Antineoplastic agents - Protein-tyrosine kinase inhibitor

Sunitinib

SUTENT® 12.5 mg hard capsules SUTENT® 25 mg hard capsules SUTENT® 50 mg hard capsules

SUTENT® 12.5 mg Hard capsules. Gelatin capsules with orange cap and orange body, printed with white ink “Pfizer” on the cap, “STN 12.5 mg” on the body, and containing yellow to orange granules. SUTENT® 25 mg Hard Capsules Gelatin capsule with caramel cap and orange body, printed with white ink “Pfizer” on the cap and “STN 25 mg ” on the body and containing yellow to orange granules. SUTENT® 50 mg Hard capsules Gelatin capsules with caramel cap and caramel body, printed with white ink “Pfizer” on the cap and “STN 50 mg” on the body and containing yellow to orange granules.

Gastrointestinal Stromal Tumour (GIST) SUTENT is indicated for the treatment of unresectable and/or metastatic malignant gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate treatment due to resistance or intolerance.

Metastatic Renal Cell Carcinoma (MRCC) SUTENT is indicated for the treatment of advanced and/ormetastatic renal cell carcinoma (MRCC).

Therapy should be initiated by a physician experienced in the treatment of renal cell carcinoma or GIST.

The recommended dose of SUTENT is one 50 mg dose orally, taken daily for 4 consecutive weeks, followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks.

Dose adjustments

Safety and Tolerability

Dose modifications in 12.5-mg steps may be applied based on individual safety and tolerability. Daily dose should not exceed 75 mg nor be decreased below 25 mg.

CYP3A4 Inhibitors/Inducers

Co-administration of potent CYP3A4 inducers such as rifampin, should be avoided. If this is not possible, the dose of SUTENT may need to be increased in 12.5 mg increments (up to 87.5 mg per day) based on careful monitoring of tolerability.

Co-administration of SUTENT with potent CYP3A4 inhibitors, such as ketoconazole, should be avoided. If this is not possible the doses of SUTENT may need to be reduced to a minimum of 37.5 mg daily, based on careful monitoring of the tolerability.

Selection of an alternate concomitant medication with no, or minimal potential to induce or inhibit CYP3A4 should be considered.

Paediatric use: The safety and efficacy of SUTENT in paediatric patients have not been established.

SUTENT should not be used in paediatric population until further data become available.

Elderly patients use: Approximately 34% of the subjects in clinical studies of SUTENT were 65 or over. No significant differences in safety or effectiveness were observed between younger and older patients.

Hepatic Insufficiency: No dose adjustment is recommended when administering SUTENT to patients with mild or moderate (Child-Pugh Class A and B) hepatic impairment. SUTENT has not been studied in subjects with Child-Pugh Class C hepatic impairment.

Renal Insufficiency: No clinical studies have been performed in patients with impaired renal function.

SUTENT may be taken with or without food.

If a dose is missed the patient should not be given an additional dose. The patient should take the usual prescribed dose on the following day.

Paediatric use: The safety and efficacy of SUTENT in paediatric patients have not been established. SUTENT should not be used in paediatric population until further data become available.

Elderly patients use: Approximately 25% of the subjects in clinical studies of SUTENT were 65 or over. No significant differences in safety or effectiveness were observed between younger and older patients.

Hypersensitivity to sunitinib malate or to any of the excipients.

Co--administration of potent CYP3A4 inducers such as rifampin, may decrease sunitinib plasma concentrations. Combination with inducers should therefore be avoided. If this is not possible, the dosage of SUTENT may need to be increased

Co-administration of strong CYP3A4 inhibitor such as ketoconazole may increase sunitinib plasma concentrations. Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential is recommended. If this is not possible, the dosage of SUTENT may need to be reduced.

Skin and tissues

Skin discolouration, possibly due to the active substance colour (yellow) is a common treatment-related adverse event occurring in approximately 30% of patients. Patients should be advised that depigmentation of the hair or skin may also occur during treatment with SUTENT. Other possible dermatologic effects may include dryness, thickness or cracking of the skin, blisters or occasional rash on the palms of the hands and soles of the feet.

Mouth pain/irritation was reported in approximately 14% of patients. Dysgeusia (taste disturbance) was reported in approximately 28% of patients.

The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation.

