Gemcitabine Mylan Pharma may be available in the countries listed below.
Gemcitabine hydrochloride (a derivative of Gemcitabine) is reported as an ingredient of Gemcitabine Mylan Pharma in the following countries:
International Drug Name Search
Lipocor may be available in the countries listed below.
Bezafibrate is reported as an ingredient of Lipocor in the following countries:
International Drug Name Search
Pravastatin Almus may be available in the countries listed below.
Pravastatin sodium salt (a derivative of Pravastatin) is reported as an ingredient of Pravastatin Almus in the following countries:
International Drug Name Search
MXL 30 mg, 60 mg, 90 mg, 120 mg, 150 mg, 200 mg prolonged release capsules.
Capsules containing morphine sulphate 30 mg, 60 mg, 90 mg, 120 mg, 150 mg, 200 mg.
For excipients, see 6.1.
Capsules, prolonged release
Hard gelatin capsules containing white to off white multiparticulates.
MXL capsules 30 mg are size 4, light blue capsules marked MS OD30.
MXL capsules 60 mg are size 3, brown capsules marked MS OD60.
MXL capsules 90 mg are size 2, pink capsules marked MS OD90.
MXL capsules 120 mg are size 1, olive capsules marked MS OD120.
MXL capsules 150 mg are size 1, blue capsules marked MS OD150.
MXL capsules 200 mg are size 0, rust capsules marked MS OD200
The prolonged relief of severe and intractable pain.
Route of administration
Oral.
The capsules may be swallowed whole or opened and the contents sprinkled on to soft cold food. The capsules and contents should not be crushed or chewed. MXL capsules should be used at 24-hourly intervals. The dosage is dependent upon the severity of the pain, the patient's age and previous history of analgesic requirements.
Adults and elderly
Patients presenting with severe uncontrolled pain, who are not currently receiving opioids, should have their dose requirements calculated through the use of immediate release morphine, where possible, before conversion to MXL capsules.
Patients presenting in pain, who are currently receiving weaker opioids should be started on:
a) 60 mg MXL capsule once-daily if they weigh over 70 kg.
b) 30 mg MXL capsule once-daily if they weigh under 70 kg, are frail or elderly.
Increasing severity of pain will require an increased dosage of MXL capsules using 30 mg, 60 mg, 90 mg, 120 mg, 150 mg or 200 mg alone or in combination to achieve pain relief. Higher doses should be made, where appropriate in 30% - 50% increments as required. The correct dosage for any individual patient is that which controls the pain with no or tolerable side effects for a full 24 hours.
Patients receiving MXL capsules in place of parenteral morphine should be given a sufficiently increased dosage to compensate for any reduction in analgesic effects associated with oral administration. Usually such increased requirement is of the order of 100%. In such patients individual dose adjustments are required.
Children aged 1 year and above
The use of MXL capsules in children has not been extensively evaluated.
For severe and intractable pain in cancer a starting dose in the range of 0.4 to 1.6 mg morphine per kg bodyweight daily is recommended. Doses should be titrated in the normal way as for adults.
Hypersensitivity to any of the constituents.
Respiratory depression, head injury, paralytic ileus, acute abdomen,delayed gastric emptying, obstructive airways disease, known morphine sensitivity, acute hepatic disease, concurrent administration of monoamine oxidase inhibitors (MAOIs) or within two weeks of discontinuation of their use. Not recommended during pregnancy or for pre-operative use or for the first 24 hours post-operatively. Children under one year of age.
As with all narcotics, a reduction in dosage may be advisable in the elderly, in hypothyroidism, in renal and chronic hepatic disease. Use with caution in patients with impaired respiratory function, convulsive disorders, acute alcoholism, delirium tremens, raised intracranial pressure, hypotension with hypovolaemia, severe cor pulmonale, opioid dependent patients, patients with a history of substance abuse, diseases of the biliary tract, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy and adrenocortical insufficiency. MXL capsules should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, MXL capsules should be discontinued immediately. As with all morphine preparations, patients who are to undergo cordotomy or other pain relieving surgical procedures should not receive MXL capsules for 24 hours prior to surgery. If further treatment with MXL capsules is then indicated the dosage should be adjusted to the new post-operative requirement.
It is not possible to ensure bio-equivalence between different brands of controlled release morphine products. Therefore, it should be emphasised that patients, once titrated to an effective dose should not be changed from MXL capsules to other slow, sustained or controlled release morphine or other potent narcotic analgesic preparations without retitration and clinical assessment.
The major risk of opioid excess is respiratory depression.
The patient may develop tolerance to the drug with chronic use and require progressively higher doses to maintain pain control. Prolonged use of this product may lead to physical dependence and a withdrawal syndrome may occur upon abrupt cessation of therapy. When a patient no longer requires therapy with morphine, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.
