Vertin may be available in the countries listed below.
Betahistine dihydrochloride (a derivative of Betahistine) is reported as an ingredient of Vertin in the following countries:
International Drug Name Search
Iopaque may be available in the countries listed below.
Iohexol is reported as an ingredient of Iopaque in the following countries:
International Drug Name Search
Vitamina B1 Angelini may be available in the countries listed below.
Thiamine hydrochloride (a derivative of Thiamine) is reported as an ingredient of Vitamina B1 Angelini in the following countries:
International Drug Name Search
EVRA transdermal patch
Each 20 cm2 transdermal patch contains 6 mg norelgestromin (NGMN) and 600 micrograms ethinyl estradiol (EE).
Each transdermal patch releases an average of 203 micrograms of NGMN and 33.9 micrograms of EE per 24 hours. Medicinal product exposure is more appropriately characterized by the pharmacokinetic profile (see section 5.2).
For a full list of excipients, see section 6.1.
Transdermal patch.
EVRA is a thin, matrix-type transdermal patch consisting of three layers.
The outside of the backing layer is beige and heat-stamped “EVRA”.
Female contraception
EVRA is intended for women of fertile age. The safety and efficacy has been established in women aged 18 to 45 years.
Posology
To achieve maximum contraceptive effectiveness, patients must be advised to use EVRA exactly as directed. For initiation instructions see 'How to start EVRA' below.
Only one patch is to be worn at a time.
Each used patch is removed and immediately replaced with a new one on the same day of the week (Change Day) on Day 8 and Day 15 of the cycle. Patch changes may occur at any time on the scheduled Change Day. The fourth week is patch-free starting on Day 22.
A new contraceptive cycle begins on the next day following patch-free week; the next EVRA patch should be applied even if there has been no bleeding or if bleeding has not yet stopped.
Under no circumstances should there be more than a 7-day patch-free interval between dosing cycles. If there are more than 7 patch-free days, the user may not be protected against pregnancy. A non-hormonal contraceptive must then be used concurrently for 7 days. As with combined oral contraceptives, the risk of ovulation increases with each day beyond the recommended contraceptive-free period. If intercourse has occurred during such an extended patch-free interval, the possibility of fertilisation should be considered.
Method of administration
EVRA should be applied to clean, dry, hairless, intact healthy skin on the buttock, abdomen, upper outer arm or upper torso, in a place where it will not be rubbed by tight clothing. EVRA should not be placed on the breasts or on skin that is red, irritated or cut. Each consecutive patch should be applied to a different place on the skin to help avoid potential irritation, although they may be kept within the same anatomic site.
The patch should be pressed down firmly until the edges stick well.
To prevent interference with the adhesive properties of the patch, no make-up, creams, lotions, powders or other topical products should be applied to the skin area where the patch is placed or where it will be applied shortly.
It is recommended that users visually check their patch daily to ensure continued proper adhesion.
Used patches should be discarded carefully in accordance with the instructions given in section 6.6.
How to start EVRA
When there has been no hormonal contraceptive use in the preceding cycle
Contraception with EVRA begins on the first day of menses. A single patch is applied and worn for one full week (7 days). The day the first patch is applied (Day 1/Start Day) determines the subsequent Change Days. The patch Change Day will be on this day every week (cycle Days 8, 15, 22 and Day 1 of the next cycle) The fourth week is patch-free starting on Day 22.
If Cycle 1 therapy starts after first day of the menstrual cycle, a non-hormonal contraceptive should be used concurrently for the first 7 consecutive days of the first treatment cycle only.
When switching from an oral combined contraceptive
Treatment with EVRA should begin on the first day of withdrawal bleeding. If there is no withdrawal bleeding within 5 days of the last active (hormone containing) tablet, pregnancy must be ruled out prior to the start of treatment with EVRA. If therapy starts after the first day of withdrawal bleeding, a non-hormonal contraceptive must be used concurrently for 7 days.
If more than 7 days elapse after taking the last active oral contraceptive tablet, the woman may have ovulated and should, therefore, be advised to consult a physician before initiating treatment with EVRA. If intercourse has occurred during such an extended pill-free interval, the possibility of pregnancy should be considered.
When changing from a progestogen-only-method
The woman may switch any day from the minipill (from an implant on the day of its removal, from an injectable when the next injection would be due), but a back-up barrier method of birth control must be used during the first 7 days.
Following abortion or miscarriage
After an abortion or miscarriage that occurs before 20 weeks gestation, EVRA may be started immediately. An additional method of contraception is not needed if EVRA is started immediately. Be advised that ovulation may occur within 10 days of an abortion or miscarriage.