Haemorrhage

Haemorrhagic events, some of which were fatal, reported through post-marketing experience, have included GI, respiratory, tumour, urinary tract and brain haemorrhages. In clinical trials treatment-related tumour haemorrhage occurred in approximately 2% of patients with GIST. These events may occur suddenly, and in the case of pulmonary tumours, may present as severe and life-threatening haemoptysis or pulmonary haemorrhage. Fatal pulmonary haemorrhage occurred in 2 patients receiving SUTENT on a clinical trial of patients with metastatic non-small cell lung cancer (NSCLC). Both patients had squamous cell histology. SUTENT is not approved for use in patients with NSCLC. Bleeding events occurred in 18% of patients receiving SUTENT in a phase 3 GIST Study compared to 17% of patients receiving placebo. In patients receiving SUTENT for treatment-naïve MRCC, 28% had bleeding events compared to 7% of patients receiving IFN- α. Seven (1.9%) patients on sunitinib malate versus 0% of patients on IFN-α experienced Grade 3 or greater treatment-related bleeding events. Of patients receiving sunitinib malate for cytokine-refractory MRCC, 26% experienced bleeding. Routine assessment of this event should include complete blood counts and physical examination.

Epistaxis was the most common treatment-related haemorrhagic adverse event, having been reported for approximately half of the patients with solid tumours who experienced haemorrhagic events. Some of these events were severe, but very rarely fatal.

Gastrointestinal events

Nausea, diarrhoea, stomatitis, dyspepsia and vomiting were the most commonly reported treatment-related gastrointestinal events.

Supportive care for gastrointestinal adverse events requiring treatment may include medication with an anti-emetic or anti-diarrhoeal medication.

Gastrointestinal tract

Serious, sometimes fatal gastrointestinal complications including gastrointestinal perforation have occurred rarely in patients with intra-abdominal malignancies treated with SUTENT. Treatment-related fatal gastrointestinal bleeding occurred in 0.5% of patients receiving placebo in the GIST Phase 3 study.

Hypertension

Treatment-related hypertension was reported in approximately 16% of patients with solid tumours. SUTENT dosing was reduced or temporarily delayed in approximately 2.7% of this patient population. None of these patients were discontinued from treatment with SUTENT. Severe hypertension >200 mmHg systolic or 110 mmHg diastolic) occurred in 4.7% of this patient population. Treatment-related hypertension was reported in approximately 24% of patients receiving sunitinib malate for treatment-naïve MRCC compared to 1% of patients receiving IFN-α. Severe hypertension occurred in 5% of treatment-naïve patients on sunitinib malate and 1% of patients on IFN-α. Patients should be screened for hypertension and controlled as appropriate. Temporary suspension is recommended in patients with severe hypertension that is not controlled with medical management. Treatment may be resumed once hypertension is appropriately controlled.

Haematological

Decreased absolute neutrophil counts of grade 3 and 4 severity were reported in 10% and 1.7% of patients on the phase 3 GIST study, respectively, and in 16% and 1.6% of patients on the phase 3 MRCC study, respectively. Decreased platelet counts of grade 3 and 4 severity were reported in 3.7% and 0.4% of patients on the phase 3 GIST study, respectively, and in 8.2% and 1.1% of patients on the phase 3 MRCC study, respectively. The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation. None of these events in the phase 3 studies were fatal, but rare fatal haematological events have been reported through post-marketing experience.

Complete blood counts should be performed at the beginning of each treatment cycle for patients receiving treatment with SUTENT.

Cardiovascular

Cardiovascular events, some of which were fatal, reported through post-marketing experience, have included left ventricular ejection fraction (LVEF) decrease and cardiac failure. In clinical trials, decreases in LVEF of 20% and below the lower limit of normal occurred in approximately 2% of SUTENT-treated GIST patients, 4% of cytokine-refractory MRCC patients, 2% of placebo-treated patients. These LVEF declines do not appear to have been progressive and often improved as treatment continued. In the treatment-naïve MRCC study, 21% patients on SUTENT and 12% of patients on interferon-α (IFN-α), had an LVEF value below the lower limit of normal. One (<1%) patient who received SUTENT was diagnosed with congestive heart failure (CHF).