Morphine has an abuse profile similar to other strong agonist opioids. Morphine may be sought and abused by people with latent or manifest addiction disorders. The development of psychological dependence to opioid analgesics in properly managed patients with pain has been reported to be rare. However, data are not available to establish the true incidence of psychological dependence in chronic pain patients. The product should be used with particular care in patients with a history of alcohol and drug abuse.
The controlled release granules must be swallowed whole, and not broken, chewed, dissolved or crushed. The administration of broken, chewed or crushed morphine granules leads to a rapid release and absorption of a potentially fatal dose of morphine (see section 4.9).
Morphine may lower the seizure threshold in patients with a history of epilepsy.
Morphine should be used with caution in patients who are concurrently receiving other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, other tranquilizers, muscle relaxants, antihypertensives and alcohol. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these drugs are taken in combination with the usual doses of morphine. Morphine should not be co-administered with monoamine oxidase inhibitors or within two weeks of such therapy.
Mixed agonist/antagonist opioid analgesics (e.g. buprenorphine, nalbuphine, pentazocine) should not be administered to a patient who has received a course of therapy with a pure opioid agonist analgesic.
Cimetidine inhibits the metabolism of morphine.
Plasma concentrations of morphine may be reduced by rifampicin.
Although there are no pharmacokinetic data available for concomitant use of ritonavir with morphine, ritonavir induces the hepatic enzymes responsible for the glucuronidation of morphine, and may possibly decrease plasma concentrations of morphine.
MXL capsules are not recommended for use in pregnancy and labour due to the risk of neonatal respiratory depression. Administration to nursing mothers is not recommended as morphine is excreted in breast milk. Withdrawal symptoms may be observed in the newborn of mothers undergoing chronic treatment.
Morphine may modify the patient's reactions to a varying extent depending on the dosage and individual susceptibility. If affected, patients should not drive or operate machinery.
In normal doses, the commonest side effects of morphine are nausea, vomiting, constipation and drowsiness. With chronic therapy, nausea and vomiting are unusual with MXL capsules but should they occur the capsules can be readily combined with an anti-emetic if required. Constipation may be treated with appropriate laxatives.
Common (incidence of
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The effects of morphine have led to its abuse and dependence may develop with regular, inappropriate use. This is not a major concern in the treatment of patients with severe pain.
Signs of morphine toxicity and overdosage are drowsiness, pin-point pupils, skeletal muscle flaccidity, bradycardia, respiratory depression and hypotension. Circulatory failure and deepening coma may occur in more severe cases. Overdosage can result in death. Rhabdomyolysis progressing to renal failure has been reported in opioid overdosage.
Crushing and taking the contents of a controlled release dosage form leads to the release of the morphine in an immediate fashion; this might result in a fatal overdose.
Treatment of morphine overdosage:
Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation.
The pure opioid antagonists are specific antidotes against the effects of opioid overdose. Other supportive measures should be employed as needed.
In the case of massive overdosage, administer naloxone 0.8 mg intravenously. Repeat at 2-3 minute intervals as necessary, or by an infusion of 2 mg in 500 ml of normal saline or 5% dextrose (0.004 mg/ml).
The infusion should be run at a rate related to the previous bolus doses administered and should be in accordance with the patient's response. However, because the duration of action of naloxone is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. MXL capsules will continue to release and add to the morphine load for up to 24 hours after administration and the management of morphine overdosage should be modified accordingly.
For less severe overdosage, administer naloxone 0.2 mg intravenously followed by increments of 0.1 mg every 2 minutes if required.
Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to morphine overdosage. Naloxone should be administered cautiously to persons who are known, or suspected, to be physically dependent on morphine. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute withdrawal syndrome.
Gastric contents may need to be emptied as this can be useful in removing unabsorbed drug, particularly when a modified release formulation has been taken.
Pharmacotherapeutic group: natural opium alkaloid
ATC code: N02A A01
Morphine acts as an agonist at opiate receptors in the CNS particularly mu and to a lesser extent kappa receptors. mu receptors are thought to mediate supraspinal analgesia, respiratory depression and euphoria and kappa receptors, spinal analgesia, miosis and sedation.
Central Nervous System
The principal actions of therapeutic value of morphine are analgesia and sedation (i.e., sleepiness and anxiolysis). Morphine produces respiratory depression by direct action on brain stem respiratory centres.
Morphine depresses the cough reflex by direct effect on the cough centre in the medulla. Antitussive effects may occur with doses lower than those usually required for analgesia.
Morphine causes miosis, even in total darkness. Pinpoint pupils are a sign of narcotic overdose but are not pathognomonic (e.g., pontine lesions of haemorrhagic or ischaemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in the setting of morphine overdose.
Gastrointestinal Tract and Other Smooth Muscle
Morphine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm resulting in constipation.
Morphine generally increases smooth muscle tone, especially the sphincters of the gastrointestinal and biliary tracts. Morphine may produce spasm of the sphincter of Oddi, thus raising intrabiliary pressure.
