Minolira

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.

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:

Incidence not known

• 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:

Less common

• 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

Incidence not known

• 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.

Minolira extended-release tablets are white to off-white, functionally scored, rectangular tablets with brown or gold color speckles and a single score line on both surfaces. Minolira are available in the following two strengths.

• 105 mg extended-release tablets: ‘M1’debossed on one surface, where ‘M’ and ‘1’ are on either side of the score line. Each tablet contains 105 mg minocycline, equivalent to 113.4 mg of minocycline hydrochloride. ·

• 135 mg extended-release tablets: ‘M3’ is debossed on one surface, where ‘M’ and ‘3’ are on either side of the score line. Each tablet contains 135 mg minocycline, equivalent to 145.8 mg of minocycline hydrochloride.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.  

The following table summarizes selected adverse reactions reported in clinical trials at a rate of ≥1% for minocycline hydrochloride extended release tablets.

Table 2: Selected Treatment-Emergent Adverse Reactions in at least 1% of Clinical Trial

Adverse Reactions	Minocycline Hydrochloride Extended-Release Tablets	Placebo
	(1 mg/kg)	N = 364
	N = 674(%)	(%)
At least one treatment­	379 (56)	197 (54)
emergent event
Headache	152 (23)	83 (23)
Fatigue	62 (9)	24 (7)
Dizziness	59 (9)	17 (5)
Pruritus	31 (5)	16 (4)
Malaise	26 (4)	9 (3)
Mood alteration	17 (3)	9 (3)
Somnolence	13 (2)	3 (1)
Urticaria	10 (2)	1 (0)
Tinnitus	10 (2)	5 (1)
Arthralgia	9 (1)	2 (0)
Vertigo	8 (1)	3 (1)
Dry mouth	7 (1)	5 (1)
Myalgia	7 (1)	4 (1)

6.2 Postmarketing Experience

Adverse reactions that have been reported with minocycline hydrochloride use in a variety of indications include:  

Skin and hypersensitivity reactions: fixed drug eruptions, balanitis, erythema multiforme, Stevens-Johnson syndrome, anaphylactoid purpura, photosensitivity, pigmentation of skin and mucous membranes, hypersensitivity reactions, angioneurotic edema, anaphylaxis, DRESS syndrome [see Warnings and Precautions (5.11)].

Autoimmune conditions: polyarthralgia, pericarditis, exacerbation of systemic lupus, pulmonary infiltrates with eosinophilia, transient lupus-like syndrome.

Central nervous system: pseudotumor cerebri, bulging fontanels in infants, decreased hearing.

Endocrine: brown-black microscopic thyroid discoloration, abnormal thyroid function.

Oncology: thyroid cancer.

Oral: glossitis, dysphagia, tooth discoloration.

Gastrointestinal: enterocolitis, pancreatitis, hepatitis, liver failure.

Genitourinary: Preliminary studies suggest that use of minocycline may have deleterious effects on human spermatogenesis [see Nonclinical Toxicology (13.1)].

Renal: reversible acute renal failure.

Hematology: hemolytic anemia, thrombocytopenia, eosinophilia.

Pregnancy

Risk Summary:

Minolira, like tetracycline class drugs, may cause permanent discoloration of teeth and reversible inhibition of bone growth when administered during pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)]. Post-marketing cases of minocycline use in pregnant women report congenital anomalies such as limb reductions. The limited data are not sufficient to inform a drug-associated risk for birth defects or miscarriage. In animal reproduction studies, minocycline induced skeletal malformations in fetuses when orally administered to pregnant rats and rabbits during the period of organogenesis at systemic exposure of approximately 3 times and 2 times, respectively, the systemic exposure to minocycline observed in patients administered Minolira (see Data). If a patient becomes pregnant while taking this drug, advise the patient of the risk to the fetus and discontinue treatment.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.  

Data  

Human Data

The use of tetracycline during tooth development (second and third trimesters of pregnancy) may cause permanent discoloration of deciduous teeth. This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses.  

Animal Data

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development of the developing fetus. [see Warnings and Precautions (5.1)].  

Minocycline induced skeletal malformations (bent limb bones) in fetuses when administered to pregnant rats and rabbits during the period of organogenesis at doses of 30 mg/kg/day and 100 mg/kg/day, respectively, (resulting in approximately 3 times and 2 times, respectively, the systemic exposure to minocycline observed in patients administered Minolira). Reduced mean fetal body weight was observed when minocycline was administered to pregnant rats during the period of organogenesis at a dose of 10 mg/kg/day (which resulted in approximately the same level of systemic exposure to minocycline as that observed in patients administered Minolira).  