After an abortion or miscarriage that occurs at or after 20 weeks gestation, EVRA may be started either on Day 21 post-abortion or on the first day of the first spontaneous menstruation, whichever comes first. The incidence of ovulation on Day 21 post abortion (at 20 weeks gestation) is not known.
Following delivery
Users who choose not to breast-feed should start contraceptive therapy with EVRA no sooner than 4 weeks after child-birth. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of EVRA or the woman has to wait for her first menstrual period.
For breast-feeding women, see section 4.6.
What to do if the patch comes off or partly detaches
If the EVRA patch partly or completely detaches and remains detached, insufficient medicinal product delivery occurs.
If EVRA remains even partly detached:
- for less than one day (up to 24 hours): it should be re-applied to the same place or replaced with a new EVRA patch immediately. No additional contraceptive is needed. The next EVRA patch should be applied on the usual “Change Day”.
- for more than one day (24 hours or more) or if the user is not aware when the patch has lifted or become detached: the user may not be protected from pregnancy: The user should stop the current contraceptive cycle and start a new cycle immediately by applying a new EVRA patch. There is now a new “Day 1” and a new “Change Day”. A non-hormonal contraceptive must be used concurrently for the first 7 days of the new cycle only.
A patch should not be reapplied if it is no longer sticky; a new patch should be applied immediately. Supplemental adhesives or bandages should not be used to hold the EVRA patch in place.
If subsequent EVRA patch change days are delayed
At the start of any patch cycle (Week One/Day 1):
The user may not be protected from pregnancy. The user should apply the first patch of the new cycle as soon as remembered. There is now a new patch “Change Day” and a new “Day 1”. A non-hormonal contraceptive must be used concurrently for the first 7 days of the new cycle. If intercourse has occurred during such an extended patch-free interval, the possibility of fertilisation should be considered.
In the middle of the cycle (Week Two/Day 8 or Week Three/Day 15):
- for one or two days (up to 48 hours): The user should apply a new EVRA patch immediately. The next EVRA patch should be applied on the usual “Change Day”. If during the 7 days preceding the first skipped day of patch application, the patch was worn correctly, no additional contraceptive use is required.
- for more than two days (48 hours or more): The user may not be protected from pregnancy. The user should stop the current contraceptive cycle and start a new four-week cycle immediately by putting on a new EVRA patch. There is now a new “Day 1” and a new “Change Day”. A non-hormonal contraceptive must be used concurrently for the first 7 consecutive days of the new cycle.
- at the end of the cycle (Week Four/Day 22): If the EVRA patch is not removed at the beginning of Week 4 (Day 22), it should be removed as soon as possible. The next cycle should begin on the usual “Change Day”, which is the day after Day 28. No additional contraceptive use is required.
Change Day adjustment
In order to postpone a menstrual period for one cycle, the woman must apply another patch at the beginning of Week 4 (Day 22) thus not observing the patch free interval. Breakthrough bleeding or spotting may occur. After 6 consecutive weeks of patch wear, there should be a patch free interval of 7 days. Following this, the regular application of EVRA is resumed.
If the user wishes to move the Change Day the current cycle should be completed, removing the third EVRA patch on the correct day. During the patch-free week a new Change Day may be selected by applying the first EVRA patch of the next cycle on the first occurrence of the desired day. In no case should there be more than 7 consecutive patch-free days. The shorter the patch-free interval, the higher the risk that the user does not have a withdrawal bleed and may experience breakthrough bleeding and spotting during the subsequent treatment cycle.
In case of minor skin irritation
If patch use results in uncomfortable irritation, a new patch may be applied to a new location until the next Change Day. Only one patch should be worn at a time.
Special populations
Body weight equal or greater than 90 kg: contraceptive efficacy may be decreased in women weighing equal or greater than 90 kg.
Renal impairment: EVRA has not been studied in women with renal impairment. No dose adjustment is necessary but as there is a suggestion in the literature that the unbound fraction of ethinyl estradiol is higher, EVRA should be used with supervision in this population.
Hepatic impairment: EVRA has not been studied in women with hepatic impairment. EVRA is contraindicated in women with hepatic impairment (see section 4.3).
Post-menopausal women: EVRA is not intended for use as hormonal replacement therapy.
Children and adolescents: EVRA is not recommended for use in children and adolescents under age 18 due to insufficient data on safety and efficacy.
EVRA should not be used in the presence of one of the following disorders. If one of these disorders occurs during the use of EVRA, EVRA must be discontinued immediately.