Cardiovascular System
Morphine may produce release of histamine with or without associated peripheral vasodilation. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Endocrine System
Opioids may influence the hypothalamic-pituitary-adrenal or -gonadal axes. Some changes that can be seen include an increase in serum prolactin, and decreases in plasma cortisol, oestrogen and testosterone in association with inappropriately low or normal ACTH, LH or FSH levels. Clinical symptoms may be manifest from these hormonal changes.
Other Pharmacological Effects
In vitro and animal studies indicate various effects of natural opioids, such as morphine, on components of the immune system; the clinical significance of these findings is unknown.
Morphine is well absorbed from the capsules and, in general, peak plasma concentrations are achieved 2-6 hours following administration. The availability is complete when compared to an immediate release oral solution or MST CONTINUS tablets. The pharmacokinetics of morphine are linear across a very wide dose range. Morphine is subject to a significant first-pass effect which results in a lower bioavailability when compared to an equivalent intravenous or intramuscular dose.
The major metabolic transformation of morphine is glucuronidation to morphine-3-glucuronide and morphine-6-glucuronide which then undergo renal excretion. These metabolites are excreted in bile and may be subject to hydrolysis and subsequent reabsorption.
Because of the high inter-patient variation in morphine pharmacokinetics, and in analgesic requirements, the daily dosage in individual patients must be titrated to achieve appropriate pain control. Daily doses of up to 11.2 g have been recorded from twelve-hourly MST CONTINUS tablets. For this reason the capsules have been formulated in strengths of 30 mg, 60 mg, 90 mg, 120 mg, 150 mg and 200 mg.
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Hydrogenated vegetable Oil BP
Macrogol 6000 Ph Eur.
Talc Ph Eur.
Magnesium stearate Ph Eur.
Capsule shells
Gelatin (containing sodium dodecylsulphate)
The following colours are also present:
30 mg: indigo carmine (E132), titanium dioxide (E171);
60 mg: indigo carmine (E132), titanium dioxide (E171), iron oxide (E172);
90 mg: erythrosine (E127), titanium dioxide (E171), iron oxide (E172);
120 mg: indigo carmine (E132), titanium dioxide (E171), iron oxide (E172);
150 mg: erythrosine (E127), indigo carmine (E132), titanium dioxide (E171),
iron oxide (E172);
200 mg: titanium dioxide (E171), iron oxide (E172).
Printing ink
Shellac DAB 10
Iron oxide, black (E172)
Propylene glycol
Not applicable
2 years
Do not store above 25°C.
PVdC (
No special requirements
Napp Pharmaceuticals Ltd
Cambridge Science Park
Milton Road
Cambridge CB4 0GW
PL 16950/0042-47
29 March 1996/ 29 March 2006
September 2009
CD (Sch 2), POM
® MXL, NAPP and the NAPP device (logo) are Registered Trade Marks.
© 2009 Napp Pharmaceuticals Ltd
Nifedipine Merck may be available in the countries listed below.
Nifedipine is reported as an ingredient of Nifedipine Merck in the following countries:
International Drug Name Search
See also: Generic Zyprexa, Generic Zyprexa Zydis
Zyprexa Relprevv is a brand name of olanzapine, approved by the FDA in the following formulation(s):
No. There is currently no therapeutically equivalent version of Zyprexa Relprevv available.
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Zyprexa Relprevv. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
Patents are granted by the U.S. Patent and Trademark Office at any time during a drug's development and may include a wide range of claims.
Exclusivity is exclusive marketing rights granted by the FDA upon approval of a drug and can run concurrently with a patent or not. Exclusivity is a statutory provision and is granted to an NDA applicant if statutory requirements are met.
Hidralazina L.CH. may be available in the countries listed below.
Hydralazine is reported as an ingredient of Hidralazina L.CH. in the following countries:
International Drug Name Search
Generic Name: codeine and guaifenesin (KOE deen and gwye FEN a sin)
Brand Names: Allfen CD, Allfen CDX, Brontex, Cheracol with Codeine, Cheratussin AC, Dex-Tuss, Diabetic Tussin C, Duraganidin NR, ExeClear-C, Guaiatussin AC, Guaifen-C, Guiatuss AC, Guiatussin with Codeine, Iophen-C NR, M-Clear WC, Mar-cof CG, Mytussin AC, Robafen AC, Robitussin-AC, Tussi-Organidin NR, Tussi-Organidin-S NR, Tussiden C, Tusso-C
Codeine is in a group of drugs called narcotics. It is a cough suppressant that affects the signals in the brain that trigger cough reflex.
Guaifenesin is an expectorant. It helps loosen mucus congestion in your chest and throat, making it easier to cough out through your mouth.
The combination of codeine and guaifenesin is used to treat cough and to reduce chest congestion caused by upper respiratory infections or the common cold.
Codeine and guaifenesin may also be used for other purposes not listed in this medication guide.
