Products» Anti-infective

Rofend®

  • Description
  • Mechanism of Action
  • Indications
  • Adverse Reactions
  • Warnings

Interferes with fungal cytochrome P450 activity (selectively inhibits 14-alpha-lanosterol demethylation), decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting fungal cell membrane formation.

>10%:

Central nervous system: Hallucination (2% to 12%; auditory and/or visual and likely serum concentration-dependent)

Ophthalmic: Visual disturbance (19%)

Renal: Increased serum creatinine (1% to 21%)

2% to 10%:

Cardiovascular: Tachycardia (≤2%)

Central nervous system: Chills (≤4%), headache (≤3%)

Dermatologic: Skin rash (≤7%)

Endocrine & metabolic: Hypokalemia (≤2%)

Gastrointestinal: Nausea (1% to 5%), vomiting (1% to 4%)

Hepatic: Increased serum alkaline phosphatase (4% to 5%), increased serum AST (2% to 4%), increased serum ALT (2% to 3%), cholestatic jaundice (1% to 2%)

Ophthalmic: Photophobia (2%)

Miscellaneous: Fever (≤6%)

<2%, postmarketing, and/or case reports (limited to important or life-threatening): Acute renal failure, adrenocortical insufficiency, agranulocytosis, alopecia, anaphylactoid reaction, anemia (aplastic, hemolytic, macrocytic, megaloblastic, or microcytic), angioedema, anorexia, anuria, arthritis, ascites, ataxia, atrial arrhythmia, atrial fibrillation, atrioventricular block, bacterial infection, bigeminy, blighted ovum, bone marrow depression, bradycardia, brain disease, bundle branch block, cardiac arrest, cardiac failure, cardiomegaly, cardiomyopathy, cellulitis, cerebral edema, cerebral hemorrhage, cerebral ischemia, cerebrovascular accident, chest pain, cholecystitis, cholelithiasis, cholestasis, chromatopsia, color blindness, coma, confusion, convulsions, corneal opacity, cyanosis, deafness, deep vein thrombophlebitis, deep vein thrombosis, delirium, dementia, dental fluorosis, depersonalization, depression, diabetes insipidus, diarrhea, discoid lupus erythematosus, disseminated intravascular coagulation, drowsiness, duodenal ulcer (active), duodenitis, dyspnea, eczema, edema, encephalitis, endocarditis, eosinophilia, erythema multiforme, esophageal ulcer, exfoliative dermatitis, extrapyramidal reaction, extrasystoles, fixed drug eruption, fungal infection, gastric ulcer, gastrointestinal hemorrhage, glucose tolerance decreased, graft versus host disease, Guillain-Barre syndrome, hematemesis, hemorrhagic cystitis, hepatic coma, hepatic failure, hepatitis, hepatomegaly, herpes simplex infection, hydronephrosis, hyperbilirubinemia, hypercholesterolemia, hyper-/hypocalcemia, hyper-/hypoglycemia, hyper-/hypomagnesemia, hyper-/hyponatremia, hyper-/hypotension, hyper-/hypothyroidism, hyperkalemia, hypersensitivity reaction, hyperuricemia, hypophosphatemia, hypoxia, impotence, increased blood urea nitrogen, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased susceptibility to infection, intestinal perforation, intracranial hypertension, jaundice, leukopenia, lymphadenopathy, lymphangitis, maculopapular rash, malignant melanoma, melanosis, multiorgan failure, myasthenia, myocardial infarction, myopathy, nephritis, nephrosis, neuropathy, nocturnal amblyopia, nodal arrhythmia, nodule, nystagmus, oculogyric crisis, optic atrophy, optic neuritis, orthostatic hypotension, osteomalacia, osteonecrosis, osteoporosis, otitis externa, palpitations, pancreatitis, pancytopenia, papilledema, paresthesia, perforated duodenal ulcer, periosteal disease, peripheral edema, peritonitis, petechia, pleural effusion, pneumonia, prolonged bleeding time, prolonged QT interval on ECG, pruritus, pseudomembranous colitis, pseudoporphyria, psoriasis, psychosis, pulmonary edema, pulmonary embolism, purpura, rectal hemorrhage, renal insufficiency, renal tubular necrosis, respiratory distress syndrome, respiratory tract infection, retinal hemorrhage, retinitis, seizure, sepsis, skin discoloration, skin photosensitivity, splenomegaly, squamous cell carcinoma, Stevens-Johnson syndrome, subconjunctival hemorrhage, substernal pain, suicidal ideation, supraventricular extrasystole, supraventricular tachycardia, syncope, thrombocytopenia, thrombophlebitis, thrombotic thrombocytopenic purpura, tongue edema, tonic-clonic seizures, torsades de pointes, toxic epidermal necrolysis, uremia, urinary incontinence, urinary retention, urinary tract infection, urticaria, uterine hemorrhage, uveitis, vaginal hemorrhage, vasodilation, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, visual field defect

Concerns related to adverse effects:

