Posaconazole

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Oropharyngeal, oesophageal candidiasis or candidaemia in patients with disease that is refractory to other appropriate antifungal agents
• Invasive aspergillosis in patients with disease that is refractory to amphotericin B, itraconazole or voriconazole or in patients who are intolerant of these medicinal products
• Fuasariosis , zygomycosis, cryptococcosis, chromoblastomycosis and mycetoma in patients with disease refractory to other therapy, or patients who are intolerant of other therapy
• Coccidioidomycosis
• Prophylaxis of invasive fungal infections in patients who are at high risk of developing these infections, such as patient with prolonged neutropenia or haematopoietic stem cell transplant recipients

Contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• Coadministration with ergot alkaloids
• Coadministration with CYP3A4 substrates terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine
• Coadministration with HMG-CoA reductase inhibitors simvastatin, lovastatin and atorvastatin

Cautions

• Pregnancy
• Breastfeeding
• Hepatic impairment
• Congenital or acquired QT prolongation and risk factors thereof
• Severe diarrhoea and vomiting
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: sus

Infections caused by Yeasts and moulds (including Candida spp., Aspergillus, Absidia, Mucor, and Rhizopus)

General dosing range

• Oral (sus): 100-800mg/day, in divided doses

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Refractory invasive fungal infections
Coccidioidomycosis

• Oral (sus): 400mg, 12hrly OR 200mg, 6hrly

Prophylaxis of invasive fungal infections

• Oral (sus): 200mg, 8hrly

Oropharyngeal candidiasis

• Oral (sus): Initial: 200mg, on day 1, then 100mg, dly; Treatment duration: 14 days

Refractory oropharyngeal or oesophageal candidiasis

• Oral (sus): 400mg, 12hrly

Not established for use in children below 13 years

Pregnancy

• FDA Pregnancy Category C

Breastfeeding

• Caution; not recommended

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Central Nervous System Disorders

• Abnormal dreams 
• Confusional state
• Sleep disorder
• Psychotic disorder 
• Depression
• Paresthesia 
• Dizziness
• Somnolence 
• Headache
• Dysgeusia
• Convulsions
• Neuropathy 
• Hypoaesthesia 
• Tremor
• Aphasia
• Insomnia
• Cerebrovascular accident 
• Encephalopathy
• Peripheral neuropathy 
• Syncope

Cardiovascular Disorders

• Long QT syndrome
• Abnormal electrocardiogram
• Palpitations
• Bradycardia
• Supraventricular extrasystoles 
• Tachycardia
• Torsade de pointes 
• Sudden death
• Ventricular tachycardia 
• Cardio-respiratory arrest 
• Cardiac failure 
• Myocardial infarction
• Hypertension
• Hypotension
• Vasculitis
• Pulmonary embolism 
• Deep vein thrombosis

Respiratory Disorders

• Cough
• Epistaxis 
• Hiccups
• Nasal congestion 
• Pleuritic pain
• Tachypnoea
• Pulmonary hypertension
• Interstitial pneumonia
• Pneumonitis

Gastrointestinal Disorders

• Nausea and vomiting 
• Abdominal pain 
• Diarrhoea 
• Dyspepsia 
• Dry mouth 
• Flatulence
• Constipation 
• Anorectal discomfort
• Pancreatitis
• Abdominal distension 
• Enteritis
• Eructation
• Gastro-oesophageal reflux disease 
• Oral oedema
• Gastrointestinal haemorrhage 
• Ileus

Genitourinary Disorders

• Menstrual disorder
• Breast pain

Hepatobiliary Disorders

• Raised hepatic function tests
• Hepatocellular damage 
• Hepatitis 
• Jaundice
• Hepatomegaly 
• Cholestasis
• Hepatic toxicity
• Hepatic failure
• Cholestatic hepatitis
• Hepatosplenomegaly 
• Liver tenderness
• Asterixis

Endocrine and Metabolic Disorders

• Adrenal insufficiency
• Decreased blood gonadotropin
• Electrolyte imbalance 
• Anorexia
• Decreased appetite 
• Hypokalaemia
• Hypomagnesaemia
• Hyperglycaemia 
• Hypoglycaemia

Musculoskeletal Disorders

• Back pain 
• Neck pain
• Musculoskeletal pain
• Pain in extremity
• Acute renal failure
• Increased blood creatinine
• Renal tubular acidosis 
• Interstitial nephritis

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritis
• Mouth ulceration 
• Alopecia
• Dermatitis 
• Erythema
• Petechiae
• Stevens Johnson syndrome 
• Vesicular rash

Sensory Disorders

• Blurred vision 
• Photophobia
• Reduced visual acuity
• Diplopia
• Scotoma
• Hearing impairment

• P-glycoprotein inhibitors
• Rifabutin
• Efavirenz
• Fosamprenavir
• Phenytoin
• Histamine 2-receptor antagonists
• Proton pump inhibitors
• Food
• CYP3A4 substrates
• Terfenadine
• Astemizole
• Cisapride
• Pimozide
• Halofantrine 
• Quinidine
• Ergot alkaloids
• HMG Co-A reductase inhibitors
• Simvastatin
• Lovastatin
• Atorvastatin
• Vinca alkaloids
• Sirolimus
• Ciclosporin
• Tacrolimus
• Protease inhibitors
• Benzodiazepines
• Calcium channel blockers
• Digoxin
• Sulfonylureas

None routine. Specific cases may require

• Hepatic function
• Serum magnesium
• Serum calcium 

Posaconazole inhibits the enzyme lanosterol 14α-demethylase (CYP51), which catalyses an essential step in ergosterol biosynthesis.

Spectrum of activity: Yeasts and moulds (including Candida spp., Aspergillus, Absidia, Mucor, and Rhizopus)

Suspension (per 1ml) 40mg

• Noxafil (MSD) originator