To make sure you can safely take codeine and guaifenesin, tell your doctor if you have any of these other conditions:
heart disease, heart rhythm disorder;
asthma, COPD, emphysema, or other breathing disorders;
a history of head injury or brain tumor;
epilepsy or other seizure disorder;
a stomach or intestinal disorder;
Addison's disease or other adrenal gland disorders;
curvature of the spine;
a thyroid disorder;
enlarged prostate; or
a history of depression, mental illness, or drug addiction;
Liquid forms of this medication may contain sugar or artificial sweetener (phenylalanine). Talk to your doctor before using this form of codeine and guaifenesin if you have diabetes or phenylketonuria (PKU).
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Cough or cold medicine is usually taken only for a short time until your symptoms clear up.
Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using codeine and guaifenesin.
Keep track of the amount of medicine used from each new bottle. Codeine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.
Since cough medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
Overdose symptoms may include extreme dizziness or drowsiness, nausea, vomiting, sweating, confusion, hallucinations, cold and clammy skin, blue-colored lips or fingernails, weak or limp muscles, pinpoint pupils, weak pulse, slow breathing, fainting, or seizures (convulsions).
severe dizziness or drowsiness;
confusion, hallucinations, unusual thoughts or behavior;
urinating less than usual or not at all; or
slow heart rate, weak pulse, fainting, weak or shallow breathing.
Less serious side effects include:
dizziness, drowsiness, headache;
warmth, redness, or tingling under your skin;
nausea, vomiting, upset stomach;
constipation; or
skin rash or itching.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Also tell your doctor if you are using any of the following drugs:
cimetidine (Tagamet);
quinidine (Quin-G);
naloxone (Narcan); or
naltrexone (Vivitrol).
This list is not complete and other drugs may interact with codeine and guaifenesin. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
See also: Diabetic Tussin C side effects (in more detail)
Diazepam Mylan may be available in the countries listed below.
Diazepam is reported as an ingredient of Diazepam Mylan in the following countries:
International Drug Name Search
Treating swelling and pain after eye surgery
Loteprednol Ointment is a corticosteroid. It decreases inflammation (eg, redness, swelling, warmth, pain) of the eye.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Loteprednol Ointment. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Loteprednol Ointment. However, no specific interactions with Loteprednol Ointment are known at this time.
Ask your health care provider if Loteprednol Ointment may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Loteprednol Ointment as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Loteprednol Ointment.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Temporary blurred vision.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); changes in vision; eye pain, redness, or swelling.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Loteprednol side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.
Store Loteprednol Ointment at room temperature, between 59 and 77 degrees F (15 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Loteprednol Ointment out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Loteprednol Ointment. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Migraleve Yellow
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Film-coated tablets.
Yellow, capsule-shaped, film-coated tablets marked MGE on one face.
For the short term treatment of acute moderate pain which is not relieved by Paracetamol, ibuprofen or aspirin alone such as migraine attacks including the symptoms of migraine headache, nausea and vomiting.
Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.
Adults and the elderly: Two Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent. If further treatment is required, two Migraleve Yellow tablets every 4 hours.
Maximum dose: 8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.
Children 10 - 14 years: One Migraleve Pink tablet to be swallowed immediately it is known that a migraine attack has started or is imminent. If further treatment is required, one Migraleve Yellow tablet every 4 hours.
Maximum dose: 4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.
Do not give to children under 10 years of age except under medical supervision.
Do not give to children under 10 years of age except under medical supervision. Hypersensitivity to any of the ingredients.
Migraine should be medically diagnosed. Because some medicines do not combine, if you are already taking prescribed medicines please consult your doctor. If symptoms persist, consult your doctor.
Some individuals may be ultra-rapid metabolisers due to a specific CYP2D6*2x2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labelled dosage regimens, individuals who are ultra-rapid metabolisers may experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing.
The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese, Japanese and Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians and Arabs.
When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and inform their patients about these risks and the signs of morphine overdose (see section 4.6 Use during pregnancy and lactation).
Migraleve tablets contain potent medicaments and should not be taken continuously for extended periods without the advice of a doctor. Do not exceed the stated dose. Migraleve Pink Tablets only: May cause drowsiness. If affected, do not drive or operate machinery. Avoid alcoholic drink. Should be used with caution in patients with severe renal disease or liver dysfunction.
Keep out of the reach and sight of children.
For products in packs of 32 tablets or fewer:
Front of pack
• Can cause addiction.
• For three days use only.
Back of Pack
• Migraleve Yellow is for use in acute moderate pain associated with migraine which has been previously diagnosed by a doctor and where other painkillers have not worked. Do not take less than four hours after taking other painkillers.
• List of indications as agreed in 4.1 of the SmPC.
• If you need to take this medicine for more than three days you must see your doctor or pharmacist.
• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. If you take this medicine for headaches for more than three days it can make them worse.
For both POM and P products:
Patient Information Leaflet
Headlines (at the start of the PIL)
• For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone such as migraine attacks including the symptoms of migraine headache, nausea and vomiting.
