Ketoconazole Bevo may be available in the countries listed below.
Ingredient matches for Ketoconazole Bevo
Ketoconazole
Ketoconazole is reported as an ingredient of Ketoconazole Bevo in the following countries:
- Greece
International Drug Name Search
Thursday, 29 September 2016
Cinryze
Generic Name: complement C1 esterase inhibitor (KOM ple ment C1 ES ter ase in HIB it or)
Brand Names: Berinert, Cinryze
What is complement C1 esterase inhibitor?
Complement C1 esterase inhibitor is a man-made form of a protein that occurs naturally in the blood stream and helps control inflammation in the body. In people with hereditary angioedema, complement C1 esterase inhibitor does not function properly or occurs in low levels.
Complement C1 esterase inhibitor is used in people with hereditary angioedema. The Berinert brand of this medication is used to treat attacks of angioedema. The Cinryze brand is used to prevent attacks of angioedema.
Complement C1 esterase inhibitor may also be used for purposes not listed in this medication guide.
What is the most important information I should know about complement C1 esterase inhibitor?
You should not use this medication if have ever had a life-threatening allergic reaction to complement C1 esterase inhibitor.
Before you receive complement C1 esterase inhibitor, tell your doctor if you have a history of stroke or blood clot.
Do not give this medication to a child without medical advice.
You may be shown how to use Cinryze in an IV at home. This medication comes with patient instructions for safe and effective use. Follow all directions carefully. Ask your doctor or pharmacist if you have any questions.
Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine. Be sure you understand how to properly mix and store the medication. Stop your IV infusion and get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing or difficult breathing; feeling like you might pass out; or swelling of your face, lips, tongue, or throat.
Other serious side effects may include sudden numbness or weakness, chest pain, confusion, pain or swelling, and problems with vision, speech, or balance.
Complement C1 esterase inhibitor is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.
What should I discuss with my health care provider before using complement C1 esterase inhibitor?
You should not use this medication if have ever had a life-threatening allergic reaction to rugae.
To make sure you can safely use complement C1 esterase inhibitor, tell your doctor if you have a history of stroke or blood clot.
FDA pregnancy category C. It is not known whether complement C1 esterase inhibitor will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether complement C1 esterase inhibitor passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Complement C1 esterase inhibitor is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication. Do not give this medication to a child without medical advice.
How should I use complement C1 esterase inhibitor?
Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Complement C1 esterase inhibitor is injected into a vein through an IV. A healthcare provider will give you a Berinert injection in a clinic or hospital setting. You may be shown how to use Cinryze in an IV at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.
This medication comes with patient instructions for safe and effective use. Ask your doctor or pharmacist if you have any questions.
Complement C1 esterase inhibitor is a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using Cinryze home, you will need to use two vials of Cinryze to make up a single dose. Follow all directions carefully. Be sure you understand how to properly mix and store the medicine.
Gently swirl but do not shake the mixed medicine or you may ruin it. Prepare your dose only when you are ready to give yourself an injection.
Mixed Berinert should be clear and colorless. Mixed Cinryze should be clear or slightly blue in color. Do not use the mixed medicine if it has changed colors, is cloudy, or has any particles in it. Call your doctor for a new prescription.
Cinryze is usually given every 3 or 4 days to prevent angioedema attacks. An IV infusion takes about 10 minutes to complete.
Complement C1 esterase inhibitor contains no preservative. Once you have pierced the rubber top of a vial with a needle, you must use that vial right away or throw it away.
Each single use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.
Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.
Store the unmixed dry powder in a refrigerator or in a dark cool place. Keep the medicine protected from light and do not allow it to freeze. Throw away any unused vial after the expiration date on the label has passed. After mixing Berinert with the diluent, use it right away or store the mixture at room temperature and use it within 8 hours. After mixing Cinryze with the diluent, use it right away or store the mixture at room temperature and use it within 3 hours.
What happens if I miss a dose?
Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.
What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.
Overdose symptoms may include sudden headache, numbness, weakness, or problems with your speech, vision, or balance.
What should I avoid while using complement C1 esterase inhibitor?
Follow your doctor's instructions about any restrictions on food, beverages, or activity.
Complement C1 esterase inhibitor side effects
Stop your IV infusion and get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing or difficult breathing; feeling like you might pass out; or swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any other serious side effect, such as:
new or worsening pain;
sudden numbness or weakness, especially on one side of the body;
sudden severe headache, confusion, problems with vision, speech, or balance;
stomach pain or swelling;
chest pain, sudden cough, rapid breathing, fast heart rate; or
pain, swelling, warmth, or redness in one or both legs.
