Apo-Voriconazole

Apo-Voriconazole Uses, Dosage, Side Effects, Food Interaction and all others data.

Apo-Voriconazole is a triazole antifungal agent which inhibits cytochrome P450-dependent enzymes thereby inhibiting ergosterol synthesis in fungal cell membranes. It has a broad spectrum of activity against all Candida species (including strains resistant to fluconazole), Aspergillus spp., Scedosporium spp., and Fusarium spp.

Apo-Voriconazole is a fungistatic triazole antifungal used to treat infections by inhibiting fungal growth. It is known to cause hepatotoxic and photosensitivity reactions in some patients.

Trade Name Apo-Voriconazole
Availability Prescription only
Generic Voriconazole
Voriconazole Other Names Voriconazol, Voriconazole, Voriconazolum
Related Drugs fluconazole, ketoconazole, Diflucan, itraconazole, amphotericin b, posaconazole, Nizoral, Cresemba, micafungin, caspofungin
Type
Formula C16H14F3N5O
Weight Average: 349.3105
Monoisotopic: 349.11504471
Protein binding

Voriconazole is 58% bound to plasma proteins .

Groups Approved
Therapeutic Class Other Antifungal preparations
Manufacturer
Available Country Canada, United States
Last Updated: September 19, 2023 at 7:00 am
Apo-Voriconazole
Apo-Voriconazole

Uses

Aspergillosis, Candida albicans, Candidaemia, Candidemia, Candidiasis, Coccidioidomycosis, Deep tissue candida infections, Disseminated candidiasis, Fungal keratitis, Histoplasmosis, Invasive aspergillosis, Scedosporiosis and fusariosis

Apo-Voriconazole is also used to associated treatment for these conditions: Aspergillosis of the Central Nervous System, Aspergillosis of the Liver, Candidemia, Candidiasis, Coccidioidomycosis, Endocarditis caused by Aspergillus, Esophageal Candidiasis, Fungal meningitis caused by Exserohilum Infection, Fusarium infection, Histoplasmosis, Infections, Fungal, Invasive Aspergillosis, Osteomyelitis caused by Aspergillus, Penicillium marneffei infection, Peritonitis caused by Aspergillus, Scedosporium Infection, Sinusitis aspergillus, Aspergillus endophthalmitis, Disseminated Candidiasis, Refractory Fungal Infections, Refractory Oral Candidiasis

How Apo-Voriconazole works

Apo-Voriconazole is used to treat fungal infections caused by a variety of organisms but including Aspergillus spp. and Candida spp. Apo-Voriconazole is a triazole antifungal exhibiting fungistatic activity against fungal pathogens. Like other triazoles, voriconazole binds to 14-alpha sterol demethylase, also known as CYP51, and inhibits the demethylation of lanosterol as part of the ergosterol synthesis pathway in yeast and other fungi. The lack of sufficient ergosterol disrupts fungal cell membrane function and limits fungal cell growth. With fungal growth limited, the host's immune system is able to clear the invading organism.

Dosage

Apo-Voriconazole dosage

Adult:

  • ≥40 kg: 400 mg (10 mL) 12 hrly for the 1st 24 hr, followed by 200 mg (5 mL) 12 hrly, may increase to 300 mg 12 hrly or reduce by decrements of 50 mg if necessary.
  • <40 kg: 200 mg (5 mL) 12 hrly for the 1st 24 hr, followed by 100 mg (2.5 mL) 12 hrly, may increase to 150 mg 12 hrly or reduce by decrements of 50 mg if necessary. For oesophageal candidiasis: Treatment should be given for at least 14 days and continued for 7 days after symptoms resolved.

Child

:2-14 yr<50 kg: 9 mg/kg (Max: 350 mg) 12 hrly.

Should be taken on an empty stomach. Take at least 1 hr before or after meals.

