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Thursday, 12 April 2012

Taxotere 80mg / 4ml concentrate and solvent for solution for infusion

1. Name Of The Medicinal Product

TAXOTERE 80 mg/4 ml concentrate for solution for infusion

2. Qualitative And Quantitative Composition

Each ml of concentrate contains 20 mg docetaxel as trihydrate.

One vial of 4 ml of concentrate contains 80 mg of docetaxel.

Excipients:

Each vial of concentrate contains 2 ml of ethanol anhydrous (1.58 g).

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Concentrate for solution for infusion (sterile concentrate).

The concentrate is a pale yellow to brownish-yellow solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Breast cancer

TAXOTERE in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with:

• operable node- positive breast cancer

• operable node-negative breast cancer .

For patients with operable node-negative breast cancer, adjuvant treatment should be restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer (see section 5.1).

TAXOTERE in combination with doxorubicin is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic therapy for this condition.

TAXOTERE monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic therapy. Previous chemotherapy should have included an anthracycline or an alkylating agent.

TAXOTERE in combination with trastuzumab is indicated for the treatment of patients with metastatic breast cancer whose tumours over express HER2 and who previously have not received chemotherapy for metastatic disease.

TAXOTERE in combination with capecitabine is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.

Non-small cell lung cancer

TAXOTERE is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.

TAXOTERE in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer, in patients who have not previously received chemotherapy for this condition.

Prostate cancer

TAXOTERE in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone refractory metastatic prostate cancer.

Gastric adenocarcinoma

TAXOTERE in combination with cisplatin and 5-fluorouracil is indicated for the treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for metastatic disease.

Head and neck cancer

TAXOTERE in combination with cisplatin and 5-fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.

4.2 Posology And Method Of Administration

The use of docetaxel should be confined to units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a physician qualified in the use of anticancer chemotherapy (see section 6.6).

Recommended dose

For breast, non-small cell lung, gastric, and head and neck cancers, premedication consisting of an oral corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can be used (see section 4.4). Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities.

For prostate cancer, given the concurrent use of prednisone or prednisolone the recommended premedication regimen is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.4).

Docetaxel is administered as a one-hour infusion every three weeks.

Breast cancer

In the adjuvant treatment of operable node-positive and node-negative breast cancer, the recommended dose of docetaxel is 75 mg/m² administered 1-hour after doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks for 6 cycles (TAC regimen) (see also Dose adjustments during treatment).

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of docetaxel is 100 mg/m² in monotherapy. In first-line treatment, docetaxel 75 mg/m² is given in combination therapy with doxorubicin (50 mg/m²).

In combination with trastuzumab the recommended dose of docetaxel is 100 mg/m² every three weeks, with trastuzumab administered weekly. In the pivotal study the initial docetaxel infusion was started the day following the first dose of trastuzumab. The subsequent docetaxel doses were administered immediately after completion of the trastuzumab infusion, if the preceding dose of trastuzumab was well tolerated. For trastuzumab dose and administration, see trastuzumab summary of product characteristics.

In combination with capecitabine, the recommended dose of docetaxel is 75 mg/m² every three weeks, combined with capecitabine at 1250 mg/m² twice daily (within 30 minutes after a meal) for 2 weeks followed by a 1-week rest period. For capecitabine dose calculation according to body surface area, see capecitabine summary of product characteristics.

Non-small cell lung cancer

In chemotherapy naïve patients treated for non-small cell lung cancer, the recommended dose regimen is docetaxel 75 mg/m² immediately followed by cisplatin 75 mg/m² over 30-60 minutes. For treatment after failure of prior platinum-based chemotherapy, the recommended dose is 75 mg/m² as a single agent.

Prostate cancer

The recommended dose of docetaxel is 75 mg/m². Prednisone or prednisolone 5 mg orally twice daily is administered continuously (see section 5.1).

Gastric adenocarcinoma

The recommended dose of docetaxel is 75 mg/m² as a 1-hour infusion, followed by cisplatin 75 mg/m², as a 1- to 3-hour infusion (both on day 1 only), followed by 5-fluorouracil 750 mg/m² per day given as a 24-hour continuous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration. Prophylactic G-CSF should be used to mitigate the risk of haematological toxicities (see also Dose adjustments during treatment).

Head and neck cancer

Patients must receive premedication with antiemetics and appropriate hydration (prior to and after cisplatin administration). Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. All patients on the docetaxel-containing arm of the TAX 323 and TAX 324 studies, received prophylactic antibiotics.

• Induction chemotherapy followed by radiotherapy (TAX 323)

For the induction treatment of inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1 hour infusion followed by cisplatin 75 mg/m² over 1 hour, on day one, followed by 5-fluorouracil as a continuous infusion at 750 mg/m² per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.

• Induction chemotherapy followed by chemoradiotherapy (TAX 324)

For the induction treatment of patients with locally advanced (technically unresectable, low probability of surgical cure, and aiming at organ preservation) squamous cell carcinoma of the head and neck (SCCHN), the recommended dose of docetaxel is 75 mg/m² as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m² administered as a 30-minute to 3-hour infusion, followed by 5-fluorouracil 1000 mg/m²/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.

For cisplatin and 5-fluorouracil dose modifications, see the corresponding summary of product characteristics.

Dose adjustments during treatment

General

Docetaxel should be administered when the neutrophil count is ³.

In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm³ for more than one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during docetaxel therapy, the dose of docetaxel should be reduced from 100 mg/m² to 75 mg/m² and/or from 75 to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.

Adjuvant therapy for breast cancer

Primary G-CSF prophylaxis should be considered in patients who receive docetaxel, doxorubicin and cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients who experience febrile neutropenia and/or neutropenic infection should have their docetaxel dose reduced to 60 mg/m² in all subsequent cycles (see sections 4.4 and 4.8). Patients who experience Grade 3 or 4 stomatitis should have their dose decreased to 60 mg/m².

In combination with cisplatin

For patients who are dosed initially at docetaxel 75 mg/m² in combination with cisplatin and whose nadir of platelet count during the previous course of therapy is < 25,000 cells/mm³, or in patients who experience febrile neutropenia, or in patients with serious non-haematologic toxicities, the docetaxel dose in subsequent cycles should be reduced to 65 mg/m². For cisplatin dose adjustments, see the corresponding summary of product characteristics.

In combination with capecitabine

• For capecitabine dose modifications, see capecitabine summary of product characteristics.

• For patients developing the first appearance of Grade 2 toxicity, which persists at the time of the next docetaxel/capecitabine treatment, delay treatment until resolved to Grade 0-1, and resume at 100% of the original dose.

• For patients developing the second appearance of Grade 2 toxicity, or the first appearance of Grade 3 toxicity, at any time during the treatment cycle, delay treatment until resolved to Grade 0-1 and then resume treatment with docetaxel 55 mg/m².

• For any subsequent appearances of toxicities, or any Grade 4 toxicities, discontinue the docetaxel dose.

For trastuzumab dose modifications, see trastuzumab summary of product characteristics.

In combination with cisplatin and 5-fluorouracil

If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/m². If subsequent episodes of complicated neutropenia occur the docetaxel dose should be reduced from 60 to 45 mg/m². In case of Grade 4 thrombocytopenia the docetaxel dose should be reduced from 75 to 60 mg/m². Patients should not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level > 1,500 cells/mm³ and platelets recover to a level > 100,000 cells/mm³. Discontinue treatment if these toxicities persist (see section 4.4).

Recommended dose modifications for toxicities in patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (5-FU):

Toxicity	Dose adjustment
Diarrhoea grade 3	First episode: reduce 5-FU dose by 20%. Second episode: then reduce docetaxel dose by 20%.
Diarrhoea grade 4	First episode: reduce docetaxel and 5-FU doses by 20%. Second episode: discontinue treatment.
Stomatitis/mucositis grade 3	First episode: reduce 5-FU dose by 20%. Second episode: stop 5-FU only, at all subsequent cycles. Third episode: reduce docetaxel dose by 20%.
Stomatitis/mucositis grade 4	First episode: stop 5-FU only, at all subsequent cycles. Second episode: reduce docetaxel dose by 20%.

For cisplatin and 5-fluorouracil dose adjustments, see the corresponding summary of product characteristics.

In the pivotal SCCHN studies patients who experienced complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended to use G-CSF to provide prophylactic coverage (eg, day 6-15) in all subsequent cycles.