- Hypersensitivity to the active substances or to any of the excipients
- Presence or history of venous thrombosis, with or without the involvement of pulmonary embolism
- Presence or history of arterial thrombosis (e.g., cerebrovascular accident, myocardial infarction, retinal thrombosis) or prodrome of a thrombosis (e.g., angina pectoris or transient ischaemic attack)
- Migraine with focal aura
- The presence of serious or multiple risk factor(s) for the occurrence of arterial thrombosis:
- Severe hypertension (Persistent blood pressure values of
- Diabetes Mellitus with vascular involvement
- Hereditary dyslipoproteinemia
- Possible hereditary predisposition for venous or arterial thrombosis, such as activated protein C (APC-) resistance, antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant)
- Known or suspected carcinoma of the breast
- Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
- Abnormal liver function related to acute or chronic hepatocellular disease
- Hepatic adenomas or carcinomas
- Undiagnosed abnormal genital bleeding
There is no clinical evidence indicating that a transdermal patch is, in any aspect, safer than combined oral contraceptives.
EVRA is not indicated during pregnancy (see section 4.6).
If any of the conditions/risk factors mentioned below is present, the benefits of the use of EVRA should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using EVRA. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should be emphatically told to contact her physician who will decide on whether its use should be discontinued.
Thromboembolic and other vascular disorders
The use of any combined hormonal contraceptive, including EVRA, carries an increased risk of venous thromboembolism (deep vein thrombosis, pulmonary embolism) compared to no use. Epidemiological studies have shown that the incidence of venous thromboembolism (VTE) in women with no other risk factors for VTE who use low dose oestrogen (<50 micrograms ethinyl estradiol) combined contraceptives ranges from about 20 to 40 cases per 100,000 women-years, but this risk estimate varies according to the type of progestagen. This compares with 5 to 10 cases per 100,000 women-years for non-users and 60 cases per 100,000 pregnancies. VTE is fatal in 1%-2% of cases.
Data from a retrospective cohort study in women aged 15 to 44 years have suggested that the incidence of VTE in women who used EVRA is increased in comparison with users of a levonorgestrel-containing OC (so-called “second generation” OC).
The incidence was 1.4 fold (95% CI 0.9-2.3) increased in women with or without other risk factors for VTE and 1.5 fold (95% CI 0.8-2.7) increased in women with no other risk factors for VTE.
Epidemiological studies have also associated the use of combined oral contraceptives (COCs) with an increased risk for arterial (myocardial infarction, transient ischaemic attack, stroke) thromboembolism.
Extremely rarely, thrombosis has been reported to occur in other blood vessels e.g., hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.
Symptoms of venous or arterial thrombosis can include:
- Unilateral leg pain, and/or swelling
- Sudden severe pain in the chest with possible radiation to the left arm
- Sudden breathlessness, sudden onset of coughing without a clear cause
- Any unusual, severe, prolonged headache
- Sudden partial or complete loss of vision
- Diplopia
- Slurred speech or aphasia
- Vertigo; collapse with or without focal seizure
- Weakness or very marked numbness suddenly affecting one side or one part of the body
- Motor disturbances
- 'Acute' abdominal pain
The risk of venous thromboembolism in combined contraceptives users increases with:
- Increasing age
- A positive family history (i.e. venous thromboembolism ever in a sibling or parent at relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any hormonal contraceptive use
- Prolonged immobilisation, major surgery to the legs, or major trauma. In these situations it is advisable to discontinue use (in the case of elective surgery at least 4 weeks in advance) and not to resume until two weeks after complete remobilisation
- Obesity (body mass index over 30 kg/m²)
- Possibly also with superficial thrombophlebitis and varicose veins. There is no consensus about the possible role of these conditions in the aetiology of venous thrombosis.
The risk of arterial thromboembolic complications in combined contraceptives users increases with:
- Increasing age;
- Smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age);
- Dyslipoproteiniaemia;
- Obesity (body mass index over 30 kg/m²);
- Hypertension;
- Valvular heart disease;
- Atrial fibrillation;
- A positive family history (arterial thrombosis ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any hormonal contraceptive use.
Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyper homocysteinaemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
Other medical conditions, which have been associated with adverse circulatory events, included diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
The increased risk for thromboembolism in the puerperium must be considered (see section 4.6).
An increase in frequency or severity of headache (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of combination contraceptives.
Women using combined contraceptives should be emphatically advised to contact their physician in case of possible symptoms of thrombosis. In case of suspected or confirmed thrombosis, hormonal contraceptive use should be discontinued. Adequate contraception should be initiated because of the teratogenicity of anti-coagulant therapy (coumarins).
Tumours
An increased risk of cervical cancer in long-term users of COCs has been reported in some epidemiological studies, but there continues to be controversy about the extent to which this finding is attributable to the compounding effects of sexual behaviour and other factors such as human papilloma virus (HPV).
A meta-analysis of 54 epidemiological studies reported that there is a slightly increased risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using COCs. The excess risk gradually disappears during the course of the 10 years after cessation of COC use. Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer. The breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users. The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both.
