NovoMix 30 Penfill 100 U / ml, NovoMix 30 FlexPen 100 U / ml

1. Name Of The Medicinal Product

NovoMix 30 Penfill 100 U/ml suspension for injection in cartridge

NovoMix 30 FlexPen 100 U/ml suspension for injection in pre-filled pen

2. Qualitative And Quantitative Composition

1 ml of the suspension contains 100 U soluble insulin aspart*/protamine-crystallised insulin aspart* in the ratio 30/70 (equivalent to 3.5 mg).

1 cartridge contains 3 ml equivalent to 300 U.

1 pre-filled pen contains 3 ml equivalent to 300 U.

*Insulin aspart is produced by recombinant DNA technology in Saccharomyces cerevisiae.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Suspension for injection in cartridge. Penfill.

Suspension for injection in pre-filled pen. FlexPen.

White suspension.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of diabetes mellitus in adults, adolescents and children aged 10 to 17 years.

4.2 Posology And Method Of Administration

Posology

The potency of insulin analogues, including insulin aspart, is expressed in units (U), whereas the potency of human insulin is expressed in international units (IU).

NovoMix 30 dosing is individual and determined in accordance with the needs of the patient. Blood glucose monitoring and insulin dose adjustments are recommended to achieve optimal glycaemic control.

In patients with type 2 diabetes NovoMix 30 can be given as monotherapy. NovoMix 30 can also be given in combination with oral antidiabetic medicinal products if the patient's blood glucose is inadequately controlled with oral antidiabetic medicinal products alone. For patients with type 2 diabetes, the recommended starting dose of NovoMix 30 is 6 U at breakfast and 6 U at dinner (evening meal). NovoMix 30 can also be initiated once daily with 12 U at dinner (evening meal). When using NovoMix 30 once daily, it is generally recommended to move to twice-daily when reaching 30 units by splitting the dose into equal breakfast and dinner doses. If twice daily dosing with NovoMix 30 results in recurrent daytime hypoglycaemic episodes, the morning dose can be split into morning and lunchtime doses (thrice daily dose).

The following titration guideline is recommended for dose adjustments:

Pre-meal blood glucose level	NovoMix 30 dose adjustment
< 4.4 mmol/l	< 80 mg/dl	- 2 U
4.4 – 6.1 mmol/l	80 – 110 mg/dl	0
6.2 – 7.8 mmol/l	111 – 140 mg/dl	+ 2 U
7.9 – 10 mmol/l	141 – 180 mg/dl	+ 4 U
> 10 mmol/l	> 180 mg/dl	+ 6 U

The lowest of three previous days' pre-meal levels should be used. The dose should not be increased if hypoglycaemia occurred within these days. Dose adjustments can be made once a week until target HbA_1c is reached. Pre-meal blood glucose levels should be used to evaluate the adequacy of the preceding dose.

The combination of NovoMix 30 with pioglitazone should only be considered following clinical evaluation of the patient's risk of developing signs or symptoms of fluid-related adverse reactions. The initiation of NovoMix 30 should be undertaken cautiously titrating to the lowest dose required to achieve glycaemic control (see section 4.4).

In patients with type 1 diabetes the individual insulin requirement is usually between 0.5 and 1.0 U/kg/day. NovoMix 30 may fully or partially meet this requirement. The daily insulin requirement may be higher in patients with insulin resistance (e.g. due to obesity), and lower in patients with residual endogenous insulin production.

Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness.

In patients with diabetes mellitus optimised metabolic control effectively delays the onset and slows the progression of diabetic late complications. Optimised metabolic control, including glucose monitoring, is therefore recommended.

Special populations

Elderly (

NovoMix 30 can be used in elderly patients; however there is limited experience with the use of NovoMix 30 in combination with oral antidiabetic medicinal products in patients older than 75 years.

As with all insulin medicinal products, in elderly patients, glucose monitoring should be intensified and insulin aspart dose adjusted on an individual basis.

Renal and hepatic impairment

Renal or hepatic impairment may reduce the patient's insulin requirements.

As with all insulin medicinal products, in patients with renal or hepatic impairment, glucose monitoring should be intensified and insulin aspart dose adjusted on an individual basis.

Paediatric population

NovoMix 30 can be used in children and adolescents aged 10 years and above when premixed insulin is preferred. For children from 6 to 9 years old limited clinical data exists (see section 5.1).

No clinical studies with NovoMix 30 have been carried out in children under the age of 6 years.

NovoMix 30 should only be used in this age group under careful medical supervision.

Transfer from other insulin medicinal products

When transferring a patient from biphasic human insulin to NovoMix 30, start with the same dose and regimen. Then titrate according to individual needs (see titration guideline in table above).

As with all insulin medicinal products, close glucose monitoring is recommended during the transfer and in the initial weeks thereafter (see section 4.4).

Method of administration

NovoMix 30 is for subcutaneous administration only. NovoMix 30 must not be administrated intravenously, as it may result in severe hypoglycaemia. Intramuscular administration should be avoided. NovoMix 30 is not to be used in insulin infusion pumps.

NovoMix 30 has a faster onset of action than biphasic human insulin and should generally be given immediately before a meal. When necessary, NovoMix 30 can be given soon after a meal.

NovoMix 30 Penfill is designed to be used with Novo Nordisk insulin delivery systems and NovoFine or NovoTwist needles. The patient should be advised not to use any counterfeit needles.

NovoMix 30 Penfill is accompanied by a package leaflet with detailed instructions for use to be followed.

NovoMix 30 FlexPen are pre-filled pens designed to be used with NovoFine or NovoTwist needles. FlexPen delivers 1-60 units in increments of 1 unit. The patient should be advised not to use any counterfeit needles.

NovoMix 30 FlexPen is colour-coded and accompanied by a package leaflet with detailed instructions for use to be followed.

NovoMix 30 is administered subcutaneously by injection in the thigh or in the abdominal wall. If convenient, the gluteal or deltoid region may be used. Injection sites should always be rotated within the same region. The influence of different injection sites on the absorption of NovoMix 30 has not been investigated. As with all insulin medicinal products, the duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special Warnings And Precautions For Use

Inadequate dosing or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia and diabetic ketoacidosis. Usually the first symptoms of hyperglycaemia develop gradually over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath. In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal.

Before travelling between different time zones the patient should seek the doctor's advice since this may mean that the patient has to take the insulin and meals at different times.

Hypoglycaemia

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.

Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement (see section 4.8 and 4.9).

Compared with biphasic human insulin, NovoMix 30 may have a more pronounced glucose lowering effect up to 6 hours after injection. This may have to be compensated for in the individual patient, through adjustment of insulin dose and/or food intake.

Patients, whose blood glucose control is greatly improved, e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia, and should be advised accordingly. Usual warning symptoms may disappear in patients with longstanding diabetes.

