8F Herpes, Hepatitis and Other Viral Infections

DNA Polymerase Inhibitors

Aciclovir, adefovir and valaciclovir exert their antiviral action in two stages, initially they become phosphorylated via viral thyymidine kinase.

The nucleotide then acts as an inhibitory substrate for viral DNA polymerase enzymes preventing viral replication and causing viral DNA chain termination without affecting the host's normal cellular processes.

Aciclovir is indicated for the treatment of infections due to herpes simplex I and II, and varicella zoster. Herpes simplex skin infections may be managed with topical preparations but oral treatment is required for varicella zoster and mucocutaneous herpes simplex infections.

Adefovir is an orally active treatment for chronic hepatitis B in adults with compensated or decompensated liver disease. It exhibits HBV antiviral activity in a number of patient populations including HBeAg-positive patients; HBeAg-negative precore mutant infected patients, those with lamivudine-resistant HBV, liver transplant recipients and those with decompensated liver disease.

Valaciclovir is an ester of aciclovir and the naturally occuring amino acid valine. It acts as a pro-drug to release aciclovir. It has a higher bioavailability than aciclovir which allows a three times daily dose regimen rather than the five times daily dosing required for aciclovir in the treatment of shingles.

Nucleoside Analogues

Famciclovir, penciclovir, idoxuridine exert their antiviral action by interfering with DNA synthesis. To become active they must be phosphorylated by virus-induced thymidine kinase and their effects are therefore selective for virally infected cells. Famciclovir is the oral prodrug of penciclovir which is extensively absorbed and rapidly converted to the active compound. It has a similar action to aciclovir but its long half-life in virus-infected cells allows once daily dosing. Penciclovir can be used topically as a cream to treat herpes labialis. Idoxuridine is a topical antiviral agent indicated for herpes zoster and herpes simplex skin infections.

Interferons

are produced either by genetic engineering (rbe), or from cultured lymphoblasts (Ins). They exert a non-specific anti-viral action.

Miscellaneous

Oseltamivir and zanamivir are antiviral agents that can be used against influenza A and B, but they must be used within 48 hours of symptoms developing to be effective.

They selectively inhibit the influenza virus surface enzyme, neuraminidase, that is essential for viral replication in the respiratory tract. When used for treatment, they reduce the duration of the illness and the incidence of lower respiratory tract complications.

Oseltamivir may also be used prophylactically during influenza epidemics, as it can have a significant effect in reducing the incidence of the disease. Neither product is a substitute for vaccination against influenza.

Amantadine inhibits viral replication, probably by preventing uncoating of the infecting virus particles. It is used for prophylaxis and treatment of influenza A, in patients likely to develop complications, and for prophylaxis in patients particularly at risk of contracting influenza.

Inosine pranobex acts as an immunopotentiator and interferes with viral nucleic acid synthesis in mucocutaneous herpes simplex infection.

Palivizumab is a monoclonal antibody used to prevent respiratory syncytial virus (RSV) infections in premature babies or infants with bronchopulmonary dysplasia. It has potent neutralising and fusion inhibiting activity against both the A and B strains of RSV.

COPEGUS Roche

Antiviral. Ribavirin 200 mg pink oval f-c tab. marked RIB 200 and ROCHE.

Indications : In combination with peginterferon alfa-2a or interferon alfa-2a for the treatment of chronic hepatitis C in naive patients and those who have relapsed following previous interferon alfa therapy.

Adults : Genotype 1HCV-Under 75kg, 2 in the morning and 3 in the evening; over 75 kg, 3 in the morning and 3 in the evening. Administer peginterferon alfa-2a 180 microgram once weekly or interferon alfa-2a 3-45 mega units three times per week. Continue treatment for 48weeks.

Genotype2 or 3 HCV-2 in the morning and 2 in the evening. Administer peginterferon alfa-2a 180 microgram once weekly. Continue treatment for 24 weeks.

Children : Under 18years, not recommended.

Contraindications : Severe cardiac disease, haemoglobinopathies (thalassemia, sickle-cell anaemia), chronic renal failure, history of severe psychiatric conditions, severe hepatic impairment, liver cirrhosis, autoimmune disease, uncontrolled thyroid disorders. Pregnancy; must have a negative pregnancy test just before initiating therapy, and effective contraception must be used during and for 6 months after treatment. Teratogenic risk also extends to female partners of male patients, effective contraception must be used during and for 6 months after treatment. Counsel patients about teratogenic effects and the need for contraception, continue pregnancy testing during therapy. Lactation.

Special Precautions : Closely monitor renal and cardiac function, haematological values and blood chemistry before and at 2-4 weekintervalsduringtherapy; discontinue if any deterioration.