In rare cases, benign liver tumours, and even more rarely, malignant liver tumours have been reported in users of COCs. In isolated cases, these tumours have led to life-threatening intra-abdominal haemorrhages. Therefore a hepatic tumour should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage occur in women using EVRA.
Other conditions
- Contraceptive efficacy may be reduced in women weighing equal or greater than 90 kg (see sections 4.2 and 5.1).
- Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using combination hormonal contraceptives.
- Although small increases of blood pressure have been reported in many women using hormonal contraceptives, clinically relevant increases are rare. A definitive relationship between hormonal contraceptive use and clinical hypertension has not been established. If, during the use of a combination hormonal contraceptive in pre-existing hypertension, constantly elevated blood pressure values or a significant increase in blood pressure do not respond adequately to antihypertensive treatment, the combination hormonal contraceptive must be withdrawn. Combination hormonal contraceptive use may be resumed if normotensive values can be achieved with antihypertensive therapy.
- The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: Jaundice and/or pruritus related to cholestasis; gallstones; porphyria; systemic erythematosus; haemolytic ureamic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis-related hearing loss.
- Acute or chronic disturbances of liver function may necessitate the discontinuation of combination hormonal contraceptives until markers of liver function return to normal. Recurrence of cholestatic-related pruritus, which occurred during a previous pregnancy or previous use of sex steroids necessitates the discontinuation of combination hormonal contraceptives.
- Although combined hormonal contraceptives may have an effect on peripheral insulin resistance and glucose tolerance there is no evidence for a need to alter the therapeutic regimen in diabetes during use of combined hormonal contraception. However, diabetic women should be carefully observed, particularly in the early stage of EVRA use.
- Worsening of endogenous depression, of epilepsy, of Crohn's disease and of ulcerative colitis has been reported during COC use.
- Chloasma may occasionally occur with the use of hormonal contraception, especially in users with a history of chloasma gravidarum. Users with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while using EVRA. Chloasma is often not fully reversible.
Medical examination/consultation
Prior to the initiation or reinstitution of EVRA a complete medical history (including family history) should be taken and pregnancy should be ruled out. Blood pressure should be measured and a physical examination should be performed guided by the contraindications (see section 4.3) and warnings (see section 4.4). The woman should also be instructed to carefully read the package leaflet and to adhere to the advice given.
The frequency and nature of subsequent examinations should be based on established guidelines and be adapted to the individual woman on the basis of clinical impression.
Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmissible diseases.
Bleeding irregularities
With all combination hormonal contraceptives, irregular blood loss (spotting or breakthrough bleeding) can occur, especially during the initial months of usage. For this reason, a medical opinion on irregular blood loss will only be useful after an adjustment period of approximately three cycles. If breakthrough bleeding persists, or breakthrough bleeding occurs after previously regular cycles, while EVRA has been used according the recommended regimen, a cause other than EVRA should be considered. Non-hormonal causes should be considered and, if necessary, adequate diagnostic measures taken to rule out organic disease or pregnancy. This may include curettage. In some women withdrawal bleeding may not occur during this patch free period. If EVRA has been taken according to the directions described in section 4.2, it is unlikely that the woman is pregnant. However, if EVRA has not been taken according to these directions prior to the first missed withdrawal bleed or if two withdrawal bleeds are missed, pregnancy must be ruled out before EVRA use is continued.
Some users may experience amenorrhoea or oligomenorrhoea after discontinuing hormonal contraception, especially when such a condition was pre-existent.
Herbal preparations containing St John's Wort (Hypericum perforatum) should not be used while taking EVRA (see section 4.5)
Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.
• Influence of other medicinal products on EVRA
Interactions between oral contraceptives and other medicinal products may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.
Hepatic metabolism
Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones (e.g. phenytoin, barbiturates, primidone, carbamazepine, rifampicin, bosentan and HIV-medication (e.g. ritonavir, nevirapine) and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing the herbal remedy St. John's Wort (hypericum perforatum)). Maximal enzyme induction is generally seen in about 10 days but may then be sustained for at least 4 weeks after the cessation of drug therapy.
Interference with Enterohepatic Circulation
Contraceptive failures have also been reported with antibiotics, such as penicillins and tetracyclines. The mechanism of this effect has not been elucidated. In a pharmacokinetic interaction study, oral administration of tetracycline hydrochloride, 500 mg four times daily for 3 days prior to and 7 days during wear of EVRA, did not significantly affect the pharmacokinetics of norelgestromin or EE.
Management
Women on short-term treatment with any of the above-mentioned classes of medicinal products or individual active substances (hepatic enzyme-inducing medicine) besides rifampicin should temporarily use a barrier method in addition to EVRA, i.e. during the time of concomitant medicinal product administration and for 7 days after their discontinuation.