Tighter control of glucose levels can increase the potential for hypoglycaemic episodes and therefore require special attention during dose intensification as outlined in section 4.2.

Since NovoMix 30 should be administered in immediate relation to a meal the rapid onset of action should be considered in patients with concomitant diseases or treatment where a delayed absorption of food might be expected.

Concomitant illness, especially infections and feverish conditions, usually increases the patient's insulin requirements. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland can require changes in insulin dose.

When patients are transferred between different types of insulin medicinal products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with their previous insulin.

Transfer from other insulin medicinal products

Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type, origin (animal, human, human insulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dose. Patients transferred to NovoMix 30 from another type of insulin may require an increased number of daily injections or a change in dose from that used with their usual insulins. If an adjustment is needed, it may occur with the first dose or during the first few weeks or months.

Injection site reactions

As with any insulin therapy, injection site reactions may occur and include pain, redness, hives, inflammation, swelling and itching. Continuous rotation of the injection site within a given area may help to reduce or prevent these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of NovoMix 30.

Combination of NovoMix with pioglitazone

Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. This should be kept in mind if treatment with the combination of pioglitazone and NovoMix is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

A number of medicinal products are known to interact with the glucose metabolism.

The following substances may reduce the patient's insulin requirements:

Oral antidiabetic medicinal products, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphonamides.

The following substances may increase the patient's insulin requirements:

Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol.

Beta-blockers may mask the symptoms of hypoglycaemia.

Octreotide/lanreotide may both increase or decrease insulin requirement.

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

4.6 Pregnancy And Lactation

Pregnancy

There is limited clinical experience with NovoMix 30 in pregnancy.

Animal reproduction studies have not revealed any differences between insulin aspart and human insulin regarding embryotoxicity or teratogenicity.

In general, intensified blood glucose control and monitoring of pregnant women with diabetes are recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimesters. After delivery, insulin requirements return rapidly to pre-pregnancy levels.

Breast-feeding

There are no restrictions on treatment with NovoMix 30 during breast-feeding. Insulin treatment of the nursing mother presents no risk to the baby. However, the NovoMix 30 dose may need to be adjusted.

Fertility

Animal reproduction studies have not revealed any differences between insulin aspart and human insulin regarding fertility.

4.7 Effects On Ability To Drive And Use Machines

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or using machines).

Patients should be advised to take precautions to avoid hypoglycaemia while driving. This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.

4.8 Undesirable Effects

a. Summary of the safety profile

Adverse reactions observed in patients using NovoMix are mainly dose-dependent and due to the pharmacologic effect of insulin.

The most frequently reported adverse reaction during treatment is hypoglycaemia. The frequencies of hypoglycaemia vary with patient population, dose regimens and level of glycaemic control, please see section c below.

At the beginning of the insulin treatment, refraction anomalies, oedema and local hypersensitivity reactions (pain, redness, hives, inflammation, swelling and itching at the injection site) may occur; these reactions are usually of transitory nature. Fast improvement in blood glucose control may be associated with acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.

b. Tabulated list of adverse reactions

Adverse reactions listed below are based on clinical trial data and classified according to MedDRA frequency and System Organ Class. Frequency categories are defined according to the following convention: Very common (

Immune system disorders	Uncommon - Urticaria, rash, eruptions
Very rare - Anaphylactic reactions*
Metabolism and nutrition disorders	Very common – Hypoglycaemia*
Nervous system disorders	Rare - Peripheral neuropathy
Eye disorders	Uncommon - Refraction disorders
Uncommon - Diabetic retinopathy
Skin and subcutaneous tissue disorders	Uncommon – Lipodystrophy*
Uncommon - Local hypersensitivity
General disorders and administration site conditions	Uncommon – Oedema

* see section c.

c. Description of selected adverse reactions

Hypoglycaemia:

The most frequently reported adverse reaction is hypoglycaemia. It may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. The symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.

In clinical trials the frequency of hypoglycaemia varied with patient population, dose regimens and level of glycaemic control. During clinical trials the overall rates of hypoglycaemia did not differ between patients treated with insulin aspart compared to human insulin.

Anaphylactic reactions:

The occurrence of generalised hypersensitivity reactions (including generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation and reduction in blood pressure ) is very rare but can potentially be life threatening.

Lipodystrophy:

Lipodystrophy is reported as uncommon. It may occur at the injection site; therefore it is recommended to rotate injection sites within an area.

d. Paediatric population

Based on post-marketing sources and clinical trials, the frequency, type and severity of adverse reactions observed in the paediatric population do not indicate any differences to the broader experience in the general population.

e. Other special populations

Based on post-marketing sources and clinical trials, the frequency, type and severity of adverse reactions observed in the elderly patients and in patients with renal or hepatic impairment do not indicate any differences to the broader experience in the general population.

4.9 Overdose

A specific overdose for insulin cannot be defined, however, hypoglycaemia may develop over sequential stages if too high doses relative to the patient's requirement are administered:

• Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient always carries sugar-containing products

• Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously, by a trained person, or with glucose given intravenously by a healthcare professional. Glucose must be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, intermediate-acting combined with fast-acting. ATC code: A10AD05.

NovoMix 30 is a biphasic suspension of 30% soluble insulin aspart (rapid-acting human insulin analogue) and 70% protamine-crystallised insulin aspart (intermediate-acting human insulin analogue).

Mechanism of action

The blood glucose lowering effect of insulin aspart is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.

NovoMix 30 is a biphasic insulin, which contains 30% soluble insulin aspart. This has a rapid onset of action, thus allowing it to be given closer to a meal (within zero to 10 minutes of the meal) when compared to soluble human insulin. The crystalline phase (70%) consists of protamine-crystallised insulin aspart, which has an activity profile that is similar to that of human NPH insulin (Figure 1).

When NovoMix 30 is injected subcutaneously, the onset of action will occur within 10 to 20 minutes of injection. The maximum effect is exerted between 1 and 4 hours after injection. The duration of action is up to 24 hours.

Figure 1: Activity profile of NovoMix 30 (^___) and biphasic human insulin 30 (---) in healthy subjects.

In a 3 month trial in patients with type 1 and type 2 diabetes NovoMix 30 showed equal control of glycosylated haemoglobin compared to treatment with biphasic human insulin 30. Insulin aspart is equipotent to human insulin on a molar basis. Compared to biphasic human insulin 30, administration of NovoMix 30 before breakfast and dinner resulted in lower postprandial blood glucose after both meals (breakfast and dinner).

A meta-analysis including nine trials in patients with type 1 and type 2 diabetes showed that fasting blood glucose was higher in patients treated with NovoMix 30, than in patients treated with biphasic human insulin 30.

In one study, 341 patients with type 2 diabetes were randomised to treatment with NovoMix 30 either alone or in combination with metformin, or to metformin together with sulfonylurea. The primary efficacy variable - HbA_1c after 16 weeks of treatment - did not differ between patients with NovoMix 30 combined with metformin and patients with metformin plus sulfonylurea. In this trial 57% of the patients had baseline HbA_1c above 9%; in these patients treatment with NovoMix 30 in combination with metformin resulted in significantly lower HbA_1c than metformin in combination with sulfonylurea.