Special populations

Patients with hepatic impairment

Based on pharmacokinetic data with docetaxel at 100 mg/m² as single agent, patients who have both elevations of transaminase (ALT and/or AST) greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, the recommended dose of docetaxel is 75 mg/m² (see sections 4.4 and 5.2). For those patients with serum bilirubin > ULN and/or ALT and AST > 3.5 times the ULN associated with alkaline phosphatase > 6 times the ULN, no dose-reduction can be recommended and docetaxel should not be used unless strictly indicated.

In combination with cisplatin and 5-fluorouracil for the treatment of patients with gastric adenocarcinoma, the pivotal clinical study excluded patients with ALT and/or AST > 1.5 × ULN associated with alkaline phosphatase > 2.5 × ULN, and bilirubin > 1 x ULN; for these patients, no dose-reductions can be recommended and docetaxel should not be used unless strictly indicated. No data are available in patients with hepatic impairment treated by docetaxel in combination in the other indications.

Paediatric population

The safety and efficacy of TAXOTERE in nasopharyngeal carcinoma in children aged 1 month to less than 18 years have not yet been established.

There is no relevant use of TAXOTERE in the paediatric population in the indications breast cancer, non-small cell lung cancer, prostate cancer, gastric carcinoma and head and neck cancer, not including type II and III less differentiated nasopharyngeal carcinoma.

Elderly

Based on a population pharmacokinetic analysis, there are no special instructions for use in the elderly.

In combination with capecitabine, for patients 60 years of age or more, a starting dose reduction of capecitabine to 75% is recommended (see capecitabine summary of product characteristics).

4.3 Contraindications

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

Patients with baseline neutrophil count of < 1,500 cells/mm³.

Patients with severe liver impairment (see sections 4.2 and 4.4).

Contraindications for other medicinal products also apply, when combined with docetaxel.

4.4 Special Warnings And Precautions For Use

For breast and non-small cell lung cancers, premedication consisting of an oral corticosteroid, such as dexamethasone 16 mg per day (e.g. 8 mg BID) for 3 days starting 1 day prior to docetaxel administration, unless contraindicated, can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions. For prostate cancer, the premedication is oral dexamethasone 8 mg, 12 hours, 3 hours and 1 hour before the docetaxel infusion (see section 4.2).

Haematology

Neutropenia is the most frequent adverse reaction of docetaxel. Neutrophil nadirs occurred at a median of 7 days but this interval may be shorter in heavily pre-treated patients. Frequent monitoring of complete blood counts should be conducted on all patients receiving docetaxel. Patients should be retreated with docetaxel when neutrophils recover to a level

In the case of severe neutropenia (< 500 cells/mm³ for seven days or more) during a course of docetaxel therapy, a reduction in dose for subsequent courses of therapy or the use of appropriate symptomatic measures are recommended (see section 4.2).

In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TCF should be closely monitored (see sections 4.2 and 4.8).

In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be closely monitored (see sections 4.2 and 4.8).

Hypersensitivity reactions

Patients should be observed closely for hypersensitivity reactions especially during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of docetaxel, thus facilities for the treatment of hypotension and bronchospasm should be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised cutaneous reactions do not require interruption of therapy. However, severe reactions, such as severe hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions should not be re-challenged with docetaxel.

Cutaneous reactions

Localised skin erythema of the extremities (palms of the hands and soles of the feet) with oedema followed by desquamation has been observed. Severe symptoms such as eruptions followed by desquamation which lead to interruption or discontinuation of docetaxel treatment were reported (see section 4.2).

Fluid retention

Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be monitored closely.

Patients with liver impairment

In patients treated with docetaxel at 100 mg/m² as single agent who have serum transaminase levels (ALT and/or AST) greater than 1.5 times the ULN concurrent with serum alkaline phosphatase levels greater than 2.5 times the ULN, there is a higher risk of developing severe adverse reactions such as toxic deaths including sepsis and gastrointestinal haemorrhage which can be fatal, febrile neutropenia, infections, thrombocytopenia, stomatitis and asthenia. Therefore, the recommended dose of docetaxel in those patients with elevated liver function test (LFTs) is 75 mg/m² and LFTs should be measured at baseline and before each cycle (see section 4.2).

For patients with serum bilirubin levels > ULN and/or ALT and AST > 3.5 times the ULN concurrent with serum alkaline phosphatase levels > 6 times the ULN, no dose-reduction can be recommended and docetaxel should not be used unless strictly indicated.

Patients with renal impairment

There are no data available in patients with severely impaired renal function treated with docetaxel.

Nervous system

The development of severe peripheral neurotoxicity requires a reduction of dose (see section 4.2).

Cardiac toxicity

Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, particularly following anthracycline (doxorubicin or epirubicin)-containing chemotherapy. This may be moderate to severe and has been associated with death (see section 4.8).

When patients are candidates for treatment with docetaxel in combination with trastuzumab, they should undergo baseline cardiac assessment. Cardiac function should be further monitored during treatment (e.g. every three months) to help identify patients who may develop cardiac dysfunction. For more details see summary of product characteristics of trastuzumab.

Others

Contraceptive measures must be taken by both men and women during treatment and for men at least 6 months after cessation of therapy (see section 4.6).

Additional cautions for use in adjuvant treatment of breast cancer

Complicated neutropenia

For patients who experience complicated neutropenia (prolonged neutropenia, febrile neutropenia or infection), G-CSF and dose reduction should be considered (see section 4.2).

Gastrointestinal reactions

Symptoms such as early abdominal pain and tenderness, fever, diarrhoea, with or without neutropenia, may be early manifestations of serious gastrointestinal toxicity and should be evaluated and treated promptly.

Congestive heart failure (CHF)

Patients should be monitored for symptoms of congestive heart failure during therapy and during the follow up period. In patients treated with the TAC regimen for node positive breast cancer, the risk of CHF has been shown to be higher during the first year after treatment (see sections 4.8 and 5.1).

Leukaemia

In the docetaxel, doxorubicin and cyclophosphamide (TAC) treated patients, the risk of delayed myelodysplasia or myeloid leukaemia requires haematological follow-up.

Patients with 4+ nodes

As the benefit observed in patient with 4+ nodes was not statistically significant on disease-free survival (DFS) and overall survival (OS), the positive benefit/risk ratio for TAC in patients with 4+ nodes was not fully demonstrated at the final analysis (see section 5.1).

Elderly

There are limited data available in patients > 70 years of age on docetaxel use in combination with doxorubicin and cyclophosphamide.

Of the 333 patients treated with docetaxel every three weeks in a prostate cancer study, 209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with docetaxel every three weeks, the incidence of related nail changes occurred at a rate

Among the 300 (221 patients in the phase III part of the study and 79 patients in the phase II part) patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer study, 74 were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of serious adverse events was higher in the elderly patients compared to younger patients. The incidence of the following adverse events (all grades): lethargy, stomatitis, neutropenic infection occurred at rates

Elderly patients treated with TCF should be closely monitored.

Excipients

This medicinal product contains 50 vol % ethanol (alcohol), i.e. up to 1.58 g (2 ml) per vial, equivalent to 40 ml of beer or 17 ml wine per vial.

Harmful for those suffering from alcoholism.

To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.

The amount of alcohol in this medicinal product may alter the effects of other medicinal products.

The amount of alcohol in this medicinal product may impair the patients ability to drive or use machines.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds which induce, inhibit or are metabolised by (and thus may inhibit the enzyme competitively) cytochrome P450-3A such as ciclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin. As a result, caution should be exercised when treating patients with these medicinal products as concomitant therapy since there is a potential for a significant interaction.

Docetaxel is highly protein bound (> 95%). Although the possible in vivo interaction of docetaxel with concomitantly administered medicinal product has not been investigated formally, in vitro interactions with tightly protein-bound agents such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylate, sulfamethoxazole and sodium valproate did not affect protein binding of docetaxel. In addition, dexamethasone did not affect protein binding of docetaxel. Docetaxel did not influence the binding of digitoxin.

The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide were not influenced by their co-administration. Limited data from a single uncontrolled study were suggestive of an interaction between docetaxel and carboplatin. When combined to docetaxel, the clearance of carboplatin was about 50% higher than values previously reported for carboplatin monotherapy.