Minocycline was assessed for effects on peri- and post-natal development of rats in a study that involved oral administration to pregnant rats during the period of organogenesis through lactation , at doses of 5, 10, or 50 mg/kg/day. In this study, body weight gain was significantly reduced in pregnant females that received 50 mg/kg/day (resulting in approximately 2.5 times the systemic exposure to minocycline observed in patients administered Minolira). No effects of treatment on the duration of the gestation period or the number of live pups born per litter were observed. Gross external anomalies observed in F1 pups (offspring of animals that received minocycline) included reduced body size, improperly rotated forelimbs, and reduced size of extremities. No effects were observed on the physical development, behavior, learning ability, or reproduction of F1 pups, and there was no effect on gross appearance of F2 pups (offspring of F1 animals).

Lactation

Risk Summary  

Tetracycline-class drugs including minocycline are present in breast milk. It is not known whether minocycline has an effect on the breastfed infant or on milk production. Because of the potential for serious adverse effects on bone and tooth development in breastfed infants from the tetracycline-class drugs, advise a woman that breastfeeding is not recommended with Minolira therapy [see Warnings and Precautions (5.1)].

Female and Males of Reproductive Potential

Contraception  

Minolira may reduce the effectiveness of low-dose oral contraceptives. Patients of reproductive potential should not rely on low-dose oral contraceptives as an effective contraceptive method, and should use an additional method of contraception during treatment with Minolira [see Drug Interactions (7.4)].

Infertility

Avoid using Minolira in males who are attempting to conceive a child. Limited human studies suggest that minocycline may have a deleterious effect on spermatogenesis. In a fertility study in rats, minocycline adversely affected spermatogenesis when orally administered to male rats at doses resulting in approximately 15 to 40 times the level of systemic exposure to minocycline observed in patients administered Minolira [see Nonclinical Toxicology (13.1)].

Pediatric Use

The safety and effectiveness of Minolira have been established in pediatric patients 12 years of age and older for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris [see Pharmacokinetics (12.3) and Clinical Studies (14)]. Tooth discoloration and inhibition of bone growth have been observed in pediatric patients [see Warnings and Precaution (5.2, 5.3)]. The safety and effectiveness of Minolira have not been established in pediatric patients less than 12 years of age.

Geriatric Use

Clinical studies of Minolira did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female rats once daily for up to 104 weeks at dosages up to 200 mg/kg/day, minocycline hydrochloride was associated in both genders with follicular cell tumors of the thyroid gland, including increased incidences of adenomas, carcinomas and the combined incidence of adenomas and carcinomas in males, and adenomas and the combined incidence of adenomas and carcinomas in females. In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female mice once daily for up to 104 weeks at dosages up to 150 mg/kg/day, exposure to minocycline hydrochloride did not result in a significantly increased incidence of neoplasms in either males or females.  

Minocycline was not mutagenic in vitro in a bacterial reverse mutation assay (Ames test) or CHO/HGPRT mammalian cell assay in the presence or absence of metabolic activation. Minocycline was not clastogenic in vitro using human peripheral blood lymphocytes or in vivo in a mouse micronucleus test.  

Male and female reproductive performance in rats was unaffected by oral doses of minocycline of up to 300 mg/kg/day (which resulted in up to approximately 40 times the level of systemic exposure to minocycline observed in patients administered Minolira). However, oral administration of 100 or 300 mg/kg/day of minocycline to male rats (resulting in approximately 15 to 40 times the level of systemic exposure to minocycline observed in patients administered Minolira) adversely affected spermatogenesis. Effects observed at 300 mg/kg/day included a reduced number of sperm cells per gram of epididymis, an apparent reduction in the percentage of sperm that were motile, and (at 100 and 300 mg/kg/day) increased numbers of morphologically abnormal sperm cells. Morphological abnormalities observed in sperm samples included absent heads, misshapen heads, and abnormal flagella.

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instruction for Use).  

Advise patients of the following:

Teratogenic effects ·

• Advise patients to avoid use of Minolira during pregnancy.·

• Advise patients that Minolira use during pregnancy may cause inhibition of fetal bone growth. ·

• Advise patients that Minolira use during pregnancy may cause discoloration of deciduous teeth.·

• Advise patients to discontinue Minolira during pregnancy.

Tooth Discoloration ·

• Advise caregivers of pediatric patients that Minolira use may cause permanent discoloration of deciduous and permanent teeth.

Lactation ·

• Advise a woman that breast feeding is not recommended during Minolira therapy.

Contraception ·

• Advise patients of reproductive potential that Minolira may reduce the effectiveness of low-dose oral contraceptives. Advise patients of reproductive potential not rely on low-dose oral contraceptives as an effective contraceptive method and to use an additional method of contraception during treatment with Minolira.

Infertility ·

• Advise males of reproductive potential that Minolira may impair fertility.

Tissue Hyperpigmentation ·

• Inform patients that Minolira may cause discoloration of skin, scars, teeth or gums.