For women on rifampicin a barrier method should be used in addition to EVRA during the time of rifampicin administration and for 28 days after its discontinuation.
In women on long-term treatment with hepatic enzyme-inducing active substances, another reliable, non-hormonal, method of contraception is recommended.
Women on treatment with antibiotics (besides rifampicin, see above) should use the barrier method until 7 days after discontinuation.
If concomitant medicinal product administration runs beyond the end of the one-week wear period, the next patch should be applied without the usual patch-free interval.
• Influence of EVRA on other medicinal products
Hormonal contraceptives may affect the metabolism of certain other active substances. Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).
• Laboratory tests
The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins, e.g. corticosteroid-binding globulin and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range.
EVRA is not indicated during pregnancy.
Epidemiological studies indicate no increased risk of birth defects in children born to women who used hormonal contraceptives prior to pregnancy. The majority of recent studies also do not indicate a teratogenic effect when hormonal contraceptives are used inadvertently during early pregnancy.
For EVRA there are no clinical data on exposed pregnancies, which allow conclusions about its safety during pregnancy.
Studies in animals have shown reproductive toxicity (see section 5.3). On the basis of available data, a potential risk of masculinisation as a consequence of an exaggerated hormonal action cannot be excluded.
If pregnancy occurs during use of EVRA, EVRA should be stopped immediately.
Lactation may be influenced by combination hormonal contraceptives as they may reduce the quantity and change the composition of breast milk. Therefore, the use of EVRA is not to be recommended until the breast-feeding mother has completely weaned her child.
EVRA has no or negligible influence on the ability to drive and use machines.
4.8.1 Clinical Trial Data
The most commonly reported adverse drug reactions (ADRs) in clinical trials were headache, nausea, and breast tenderness, occurring in approximately 21.0%, 16.6%, and 15.9% of patients, respectively.
Frequency estimate: very common (
|
| ||||
| |||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
4.8.2 Postmarketing Data
Additional adverse drug reactions first identified during postmarketing experience with EVRA are listed below:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Vetogent may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Gentamicin sulfate (a derivative of Gentamicin) is reported as an ingredient of Vetogent in the following countries:
International Drug Name Search
Vetofer may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Iron Dextran is reported as an ingredient of Vetofer in the following countries:
International Drug Name Search
Estradiol Acetate may be available in the countries listed below.
Estradiol Acetate (USAN) is known as Estradiol in the US.
International Drug Name Search
Glossary
| USAN | United States Adopted Name |
hep-a-TYE-tis B VAX-een re-KOM-bin-ant
In the U.S.
Available Dosage Forms:
Therapeutic Class: Vaccine
Hepatitis B vaccine recombinant is used to prevent infection by the hepatitis B virus. The vaccine works by causing your body to produce its own protection (antibodies) against the disease.
Hepatitis B vaccine recombinant is made without any human blood or blood products or any other substances of human origin. It cannot give you the hepatitis B virus (HBV) or the human immunodeficiency virus (HIV).
HBV infection is a major cause of serious liver diseases, such as hepatitis and cirrhosis, and a type of liver cancer called primary hepatocellular carcinoma.
Pregnant women who have hepatitis B infection or are carriers of hepatitis B virus can give the disease to their babies when they are born. These babies often suffer serious long-term illnesses from the disease.
Immunization against hepatitis B disease is recommended for all newborn babies, infants, children, and adolescents up to 19 years of age. It is also recommended for adults who live in areas that have a high rate of hepatitis B disease or who may be at increased risk of infection from hepatitis B virus. These adults include:
This vaccine is available only from your doctor or other authorized health care professional.
In deciding to use a vaccine, the risks of taking the vaccine must be weighed against the good it will do. This is a decision you and your doctor will make. For this vaccine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to hepatitis b vaccine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of hepatitis B vaccine recombinant in children.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of hepatitis B vaccine recombinant in the elderly.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | C | Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. |
Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of this vaccine. Make sure you tell your doctor if you have any other medical problems, especially:
A nurse or other trained health professional will give you this vaccine. This vaccine is given as a shot into one of your muscles. If you have bleeding problems such as hemophilia, the vaccine may be given as a shot under your skin.
This vaccine is usually given as 3 doses. After the first dose, two more doses are given 1 month and 6 months after the first dose, unless your doctor tells you otherwise.
It is very important that you or your child return to your doctor’s office at the right time for the second and third dose. Be sure to notify your doctor of any unwanted effects that occur after you or your child receive this vaccine.
This vaccine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Tell your doctor right away if you or your child have a rash, itching, swelling of the tongue and throat, or trouble breathing after you get the injection.
Tell your doctor if you or your child are allergic to latex. The needle cover and the rubber plunger of the prefilled syringe contain dry natural latex rubber, which may cause an allergic reaction in people with a latex allergy.