In one study, patients with type 2 diabetes, insufficiently controlled on oral hypoglycaemic agents alone, were randomised to treatment with twice daily NovoMix 30 (117 patients) or once daily insulin glargine (116 patients). After 28 weeks treatment following the dosing guideline outlined in section 4.2, the mean reduction in HbA_1c was 2.8% with NovoMix 30 (mean at baseline = 9.7%). With NovoMix 30, 66% and 42% of the patients reached HbA_1c levels below 7% and 6.5%, respectively, and mean FPG was reduced by about 7 mmol/L (from 14.0 mmol/L at baseline to 7.1 mmol/L).

In patients with type 2 diabetes a meta-analysis showed a reduced risk of overall nocturnal hypoglycaemic episodes and major hypoglycaemia with NovoMix 30 compared to biphasic human insulin 30. The risk of overall daytime hypoglycaemic episodes was increased in patients treated with NovoMix 30.

Paediatric population

A 16-week clinical trial comparing postprandial glycaemic control of meal-related NovoMix 30 with meal-related human insulin/biphasic human insulin 30 and bedtime NPH insulin was performed in 167 subjects aged 10 to 18 years. Mean HbA_1c remained similar to baseline throughout the trial in both treatment groups, and there was no difference in hypoglycaemia rate with NovoMix 30 or biphasic human insulin 30.

In a smaller (54 subjects) and younger (age range 6 to 12 years) population, treated in a double-blind, cross-over trial (12 weeks on each treatment) the rate of hypoglycaemic episodes and the postprandial glucose increase was significantly lower with NovoMix 30 compared to biphasic human insulin 30. Final HbA_1c was significantly lower in the biphasic human insulin 30 treated group compared with NovoMix 30.

5.2 Pharmacokinetic Properties

Absorption, distribution and elimination

In insulin aspart substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin. The insulin aspart in the soluble phase of NovoMix 30 comprises 30% of the total insulin; this is absorbed more rapidly from the subcutaneous layer than the soluble insulin component of biphasic human insulin. The remaining 70% is in crystalline form as protamine-crystallised insulin aspart; this has a prolonged absorption profile similar to human NPH insulin.

The maximum serum insulin concentration is, on average, 50% higher with NovoMix 30 than with biphasic human insulin 30. The time to maximum concentration is, on average, half of that for biphasic human insulin 30. In healthy volunteers a mean maximum serum concentration of 140 ± 32 pmol/l was reached about 60 minutes after a subcutaneous dose of 0.20 U/kg body weight. The mean half life (t_½) of NovoMix 30, reflecting the absorption rate of the protamine bound fraction, was about 8-9 hours. Serum insulin levels returned to baseline 15-18 hours after a subcutaneous dose. In type 2 diabetic patients, the maximum concentration was reached about 95 minutes after dosing, and concentrations well above zero for not less than 14 hours post-dosing were measured.

Special populations

The pharmacokinetics of NovoMix 30 has not been investigated in elderly patients, or patients with renal or hepatic impairment.

Paediatric population

The pharmacokinetics of NovoMix 30 has not been investigated in children or adolescents. However, the pharmacokinetic and pharmacodynamic properties of soluble insulin aspart have been investigated in children (6–12 years) and adolescents (13–17 years) with type 1 diabetes. Insulin aspart was rapidly absorbed in both age groups, with similar t_max as in adults. However, C_max differed between the age groups, stressing the importance of the individual titration of insulin aspart.

5.3 Preclinical Safety Data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.

In in vitro tests, including binding to insulin and IGF-1 receptor sites and effects on cell growth, insulin aspart behaved in a manner that closely resembled human insulin. Studies also demonstrate that the dissociation of binding to the insulin receptor of insulin aspart is equivalent to human insulin.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Glycerol

Phenol

Metacresol

Zinc chloride

Disodium phosphate dihydrate

Sodium chloride

Protamine sulphate

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

6.2 Incompatibilities

In absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf Life

2 years.

After first opening: A maximum of 4 weeks when stored below 30°C.

6.4 Special Precautions For Storage

Store in a refrigerator (2°C – 8°C). Keep away from the cooling element. Do not freeze.

NovoMix 30 Penfill:

Keep the cartridge in the outer carton in order to protect from light.

NovoMix 30 FlexPen:

Keep the cap on FlexPen in order to protect from light.

After first opening or carried as a spare: Do not refrigerate. Store below 30°C.

NovoMix 30 must be protected from excessive heat and light.

6.5 Nature And Contents Of Container

NovoMix 30 Penfill:

3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a stopper (bromobutyl/polyisoprene) in a carton. The cartridge contains a glass ball to facilitate resuspension.

Pack sizes of 5 and 10 cartridges. Not all pack sizes may be marketed.

NovoMix 30 FlexPen:

3 ml suspension in cartridge (type 1 glass) with a plunger (bromobutyl) and a stopper (bromobutyl/polyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene. The cartridge contains a glass ball to facilitate resuspension.

Pack sizes of 1 (with or without needles), 5 (without needles) and 10 (without needles) pre-filled pens. Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Needles, NovoMix 30 Penfill and NovoMix 30 FlexPen must not be shared. The cartridge must not be refilled.

After removing NovoMix 30 Penfill and NovoMix 30 FlexPen from the refrigerator, it is recommended to allow NovoMix 30 Penfill and NovoMix 30 FlexPen to reach room temperature before resuspending the insulin as instructed for first time use.

NovoMix 30 must not be used if the resuspended liquid does not appear uniformly white and cloudy.

The necessity of resuspending the NovoMix 30 suspension immediately before use is to be stressed to the patient.

NovoMix 30 which has been frozen must not be used.

The patient should be advised to discard the needle after each injection.

7. Marketing Authorisation Holder

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd

Denmark

8. Marketing Authorisation Number(S)

NovoMix 30 Penfill	EU/1/00/142/004
NovoMix 30 FlexPen	EU/1/00/142/009

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 1 August 2000

Date of last renewal: 2 July 2010

10. Date Of Revision Of The Text

02/2011

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

Matrifen

m a t r i f e n^TM

Matrifen 12 micrograms/hour transdermal patch

Matrifen 25 micrograms/hour transdermal patch

Matrifen 50 micrograms/hour transdermal patch

Matrifen 75 micrograms/hour transdermal patch

Matrifen 100 micrograms/hour transdermal patch

Fentanyl

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.



• If you have further questions, please ask your doctor or your pharmacist.



• This medicine has been prescribed for you personally and you should not pass it on to others. It may harm them, even if their symptoms are the same as yours.