  • Arrhythmias/QT prolongation: QT interval prolongation has been associated with voriconazole use; rare cases of arrhythmia (including torsade de pointes), cardiac arrest, and sudden death have been reported, usually in seriously ill patients with comorbidities and/or risk factors (eg, prior cardiotoxic chemotherapy, cardiomyopathy [especially with concomitant heart failure], electrolyte imbalance, or concomitant QTc-prolonging drugs). Also use with caution in patients with potentially proarrhythmic conditions (eg, congenital or acquired QT syndrome, sinus bradycardia, or preexisting symptomatic arrhythmias); correct electrolyte abnormalities (eg, hypokalemia, hypomagnesemia, hypocalcemia) prior to initiating and during therapy.
  • Dermatologic reactions: Rare cases of malignancy (melanoma, squamous cell carcinoma [SCC]) have been reported in patients with prior onset of severe photosensitivity reactions or exposure to standard dose long-term voriconazole therapy (in lung transplant recipients, SCC increased by ~6% per 60 days with a 28% absolute risk increase at 5 years [Singer 2012]). Other serious exfoliative cutaneous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, have also been reported. Patients, including children, should avoid exposure to direct sunlight and should use protective clothing and high SPF sunscreen; may cause photosensitivity, especially with long-term use. Discontinue use in patients who develop an exfoliative cutaneous reaction or a skin lesion consistent with squamous cell carcinoma or melanoma. Periodic total body skin examinations should be performed, particularly with prolonged use. If phototoxic reactions occur, referral to a dermatologist and voriconazole discontinuation should be considered. If therapy is continued, dermatologic evaluation should be performed on a systematic and regular basis to allow early detection and management of premalignant lesions. Pediatric patients are at particular risk for phototoxicity (see Special Populations).
  • Hepatic toxicity: Serious (and rarely fatal) hepatic reactions (eg, hepatitis, cholestasis, fulminant failure) have been observed with voriconazole. In lung transplant recipients, median time to hepatic toxicity was 14 days with the majority occurring within 30 days of therapy initiation (Luong 2012). Use with caution in patients with serious underlying medical conditions (eg, hematologic malignancy); hepatic reactions have occurred in patients with no identifiable underlying risk factors. Liver dysfunction is usually reversible upon therapy discontinuation. Monitor serum transaminase and bilirubin at baseline and at least weekly for the first month of treatment. Monitoring frequency can then be reduced to monthly during continued use if no abnormalities are noted. If marked elevations occur compared to baseline, discontinue unless benefit/risk of treatment justifies continued use.
  • Infusion-related reactions: Anaphylactoid-type reactions including tachycardia, dyspnea, chest tightness, faintness, nausea, rash, pruritus, fever, sweating and flushing have been observed; symptoms have appeared immediately upon initiating the infusion. Stop infusion for severe reactions or as clinical presentation indicates.
  • Ocular effects: Visual changes, including blurred vision, changes in visual acuity, color perception, and photophobia, are commonly associated with treatment; postmarketing cases of optic neuritis and papilledema (lasting >1 month) have also been reported. Patients should be warned to avoid tasks which depend on vision, including operating machinery or driving. Changes are reversible on discontinuation following brief exposure/treatment regimens (≤28 days); reversibility following long-term administration has not been evaluated. If treatment continues >28 days, visual function (eg, acuity, visual field, color perception) should be monitored.
  • Renal toxicity: Acute renal failure has been observed in severely ill patients; use with caution in patients receiving concomitant nephrotoxic medications. Evaluate renal function (particularly serum creatinine) at baseline and periodically during therapy.
  • Skeletal effects: Fluorosis and/or periostitis may occur during long-term therapy. If patient develops skeletal pain and radiologic findings of fluorosis or periostitis, discontinue therapy.
  • Toxicity symptoms: Voriconazole demonstrates nonlinear pharmacokinetics. Dose modifications may result in unpredictable changes in serum concentrations and contribute to toxicity. For toxicity, the strongest correlations have been made between voriconazole trough concentrations and neurological and dermatological adverse events (Dolton 2012; Hamada 2012; Mitsani 2012; Park 2012; Soler-Palacin 2012). In these studies, increased toxicity was noted when trough concentrations exceeded threshold values. There are much less data supporting the existence between a cutoff threshold and hepatotoxicity. It is important to note that cutoff trough threshold values ranged widely among studies; however, an upper limit of <5.0 mg/L would be reasonable for most disease states (see CDC recommendations for Exserohilum rostratumin Reference Range section) (CDC 2012).

Disease-related concerns:

  • Electrolyte abnormalities: Correct electrolyte abnormalities (eg, hypokalemia, hypomagnesemia, hypocalcemia) prior to initiating and during therapy.
  • Hepatic impairment: Use with caution; elevated liver function tests and clinical signs of liver damage, such as jaundice, have been associated with voriconazole. Adjustments to maintenance dosing is required in mild to moderate hepatic cirrhosis (Child-Pugh class A and B). In patients with severe hepatic insufficiency use only if the benefit outweighs the potential risk. Evaluate hepatic function (particularly liver function tests and bilirubin) at baseline and periodically during therapy.
  • Pancreatitis: Monitor pancreatic function in patients (children and adults) at risk for acute pancreatitis (eg, recent chemotherapy or hematopoietic stem cell transplantation). Pancreatitis has occurred in pediatric patients.
  • Renal impairment: Avoid the use of IV voriconazole in patients with renal impairment. See “Dosage forms specific issues: Injection: formulation.” Evaluate renal function (particularly serum creatinine) at baseline and periodically during therapy.

