1.NAME OF THE MEDICINAL PRODUCT
Oxytetracycline Tablets USP 250mg Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains

Oxytetracycline Dihydrate USP    250mg
Excipients             q.s.

3. PHARMACEUTICAL FORM
Yellow film-coated tablets.
Yellow, circular, biconvex film-coated tablets

4. CLINICAL PARTICULARS

4.1 Therapeutic indications
Oxytetracycline is a bacteriostatic broad-spectrum antibiotic, active against a wide variety of Gram-positive and Gram-negative organisms.

Infections caused by oxytetracycline-sensitive organisms include:

1) Respiratory tract infections: Pneumonia, whooping cough and other lower respiratory tract infections due to susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and other organisms. Mycoplasma pneumoniae pneumonia. Treatment of chronic bronchitis (including the prophylaxis of acute exacerbations).

2) Urinary tract infections: caused by susceptible strains of the Klebsiella species. Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.

3) Sexually transmitted diseases: Infections due to Chlamydia trachomatis including uncomplicated urethral, endocervical or rectal infections. Non-gonococcal urethritis caused by Ureaplasma urealyticum. Oxytetracycline is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum. Oxytetracycline is an alternative drug in the treatment of gonorrhoea and syphilis.

4) Skin Infections: Acne vulgaris when antibiotic therapy is considered necessary and severe rosacea.

5) Ophthalmic infections: Trachoma, although the infectious agent, as judged by immunofluorescence, is not always eliminated. Inclusion conjunctivitis may be treated with oral oxytetracycline alone or in combination with topical agents.

6) Rickettsial infections: Rocky Mountain spotted fever, typhus group, Q fever and Coxiella endocarditis and tick fevers.

7) Other infections: Stagnant loop syndrome. Psittacosis, brucellosis (in combination with streptomycin), cholera, bubonic plague, louse and tick-borne relapsing fever, tularaemia, glanders, melioidosis and acute intestinal amoebiasis (as an adjunct to amoebicides).

Oxytetracycline is an alternative drug in the treatment of leptospirosis, gas-gangrene and tetanus.

4.2  Posology and method of administration
Posology

Oxytetracycline should be given one hour before or two hours after meals, since food and some dairy products interfere with absorption. Therapy should be continued for up to three days after symptoms have subsided.

All infections due to Group A beta-haemolytic streptococci should be treated for at least 10 days.

Adults (including the elderly) and children over 12 years: The minimum recommended dosage is 250mg every six hours. Therapeutic levels are attained more rapidly by the administration of 500mg initially, followed by 250mg every six hours. For severe infections, the dosage may be increased to 500mg every six hours.

Children under 12 years: Contraindicated in this age group.

Elderly: Usual adult dose. Caution should be observed as subclinical renal insufficiency may lead to drug accumulation.

Renal impairment: In general, tetracyclines are contraindicated in renal impairment and the dosing recommendations only apply if use of this class of drug is deemed absolutely essential. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.

Dosage Recommendations in Specific Infections:

Skin infections: 250-500mg daily in single or divided doses should be administered for at least 3 months in the treatment of acne vulgaris and severe rosacea.

Streptococcal infections: A therapeutic dose of oxytetracycline should be administered for at least 10 days.

Brucellosis: 500mg four times daily accompanied by streptomycin.

Sexually transmitted diseases: 500mg four times daily for 7 days is recommended in the following infections: uncomplicated gonococcal infections (except anorectal infections in men); uncomplicated urethra;, endocervical or rectal infection caused by Chlamydia trachomatis; non-gonoccocal urethritis caused by Ureaplasma urealyticum.

Acute epididymo-orchitis caused by Chlamydia trachomatis, or Neisseria gonorroeae: 500mg four times daily for 10 days.

Primary and Secondary syphilis: 500mg four times daily for 15 days. Syphilis of more than one year’s duration, (latent syphilis of uncertain or more than one year’s duration, cardiovascular or late benign syphilis) except neurosyphilis, should be treated with 500mg four times daily for 30 days. Patient compliance with this regimen may be difficult so care should be taken to encourage optimal compliance. Close follow-up including laboratory tests, is recommended.

Method of Adminstration

For oral administration.