• If any of the side effects are serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Matrifen is and what it is used for


• 2. Before you use Matrifen


• 3. How to use Matrifen


• 4. Possible side effects


• 5. Storing Matrifen


• 6. Further information

What Matrifen Is And What It Is Used For

Matrifen belongs to a group of strong painkillers called opioids and acts through blocking the pain signals to the brain.

In Matrifen transdermal patch the active substance fentanyl is deposited. Fentanyl is gradually released from the patch, passes through the skin and into the body, where it relieves severe and long-lasting pain, which can only be relieved by opioids. One transdermal patch relieves pain for 72 hours (3 days).

Before You Use Matrifen

WARNING

Matrifen is a drug that could be life-threatening to children. This is also the case with used transdermal patches. Bear in mind that the design of this medicinal product could be tempting to a child.

Matrifen can have life-threatening side-effects in persons that are not using prescribed opioid drugs on a regular basis.

Do not use Matrifen:

• if you are hypersensitive (allergic) to fentanyl or any of the ingredients of the product



• If you suffer from short-term pain (e.g. after a surgical procedure)



• if your central nervous system is severely impaired, for instance by brain injury



• if you concomitantly take MAO-inhibitors (e.g. moclobemide against depression or selegiline against Parkinson’s disease) or have taken such medicine during the last 14 days.

Take special care with Matrifen

Before starting to use Matrifen you should inform your doctor if you suffer from any of the following disorders:

• asthma, respiratory depression or any lung disease



• irregular heartbeat



• low blood pressure



• impaired liver function



• impaired kidney function



• if you have had a head injury or brain disease (e.g. a tumour)



• if you suffer from a disease causing fatigue and weakness of the muscles (myasthenia gravis).

Inform your doctor if you develop a fever during the treatment, as the increased body temperature may cause too much medicine to pass through the skin. For the same reason you should avoid exposing the patch on the skin to direct heat such as electric blankets, hot-water bottles, sauna, solarium or hot baths. It is acceptable to stay outside in the sun, but you must protect the patch with a piece of clothing during hot summer days.

The transdermal patches should not be divided or cut. Decreasing relief of pain (tolerance), physical or psychological dependence may develop if you use Matrifen for a longer period. However, this is rarely seen during treatment of pain due to cancer.

Elderly patients should be monitored when using Matrifen.

Matrifen should not be given to children under 2 years of age or to children who have not previously been treated with strong painkillers such as morphine.

Taking other medicines:

Certain other medicines may affect or be affected by Matrifen. Some of these medicines are:

• Painkillers (e.g. opioids such as pen-tazocin, buprenorphine morphine and codeine), medicines to treat anxiety and tranquilisers, sleeping medicines, general anaesthetics, phenothiazines (medicine against psychosis), sedating antihistamines (certain medicines for allergy and travel sickness causing drowsiness) and muscle relaxants



• Barbituric acid derivatives (medicine for epilepsy)



• Ritonavir (for HIV)



• Itraconazole and ketoconazole (for fungal infections)



• MAO-inhibitors (e.g. moclobemide for depression or selegiline for Parkinson’s disease)



• Macrolide antibiotics (e.g. azithromycin and erythromycin).

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

Using Matrifen with food and drink

Alcohol may increase the risk of breathing problems.

Pregnancy and breast-feeding

Do not use Matrifen if you are pregnant or breastfeeding unless your doctor has weighed the risks of not using to be greater than using Matrifen. Safe use during pregnancy has not been established.

Long-term treatment during pregnancy may cause withdrawal symptoms in the newborn child. If you become pregnant during treatment with Matrifen, consult your doctor.

Driving and using machines:

Fentanyl transdermal patch may impair your mental and/or physical ability to perform potentially hazardous tasks such as driving or operating machinery. During treatment with Matrifen certain undesirable effects may occur (for example drowsiness, apathy or sickness). This should be kept in mind when doing things that require your full attention, for instance during driving a car. You alone are responsible to decide if you are in a fit condition to drive a motor vehicle or perform other tasks that demands increased concentration. Because of their effects or side effects, one of the factors that can reduce your ability to these things safely is your use of medicines. Read all the information in this leaflet for guidance. Discuss with your doctor or pharmacist if you are unsure about anything.

Used transdermal patches

High quantities of drug remain in the transdermal patches even after use. Used transdermal patches, as well as any unused transdermal patches should therefore be kept out of reach and sight of children and pets, and discarded according to local requirements or returned to the pharmacy.

How To Use Matrifen

Always use Matrifen exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

The dose is determined by your doctor, who will adjust it for you individually. Always follow your doctor’s instructions.

The normal dose is usually one patch every three days. According to your reaction the strength of the patch or the number of patches may need to be adjusted. The effect is reached within 24 hours after the first patch has been applied. Do not discontinue treatment without consulting your doctor.

How to apply Matrifen transdermal patch

• Find a flat part of your upper body (trunk) or upper arm, where the skin is without hair, cuts, spots or other skin blemishes. The body part must not have been irradiated in connection with radiation therapy.



• The patch should be applied to the upper back when the product is used by children. This reduces the possibility of the removal by the child.



• If the skin is hairy, then cut the hair with scissors. Do not shave, as shaving irritates the skin. If the skin needs washing, wash with water. Do not use soap, oil, lotions, alcohol or other cleansers that may irritate the skin. The skin must be completely dry before applying the patch.



• The patch must be stuck on immediately after opening the package. When the protective plastic has been removed, the patch is applied by pressing it firmly onto the skin with the palm of the hand for approximately 30 seconds to make sure that the patch sticks well to the skin. Pay special attention to see that the patch sticks properly at the edges.



• A Matrifen transdermal patch is used for 72 hours (3 days). On the outer package you can write the date and time you applied the patch. This may help you remember when to change your patch.



• The patch should not be divided or cut.

How to change the transdermal patch

• After 72 hours (3 days) you can remove the patch. Usually the patch does not come off by itself.



• Fold the used patch in half so that the sticky edges adhere to each other. Put back used patches in the outer package and hand in to your pharmacist or discard according to local requirements.



• Apply a new patch as described above but on another part of the skin. At least 3 days should go by before the same part is used again.

If you use more Matrifen than you should:

If you have stuck on more patches than prescribed, remove the patches and contact your doctor, hospital or Poisons Information Service for their opinion of the risk.

The most common sign of overdose is reduced ability to breathe. Symptoms are that the person breathes abnormally slowly or weakly. If this should occur – remove the patches and contact a doctor immediately. While waiting for the doctor, keep the person awake by talking to or shaking her/him now and then.

Other signs and symptoms of overdose are drowsiness, low body temperature, slow heart rate, decreased muscle tone, deep sedation, loss of muscle co-ordination, constriction of the pupils and convulsions.

If you forget to use or change your patch:

You should change your patch at the same time every three days, if not otherwise instructed by your doctor. If you forget to change your patch, change it as soon as you remember.