Treatment-related adverse events of 'cardiac failure', 'cardiac failure congestive' or 'left ventricular failure' were reported in 0.7% of patients with solid tumours and 1% of patients treated with placebo. All patients had GIST. In the phase 3 GIST study (n=312), treatment-related fatal cardiac events occurred in 1% of patients on each arm of the study (i.e. SUTENT and placebo arms). In a phase 2 study in cytokine-refractory MRCC patients, 0.9% of patients experienced treatment-related fatal myocardial infarction and in the phase 3 study in treatment-naïve MRCC patients, 0.6% of patients on the IFN-α arm and 0 patients on the SUTENT arm experienced fatal cardiac events. The relationship, if any, between receptor tyrosine kinase (RTK) inhibition and cardiac function remains unclear.

Patients who presented with cardiac events within 12 months prior to SUTENT administration, such as myocardial infarction (including severe/unstable angina), coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF), cerebrovascular accident or transient ischemic attack, or pulmonary embolism were excluded from SUTENT clinical studies.

Close monitoring for clinical signs and symptoms of CHF should be performed, especially in patients with cardiac risk factors and/or history of coronary artery disease.

Physicians are advised to weigh this risk against the potential benefits of the drug. These patients should be carefully monitored for clinical signs and symptoms of CHF while receiving SUTENT. Baseline and periodic evaluations of LVEF should also be considered while the patient is receiving SUTENT. In patients without cardiac risk factors, a baseline evaluation of ejection fraction should be considered.

In the presence of clinical manifestations of CHF, discontinuation of SUTENT is recommended. The dose of SUTENT should be interrupted and/or reduced in patients without clinical evidence of CHF but with an ejection fraction <50% and >20% below baseline.

QT Interval prolongation

Data from non-clinical (in vitro and in vivo) studies, at doses higher than the recommended human dose, indicate that sunitinib has the potential to inhibit the cardiac action potential repolarization process (e.g. prolongation of QT interval).

Increases in the QTc interval to over 500 msec occurred in 0.5% and changes from baseline in excess of 60 msec occurred in 1.1% of the 450 solid tumours patients; both these parameters are recognized as potentially significant changes. At approximately twice therapeutic concentrations, SUTENT has been shown to prolong the QTcF Inteval (Frederica's Correction).

QT interval prolongation was investigated in a trial in 24 patients, aged 20-87 years, with advanced malignancies. The results of this study demonstrated that sunitinib had an effect on QTc (defined as a mean placebo-adjusted change of > 10 msec with a 90% CI upper limit > 15 msec) at therapeutic concentration (day 3) using the within-day baseline correction method, and at greater than therapeutic concentration (Day 9) using both baseline correction methods. No patients had a QTc value >500 msec. Although an effect on QTcF was observed on Day 3 at 24 hours post-dose (i.e. at therapeutic plasma concentration expected after the recommended starting dose of 50 mg) with the within-day baseline correction method, the clinical significance of this finding is unclear.

Using comprehensive serial ECG assessments at times corresponding to either therapeutic or greater than therapeutic exposures, none of the patients in the evaluable or ITT populations were observed to develop QTc prolongation considered as “severe” (i.e. equal to or greater than Grade 3 by CTCAE version 3.0).

At therapeutic plasma concentrations, the maximum QTcF (Frederica's correction) mean change from baseline was 9.6 msec (90% CI 15.1msec). At approximately twice therapeutic concentrations, the maximum QTcF change from baseline was 15.4 msec (90% CI 22.4 msec). Moxifloxacin (400 mg) used as a positive control showed a 5.6 msec maximum mean QTcF change from baseline. No subjects experienced an effect on the QTc inteval greater than Grade 2 (CTCAE version 3.0). No patient presented with a cardiac arrhythmia.

QT interval prolongation may lead to an increased risk of ventricular arrhythmias including Torsade de pointes. Torsade de pointes has been observed in <0.1% of SUTENT-exposed patients. SUTENT should be used with caution in patients with a known history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances. Concomitant treatment with potent CYP3A4 inhibitors, which may increase sunitinib plasma concentrations, should be used with caution and the dose of SUTENT reduced.

Venous Thromboembolic Events

Treatment-related venous thromboembolic events were reported in approximately 1.0% of patients with solid tumours who received SUTENT on clinical trials, including GIST and MRCC.

Seven patients (3%) on SUTENT and none on placebo in a phase 3 GIST study experienced venous thromboembolic events; five of the seven were Grade 3 deep venous thromboses (DVT), and two were Grade 1 or 2. Four of these seven GIST patients discontinued treatment following first observation of DVT.