4.3 Contraindications
Known hypersensitivity to any of the tetracyclines or any of the other ingredients in the formulation; chronic renal/hepatic dysfunction; systemic lupus erythematosus; children under 12 years; pregnancy and breastfeeding women; patients receiving vitamin A or retinoid therapy.

4.4 Special Warnings and precautions for use
Tetracycline drugs may cause permanent tooth discoloration (yellow-grey-brown), if administered during tooth development, in the last half of pregnancy and in infancy up to twelve years of age. Enamel hypoplasia has also been reported. This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses.

The anti-anabolic action of tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired renal function, higher serum levels of oxytetracycline may lead to azotaemia, hyperphosphataemia and acidosis.

When treating venereal disease, where co-existent syphilis is suspected, proper diagnostic procedures should be utilised. In all such cases, monthly serological tests should be made for at least four months.

The use of antibiotics may occasionally result in the overgrowth of nonsusceptible organisms including Candida. Constant observation of the patients is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.

In long-term therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies should be performed.

High doses of tetracyclines have been associated with a syndrome involving fatty liver degeneration and pancreatitis.

The use of tetracyclines in general is contraindicated in renal impairment due to excessive systemic accumulation and used with caution in patients with hepatic impairment or those receiving drugs which may have hepatotoxic effects; high doses should be avoided.

Care is advised when administering to patients with myasthenia gravis.

Photosensitivity reactions may occur in hypersensitive persons and such patients should be warned to avoid direct exposure to natural or artificial sunlight and to discontinue therapy at the first sign of skin discomfort.

4.5 Interaction with other medicinal products and other forms of interaction
Antacids containing aluminium, calcium, iron, magnesium or zinc may impair absorption of oxytetracycline. Allow two to three hours between doses of oxytetracycline and antacids.

Since oxytetracycline has been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require a downward adjustment of their anticoagulant dosage. Oxytetracycline may prolong the action of coumarin anticoagulants.

Antidiarrhoeal preparations such as kaolin-pectin and bismuth subsalicylate hinder absorption of tetracyclines.

Combination of tetracyclines with diuretics may be detrimental to renal function.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving oxytetracycline in conjunction with penicillin.

A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of oxytetracycline with oral contraceptives and alternative contraceptive advice should be sought where necessary.

There have been reports of nephrotoxicity (increased blood urea nitrogen and serum creatinine) and death in some cases when oxytetracycline therapy has been combined with methoxyflurane.

Oxytetracycline may increase the hypoglycaemic effects of insulin and sulphonylureas in patients with diabetes mellitus.

Benign intracranial hypertension has been reported following the concomitant use of tetracyclines and vitamin A or retinoids and therefore concurrent use is contraindicated.

4.6 Fertility, Pregnancy and lactation
Not to be used in pregnancy unless essential to the patient’s welfare. Tetracyclines cross the placenta and may have toxic effects on foetal tissues, particularly on skeletal development, (see “Warnings” on tooth development).

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the foetus. Tetracyclines are also excreted in breast milk and are therefore contraindicated in nursing mothers.

Use in newborns, infants and children: All tetracyclines form a stable calcium complex in any bone-forming tissue.

A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25mg/kg every 6 hours. This reaction was reversed when drug was discontinued.

4.7 Effects on ability to drive and use machines
None known.

4.8 Undesirable Effects
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); Frequency not known (cannot be estimated from the available data).

Blood and lymphatic disorders:

Frequency not known: Haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia.

Endocrine disorders:

Frequency not known: brown-black microscopic discoloration of thyroid tissue in use over prolonged periods (No abnormalities of thyroid function are known to occur).

Nervous system disorders:

Frequency not known: Bulging fontanelles in infants, benign intracranial hypertension.

(Treatment should cease if evidence of raised intracranial pressure develops.)

Cardiac disorders:

Frequency not known: Pericarditis.

Gastrointestinal disorders:

Rare: oesophagitis, oesophageal ulceration

(Reported in patients receiving capsule and tablet forms of drugs in the tetracycline class. Most of these patients took medication immediately before going to bed.)

