Misoprostol Tablets 200µg Taj Pharma

NAME OF THE MEDICINAL PRODUCT

Misoprostol Tablets 200µg Taj Pharma

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains:
Misoprostol…………………………..200µg
Excipients……………………………….q.s.

For the full list of excipients, see section 6.1.

PHARMACEUTICAL FORM

Tablet

CLINICAL PARTICULARS

4.1 Therapeutic indications

Misoprostol Tablets is indicated for the healing of duodenal ulcer and gastric ulcer including those induced by nonsteroidal anti-inflammatory drugs (NSAID) in arthritic patients at risk, whilst continuing their NSAID therapy. In addition, Misoprostol Tablets can be used for the prophylaxis of NSAID-induced ulcers.

4.2 Posology and method of administration

Posology

Adults

Healing of duodenal ulcer, gastric ulcer and NSAID-induced peptic ulcer: 800 micrograms daily in two or four divided doses taken with breakfast and / or each main meal and at bedtime.

Treatment should be given initially for at least 4 weeks even if symptomatic relief has been achieved sooner. In most patients ulcers will be healed in 4 weeks but treatment may be continued for up to 8 weeks if required. If the ulcer relapses further treatment courses may be given.

Prophylaxis of NSAID-induced peptic ulcer: 200 micrograms twice daily, three times daily or four times daily. Treatment can be continued as required. Dosage should be individualised according to the clinical condition of each patient.

Renal impairment: Available evidence indicates that no adjustment of dosage is necessary in patients with renal impairment.

Hepatic impairment: Misoprostol Tablets is metabolised by fatty acid oxidising systems present in organs throughout the body. Its metabolism and plasma levels are therefore unlikely to be affected markedly in patients with hepatic impairment.

Elderly

The usual dosage may be used.

Paediatric population

Use of Misoprostol Tablets in children has not yet been evaluated in the treatment of peptic ulceration or NSAID-induced peptic ulcer disease.

4.3 Contraindications

Misoprostol is contraindicated:

In women of childbearing potential who are not using effective contraception (see sections 4.4, 4.6 and 4.8)
In women who are pregnant, or in whom pregnancy has not been excluded, or who are planning a pregnancy as misoprostol increases uterine tone and contractions in pregnancy which may cause partial or complete expulsion of the products of conception (see sections 4.4, 4.6 and 4.8). Use in pregnancy has been associated with birth defects.
In patients with a known hypersensitivity to misoprostol or to any other component of the product, or to other prostaglandins.

4.4 Special warnings and precautions for use

In women of childbearing potential Misoprostol Tablets must not bestarted on misoprostol until pregnancy is excluded, and should be fully counselled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, use of the product should be discontinued (see sections 4.3, 4.6 and 4.8).

In such patients it is advised that Misoprostol Tablets should only be used if the patient:

takes effective contraceptive measures
has been advised of the risks of taking Misoprostol Tablets if pregnant (see section 4.3)

Gastrointestinal bleeding, ulceration, and perforation have occurred in NSAID-treated patients receiving misoprostol. Physicians and patients should remain alert for ulceration, even in the absence of gastrointestinal symptoms, and, where appropriate, endoscopy and biopsy should be carried out before use to ensure that malignant disease is absent in the upper gastrointestinal tract. These investigations and any others considered necessary by the clinician should be repeated at appropriate intervals for follow-up purposes.

Symptomatic responses to misoprostol do not preclude the presence of gastric malignancy.

Misoprostol should be used with caution in patients with conditions that predispose them to diarrhoea, such as inflammatory bowel disease. To minimise the risk of diarrhoea, misoprostol should be taken with food, and magnesium-containing antacids should be avoided (see section 4.5).

Misoprostol should be used with caution in patients in whom dehydration would be dangerous. These patients should be monitored carefully.

The results of clinical studies indicate that Misoprostol Tablets does not produce hypotension at dosages effective in promoting the healing of gastric and duodenal ulcers. Nevertheless, Misoprostol Tablets should be used with caution in the presence of disease states where hypotension might precipitate severe complications, e.g. cerebrovascular disease, coronary artery disease or severe peripheral vascular disease including hypertension.