Less serious side effects may include:
nausea, vomiting, stomach pain;
altered sense of taste;
cold symptoms such as stuffy nose, sneezing, sore throat;
mild itching or rash; or
mild headache.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect complement C1 esterase inhibitor?
There may be other drugs that can interact with this medication. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
More Cinryze resources
- Cinryze Side Effects (in more detail)
- Cinryze Use in Pregnancy & Breastfeeding
- Cinryze Support Group
- 3 Reviews for Cinryze - Add your own review/rating
- Cinryze Monograph (AHFS DI)
- Cinryze Prescribing Information (FDA)
- Cinryze Advanced Consumer (Micromedex) - Includes Dosage Information
- Cinryze MedFacts Consumer Leaflet (Wolters Kluwer)
- Cinryze Consumer Overview
- Berinert Prescribing Information (FDA)
- Berinert MedFacts Consumer Leaflet (Wolters Kluwer)
- Berinert Consumer Overview
Compare Cinryze with other medications
- Hereditary Angioedema
Where can I get more information?
- Your doctor or pharmacist can provide more information about complement C1 esterase inhibitor.
See also: Cinryze side effects (in more detail)
Keto
Keto may be available in the countries listed below.
Ingredient matches for Keto
Ketoprofen
Ketoprofen is reported as an ingredient of Keto in the following countries:
- Estonia
- Finland
- Latvia
- Lithuania
- Venezuela
International Drug Name Search
Wednesday, 28 September 2016
Hytrinex
Hytrinex may be available in the countries listed below.
Ingredient matches for Hytrinex
Terazosin
Terazosin hydrochloride (a derivative of Terazosin) is reported as an ingredient of Hytrinex in the following countries:
- Sweden
International Drug Name Search
Amoxapine
In the US, Amoxapine (amoxapine systemic) is a member of the drug class tricyclic antidepressants and is used to treat Depression.
US matches:
- Amoxapine
Scheme
Rec.INN
ATC (Anatomical Therapeutic Chemical Classification)
N06AA17
CAS registry number (Chemical Abstracts Service)
0014028-44-5
Chemical Formula
C17-H16-Cl-N3-O
Molecular Weight
313
Therapeutic Category
Antidepressant, tricyclic
Chemical Name
Dibenz[b,f][1,4]oxazepine, 2-chloro-11-(1-piperazinyl)-
Foreign Names
- Amoxapinum (Latin)
- Amoxapin (German)
- Amoxapine (French)
- Amoxapina (Spanish)
Generic Names
- Amoxapine (OS: USAN, DCF, BAN)
- CL 67772 (IS: Lederle)
- Amoxapine (PH: USP 32, JP XV)
Brand Names
- Amoxan
Wyeth KK, Japan - Amoxapine
Watson, United States - Défanyl
Eisai, France - Demolox
Wyeth, India
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Click for further information on drug naming conventions and International Nonproprietary Names.
Fluoxetina AC Farma
Fluoxetina AC Farma may be available in the countries listed below.
Ingredient matches for Fluoxetina AC Farma
Fluoxetine
Fluoxetine hydrochloride (a derivative of Fluoxetine) is reported as an ingredient of Fluoxetina AC Farma in the following countries:
- Peru
International Drug Name Search
Medovir
Medovir may be available in the countries listed below.
Ingredient matches for Medovir
Acyclovir
Aciclovir is reported as an ingredient of Medovir in the following countries:
- Bahrain
- Cyprus
- Ethiopia
- Hong Kong
- Iraq
- Jordan
- Malta
- Russian Federation
- Singapore
- Sri Lanka
- Sudan
- Taiwan
- Yemen
International Drug Name Search
Tuesday, 27 September 2016
Navelbine 30mg soft capsule
1. Name Of The Medicinal Product
NAVELBINE® 30 mg soft capsule
2. Qualitative And Quantitative Composition
Each soft capsule contains 30mg vinorelbine as tartrate
For a full list of excipients, see section 6.1
3. Pharmaceutical Form
Soft capsule.
Pink soft capsule printed N30.
4. Clinical Particulars
4.1 Therapeutic Indications
As a single agent or in combination for:
• The first line treatment of stage 3 or 4 non small cell lung cancer.
• The treatment of advanced breast cancer stage 3 and 4 relapsing after or refractory to an anthracycline containing regimen.
4.2 Posology And Method Of Administration
In adult patients
As a single agent, the recommended regimen is:
First three administrations
60mg/m² of body surface area, administered once weekly
Subsequent administrations
Beyond the third administration, it is recommended to increase the dose of Navelbine to 80mg/m² once weekly except in those patients for whom the neutrophil count dropped once below 500/mm3 or more than once between 500 and 1000/mm3 during the first three administrations at 60mg/m².
