Famciclovir – Dosage

What is famciclovir?

Famciclovir is an antiviral drug which is active against the Herpes viruses, including herpes simplex 1 and 2 (cold sores and genital herpes) and varicella-zoster (shingles and chickenpox). It belongs to a class of drugs called nucleoside analogs that mimic one of the building blocks of DNA. It stops the spread of herpes virus in the body by preventing the replication of viral DNA that is necessary for viruses to multiply. Other drugs in the same class include acyclovir (Zovirax) and valacyclovir (Valtrex). Famciclovir is actually a “prodrug,” that is, not active directly against viruses. Instead, famciclovir is converted to penciclovir in the body, and it is the penciclovir that is active against the viruses. Famciclovir is active against the same viruses as acyclovir but has a longer duration of action. Therefore, it can be taken fewer times each day.

Properties and Characteristics of Famciclovir

Drug class	Antiviral drugs, Purine nucleosides
Brand Names	Famciclovir, Famvir, Famicimac
Synonyms	Famciclovir, Famciclovirum
Molecular Formula	C14H19N5O4
Molecular Weight	321.3318 g/mol
IUPAC Names	2-[(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate
Structural formula of main components
Pure active ingredient	Famciclovir
Appearance	Solid and White shiny plates
Melting point	102-104 °C
Solubility	Soluble in water at 25 °C
Excretion	Renal elimination
Available Forms	Oral Tablet
Storage	Store at room temperature, 68°F to 77°F (20°C to 25°C)
Prescription	Doctor prescription is required before consumption

Uses of Famciclovir

Famciclovir is used to treat infections caused by certain types of viruses. It treats shingles caused by herpes zoster. It also treats outbreaks of herpes simplex that cause cold sores around the mouth, sores around the anus, and genital herpes. In people with frequent outbreaks of genital herpes, famciclovir is used to help reduce the number of future episodes. Famciclovir is an antiviral drug. However, it is not a cure for these infections. The viruses that cause these infections continue to live in the body even between outbreaks.

Famciclovir decreases the severity and length of these outbreaks. It helps the sores heal faster, keeps new sores from forming, and decreases pain/itching. This medication may also help reduce how long pain remains after the sores heal. In addition, in people with a weakened immune system, famciclovir can decrease the risk of the virus spreading to other parts of the body and causing serious infections.

What are side effects of Famciclovir?

Famciclovir may cause serious side effects including:

• Confusion,
• Little or no urination,
• Swelling in your feet or ankles,
• Tiredness, and
• Shortness of breath

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Famciclovir include:

• Headache,
• Nausea,
• Stomach pain,
• Gas,
• Diarrhea,
• Tired feeling,
• Dizziness,
• Sleepiness,
• Itching or skin rash, or
• Numbness or tingly feeling.

Tell your doctor if you have serious side effects of Famciclovir including:

• Mental/mood changes (such as agitation, slowed thinking, confusion, hallucinations),
• Changes in the amount of urine,
• Yellowing eyes or skin, or
• Easy bruising or bleeding.

Seek medical care or call 911 at once if you have the following serious side effects:

• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Mechanism of action

Famciclovir undergoes rapid biotransformation to the active antiviral compound penciclovir, which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). In cells infected with HSV-1, HSV-2 or VZV, viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted to penciclovir triphosphate by cellular kinases. In vitro studies demonstrate that penciclovir triphosphate inhibits HSV-2 DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited.

Drug Interactions

Potential for Famciclovir to affect other drugs

The steady-state pharmacokinetics of digoxin were not altered by concomitant administration of multiple doses of famciclovir (500 mg three times daily). No clinically significant effect on the pharmacokinetics of zidovudine, its metabolite zidovudine glucuronide, or emtricitabine was observed following a single oral dose of 500 mg famciclovir coadministered with zidovudine or emtricitabine.

An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes.