There is no evidence that Misoprostol Tablets has adverse effects on glucose metabolism in human volunteers or patients with diabetes mellitus.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant administration of NSAIDs and misoprostol in rare cases can cause a transaminase increase and peripheral oedema.

Misoprostol Tablets is predominantly metabolised via fatty acid oxidising systems and has shown no adverse effect on the hepatic microsomal mixed function oxidase (P450) enzyme system. In specific studies no clinically significant pharmacokinetic interaction has been demonstrated with antipyrine or diazepam. A modest increase in propranolol concentrations (mean approximately 20% in AUC, 30% in C_max) has been observed with multiple dosing of misoprostol. In extensive clinical studies no drug interactions have been attributed to Misoprostol Tablets. Drug interaction studies with misoprostol and several NSAIDs showed no clinically significant effect on the kinetics of ibuprofen, diclofenac, piroxicam, aspirin, naproxen or indomethacin.

Magnesium-containing antacids should be avoided during treatment with misoprostol as this may worsen the misoprostol-induced diarrhoea.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

Women of childbearing potential must be informed about the risk of teratogenicity prior to treatment with Misoprostol Tablets. Treatment must not be initiated until pregnancy is excluded, and women should be fully counselled on the importance of adequate contraception while undergoing treatment. If pregnancy is suspected, treatment must be immediately discontinued (see sections 4.3 and 4.4).

Pregnancy

Misoprostol

Misoprostol induces uterine contractions and is associated with abortion, premature birth, foetal death and foetal malformations.

Approximately a 3-fold increased risk of malformations was reported in pregnancies exposed to misoprostol during the first trimester, compared to a control group incidence of 2%. In particular, prenatal exposure to misoprostol has been associated with Moebius syndrome (congenital facial paralysis leading to hypomimia, troubles of suckling and deglutition and eye movements, with or without limb defects); amniotic band syndrome (limb deformities/ amputations, especially clubfoot, acheiria, olygodactyly, cleft palate inter alia) and central nervous system anomalies (cerebral and cranial anomalies as anencephaly, hydrocephaly, cerebellar hypoplasia, neural tube defects). Other defects including arthrogryposis have been observed.

Consequently:

– Women should be informed of the risk of teratogenicity.

– Should the patient wish to continue with her pregnancy after exposure of misoprostol in utero, a careful ultrasound scan monitoring of the pregnancy, with special attention to the limbs and head must be carried out.

The risk of uterine rupture increases with advancing gestational age and with prior uterine surgery, including Caesarean delivery. Grand multiparity also appears to be a risk factor for uterine rupture.

Breast-feeding

Misoprostol is rapidly metabolised in the mother to misoprostol acid, which is biologically active and is excreted in breast milk. Misoprostol should not be administered to nursing mothers because the excretion of misoprostol acid could cause undesirable effects such as diarrhoea in nursing infants.

4.7 Effects on ability to drive and use machines

Misoprostol Tablets can cause dizziness. Patients should be cautioned about operating machinery and driving.

4.8 Undesirable effects

The Adverse reaction terms were then categorised utilising the incidence rate as follows:

Very Common: ≥ 1/10 (≥10%)

Common: ≥ 1/100 and < 1/10, (≥1% and <10%)

Uncommon: ≥ 1/1000 and < 1/100, (≥0.1% and <1%)

Rare: ≥ 1/10,000 and < 1/1000, (≥0.01% and <0.1%)

Very Rare: < 1/10,000, (<0.01%)

Not Known

Immune System Disorder

Not Known

Anaphylactic reaction

Nervous System Disorders

Common

Dizziness, headache

Gastrointestinal Disorders

Very common

Common

Diarrhoea*

Abdominal pain*, constipation, dyspepsia, flatulence, nausea, vomiting

Skin and Subcutaneous Tissue Disorders

Very Common

Rash

Pregnancy, puerperium, and perinatal conditions

Rare

Not Known

Uterine rupture**

Amniotic fluid embolism, abnormal uterine contractions, foetal death, incomplete abortion, premature birth, retained placenta, uterine perforation

Reproductive System and Breast Disorders

Uncommon

Rare

Not Known

Vaginal haemorrhage (including postmenopausal bleeding), intermenstrual bleeding, menstrual disorder, uterine cramping

Menorrhagia, dysmenorrhoea

Uterine haemorrhage

Congenital, Familial and Genetic Disorders

Common

Foetal malformations

General Disorders and Administration Site Conditions

Not Known

Uncommon

Chills

Pyrexia

* Diarrhoea and abdominal pain were dose-related, usually developed early in the course of therapy, and were typically self-limiting. Rare instances of profound diarrhoea leading to severe dehydration has been reported.

