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 

HIV infections 

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%

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.

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.

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

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.

Reports not available

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.