Frequency not known: Gastrointestinal irritations giving rise to nausea, abdominal discomfort, vomiting, diarrhoea, anorexia, dysphagia (If gastric irritation occurs, tablets should be taken with food.). Pseudomembranous colitis, intestinal overgrowth of resistant organisms (Candida albicans, in particular), may occur and cause glossitis, rectal and vaginal irritation and inflammatory lesions (with candidial overgrowth) in the anogenital regions. Similarly, resistant staphylococci may cause enterocolitis. Tooth discolouration, pancreatitis.

Hepatobiliary system disorders:

Frequency not known: Hepatotoxicity (hepatitis, jaundice and hepatic failure), fatty liver degeneration.

Skin and subcutaneous tissue disorders:

Uncommon: Exfoliative dermatitis

Frequency not known: Macropapular and erythematous rashes, photo-erythema (Patients exposed to direct sunlight or ultraviolet light should be advised to discontinue treatment if any skin reaction occurs). Hypersensitivity reactions: urticaria, angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus.

Renal and urinary disorders:

Frequency not known: Renal dysfunction.

4.9 Overdose
There is no specific antidote. Gastric lavage in the first hours after ingestion along with oral administration of milk or antacids is recommended.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
Oxytetracycline is a bacteriostatic antibiotic with a broad spectrum of activity against bacteria, and also some antiprotozoal properties.

5.2 Pharmacokinetic properties
The tetracyclines are incompletely and irregularly absorbed from the gastrointestinal tract.

The degree of absorption is diminished by the soluble salts of divalent and trivalent metals, with which tetracyclines form stable complexes and to a variable degree by milk or food. Plasma concentrations will depend upon the degree of absorption. Peak plasma concentrations occur about 1 to 3 hours after ingestion.

It is recommended that tetracyclines should be given before food.

A dose of 500mg every 6 hours by mouth is reported to produce steady-state plasma concentrations of 3 to 4µg per ml.

In the circulation, tetracyclines are bound to plasma proteins in varying degrees, but reported values differ considerably: from about 20 to 40% for oxytetracycline.

They are widely distributed throughout the body tissues and fluids. Small amounts appear in saliva, and the fluids of the eye and lung.

Tetracyclines appear in the milk of nursing mothers where concentrations may be 60% or more of those in the plasma. they diffuse across the placenta and appear in the foetal circulation in concentrations of about 25 to 75% of those in the maternal blood. Tetracyclines are retained at sites of new bone formation and recent calcification and in developing teeth.

The tetracyclines are excreted in the urine and in the faeces. Renal clearance is by glomerular filtration.

The tetracyclines are excreted in the bile where concentrations 5 to 25 times those in plasma can occur. Since there is some enterohepatic reabsorption complete elimination is slow. Considerable quantities occur in the faeces after administration by mouth.

5.3 Preclinical safety data
Not applicable.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Also contains: magnesium stearate, maize starch, propylene glycol, colloidal silica, sodium lauryl sulphate, E104, E110, E171, E463, E464, E553

6.2 Incompatibilities
None known.

6.3  Shelf life
Shelf-life
Three years from the date of manufacture.

Shelf-life after dilution/reconstitution
Not applicable.

Shelf-life after first opening
Not applicable.

6.4 Special precautions for storage
Keep container tightly closed.
Store below 25°C in a dry place.

6.5 Nature and contents of container
The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps.

The product may also be supplied in blister packs in cartons:
a) Carton: Printed carton manufactured from white folding box board.
b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-7g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.

Pack size: 7’s, 10’s, 14’s, 21’s, 28’s, 30’s, 56’s, 60’s, 84’s, 100’s, 112’s, 250’s, 500’s, 1000’s

Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.

Maximum size of bulk packs: 50,000.

6.6 Special precautions for disposal and other handling
Not applicable.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Oxytetracycline Tablets USP 250mg Taj Pharma

Package leaflet: Information for the patient

Oxytetracycline Tablets USP 250mg Taj Pharma

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
– Keep this leaflet. You may need to read it again.
 – If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
– If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

What is in this leaflet
1. What  Oxytetracycline is and what it is used for
2. Before you are given Oxytetracycline
3. How you will be given  Oxytetracycline
4. Possible side effects
5. How Oxytetracycline is stored
6. Further Information

1. What Oxytetracycline is and what it is used for
Oxytetracycline belongs to a group of medicines called tetracycline antibiotics. It can be used to treat a wide range of bacterial infections, such as:
• infections of the lungs, including whooping cough, bronchitis and pneumonia
• urinary tract infections
• sexually transmitted diseases including chlamydia, gonorrhoea and syphilis
• skin infections including acne
• infections of the eye including conjunctivitis
• rickettsial infections (infections spread by lice, fleas and ticks) including Q fever and tick fevers
• other infections including brucellosis (an infection spread from infected animals through untreated milk or direct contact), psittacosis (an infection spread from birds), plague and cholera.

If you are not sure why you have been prescribed these tablets then please ask your doctor.

2. Before you are given Oxytetracycline
Do not take Oxytetracycline, and tell your doctor if you:
• are allergic to oxytetracycline, other tetracycline antibiotics, or any of the other ingredients in the tablets (listed in section 6 of this leaflet)

  • have kidney problems
    • are pregnant, planning a pregnancy or are breast-feeding
    • are a child under 12 years of age
    • are receiving treatment with vitamin A or retinoid medicines such as isotretinoin, tretinoin or acitretin
    • have Systemic Lupus Erythematosus (SLE), an inflammatory disease which causes skin rashes, fever and joint pain

Warnings and precautions
Talk to your doctor before taking Oxytetracycline if you:
• have any problems with your liver
• have muscle weakness (myasthenia gravis)

Tests
If you are taking Oxytetracycline for a long time, your doctor may ask you to have some tests to check on your blood, kidneys and liver.
Taking Oxytetracycline can affect the results of some clinical tests. If you are going to have a test, it is important to tell your doctor or nurse that you are taking Oxytetracycline.

Other medicines and Oxytetracycline
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, even medicines bought without a prescription.
In particular, tell your doctor or pharmacist if you are taking any of the following medicines, as they may affect how Oxytetracycline works:
• penicillin antibiotics to treat bacterial infections, such as amoxicillin, flucloxacillin or phenoxymethylpenicillin
• antacids to treat indigestion or heartburn, or over the counter medicines or supplements containing aluminium, calcium, iron, magnesium, bismuth or zinc. These medicines should not be taken at the same time as Oxytetracycline as they can affect the body’s absorption of Oxytetracycline. You should allow 2-3 hours between doses of these medicines and Oxytetracycline.
• vitamin A
• retinoids to treat eczema, acne or other skin conditions, such as tretinoin or adapalene  medicines to control diarrhoea, such as kaolin-pectin orl bismuth subsalicylate
• medicines to treat diabetes, such as insulin gliclazide or tolbutamide
• medicines to increase urine production (diuretics), such as furosemide or spironolactone
• medicines to thin the blood and stop blood clots forming, such as warfarin or phenindione
• strontium ranelate to treat osteoporosis
• ergotamine to treat migraines

Oxytetracycline can make birth control pills less effective. You should use an additional form of contraception while you are taking Oxytetracycline and for 7 days after stopping.
If you go into hospital or have treatment for any other conditions, you must tell the doctor, dentist or nurse that you are taking Oxytetracycline.

Oxytetracycline with food and drink
Avoid taking this medicine at the same time as milk or food, in particular dairy products, as they can affect the body’s absorption of Oxytetracycline.

Pregnancy and breast-feeding
Do not take Oxytetracycline if you pregnant, planning a pregnancy or breast-feeding, unless your doctor has advised you to, as it may affect the development of your baby.
Ask your doctor for advice before taking any medicines.

Driving and using machines
Oxytetracycline is not known to affect the ability to drive or operate machinery.

Oxytetracycline contains sunset yellow (E110)
Oxytetracycline Tablets contain sunset yellow (E110) which may cause allergic reactions.

3. How you will be given Oxytetracycline
Always take Oxytetracycline exactly as your doctor has told you.
Swallow each tablet whole with a glass of water, ideally on an empty stomach, (either one hour before or two hours after a meal).
Do not take Oxytetracycline immediately before going to bed.

Dosage
Your doctor will decide your exact dose, as it depends on your condition.

Adults, elderly and children over 12 years: typical dose is 250 mg every six hours. If you have a severe infection, your doctor may increase your dose to 500 mg every six hours.