Add 46 ml of water to the bottle containing 45 g of voriconazole to provide a susp containing 40 mg/mL. Shake vigorously for about 1 min.

Side Effects

Anaphylactoid reactions (e.g. flushing, fever, sweating, tachycardia, chest tightness, dyspnoea, faintness, nausea, pruritus, rash). Photosensitivity reactions, skeletal effects e.g. fluorosis, periortitis (in long-term therapy), visual disturbances (e.g. abnormal or blurred vision, color vision change, photophobia), GI effects (nausea, vomiting, diarrhoea, abdominal pain), fever, rash, chills, headache, abnormal LFT result, tachycardia, hallucinations.

Toxicity

Symptoms of overdose include photophobia and possible QTc prolongation. In case of overdose, supportive care and ECG monitoring are recommended. Activated charcoal may aid in the removal of unabsorbed drug. Apo-Voriconazole is cleared by hemodialysis at a rate of 121 mL/min which may be helpful in removing absorbed drug. Carcinogenicity studies found hepatocellular adenomas in female rats at doses of 50 mg/kg and hepatocellular carcinomas found in male rats at doses of 6 and 50 mg/kg. These doses are equivalent to 0.2 and 1.6 times the recommended maintenance dose (RMD). Studies in mice detected hepatocellular carcinomas in males at doses of 100 mg/kg or 1.4 times the RMD. Hepatocellular adenomas were detected in both male and female mice.

Precaution

Patients with potentially proarrhythmic conditions, risk for acute pancreatitis. Correct electrolyte disturbances e.g. hypokalaemia, hypomagnesaemia and hypocalcaemia prior to treatment. Hepatic and renal impairment. Pregnancy and lactation.

Interaction

Increased prothrombin time w/ oral anticoagulants. May increase plasma concentrations of ciclosporin and tacrolimus, long-acting opiates (e.g. oxycodone, methadone), NSAIDs (e.g. ibuprofen, diclofenac), omeprazole, short-acting opiates (e.g. alfentanil, fentanyl). Decreased voriconazole plasma concentration and increased phenytoin plasma concentrations when used concomitantly. May increase plasma concentration with oral contraceptives.

Food Interaction

  • Take separate from meals. Take voriconazole at least one hour before or after eating for optimal absorption.

[Moderate] ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole.

According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

Volume of Distribution

The estimated volume of distribution of voriconazole is 4.6 L/kg . Population pharmacokinetic studies estimate the median volume of distribution to be 77.6 L with the central compartment estimated at 1.07 L/kg Apo-Voriconazole is known to achieve therapeutic concentrations in many tissues including the brain, lungs, liver, spleen, kidneys, and heart.

Elimination Route

The oral bioavailability is estimated to be 96% in healthy adults. Population pharmacokinetic studies report a reduced bioavailability pediatric patients with a mean of 61.8% (range 44.6–64.5%) thought to be due to differences in first-pass metabolism or due to differences in diet . Of note, transplant patients also have reduced bioavailability but this is known to increase with time after transplantation and may be due in part to gastrointestinal upset from surgery and some transplant medications. Tmax is 1-2 hours with oral administration. When administered with a high-fat meal Cmax decreases by 34% and AUC by 24%. pH does not have an effect on absorption of voriconazole. Differences in Cmax and AUC have been observed between healthy adult males and females with Cmax increasing by 83% and AUC by 113% although this has not been observed to significantly impact medication safety profiles.

Half Life

Apo-Voriconazole follows non-linear kinetics and has a terminal half-life of elimination which is dose-dependent.

Clearance

The clearance of voriconazole is estimated to be a mean of 5.25-7 L/h in healthy adults for the linear portion of the drug's kinetics.

Elimination Route

Apo-Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Hypersensitivity. Co-admin with CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide, quinidine, rifampicin, carbamazepine, long-acting barbiturates (e.g. phenobarbital, mephobarbital), ergot alkaloids (e.g. ergotamine and dihydroergotamine), efavirenz (≥400 mg once daily), ritonavir (≥400 mg bid), sirolimus, rifabutin, St John's wort.