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Dose modification
For any administration planned to be given at 80mg/m², if the neutrophil count is below 500/mm3 or more than once between 500 and 1000 / mm3 the administration should be delayed until recovery and the dose reduced from 80 to 60mg/m2 per week during the 3 following administrations.
If the neutrophil count is below 1500 /mm3 and/or the platelet count below 100000/mm3, then the treatment should be delayed until recovery.
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It is possible to re-escalate the dose from 60 to 80 mg/m2 per week if the neutrophil count did not drop below 500/mm3 or more than once between 500 and 1000/mm3 during 3 administrations given at 60 mg/m2 according to the rules previously defined for the first 3 administrations.
For combination regimens, the dose and schedule will be adapted to the treatment protocol.
Based on clinical studies, the oral dose of 80 mg/m2 was demonstrated to correspond to 30 mg/m2 of the iv form and 60 mg/m2 to 25 mg/m2.
This has been the base for combination regimens alternating iv and oral forms improving patient convenience.
Capsules of different strengths (20, 30, 80 mg) are available in order to choose the adequate combination for the right dosage.
The following table gives the dose required for appropriate ranges of body surface area (BSA).
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Even for patients with BSA 2 the total dose should never exceed 120 mg per week at 60 mg /m2 and 160 mg per week at 80 mg/m2. |
Administration
Navelbine must be given strictly by the oral route.
Navelbine must be swallowed whole with water, without chewing, sucking or dissolving the capsule.
It is recommended to administer the capsule with some food.
Administration in the elderly
Clinical experience has not detected any significant differences among elderly patients with regard to the response rate, although greater sensitivity in some of these patients cannot be excluded. Age does not modify the pharmacokinetics of vinorelbine: see section 5.2.
Administration in children
Safety and efficacy in children have not been established and administration is therefore not recommended.
Administration in patients with liver insufficiency
Navelbine can be administered at the standard dose of 60 mg/m²/week in patients with mild liver impairment (bilirubin < 1.5 x ULN, and ALAT and/or ASAT from 1.5 to 2.5 x ULN). In patients with moderate liver impairment (bilirubin from 1.5 to 3 x ULN, whatever the levels of ALAT and ASAT), Navelbine should be administered at a dose of 50 mg/m²/week. The administration of Navelbine in patients with severe hepatic impairment is contra-indicated: see sections 4.3, 4.4, 5.2.
Administration in patients with renal insufficiency
Given the minor renal excretion, there is no pharmacokinetic justification for reducing the dose of Navelbine in patients with serious renal insufficiency: see sections 4.4, 5.2.
Specific instructions must be observed for handling Navelbine: see section 6.6
4.3 Contraindications
- Known hypersensitivity to vinorelbine or other vinca-alkaloids or to any of the constituents.
- Disease significantly affecting absorption
- Previous significant surgical resection of stomach or small bowel.
- Neutrophil count < 1500/mm3 or severe infection current or recent (within 2 weeks).
- Platelet count < 100000/mm3
- Severe hepatic insufficiency
- Pregnancy: see section 4.6
- Lactation: see section 4.6
- Patients requiring long-term oxygen therapy
- In combination with yellow fever vaccine: see section 4.5
4.4 Special Warnings And Precautions For Use
Special warnings
Navelbine should be prescribed by a physician who is experienced in the use of chemotherapy with facilities for monitoring cytotoxic drugs.
If the patient chews or sucks the capsule by error, the liquid is an irritant. Proceed to mouth rinses with water or preferably a normal saline solution.
In the event of the capsule being cut or damaged, the liquid content is an irritant, and so may cause damage if in contact with skin, mucosa or eyes. Damaged capsules should not be swallowed and should be returned to the pharmacy or to the doctor in order to be properly destroyed. If any contact occurs, immediate thorough washing with water or preferably with normal saline solution should be undertaken.
In the case of vomiting within a few hours after drug intake, do not re-administer. Supportive treatment such as metoclopramide or 5HT3 antagonists (e.g. ondansetron, granisetron) may reduce the occurrence of this: see section 4.5. Navelbine soft capsule is associated with a higher incidence of nausea/vomiting than the intravenous formulation. Primary prophylaxis with antiemetics and administration of the capsules with some food is recommended as this has also been shown to reduce the incidence of nausea and vomiting: see section 4.2.
Patients receiving concomitant morphine or opioid analgesics: laxatives and careful monitoring of bowel mobility are recommended. Prescription of laxatives may be appropriate in patients with prior history of constipation.
Due to sorbitol content, patients with rare hereditary problems with fructose intolerance should not take the capsules.