Seven patients (1.9%) receiving SUTENT in the phase 3 for treatment-naïve MRCC study and four patients (2%) on the two cytokine-refractory MRCC studies had treatment-related venous thromboembolic events reported. Six of these patients had pulmonary embolisms, one was Grade 3 and five were Grade 4, and five of these patients had DVT, one each with Grade 1 and 2, and three with Grade 3. Dose interruption occurred in one.

In treatment-naïve MRCC patients receiving IFN-α, six (2%) venous thromboembolic events occurred; one patient (<1%) experienced a Grade 3 DVT and five patients (1%) had pulmonary embolism, one Grade 1 and four with Grade 4.

No cases with fatal outcome were reported in GIST and MRCC registrational studies. Cases with fatal out-come had been observed in post-marketing setting.

Respiratory events

Patients who presented with pulmonary embolism within the previous 12 months were excluded from SUTENT clinical studies.

In patients who received SUTENT in Phase 3 registrational studies, treatment-related pulmonary events (i.e. dyspnoea, pleural effusion, pulmonary embolism or pulmonary oedema)were reported in approximately 5% of patients with GIST and in approximately 14% of patients with MRCC. Rare cases with fatal outcome were reported.

Approximately 8% of patients with solid tumours, including GIST and MRCC, who received SUTENT in clinical trials experienced treatment-related pulmonary events.

Cases of Pulmonary embolism were observed in approximately 1.3% of patients with GIST and in approximately 0.8% of patients with MRCC, who received Sutent in Phase 3 studies.

Thyroid Dysfunction

Baseline laboratory measurement of thyroid function is recommended and patients with hypothyroidism or hyperthyroidism should be treated as per standard medical practice prior to the start of sunitinib treatment. All patients should be observed closely for signs and symptoms of thyroid dysfunction on sunitinib treatment. Patients with signs and/or symptoms suggestive of thyroid dysfunction should have laboratory monitoring of thyroid function performed and be treated as per standard medical practice.

Hypothyroidism was reported as an adverse event in 7 patients (4%) across the two cytokine-refractory MRCC studies in nine patients (2%) on SUTENT and one patient (<1%) in the IFN-α arm in the treatment-naïve MRCC study. Additionally, TSH elevations were reported in 4 cytokine-refractory MRCC patients (2%). Overall, 7% of the MRCC population had either clinical or laboratory evidence of treatment-emergent hypothyroidism. Treatment-emergent acquired hypothyroidism was noted in 8 GIST patients (4%) on SUTENT versus 1 (1%) on placebo.

Rare cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience.

Pancreatitis

Increases in serum lipase and amylase activities were observed in patients with various solid tumours who received SUTENT. Increases in lipase activities were transient and were generally not accompanied by signs or symptoms of pancreatitis in subjects with various solid tumours. Pancreatitis has been observed rarely (<1%) in patients receiving SUTENT for GIST or MRCC.

Cases of serious pancreatic events, some with fatal outcome, have been reported. If symptoms of pancreatitis are present, patients should have SUTENT discontinued and be provided with appropriate supportive care.

Hepatic Function

Serious cases of SUTENT-related hepatobiliary events have been reported in patients with solid tumours; hepatic failure was observed in <1% of these patients. Cases of hepatobiliary events some with fatal outcome, have been reported. If signs or symptoms of hepatic failure are present, SUTENT should be discontinued and appropriate supportive care should be provided.

Renal function

The safety of continued SUTENT treatment in patients with moderate to severe proteinuria has not been systematically evaluated.

Cases of proteinuria and rare cases of nephrotic syndrome have been reported. Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria. Discontinue SUTENT in patients with nephrotic syndrome.

Seizures

In clinical studies of SUTENT and from post-marketing experience, seizures have been observed in subjects with or without radiological evidence of brain metastases. In addition, there have been rare (<1%) reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS). Patients with seizures and signs/symptoms consistent with RPLS, such as hypertension, headache, decreased alertness, altered mental functioning and visual loss, including cortical blindness should be controlled with medical management including control of hypertension. Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.

Drugs that may increase sunitinib plasma concentrations.

Concomitant administration of sunitinib malate with the potent CYP3A4 inhibitor, ketoconazole, resulted in a 49% and 51% increase of the complex [sunitinib + primary metabolite] C_max and AUC_0- values, respectively, after a single dose of sunitinib malate in healthy volunteers.

Administration of SUTENT with potent inhibitors of the CYP3A4 family (e.g. ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice) may increase sunitinib concentrations

Combination with inhibitors should therefore be avoided, or the selection of an alternate concomitant medication with no, or minimal potential to inhibit CYP3A4 should be considered.