• You should only take this product for a maximum of three days at a time. If you need to take it for longer than three days you should see your doctor or pharmacist for advice.
• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. This can give you withdrawal symptoms from the medicine when you stop taking it.
• If you take this medicine for headaches for more than three days it can make them worse.
Section 1: What this medicine is for
For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone such as migraine attacks including the symptoms of migraine headache, nausea and vomiting.
Section 2: Before taking this medicine
• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. This can give you withdrawal symptoms from the medicine when you stop taking it.
• If you take this painkiller for headaches for more than three days it can make them worse.
Section 3: How to take this medicine
Under the sub-heading 'Check the tables below to see how much medicine to take'
• Do not take less than four hours after taking other painkillers.
• Do not take for more than 3 days. If you need to use this medicine for more than three days you must speak to your doctor or pharmacist.
Under the sub-heading 'Special warnings about addiction'
• This medicine contains codeine which can cause addiction if you take it continuously for more than three days. When you stop taking it you may get withdrawal symptoms. You should talk to your doctor or pharmacist if you think you are suffering from withdrawal symptoms.
Section 4: Possible Side-effects
Some people may have side-effects when taking this medicine. If you have any unwanted side-effects you should seek advice from your doctor, pharmacist or other healthcare professional. Also you can help to make sure that medicines remain safe as possible by reporting any unwanted side-effects via the internet at www.yellowcard.gov.uk ; alternatively you can call Freephone 0808 100 3352 (available between 10am-2pm Monday – Friday) or fill in a paper form available from your local pharmacy.
Under the sub-heading 'How do I know if I am addicted?'
If you take the medicine according to the instructions on the pack it is unlikely that you will become addicted to the medicine. However, if the following apply to you it is important that you talk to your doctor:
• You need to take the medicine for longer periods of time.
• You need to take more than the recommended dose.
• When you stop taking the medicine you feel unwell but you feel better when you start taking the medicine again.
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
Although experiments in some animal species gave rise to adverse effects following the administration of buclizine to pregnant animals e.g. foetal abnormalities and maternal deaths, these occurred at doses in excess of 120 times the human daily dose. Whilst there are no specific reasons for contra-indicating Migraleve during pregnancy, as with all drugs it is recommended that Migraleve be used in pregnancy only when the physician has considered the need in respect of the patients' welfare.
Migraleve is not contra-indicated in breast-feeding mothers; however, codeine and its active metabolite, morphine, are secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low. Some women rapidly metabolise codeine, which may result in higher serum levels of codeine's active metabolite, morphine, in breast milk and, therefore, potentially dangerous levels of serum morphine in their breastfed infants. This could lead to potentially serious adverse reactions, including death, in nursing infants. Mothers using codeine should be informed about how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breast-feeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers should be instructed to talk to the baby's doctor immediately or seek emergency medical care.
Nursing mothers who rapidly metabolise codeine may also experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating paediatricians about the use of codeine during breast-feeding.
Migraleve Pink Tablets only: May cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.
Rare allergic reactions to paracetamol, such as skin rashes, hives or itching. Codeine may cause constipation.
Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped.
Prolonged use of a painkiller for headaches can make them worse.
Paracetamol
Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).
Risk Factors:
If the patient
• Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.
Or
• Regularly consumes ethanol in excess of recommended amounts.
Or
• Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section. Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable) but results should not delay initiation of treatment beyond 8 hours after ingestion, as the effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital.
Codeine
The effects in codeine overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.
Codeine overdose associated with central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.
Management of codeine overdose includes general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.
Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.
Paracetamol has analgesic, antipyretic and mild, acute anti-inflammatory properties. Paracetamol inhibits prostaglandin synthesis, especially in the CNS. Paracetamol does not inhibit chronic inflammatory reactions.
Codeine is an opioid analgesic. Codeine also has anti-tussive properties.
The combination of paracetamol and codeine has been shown to have hyperadditive analgesic effects in animals.
Paracetamol is rapidly absorbed from the upper G.I. tract after oral administration, with the small intestine being an important site of absorption. Peak blood levels of 15-20 mcg/ml after normal 1 g oral doses of paracetamol occur within 30 - 90 minutes. Depending upon dosage form, it is rapidly distributed throughout the body and is primarily metabolised in the liver with excretion via the kidney. Elimination half-life is about 2 hours after reaching a peak following a 1 g oral dose. Paracetamol crosses the placental barrier and is present in breast milk.
Codeine is absorbed from the gastro-intestinal tract and peak plasma concentrations occur after one hour. Codeine is metabolised by O- and N-demethylation in the liver to morphine, norcodeine and other metabolites. Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. Codeine is not extensively bound to plasma proteins. The plasma half-life has been reported to be between 3 and 4 hours.
No data presented.