Acute Overdose

Symptom: Photophobia. Management: May remove via haemodialysis.

Storage Condition

Tablet: Store between 15-30° C. Powd for oral susp: Store between 2-8°C. Reconstituted oral susp: Store between 15-30° C (do not refrigerate or freeze), stable for up to 14 days.

Innovators Monograph

You find simplified version here Apo-Voriconazole

Apo-Voriconazole contains Voriconazole see full prescribing information from innovator Apo-Voriconazole Monograph, Apo-Voriconazole MSDS, Apo-Voriconazole FDA label

FAQ

What is Apo-Voriconazole used to treat?

Apo-Voriconazole is prescribed to treat a fungal infection within your body.It is used in adults and children 2 years of age and older to treat serious fungal infections such as invasive aspergillosis esophageal candidiasis  infection that may cause white patching in the mouth , and candidemia . It is also used to treat certain other fungal infections when other medications will not work for certain patients.

How long can I take Apo-Voriconazole?

Apo-Voriconazole take two doses a day, twelve hours apart.

What is the side effect of Apo-Voriconazole?

The most frequently reported side effects in clinical trials were visual impairment, fever, nausea, rash, vomiting, diarrhea, chills, headache, increased liver function test, peripheral edema, respiratory distress, abdominal pain, tachycardia, and hallucinations.

Does Apo-Voriconazole cause hair loss?

Increasing hair loss among our patients treated with Apo-Voriconazole.

Can I drink alcohol with Apo-Voriconazole?

Avoid alcoholic beverages since they can increase the risk of serious liver problems. 

Can I take Apo-Voriconazole with food?

Take Apo-Voriconazole on an empty stomach 1 hour before or 2 hours after a meal unless otherwise directed by your doctor.

When do you take Apo-Voriconazole levels?

Apo-Voriconazole levels should be drawn 12 hours after the last dose after the patient has received at least 5-7 days of consistent Apo-Voriconazole therapy.

Does Apo-Voriconazole affect kidney?

Renal damage during Apo-Voriconazole therapy occurred in 13 (30.2%) patients with initial normal renal function and in 4 (15.4%) in patients with impaired renal function.

Is Apo-Voriconazole safe during pregnancy?

brans are contraindicated during pregnancy because of fetal toxicity.

Is Apo-Voriconazole safe during breasfeeding?

Women taking this drug should not breastfeed.

How long does it take for Apo-Voriconazole to get out of Apo-Voriconazole system?

Apo-Voriconazole is approximately 6 hours,

Will Apo-Voriconazole safe for liver ?

Apo-Voriconazole is known to be associated with a risk of liver toxicity, phototoxicity, and squamous cell carcinoma of the skin.

How does Apo-Voriconazole work?

Apo-Voriconazole is in a class of antifungal medications called triazoles. It works by slowing the growth of the fungi that cause infection.

How long shouId I take Apo-Voriconazole?

Apo-Voriconazole is prescribed to treat a fungal infection within your body. Take two doses a day, twelve hours apart. You should take Apo-Voriconazole when your stomach is empty.

How is Apo-Voriconazole eliminated from the body?

Apo-Voriconazole is eliminated predominantly by metabolism, it is likely that its non-linear pharmacokinetic profile is probably due to saturation of its metabolism with respect to dose.

Can I stop taking Apo-Voriconazole?

Continue to take Apo-Voriconazole even if you feel well. Do not stop taking Apo-Voriconazole without talking to your doctor.

Is Apo-Voriconazole toxic?

Apo-Voriconazole is a safe and often well-tolerated drug, it was found to be associated with some adverse effects such as neurotoxicity, visual disturbances, and dermatologic reactions.

*** Taking medicines without doctor's advice can cause long-term problems.
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