This vaccine may not protect you against hepatitis B infection if you are already infected with the virus at the time you receive the shot.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor or nurse immediately if any of the following side effects occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
See also: hepatitis b vaccine Intramuscular side effects (in more detail)
The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
OxyNorm® 10 mg/ml, solution for injection or infusion
Oxycodone hydrochloride 10 mg/ml (equivalent to 9 mg/ml oxycodone)
For excipients, see Section 6.1
Solution for injection or infusion.
For the treatment of moderate to severe pain in patients with cancer and post-operative pain. For the treatment of severe pain requiring the use of a strong opioid.
Route of administration:
Subcutaneous injection or infusion
Intravenous injection or infusion.
Posology:
The dose should be adjusted according to the severity of pain, the total condition of the patient and previous or concurrent medication.
Adults over 18 years:
The following starting doses are recommended. A gradual increase in dose may be required if analgesia is inadequate or if pain severity increases.
i.v. (Bolus): Dilute to 1 mg/ml in 0.9% saline, 5% dextrose or water for injections. Administer a bolus dose of 1 to 10 mg slowly over 1-2 minutes.
Doses should not be administered more frequently than every 4 hours.
i.v. (Infusion): Dilute to 1 mg/ml in 0.9% saline, 5% dextrose or water for injections. A starting dose of 2 mg/hour is recommended.
i.v. (PCA): Dilute to 1 mg/ml in 0.9% saline, 5% dextrose or water for injections. Bolus doses of 0.03 mg/kg should be administered with a minimum lock-out time of 5 minutes.
s.c. (Bolus): Use as 10 mg/ml concentration. A starting dose of 5 mg is recommended, repeated at 4-hourly intervals as required.
s.c. (Infusion): Dilute in 0.9% saline, 5% dextrose or water for injections if required. A starting dose of 7.5 mg/day is recommended in opioid naïve patients, titrating gradually according to symptom control. Cancer patients transferring from oral oxycodone may require much higher doses (see below).
Transferring patients between oral and parenteral oxycodone:
The dose should be based on the following ratio: 2 mg of oral oxycodone is equivalent to 1 mg of parenteral oxycodone. It must be emphasised that this is a guide to the dose required. Inter-patient variability requires that each patient is carefully titrated to the appropriate dose.
Elderly:
Elderly patients should be treated with caution. The lowest dose should be administered with careful titration to pain control.
Patients with renal and hepatic impairment:
Patients with mild to moderate renal impairment and/or mild hepatic impairment should be treated with caution. The lowest dose should be given with careful titration to pain control.
Children under 18 years:
There are no data on the use of OxyNorm injection in patients under 18 years of age.
Use in non-malignant pain:
Opioids are not first-line therapy for chronic non-malignant pain, nor are they recommended as the only treatment. Types of chronic pain which have been shown to be alleviated by strong opioids include chronic osteoarthritic pain and intervertebral disc disease. The need for continued treatment in non-malignant pain should be assessed at regular intervals.
Cessation of therapy:
When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.
OxyNorm injection is contraindicated in patients with known hypersensitivity to oxycodone or any of the other constituents, or in any situation where opioids are contraindicated; respiratory depression; head injury; paralytic ileus; acute abdomen; chronic obstructive airways disease; cor pulmonale; chronic bronchial asthma; hypercarbia; moderate to severe hepatic impairment; severe renal impairment (creatinine clearance <10 ml/min); chronic constipation; concurrent administration of monoamine oxidase inhibitors or within 2 weeks of discontinuation of their use; pregnancy.
The major risk of opioid excess is respiratory depression. As with all opioids, a reduction in dosage may be advisable in hypothyroidism. Use with caution in patients with raised intracranial pressure, hypotension, hypovolaemia, toxic psychoses, diseases of the biliary tract, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency, acute alcoholism, delirium tremens, pancreatitis, chronic renal and hepatic disease or severe pulmonary disease and debilitated, elderly and infirm patients. OxyNorm injection should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, OxyNorm injection should be discontinued immediately.
The patient may develop tolerance to oxycodone with chronic use and require progressively higher doses to maintain pain control. The patient may develop physical dependence, in which case an abstinence syndrome may be seen following abrupt cessation.
For appropriate patients who suffer with chronic non-malignant pain, opioids should be used as part of a comprehensive treatment programme involving other medications and treatment modalities. A crucial part of the assessment of a patient with chronic non-malignant pain is the patient's addiction and substance abuse history. There is potential for development of psychological dependence (addiction) to opioid analgesics, including oxycodone. OxyNorm injection, like all opioids, should be used with particular care in patients with a history of alcohol and drug abuse.