Gelatin
Magnesium Stearate
Colloidal Anhydrous Silica
Stearic Acid
Pregelatinised Maize Starch
Hypromellose
Titanium Dioxide (E171)
Macrogol 400
Iron Oxide Yellow (E172)
Quinoline Yellow (E104)
Aluminium Oxide
None known.
36 months
None.
Packs of 12, 24 and 48 tablets
Blister strips consist of clear amber PVC blister film and paper/aluminium foil child-resistant blister lidding.
None.
McNeil Products Limited
Foundation Park
Roxborough Way
Maidenhead
Berkshire SL6 3UG
United Kingdom
PL 15513/0104
23 April 2001/ 28 January 2009
12 April 2010
Packs of 12 and 24 tablets: P
Packs of 48 tablets: POM
Zolafren may be available in the countries listed below.
Olanzapine is reported as an ingredient of Zolafren in the following countries:
International Drug Name Search
Generic Name: fluoride topical (FLOR ide TOP i kal)
Brand Names: ACT Fluoride Rinse, ACT Kids Fluoride Rinse, ACT Restoring Mouthwash Cinnamon, ACT Restoring Mouthwash Mint, ACT Restoring Mouthwash Spearmint, ACT Restoring Mouthwash Vanilla Mint, Control Rx, Denta 5000 Plus, Dentagel, Ethedent, Fluoridex, Fluoridex Daily Defense, Fluoridex Daily Defense Enhanced Whitening, Fluorigard, Fluorinse, Gel-Kam, Gel-Kam Dental Therapy Pak, Gel-Kam Dentinbloc, Gel-Kam Sensitivity Therapy, NaFrinse Daily/Acidulated, NaFrinse Daily/Neutral, Nafrinse Solution, NaFrinse Weekly, Neutracare Gel, Neutragard, Neutragard Advanced, Neutral Sodium Fluoride Rinse, Omnii Gel, Omnii Gel Just For Kids, Oral B Anti-Cavity, Perfect Choice, Perio Med, Phos-Flur, Prevident, Prevident 500 Plus Boost, PreviDent 5000 Booster, Prevident 5000 Dry Mouth, Prevident 5000 Plus, Prevident 5000 Sensitive, Prevident Dental Rinse, SF, SF 5000 Plus, Stop, Thera-Flur-N
Fluoride is a substance that strengthens tooth enamel. This helps to prevent dental cavities.
Fluoride topical is used as a medication to prevent tooth decay in patients that have a low level of fluoride topical in their drinking water. Fluoride topical is also used to prevent tooth decay in patients who undergo radiation of the head and/or neck, which may cause dryness of the mouth and an increased incidence of tooth decay.
Fluoride may also be used for other purposes not listed in this medication guide.
Before using fluoride topical, tell your dentist and doctor if you are on a low salt or a salt free diet. You may not be able to use fluoride topical, or you may need special tests while you are using it.
Overdose symptoms may result if you swallow large amounts of fluoride while using it.
Before using fluoride topical, tell your dentist and doctor if you are on a low salt or a salt free diet. You may not be able to use fluoride topical, or you may need special tests while you are using it.
If you have gum disease, some forms of fluoride topical may be irritating to your gums. Talk to your dentist or doctor if you have bothersome mouth irritation while using fluoride topical.
Use this medication exactly as directed on the label, or as it was prescribed by your dentist or doctor. Do not use it in larger amounts or for longer than recommended. Follow the directions on your prescription label.
Fluoride topical should be used immediately after brushing or flossing your teeth. For best results, use the medication just before bedtime, unless your doctor tells you otherwise.
Swish this medication in your mouth without swallowing. Then spit it out.
Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.
Overdose symptoms may include nausea, vomiting, stomach pain, diarrhea, drooling, numbness or tingling, loss of feeling anywhere in your body, muscle stiffness, or seizure (convulsions).
Overdose symptoms may result if you swallow large amounts of fluoride while using it.
discolored teeth;
weakened tooth enamel; or
any changes in the appearance of your teeth.
Less serious side effects may include:
stomach upset;
headache; or
weakness.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
It is not likely that other drugs you take orally or inject will have an effect on topically applied fluoride. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.
See also: NaFrinse Weekly side effects (in more detail)
Ondemet 4mg Tablets
Ondemet 4 mg
Each film-coated tablet contains 4 mg ondansetron (as hydrochloride dihydrate).
Excipients:
Each film-coated tablet contains 84.50 mg lactose monohydrate.
For a full list of excipients, see section 6.1.
Film coated tablet
4 mg: pale yellow, round biconvex, film-coated tablet embossed with 41 on one side, diameter 7.2 mm.
Ondansetron is indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy, and for the prevention of post-operative nausea and vomiting (PONV).
Oral use
For the different dosage regimens appropriate strengths and formulations are available.
Chemotherapy and radiotherapy induced nausea and vomiting
Adults
The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of Ondansetron should be flexible and selected as shown below.