Close haematological monitoring must be undertaken during treatment (determination of haemoglobin level and the leucocyte, neutrophil and platelet counts on the day of each new administration).
Dosing should be determined by haematological status:
- If the neutrophil count is below 1500 /mm3 and/or the platelet count is below 100000/mm3, then the treatment should be delayed until recovery.
- For dose escalation from 60 to 80 mg/m2 per week, after the third administration: see section 4.2.
- For the administrations given at 80mg/m², if the neutrophil count is below 500/mm3 or more than once between 500 and 1000 /mm3, then the treatment should be delayed until recovery. The administration should not only be delayed but also reduced to 60mg/m² per week. It is possible to reescalate the dose from 60 to 80 mg/m2 per week: see section 4.2.
During clinical trials where treatments were initiated at 80 mg/m2, a few patients developed excessive neutropenic complications including those with a poor performance status. Therefore it is recommended that the starting dose should be 60 mg/m2 escalating to 80 mg/m2 if the dose is tolerated as described in section 4.2.
If patients present signs or symptoms suggestive of infection, a prompt investigation should be carried out.
Special precautions for use
Special care should be taken when prescribing for patients with:
- history of ischemic heart disease: see section 4.8
- poor performance status
Navelbine should not be given concomitantly with radiotherapy if the treatment field includes the liver.
This product is specifically contra-indicated with yellow fever vaccine and its concomitant use with other live attenuated vaccines is not recommended: see section 4.3.
Caution must be exercised when combining Navelbine and strong inhibitors or inducers of CYP3A4 (see section 4.5), and its combination with phenytoin (like all cytotoxics) and with itraconazole (like all vinca alkaloids) is not recommended.
Oral Navelbine was studied in patients with liver impairment at the following doses:
- 60 mg/m² in 7 patients with mild liver impairment (bilirubin < 1.5 x ULN, and ALAT and/or ASAT from 1.5 to 2.5 x ULN);
- 50 mg/m² in 6 patients with moderate liver impairment (bilirubin from 1.5 to 3 x ULN, whatever the levels of ALAT and ASAT).
Total clearance of vinorelbine was neither modified between mild and moderate liver impairment nor was it altered in hepatically impaired patients when compared with clearance in patients with normal liver function.
Oral Navelbine was not studied in patients with severe hepatic impairment therefore its use is contra-indicated in these patients: see sections 4.2, 4.3, 5.2.
As there is a low level of renal excretion there is no pharmacokinetic rationale for reducing the dose of Navelbine in patients with impaired kidney function: see sections 4.2, 5.2.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Concomitant use contraindicated
Yellow fever vaccine: as with all cytotoxics, risk of fatal generalised vaccine disease: see section 4.3.
Concomitant use not recommended
Live attenuated vaccines: (for yellow fever vaccine, see concomitant use contraindicated) as with all cytotoxics, risk of generalised vaccine disease, possibly fatal. This risk is increased in patients already immunodepressed by their underlying disease. It is recommended to use an inactivated vaccine when one exists (e.g. poliomyelitis): see section 4.4
Phenytoin: as with all cytotoxics, risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic drug or risk of toxicity enhancement or loss of efficacy of the cytotoxic drug due to increased hepatic metabolism by phenytoin.
Itraconazole: as with all vinca-alkaloids, increased neurotoxicity of vinca-alkaloids due to the decrease of their hepatic metabolism.
Concomitant use to take into consideration
Cisplatin: There is no mutual pharmacokinetic interaction when combining Navelbine with cisplatin over several cycles of treatment. However, the incidence of granulocytopenia associated with Navelbine use in combination with cisplatin is higher than associated with Navelbine single agent.
Mitomycin C: risk of bronchospasm and dyspnoea are increased, in rare case an interstitial pneumonitis was observed.
Ciclosporin, tacrolimus: excessive immunodepression with risk of lymphoproliferation.
As vinca-alkaloids are known as substrates for P-glycoprotein, and in the absence of specific study, caution should be exercised when combining Navelbine with strong modulators of this membrane transporter.
The combination of NAVELBINE with other drugs with known bone marrow toxicity is likely to exacerbate the myelosuppressive adverse effects.
No clinically significant pharmacokinetic interaction was observed when combining Navelbine with several other chemotherapeutic agents (paclitaxel, docetaxel, capecitabine and oral cyclophosphamide).
As CYP3A4 is mainly involved in the metabolism of vinorelbine, combination with strong inhibitors of this isoenzyme (e.g. azole antifungals such as ketoconazole and itraconazole) could increase blood concentrations of vinorelbine and combination with strong inducers of this isoenzyme (e.g. rifampicin, phenytoin) could decrease blood concentrations of vinorelbine.