Congestive heart failure, myocardial infarction, arrhythmia; perform ECG before and during therapy. Withdraw if acute hypersensitivity, liver function abnormalities, psychiatric or thyroid disorders develop. Gout.

Drug Interactions : Nucleoside reverse transcriptase inhibitors.

Adverse Drug Reactions : Haemolysis, anaemia, psychiatric j disorders, suicidal ideation, thyroid disorders, hyperuricaemia.

FAMVIR Novartis

Guanine analogue. Famciclovir 250 mg, 500 mg, 750 mg; white f-c tabs.

250 mg-21 (treatment pack), 500 mg-30 (immunocomp. treatment pack), 750 mg-7 (treatment pack),

Indications : Treatment of herpes zoster in immunocompetent and immunocompromised patients.

Adults : 750 mg once daily at approx. the same time each day for 7 days, or 250 mg three times daily for 7 days. In immunocompromised, 500 mg three times daily for 10 days. Start treatment as soon as possible after onset of rash.

Children : Not recommended.

Special Precautions : Renal impairment. Pregnancy, lactation.

Averse Drug Reactions : Headache, nausea.

HEPSERA Gilead

Nucleotide reverse transcriptase inhibitor. Adefovir dipivoxil 10 mg white tab. marked with GILEAD, tab. strength and liver shape.

Indications : Treatment of chronic hepatitis B in adults with compensated liver disease with evidence of active viral replication, persistently elevated ALT levels and histological evidence of active liver inflammation and fibrosis. Treatment of chronic hepatitis B in adults with decompensated liver disease.

Adults : 1 daily. Treatment duration.

Children : Under 18 years, not recommended.

Contraindications : Lactation.

Special Precautions : Monitor patients every 6 months for hepatitis B biochemical, virological and serological markers to determine treatment duration. Renal impairment. Monitor renal function every 3 months. Cirrhosis; monitor closely for hepatic decompensation.

Monitor patients closely for several months after stopping therapy for acute exacerbations of hepatitis. Patients (particularly obese women) with hepatomegaly, hepatitis, other risk factors of liver disease; risk of lactic acidosis, sometimes fatal. Co-infection with hepatitis C or D or HIV. Elderly. Pregnancy.

Drug Interactions : Drugs excreted by or which affect renal tubular excretion (hOAT1).

Adverse Drug Reactions : GI upset, asthenia, abdominal pain, headache, raised serum creatinine levels, renal insufficiency, renal failure. V Report any adverse reaction to CSM.

HERPID Yamanouchi

Thymidine analogue. Idoxuridine 5%, dimethyl sulFoxide to 100%; soln. Smlwith applicatorbrush,

Indications : Herpes zoster and herpes simplex skin infections.

Adults : Apply four times daily for 4 days.

Children : Not recommended.

Contraindications : Dermographia. Pregnancy.

Special Precautions : Lactation.

Adverse Drug Reactions : Transient stinging, taste disturbance, skin reactions.

IMUNOVIR Ardern

Immunomodulator. Inosine pranobex 500 mg white tab.

Indications : Herpes simplex (type 1 and/or II) infections of skin and mucous membrances. Subacute sclerosing panencephalitis.

Adults : Herpes simplex, 1g four times daily for 7-14 days. Subacute sclerosing panencephalitis, 50-100 mg/kg daily in divided doses every 4 hours.

Children : Not recommended.

Special Precautions : Renal impairment, gout or hyperuricaemia.

Adverse Drug Reactions : Elevated levels of uric acid.

LYSOVIR Alliance

Viral replication inhibitor. Amantadine hydrochlor. 100 g brownred cap. marked GEIGY.

Indications : Prophylaxis and treatment of influenza A.

Adults : Treatmet : 100mg daily for 4-5 days; prophylaxis : 100 mg daily for as long as protection is required, usually 6 weeks or 2-3 weeks if after vaccination.

Elderly : A daily dose of less than 100mg, or 100mg given at intervals of greater than one day, may be appropriate.

Children : Under 10 years, not recommended; 10-15 years, 100 mg daily.

Contraindications : History of convulsions or gastric ulceration, severe renal diseae. Pregnancy, lactation.

Special Precautions : Confusional orhallucinatory states, liver or renal dysfunction, congestive heart failure, history of cariovascular disorders. Elderly, Withdraw gradually.

Drug Interactions : Anticholinegic agents, levodopa, CNS stimulants, CNS depressants, combination diuretics.

Adverse Drug Reactions : Livedo reticularis, peripheral oedema, skin rash, CNS disturbances.

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