Emetogenic chemotherapy and radiotherapy
For patients receiving emetogenic chemotherapy or radiotherapy ondansetron can be given either by oral or intravenous administration.
For most patients receiving emetogenic chemotherapy or radiotherapy, ondansetron should initially be administered intravenously immediately before treatment, followed by 8 mg orally twelve hourly.
For oral administration: 8 mg 1-2 hours before treatment, followed by 8 mg 12 hours later.
To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with ondansetron should be continued for up to 5 days after a course of treatment. The recommended dose for oral administration is 8 mg twice daily.
Highly emetogenic chemotherapy
For patients receiving highly emetogenic chemotherapy, e.g. high-dose cisplatin, ondansetron can be given by intravenous administration.
To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with ondansetron should be continued for up to 5 days after a course of treatment. The recommended dose for oral administration is 8 mg twice daily.
Children (aged 2 years and over) and adolescents (< 18 years)
Experience in paediatric patients is limited. In children older than two years, ondansetron may be administered as a single intravenous dose of 5 mg/m2 over 15 minutes immediately before chemotherapy, followed by 4 mg orally twelve hours later. Oral treatment with a dose according to the body area should be continued for up to 5 days after a course of treatment. Children with a total body area between 0.6 and 1.2 m2 should receive a dosage schedule of 4 mg 3 times a day, while children with a body area above 1.2 m2 should receive 8 mg 3 times a day.
There is no experience in children younger than 2 years old.
Ondansetron film-coated tablets cannot be used in children with a total body surface below 0.6 m2.
Elderly
Ondansetron is well tolerated by patients over 65 years and no alteration of dosage, dosing frequency or route of administration are required.
Please refer also to ”Special populations”.
Post-operative nausea and vomiting (PONV)
Adults
Prevention of PONV
For the prevention of PONV ondansetron can be administered orally or by intravenous injection.
For oral administration:
16 mg one hour prior to anaesthesia.
Alternatively, 8 mg one hour prior to anaesthesia followed by two further doses of 8 mg at eight hourly intervals.
Treatment of established PONV
For the treatment of established PONV intravenous administration is recommended.
Children (aged 2 years and over) and adolescents (< 18 years)
For the prevention and treatment of PONV slow intravenous injection is recommended.
Elderly
There is limited experience in the use of ondansetron in the prevention and treatment of post-operative nausea and vomiting (PONV) in the elderly, however ondansetron is well tolerated in patients over 65 years receiving chemotherapy.
Please refer also to ”Special populations”.
Special populations
Patients with renal impairment
No alteration of daily dosage or frequency of dosing, or route of administration are required.
Patients with hepatic impairment
Clearance of Ondansetron is significantly reduced and serum half life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg should not be exceeded.
Patients with poor sparteine/debrisoquine metabolism
The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisoquine. Consequently in such patients, repeat dosing will give medicinal product exposure levels no different from those of the general population. No alteration of daily dosage or frequency of dosing are required.
Hypersensitivity to ondansetron or to other selective 5-HT3-receptor antagonists (e.g. granisetron, dolasetron) or to any of the excipients.
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.
Very rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported. Therefore caution should be exercised in patients with cardiac rhythm or conduction disturbances, in patients treated with anti-arrhythmic agents or beta-adrenergic blocking agents and in patients with significant electrolyte disturbances.
As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.
In patients with adenotonsillar surgery prevention of nausea and vomiting with ondansetron may mask occult bleeding. Therefore, such patients should be followed carefully after ondansetron.
Since there is little experience to date of the use of ondansetron in cardiac patients, caution should be exercised if ondansetron is coadministered with anaesthetics to patients with arrhythmias or cardiac conduction disorders or to patients who are being treated with antiarrhythmic agents or beta-blockers.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Ondansetron film-coated tablets should not be used in children with a total body surface below 0.6 m2.
The medicinal product should not be used for children younger than two years, as for these patients the experience is limited.
There is no evidence that ondansetron either induces or inhibits the metabolism of other medicinal products commonly coadministered with it. Specific studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, propofol and thiopental.
Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising ondansetron, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall ondansetron clearance or dose requirement.
Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.
Tramadol: Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.
Pregnancy
Use in pregnancy has not been established and is not recommended.
To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. If it is absolutely necessary that Ondansetron be given caution should be exercised when prescribing to pregnant women especially in the first trimester. A careful risk/benefit assessment should be performed.
Lactation
Tests have shown that ondansetron passes into the milk of lactating animals (see section 5.3). It is therefore recommended that mothers receiving ondansetron should not breast-feed their babies.
Ondansetron has no or negligible influence on the ability to drive and use machines.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (
The following frequencies are estimated at the standard recommended doses of ondansetron according to indication and formulation.
Immune system disorders
Rare: Immediate hypersensitivity reactions sometimes severe, including anaphylaxis.
Nervous system disorders
Very common: Headache.