Anti-emetic drugs such as 5HT3 antagonists (e.g. ondansetron, granisetron) do not modify the pharmacokinetics of Navelbine soft capsules (see section 4.4).
Anticoagulant treatment: as with all cytotoxics, the frequency of INR (International Normalised Ratio) monitoring should be increased due to the potential interaction with oral anticoagulants and increased variability of coagulation in patients with cancer.
Food does not modify the pharmacokinetics of vinorelbine.
4.6 Pregnancy And Lactation
Pregnancy
Navelbine is suspected to cause serious birth effects when administered during pregnancy: see section 5.3.
Navelbine is contra-indicated in pregnancy: see section 4.3.
In case of a vital indication for treatment with Navelbine during pregnancy a medical consultation concerning the risk of harmful effects for the child should be conducted. If pregnancy occurs during treatment genetic counseling should be offered.
Women of child-bearing potential
Women of child-bearing potential must use effective contraception during treatment and up to 3 months after treatment: see section 4.3
Lactation
It is unknown whether vinorelbine is excreted in human breast milk.
The excretion of vinorelbine in milk has not been studied in animal studies.
A risk to the suckling child cannot be excluded therefore breast feeding must be discontinued before starting treatment with Navelbine: see section 4.3.
Fertility
Men being treated with Navelbine are advised not to father a child during and minimally up to 3 months after treatment: see section 4.3.
Prior to treatment advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment with vinorelbine.
4.7 Effects On Ability To Drive And Use Machines
No studies on the effects on the ability to drive and use machines have been performed but on the basis of the pharmacodynamic profile vinorelbine does not affect the ability to drive and use machines. However, caution is necessary in patients treated with vinorelbine considering some adverse effects of the drug: see section 4.8.
4.8 Undesirable Effects
The overall reported frequency of undesirable effects was determined from clinical studies in 316 patients (132 patients with non small cell lung cancer and 184 patients with breast cancer) who received the recommended regimen of Navelbine (first three administrations at 60mg/m²/week followed by 80mg/m²/week).
Adverse reactions reported are listed below, by system organ and by frequency.
Additional Adverse reactions from Post Marketing experience has been added according to the MedDRA classification with the frequency Not known.
The reactions were described using the NCI common toxicity criteria
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Undesirable effects reported with Navelbine soft capsule:
Pre-marketing experience:
The most commonly reported adverse drug reactions are bone marrow depression with neutropenia, anaemia and thrombocytopenia, gastrointestinal toxicity with nausea, vomiting, diarrhoea, stomatitis and constipation. Fatigue and fever were also reported very commonly.
Post-marketing experience:
Navelbine soft capsule is used as single agent or in combination with other chemotherapeutic agents or targeted therapy agents such as cisplatin, capecitabine, carboplatin, epirubicin, trastuzumab, erlotinib, sorafenib.
The most commonly system organ classes involved during post-marketing experience are: 'Blood and lymphatic system disorders', 'Gastrointestinal disorders', 'Infections and infestations' and 'General disorders and administration site conditions'. This information is consistent with the pre-marketing experience.
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Undesirable effects with Navelbine, concentrate for infusion:
Some undesirable effects were observed with Navelbine, concentrate for solution for infusion during pre- and post-marketing experience which were not reported with Navelbine soft capsule.
In order to provide the complete information and to further the safety of use of Navelbine soft capsule, these effects are presented below:
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4.9 Overdose
Symptoms
Overdosage with Navelbine soft capsules could produce bone marrow hypoplasia sometimes associated with infection, fever, paralytic ileus and hepatic disorders.
Emergency procedure
General supportive measures together with blood transfusion, growth factors, and broad spectrum antibiotic therapy should be instituted as deemed necessary by the physician. A close monitoring of hepatic function recommended.
Antidote
There is no known antidote for overdosage of Navelbine.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Vinca alkaloïds and analogues (ATC Code: L01C A04)
Navelbine is a antineoplastic drug of the vinca alkaloid family but unlike all the other vinca alkaloids, the catharantine moiety of vinorelbine has been structurally modified. At the molecular level, it acts on the dynamic equilibrium of tubulin in the microtubular apparatus of the cell. It inhibits tubulin polymerization and binds preferentially to mitotic microtubules, affecting axonal microtubules at high concentrations only. The induction of tubulin spiralization is less than that produced by vincristine.
Navelbine blocks mitosis at G2-M, causing cell death in interphase or at the following mitosis.