Docetaxel pharmacokinetics in the presence of prednisone was studied in patients with metastatic prostate cancer. Docetaxel is metabolised by CYP3A4 and prednisone is known to induce CYP3A4. No statistically significant effect of prednisone on the pharmacokinetics of docetaxel was observed.

Docetaxel should be administered with caution in patients concomitantly receiving potent CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, azole antifungals like ketoconazole or itraconazole). A drug interaction study performed in patients receiving ketoconazole and docetaxel showed that the clearance of docetaxel was reduced by half by ketoconazole, probably because the metabolism of docetaxel involves CYP3A4 as a major (single) metabolic pathway. Reduced tolerance of docetaxel may occur, even at lower doses.

4.6 Pregnancy And Lactation

There is no information on the use of docetaxel in pregnant women. Docetaxel has been shown to be both embryotoxic and foetotoxic in rabbits and rats, and to reduce fertility in rats. As with other cytotoxic medicinal products, docetaxel may cause foetal harm when administered to pregnant women. Therefore, docetaxel must not be used during pregnancy unless clearly indicated.

Women of childbearing potential /contraception:

Women of childbearing age receiving docetaxel should be advised to avoid becoming pregnant, and to inform the treating physician immediately should this occur.

An effective method of contraception should be used during treatment.

In non clinical studies, docetaxel has genotoxic effects and may alter male fertility (see section 5.3). Therefore, men being treated with docetaxel are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.

Lactation:

Docetaxel is a lipophilic substance but it is not known whether it is excreted in human milk. Consequently, because of the potential for adverse reactions in nursing infants, breast feeding must be discontinued for the duration of docetaxel therapy.

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.

4.8 Undesirable Effects

The adverse reactions considered to be possibly or probably related to the administration of docetaxel have been obtained in:

• 1312 and 121 patients who received 100 mg/m² and 75 mg/m² of docetaxel as a single agent respectively.

• 258 patients who received docetaxel in combination with doxorubicin.

• 406 patients who received docetaxel in combination with cisplatin.

• 92 patients treated with docetaxel in combination with trastuzumab.

• 255 patients who received docetaxel in combination with capecitabine.

• 332 patients who received docetaxel in combination with prednisone or prednisolone (clinically important treatment related adverse events are presented).

• 1276 patients (744 and 532 in TAX 316 and GEICAM 9805 respectively) who received docetaxel in combination with doxorubicin and cyclophosphamide (clinically important treatment related adverse events are presented).

• 300 gastric adenocarcinoma patients (221 patients in the phase III part of the study and 79 patients in the phase II part) who received docetaxel in combination with cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented).

• 174 and 251 head and neck cancer patients who received docetaxel in combination with cisplatin and 5-fluorouracil (clinically important treatment related adverse events are presented).

These reactions were described using the NCI Common Toxicity Criteria (grade 3 = G3; grade 3-4 = G3/4; grade 4 = G4), the COSTART and the MedDRA terms. Frequencies are defined as: very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

The most commonly reported adverse reactions of docetaxel alone are: neutropenia (which was reversible and not cumulative; the median day to nadir was 7 days and the median duration of severe neutropenia (< 500 cells/mm³) was 7 days), anaemia, alopecia, nausea, vomiting, stomatitis, diarrhoea and asthenia. The severity of adverse events of docetaxel may be increased when docetaxel is given in combination with other chemotherapeutic agents.

For combination with trastuzumab, adverse events (all grades) reported in

For combination with capecitabine, the most frequent treatment-related undesirable effects (

The following adverse reactions are frequently observed with docetaxel:

Immune system disorders

Hypersensitivity reactions have generally occurred within a few minutes following the start of the infusion of docetaxel and were usually mild to moderate. The most frequently reported symptoms were flushing, rash with or without pruritus, chest tightness, back pain, dyspnoea and fever or chills. Severe reactions were characterised by hypotension and/or bronchospasm or generalized rash/erythema (see section 4.4).

Nervous system disorders

The development of severe peripheral neurotoxicity requires a reduction of dose (see sections 4.2 and 4.4). Mild to moderate neuro-sensory signs are characterised by paresthesia, dysesthesia or pain including burning. Neuro-motor events are mainly characterised by weakness.

Skin and subcutaneous tissue disorders

Reversible cutaneous reactions have been observed and were generally considered as mild to moderate. Reactions were characterised by a rash including localised eruptions mainly on the feet and hands (including severe hand and foot syndrome), but also on the arms, face or thorax, and frequently associated with pruritus. Eruptions generally occurred within one week after the docetaxel infusion. Less frequently, severe symptoms such as eruptions followed by desquamation which rarely lead to interruption or discontinuation of docetaxel treatment were reported (see sections 4.2 and 4.4). Severe nail disorders are characterised by hypo- or hyperpigmentation and sometimes pain and onycholysis.

General disorders and administration site conditions

Infusion site reactions were generally mild and consisted of hyper pigmentation, inflammation, redness or dryness of the skin, phlebitis or extravasation and swelling of the vein.

Fluid retention includes events such as peripheral oedema and less frequently pleural effusion, pericardial effusion, ascites and weight gain. The peripheral oedema usually starts at the lower extremities and may become generalised with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity (see section 4.4).

TAXOTERE 100 mg/m² single agent

MedDRA system organ classes	Very common adverse reactions	Common adverse reactions	Uncommon adverse reactions
Infections and infestations	Infections (G3/4: 5.7%; including sepsis and pneumonia, fatal in 1.7%)	Infection associated with G4 neutropenia (G3/4: 4.6%)
Blood and lymphatic system disorders	Neutropenia (G4: 76.4%); Anaemia (G3/4: 8.9%); Febrile neutropenia	Thrombocytopenia (G4: 0.2%)
Immune system disorders	Hypersensitivity (G3/4: 5.3%)
Metabolism and nutrition disorders	Anorexia
Nervous system disorders	Peripheral sensory neuropathy (G3: 4.1%); Peripheral motor neuropathy (G3/4: 4%); Dysgeusia (severe: 0.07%)
Cardiac disorders		Arrhythmia (G3/4: 0.7%)	Cardiac failure
Vascular disorders		Hypotension; Hypertension; Haemorrhage
Respiratory, thoracic and mediastinal disorders	Dyspnoea (severe: 2.7%)
Gastrointestinal disorders	Stomatitis (G3/4: 5.3%); Diarrhoea (G3/4: 4%); Nausea (G3/4: 4%); Vomiting (G3/4: 3%)	Constipation (severe: 0.2%); Abdominal pain (severe: 1%); Gastrointestinal haemorrhage (severe: 0.3%)	Oesophagitis (severe: 0.4%)
Skin and subcutaneous tissue disorders	Alopecia; Skin reaction (G3/4: 5.9%); Nail disorders (severe: 2.6%)
Musculoskeletal and connective tissue disorders	Myalgia (severe: 1.4%)	Arthralgia
General disorders and administration site conditions	Fluid retention (severe: 6.5%); Asthenia (severe: 11.2%); Pain	Infusion site reaction; Non-cardiac chest pain (severe: 0.4%)
Investigations		G3/4 Blood bilirubin increased (< 5%); G3/4 Blood alkaline phosphatase increased (< 4%); G3/4 AST increased (< 3%); G3/4 ALT increased (< 2%)

Blood and lymphatic system disorders

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.

Nervous system disorders

Reversibility data are available among 35.3% of patients who developed neurotoxicity following docetaxel treatment at 100 mg/m² as single agent. The events were spontaneously reversible within 3 months.

Skin and subcutaneous tissue disorders

Very rare: one case of alopecia non-reversible at the end of the study. 73% of the cutaneous reactions were reversible within 21 days.

General disorders and administration site conditions

The median cumulative dose to treatment discontinuation was more than 1,000 mg/m² and the median time to fluid retention reversibility was 16.4 weeks (range 0 to 42 weeks). The onset of moderate and severe retention is delayed (median cumulative dose: 818.9 mg/m²) in patients with premedication compared with patients without premedication (median cumulative dose: 489.7 mg/m²); however, it has been reported in some patients during the early courses of therapy.