**Uterine rupture has been uncommonly reported after prostaglandin intake during the second or third trimester of pregnancy. Uterine ruptures occurred particularly in multiparous women or in women with a caesarean section scar.

Diarrhoea can be minimised by using single doses not exceeding 200 micrograms with food and by avoiding the use of predominantly magnesium containing antacids when an antacid is required.

The pattern of adverse events associated with Misoprostol Tablets is similar when an NSAID is given concomitantly.

Clinical trials:

In clinical trials, over 15,000 patients and subjects received at least one dose of misoprostol. Adverse reactions involved primarily the gastrointestinal system.

Diarrhoea and abdominal pain were dose-related, usually developed early in the course of therapy, and were typically self-limiting. Rare instances of profound diarrhoea leading to severe dehydration have been reported.

The profile for adverse reactions with >1% incidence was similar for subacute (four to twelve weeks duration) and long- term (up to one year) clinical trials.

The safety of long-term (greater than 12 weeks) administration of misoprostol has been demonstrated in several studies in which patients were treated continuously for up to one year. This includes no adverse or unusual change in the morphology of gastric mucosa, as determined by gastric biopsy.

Special populations:

There were no significant differences in the safety profile of misoprostol in patients who were 65 years of age or older, compared with younger patients.

The use of misoprostol in children has not been evaluated.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Signs and symptoms of overdose

The toxic dose of misoprostol in humans has not been determined. Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhoea, fever, palpitations, hypotension, or bradycardia.

Treatment of overdose

Because misoprostol is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage. In cases of overdose, standard supportive measures should be adopted as required.

In clinical trials patients have tolerated 1200 micrograms daily for three months without significant adverse effects.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: prostaglandins.

Misoprostol Tablets is an analogue of naturally occurring prostaglandin E1 which promotes peptic ulcer healing and symptomatic relief.

Mechanism of action

Misoprostol Tablets protects the gastroduodenal mucosa by inhibiting basal, stimulated and nocturnal acid secretion and by reducing the volume of gastric secretions, the proteolytic activity of the gastric fluid, and increasing bicarbonate and mucus secretion.

5.2 Pharmacokinetic properties

Misoprostol Tablets is rapidly absorbed following oral administration, with peak plasma levels of the active metabolite (misoprostol acid) occurring after about 30 minutes. The plasma elimination half-life of misoprostol acid is 20-40 minutes. No accumulation of misoprostol acid in plasma occurs after repeated dosing of 400 micrograms twice daily.

5.3 Preclinical safety data

In single and repeat-dose studies in dogs, rats and mice at multiples of the human dose, toxicological findings were consistent with the known pharmacological effects of the E-type prostaglandins, the main symptoms being diarrhoea, vomiting, mydriasis, tremors and hyperpyrexia. Gastric mucosal hyperplasia was also observed in the mouse, rat and the dog. In the rat and the dog the hyperplasia was reversible on discontinuation of misoprostol following one year of dosing. Histological examination of gastric biopsies in humans has shown no adverse tissue response after up to one year’s treatment. In studies of fertility, teratogenicity and peri/post-natal toxicity in rats and rabbits there were no major findings. A decrease in implantations and some pup growth retardation was observed at doses greater than 100 times the human dose. It was concluded that misoprostol does not significantly affect fertility, is not teratogenic or embryotoxic and does not affect rat pups in the peri/post-natal period.