If opioid treatment is considered appropriate for the patient, then the main aim of treatment is not to minimise the dose of opioid but rather to achieve a dose which provides adequate pain relief with a minimum of side effects. There must be frequent contact between physician and patient so that dosage adjustments can be made. It is strongly recommended that the physician defines treatment outcomes in accordance with pain management guidelines. The physician and patient can then agree to discontinue treatment if these objectives are not met.
Oxycodone has an abuse profile similar to other strong opioids and should be used with caution in opioid-dependent patients. Oxycodone may be sought and abused by people with latent or manifest addiction disorders.
As with other opioids, infants who are born to dependent mothers may exhibit withdrawal symptoms and may have respiratory depression at birth.
There is an enhanced CNS depressant effect with drugs such as tranquillisers, anaesthetics, hypnotics, anti-depressants, sedatives, phenothiazines, neuroleptic drugs, alcohol, other opioids, muscle relaxants and antihypertensives. Monoamine oxidase inhibitors are known to interact with narcotic analgesics, producing CNS excitation or depression with hypertensive or hypotensive crisis.
Oxycodone is metabolised in part via the CYP2D6 and CYP3A4 pathways. While these pathways may be blocked by a variety of drugs, such blockade has not yet been shown to be of clinical significance with this agent.
The effect of oxycodone in human reproduction has not been adequately studied. No studies on fertility or the post-natal effects of intrauterine exposure have been carried out. However, studies in rats and rabbits with oral doses of oxycodone equivalent to 3 and 47 times an adult dose of 160 mg/day, respectively, did not reveal evidence of harm to the foetus due to oxycodone. OxyNorm injection is not recommended for use in pregnancy nor during labour. Infants born to mothers who have received opioids during pregnancy should be monitored for respiratory depression.
Oxycodone may be secreted in breast milk and may cause respiratory depression in the newborn. Oxycodone should therefore not be used in breast-feeding mothers.
Oxycodone may modify patients' reactions to a varying extent depending on the dosage and individual susceptibility. Therefore patients should not drive or operate machinery, if affected.
Adverse drug reactions are typical of full opioid agonists. Tolerance and dependence may occur (see Tolerance and Dependence, below). Constipation may be prevented with an appropriate laxative. If nausea or vomiting are troublesome, oxycodone may be combined with an antiemetic.
Common (incidence of
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Tolerance and Dependence:
The patient may develop tolerance to the drug with chronic use and require progressively higher doses to maintain pain control. Prolonged use of OxyNorm injection may lead to physical dependence and a withdrawal syndrome may occur upon abrupt cessation of therapy. When a patient no longer requires therapy with oxycodone, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal. The opioid abstinence or withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, or increased blood pressure, respiratory rate or heart rate.
Symptoms of overdosage
Signs of oxycodone toxicity and overdosage are pin-point pupils, respiratory depression, hypotension and hallucinations. Nausea and vomiting are common in less severe cases. Non-cardiac pulmonary oedema and rhabdomyolysis are particularly common after intravenous injection of opioid analgesics. Circulatory failure and somnolence progressing to stupor or coma, skeletal muscle flaccidity, bradycardia and death may occur in more severe cases.
The effects of overdosage will be potentiated by the simultaneous ingestion of alcohol or other psychotropic drugs
Treatment of overdosage
Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation.
In the case of massive overdosage, administer naloxone intravenously (0.4 to 2mg for an adult and 0.01mg/kg body weight for children) if the patient is in a coma or respiratory depression is present. Repeat the dose at 2 minute intervals if there is no response. If repeated doses are required then an infusion of 60% of the initial dose per hour is a useful starting point. A solution of 10 mg made up in 50 ml dextrose will produce 200 micrograms/ml for infusion using an IV pump (dose adjusted to the clinical response). Infusions are not a substitute for frequent review of the patient's clinical state.
Intramuscular naloxone is an alternative in the event that IV access is not possible. As the duration of action of naloxone is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. Naloxone is a competitive antagonist and large doses (4 mg) may be required in seriously poisoned patients.
For less severe overdosage, administer naloxone 0.2 mg intravenously followed by increments of 0.1 mg every 2 minutes if required.
The patient should be observed for at least 6 hours after the last dose of naloxone.
Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdosage. Naloxone should be administered cautiously to persons who are known, or suspected, to be physically dependent on oxycodone. In such cases, an abrupt or complete reversal of opioid effects may precipitate pain and an acute withdrawal syndrome.
Pharmacotherapeutic group: Natural opium alkaloids
ATC code: N02A A05
Oxycodone is a full opioid agonist with no antagonist properties. It has an affinity for kappa, mu and delta opioid receptors in the brain and spinal cord. Oxycodone is similar to morphine in its action. The therapeutic effect is mainly analgesic, anxiolytic, antitussive and sedative.