TAXOTERE 75 mg/m² single agent

MedDRA system organ classes	Very common adverse reactions	Common adverse reactions
Infections and infestations	Infections (G3/4: 5%)
Blood and lymphatic system disorders	Neutropenia (G4: 54.2%); Anaemia (G3/4: 10.8%); Thrombocytopenia (G4: 1.7%)	Febrile neutropenia
Immune system disorders		Hypersensitivity (no severe)
Metabolism and nutrition disorders	Anorexia
Nervous system disorders	Peripheral sensory neuropathy (G3/4: 0.8%)	Peripheral motor neuropathy (G3/4: 2.5%)
Cardiac disorders		Arrhythmia (no severe)
Vascular disorders		Hypotension
Gastrointestinal disorders	Nausea (G3/4: 3.3%); Stomatitis (G3/4: 1.7%); Vomiting (G3/4: 0.8%); Diarrhoea (G3/4: 1.7%)	Constipation
Skin and subcutaneous tissue disorders	Alopecia; Skin reaction (G3/4: 0.8%)	Nail disorders (severe: 0.8%)

Wednesday, 11 April 2012

Ablavar

Generic Name: gadofosveset trisodium (GAD oh FOS ve set trye SOE dee um)

Brand Names: Ablavar

What is Ablavar (gadofosveset trisodium)?

Gadofosveset trisodium is a contrast agent that produces magnetic effects. It is used in combination with magnetic resonance angiography (MRA) to allow blood vessels, organs, and other non-bony tissues to be seen more clearly on the MRA.

Gadofosveset trisodium is used to help diagnose certain disorders of the heart and blood vessels.

Gadofosveset trisodium may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Ablavar (gadofosveset trisodium)?

Gadofosveset trisodium can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

burning, itching, swelling, scaling, and tightening or hardening of your skin;

muscle weakness;

joint stiffness in your arms, hands, legs, or feet;

deep bone pain in your ribs or your hips;

trouble moving; or

skin redness or discoloration.

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadofosveset trisodium.

Also tell your doctor if you have diabetes, high blood pressure, liver disease (or liver transplant), a heart rhythm disorder, a personal or family history of "Long QT Syndrome," asthma or allergies, if you are over 60 years old, if you have ever had a reaction to a contrast agent, or if you have recently had an injury, surgery, or severe infection.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

What should I discuss with my health care provider before receiving Ablavar (gadofosveset trisodium)?

Gadofosveset trisodium can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

burning, itching, swelling, scaling, and tightening or hardening of your skin;

muscle weakness;

joint stiffness in your arms, hands, legs, or feet;

deep bone pain in your ribs or your hips;

trouble moving; or

skin redness or discoloration.

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadofosveset trisodium.

To make sure you can safely receive this medication, tell your doctor if you have any of these other conditions:

diabetes;

high blood pressure;

liver disease (or liver transplant);

a heart rhythm disorder;

a personal or family history of "Long QT Syndrome";

asthma, hay fever, or a history of food or drug allergies;

if you have ever had any type of reaction to a contrast agent; or

if you have recently had an injury, surgery, or severe infection.

FDA pregnancy category C. It is not known whether gadofosveset trisodium will harm an unborn baby. Before you receive this medication, tell your doctor if you are pregnant. It is not known whether gadofosveset trisodium passes into breast milk or if it could harm a nursing baby. Do not receive this medication without telling your doctor if you are breast-feeding a baby.

How is gadofosveset trisodium given?

Gadofosveset trisodium is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting during your MRA.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

What happens if I miss a dose?

Since gadofosveset trisodium is used only during your MRA, you will not be on a dosing schedule.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid after receiving Ablavar (gadofosveset trisodium)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Ablavar (gadofosveset trisodium) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

urinating less than usual or not at all;

drowsiness, confusion, mood changes, increased thirst, loss of appetite;

swelling, weight gain, feeling short of breath; or

fast, uneven heart rate.

Less serious side effects may include:

mild itching;

headache, dizziness;

nausea, unusual or unpleasant taste in your mouth;

warmth, redness, burning, or tingly feeling under your skin;

cold feeling, warmth, pain, bruising, or burning where the injection was given; or

numbness or tingling in your hands or feet.

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 Ablavar (gadofosveset trisodium)?

This medication can harm the kidneys in certain people, and this effect may be increased if you also use other medicines harmful to the kidneys. Before you receive gadofosveset trisodium, tell your doctor about all other medications you use. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.

There may be other drugs that can affect gadofosveset trisodium. 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 Ablavar resources

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

Ablavar Advanced Consumer (Micromedex) - Includes Dosage Information

Gadofosveset Trisodium Professional Patient Advice (Wolters Kluwer)

Vasovist Prescribing Information (FDA)

Vasovist Consumer Overview

Compare Ablavar with other medications

Magnetic Resonance Angiography

Where can I get more information?

Your doctor or pharmacist can provide more information about gadofosveset trisodium.

See also: Ablavar side effects (in more detail)

Aggrastat

Generic Name: Tirofiban
Class: Platelet-Aggregation Inhibitors
ATC Class: B01AC17
Chemical Name: N-(butylsulfonyl)-4-[4-(4-piperidyl)butoxy]-l-phenylalanine monohydrochloride monohydrate
Molecular Formula: C₂₂H₃₆N₂O₅S
CAS Number: 144494-65-5

Introduction

Platelet-aggregation inhibitor;¹ ¹⁵ ²² a platelet glycoprotein (GP IIb/IIIa)-receptor inhibitor.^b

Uses for Aggrastat

Unstable Angina and Non-ST-Segment Elevation MI

Adjunct to anticoagulant therapy (e.g., unfractionated heparin, low molecular weight heparin), aspirin, and/or clopidogrel to reduce risk of acute cardiac ischemic events (death and/or MI) in patients with non-ST-segment elevation acute coronary syndrome (i.e., unstable angina or non-ST-segment elevation MI), including those who are to receive medical management or to undergo PCI.¹ ⁵ ⁶ ²¹ ⁹¹ ¹⁰⁰ ¹⁰³ ¹⁰⁴ ¹⁰⁷ ¹¹⁶

Adjunctive therapy with a GP IIb/IIIa-receptor inhibitor can reduce the incidence of cardiac ischemic events, including subsequent MI and death, in patients with non-ST-segment-elevation acute coronary syndromes.⁵ ⁶ ¹¹ ³⁵ ³⁶ ⁴² ⁴⁶ ⁵¹ ⁷¹ ⁷² ⁷³ ⁸⁰ ⁸³ ⁸⁴ ⁸⁵ ⁹¹ ¹⁰³ ¹¹¹

The American College of Chest Physicians (ACCP) recommends initial (at presentation or diagnosis, “upstream”) treatment with certain GP IIb/IIIa-receptor inhibitors (i.e., tirofiban or eptifibatide) or clopidogrel in conjunction with an anticoagulant and aspirin in patients with non-ST-segment-elevation acute coronary syndromes who have at least a moderate risk for adverse cardiac ischemic events and who will undergo an early invasive procedure.¹¹¹ Alternatively, ACCP suggests use of eptifibatide or tirofiban in addition to clopidogrel and in conjunction with anticoagulation and aspirin therapy as initial treatment for patients at moderate or greater risk who will undergo an early or delayed invasive procedure.¹⁰⁷ ¹¹¹

ACCP recommends bivalirudin with provisional use of a GP IIb/IIIa-receptor inhibitor or unfractionated heparin and a GP IIb/IIIa-receptor inhibitor in patients who are at a low to moderate risk for an ischemic event who are undergoing PCI.¹¹¹ In patients undergoing elective PCI with stent placement, ACC and AHA consider the use of GP IIb/IIIa-receptor inhibitors (abciximab, eptifibatide, tirofiban) to be reasonable.¹⁰³

ACCP, ACC, and AHA currently recommend therapy with a GP IIb/IIIa-receptor inhibitor in all patients undergoing PCI, particularly in patients who have refractory non-ST-segment-elevation acute coronary syndromes or other high-risk features.¹⁰³ ¹⁰⁴ ¹⁰⁹ ¹¹¹ ACC/AHA/SCAI recommend a GP IIb/IIIa-receptor inhibitor (abciximab, eptifibatide, tirofiban) without clopidogrel prior to diagnostic angiogram or just before PCI;¹⁰³ ¹⁰⁹ however, ACCP recommends a GPIIb/IIIa-receptor inhibitor with clopidogrel in such patients.¹¹¹

ACCP does not recommend use of tirofiban as an alternative to abciximab in patients undergoing PCI in whom a GP IIb/IIIa-receptor inhibitor has not been initiated previously (“upstream”).¹⁰⁶ ¹¹¹

