CANDIVOR (Voriconazole for Injection 200 mg)

CANDIVOR (Voriconazole for Injection 200 mg)

CANDIVOR (Voriconazole for Injection 200 mg)

VORICONAZOLE FOR INJECTION is a broad spectrum, triazole antifungal agent.

Pharmacotherapeutic group: Antimycotics for systemic use, triazole derivatives, ATC code: J02AC03.

The proposed Voriconazole for Injection 200 mg/vial are available as a white to offwhite lyophilized cake filled in 30 mL clear, Type I molded glass and sealed with grey bromobutyl lyophilisation rubber stopper and white colored flip off seal.

The primary mode of action of VORICONAZOLE FOR INJECTION is inhabitation of fungal cytochrome P450- mediated 14 alpha-lansoterol demethylation, an essential step in fungal ergosterol biosynthesis. The accumulation of alpha-methu sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the antifungal activity of VORICONAZOLE FOR INJECTION. It is shown to be more selective for fungal cytochrome  P450 enzymes than for various mammalian cytochrome P 450 enzymes systems.

In vitro, VORICONAZOLE FOR INJECTION displays broad spectrum antifungal activity with antifungal potency against candida species (including fluconazole resistant C.kruseai and resistant strains of C.glabrata and C.albicans) and fungicidal activity against all aspergillus specious tested. In addition VORICONAZOLE FOR INJECTION shows in vitro fungicidal activity against emerging fungal pathogens, including those such as Scedosporium of Fusarium which have limited susceptibility to existing antifungal agents.

Therapeutic indications

Voriconazole For Injection is indicated for use in treatment of the following conditions:

  • Treatment of invasive Aspergillosis
  • Treatment of fluconazole-resistant serious invasive candida infection (including C.krusei)
  • Esophageal candidiasis.
  • Serious fungal infection caused by Scedosporium spp. (A sexual form of Pseudallescheria body) and Fusarium spp., including Fusarium solani in patients intolerant of or refractory to other therapy.

Specimens for fungal culture and other relevant laboratory studies (including histopathology) should be obtained prior to therapy to isolate and identify causative organism(s), therapy may be instituted before the result of the cultures and other laboratory studies are known however once these results become available, a liable therapy should be adjusted accordingly.

Posology and method of administration

Voriconazole I.V. for Injection requires reconstitution to 10 mg/mL and subsequent dilution to 5 mg/mL or less prior to administration as an infusion, at a maximum rate of 3 mg/kg per hour over 1 to 2 hours.

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Contraindications

Voriconazole For Injection is contraindicated in patients with known hypersensitivity to voriconazole For Injection or to any of the excipients.

Co-administration of CY3A4 substrates, terfenadine, astemizole cisapride, pimozide or quinidine since increased plasma concentration of these drugs can lead to QTc prolongation and rare occurrences of torsades de points.

Coadministration of Voriconazole For Injection with sirolimus is contraindicated because Voriconazole For Injection significantly increases plasma concentrations sirolimus.

Co-administration of Voriconazole For Injection with rifampin, carbamazepine and long-acting barbiturates (e.g. phenobarbital mephobarbital) is contraindicated since these drugs are likely to decrease Plasma Voriconazole For Injection concentrations significantly.

Co-administration of Voriconazole For Injection with ritonavir (400 mg twice daily) is contraindicated because ritonavir significantly decreases plasma Voriconazole For Injection.

Co-administration of Voriconazole For Injection with rifabutin is contraindicated since Voriconazole For Injection significantly increases rifabutin plasma concentration and nlabulin also significantly decreases VORICONAZOLE FOR INJECTION plasma concentrations.

Co-administration of Voriconazole For Injection with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because Voriconazole For Injection may increase the plasma concentration of ergot alkaloids which may lead to ergotism.

Special warnings and precautions for use

Caution should be used when prescribing VORICONAZOLE FOR INJECTION to patients with hypersensitivity to other azoles.

Some azoles including VORICONAZOLE FOR INJECTION have been associated with prolongation of QTc interval. There have been rare cases of torsades de pointers in patients taking VORICONAZOLE FOR INJECTION these reports involved seriously ill patients with multiple confounding risk factors such as history of cardiotoxic chemotherapy; cardiomyopathy, hypokalaemia and concomitant medication that may have been contributory. VORICONAZOLE FOR INJECTION should be administered with caution to patients with these potentially proarrhythmic conditions such as congenital or acquired or QTc prolongation, cardiomyopathy in particular when heart failure is present, sinus bradycardia, existing symptomatic arrthymias and concomitant medication that is known to prolong QTc interval.

If treatment continues beyond 28 days, visual function including visual acuity, visual field and color perception should mentioned VORICONAZOLE FOR INJECTION may cause vision changes, therefore patients on this drug should be advised to avoid potentially hazardous tasks, such as driving or operating machinery, if they perceive any change in vision.

