Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about CYTOTEC.

It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking CYTOTEC against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What CYTOTEC is used for

• To treat acute ulcers in the stomach (gastric ulcers), or in the first part of the small intestine (duodenal ulcers).
• To prevent development of stomach ulcers, which may sometimes be caused by arthritis medicines that are called non-steroidal anti-inflammatory drugs (NSAIDs).
• To prevent bleeding in the stomach or upper intestine in hospital patients after surgery.

CYTOTEC makes your stomach produce less acid, and it helps your stomach protect itself against damage from acid and certain other substances, such as NSAIDs.

The active ingredient in CYTOTEC is called misoprostol. Misoprostol is very similar to a group of substances called prostaglandins, which occur naturally in the stomach and other parts of the body. When the amount of these natural prostaglandins is lower than normal, there is a risk that ulcers may occur in the stomach or duodenum. This reduction in prostaglandins is often a side effect of NSAIDs. CYTOTEC can replace prostaglandins and help to prevent ulcers, or help heal the ulcer if you already have one. If you are taking an NSAID, CYTOTEC helps protect your stomach while you continue to receive the benefit of pain relief and reduction in joint swelling from your arthritis medicine.

Your doctor, however, may prescribe CYTOTEC for another purpose.

Ask your doctor if you have any questions about why CYTOTEC has been prescribed for you.

There is no evidence that CYTOTEC is addictive.

Before you take CYTOTEC

When you must not use it

Do not take CYTOTEC if:

• you are allergic to CYTOTEC (or another prostaglandin medicine) or any of the tablet ingredients listed at the end of this leaflet.
  If you have an allergic reaction you may get a skin rash, difficulty in breathing, hayfever or faintness.
• you are pregnant, or there is a possibility you may be pregnant, or if you intend to become pregnant.

Tell your doctor if you become pregnant while you are taking CYTOTEC. The effects of CYTOTEC may be harmful to a developing baby (fetus).

If it is possible for you to become pregnant, you should use adequate contraception while you are taking CYTOTEC. Examples of adequate contraception are oral contraceptives ("the pill") or intra-uterine devices (IUDs).

CYTOTEC must not be used by pregnant women as it may cause miscarriage, and this could lead to potentially dangerous bleeding, hospitalisation, surgery, infertility or death. You should not become pregnant while taking CYTOTEC.

Do not use CYTOTEC after the expiry date (EXP) printed on the pack. It may have no effect at all, or worse, an entirely unexpected effect if you use it after the expiry date.

Do not use CYTOTEC if the packaging shows signs of tampering.

Do not use it to treat any other complaints unless your doctor says to.

Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Before you start to use it:

You must tell your doctor if:

1. You are allergic to any other medicines or any foods, dyes or preservatives
2. you have any other medical conditions, especially:

• epilepsy
• asthma
• diseases of the heart or blood vessels.
• bowel disease

3. you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.
4. you are breast feeding.

CYTOTEC passes into breast milk, therefore it is not recommended that you take CYTOTEC if you are breast feeding.

Use in children.
The effects of CYTOTEC have only been studied in adults, and there is no specific information comparing its use in children with use in adults.

How to take CYTOTEC

The usual dosage of CYTOTEC is one tablet two, three or four times a day.

CYTOTEC is best taken with food. Do not take CYTOTEC on an empty stomach.

Follow your doctor's instructions exactly, on how much CYTOTEC to take, and for how long to take it. If you are taking an NSAID, CYTOTEC may be prescribed for as long as you are taking the NSAID, whether or not you have stomach pain or other symptoms of ulcers. Some ulcers are painless, particularly those caused by NSAIDs.

If you miss a dose

If you miss a dose of CYTOTEC, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Do not take two doses together.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose):

If you think that you or anyone else may have taken too much CYTOTEC, immediately telephone your doctor or Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764 766) for advice, or go to Accident and Emergency at your nearest hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

Signs that may indicate an overdose of CYTOTEC include: sedation (feeling sleepy), shaking, fits, shortness of breath, stomach pains, diarrhoea, contraction of the uterus (womb), heart palpitations, low blood pressure or slow heart beat.

While you are using CYTOTEC

Things you must do

Use CYTOTEC exactly as your doctor has prescribed.

Stop taking CYTOTEC if you become pregnant or you think you may be pregnant.