If this is not possible, the dosage of SUTENT may need to be reduced to a minimum of 37.5 mg daily, based on careful monitoring of the tolerability.

Drugs that may decrease sunitinib plasma concentrations:

Concomitant use of SUTENT with the CYP3A4 inducer, rifampin, resulted in a 23% and 46% reduction of the complex [sunitinib + primary metabolite] C_max and AUC_0- values, respectively, after a single dose of SUTENT in healthy volunteers.

Administration of SUTENT with potent inducers of the CYP3A4 family (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital or Hypericum perforatum known also as St. John's Wort) may decrease sunitinib concentrations. Combination with inducers should therefore be avoided, or selection of an alternate concomitant medication with no, or minimal potential to induce CYP3A4 should be considered. If this is not possible, the dosage of SUTENT may need to be increased in 12.5 mg increments (up to 87.5 mg per day) based on careful monitoring of tolerability .

To maintain sunitinib target concentrations, selection of co-medications with less enzyme induction potential, should be considered. If this is not possible, dose-adjustments of SUTENT may be necessary..

Haemorrhage has been observed rarely in patients treated with SUTENT. Patients receiving concomitant treatment with anti-coagulants (e.g. warfarin; acenocumarole) may be periodically monitored by complete blood counts (platelets), coagulation factors (PT/INR), and physical examination

The most important treatment-related serious adverse events associated with SUTENT treatment of patients with solid tumours were pulmonary embolism (1%), thrombocytopoenia (1%), tumour haemorrhage (0.9%), febrile neutropoenia (0.4%), and hypertension (0.4%). The most common treatment-related adverse events (experienced by at least 20% of the patients) of any grade included: fatigue; gastrointestinal disorders, such as diarrhoea, nausea, stomatitis, dyspepsia and vomiting; skin discolouration; dysgeusia and anorexia. Fatigue, hypertension and neutropoenia were the most common treatment-related adverse events of Grade 3 maximum severity and increased lipase was the most frequently occurring treatment-related adverse event of Grade 4 maximum severity in patients with solid tumours. Hepatitis and hepatic failure occurred in <1% of patients and prolonged QT interval in < 0.1%.

Fatal events that were considered possibly related to SUTENT included multi-system organ failure, disseminated intravascular coagulation, peritonoeal haemorrhage, rhabdomyolysis, cerebrovascular accident, dehydration, adrenal insufficiency, renal failure, respiratory failure, pleural effusion, pneumothorax, shock, and sudden death.

Treatment-related adverse reactions that were reported in >2% of solid tumour patients are listed below, by system organ class, frequency and grade of severity. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Frequencies are defined as: Very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000).

Treatment-Related Adverse Reactions reported in GIST studies

The following terms have been combined:

^a Anorexia and decreased appetite

^b Dysgeusia, ageusia and taste disturbance

^c Abdominal pain and abdominal pain upper

^d Oedema, oedema peripheral and oedema face

^e White blood cell count decreased, neutrophil count decreased, and leukocyte count decreased

Treatment-Related Adverse Reactions reported in cytokine-refractory and treatment-naïve MRCC studies