If you are very late changing your patch, you should contact your doctor because you might need some extra painkillers.

Matrifen Side Effects

Like all medicines, Matrifen can have side effects, although not everybody gets them.

If any of the following serious, very rare side effects occur, you should discontinue treatment and immediately contact your doctor or go to a hospital: severe respiratory depression (severe breathlesness, rattling breath) or complete block of the digestion channel (convulsive pain, vomiting, flatulence).

Other side effects

Very common (occur in more than 1 of 10 patients):

Drowsiness, headache, feeling sick, vomiting, constipation, sweating, itching.

Common (occur in more than 1 of 100 patients):
Apathy, confusion, depression, anxiety, nervousness, hallucinations, reduced appetite, dry mouth, stomach upset, skin irritation at the application site.

Uncommon (occur in less than 1 of 100 patients):
Unnatural feeling of happiness, loss of memory, difficulties in sleeping, restlessness, shivering, feelings of stinging in the skin (like ants are crawling on the skin called paraesthesia), speech disturbances, irregular heartbeat, high or low blood pressure, difficulty in breathing, diarrhoea, rash, blushing, difficulties in passing urine.

Rare (occur in less than 1 of 1000 patients): Hazy vision, dilated blood vessels, hiccups, serious allergic reaction (difficulty in breathing, wheeze while breathing, rash), swelling, feeling cold.

Very rare (occur in less than 1 of 10,000 patients):

Delusions, loss of physical strength, disorder in the sexual functions disorders, loss of muscle co-ordination, convulsions, slow or weak breath, difficulty breathing, blood in the mouth due to unusual accumulation of blood in the lungs, sore throat, stomach pain due to block of the digestion channel (ileus), feeling bloated due to painful gases in the stomach or the guts, unusually low production of urine, pain in the urine bladder.

Other adverse reactions Decreasing relief of pain (tolerance), physical and psychological dependence can develop during longterm use of fentanyl.

Opioid withdrawal symptoms (for instance: nausea, vomiting, diarrhoea, anxiety and shivering) may occur in patients after switching from previously prescribed opioid analgesics to Matrifen transdermal patch.

The side effects observed in children and adolescents treated with fentanyl are similar to those observed in adults. However some side effects are more common in children and adolescents (fever, being or feeling sick and nausea).

Please inform your doctor if any of the side effects are serious or if you experience disturbing side effects or notice any side effects not mentioned in this leaflet.

How To Store Matrifen

Keep out of the reach and sight of children, even after use. High quantities of the drug remain in the transderm al patches even after use.

Do not use Matrifen after the expiry date stated on the package. The expiry date refers to the last day of that month.

For environmental and safety reasons, used as well as unused and out of date patches must be discarded to local requirements or returned to the pharmacy for disposal. Used patches should be folded in half with the sticky sides together and kept in the outer package until discarded or delivered to the pharmacy.

Further Information

What Matrifen transdermal patch contains

The active substance is: Fentanyl. Each transdermal patch contains 1.38 mg, 2.75 mg, 5.5 mg, 8.25 mg or 11 mg in a patch of 4.2, 8.4, 16.8, 25.2 or 33.6 cm² and releases 12, 25, 50, 75 or 100 micrograms/hour.

Other ingredients are: Dipropylene glycol, hydroxypropyl cellulose, dimeticone, silicone adhesives (amine resistant), ethylenvinylacetate (EVA, release membrane), polyethylene terephthalate (PET, backing film), fluoropolymercoated polyester (protective film) and printing ink.

What Matrifen looks like and contents of the pack

Matrifen is a transparent and rectangular transdermal patch. The transdermal patches are equipped with a coloured imprint with the trade name, active substance and strength:

• Matrifen 12 micrograms/hour patch: brown imprint


• Matrifen 25 micrograms/hour patch: red imprint


• Matrifen 50 micrograms/hour patch: green imprint


• Matrifen 75 micrograms/hour patch: light blue imprint


• Matrifen 100 micrograms/hour patch: grey imprint

The patches are supplied in cartons containing 1, 2, 3, 4, 5, 8, 10, 16 and 20 patches. Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Nycomed UK Ltd.

Three Globeside Business Park

Fieldhouse Lane

Marlow

Bucks

SL7 1HZ

UK

Manufacturer:

Nycomed Danmark ApS

PO Box 88

Langebjerg 1

DK-4000 Roskilde

Denmark

Nycomed GmbH

Robert-Bosch-Strasse 8

78224 Singen

Germany

This medicinal product is authorised in the Member States of the EEA under the following names:

Matrifen: Belgium, Czech Republic, Denmark, Estonia, Finland, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, The Netherlands, Norway, Poland, Slovak Republic, Slovenia, Sweden, United Kingdom

Fentanilo, Matrifen: Portugal.

This leaflet was last approved in November 2008

GBR/IRL-5

650XXXX

Hypercalciuria Medications

Definition of Hypercalciuria: The excretion of abnormally large amounts of calcium in the urine, seen in cases of hyperparathyroidism.

Drugs associated with Hypercalciuria

The following drugs and medications are in some way related to, or used in the treatment of Hypercalciuria. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Drug List:

Mithracin

Myozyme

Pronunciation: AL-gloo-KOE-si-dase
Generic Name: Alglucosidase Alfa
Brand Name: Examples include Lumizyme and Myozyme

Myozyme may cause severe allergic reactions, including anaphylactic shock. The reaction may occur while you receive Myozyme or up to several hours after. Tell your health care provider immediately if you experience rash; hives; trouble breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; or unusual hoarseness while receiving Myozyme. Only use Myozyme where appropriate measures to treat a severe allergic reaction are available.

Certain brands of Myozyme are only available through a restricted distribution program. Patients who receive certain brands of Myozyme must be enrolled and meet all the conditions of this program.

Myozyme is used for:

Treating Pompe disease (alfa-glucosidase deficiency) in certain patients.

Myozyme is a glycoprotein. It works by replacing the enzyme alfa-glucosidase in the body.

Do NOT use Myozyme if:

• you are allergic to any ingredient in Myozyme

Contact your doctor or health care provider right away if any of these apply to you.

Before using Myozyme:

Some medical conditions may interact with Myozyme. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have ever had a reaction (eg, swelling, trouble breathing) to any intravenous (IV) medicine


• if you are or have recently been ill


• if you have heart problems (eg, enlarged heart) or lung problems

Some MEDICINES MAY INTERACT with Myozyme. However, no specific interactions with Myozyme are known at this time.

Ask your health care provider if Myozyme 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.

How to use Myozyme:

Use Myozyme as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Myozyme will be given as an injection at your doctor's office, hospital, or clinic.


• Do not use Myozyme if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.


• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.


• Continue to use Myozyme even if you feel well. Do not miss any doses.


• If you miss a dose of Myozyme, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Myozyme.

Important safety information:

• Tell your doctor or dentist that you use Myozyme before you receive any medical or dental care, emergency care, or surgery.