Tirofiban and eptifibatide not recommended by AHA in women with non-ST-segment elevation acute coronary syndromes who are at lower risk for adverse events and are managed with conservative strategy, because of little demonstrated benefit and possible detrimental effects.¹⁰⁹

Aggrastat Dosage and Administration

General

Administer as soon as possible following diagnosis.²¹ ⁹¹

Discontinue at least 4–6 hours prior to CABG.²¹ ⁹¹

Adjunctive Antithrombotic Therapy

In clinical trials, almost all patients receiving tirofiban also received concomitant aspirin and/or unfractionated heparin.¹ ⁵ ⁶ ¹¹ ¹⁴ Tirofiban and heparin may be administered through the same IV line.¹

Used in conjunction with aspirin and unfractionated heparin in clinical studies.¹ ⁵ ⁶ ¹¹ ¹⁴

Aspirin: In clinical studies, patients received 300–325 mg daily for at least 48 hours after randomization or within 12 hours prior to PCI, unless the drug was contraindicated; some patients received aspirin indefinitely.¹ ⁵ ⁶ ¹¹ ¹⁴ ACCP recommends initial and maintenance aspirin dosages of 162–325 mg and 75–100 mg daily, respectively.¹¹¹ ¹¹⁴ ACC/AHA/SCAI recommend 300–325 mg ≥2 hours, preferably 24 hours, prior to PCI in patients not already receiving maintenance therapy with aspirin.¹⁰³ ¹¹² In patients already receiving maintenance therapy with aspirin, give 75–325 mg before the procedure.¹⁰³ ¹¹²

Clopidogrel in patients managed with conservative medical therapy or early or delayed invasive procedures: Initially, a loading dose of 300 mg is recommended;¹¹¹ initiate as soon as possible during hospitalization and continue at a maintenance dosage of 75 mg once daily.¹⁰⁴ ¹¹⁴ Some clinicians recommend continuing therapy with clopidogrel and aspirin for ≥1 month but ideally up to 1 year in patients receiving medical management only.¹⁰⁴ ¹¹⁴ ¹¹⁶ ACCP recommends a maintenance clopidogrel dosage of 75 mg once daily for 12 months in conjunction with aspirin, and then continuance of aspirin indefinitely for patients managed with a conservative medical approach.¹¹⁴

Heparin during medical management: In clinical studies, patients received an IV loading dose of 5000 units followed by continuous IV infusion of 1000 units/hour.¹ ⁵ ⁶ (See Laboratory Monitoring under Cautions.)

Heparin prior to PCI: In clinical studies, patients undergoing PCI after at least 48 hours of medical management received an IV loading dose of 5000–7500 units followed by continuous IV infusion of 1000 units/hour titrated to an aPTT approximately 2 times the control value with additional IV injections of heparin as needed. (See Laboratory Monitoring under Cautions.)¹ ⁶

Heparin prior to urgent PCI: In a clinical study, patients at high risk for abrupt closure of the affected coronary artery who underwent urgent or emergency PCI received an IV loading dose of 10,000 units (body weight ≥70 kg) or 150 units/kg (body weight <70 kg).¹ ¹¹ ³⁷ ⁴⁴ In clinical studies, additional injections during PCI were administered to maintain target activated clotting time (ACT) between 300–400 seconds.¹ ¹¹ ³⁷ ⁴⁴ ACCP, ACC, AHA, and SCAI⁵³ ¹⁰³ suggest use of lower dosages of concomitant IV heparin (50–70 units/kg) prior to PCI and targeted to an ACT of ≥200 seconds.¹ ¹⁸ ³⁵ ⁴⁴ ⁵³ ⁷¹ ⁷⁴ ⁷⁷ ⁸⁰ ⁸¹ ⁹⁵ ⁹⁶ ¹⁰² ¹⁰⁶ ¹¹⁰ ¹¹¹ Additional injections of heparin sodium may be given during PCI to maintain an ACT of 200–300 seconds.¹⁰³ ¹¹² (See Laboratory Monitoring under Cautions.)

Postprocedural use of heparin not recommended.⁶ ¹¹ ⁴² ⁵² ⁵³ ¹⁰² ¹⁰³ ¹⁰⁶

Fondaparinux: In patients managed initially with fondaparinux, a GP IIb/IIIa-receptor inhibitor, and a delayed invasive strategy, ACCP recommends additional IV injections of fondaparinux sodium† (2.5 mg) and heparin sodium (e.g., 50–60 units/kg) be given at the time of the procedure.¹¹¹ ¹¹²

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using either diluted injection concentrate or premixed injection in plastic (IntraVia™) containers.¹ ¹

Discard unused portion.¹

The plastic container of the premixed injection may be somewhat opaque because of moisture absorption during sterilization; this opacity will diminish gradually.¹

Do not introduce additives into the injection container.¹

Do not use the plastic IV container in series connections with other plastic containers; such use may result in air embolism.¹

Dilution

Tirofiban hydrochloride injection concentrate for IV infusion must be diluted to 50 mcg/mL (the same concentration as the premixed injection) before administration.¹

Prepare injection concentrate for infusion by withdrawing and discarding 50 or 100 mL of solution from a 250- or 500-mL bag, respectively, of 0.9% sodium chloride or 5% dextrose injection and replacing this volume with an equivalent volume (i.e., 50 or 100 mL, respectively) of tirofiban hydrochloride injection to achieve a final concentration of 50 mcg/mL.¹ ²¹

Alternatively, a vial labeled as containing 5 mg of tirofiban may be added to a 100 mL bag of 0.9% sodium chloride injection or 5% dextrose injection.¹

Mix solutions well prior to infusion.¹

Rate of Administration

Administer as a continuous infusion.¹ ²⁰ ²¹ ⁹¹

Dosage

Available as tirofiban hydrochloride; dosage expressed in terms of tirofiban.¹

Adults

Unstable Angina and Non-ST-Segment Elevation MI

IV

Patients receiving medical therapy: IV loading dose of 0.4 mcg/kg per minute for 30 minutes given as soon as possible after diagnosis, followed by continuous IV infusion of 0.1 mcg/kg per minute for at least 24–48 hours.²¹ ⁹¹

Patients who undergo PCI: IV loading dose of 0.4 mcg/kg per minute for 30 minutes followed by continuous IV infusion of 0.1 mcg/kg per minute given during angiography and for 12–24 hours after angioplasty or atherectomy.¹ ²⁰ ²¹ ⁹¹

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹ ²⁰

Renal Impairment

In patients with severe renal impairment (i.e., Cl_cr≤ 30 mL/minute), decrease the usual loading and maintenance rate of infusion by 50%.¹

Geriatric Patients

Dosage adjustment not required.¹

Cautions for Aggrastat

Contraindications

Active internal bleeding or history of bleeding diathesis ¹ ⁵ ⁶ ¹⁴ ²⁰ ²¹ ⁹¹ within previous 30 days.¹ ²⁰ ²¹ ⁹¹

History of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm.¹ ⁵²

History of thrombocytopenia following prior exposure to tirofiban.¹ ⁵ ⁶ ¹¹ ²⁰ ⁵²

History of stroke within 30 days or any history of hemorrhagic stroke.¹ ⁵ ⁶ ¹¹ ¹⁴ ²⁰ ⁵²

Recent (within 30 days) major surgery or severe physical trauma.¹ ⁵ ²⁰ ⁵²

History, symptoms, or findings suggestive of aortic dissection.¹ ²⁰

Severe uncontrolled hypertension (SBP >180 or DBP >110 mm Hg).¹ ⁵ ²⁰

Concomitant therapy with another parenteral GP IIb/IIIa-receptor inhibitor.¹ ²⁰

Acute pericarditis.¹ ²⁰

Known hypersensitivity to tirofiban or any ingredient in the formulation.¹ ²⁰

Warnings/Precautions

Warnings

Hematologic Effects

Risk of major bleeding (e.g., intracranial hemorrhage, GU or GI bleeding, bleeding at arterial access site) and minor bleeding (e.g., spontaneous gross hematuria, spontaneous hematemesis); may require blood or platelet transfusions.¹ ⁵ ⁶ ¹¹ ²⁰ ²¹ ⁹¹ (See Bleeding Precautions and also see Laboratory Monitoring under Cautions.)