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 and testosterone. Clinical symptoms may be manifest from these hormonal changes.
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. Whether oxycodone, a semisynthetic opioid, has immunological effects similar to morphine is unknown.
Pharmacokinetic studies in healthy subjects demonstrated an equivalent availability of oxycodone from OxyNorm injection when administered by the intravenous and subcutaneous routes, as a single bolus dose or a continuous infusion over 8 hours.
Following absorption, oxycodone is distributed throughout the entire body. Approximately 45% is bound to plasma protein. It is metabolised in the liver to produce noroxycodone, oxymorphone and various conjugated glucuronides. The analgesic effects of the metabolites are clinically insignificant.
The active drug and its metabolites are excreted in both urine and faeces.
The plasma concentrations of oxycodone are only minimally affected by age, being 15% greater in elderly as compared to young subjects.
Female subjects have, on average, plasma oxycodone concentrations up to 25% higher than males on a body weight adjusted basis.
The drug penetrates the placenta and can be found in breast milk.
When compared to normal subjects, patients with mild to severe hepatic dysfunction may have higher plasma concentrations of oxycodone and noroxycodone, and lower plasma concentrations of oxymorphone. There may be an increase in the elimination half-life of oxycodone and this may be accompanied by an increase in drug effects.
When compared to normal subjects, patients with mild to severe renal dysfunction may have higher plasma concentrations of oxycodone and its metabolites. There may be an increase in the elimination half-life of oxycodone and this may be accompanied by an increase in drug effects.
Oxycodone was not mutagenic in the following assays: Ames Salmonella and E. Coli test with and without metabolic activation at doses of up to 5000 mg, chromosomal aberration test in human lymphocytes (in the absence of metabolic activation and with activation after 48 hours of exposure) at doses of up to 1500 mg/ml, and in the in vivo bone marrow micronucleus assay in mice (at plasma levels of up to 48 mg/ml). Mutagenic results occurred in the presence of metabolic activation in the human chromosomal aberration test (at greater than or equal to 1250 mg/ml) at 24 but not 48 hours of exposure and in the mouse lymphoma assay at doses of 50 mg/ml or greater with metabolic activation and at 400 mg/ml or greater without metabolic activation. The data from these tests indicate that the genotoxic risk to humans may be considered low.
Studies of oxycodone in animals to evaluate its carcinogenic potential have not been conducted owing to the length of clinical experience with the drug substance.
Citric acid monohydrate
Sodium citrate
Sodium chloride
Hydrochloric acid, dilute
Sodium hydroxide
Water for injections
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Cyclizine at concentrations of 3 mg/ml or less, when mixed with OxyNorm injection, either undiluted or diluted with water for injections, shows no sign of precipitation over a period of 24 hours storage at room temperature. Precipitation has been shown to occur in mixtures with OxyNorm injection at cyclizine concentrations greater than 3 mg/ml or when diluted with 0.9% saline. It is recommended that water for injections be used as a diluent when cyclizine and oxycodone hydrochloride are co-administered either intravenously or subcutaneously as an infusion.
Prochlorperazine is chemically incompatible with OxyNorm injection.
3 years unopened.
After opening use immediately.
For further information see Section 6.6.
No special precautions for storage prior to opening.
For further information on use after opening see Section 6.6.
Clear glass ampoules: 1 ml and 2 ml.
Pack size: 5 ampoules.
Not all pack sizes may be marketed.
Each ampoule is for single use in a single patient. The injection should be given immediately after opening the ampoule, and any unused portion be discarded. Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution, dilution, etc has taken place in controlled and validated aseptic conditions.
OxyNorm injection has been shown to be compatible with the following drugs:
Hyoscine butylbromide
Hyoscine hydrobromide
Dexamethasone sodium phosphate
Haloperidol
Midazolam hydrochloride
Metoclopramide hydrochloride
Levomepromazine hydrochloride
OxyNorm injection, undiluted or diluted to 1 mg/ml with 0.9% w/v saline, 5% w/v dextrose or water for injections, is physically and chemically stable when in contact with representative brands of polypropylene or polycarbonate syringes, polyethylene or PVC tubing, and PVC or EVA infusion bags, over a 24 hour period at room temperature.
The injection, whether undiluted or diluted to 1 mg/ml in the infusion fluids used in these studies and contained in the various assemblies, does not need to be protected from light.
Inappropriate handling of the undiluted solution after opening of the original ampoule, or of the diluted solutions may compromise the sterility of the product.
Napp Pharmaceuticals Ltd
Cambridge Science Park
Milton Road
Cambridge CB4 0GW
PL 16950/0128
14 April 2003
September 2008
CD (Sch 2) POM
®OxyNorm and the NAPP device are Registered Trade Marks.
© Napp Pharmaceuticals Limited 2008.