Safety and efficacy of Navelbine in paediatric patients have not been established. Clinical data from two single-arm Phase II studies using intravenous vinorelbine in 33 and 46 paediatric patients with recurrent solid tumours, including rhabdomyosarcoma, other soft tissue sarcoma, Ewing sarcoma, liposarcoma, synovial sarcoma, fibrosarcoma, central nervous system cancer, osteosarcoma, neuroblastoma at doses of 30 to 33.75mg/m2 D1 and D8 every 3 weeks or once weekly for 6 weeks every 8 weeks showed no meaningful clinical activity. The toxicity profile was similar to that reported in adult patients (see section 4.2).
5.2 Pharmacokinetic Properties
Pharmacokinetic parameters of vinorelbine were evaluated in blood.
Absorption
After oral administration, vinorelbine is rapidly absorbed and the Tmax is reached between 1.5 to 3 h with a blood concentration peak (Cmax) of approximately 130 ng/ml after a dose of 80 mg/m².
Absolute bioavailability is approximately 40% and a simultaneous intake of food does not alter the exposure to vinorelbine.
Oral vinorelbine at 60 and 80 mg/m2 leads to blood exposure comparable to that achieved with intravenous vinorelbine at 25 and 30 mg/m2, respectively.
The blood exposure to vinorelbine increases proportionally with the dose up to 100mg/m2. Interindividual variability of the exposure is similar after administration by intravenous and oral routes.
Distribution
The steady-state volume of distribution is large, on average 21.2 l.kg-1(range: 7.5 - 39.7 l.kg-1), which indicates extensive tissue distribution.
Binding to plasma proteins is weak (13.5%), vinorelbine binds strongly to blood cells and especially to platelets (78%).
There is a significant uptake of vinorelbine in lungs, as assessed by pulmonary surgical biopsies which showed concentration up to a 300- fold higher concentration than in serum. Vinorelbine is not found in the central nervous system.
Biotransformation
All metabolites of vinorelbine are formed by CYP3A4 isoform of cytochromes P450, except 4-O-deacetylvinorelbine likely to be formed by carboxylesterases. 4-O-deacetylvinorelbine is the only active metabolite and the main one observed in blood.
Neither sulfate nor glucuronide conjugates are found.
Elimination
The mean terminal half-life of vinorelbine is around 40 hours. Blood clearance is high, approaching hepatic blood flow, and is 0.72 l.h-1.kg-1 (range: 0.32-1.26 l.h-1.kg-1).
Renal elimination is low (<5 % of the dose administered) and consists mostly in parent compound. Biliary excretion is the predominant elimination route of both unchanged vinorelbine, which is the main recovered compound, and its metabolites.
Special patients groups
Renal and liver impairment:
The effects of renal dysfunction on the pharmacokinetics of vinorelbine have not been studied. However, dose reduction in case of reduced renal function is not indicated with vinorelbine due to the low level of renal elimination.
Pharmacokinetics of orally administered vinorelbine were not modified after administration of 60 mg/m² in 7 patients with mild liver impairment (bilirubin < 1.5 x ULN, and ALAT and/or ASAT from 1.5 to 2.5 x ULN) and of 50 mg/m² in 6 patients with moderate liver impairment (bilirubin from 1.5 to 3 x ULN, whatever the levels of ALAT and ASAT). Total clearance of vinorelbine was neither modified between mild and moderate impairment nor was it altered in hepatically impaired patients when compared with clearance in patients with normal liver function.
No data is available for patients with severe liver impairment therefore Navelbine is contra-indicated in these patients: see sections 4.2, 4.3 and 4.4.
Elderly patients
A study with oral vinorelbine in elderly patients (
Pharmacokinetics/Pharmacodynamic relationships
A strong relationship has been demonstrated between blood exposure and depletion of leucocytes or PMNs.
5.3 Preclinical Safety Data
Pre-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity.
Vinorelbine induced chromosome changes but was not mutagenic in Ames test. It is assumed that vinorelbine can cause mutagenic effects (induction of aneuploidy of polyploidy) in man.
In animal reproductive studies, vinorelbine was embryo-feto-lethal and teratogenic.
No haemodynamic effects were found in dogs receiving vinorelbine at maximal tolerated dose; only some minor, non significant disturbances of repolarisation were observed as with other vinca alkaloids tested.
No effect on the cardiovascular system was observed in primates receiving repeated doses of vinorelbine over 39 weeks.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Fill solution:
Ethanol, anhydrous
Water, purified
Glycerol
Macrogol 400
Shell capsule:
Gelatin
Glycerol 85%
Sorbitol/Sorbitan Anidrisorb 85/70)
Red iron oxide E172
Titanium dioxide E171
Triglycerides, medium chain
Phosal 53 MCT (Phosphatidylcholine; Glycerides; Ethanol, anhydrous)
Edible printing ink:
Cochineal extract E120
Hypromellose
Propylene glycol
6.2 Incompatibilities
No
Ketamina
Ketamina may be available in the countries listed below.
Ingredient matches for Ketamina
Ketamine
Ketamina (DCIT) is known as Ketamine in the US.
International Drug Name Search
Glossary
| DCIT | Denominazione Comune Italiana |
Click for further information on drug naming conventions and International Nonproprietary Names.
Esgic Tablets
HEPATOTOXICITY
ACETAMINOPHEN HAS BEEN ASSOCIATED WITH CASES OF ACUTE LIVER FAILURE, AT TIMES RESULTING IN LIVER TRANSPLANT AND DEATH. MOST OF THE CASES OF LIVER INJURY ARE ASSOCIATED WITH THE USE OF ACETAMINOPHEN AT DOSES THAT EXCEED 4000 MILLIGRAMS PER DAY, AND OFTEN INVOLVE MORE THAN ONE ACETAMINOPHEN-CONTAINING PRODUCT.
Esgic Tablets Description
Butalbital, acetaminophen and caffeine are supplied in tablet form for oral administration.
Each Tablet contains the following active ingredients:
Butalbital ...................50 mg
Warning: May be habit-forming.
Acetaminophen ..........325 mg
Caffeine ......................40 mg
In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, microcrystalline cellulose, povidone, pregelatinized corn starch and stearic acid.
Butalbital (5-allyl-5-isobutylbarbituric acid) is a short to intermediate-acting barbiturate. It has the following structural formula:
C11H16N2O3 MW = 224.26
Acetaminophen (4'-hydroxyacetanilide) is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:
C8H9NO2 MW = 151.16
Caffeine (1,3,7-trimethylxanthine) is a central nervous system stimulant. It has the following structural formula:
C8H10N4O2 MW = 194.19
Esgic Tablets - Clinical Pharmacology
This combination drug product is intended as a treatment for tension headache.
It consists of a fixed combination of butalbital, acetaminophen and caffeine. The role each component plays in the relief of the complex of symptoms known as tension headache is incompletely understood.
Pharmacokinetics
The behavior of the individual components is described below.
Butalbital: Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most tissues in the body. Barbiturates in general may appear in breast milk and readily cross the placental barrier. They are bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility.
Elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drug or metabolites. The plasma half-life is about 35 hours. Urinary excretion products include parent drug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5 (3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. Of the material excreted in the urine, 32% is conjugated.
The in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5 to 20 mcg/mL. This falls within the range of plasma protein binding (20 to 45%) reported with other barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. The plasma-to-blood concentration ratio was almost unity, indicating that there is no preferential distribution of butalbital into either plasma or blood cells (See OVERDOSAGE for toxicity information.)
Acetaminophen: Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug. (See OVERDOSAGE for toxicity information.)
Caffeine: Like most xanthines, caffeine is rapidly absorbed and distributed in all body tissues and fluids, including the CNS, fetal tissues, and breast milk.
Caffeine is cleared through metabolism and excretion in the urine. The plasma half-life is about 3 hours. Hepatic biotransformation prior to excretion, results in about equal amounts of 1-methylxanthine and 1-methyluric acid. Of the 70% of the dose that is recovered in the urine, only 3% is unchanged drug. (See OVERDOSAGE for toxicity information.)
Indications and Usage for Esgic Tablets
Esgic® Tablets (butalbital, acetaminophen and caffeine tablets, USP 50 mg/325 mg/40 mg) are indicated for the relief of the symptom complex of tension (or muscle contraction) headache.
Evidence supporting the efficacy and safety of this combination product in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because butalbital is habit-forming and potentially abusable.
Contraindications
This product is contraindicated under the following conditions:
- Hypersensitivity or intolerance to any component of this product.
- Patients with porphyria.
Warnings
Butalbital is habit-forming and potentially abusable. Consequently, the extended use of this product is not recommended.
Hepatotoxicity
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.
The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.
Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.
Hypersensitivity/anaphylaxis
There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue Esgic® Tablets immediately and seek medical care if they experience these symptoms. Do not prescribe Esgic® Tablets for patients with acetaminophen allergy.
Precautions
General
Esgic® Tablets should be prescribed with caution in certain special-risk patients, such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, or acute abdominal conditions.
Information for Patients/Caregivers
- Do not take Esgic® Tablets if you are allergic to any of its ingredients.
- If you develop signs of allergy such as a rash or difficulty breathing, stop taking Esgic® Tablets and contact your healthcare provider immediately.
- Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more than the recommended dose.
This product may impair mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking this product.