Pseudomembranous Colitis ·

• Advise patients that pseudomembranous colitis can occur with minocycline therapy, including Minolira. Advise patients to seek medical attention if they develop watery or bloody stools.

Hepatotoxicity ·

• Inform patients about the possibility of hepatotoxicity. Advise patients to seek medical advice if they experience symptoms or signs of hepatotoxicity, including loss of appetite, tiredness, diarrhea, jaundice, increased bleeding tendencies, confusion, and sleepiness.

Central Nervous System Effects ·

• Inform patients that central nervous system adverse reactions including dizziness or vertigo have been reported with minocycline therapy. Caution patients about driving vehicles or using hazardous machinery if they experience such symptoms while on Minolira.

Intracranial Hypertension ·

• Inform patients that intracranial hypertension can occur with minocycline therapy. Advise patients to seek medical attention if they develop unusual headache, visual symptoms, such as blurred vision, diplopia, and vision loss. ·

• Inform patients that autoimmune syndromes, including drug-induced lupus-like syndrome, autoimmune hepatitis, vasculitis and serum sickness have been observed with tetracycline-class drugs, including minocycline. Symptoms may be manifested by arthralgia, fever, rash and malaise. ·

• Advise patients who experience such symptoms to stop the drug immediately and seek medical help.

Photosensitivity ·

• Inform patients that photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including minocycline. ·

• Advise patients to minimize or avoid exposure to natural or artificial UV light (tanning beds or UVA/B treatment) while using Minolira. ·

• Discuss other sun protection measures, if patients need to be outdoors while using Minolira. ·

• Advise patients to discontinue treatment at the first evidence of sunburn.

Important Administration Instructions ·

• Inform patients to take Minolira as directed. Missing doses or not completing the full course of therapy may decrease the effectiveness of the current treatment course and increase the likelihood that bacteria will develop resistance and will not be treatable by other antibacterial drugs in the future.·

• Advise patient not to chew or crush the tablet.·

• Advise patients to split Minolira tablet across the score line, if required depending on patient’s body weight.    

Manufactured by:

Dr. Reddy’s Laboratories Limited 

FTO-SEZ-Process-Unit-01

Survey No: 57 to 59, 60, 62 & 72

Sector No: 9 to14 & 17 to 20, Devunipalavalasa Village

Ranasthalam Mandal

Srikakulam District

Andhra Pradesh, India  

Marketed by:

Promius Pharma, LLC

107 College Road East

Princeton, NJ 08540, USA

Minolira (min-oh-li'-rah)

(minocycline hydrochloride)

extended-release tablets  

What is Minolira?

Minolira is prescription medicine used to treat only pimples and red bumps (non-nodular inflammatory lesions) that happen with moderate to severe acne vulgaris in people 12 years and older.

Minolira should not be used for the treatment of infections.

It is not known if Minolira is safe and effective in children under the age of 12 years.

Who should not take Minolira?

• Do not take Minolira if you are allergic to medicines in the tetracycline class. Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.  

Before you take Minolira, tell your healthcare provider about all of your medical conditions, including if you:

• have kidney problems

• have liver problems

• have diarrhea or watery stools

• have vision problems.

• are pregnant or plan to become pregnant. Minolira may harm your unborn baby. Taking Minolira while you are pregnant may cause serious side effects on the growth of bone and teeth of your baby. Stop taking Minolira and call your healthcare provider right away if you become pregnant during treatment with Minolira.

• are breastfeeding or plan to breastfeed. Minolira can pass into your breast milk and may harm your baby. You should not breastfeed during treatment with Minolira.

Tell your healthcare provider about all the other medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Minolira and other medicines may affect each other causing serious side effects.

Especially tell your healthcare provider if you take:

• birth control pills. Minolira may reduce the effectiveness of certain birth control pills. You could become pregnant. You should use a second form of birth control during treatment with Minolira. Talk to your healthcare provider about what types of birth control you can use to prevent pregnancy during treatment with Minolira.

• a medicine taken by mouth that contains isotretinoin.

How should I take Minolira?  

See the detailed “Instructions for Use” that comes with Minolira for information about breaking your Minolira extended-release tablets.

• Take Minolira exactly as your healthcare provider tells you.

• Your healthcare provider will tell you how much Minolira to take and if you will need to break your Minolira extended-release tablets based on your weight. Minolira comes in 2 strengths:

• 105 mg extended-release tablets
• 135 mg extended-release tablets

• Do not miss your dose of Minolira. Missing doses or not taking all doses of Minolira may:

• make the treatment not work as well
• increase the chance that the bacteria will become resistant to Minolira

• Take Minolira with or without food. Taking Minolira with food may lower your risk of getting irritation or ulcers in your esophagus. Your esophagus is the tube that connects your mouth to your stomach.

• Do not crush or chew Minolira tablets.