There have been uncommon cases of serious hepatic reactions during treatment with VORICONAZOLE FOR INJECTION (including clinical hepatitis, cholestasis failure, including fatalities) liver function test should be evaluated at the start of and during the course of VORICONAZOLE FOR INJECTION therapy. Patients who develop abnormal liver function test during VORICONAZOLE FOR INJECTION therapy should be monitored for the development of more severe hepatic injury. Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin). Discontinuation of VORICONAZOLE FOR INJECTION must be considered clinical signs and symptoms consistent with liver disease develop that may be attributable to VORICONAZOLE FOR INJECTION.

VORICONAZOLE FOR INJECTION labels contain lactose and should not be given to patients with rare hereditary problems of galactose in clearances. Lapplactose deficience/ or glucose galactose malabsorption.

Electrolytes distrubances such as hypokalemia, hypomagnesemia and hypocalcemia should be monitored and corrected if necessary, prior to initiation and during VORICONAZOLE FOR INJECTION therapy.

Anaphylactic type reactions including flushing, fever, sweating, tachycardia, chest tightness, dyspnoea, faintness, nausea, pruritus and rash have been observed during administration of intravenous infusion of VORICONAZOLE FOR INJECTION in healthy subject’s symptoms appeared immediate upon initiating the infusion. Depending on the diversity of symptoms consideration should be given to stopping the treatment.

Acute renal failure has been observed in severely if patients undergoing treatment with VORICONAZOLE FOR INJECTION patients being treated with are likely to be treated concomitantly with nephrotoxic medications and have concurrent conditions that may result in decreased renal function. This should include laboratory evaluations, particularly serum creatinine.

Patients have rarely developed serious cutaneous reactions. Such as Stevens – Johnson syndrome toxic epidermal necrolysis and erythema multiforme doing treatment with VORICONAZOLE FOR INJECTION. If patients develop a rash they should be monitored closely and consideration given to discontinuation of VORICONAZOLE FOR INJECTION, VORICONAZOLE FOR INJECTION has been infrequently associated with photosensitivity skin reaction. Especially during long term therapy it is recommended that patients avoid strong direct sunlight during VORICONAZOLE FOR INJECTION therapy.

Interaction with other medicinal products and other forms of interaction

Voriconazole For Injection is metabolised by the human cytochrome P450 enzymes CYP2C19, CYP2C9 and CYP3A4 Inhibitors or inducers of these three enzymes may increase or decrease Voriconazole For Injection systemic exposure (plasma concentrations) respectively.

Co-administration of Voriconazole For Injection at 400mg twice daily with rifabutin 300mg twice daily increased the Cmax and AUC of rifabutin by an average of 3 times and 4 times respectively compared to when rifabutin is given alone. Co-administration of Voriconazole For Injection and rifabutin is contraindicated.

Co-administration of Voriconazole For Injection with ergot alkaloids (ergotamine and dihydroergotamine) is contraindicated because Voriconazole For Injection may increase the plasma concentration of ergot alkaloids, which may lead to ergotism.

Cimetidine (400mg twice daily) increased Voriconazole For Injection steady Cmax and AUC by an average of 18% and 23% respectively following oral doses of 200mg Voriconazole For Injection.

No dosage adjustment of Voriconazole For Injection concentrations significantly.

Concomitant administration of Voriconazole For Injection with terfenadine, astemizole, cisapride, pimozide or quinidine may result in inhibition of metabolism of these drugs. Increased plasma concentrations of these drugs can lead to QTc prolongation and are occurences of torsade de points co-administration of Voriconazole For Injection with these drugs is thus contraindicated.

Co-administration Voriconazole For Injection (300mg twice daily) with warfarin (300mg single dose) significantly increased maximum prothrombin time by approximately 2 times that of placebo close monitoring of prothrombin time or other suitable anticoagulation test is recommended if warfarin and Voriconazole For Injection are co-administered and the warfarin dose adjusted accordingly.

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Fertility, Pregnancy and lactation

VORICONAZOLE FOR INJECTION can cause foetal harm when administered to pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the foetus. VORICONAZOLE FOR INJECTION must not be used during pregnancy unless the benefits to the mother clearly out weight the potential risk to the foetus. Women of child bearing potential should be effective contraception during treatment.

OVERDOSAGE

There is no known antidote to voriconazole.

Voriconazole is hemodialyzed with clearance of 121 mL/min. The intravenous vehicle, SBECD, is hemodialyzed with clearance of 55 mL/min. In an overdose, hemodialysis may assist in the removal of voriconazole and SBECD from the body.

The minimum lethal oral dose in mice and rats was 300 mg/kg (equivalent to 4 and 7 times the recommended maintenance dose (RMD), based on body surface area). At this dose, clinical signs observed in both mice and rats included salivation, mydriasis, titubation (loss of balance while moving), depressed behavior, prostration, partially closed eyes, and dyspnea. Other signs in mice were convulsions, corneal opacification and swollen abdomen.

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