Pulmonary alveolar hemorrhage, spinal-epidural hematoma, retroperitoneal bleeding, and hemopericardium reported rarely.¹

Fatal hemorrhage reported rarely.¹

Use with caution in patients with platelet count <150,000/mm³, anemia (hemoglobin <10–12 g/dL), hemorrhagic retinopathy, and those requiring chronic hemodialysis.¹ ²⁰ ⁹¹

Use with caution in patients receiving other drugs that affect hemostasis (e.g., thrombolytic agents, oral anticoagulants, NSAIAs, dipyridamole, ticlopidine, and clopidogrel).¹ ²⁰ ²¹ ⁹¹ (See Specific Drugs under Interactions.)

If bleeding cannot be controlled by pressure, discontinue tirofiban and concomitant heparin.¹ ²⁰

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and other severe allergic reactions reported on the first day of infusion, during initial treatment, and during readministration of the drug.¹ ²¹

Severe allergic reactions sometimes associated with severe thrombocytopenia (platelet counts <10,000/mm³).¹

General Precautions

Bleeding Precautions

To reduce risk of bleeding, adhere to strict anticoagulation guidelines; use a short course of low-dose, weight-adjusted heparin; avoid vascular and other trauma; carefully manage vascular (e.g., femoral artery) access site; and monitor all potential bleeding sites during and following treatment.¹ ⁵ ⁶ ¹¹ ²¹ ⁹¹

In patients undergoing PCI, use caution in the placement, maintenance, and removal of vascular access sheath; avoid femoral vein sheath placement.¹ ¹⁸ ³⁵ ³⁷ ⁴² ⁴⁶ ⁵² When inserting sheath, puncture only anterior wall of femoral artery; avoid Seldinger (through and through) technique.¹ ¹⁸ ²⁰ ⁵² ⁷⁷ ⁸¹ Observe appropriate precautions while sheath is in place (e.g., complete bed rest, elevation of head ≤30°, restrain limb in which sheath is inserted, frequent monitoring of vascular access site and distal pulse in the involved limb).¹ ¹⁸ ¹⁹ ²⁰ ⁵² Following PCI, consider early sheath removal (during tirofiban IV infusion).¹ Prior to removal of sheath, discontinue heparin for 3–4 hours and allow aPTT to return to <45 seconds or ACT to <180 seconds.¹ ¹¹ ¹⁴ ²⁰ ³⁰ ⁴¹ ⁵² ⁵³ ⁷⁰ Discontinue tirofiban and heparin and achieve hemostasis (by applying pressure to femoral artery for at least 20–30 minutes after sheath removal¹⁸ ¹⁹ ) at least 4 hours before hospital discharge.¹ ²⁰ Measure and monitor hematomas for enlargement.¹⁸

To avoid vascular and other trauma, minimize needle punctures (e.g., arterial, IM, IV, lumbar, sub-Q, intradermal), cutdown sites, and use of nasotracheal intubation, nasogastric tubes, urinary catheters,¹ ¹⁸ ²⁰ and automatic BP cuffs¹⁸ during and following treatment;¹ ¹⁸ avoid establishment of IV access at noncompressible sites (e.g., subclavian or jugular veins);¹ ¹⁸ consider using an indwelling venipuncture device (e.g., heparin lock) for drawing blood; document and monitor vascular puncture sites; and remove dressings gently and carefully.¹⁸

Thrombocytopenia

Thrombocytopenia reported.¹ ⁵ ³² ³⁷ ⁴³ ⁴⁴ ⁴⁵ ⁵⁰ ⁵² Severe thrombocytopenia (platelet count <20,000/mm³) reported less frequently than with abciximab.¹⁸ ³⁰ ³² ³⁵ ³⁷ ⁴⁴ ⁵⁰ ⁵³

Determine platelet counts prior to treatment and periodically (e.g., within the first 6 hours of the loading infusion, and daily thereafter) during concomitant tirofiban and heparin therapy.¹ ¹¹ ²⁰ ⁴³ ⁴⁴ Consider possibility of pseudothrombocytopenia or heparin-induced thrombocytopenia in patients receiving concomitant heparin therapy.¹ ²⁰ ³⁵ ³⁷ ⁵² (See Thrombocytopenia under Cautions.)

If true thrombocytopenia is verified, discontinue tirofiban and initiate appropriate treatment and monitoring.¹ Thrombocytopenia usually reversible following discontinuance of GP IIb/IIIa-receptor inhibitors and anticoagulant (heparin) therapy; consider platelet transfusions for the management of severe thrombocytopenia.³⁵ ³⁷ ⁴³ ⁵²

Use with caution in patients with platelet count <150,000/mm³;¹ ²⁰ contraindicated in patients with a history of thrombocytopenia following prior exposure to tirofiban.¹ ⁵ ⁶ ¹¹ ²⁰ ⁵²

Laboratory Monitoring

Prior to administration, within the first 6 hours of the loading infusion and at least daily thereafter, obtain hematocrit and hemoglobin,¹ ¹¹ ²⁰ ³⁵ ⁴³ ⁴⁴ and platelet counts.¹ ¹¹ ²⁰ ³⁵ ⁴³ ⁴⁴

Closely monitor ACT or aPTT.¹ ³⁰ ⁵² ⁷⁰ Monitor aPTT 6 hours after the start of the heparin infusion and maintain at 50–70 seconds or approximately 2 times the control value unless PCI is to be performed.¹ ⁶ ³⁰ In patients undergoing PCI, measure the ACT.²¹ ⁵² ⁷⁰ ¹⁰³ In patients undergoing PCI in clinical studies, ACT was maintained between 300–400 seconds during PCI;¹ ¹¹ ³⁷ ⁴⁴ ACCP suggests targeting ACT between 200–250 seconds to reduce risk of major bleeding.¹ ¹⁸ ³⁵ ⁴⁴ ⁵³ ⁷¹ ⁷⁴ ⁷⁷ ⁸⁰ ⁸¹ ⁹⁵ ⁹⁶ ¹⁰² Monitor aPTT or ACT prior to arterial sheath removal; do not remove sheath unless aPTT <45 seconds or ACT <180 seconds.¹ ³⁰ ⁴¹ ⁵³ ⁷⁰ ¹⁰²

Determine platelet counts prior to administration, within the first 6 hours of the loading infusion and at least daily thereafter.¹ ¹¹ ²⁰ ⁴³ ⁴⁴ Perform additional platelet counts if a patient experiences a reduction in platelet count to <90,000/mm³ to exclude the possibility of pseudothrombocytopenia.¹ ¹⁸ ⁹⁰

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk in rats;¹ not known whether distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.¹ ²⁰

Geriatric Use

No substantial differences in efficacy relative to younger adults.¹ However, increased incidence of bleeding complications and non-bleeding adverse events in some studies.¹ ²⁰

Women

Increased incidence of minor bleeding complications and non-bleeding adverse events in some studies.¹ ¹⁰³ ¹⁰⁹

Hepatic Impairment

Clearance not affected in patients with mild to moderate hepatic impairment;¹ ²⁰ information on plasma clearance limited in patients with severe hepatic impairment since these patients were excluded from participation in clinical studies.²¹

Renal Impairment

Substantially decreased clearance (>50%) in patients with severe renal impairment (i.e., Cl_cr ≤30 mL/minute), including patients requiring hemodialysis;¹ reduced dosage recommended in such patients.¹ ²⁰ (See Renal Impairment under Dosage and Administration.)

