats, fever, and eosinophilia have developed in several patients receiving this drug. These effects were thought to be due to drug hypersensitivity.

Case reports have described a severe CNS -pulmonary hypersensitivity syndrome requiring high-dose corticosteroid therapy. Signs and symptoms have included dry cough, fever, ataxia, muscle weakness, numbness, visual abnormalities, abnormal brain MRI, seizures, pulmonary infiltrates, elevated serum IgE, elevated erythrocyte sedimentation rate (ESR), and eosinophilia.

Eosinophilic pneumonia with relapsing acute respiratory failure requiring mechanical ventilation and corticosteroids has been reported in a 54-year-old woman. Initial symptoms included dry cough, low-grade fever, fatigue, and dyspnea. Eosinophilia, elevated leukocytes, and C-reactive protein (CRP) were noted. At 14 days after being discharged and resuming this drug, the patient developed rapidly progressive respiratory failure again requiring mechanical ventilation.

Late-onset drug fever (associated with fever, sore throat, abdominal pain, weakness, loose bloody stools, fatigue, 40-pound weight loss, ESR 99 mm/hr, CRP 5 mg/dL, and mild increases in liver enzymes) has been reported in a 15-year-old boy after using this drug for 24 months for acne. After 1 year of therapy, at least 1 other case of late-onset drug fever occurred. Other reported cases of drug fever generally occurred after 2 to 4 weeks of drug exposure.[Ref]

Rare (0.01% to 0.1%): Anaphylaxis/anaphylactoid reaction (including shock, fatalities)
Frequency not reported: Hypersensitivity, hypersensitivity syndrome (consisting of cutaneous reaction [e.g., rash, exfoliative dermatitis], eosinophilia, and at least 1 of the following: hepatitis, pneumonitis, nephritis, myocarditis, pericarditis; with or without fever, lymphadenopathy), serum sickness-like syndrome (consisting of fever, urticaria/rash, arthralgia, arthritis, joint stiffness/swelling, lymphadenopathy; with or without eosinophilia), autoimmune vasculitis, drug fever, eosinophilic pneumonitis, drug hypersensitivity (e.g., pulmonary infiltrates, night sweats, fever, eosinophilia), serum sickness, serum sickness-like reactions, severe central nervous system (CNS)-pulmonary hypersensitivity syndrome
Postmarketing reports: Hypersensitivity reactions, anaphylaxis[Ref]

Immunologic

Frequency not reported: Positive antineutrophil cytoplasmic antibody (ANCA) titers, polyarteritis nodosa, ANCA-positive crescentic glomerulonephritis, ANCA-positive vasculitis, autoimmune hepatitis, necrotizing vasculitis and systemic reactions[Ref]

Rare cases of necrotizing vasculitis and systemic reactions have been reported, characterized by lymphadenopathy, eosinophilia, increased liver function enzyme levels, and dermatologic involvement. In each case, this drug was discontinued and in some cases, corticosteroid therapy was necessary to assist in the resolution of symptoms.[Ref]

Hepatic

Some hepatic reactions had an autoimmune basis and occurred after several months of therapy.

In 1 case, a patient developed rapidly progressing liver failure after using this drug for 4 weeks for acne. The patient had stopped this drug 2 weeks prior to onset of malaise. Liver transplantation was considered, but the patient slowly recovered without significant intervention.

Other reports of immunologically-mediated progressive liver dysfunction have rarely occurred. In 1 case, a patient received a liver transplant after fulminant hepatic failure which was thought to be related to a 3-year history of daily therapy to treat acne. The dose of this drug ranged from 50 to 200 mg/day. A second patient had been using this drug to treat acne for 1 year just prior to seeking medical attention for an "influenza-like" syndrome. Upon hospitalization, it was determined that the patient was experiencing an autoimmune-mediated hepatitis, most probably related to this drug. Resolution of symptoms occurred in both of these cases after therapy was discontinued and each patient had received appropriate supportive medical care.

Hepatitis and liver failure have also been reported during postmarketing experience.[Ref]

Rare (0.01% to 0.1%): Increased liver enzymes, hepatitis, autoimmune hepatitis/hepatotoxicity
Very rare (less than 0.01%): Hepatic cholestasis, hepatic failure (including fatalities), hyperbilirubinemia, jaundice
Frequency not reported: Autoimmune hepatitis with lupus-like symptoms, increased liver function test values, acute hepatic failure, liver injury, acute hypersensitivity hepatitis associated with eosinophilia and dermatitis[Ref]

Renal

Rare (0.01% to 0.1%): Increased BUN/serum urea, interstitial nephritis, acute renal failure
Postmarketing reports: Reversible acute renal failure

Tetracyclines:
-Frequency not reported: Aggravation of preexisting renal failure, azotemia/uremia, nephrotoxicity (associated with acute fatty liver), renal tubular damage, Fanconi-like syndrome[Ref]

Nephrotoxicity associated with acute fatty liver has been reported with high tetracycline doses. High serum levels of tetracyclines have been associated with azotemia, hyperphosphatemia, and acidosis in patients with renal dysfunction.

Degraded tetracycline may cause renal tubular damage and a Fanconi-like syndrome.[Ref]

Hematologic

Rare (0.01% to 0.1%): Eosinophilia, leukopenia, neutropenia, thrombocytopenia
Very rare (less than 0.01%): Hemolytic anemia, pancytopenia
Frequency not reported: Agranulocytosis, antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis[Ref]

Hemolytic anemia, thrombocytopenia, and eosinophilia have also been reported during postmarketing experience.[Ref]

Respiratory

Rare (0.01% to 0.1%): Cough, dyspnea, pulmonary infiltration
Very rare (less than 0.01%): Bronchospasm, exacerbation of asthma, pulmonary eosinophilia
Frequency not reported: Pneumonitis, hypersensitivity pneumonitis, pulmonary lupus, eosinophilic pneumonia, pleural effusions, relapsing acute respiratory failure
Postmarketing reports: Pulmonary infiltrates with eosinophilia[Ref]

Cardiovascular

Rare (0.01% to 0.1%): Myocarditis, pericarditis[Ref]

Metabolic

High serum levels of tetracyclines have been associated with azotemia, hyperphosphatemia, and acidosis in patients with renal dysfunction.[Ref]

Rare (0.01% to 0.1%): Anorexia

Tetracyclines:
-Frequency not reported: Hyperphosphatemia, acidosis[Ref]

Endocrine

Very rare (less than 0.01%): Abnormal thyroid function, brown-black microscopic thyroid discoloration
Frequency not reported: Discolored breast secretions[Ref]

A condition characterized by dark pigmentation (brown-black microscopic discoloration) of the thyroid gland has been reported; however, there was no clinical or laboratory evidence of thyroid dysfunction (unknown clinical implications).

Brown-black microscopic thyroid discoloration and abnormal thyroid function have also been reported during postmarketing experience.[Ref]

Genitourinary

Very rare (less than 0.01%): Balanitis (due to lesions on the glans penis), vulvovaginitis
Postmarketing reports: Deleterious effects on spermatogenesis[Ref]

Balanitis has also been reported during postmarketing experience.[Ref]

Local

Frequency not reported: Injection site erythema, injection site pain[Ref]

Oncologic

Frequency not reported: Papillary thyroid cancer
Postmarketing reports: Thyroid cancer

Ocular

Frequency not reported: Discoloration of conjunctiva, discoloration of lacrimal secretions, grey scleral pigmentation, macular pigmentation[Ref]

Cases of grey scleral pigmentation and macular pigmentation have been reported in elderly patients after chronic use of this drug (5 to 12 years).[Ref]

Some side effects of Cleeravue-M may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.