System Organ Class	Frequency	Adverse Reactions	All Grades n (%)	Grade 3 n (%)	Grade 4 n (%)
Blood and lymphatic system disorders	Very common	Neutropoenia	89 (16.4%)	46 (8.5%)	5 (0.9%)
	Very common	Thrombocytopoenia	86 (15.8%)	37 (6.8%)	5 (0.9%)
	Very common	Anaemia	67 (12.3%)	20 (3.7%)	3 (0.6%)
	Common	Leukopoenia	45 (8.3%)	16 (2.9%)	0 (0%)
	Common	Lymphopenia	21 (3.9%)	12 (2.2%)	1 (0.2%)
Endocrine disorders	Very common	Hypothyroidism	67 (12.3%)	7 (1.3%)	0 (0%)
Eye disorders	Common	Lacrimation increased	39 (7.2%)	0 (0%)	0 (0%)
	Common	Eyelid oedema	12 (2.2%)	0 (0%)	0 (0%)
Metabolism and nutrition disorders	Common	Decreased appetite a	205 (37.7%)	9 (1.7%)	0 (0%)
	Common	Dehydration	33 (6.1%)	7 (1.3%)	1 (0.2%)
Nervous system disorders	Very common	Taste disturbance b	250 (46.0%)	1 (0.2%)	0 (0%)
	Very common	Headache	82 (15.1%)	3 (0.6%)	0 (0%)
	Common	Dizziness	38 (7.0%)	2 (0.4%)	0 (0%)
	Common	Paraesthesia	36 (5.9%)	0 (0%)	0 (0%)
	Common	Neuropathy peripheral	33 (6.1%)	1 (0.2%)	0 (0%)
	Common	Hypoaesthesia	20 (3.7%)	0 (0%)	0 (0%)
	Common	Hyperaesthesia	17 (3.1%)	0 (0%)	0 (0%)
Vascular disorders	Very common	Hypertension	143 (26.3%)	55 (10.1%)	0 (0%)
	Common	Flushing	17 (3.1%)	0 (0%)	0 (0%)
	Common	Hot flush	12 (2.2%)	0 (0%)	0 (0%)
Respiratory, thoracic and mediastinal disorders	Very common	Epistaxis	86 (15.8%)	3 (0.6%)	0 (0%)
	Common	Dyspnoea	45 (8.3%)	6 (1.1%)	< Manufacturer : Pfizer Ltd Drug Availability : (POM) Drug Updated : 12 August 2009 Disease Knowledge Centres – evidence based educational and clinical tools written for doctors and physicians Hypertension Insomnia Lysosomal Storage Disorders Men's Health Migraine Neuropathic Pain Niemann-pick Type C NSCLC Ophthalmics Opioids and Pain Parkinson's Disease Renal Anaemia Soft Tissue Sarcoma Disease Knowledge Centres feed Alzheimer's Disease Arthritis Asthma Benign Prostatic Hyperplasia (BPH) Cholesterol Chronic Myeloid Leukemia (CML) Cystic Fibrosis Contraception Diabetes Gastrointestinal Stromal Tumours (GIST) Hepatitis Human Papillomavirus (HPV) & Cervical Cancer New and updated Drugs UK Drugs Carnitor 330 mg Tablets AMIKIN INJECTION 100MG/2ML ACLASTA 5 mg Buccastem 3 mg CalCough Infant Syrup Carnitor 1 g Chewable Tablets Dulcobalance Clarityn Allergy 10mg Tablets DoxaduraTM XL 4mg Prolonged Release Tablets Clarityn Allergy 1mg/ml Syrup Dyloject® 75 mg/2 ml Solution for Injection MIGRALEVE Meggezones MEPACT 4 mg Powder LUMIGAN 0.1 mg/ml eye drops Irinotecan medac 20 mg/ml Quinoric 200mg Film-Coated Tablets Rinstead Sugar Free Pastilles Pantoprazole 20 mg Gastro-resistant Tablets Renvela 2.4 g powder for oral suspension Spanish Drugs Vogalen 5 mg/5 ml jarabe 150 ml Vitantial 250 mg 20 grageas Wilzin cápsulas duras Yondelis solución para perfusión Xarelto 10 mg comprimidos recubiertos con película Xenical 120 mg 84 capsulas Acetato clohexidina baxt 0.05% solucion 1000 ml Wincoram 5 mg/ml 5 ampollas 20 ml Zeffix 25 mg/5 ml solu 240 ml Zeffix 100 mg 28 comprimidos Zorac 0.1% gel 60 g Zorac 0.1% gel 15 g Zorac 0.05% gel 15 g Zulex 333 mg 84 comprimidos AVAGLIM 4 mg/4 mg comprimidos recubiertos con película AMMONAPS 500 mg comprimidos Apidra 100 Unidades/ml solución inyectable en un vial. Sanofi Pharma Bristol-Myers Squibb SNC Aranesp 10 microgramos solución inyectable en jeringa precargada. Arava 10 mg comprimidos recubiertos con película German Drugs Xarelto 10 mg Filmtabletten Farmorubicin® 10 mg HL | 20 mg HL | -50 mg HL; -Lösung 10 mg | -20 mg | -50 mg