Use with caution in patients requiring chronic hemodialysis.¹ ²⁰ ⁹¹

Common Adverse Effects

Bleeding,¹ pelvic pain,¹ coronary artery dissection,¹ bradycardia,¹ leg pain,¹ dizziness,¹ edema/swelling, ¹ vasovagal reaction,¹ sweating.¹

Interactions for Aggrastat

Specific Drugs

Drug	Interaction	Comments
Anticoagulants, oral	Potential increased risk of bleeding¹	Use with caution¹ ²⁰ ²¹ ⁹¹
Clopidogrel	Potential increased risk of bleeding¹ ⁴ ²²	Use with caution¹ ²⁰ ²¹ ⁹¹
Dextran	Increased risk of bleeding¹	Some clinicians recommend against concomitant use⁹¹
Dipyridamole	Potential increased risk of bleeding¹	Use with caution¹ ²⁰ ²¹ ⁹¹
GP IIb/IIIa-receptor inhibitors (abciximab, eptifibatide)	Possible additive pharmacologic effects¹ ⁴	Concomitant use contraindicated¹
Heparin	Increased risk of bleeding; ¹ ⁵ ⁶ ¹¹ ¹⁴ possible additive effects on ACT⁵⁶ ¹⁰⁰	Monitor aPTT or ACT during therapy;¹ ⁵ ⁶ ¹¹ ³⁷ ⁴⁴ consider dosage adjustment of heparin⁵⁶ ¹⁰⁰
Levothyroxine	Possible increased tirofiban clearance ¹	Clinical importance not known¹
NSAIAs	Potential increased risk of bleeding¹	Use with caution¹ ²⁰ ²¹ ⁹¹
Omeprazole	Possible increased tirofiban clearance ¹	Clinical importance not known¹
Thrombolytics	Increased risk of bleeding¹	Use concomitantly with caution; no concomitant use studies to date²⁰ ²¹ ⁹¹
Ticlopidine	Potential increased risk of bleeding¹ ⁴ ²²	Use with caution¹ ²⁰ ²¹ ⁹¹

Aggrastat Pharmacokinetics

Absorption

Onset

Rapid onset;¹¹ ¹⁴ ²⁰ 90% inhibition of platelet aggregation occurs by the end of the IV loading infusion administration.¹ ²⁰ ²¹

Duration

Short duration of action;¹¹ ¹⁴ ²⁰ platelet aggregation persists during maintenance infusion.¹ ²⁰ ²¹ Platelet function generally recovers within 4–8 hours following discontinuance of infusion.¹ ²⁰

Distribution

Extent

Distributed into milk in rats and crosses the placenta in pregnant rats and rabbits.¹ ²⁰ Not known whether tirofiban crosses the placenta or is distributed into milk in humans.¹ ²⁰

Plasma Protein Binding

Approximately 65%.¹ ⁴ ²⁰

Elimination

Metabolism

Metabolism appears limited.¹ ²⁰

Elimination Route

Excreted in urine (65%) and in feces (25%) mainly as unchanged drug.¹ ²⁰

Half-life

Approximately 1.2–2 hours.¹ ³ ⁴ ¹⁵ ²⁰ ²² ⁹¹

Special Populations

Plasma clearance may decrease substantially (>50%) in patients with severe renal impairment (i.e., Cl_cr ≤30 mL/minute and those requiring hemodialysis) ¹ (See Renal Impairment under Dosage and Administration.)

Removed by hemodialysis.¹ ²⁰

Plasma clearance decreased approximately 19–26% in geriatric patients.²⁰

Stability

Storage

Parenteral

For Injection, Concentrate, for IV Infusion

25°C (may be exposed to 15–30°C).¹ ²⁰ Do not freeze; protect from light.¹ ²⁰

Contains no preservative; discard unused solution.¹

Injection, for IV Infusion

25°C (may be exposed to 15–30°C).¹ Do not freeze; protect from light.¹

Contains no preservative; discard unused solution.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextrose 5% in sodium chloride 0.45%
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility

Y-Site Compatibility1HID
Compatible
Amiodarone HCl
Atropine sulfate
Bivalirudin
Dobutamine HCl
Dopamine HCl
Epinephrine HCl
Famotidine HCl
Furosemide
Heparin sodium
Lidocaine HCl
Midazolam HCl
Morphine sulfate
Nitroglycerin
Potassium chloride
Propranolol HCl
Incompatible¹ ^HID
Diazepam

ActionsActions

Binds selectively to platelet GP IIb/IIIa receptors and reversibly inhibits platelet aggregation (by preventing binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa receptors).¹ ¹¹ ¹⁶ ¹⁷ ²² ²⁴ ⁴³ ⁴⁵

Modest effect on hemostatic indices (e.g., bleeding times);¹ ² normal hemostasis restored more rapidly than with abciximab.⁸ ³¹ ³² ³⁵ ⁷⁴ ⁹¹

Usually does not affect aPTT when administered as monotherapy.⁵ ⁶

Advice to Patients

Risk of serious bleeding or hemorrhage.¹

Importance of close laboratory monitoring.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).¹

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Tirofiban Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, concentrate, for IV infusion	250 mcg (of tirofiban) per mL (5 and 12.5 mg)	Aggrastat	Medicure

Tirofiban Hydrochloride in Sodium Chloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV infusion	50 mcg (of tirofiban) per mL (5 and 12.5 mg) in 0.9% Sodium Chloride	Aggrastat Premixed in Iso-osmotic Sodium Chloride Injection (in IntraVia flexible container)	Medicure

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Medicure Pharma. Aggrastat (tirofiban hydrochloride) injection premixed and injection prescribing information. Somerset, NJ; 2007 Nov.

2. Anon. Tirofiban hydrochloride. Drugs Future. 1995; 20:897-901.

3. Umemura K, Kondo K, Ikeda Y et al. Enhancement by ticlopidine of the inhibitory effect on in vitro platelet aggregation of the glycoprotein IIb/IIIa inhibitor tirofiban. Thromb Haemost. 1997; 78: 1381-4.

4. Barrett JS, Murphy G, Peerlinck K et al. Pharmacokinetics andpharmacodynamics of MK-383, a selective non-peptide platelet glycoprotein-IIb/IIIa receptor antagonist, in healthy men. Clin Pharmacol Ther. 1994; 56:377-88. [IDIS 338167] [PubMed 7955799]

5. The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med. 1998; 338:1498-1505. [IDIS 409093] [PubMed 9599104]

6. The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med. 1998; 338:1488-97. [IDIS 405092] [PubMed 9599103]

7. Agency for Health Care Policy and Research. Diagnosing and managing unstable angina. 1994. (AHCPR publication no. 94-0603)

8. Chesebro JH, Badimon JJ. Platelet glycoprotein IIb/IIIa receptor blockade in unstable coronary disease. N Engl J Med. 1998; 338:1539-41. [IDIS 405098] [PubMed 9593795]

9. Théroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation. 1997; 97:1195-206.

10. Braunwald E, Maseri A, Armstrong PW et al. Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes. Eur Heart J. 1998; 19(Suppl. D):D22-30. [PubMed 9597519]

11. The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation. 1997; 96:1445-53. [IDIS 393118] [PubMed 9315530]

12. Tcheng JE. Platelet glycoprotein IIb/IIIa integrin blockade: recent clinical trials in interventional cardiology. Thromb Haemost. 1997; 78:205-9. [IDIS 392079] [PubMed 9198154]

13. Hahn SS, Chae C, Giugliano R et al. Troponin I levels in unstable angina/non-Q wave myocardial infarction patients treated with tirofiban, a glycoprotein IIb/IIIa antagonist. J Am Coll Cardiol. 1998; 31(Suppl. A):229A.

14. Kereiakes DJ, Kleiman NS, Ambrose J et al. Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol. 1996; 27:536-42. [IDIS 364310] [PubMed 8606262]

15. Peerlinck, De Lepeleire I, Goldberg M et al. MK-383 (L-700,462), a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist, is active in man. Circulation. 1993; 88:1512-7. [IDIS 321320] [PubMed 8403299]

16. Hartman GD, Egbertson MS, Halczenko W et al. Non-peptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors. J Med Chem. 1992; 35:4640-2. [PubMed 1469694]

17. Egbertson MS, Chang CTC, Duggan ME et al. Non-peptide fibrinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for arg-gly-asp. J Med Chem. 1994; 37:2537-51. [PubMed 8057299]

18. Eli Lilly and Company. ReoPro (abciximab) injection for intravenous use prescribing information. In

Tannate-12D S Suspension

Pronunciation: car-beta-PEN-tane/fen-ill-EF-rin/peer-IL-a-meen
Generic Name: Carbetapentane/Phenylephrine/Pyrilamine
Brand Name: Examples include Tannate-12D S and Tussi 12D S

Tannate-12D S Suspension is used for:

Relieving symptoms of sinus congestion, runny nose, sneezing, and cough due to colds, upper respiratory infections, and allergies. It may also be used for other conditions as determined by your doctor.

Tannate-12D S Suspension is a decongestant, antihistamine, and cough suppressant combination. It works by constricting blood vessels and reducing swelling in the nasal passages. The antihistamine works by blocking the action of histamine, which helps reduce symptoms, such as watery eyes and sneezing, while the cough suppressant works in the brain to help decrease the cough reflex to reduce a dry cough.