• If you take too much Minolira, call your healthcare provider right away or go to the nearest hospital emergency room.

What should I avoid while taking Minolira?  

• Avoid sunlight or artificial sunlight, such as sunlamps or tanning beds. You could get severe sunburn. Use sunscreen and wear loose-fitting clothes that cover your skin while out in sunlight. Stop taking Minolira if you get sunburn.

• You should not drive or operate dangerous machinery until you know how Minolira affects you. Minolira may cause you to feel dizzy or lightheaded, or have a spinning feeling (vertigo).

What are possible side effects of Minolira?

Minolira may cause serious side effects, including:  

• Harm to an unborn baby. See “What should I tell my healthcare provider before takingMinolira?”  

• Permanent teeth discoloration.   Minolira may permanently turn a baby or child's teeth yellow-gray-brown during tooth development. You should not use Minolira during tooth development. Tooth development happens in the second and third trimesters of pregnancy, and from birth to 8 years of age.

• Slow bone growth. Minolira may slow bone growth in infants and children. Slow bone growth is reversible after stopping treatment with Minolira.

• Diarrhea. Diarrhea can happen with most antibiotics, including Minolira. This diarrhea may be caused by an infection (Clostridium difficile) in your intestines. Call your healthcare provider right away if you get watery or bloody stools.

• Liver problems. Minolira can cause liver problems that may lead to death. Stop taking Minolira and call your healthcare provider right away if you get any of the following signs or symptoms of liver problems:

• loss of appetite	• bleeding more easily than normal
• tiredness	• confusion
• diarrhea	• sleepiness
• yellowing of your skin or the whites of your eyes

• Increased pressure around the brain (intracranial hypertension). This condition may lead to vision changes and permanent vision loss. You may be more likely to get intracranial hypertension if you are a female of childbearing potential and are overweight or have a history of intracranial hypertension. Stop taking Minolira and tell your healthcare provider right away if you have blurred vision, double vision, vision loss, or headaches.
• Immune system reactions including a lupus-like syndrome, hepatitis, and inflammation of blood or lymph vessels (vasculitis). Call your healthcare provider right away if you get a fever, rash, joint pain, or body weakness.
• Serious skin or allergic reactionsthat may affect parts of your body such as your liver, lungs, kidneys and heart. Sometimes these can lead to death. Stop taking Minolira and go to the nearest hospital emergency room right away if you have any of the following signs or symptoms:

• skin rash, hives, sores in your mouth, or your skin blisters and peels
• swelling of your face, eyes, lips, tongue, or throat
• trouble swallowing or breathing
• blood in your urine
• fever, yellowing of the skin or the whites of your eyes, dark colored urine
• pain on the right side of the stomach area (abdominal pain)
• chest pain or abnormal heartbeats
• swelling in your legs, ankles, and feet
• darkening of your nails, skin, eyes, scars, teeth, and gums

• Discoloration (hyperpigmentation). Minolira can cause darkening of your skin, scars, teeth, gums, nails, and whites of your eyes.

The most common side effects of Minolira include:

• headache • tiredness • dizziness • itching

Minolira may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.

Your healthcare provider may tell you to decrease your dose or completely stop taking Minolira if you develop certain serious side effects during treatment with Minolira.

Your healthcare provider may do blood tests to check you for side effects during treatment with Minolira.

These are not all the side effects of Minolira. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Promius Pharma, LLC. at 1-888-966-8766.

How should I store Minolira?  

• Store Minolira at room temperature between 68ºF to 77ºF (20ºC to 25ºC).

• Keep Minolira in the container that it comes in and keep the container tightly closed.

• Keep Minolira away from light and moisture.

Keep Minolira and all medicines out of the reach of children.

General information about the safe and effectivse use of Minolira.

Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use Minolira for a condition for which it was not prescribed. Do not give Minolira to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about Minolira that is written for health professionals.  

What are the ingredients in Minolira?

Active ingredient: minocycline hydrochloride.

Inactive ingredients: ethyl cellulose, hypromellose, isopropyl alcohol, microcrystalline cellulose, polyethylene glycol 400, purified water, silicified microcrystalline cellulose, sodium stearyl fumarate, talc, triethyl citrate

Both 105 mg and 135 mg tablets also contain Opadry clear which contains hydroxyl propyl cellulose and hypromellose.

Marketed by:

Promius Pharma, LLC.

107 College Road East, Princeton, NJ 08540, USA  

Minolira is a registered trademark of Dr. Reddy’s Laboratories Limited

Item No. XXXX

Manufactured by:

Dr. Reddy’s Laboratories Limited

FTO-SEZ, Process Unit-01,

Devunipalavalasa Village,

Srikakulam (District),

Andhra Pradesh, India

Pin-:532409  

This Patient Information has been approved by the U.S. Food and Drug Administration

Issued: 05/2017

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 Minolira may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.