Uncommon: Extrapyramidal reactions (such as oculogyric crisis/dystonic reactions) have been observed without definitive evidence of persistent clinical sequelae; seizures.
Eye disorders
Rare: Transient visual disturbances (eg. blurred vision) predominantly during rapid intravenous administration.
Very rare: transient blindness predominantly during intravenous administration.
The majority of the blindness cases reported resolved within 20 minutes. Most patients had received chemotherapeutic agents, which included cisplatin. Some cases of transient blindness were reported as cortical in origin.
Cardiac disorders
Uncommon: Arrhythmias, chest pain with or without ST segment depression, bradycardia.
Very rare: Transient ECG changes including QT interval prolongation.
Vascular disorders
Common: Sensation of warmth or flushing.
Uncommon: Hypotension.
Respiratory, thoracic and mediastinal disorders
Uncommon: Hiccups.
Gastrointestinal disorders
Common: Constipation. Local burning sensation following insertion of suppositories.
Hepatobiliary disorders
Uncommon: Asymptomatic increases in liver function tests.
These events were observed commonly in patients receiving chemotherapy with cisplatin.
Little is known at present about overdosage with ondansetron, however, a limited number of patients received overdoses. Manifestations that have been reported include visual disturbances, severe constipation, hypotension and a vasovagal episode with transient second degree AV block. In all instances, the events resolved completely. There is no specific antidote for ondansetron, therefore in all cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate.
Pharmacotherapeutic group: Antiemetics and antinauseants, Serotonin (5-HT3) antagonists
ATC Code: A04AA01
Ondansetron is a potent, highly selective 5-HT3 receptor-antagonist.
Its precise antiemetic and antinauseal mechanism of action is not known. Chemotherapeutic agents and radiotherapy may cause release of 5-HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT3 receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5-HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of 5-HT3 receptors on neurons located both in the peripheral and central nervous system. The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.
In a pharmaco-psychological study in volunteers ondansetron has not shown a sedative effect.
Ondansetron does not alter plasma prolactin concentrations.
The role of ondansetron in opiate-induced emesis is not yet established.
Following oral administration, ondansetron is passively and completely absorbed from the gastrointestinal tract and undergoes first pass metabolism (bioavailability is about 60%). Peak plasma concentrations of about 30 ng/ml are attained approximately 1.5 hours after an 8 mg dose. For doses above 8 mg the increase in ondansetron systemic exposure with dose is greater than proportional; this may reflect some reduction in first pass metabolism at higher oral doses. Bioavailability, following oral administration, is slightly enhanced by the presence of food but unaffected by antacids. Studies in healthy elderly volunteers have shown slight, but clinically insignificant, age-related increases in both oral bioavailability (65%) and half-life (5 hours) of ondansetron. Gender differences were shown in the disposition of ondansetron, with females having a greater rate and extent of absorption following an oral dose and reduced systemic clearance and volume of distribution (adjusted for weight).
The disposition of ondansetron following oral, intramuscular(IM) and intravenous(IV) dosing is similar with a terminal half life of about 3 hours and steady state volume of distribution of about 140 L. Equivalent systemic exposure is achieved after IM and IV administration of ondansetron.
The protein binding of ondansetron is 70-76%. A direct effect of plasma concentration and anti-emetic effect has not been established. Ondansetron is cleared from the systemic circulation predominantly by hepatic metabolism through multiple enzymatic pathways. Less than 5% of the absorbed dose is excreted unchanged in the urine. The absence of the enzyme CYP2D6 has no effect on ondansetron's pharmacokinetics. The pharmacokinetic properties of ondansetron are unchanged on repeat dosing.
Following oral, intravenous or intramuscular dosing in patients with severe hepatic impairment, ondansetron's systemic clearance is markedly reduced with prolonged elimination half-lives (15-32 h) and an oral bioavailability approaching 100% due to reduced pre-systemic metabolism.
Preclinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
Ondansetron and its metabolites accumulate in the milk of rats, milk/plasma-ratio was 5.2.1.
A study in cloned human cardiac ion channels has shown ondansetron has the potential to affect cardiac repolarisation via blockade of HERG potassium channels. The clinical relevance of this finding is uncertain.
Tablet core:
Cellulose, microcrystalline
Lactose monohydrate
Starch, pregelatinised (maize)
Magnesium stearate
Film coating:
Hypromellose
Hydroxypropylcellulose
Propylene glycol
Sorbitan oleate
Sorbic acid
Vanillin
Titanium dioxide (E171)
Quinoline yellow (E 104).
Not applicable.
3 years.
This medicinal product does not require any special storage precautions.
Blister (PVC/Al)
4 mg: 6, 10, 30, 50 and 100 film coated tablets.
Not all pack sizes may be marketed.
No special requirements.
Beacon Pharmaceuticals Ltd
The Regent
The Broadway
Crowborough
East Sussex
TN6 1DA
UK
PL 18157/0016
08/06/2009
08/06/2009