Tell all doctors, dentist and pharmacists who are treating you that you are taking CYTOTEC.

If an antacid is needed for stomach pain, use one which does not contain magnesium. Aluminium-containing antacids may be used when needed for relief of pain. Ask your doctor or pharmacist for advice if necessary.

Side effects

Check with your doctor as soon as possible if you have any problems while taking CYTOTEC even if you think they are not connected with the medicine or are not listed in this leaflet.

Like other medicines, CYTOTEC can cause some side effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

Stomach pains and diarrhoea are the most common side effects and are usually mild to moderate. If either of these effects occur, they usually settle down within a week or two. If you take CYTOTEC with food, you will have less chance of getting diarrhoea (or it will not be as bad, if you do get it). If you use an antacid (to reduce acid in your stomach), ask the pharmacist to recommend one which contains aluminium, since antacids which contain magnesium may make diarrhoea worse. Tell your doctor if stomach pains or diarrhoea are severe or do not stop after a week.

Other side effects include nausea, vomiting, flatulence (wind), indigestion, constipation, headaches, chills, fever or dizziness.

Occasionally women have menstrual problems.

Other side effects not listed above may occur in some patients. Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using CYTOTEC

Storage

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Do not store CYTOTEC or any other medicine in the bathroom or near a sink. Do not leave your tablets in the car or on windowsills.

Keep CYTOTEC in a cool dry place where the temperature stays below 25°C. Heat or moisture may cause CYTOTEC tablets to deteriorate.

Keep your tablets in their blister until it is time to take them. If you take the tablets out of the blister they may not keep well.

Disposal

If your doctor tells you to stop taking CYTOTEC, ask your pharmacist what to do with any tablets left over.

Product description

CYTOTEC tablets are scored, white, hexagonal tablets, marked on one side with SEARLE/1461.

Packs contain 120 tablets.

Ingredients

Each CYTOTEC tablet contains 200 micrograms of misoprostol as the active ingredient.

Other ingredients in each tablet are:

• cellulose-microcrystalline
• hypromellose
• sodium starch glycollate
• castor oil-hydrogenated

Supplier

CYTOTEC is supplied in Australia by:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

Australian Registration Number
AUST R 63983

This leaflet was revised in December 2019.

®Registered trademark

©Pfizer Australia Pty Ltd

Published by MIMS January 2020

1 Name of Medicine

Misoprostol.

2 Qualitative and Quantitative Composition

Cytotec tablets contain 200 micrograms of misoprostol.

3 Pharmaceutical Form

Tablets 200 micrograms.

4 Clinical Particulars

4.1 Therapeutic Indications

Cytotec is indicated in the treatment of acute duodenal and gastric ulcers.
Cytotec is indicated in the prevention of stress-induced upper gastrointestinal mucosal bleeding and lesions in postsurgical patients in intensive care units.
Cytotec is indicated for the prevention of gastric ulceration in patients in whom NSAID therapy is essential and who have been assessed at high risk of gastric ulceration or the complications of gastric ulceration.

4.2 Dose and Method of Administration

Dosage.

Treatment of duodenal ulcers.

Treatment of gastric ulcers.

Prevention of stress induced mucosal bleeding and lesions in postsurgical ICU patients.

Prevention of NSAID induced gastric ulceration.

Dosage adjustment.

Elderly.

Use in renal impairment.

4.3 Contraindications

Cytotec should not be administered to anyone with a known hypersensitivity to misoprostol or any other ingredient of the product, or to other prostaglandins.
Cytotec is contraindicated in pregnancy, or in patients in whom pregnancy has not been excluded (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy; Section 4.8 Adverse Effects (Undesirable Effects), Post-marketing experience).

4.4 Special Warnings and Precautions for Use

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.
Symptomatic responses to misoprostol do not preclude the presence of gastric malignancy.
Patients with conditions that predispose to diarrhoea, such as inflammatory bowel disease, or those in whom dehydration would be dangerous, should be monitored carefully.