Do NOT use Tannate-12D S Suspension if:

you are allergic to any ingredient in Tannate-12D S Suspension

you have severe high blood pressure, severe heart blood vessel disease, rapid heartbeat, or severe heart problems

you are unable to urinate or are having an asthma attack

you take sodium oxybate (GHB) or you have taken furazolidone or a monoamine oxidase (MAO) inhibitor (eg, phenelzine) within the last 14 days

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

Before using Tannate-12D S Suspension:

Some medical conditions may interact with Tannate-12D S Suspension. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, plan to become pregnant, or are breast-feeding

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

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

if you have a fast, slow, or irregular heartbeat

if you have a history of adrenal gland problems (eg, adrenal gland tumor); heart problems; high blood pressure; diabetes; heart blood vessel problems; stroke; glaucoma; a blockage of your bladder, stomach, or intestines; ulcers; trouble urinating; an enlarged prostate or other prostate problems; seizures; or an overactive thyroid

if you have a history of asthma, chronic cough, lung problems (eg, chronic bronchitis, emphysema), or chronic obstructive pulmonary disease (COPD), or if your cough occurs with large amounts of mucus

Some MEDICINES MAY INTERACT with Tannate-12D S Suspension. Tell your health care provider if you are taking any other medicines, especially any of the following:

Beta-blockers (eg, propranolol), COMT inhibitors (eg, tolcapone), furazolidone, indomethacin, MAO inhibitors (eg, phenelzine), sodium oxybate (GHB), or tricyclic antidepressants (eg, amitriptyline) because side effects of Tannate-12D S Suspension may be increased

Digoxin or droxidopa because risk of irregular heartbeat or heart attack may be increased

Bromocriptine or hydantoins (eg, phenytoin) because side effects ma y be increased by Tannate-12D S Suspension

Guanadrel, guanethidine, mecamylamine, methyldopa, or reserpine because effectiveness may be decreased by Tannate-12D S Suspension

This may not be a complete list of all interactions that may occur. Ask your health care provider if Tannate-12D S Suspension may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Tannate-12D S Suspension:

Use Tannate-12D S Suspension as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Tannate-12D S Suspension may be taken with or without food.

Shake well before using.

Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.

If you miss a dose of Tannate-12D S Suspension, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Tannate-12D S Suspension.

Important safety information:

Tannate-12D S Suspension may cause dizziness, drowsiness, or blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Tannate-12D S Suspension. Using Tannate-12D S Suspension alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.

Do not take diet or appetite control medicines while you are taking Tannate-12D S Suspension without checking with your doctor.

Tannate-12D S Suspension contains phenylephrine. Before you begin taking any new prescription or nonprescription medicine, read the ingredients to see if it also contains phenylephrine. If it does or if you are uncertain, contact your doctor or pharmacist.

Do NOT exceed the recommended dose or take Tannate-12D S Suspension for longer than prescribed without checking with your doctor.

If your symptoms do not improve within 5 to 7 days or if they become worse, check with your doctor.

Tannate-12D S Suspension may cause increased sensitivity to the sun. Avoid exposure to the sun, sunlamps, or tanning booths until you know how you react to Tannate-12D S Suspension. Use a sunscreen or protective clothing if you must be outside for a prolonged period.

If you are scheduled for allergy skin testing, do not take Tannate-12D S Suspension for several days before the test because it may decrease your response to the skin tests.

Before you have any medical or dental treatments, emergency care, or surgery, tell the doctor or dentist that you are using Tannate-12D S Suspension.

Use Tannate-12D S Suspension with caution in the ELDERLY because they may be more sensitive to its effects.

Caution is advised when using Tannate-12D S Suspension in CHILDREN because they may be more sensitive to its effects.

PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Tannate-12D S Suspension, discuss with your doctor the benefits and risks of using Tannate-12D S Suspension during pregnancy. It is unknown if Tannate-12D S Suspension is excreted in breast milk. Do not breast-feed while taking Tannate-12D S Suspension.

Possible side effects of Tannate-12D S Suspension:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; excitability; headache; loss of appetite; nausea; nervousness or anxiety; trouble sleeping; upset stomach; vomiting; weakness.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); difficulty urinating or inability to urinate; fast or irregular heartbeat; hallucinations; seizures; severe dizziness, lightheadedness, or headache; tremor; trouble sleeping; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Tannate-12D S side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include blurred vision; confusion; hallucinations; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; unusually fast, slow, or irregular heartbeat; vomiting.

Proper storage of Tannate-12D S Suspension:

Store Tannate-12D S Suspension at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Tannate-12D S Suspension out of the reach of children and away from pets.

General information:

If you have any questions about Tannate-12D S Suspension, please talk with your doctor, pharmacist, or other health care provider.

Tannate-12D S Suspension is to be used only by the patient for whom it is prescribed. Do not share it with other people.

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

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

This information is a summary only. It does not contain all information about Tannate-12D S Suspension. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Tannate-12D S resources

Tannate-12D S Side Effects (in more detail)
Tannate-12D S Use in Pregnancy & Breastfeeding
Tannate-12D S Drug Interactions
0 Reviews for Tannate-12D S - Add your own review/rating

Compare Tannate-12D S with other medications

Cough and Nasal Congestion

Sunday, 8 April 2012

Northyx

Generic Name: methimazole (me THIM a zole)

Brand Names: Northyx, Tapazole

What is Northyx (methimazole)?

Methimazole prevents the thyroid gland from producing too much thyroid hormone.

Methimazole is used to treat hyperthyroidism (overactive thyroid). It is also used before thyroid surgery or radioactive iodine treatment.

Methimazole may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Northyx (methimazole)?

Do not use methimazole if you are pregnant. It could harm the unborn baby. Do not take methimazole if you are breast-feeding a baby. Methimazole can increase your risk of bleeding. If you need to have surgery, tell the surgeon ahead of time that you are using this medication.

Methimazole can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Visit your doctor regularly.

Do not receive a "live" vaccine while you are being treated with methimazole, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Keep using this medication even if you feel fine or have no symptoms of hyperthyroidism. You may need to keep taking methimazole long term to control your condition. Stopping the medication could cause your symptoms to return.

What should I discuss with my healthcare provider before taking Northyx (methimazole)?

Do not use this medication if you are allergic to methimazole.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely take this medication:

liver disease;

a blood cell disorder; or

a weak immune system.

FDA pregnancy category D. Do not use methimazole if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. Methimazole can pass into breast milk and may harm a nursing baby. Do not use methimazole if you are breast-feeding a baby.

How should I take Northyx (methimazole)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Take methimazole with a full glass of water.

Methimazole can be taken with or without food, but you should take it the same way each time.

Methimazole can increase your risk of bleeding. If you need to have any type of surgery, tell the surgeon ahead of time that you are using this medication.

It is important to use methimazole regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Keep using this medication even if you feel fine or have no symptoms of hyperthyroidism. You may need to keep taking methimazole long term to control your condition. Stopping the medication could cause your symptoms to return. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include nausea, vomiting, upset stomach, headache, joint pain, fever, itching, swelling, or pale skin and easy bruising or bleeding.

What should I avoid while taking Northyx (methimazole)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using methimazole, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), oral polio, chickenpox (varicella), BCG (Bacillus Calmette and Guérin), and nasal flu vaccine.

Northyx (methimazole) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using methimazole and call your doctor at once if you have a serious side effect such as:

fever, chills, sore throat, body aches, flu symptoms;

easy bruising or bleeding, unusual weakness;

blood in your urine or stools;

severe blistering, peeling, and red skin rash; or

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

headache, drowsiness, dizziness;

mild nausea, vomiting, or stomach upset;

itching, minor skin rash;

muscle, joint, or nerve pain;

swelling; or

hair loss.

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 Northyx (methimazole)?

Tell your doctor about all other medicines you use, especially:

theophylline (Theo-Dur, Elixophyllin, Uniphyl, and others);

a blood thinner such as warfarin (Coumadin);

digoxin (digitalis, Lanoxin); or

a beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others.

This list is not complete and other drugs may interact with methimazole. 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 Northyx resources

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

Methimazole Prescribing Information (FDA)

Methimazole Professional Patient Advice (Wolters Kluwer)

Methimazole Monograph (AHFS DI)

Methimazole MedFacts Consumer Leaflet (Wolters Kluwer)

methimazole Advanced Consumer (Micromedex) - Includes Dosage Information

Tapazole Prescribing Information (FDA)

Compare Northyx with other medications

Hyperthyroidism

Where can I get more information?

Your pharmacist can provide more information about methimazole.

See also: Northyx side effects (in more detail)