Concurrent drug therapy issues:

  • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

  • Pediatric pharmacokinetics: In pediatric patients, voriconazole pharmacokinetics are complex. In patients >14 years of age or 12 to 14 years and weighing >50 kg, data suggest that pharmacokinetics are similar to adults (Friberg 2012). In patients <12 years of age, the full pharmacokinetic profile for voriconazole is not completely defined and for patients <2 years, the data are sparse. In children 2 to <12 years, current data suggest voriconazole undergoes a high degree of variability in exposure with linear elimination at lower doses and nonlinear elimination at higher doses; therefore, to achieve similar AUC as adults, increased dosage is necessary in children (Friberg 2012; Karlsson 2009; Walsh 2004).
  • Pediatric dermatologic reactions: Frequency of phototoxic reactions is higher in pediatric patients. Stringent photoprotective measures are necessary in children due to the risk of squamous cell carcinoma. In children experiencing photoaging injuries (eg, lentigines or ephelides), avoidance of sun and dermatologic follow-up are warranted even after treatment is discontinued.

Dosage form specific issues:

  • Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [“Inactive” 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.
  • Injection: Avoid/limit use of IV formulation in patients with moderate to severe renal impairment (CrCl <50 mL/minute); injection contains excipient cyclodextrin (sulfobutyl ether beta-cyclodextrin [SBECD]), which may accumulate, although the clinical significance of this finding is uncertain (Luke 2010); consider using oral voriconazole in these patients unless benefit of injection outweighs the risk. If injection is used in patients CrCl <50 mL/minute, monitor serum creatinine closely; if increases occur, consider changing therapy to oral voriconazole.
  • Oral:

– Lactose: Tablets contain lactose; avoid administration in hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

– Sucrose: Suspension contains sucrose; use caution with fructose intolerance, sucrase-isomaltase deficiency, or glucose-galactose malabsorption.

Other warnings/precautions:

  • Monitoring: Evaluate renal function (particularly serum creatinine) and hepatic function (particularly liver function tests and bilirubin) at baseline and periodically during therapy.

OUR MEDICATIONS RANGE

  • Anti-infective
  • Anti-inflammatory
  • Anticoagulant
  • Antidiabetic
  • Antidote
  • Gastrointestinal
  • Infertility
  • Neurology
  • Oncology
  • Osteoporosis
Anti-infective
Anti-infectives is a general term used to describe any medicine that is capable of inhibiting the spread of an infectious organism or by killing the infectious organism outright. This term encompasses antibiotics, antifungals, anthelmintics, antimalarials, antiprotozoals, antituberculosis agents, and antivirals.

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Anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain.

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Anticoagulant
Anticoagulants are medicines that increase the time it takes for blood to clot. They are commonly called blood thinners. There are several different types of the anticoagulant. Each type works at a different level on the blood coagulation pathway. Some can be given by the mouth; others can only be given by injection.

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Antidiabetic
Antidiabetic agents refer to all the different types of medicine involved in the treatment of diabetes. All these agents aim to reduce blood sugar levels to an acceptable range (called achieving normoglycemia) and relieve symptoms of diabetes such as thirst, excessive urination, and ketoacidosis (a serious complication of diabetes that occurs when the body cannot use glucose as a fuel source).

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Antidote
An antidote is a drug, chelating substance, or a chemical that counteracts (neutralizes) the effects of another drug or a poison. There are dozens of different antidotes; however, some may only counteract one particular drug, whereas others (such as charcoal) may help reduce the toxicity of numerous drugs. Most antidotes are not 100% effective, and fatalities may still occur even when an antidote has been given.

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Gastrointestinal
Occasional heartburn or acid indigestion can be treated with an over-the-counter antacid, such as Rolaids, Maalox, Mylanta, Tums, Pepto-Bismol, or Chooz. Your doctor may also include an antacid in your treatment regimen in addition to another form of GI medication.

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Infertility
If you’re trying to get pregnant and it’s not working, you may be exploring medical treatment. Fertility drugs were first introduced in the United States in the 1960s and have helped countless people get pregnant. One of today’s most common fertility drugs may be an option for you or your partner.

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Neurology
Neurology is the branch of medicine concerned with the study and treatment of disorders of the nervous system. The nervous system is a complex, sophisticated system that regulates and coordinates body activities. ... Central nervous system: the brain and spinal cord.

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Oncology
Oncology is a branch of medicine that deals with the prevention, diagnosis, and treatment of cancer. A medical professional who practices oncology is an oncologist. The name's etymological origin is the Greek word ὄγκος, meaning 1. "burden, volume, mass" and 2. "barb", and the Greek word λόγος, meaning "study"

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Osteoporosis
Osteoporosis treatment may involve medication along with lifestyle change. Get answers to some of the most common questions about osteoporosis treatment.

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