Children under 12 years: Oxytetracycline must not be used in children under 12 years old, as it can stain teeth and affect bone development.

If you take more Oxytetracycline than you should
Contact your doctor or go to the nearest hospital casualty department immediately. Take the package with you so the doctor knows what has been taken.

If you forget to take Oxytetracycline
Do not worry, take it as soon as you remember. However, if it is nearly time for your next dose, skip the missed dose and take your next scheduled dose at the correct time. Do not take a double dose to make up for the one you have missed.

If you stop taking Oxytetracycline
You should continue taking Oxytetracycline for as long as your doctor has told you to, even if you start to feel better. If you stop before finishing the prescribed course of treatment your infection may still be present or may reappear.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Side Effects
Like all medicines, Oxytetracycline can cause side effects, although not everybody gets them.

If you get any of the following serious side effects, STOP TAKING Oxytetracycline and contact your doctor or go to the nearest hospital casualty department immediately:
• allergic reactions, the symptoms of which may include itching, rash, swelling of the hands, feet, face, lips, tongue or throat, which can cause difficulty in swallowing or breathing
• increased pressure within the skull, which can cause severe headaches or problems with your vision
• swelling of the sac around the heart (pericarditis), the signs of which may include chest pain, difficulty breathing, fever and dry cough

If you get any of the following side effects, stop taking Oxytetracycline and tell your doctor as soon as possible:
• increased sensitivity to sunlight or artificial sunlight (sun-beds or sun-lamps) causing itching, stinging and burning of the skin. You should limit your exposure to natural sunlight, and avoid exposure to artificial sunlight, where possible.
• changes to your blood, such as altered numbers of redl blood cells, white blood cells, or blood platelets. This may cause symptoms including unexplained bleeding, bruising, increased risk of infections, sore throat, fever, weakness, breathlessness, pale skin and general illness. A blood test can be taken to check.

Tell your doctor if you get any of the following side effects:
• stomach upsets such as feeling sick (nausea), stomach ache, being sick (vomiting), diarrhoea. If you experience severe stomach upset you should take Oxytetracycline with food.
• loss of appetite, difficulty swallowing, inflammation of the digestive tract
• inflammation of the colon, which causes fever, severe diarrhoea and abdominal pain
• overgrowth of some resistant organisms causing infections, such as thrush, affecting the genitals or anus
• tooth discolouration. This is more common during long-term or repeated use of Oxytetracycline.
• inflammation or ulceration of the gullet, causing heartburn, sore throat, difficulty swallowing, nausea, vomiting or chest pain  inflammation of the pancreas (pancreatitis), which can cause severe stomach pain that reached through to your back
• liver damage, inflammation of the liver (hepatitis), which causes yellowing of the skin and whites of the eyes (jaundice), liver failure, worsening of fat build-up within liver cells
• scaling and peeling of the skin
• problems with your kidneys, causing changes in your urine, tiredness, weakness, shortness of breath and swelling due to fluid retention
• worsening of the inflammatory disease Systemic Lupus Erythematosus (SLE), which causes skin rashes, fever and joint pain.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5. How Oxytetracycline is stored
Keep out of the sight and reach of children.
Do not store above 25°C. Store in the original package or container and keep the container tightly closed.
Do not use these tablets after the expiry date, which is stated on the package or container. The expiry date refers to the last day of that month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information

What Oxytetracycline contains
The active substance (the ingredient that makes the tablet work) in Oxytetracycline Tablets is oxytetracycline dihydrate.
Each tablet contains: Oxytetracycline Dihydrate USP            250mg
The other ingredients are maize starch, pregelatinated maize starch, povidone, sodium starch glycollate, sodium lauryl sulphate, magnesium stearate, titanium dioxide (E171), quinoline yellow (E104), hydroxypropyl cellulose (E463), sunset yellow (E110), hypromellose, ethylcellulose and diethylphthalate.

What Oxytetracycline looks like and contents of the pack
Oxytetracycline 250 mg Tablets are pale yellow biconvex, film-coated tablets.
The tablets come in blisters packs and containers of 28, 30, 50, 56, 60, 84, 100, 250, 500 & 1000 tablets.
Not all pack sizes may be marketed.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com