Misoprostol was negative in a battery of 6 in vitro assays and one in vivo test to assess mutagenic potential. In carcinogenicity studies in the rat and mouse it was concluded that there was no risk of carcinogenic hazard.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose, Sodium starch glycolate (Type A), Hydrogenated castor oil

Hypromellose

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 30°C. Store in the original package to protect from moisture.

6.5 Nature and contents of container

Cold-formed aluminium blister packs of 56, 60, 112, 120 or 140 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

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

MISOPROSTOL TABLETS
200µG
TAJ PHARMA

PACKAGE LEAFLET: INFORMATION FOR THE USER

Misoprostol

Read all of this leaflet carefully before you start using 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 you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

WHAT IS IN THIS LEAFLET

What Misoprostol is and what it is used for
What you need to know before you take Misoprostol
How to take Misoprostol
Possible side effects
How to store Misoprostol
Contents of the pack and other information1. WHAT MISOPROSTOL IS AND WHAT IT IS USED FOR

Misoprostol tablets contain misoprostol which is similar to a chemical substance called ‘prostaglandin’ which your body produces naturally. Prostaglandins are produced in the stomach and intestine and help to protect the lining. Misoprostol belongs to a group of medicines known as ‘anti-ulcer agents’.
The Misoprostol tablets may help prevent you getting ulcers in your stomach or the part it empties into, called the duodenum. These ulcers could be caused by taking non-steroidal anti-inflammatory drugs (NSAIDs) like diclofenac and naproxen. The way NSAIDs work means they reduce the amount of prostaglandins in your stomach and intestine. This can cause indigestion and lead to ulcers forming. The Misoprostol tablets will replace these prostaglandins and help to protect your stomach and intestine, so you can continue getting benefit from your NSAID. Misoprostol also reduces acid and increases bicarbonate in your stomach secretions.
Misoprostol can also be used to heal existing ulcers.

WHAT YOU NEED TO KNOW BEFORE YOU TAKE MISOPROSTOL

Misoprostol may not be suitable for everyone. Please read the following list carefully to see if any of these apply to you. Consult your doctor if you are not sure.

Do not take Misoprostol

if you are allergic to misoprostol or any of the other ingredients of this medicine (listed in section 6), or other prostaglandin medicines.
If you are a woman of childbearing age and you are not using an effective contraceptive method to avoid becoming prgenant (see Section ‘Pregnancy’ for further information).
if you are pregnant or trying to become pregnant or do not have a negative pregnancy test because it may cause a miscarriage, premature birth or birth defects (see section ‘Pregnancy’ for further information).

if you are breastfeeding (as this may give your baby diarrhoea).

Warnings and precautions

Talk to your doctor or pharmacist before taking Misoprostol. Tell your doctor if you have any of the following conditions to help him or her decide if Misoprostol is suitable for you:

if you are pregnant or plan to become pregnant (see subsection “pregnancy” below). Due to the risk for the foetus, your treatment with Misoprostol must be discontinued immediately.
if you are a woman of childbearing age (see subsection “pregnancy” below). Due to the risk for the foetus, it is important to use effective contraception while you are taking Misoprostol.
heart disease.
low or high blood pressure, or any disease of the blood vessels.
inflammatory bowel disease.
prone to dehydration.

If you are a younger woman who has not yet gone through the menopause, your doctor will have only prescribed Misoprostol if he is satisfied you are at high risk of developing ulcers from your NSAID medicine.

Other medicines and Misoprostol

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

You can take Misoprostol with most medicines without any problems. If you use an antacid (something to reduce acid in the stomach) you should avoid antacids with magnesium in them as these may make diarrhoea worse.

If you are taking any medicines for a heart condition, please consult your doctor.

Use with NSAIDs in rare cases can result in swelling of feet or hands and an increase in liver enzymes.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription

Misoprostol with food, drink and alcohol

Please refer to section 3.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Do not take Misoprostol if you are pregnant or plan to become pregnant. Your doctor will make you aware of the risks if you do become pregnant as Misoprostol may cause a miscarriage, premature birth or birth defects. Pregnancies exposed to misoprostal during the first trimester have been associated with approximately a 3-fold increased risk of birth defects, in particular facial paralysis, limb defects, cerebral and cranial anomalies. If you are exposed to Misoprostol during pregnancy, talk with your doctor. If you decide to continue with the pregnancy, careful pre-natal monitoring and repeated ultrasound examinations, with a special attention to the limbs and head must be carried out.