Alcohol and other CNS depressants may produce an additive CNS depression when taken with this combination product, and should be avoided.
Butalbital may be habit-forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.
For information on use in geriatric patient. (See PRECAUTIONS/Geriatric Use.)
Laboratory Tests
In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.
Drug Interactions
The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors.
Butalbital, acetaminophen and caffeine may enhance the effects of: other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.
Drug/Laboratory Test Interactions
Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No adequate studies have been conducted in animals to determine whether acetaminophen or butalbital have a potential for carcinogenesis, mutagenesis or impairment of fertility.
Pregnancy
Teratogenic Effects
Pregnancy Category C
Animal reproduction studies have not been conducted with this combination product. It is also not known whether butalbital, acetaminophen and caffeine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. This product should be given to a pregnant woman only when clearly needed.
Nonteratogenic Effects
Withdrawal seizures were reported in a two-day-old male infant whose mother had taken a butalbital-containing drug during the last two months of pregnancy. Butalbital was found in the infant’s serum. The infant was given phenobarbital 5 mg/kg, which was tapered without further seizure or other withdrawal symptoms.
Nursing Mothers
Caffeine, barbiturates and acetaminophen are excreted in breast milk in small amounts, but the significance of their effects on nursing infants is not known. Because of potential for serious adverse reactions in nursing infants from butalbital, acetaminophen and caffeine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 12 have not been established.
Geriatric Use
Clinical studies of butalbital, acetaminophen and caffeine tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Butalbital is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Adverse Reactions
Frequently Observed
The most frequently reported adverse reactions are drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, abdominal pain, and intoxicated feeling.
Infrequently Observed
All adverse events tabulated below are classified as infrequent.
Central Nervous System: headache, shaky feeling, tingling, agitation, fainting, fatigue, heavy eyelids, high energy, hot spells, numbness, sluggishness, seizure. Mental confusion, excitement or depression can also occur due to intolerance, particularly in elderly or debilitated patients, or due to overdosage of butalbital.
Autonomic Nervous System: dry mouth, hyperhidrosis.
Gastrointestinal: difficulty swallowing, heartburn, flatulence, constipation.
Cardiovascular: tachycardia.
Musculoskeletal: leg pain, muscle fatigue.
Genitourinary: diuresis.
Miscellaneous: pruritus, fever, earache, nasal congestion, tinnitus, euphoria, allergic reactions.
Several cases of dermatological reactions, including toxic epidermal necrolysis and erythema multiforme, have been reported.
The following adverse drug events may be borne in mind as potential effects of the components of this product. Potential effects of high dosage are listed in the OVERDOSAGE section.
Acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis.
Caffeine: cardiac stimulation, irritability, tremor, dependence, nephrotoxicity, hyperglycemia.
Drug Abuse and Dependence
Abuse and Dependence
Butalbital: Barbiturates may be habit-forming: Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates. The average daily dose for the barbiturate addict is usually about 1500 mg. As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than two-fold. As this occurs, the margin between an intoxication dosage and fatal dosage becomes smaller. The lethal dose of a barbiturate is far less if alcohol is also ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug. Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens. One method involves initiating treatment at the patient’s regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.
Overdosage
Following an acute overdosage of butalbital, acetaminophen and caffeine, toxicity may result from the barbiturate or the acetaminophen. Toxicity due to caffeine is less likely, due to the relatively small amounts in this formulation.
Signs and Symptoms
Toxicity from barbiturate poisoning includes drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock.
In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necroses, hypoglycemic coma and coagulation defects may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.
Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium, tachycardia and extrasystoles.
Treatment
A single or multiple drug overdose with this combination product is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.
Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered.
Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.
Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.
Esgic Tablets Dosage and Administration
One or two tablets every four hours as needed. Total daily dosage should not exceed 6 tablets.
Extended and repeated use of this product is not recommended because of the potential for physical dependence.
How is Esgic Tablets Supplied
Esgic® Tablets (butalbital 50 mg [Warning: May be habit-forming], acetaminophen 325 mg and caffeine 40 mg) are white, capsule-shaped, single-scored tablets debossed "
Storage
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container with a child-resistant closure.
Rx only
Manufactured by:
MIKART, INC.
Atlanta, GA 30318
For:
GILBERT LABORATORIES
Affiliate of Forest Pharmaceuticals, Inc.
St. Louis, Missouri 63045
Code 687A00
Rev. 06/11
PRINCIPAL DISPLAY PANEL
| ESGIC butalbital, acetaminophen and caffeine tablet | ||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| ANDA | ANDA089175 | 06/01/1997 | |
| Labeler - Forest Laboratories, Inc. (001288281) |
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