• Lab tests, including liver function and immune system, may be performed while you use Myozyme. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Certain brands of Myozyme should only be used for specific types of Pompe disease. Check with you doctor if you have any questions about this information.


• Caution is advised when using Myozyme in CHILDREN; they may be more sensitive to its effects.


• Certain brands of Myozyme should be used with extreme caution in CHILDREN younger than 8 years old; safety and effectiveness in these children have not been confirmed. Check with your doctor if you have questions about this information.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Myozyme while you are pregnant. It is not known if Myozyme is found in breast milk. If you are or will be breast-feeding while you use Myozyme, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Myozyme:

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:

Constipation; diarrhea; heartburn; runny nose; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue; unusual hoarseness); agitation, irritability, or restlessness; blue skin or nails; chest pain or tightness; chills; cold hands or feet; cough; ear pain; excessive or cold sweat; fast, slow, or irregular heartbeat; feeling hot; fever; flushing; headache; hearing changes; increased tear production; muscle pain, stiffness, or twitching; nausea; nosebleed; pain, swelling, or redness at the injection site; pale skin; purplish skin discoloration; rapid or difficult breathing; severe headache, dizziness, or vomiting; shortness of breath; sore throat; stomach or back pain; swelling of the hands, legs, or feet; throat tightness; tremor; unexplained cough; unusual tiredness or weakness; vision changes; wheezing; white patches in the mouth.

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: Myozyme side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Myozyme:

Myozyme is usually handled and stored by a health care provider. If you are using Myozyme at home, store Myozyme as directed by your pharmacist or health care provider. Keep Myozyme out of the reach of children and away from pets.

General information:

• If you have any questions about Myozyme, please talk with your doctor, pharmacist, or other health care provider.


• Myozyme is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Myozyme. 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.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Myozyme resources

• Myozyme Side Effects (in more detail)
• Myozyme Use in Pregnancy & Breastfeeding
• Myozyme Support Group
• 0 Reviews for Myozyme - Add your own review/rating

• Myozyme Prescribing Information (FDA)


• Myozyme Advanced Consumer (Micromedex) - Includes Dosage Information


• Myozyme Monograph (AHFS DI)


• Myozyme Consumer Overview


• Alglucosidase Alfa Professional Patient Advice (Wolters Kluwer)


• Lumizyme Consumer Overview


• Lumizyme Prescribing Information (FDA)

Compare Myozyme with other medications

• Pompe disease

Amevive

Generic Name: Alefacept (a-LE-fa-sept)
Brand Name: Amevive

Amevive is used for:

Treating moderate to severe psoriasis.

Amevive is an immunosuppressant. It works by decreasing the activity of immune cells and decreasing the rate of skin cell multiplication.

Do NOT use Amevive if:

• you are allergic to any ingredient in Amevive


• you are taking a medicine that can suppress your immune system (eg, cancer chemotherapy, prednisone, cyclosporine)


• if you have or are at high risk of developing tumors

Contact your doctor or health care provider right away if any of these apply to you.

Before using Amevive:

Some medical conditions may interact with Amevive. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of cancer, recurrent infection (eg, pneumonia, skin infections, tuberculosis), or immune system disorder (immunosuppression)


• if you are receiving phototherapy or planning to receive vaccinations


• if you have herpes or syphilis

Some MEDICINES MAY INTERACT with Amevive. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Certain immunosuppressants (eg, chemotherapy, prednisone, methotrexate , cyclosporine) because too much immune system suppression may occur, increasing risk of side effects including risk of infection

This may not be a complete list of all interactions that may occur. Ask your health care provider if Amevive 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.

How to use Amevive:

Use Amevive as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Amevive comes with an additional patient leaflet. Read it carefully and reread it each time you get Amevive refilled.


• Amevive is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Amevive at home, carefully follow the injection procedures taught to you by your health care provider.


• Amevive is given by vein (intravenously [IV]) once weekly. Plan your injection on the same day each week to help you remember to administer it.


• Do not shake Amevive. This will prevent foaming of the medicine.


• If Amevive contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.


• Use Amevive regularly to receive the most benefit from it.


• Keep this product, as well as syringes and needles, out of the reach of children. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor, nurse, or pharmacist to explain local regulations for proper disposal.


• If you miss a dose of Amevive, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Amevive.

Important safety information:

• Amevive may cause dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Amevive. Using Amevive alone, with certain other medicines, or with alcohol may lessen your ability to drive or to perform other potentially dangerous tasks.


• Avoid vaccinations with live virus vaccines (eg, measles, mumps, oral polio) while you are taking Amevive. Avoid contact with people who have recently received the oral polio vaccine.


• Carry an identification card at all times that says you taking this medication.


• Amevive may slightly increase your risk of developing a cancer. Contact your health care provider at once if you develop signs or symptoms of a tumor or infection.


• LAB TESTS, including T lymphocyte counts, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• Use Amevive with caution in the ELDERLY because they may be more sensitive to its effects.


• Amevive is not recommended for use in CHILDREN; safety and effectiveness have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you plan on becoming pregnant, discuss with your doctor the benefits and risks of using Amevive during pregnancy. Notify your health care provider if you become pregnant while using Amevive or within 8 weeks after stopping treatment. It is unknown if Amevive is excreted in breast milk. Do not breast-feed while taking Amevive.

Possible side effects of Amevive:

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:

Dizziness; increased cough; muscle aches or pain; nausea; pain or swelling at the injection site; sore throat or throat inflammation.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; chills; fever; new or altered skin lesions or spots; painful or frequent urination; persistent sore throat; serious infections; swollen glands; unusual lumps; unusual vaginal discharge ; white patches in the mouth (oral thrush).

This is not a complete list of all side effects that may occur. If you have questions or need medical advice about side effects, contact your doctor or health care provider. You may report side effects to the FDA at 1-800-FDA-1088 (1-800-332-1088) or at http://www.fda.gov/medwatch.

See also: Amevive side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center (http://www.aapcc.org/DNN/), or emergency room immediately. Symptoms may include chills; headache; joint pain.

Proper storage of Amevive:

Store Amevive at room temperature between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Keep in the original carton until ready for use. Once prepared, the diluted solution should be refrigerated at 36 to 46 degrees F (2 to 8 degrees C) and used within 4 hours. Check the expiration date on the label and properly discard any unused medicine after that time. Do not store in the bathroom. Keep Amevive out of the reach of children and away from pets.

General information:

• If you have any questions about Amevive, please talk with your doctor, pharmacist, or other health care provider.


• Amevive is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.