Nosocomial pulmonary infections.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The serum protein binding of misoprostol acid was not affected by indomethacin, ranitidine, digoxin, phenylbutazone, warfarin, diazepam, methyldopa, propranolol, triamterene, cimetidine, paracetamol, ibuprofen, chlorpropamide, and hydrochlorothiazide.
With salicylic acid (300 micrograms/mL) the protein binding of misoprostol was lowered from 84% to 52% which is not considered clinically significant since the binding of misoprostol acid is not extensive and its elimination half-life is very short.
In laboratory studies, misoprostol has no significant effect on the cytochrome P450-linked hepatic mixed function oxidase system, and therefore should not affect the metabolism of theophylline, warfarin, benzodiazepines or other drugs normally metabolised by this system. No drug interactions have been attributed to misoprostol in extensive clinical trials. As such, other drugs would be unlikely to interfere with misoprostol's metabolism in either normal or hepatically impaired patients. There are no data on clinical safety beyond 12 months for the use of concurrent misoprostol and NSAIDs.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

In clinical trials, the most frequent adverse events were diarrhoea, abdominal pain, and loose stools. These events occurred in approximately one-tenth of patients receiving Cytotec 800 micrograms daily in two or four divided doses. The events were usually transient and mild to moderate in severity. Diarrhoea, when it occurred, usually developed early in the course of treatment, was dose related, self-limiting and required discontinuation of Cytotec in less than 2% of the patients, though it has occasionally been reported to lead to severe dehydration. The incidence of diarrhoea can be minimised by administering Cytotec immediately after meals and at bedtime, and by avoiding the use of magnesium containing antacids. Dose adjustment may also be helpful. Abdominal pain has been associated with Cytotec therapy, and in controlled trials with concomitant NSAIDs the incidence was not significantly different from placebo.
Women who received Cytotec during clinical trials reported the following gynaecological disorders: uterine cramping, menorrhagia, menstrual disorder, spotting, dysmenorrhoea, intermenstrual bleeding and vaginal haemorrhage (including postmenopausal bleeding). The incidence of each of these adverse reactions in women was < 1%.
In clinical trials, the following adverse reactions were reported by more than 1% but less than 3% of the subjects receiving Cytotec and may be causally related to the drug: nausea, headache, flatulence, dyspepsia, vomiting, constipation and dizziness.

Elderly.

Post-marketing experience.

Immune system disorder.

Pregnancy, puerperium, and perinatal conditions.

Reproductive system and breast disorders.

Congenital, familial and genetic disorders.

General disorders and administration site conditions.

Reporting suspected adverse effects.

4.9 Overdose

Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnoea, abdominal pain, diarrhoea, fever, palpitations, hypotension or bradycardia. Hypertension and tachycardia have also been reported following overdoses. Overdose in pregnancy has resulted in uterine contractions with foetal death.
The toxic dose of Cytotec in human beings has not been determined. Cumulative total daily doses of 1600 micrograms have been tolerated with only symptoms of gastrointestinal discomfort being reported.
There is no specific antidote. Treatment should be symptomatic and supportive. Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal is most effective when administered within 1-hour of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected. Because misoprostol is metabolised like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Acid secretion.

Mucosal cytoprotective activity.

Clinical trials.

5.2 Pharmacokinetic Properties

Cytotec is rapidly absorbed following oral administration, with peak plasma levels of the active metabolite (misoprostol acid) occurring in about 30 minutes, as measured either by radioactive or cold (radioimmunoassay) methods. Misoprostol acid undergoes further metabolism by fatty acid oxidizing systems (beta and omega oxidation) which are present in numerous tissues in the body. The plasma elimination half-life of misoprostol acid is 20 - 40 minutes. The plasma elimination half-life of additional misoprostol metabolites is 1.5 hours.
Seventy-three percent of the radioactivity of an oral dose of radiolabelled misoprostol is excreted in the urine, with an additional 15% excreted in the faeces. About 56% of total radioactivity was eliminated in urine within 8 hours.
The serum protein binding of misoprostol acid, the primary metabolite, was in the range of 80 - 90% and was concentration independent in the therapeutic range. There was no accumulation of misoprostol in red blood cells.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, hypromellose, sodium starch glycollate, hydrogenated castor oil.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C and protect from moisture.

6.5 Nature and Contents of Container

The following presentations are registered: cold formed blister packs of 20 and 120* tablets and bottles of 12, 28, 60 and 120 tablets.
* Currently marketed pack size.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Misoprostol is a water soluble, viscous liquid.
Misoprostol is a synthetic prostaglandin E₁ analogue. Misoprostol has a molecular formula of C₂₂H₃₈O₅ and a molecular weight of 382.5.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes