Drug Interaction:
Interacting drugs- summary
Nephrotoxic drugs + elimination of foscarnet impaired by drugs that inhibit renal Foscarnet tubular secretion. Avoid the use of foscarnet in combination with potentially nephrotoxic drugs
Foscarnet +
Pentamidine pentamidine have caused hypocalemia. Toxicity associated with concomittant use of aerolized pentamidine has not been reported
Zidovudine Although the combination is well tolerated, additive effects on anemia have occured. However, no evidence of increased mylosuppression was seen
Indication:
HIV infections
Adverse Reaction:
Most frequently reported events-
Fever 65%, nausea 47%, anemia 33%, diarrhea 30%, abnormal renal function including renal failure, decreased CCR and increased serum creatinine 27%, vomiting, headache 26%, seizure 10%.
Adverse reactions categorized as - severe - were- death 14%, abnormal renal function 14% marrow suppression 10%, anemia 9% seizures 7% Injecton site- injection site pain or inflammation 1% to 5%
Special senses - vision abnormalites > 5% taste perversions , eye abnormalites, eye pain, conjuntivitis 1 to 5% diplopia, blindness, retinal detachment, mydriasis, photophobia,deafness, earache, tinnitus < 1%
Contra-Indications:
Hypersensitivity to foscanet
Special precautions:
Monitor renal function due to foscarnet administration. Electrolyte- monitor serum electrolytes. Diagnosis of CMV retinitis. Anemia occurance in some patients
Monitoring-
Renal- the majority of patients will experience some decrease in renal function due to foscarnet administration. It is recommended that Ccr, either measured or estimated during the modified Cockcroft and Gault equation based on serum creatinine, be determined at baseline, 2 to 3 times/week during induction therapy and at least once every 1 to 2 weeks during maintenace therapy with foscarnet dose adjusted accordingly.
Electrolytes- because of foscarnets propensity to chelate divalent metals ions and alter levels of serum electrolytes, closely monitor patients for such changes.
Diagnosis of CMV retinitis- should be made with indirect opthalmoscopy. The diagnosis of CMV retinitis may be supported by culture of CMV from urine, blood, throat or other sites,but a negative CMV culture dose not rule out CMV retinitis.
Toxicity/local irritation- adequate hydration with close attention to personal hygiene may minimize the occurence of such events.
Anemia- occured in 33% of patients.This anemia was usually manageble with transfusions and required discontinuation of foscarnet in < 1% of patients in the studies.
Warnings-
Mineral and electrolyte imbalances- foscarnet has been associated with changes in serum electrlytes including hypocalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia. Therfore advise patients to report symptoms of low ionized calcium such as perioral tingling, numbness in the extremities and paresthesias.
Neurotoxicity and seizures- foscarnet was associated with seizures. If factors predisposing to seizures are present,carefully monitor electrolytes including calcium and magnesium.
Other CNS infections- safety and efficay have not been established for the treatment of other CMV infections (eg. pneumonitis, gastroenteritis, ) congenital or neonatal CMV disease , non-immunocompromised individuals.
Other HIV infections- safety and efficacy have not been established for treatment of other HSV infections (eg. retinitis,encephalitis).
Nephrotoxicity- the major toxicity of foscarnet is renal impairment. Because of foscarnets potential to cause renal impairment dose adjustment for decreased baseline renal function and any change in renal function during treatment is necessary.
Elderly- because these individuals frequently have reduced glomerular filtration, pay particulr attention to assesing renal function before and during administration.
Pregnancy-Use during pregnancy only if clearly needed.
Lactaton- Excercise caution if forcarnet is administred to nursing woman.
Children- Administer to children only after careful evaluation and only if if potential benefits for treatment for treatment outweigh the risks.
Dosages/ Overdosage Etc:
Indications:
HIV infections
Dosage:
Do not administer by rapid bolus IV injection. Toxicity may be increased as a result of excessive plasma levels.
Take care to avoid unintential overdose, carefully control the rate of infusion by using infusion pump. Inspite of use of infusion pump, overdose have occured. Standard 24mg/ml solution may be used without dilution when using a central venous catheter for infusion. Since the dose is calculated by body weight, it may be desirable to remove and discard any quantity from the bottle before starting with the infusion to avoid overdosage.
Overdosage-
Symptoms In controlled clinical trials, overdosage was reported in 10 patients. All 10 patients experienced adverse effects and all except 1 made a complete recovery. One patient died after receiving a total daily dose of 12.5g for 3 days instead of 10.9g The patient sufferd a grandmal seizure and became comatose.
Treatment
1. There is no specific antidote.
2. Hemodialysis and hydration may be of benefit in reducing drug plasma levels in patients who receive an overdosage, but these have not been evaluated in trial settings
3. Observe the patients for signs and symptoms of renal impairment and electrolyte imbalance.
4. Institute medical treatment if clinically warranted.
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Other Information:
EVIDENCE BASED MEDICINE (MIMS April 2003)
Post-herpetic Neuralgia
Comparitive effectiveness of various interventions
Prevention of post-herpetic neuralgia
Beneficial
1. Oral antiviral agents such as acyclovir, famciclovir, valaciclovir, netivudine
2. Tricyclic antidepressants (amitriptyline)
Unknown effectiveness
1. Levodopa
2. Amantadine
3. Isoprinosine
4. Adenosine monophosphate
Unlikely to be beneficial
1. Topical antiviral agents (idoxurine) for relief of acute oain only
2. Cimetidine
Ineffective or harmful
1. Corticosteroids
Relieving established post-herpetic neuralgia
Beneficial
1. Tricyclic antidepressants (amitriptyline)
2. Oxycodone (opiod)
3. Gabapentin (anticonvulasant)
Unknown effectiveness
1. Capsaicin (topical counterirritant)
2. Topical lignocaine
Ineffective or harmful
1. Epidural morphine
2. Dextromethorphan
KEY POINTS
1. Daily acyclovir reduced the relative risk of of post-herpetic pain at six months by about 50 % compared with placebo
2. Famciclovir significantly reduced pain duration after acute herpes zoster.
3. Idoxuridine was associated with short term pain relief in acute herpes zoster but did not prevent post-herpetic neuralgia
4. Conflicting evidence on whether corticosteroids alone prevent post-herpetic neuralgia. Limited evidence that high dose steroids and antiviral agents combined may speed healing of acute zoster. No evidence that it reduces post-herpetic neuralgia
5. Amitriptyline started during the acute episode reduced prevalence of post-herpetic neuralgia at six months.
6. Insufficient evidence on the effect of other drug tretment.
Patient Information:
1. CMV retinitis - foscarnet is not a cure for CMV retinitis, patients may conitinue to experience progression of retinitis during or following treatment. Regular opthalmologic examinationa are necessary.
2. HSV - infections- Foscarnet is not a cure for HSV infections. while complete healing may occur, relapse occurs in most patients. Because relapse may be due to acyclovir sensitive HSV sensitivity trsting of viral isolate is advised.
3. Major toxicities of foscarnet are renal impairment, electrolyte disturbances and seizures. Dose modifications or discontinuance may be required
4. Close monitoring while therapy is essential. advice patients of the importance of perioral tingling, numbness in the extremities or parathesia during or after infusion as possible symptoms of electrolye abnormalies. Should symptoms occur stop the infusion and seek appropiate advice
Ref - USP PDI Vol II 17th Edition (1997)
1.Allergies-
Tell your doctor if you are have ever had any unusual or allergic reaction to
foscarnet. Also tell your healthcare care professional if you are allergic to any other
substances such as foods. preservatives or dyes.
2.Pregnancy-
Foscarnet has not been studied in pregnant women. However,studies in animals,
has not shown that foscarnet cause birth defects or other problems in animal studies.
However, before taking this medicine make sure that your doctor knows if you are
pregnant or if you become pregnant.
3. Breast-feeding-
Mothers who are taking this medicine and who wish to breast feed should discuss this
with their doctor.
4.Children-
You must discuss with the childs doctor the good that this medicine may do as well
as the risks of using it.
5.Older adults-
There is no specific information comparing use of forcarnet in the elderly with use
in other age groups. Consult your doctor
6. Other medicines-
It is important that your your doctor should know if you are using any of the following
medicines-
Carmustine or
Cisplatin or
Cyclosporine or
Deferoxamine or
Gold salts or
Tiopronin - use of these medicines may increase the chance of side effects
affecting the kidneys
7. Other medical problems-
The presence of other medical problems may affect the use of foscarnet.
Make sure you tell your doctor if you have any other medical problems
especially-
Anemia - forscarnet may cause or worsen anemia
Dehydration- or
Kidney disease- patients who are dehydrated or having kidney
disease may have increased side effects
Pharmacology/ Pharmacokinetics:
Pharmacology:
Foscarnet is an organic analog of inorganic pyrophosphate that inhibits its replication of all known hyperviruses in vitro. Focarnet exerts antiviral activity by selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases and reverse transscriptases.
Interaction with Food:
Reports not available
Pregnancy and lactation:
Pregnancy:
Use during pregnancy only if clearly needed.
Lactation:
Excercise caution if foscarnet is administered to nursing mothers
Children-
Administer to children only after careful evaluation and only if if potential benefits for treatment outweigh the risks.