Latensin® Corto-Tavegil® Melleril® retard 30; -Tropflösung Methergin®; -Injektionslösung Optalidon® N Optalidon® special NOC Optalidon® special NOC Pravidel® 2,5 mg Pravidel® 2,5 mg Pravidel® 5 mg | -10 mg Sandoglobulin® Sandomigran® Syntocinon® Spray Syntocinon® 3 I.E. | -10 I.E. Melleril® 25 | -100; -retard 200 Melleretten® Macalvit® Corto-Tavegil® Norweigan Drugs Foradil Hivid Haldol Hycamtin Haemaccel Fungizone Flutide Forene Garamycin Flunitec Heparin Geavir Insulin Komb 25/75 Fortum Insulin Rapid Foscavir Intralipid Kabikinase Fragmin Fraxiparine Netherlands Drugs Levodopa-Carbidopa Tabletten Megalotect DKTP-Vaccin RIVM DTP-Vaccin RIVM Arilvax Act-Hib Havrix Avaxim Hepatitis B Immunoglobuline 300 IE Hepatitis B Immunoglobuline Vesparax Orfenadrine Dragees HB-VAX-DNA Botulismeserum BMR-Vaccin RIVM Dopergin Sinemet Fungizone ad perfusionem Diflucan Ancotil Swedish Drugs Tagamet®, Tabletter 400 mg, SmithKline Beecham AB Dichlotride®, Tabletter 25 mg, Merck Sharp & Dohme (Sweden) AB Dichlotride®, Tabletter 50 mg, Merck Sharp & Dohme (Sweden) AB Rytmonorm®, Tabletter 150 mg, Abbott Scandinavia AB Rytmonorm®, Tabletter 300 mg, Abbott Scandinavia AB Xylocain®, Injektionsvätska 20 mg/ml, Astra Läkemedel AB Xylocain®, Salva 5 %, Astra Läkemedel AB Xylocain®, Injektionsvätska 5 mg/ml, Astra Läkemedel AB Xylocain®, Injektionsvätska 10 mg/ml, Astra Läkemedel AB Xylocain®, Gel 2 %, Astra Läkemedel AB Xylocain®, Lösning för anestesi 40 mg/ml, Astra Läkemedel AB Xylocain®, Gurgelvatten 5 mg/ml, Astra Läkemedel AB Xylocain®, Gel (utan konserveringsmedel) 2 %, Astra Läkemedel AB Diflucan®, Pulver till mixtur 40 mg/ml, Pfizer AB Diflucan®, Pulver till mixtur 10 mg/ml, Pfizer AB Diflucan®, Kapslar 200 mg, Pfizer AB Tagamet®, Tabletter 800 mg, SmithKline Beecham AB Tagamet®, Brustabletter 800 mg, SmithKline Beecham AB Tagamet®, Brustabletter 400 mg, SmithKline Beecham AB Duphalac®, Oral lösning 670 mg/ml, Solvay Pharma AB French Drugs RELISTOR 12 mg/0,6 ml solution injectable YTRACIS, précurseur radiopharmaceutique, en solution. DepoCyte 50 mg, suspension injectable Diacomit 250 mg gélule DUKORAL, suspension et granulés effervescents pour suspension buvable. Livensa 300 microgrammes/24 heures dispositif transdermique DULOXETINE BOEHRINGER INGELHEIM DuoTrav 40 microgrammes/ml + 5 mg/ml collyre en solution Dynastat 20 mg poudre pour solution injectable Dynepo 1000 UI/0,5 ml, solution injectable en seringue préremplie. DaTSCAN 74 MBq/ml, solution injectable Daronrix, suspension injectable KOGENATE Bayer 250 UI poudre et solvant pour solution injectable. Lucentis 10 mg/ml solution injectable LUMIGAN 0,3 mg/ml, collyre en solution Luveris 75 UI poudre et solvant pour solution injectable. LYRICA 25 mg gélules Lysodren 500 mg, comprimés Kentera 3,9 mg / 24 heures, dispositif transdermique Keppra 250 mg, comprimés pelliculés Portuguese Drugs Truvada Tysabri Trizivir Trisenox Trevaclyn Tritanrix HepB Tredaptive Twinrix Adult Tygacil Tyverb Temodal Tevagrastim Thalidomide Celgene Thelin Topotecan Actavis Travatan Tractocile Topotecan Teva Thyrogen Torisel Italian Drugs Karvezide 150 mg/12,5 mg compresse Xelevia 25 mg compresse rivestite con film Kivexa 600 mg/300 mg compresse rivestite con film Dafiro 5 mg/80 mg compresse rivestite con film RoActemra 20 mg/ml concentrato per soluzione per infusione. Kinzalkomb 40 mg/12,5 mg compresse Revasc 15 mg/0,5 ml polvere e solvente per soluzione iniettabile DULOXETINE BOEHRINGER INGELHEIM 40 mg capsule rigide