This information is a summary only. It does not contain all information about Amevive. 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.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Amevive resources

• Amevive Side Effects (in more detail)
• Amevive Use in Pregnancy & Breastfeeding
• Amevive Drug Interactions
• Amevive Support Group
• 1 Review for Amevive - Add your own review/rating

Compare Amevive with other medications

• Psoriasis

Aripiprazole Solution

Pronunciation: AR-i-PIP-ra-zole
Generic Name: Aripiprazole
Brand Name: Abilify

Aripiprazole Solution is an antipsychotic. It may increase the risk of death when used to treat mental problems caused by dementia in elderly patients. Most of the deaths were linked to heart problems or infection. Aripiprazole Solution is not approved to treat mental problems caused by dementia.

Antidepressants may increase the risk of suicidal thoughts or actions in children, teenagers, and young adults. However, depression and certain other mental problems may also increase the risk of suicide. Talk with the patient's doctor to be sure that the benefits of using Aripiprazole Solution outweigh the risks.

Families and caregivers must closely watch patients who take Aripiprazole Solution. It is important to keep in close contact with the patient's doctor. Tell the doctor right away if the patient has symptoms like worsened depression, suicidal thoughts, or changes in behavior. Discuss any questions with the patient's doctor.

Aripiprazole Solution is used for:

Treating schizophrenia, bipolar disorder, and irritability associated with autistic disorder. It is also used along with other medicines to treat depression. It may also be used for other conditions as determined by your doctor.

Aripiprazole Solution is an atypical antipsychotic. Exactly how it works is not known. It affects certain substances in the brain.

Do NOT use Aripiprazole Solution if:

• you are allergic to any ingredient in Aripiprazole Solution

Contact your doctor or health care provider right away if this applies to you.

Video: Treatment for Depression

Treatments for depression are getting better everyday and there are things you can start doing right away.

Before using Aripiprazole Solution:

Some medical conditions may interact with Aripiprazole Solution. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of heart problems (eg, heart failure, irregular heartbeat, heart attack), low blood pressure, blood vessel problems, or stroke


• if you have a history of low white blood cell levels, including low white blood cell levels caused by any medicine


• if you have a history of seizures, dementia, Alzheimer disease, depression or other mental or mood disorders, or suicidal thoughts or attempts


• if you have trouble swallowing or a history of neuroleptic malignant syndrome (NMS)


• if you are dehydrated, have low blood volume, or are taking medicine for high blood pressure


• if you or a family member has a history of diabetes or you are very overweight

Some MEDICINES MAY INTERACT with Aripiprazole Solution. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticholinergics (eg, benztropine, methscopolamine) because the risk of overheating may be increased


• Benzodiazepines (eg, lorazepam), clarithromycin, imidazole antifungals (eg, ketoconazole), quinidine, selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), or voriconazole because they may increase the risk of Aripiprazole Solution's side effects


• Carbamazepine, hydantoins (eg, phenytoin), or rifampin because they may decrease Aripiprazole Solution's effectiveness


• Alpha-blockers (eg, terazosin) because the risk of their side effects may be increased by Aripiprazole Solution

This may not be a complete list of all interactions that may occur. Ask your health care provider if Aripiprazole Solution 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.

How to use Aripiprazole Solution:

Use Aripiprazole Solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Aripiprazole Solution comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Aripiprazole Solution refilled.


• Take Aripiprazole Solution by mouth with or without food.


• Taking Aripiprazole Solution at the same time each day will help you remember to take it.


• Take Aripiprazole Solution on a regular schedule to get the most benefit from it.


• Use the measuring cup that comes with Aripiprazole Solution to measure your dose. Ask your pharmacist for help if you are unsure of how to measure your dose.


• Continue to take Aripiprazole Solution even if you feel well. Do not miss any doses.


• If you miss a dose of Aripiprazole Solution, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Aripiprazole Solution.

Important safety information:

• Aripiprazole Solution may cause drowsiness, dizziness, or lightheadedness. These effects may be worse if you take it with alcohol or certain medicines. Use Aripiprazole Solution with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol while you are using Aripiprazole Solution.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Aripiprazole Solution; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Aripiprazole Solution may cause dizziness, lightheadedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.


• Children, teenagers, and young adults who take Aripiprazole Solution may be at increased risk for suicidal thoughts or actions. Watch all patients who take Aripiprazole Solution closely. Contact the doctor at once if new, worsened, or sudden symptoms, such as depressed mood; anxious, restless, or irritable behavior; panic attacks; or unusual changes in mood or behavior, occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur.


• Neuroleptic malignant syndrome (NMS) is a possibly fatal syndrome that can be caused by Aripiprazole Solution. Symptoms may include fever; stiff muscles; confusion; abnormal thinking; fast or irregular heartbeat; and sweating. Contact your doctor at once if you have any of these symptoms.


• Some patients who take Aripiprazole Solution may develop muscle movements that they cannot control. This is more likely to happen in elderly patients, especially women. The chance that this will happen or that it will become permanent is greater in those who take Aripiprazole Solution in higher doses or for a long time. Muscle problems may also occur after short-term treatment with low doses. Tell your doctor at once if you have muscle problems with your arms; legs; or your tongue, face, mouth, or jaw (eg, tongue sticking out, puffing of cheeks, mouth puckering, chewing movements) while taking Aripiprazole Solution.


• Do not become overheated or dehydrated in hot weather or while you are being active; heatstroke may occur.


• Aripiprazole Solution may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• Aripiprazole Solution may raise your blood sugar or increase your risk of developing diabetes. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. If these symptoms occur, tell your doctor right away.


• Diabetes patients - Aripiprazole Solution may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Lab tests, including fasting blood sugar levels and complete blood cell counts, may be performed while you use Aripiprazole Solution. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Aripiprazole Solution with caution in the ELDERLY; they may be more sensitive to its effects, especially uncontrolled muscle movements or seizures.


• Aripiprazole Solution should be used with extreme caution in CHILDREN younger than 6 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: It is not known if Aripiprazole Solution can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Aripiprazole Solution while you are pregnant. Using Aripiprazole Solution during the third trimester may result in uncontrolled muscle movements or withdrawal symptoms in the newborn. Discuss any questions or concerns with your doctor. It is not known if Aripiprazole Solution is found in breast milk. Do not breast-feed while taking Aripiprazole Solution.

Possible side effects of Aripiprazole Solution:

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:

Abnormal dreams; blurred vision; constipation; dizziness; drowsiness; headache; increased appetite (in children); increased saliva production; lightheadedness; nausea; sore throat (in children); stomach upset; tiredness; trouble sleeping; vomiting; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal thinking; chest pain; confusion; fainting; fast, slow, or irregular heartbeat; fever, chills, or sore throat; increased sweating; involuntary movements of the tongue, face, mouth, jaw, arms, legs, or back (eg, chewing movements, puckering of mouth, puffing of cheeks); loss of control over urination; loss of coordination; muscle tremor, jerking, or stiffness; new or worsening mental or mood problems (eg, anxiety, depression, agitation, panic attacks, aggressiveness, impulsiveness, irritability, hostility, exaggerated feeling of well-being, inability to sit still); one-sided weakness; seizures; severe or persistent restlessness; shortness of breath; suicidal thoughts or attempts; swelling of the hands, ankles, or feet; symptoms of high blood sugar (eg, increased thirst, urination, or appetite; unusual weakness); trouble swallowing; trouble walking; unusual bruising; unusual tiredness or weakness; vision or speech changes.