Misoprostol can cause a miscarriage or damage to your womb, so it is very important to use reliable contraception while taking this medicine. The risk of damage to your womb is greater in the later stages of pregnancy, and if you have had a previous Caesarean delivery or have given birth to five or more children. If you want to try for a baby, tell your doctor as you will have to stop taking Misoprostol and use a different treatment.

Misoprostol should not be taken by pregnant women and in women planning a pregnancy. Do not breastfeed while taking Misoprostol.

Driving and using machines

Dizziness has been reported after taking Misoprostol. Be cautious when driving or operating machinery until you know how the medicine affects you.

HOW TO TAKE MISOPROSTOL

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

You should take Misoprostol with food.

Misoprostol is suitable only for adults aged 18 years and over.

To heal ulcers in your stomach or duodenum

You should normally take two 200 microgram Misoprostol tablets twice a day with food. Alternatively you can take one Misoprostol tablet four times a day, at regular intervals with food.

Treatment will usually last for 4 weeks, but may be extended up to 8 weeks.

If your ulcers are not completely healed after this period, further treatment may be given.

To prevent ulcers when taking NSAID medicines

You should usually take one 200 microgram tablet, two, three or four times a day. Your doctor will adjust your dose to suit you.

You will need to continue to take Misoprostol as long as is needed to protect your stomach or gut, and must keep taking the tablets until your doctor advises you to stop.

If you take more Misoprostol than you should

If you take too many tablets, contact your doctor or accident and emergency department straight away.

If you forget to take Misoprostol

If you forget to take a dose of your tablets, take them as soon as you remember. But if it is almost time for your next dose, do not take the tablet(s) you have missed.

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

POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects although not everybody gets them. Most of these don’t happen very often, are not serious and will often wear off after a while. If you are worried about any side effects, then talk to your doctor.

Stop taking the tablets and get emergency medical help immediately if you have any of the symptoms below which could represent an allergic reaction:

swelling of the face, lips, tongue or throat (angioedema)

difficulty in breathing

swelling of the extremities (hands and feet)

If you get any of the following symptoms, tell your doctor immediately:

prolonged heavy or painful bleeding
abnormal contractions of the womb

The following side effects have been reported with Misoprostol:

Very common: may affect more than 1 in 10 people

skin rashes
diarrhoea

Diarrhoea is the most common problem and is occasionally severe. You have less chance of getting diarrhoea if you take Misoprostol with food. If you use an antacid (something to reduce acid in the stomach) you should avoid antacids with magnesium in them as these may make diarrhoea worse. Your pharmacist can help you choose a suitable antacid.

Common: may affect up to 1 in 10 people

dizziness
headache
stomach pain
constipation
wind
indigestion
feeling or being sick
Birth defects (foetal malformations). If you become pregnant during treatment, stop taking Misoprostol immediately and seek medical advice.

Uncommon: may affect up to 1 in 100 people

fever
irregular periods
periods problems
severe uterine pain
some older women may have vaginal bleeding even though they have gone through the menopause

Rare: may affect up to 1 in 1,000 people

cramping
Tearing of the womb (uterine rupture) after administration of prostaglandins in the second or third trimester of pregnancy, mainly in women with previous deliveries of a child or with a scar of a caesarian section. Seek urgent medical attention.

Not known: frequency cannot be estimated from the available data

allergic reactions, including swelling of the hands and feet, face, lips, tongue or throat and which may cause great difficulty in breathing
prolonged heavy or painful bleeding
chills
high temperature
abnormal contractions of the womb
bleeding from the womb
placenta remaining in the womb after birth, termination or miscarriage
amniotic fluid (the fluid which surrounds the baby when pregnant) entering the mother’s bloodstream causing an allergic reaction

incomplete miscarriage and premature birth

foetal death

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.

HOW TO STORE MISOPROSTOL

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister strip after EXP. The expiry date refers to the last day of that month.

Do not store above 30ºC. Keep the blister in the outer carton.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.