gastroresistenti Renagel 400 mg compresse rivestite con film Diacomit 250 mg capsule rigide Dynepo 1.000 UI/0,5 ml soluzione iniettabile in siringa pre-riempita Gardasil, sospensione iniettabile. REGRANEX 0,01% gel Glivec 50 mg capsule rigide GONAL-f 75 UI polvere e solvente per soluzione iniettabile. Fabrazyme 35 mg, polvere per concentrato per soluzione per infusione. Fareston 60 mg compresse Rapilysin 10 U polvere e solvente per soluzione iniettabile. Rapamune 1 mg/ml soluzione orale. Ketek 400 mg compresse rivestite con film. Cholesterol Cardiovascular Disease Risk Assessment Treatment Options Diet and Exercise DRUG UPDATES Carnitor 330 mg Tablets AMIKIN INJECTION 100MG/2ML ACLASTA 5 mg Buccastem 3 mg CalCough Infant Syrup Carnitor 1 g Chewable Tablets Dulcobalance Clarityn Allergy 10mg Tablets DoxaduraTM XL 4mg Prolonged Release Tablets Clarityn Allergy 1mg/ml Syrup HEALTH JOBS Latest healthcare vacancies for a variety of medical specialties CONNECT EPG Mobile Congress Diary DISEASE CENTRES Neuropathic Pain Soft Tissue Sarcoma Niemann-Pick Type C Cystic Fibrosis Cholesterol Contraception Hepatitis Renal Anaemia CML GIST Parkinsons Insomnia Asthma LSD’s NSCLC Alzheimer's Diabetes Opioids and Pain BPH Men's Health Arthritis Hypertension Migraine Cervical Cancer Ophthalmics QUICK SEARCH ADHD Alzheimers Anxiety Disorders Arthritis Asthma BPH Breast Cancer Cervical Cancer Cholesterol Colorectal Cancer Depression Diabetes Erectile Dysfunction Hypertension Insomnia Men's Health Meningitis Migraine Pain Management Parkinson's Pharma News Pregnancy Renal anaemia Thrombosis GUIDELINES Arthritis Benign Prostatic Hyperplasia Dyspepsia Ear Infection Hepatitis Hypogonadism Infertility Inflammatory bowel disease Narcolepsy Obsessive-compulsive disorder Psoriasis Ulcerative Colitis Management DRUG DATA Deutsch     English Español Norsk Nederlands Svenska Français Português Italiano REFFERENCES ADHD to Diabetes     GIST to HPV Hypertension to Migraine Niemann-Pick to Parkinsons Renal Anaemia to Thrombosis Disease, Drug and Treatment Knowledge Centres Alzheimer's Disease - Arthritis - Asthma - BPH - Cholesterol - CML - Contraception - Cystic Fibrosis - Diabetes - GIST - Hepatitis - Human Papillomavirus (HPV) & Cervical Cancer - Hypertension - Insomnia - Lysosomal Storage Disorders - Men's Health - Migraine - Niemann-Pick Type C - Non-Small Cell Lung Cancer - Ophthalmics - Opioids and Pain - Parkinson's Disease - Thrombosis - Renal Anaemia - Respiratory - Rheumotology - Soft Tissue Sarcoma - Psychiatry - Oncology - Endocrine - Cardiology - Immunology - Infectious diseases - Urology - Medical Education - Physician - Drug - Doctor - Database - Medicine - Treatment - Allergy - Chest - Dermatology - Gastroenterology - Geriatrics - Gynaecology - Intensive Care - Internal Medicine - Research - Nephrology - Neurology - Nutrition - Orthopaedics - Otorhinolaryngology - Paediatric - Pathology - Surgery Browse the A to Z drug index for physician focused medicine knowledge, medical news, diagnosis & treatment guidelines Aa  | Bb  | Cc  | Dd  | Ee  | Ff  | Gg  | Hh  | Ii  | Jj  | Kk  | Ll  | Mm  | Nn  | Oo  | Pp  | Qq  | Rr  | Ss  | Tt  | Uu  | Vv  | Ww  | Xx  | Yy  | Zz Register | Patients | Feedback | About Us | Drugs | Knowledge Centres | Medical News | Member Services Professional Development | Software | Terms of Use | Privacy Policy | Contact Us | Site Map XML Sitemap | Drug Index A to Z | Drugs by Class Copyright © 1999 - 2010 EPG ONLINE