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: Aripiprazole side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include aggression; confusion; fast, slow, or irregular heartbeat; loss of consciousness; seizures; severe drowsiness, dizziness, or vomiting; tremor; trouble breathing; unusual mental changes.

Proper storage of Aripiprazole Solution:

Store Aripiprazole Solution at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Throw away any unused medicine after the bottle has been open for 6 months. Throw away any unused medicine after the expiration date on the bottle has passed. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Aripiprazole Solution out of the reach of children and away from pets.

General information:

• If you have any questions about Aripiprazole Solution, please talk with your doctor, pharmacist, or other health care provider.


• Aripiprazole Solution is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Aripiprazole Solution. 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.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Aripiprazole resources

• Aripiprazole Side Effects (in more detail)
• Aripiprazole Use in Pregnancy & Breastfeeding
• Aripiprazole Drug Interactions
• Aripiprazole Support Group
• 211 Reviews for Aripiprazole - Add your own review/rating

Compare Aripiprazole with other medications

• Agitated State
• Autism
• Bipolar Disorder
• Borderline Personality Disorder
• Depression
• Obsessive Compulsive Disorder
• Post Traumatic Stress Disorder
• Schizoaffective Disorder
• Schizophrenia
• Tourette's Syndrome

Garamycin

Generic Name: gentamicin (gen tah MY sin)

Brand Names: Garamycin

What is Garamycin (gentamicin)?

Gentamicin is an antibiotic. It fights bacteria in the body.

Gentamicin is used to treat severe or serious bacterial infections.

Gentamicin may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Garamycin (gentamicin)?

If you are injecting gentamicin at home, your healthcare provider will give you detailed instructions on how and where to inject the medication. If you do not understand these directions, do not attempt to inject the medication. Contact your healthcare provider for further instructions.

Gentamicin may cause damage to the kidneys and/or nerves. Kidney function and drug levels in the blood may be monitored with blood tests during treatment. Tell your doctor if you experience hearing loss, dizziness, numbness, skin tingling, muscle twitching, or seizures which may be signs of nerve damage.

What should I discuss with my healthcare provider before using Garamycin (gentamicin)?

Do not use gentamicin without first talking to your doctor if you have

• 
  

  sulfite sensitivity;

  
  


• kidney disease;


• 
  

  hearing loss or loss of balance due to ear problems;

  
  


• 
  

  Parkinson's disease; or

  
  


• 
  

  a neuromuscular disorder such as myasthenia gravis.

  
  

You may not be able to use gentamicin, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Do not use gentamicin without first talking to your doctor if you are pregnant or could become pregnant during treatment. Do not use gentamicin without first talking to your doctor if you are breast-feeding a baby.

How should I take Garamycin (gentamicin)?

If you are injecting gentamicin at home, your healthcare provider will give you detailed instructions on how and where to inject the medication. If you do not understand these directions, do not attempt to inject the medication. Contact your healthcare provider for further instructions.

Do not use any gentamicin that is discolored, has particles in it, or looks different from your previous doses. Throw away any unused gentamicin after the amount of time determined by your pharmacist or doctor.

Adequate hydration is important during treatment with gentamicin. Fluids may be administered intravenously during treatment.

It is important that the medication be given on a regular schedule and for the entire amount of time prescribed by your doctor.

Gentamicin may cause damage to the kidneys and/or nerves. Kidney function and drug levels in the blood may be monitored with blood tests during treatment. Tell your doctor if you experience hearing loss, dizziness, numbness, skin tingling, muscle twitching, or seizures which may be signs of nerve damage.

Dispose of used needles and syringes in a puncture resistant container out of the reach of children.

Your healthcare provider will store gentamicin as directed by the manufacturer or give you detailed storage instructions if you are storing the medication at home.

What happens if I miss a dose?

Contact your doctor if a dose is missed.

What happens if I overdose?

Contact your doctor or seek emergency medical attention if an overdose is suspected. An overdose of the medication may result in damage to the kidneys or hearing loss, dizziness, numbness, skin tingling, muscle twitching, or seizures (which may be signs of nerve damage).

What should I avoid while taking Garamycin (gentamicin)?

There are no restrictions on food, beverages, or activity while taking gentamicin unless otherwise directed by your doctor.

Garamycin (gentamicin) side effects

If you experience any of the following serious side effects, stop taking gentamicin and seek emergency medical attention:

• 
  

  an allergic reaction (shortness of breath; closing of the throat; hives; swelling of the lips, face, or tongue; rash; or fainting);

  
  


• 
  

  little or no urine;

  
  


• 
  

  decreased hearing or ringing in the ears;

  
  


• 
  

  dizziness, clumsiness, or unsteadiness;

  
  


• 
  

  numbness, skin tingling, muscle twitching, or seizures; or

  
  


• 
  

  severe watery diarrhea and abdominal cramps.

  
  

Other, less serious side effects may be more likely to occur. Continue to take gentamicin and talk to your doctor if you experience

• 
  

  increased thirst;

  
  


• 
  

  loss of appetite;

  
  


• 
  

  nausea or vomiting;

  
  


• 
  

  a rash.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Garamycin (gentamicin)?

Other drugs, especially those that affect the kidneys, can interact with gentamicin resulting in dangerous side effects and/or decreased effectiveness. Do not take any other prescription or over-the-counter medicines, including vitamins, minerals, and herbal products, without first talking to your doctor during treatment with gentamicin.

More Garamycin resources

• Garamycin Side Effects (in more detail)
• Garamycin Use in Pregnancy & Breastfeeding
• Garamycin Drug Interactions
• Garamycin Support Group
• 0 Reviews for Garamycin - Add your own review/rating

• Garamycin Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• Garamycin Injection Advanced Consumer (Micromedex) - Includes Dosage Information


• Gentamicin Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Gentamicin Professional Patient Advice (Wolters Kluwer)


• Gentamicin Sulfate Monograph (AHFS DI)

Compare Garamycin with other medications

• Bacteremia
• Bacterial Endocarditis Prevention
• Bacterial Infection
• Bone infection
• Brucellosis
• Burns, External
• Cystic Fibrosis
• Endocarditis
• Endometritis
• Febrile Neutropenia
• Intraabdominal Infection
• Kidney Infections
• Meningitis
• Pelvic Inflammatory Disease
• Peritonitis
• Plague
• Pneumonia
• Rabbit Fever
• Skin Infection
• Surgical Prophylaxis

Where can I get more information?

• Your pharmacist has additional information about gentamicin written for health professionals that you may read.

See also: Garamycin side effects (in more detail)