Potential For Other Drugs to Affect Penciclovir

No clinically significant alterations in penciclovir pharmacokinetics were observed following single-dose administration of 500 mg famciclovir after pretreatment with multiple doses of allopurinol, cimetidine, theophylline, zidovudine, promethazine, when given shortly after an antacid (magnesium and aluminum hydroxide), or concomitantly with emtricitabine. No clinically significant effect on penciclovir pharmacokinetics was observed following multiple-dose (three times daily) administration of famciclovir (500 mg) with multiple doses of digoxin.

Concurrent use with probenecid or other drugs significantly eliminated by active renal tubular secretion may result in increased plasma concentrations of penciclovir.

The conversion of 6-deoxy penciclovir to penciclovir is catalysed by aldehyde oxidase. Interactions with other drugs metabolized by this enzyme and/or inhibiting this enzyme could potentially occur. Clinical interaction studies of famciclovir with cimetidine and promethazine, in vitro inhibitors of aldehyde oxidase, did not show relevant effects on the formation of penciclovir. Raloxifene, a potent aldehyde oxidase inhibitor in vitro, could decrease the formation of penciclovir. However, a clinical drug-drug interaction study to determine the magnitude of interaction between penciclovir and raloxifene has not been conducted.

Dosage and Administration

Famciclovir should be administered shortly after the signs and symptoms of a herpes zoster infection appear, or within 72 hours appearance of a varicella-zoster rash. If the lesions do not progressively crust over throughout treatment, talk to your doctor about extending the regimen up to 10 days.

Adults 

• Active herpes zoster lesion – 500 mg POTID x 7 days
• Genital herpes simplex virus (initial episode) – 250 mg PO TID x 7-10 days
  • In HIV-infected patients, as per HIV guidelines – 500 mg PO BID for 5 to 14 days
• Genital herpes simplex virus (recurrent episodes in immunocompetent patients): 125 mg PO BID x 5 days or 500 mg PO x 1, then 250mg PO BID x 2 days or 1 gm PO BID x 1 day. In HIV-infected patients – 500 mg PO BID for seven days.
• For genital chronic suppression therapy – 250 mg BID x 7 days.

For patients with moderate to severe renal impairment: the patient should increase the time between each administered dose to prevent penciclovir accumulation.

The proper doses may be altered to best suit the patient based on the doctor’s recommendations. The kidneys primarily excrete famciclovir. With the reduction in renal function, the clearance of penciclovir, a famciclovir metabolite, is found to be decreased linearly. Thus, in renal insufficiency, dosage adjustment is recommended.

Overdose

Accidental, repeated overdoses of oral Famciclovir over several days have resulted in nausea, vomiting, confusion and headache. Consult your doctor in case of overdose.

What special precautions should I follow?

Before taking famciclovir,

• tell your doctor and pharmacist if you are allergic to famciclovir, penciclovir cream (Denavir), acyclovir (Zovirax), any other medications, or lactose.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplement, and herbal products you are taking or plan to take, especially probenecid (Benemid).
• tell your doctor if you have or have ever had problems with your immune system, human immunodeficiency virus infection (HIV), or acquired immunodeficiency syndrome (AIDS); galactose intolerance or glucose-galactose malabsorption (inherited conditions where the body is not able to tolerate lactose); or kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking famciclovir, call your doctor.
• you should know that famciclovir may make you drowsy, dizzy, confused, or disoriented. Do not drive a car or operate machinery until you know how this medication affects you.

Pregnancy & Lactation

Pregnancy

Available data from pharmacovigilance reports in pregnant women have not identified a drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; there are risks to fetus associated with untreated herpes simplex virus during pregnancy; after oral administration, famciclovir (prodrug) is converted to penciclovir (active drug); in animal reproduction studies with famciclovir, no evidence of adverse developmental outcomes observed at systemic exposures of penciclovir (AUC) slightly higher than those at maximum recommended human dose (MRHD).

Lactation

There are no data on presence of famciclovir (prodrug) or penciclovir (active drug) in human milk, effects on breastfed infant, or on milk production; animal data indicate that penciclovir is present in the milk of lactating rats; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition