Interacting drugs- summary
 

+ Zalcitabine -

Antacids +
Zalcitabibne absorption is moderately reduced, when
  co-administered with Magensium  and Alumininium.
  Do not ingest simultaneously

Chloramphenicol/Cisplatin/ Dapsone/Didanosine/Disulfram/Ethionamide/Glutethimide/
Gold/Hydrazine/Iodoquinol/Isoniazid/ Metronidazole/Nitrofurantoin/ Phenytoin/Ribavarin
These drugs are associated with peripheral neuropathy
 Avoid concomittant use

+ Cimetidine 
   Concomittant use decreases zalcitabine elimination,  by
   inhibition of renal tubular secretion

+ Metoclopramide
   Zalcitabine bioavailability is mildly reduced- about 10%

 + Pentamine & other agents potential to cause pancreatitis 
    Interrupt treatment when the use of a drug that has the potential to
    cause pancreatitis is required
   
   + Probenecid 
    Concomittant use decreases zalcitabine elimination,  by
    inhibition of renal tubular secretion                      
                 

ADVERSE REACTIONS-

GI -     

 Diarrhea     9%  Abdominal pain  8%  Oral ulcers   7%    Dysphagia  4% 

Nausea   4%  Vomiting  3%   Mouth lesions    3 % Swallowing  painful   2%
Acute pharyngitis  2%    Melena  1%  Flatulence  1  Constipation  rare                 
                        
Metabolic/nutrional-

Hypoglycemia, triglyceride abnormal, hypophosphatemia, hypernatremia, bilirubin increased, appetite loss of, abnormal weight loss, hypomagnesemia, hypocallcium, creatinine, amylase increased, hyperglycemia.

Musculoskeletal-

Joint pain, weakness of muscle, myalgia, CPR elevated.

CNS-

Dizziness, confusion, loss of memory, decreased concentration, anxiety state, depression, headache, insomnia.

Renal-

Dysuria, urination frequency

Respiratory-

Nasal discharge, cough, rales, ronchi, dyspnea/respiratory distress

Dermatologic-

Pruritic disorder, rash, night sweats, lip blister, lesions

Special senses-

Ear problem, pain, smell dysfunction

Miscellaneous-

Fever, malaise/fatigue, chest pain, general debilitation,chills, LDH abnormal, GGT abnormal,lymphodenopathy, vaginal discharge

Hypersens to the drug

Special precautions:

Monitoring- perform regular blood counts, and clinical chemistry tests. Monitor serum amylase levels.

HIV infection- patients receiving zalcitabine or any other antiretroviral therapy may continue to develop oppurtunistic infections and other complications of HIV infection. should be under close observation of healthcare personnels.

Warnings

Peripheral neuropathy- the major toxicity is peripheral neuropathy. Rates were similar among patients with zalcibatine monotherapy and in combination with zidovudine.

Pancreatitis- documented fatal pancreatitis has occured with zalcitabine alone or in combination with zidovudine. Carefully follow patients with a history of pancreatitis or known risk factors for the development of pancreatitis while on zalcitabine.

Hepatic toxicity- interupt or discontinue therapy in the setting of deterioration of liver function tests, hepatic steatosis, progressive hepatomegaly or unexplained lactic acidosis.

Oral ulcers- severe oral ulcers occured in 3% of patients on two trials.

Esophageal ulcers- infrequent cases of esophageal ulcers have been attributed to zalcitabine therapy.

Cardiomyopathy/congestive heart failure- have occured with the use of nucleoside antiretroviral agents in AIDS patients. Infrequent cases have occured in patients receiving zalcitabine.

Anaphylactoid reactions- there has been report of anaphylactoid reaction in patients receiving zalcitabine and zidovudine. There have several reports of urticaria without signs of anaphylaxis.

Combination therapy- in vitro combintion studies demonstarted that zalcitabine and ziduvudine have an additive or synergistic antiviral effect , depending on cell line used, without increased cytotoxicity over observed for either agent alone.

Renal function impairement- patients with renal mpairment may be at greter risk of toxicity due increased drug clearance. Dosage reduction is recommended.

Pregnancy- fertile woman should not receive zalcitabine unless they are using effective contraceptive during therapy.

Lactation- It is currently recommended in the US that HIV-infected women do not breastfeed infants regardless of the use of antiretoviral agents.

Children- safety and efficacy of zalcitabine in combination with zidovudine or as monotherapy in HIV infected children < 13 years have not been established.

Approved by FDA on June 19, 1992

Indications:

HIV infections

Dosage:

Monotherapy- 0.75mg every 8 hrs(2.25mg total daily dose)

Combination therapy- 0.75mg administered concomittantly with 200mg zodovudine every 8 hrs

Overdosage

Symptoms Mixed overdoses including zalcitabine and other drugs have led to drowsiness, and vomiting or increased GST or creatinine phosphokinase

Treatment

1. There is no known antidote.

2. It is not known whether zalcitabine is dialyzable by peritoneal dialysis or hemodialysis.

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.

Pharmacology:

Zalcitabine, active against HIV, is a synthetic pyrimidine nucleoside analog of the natural occuring nucleoside.

Rate of absorption is reduced when administered with food.

Pregnancy:

Fertile women should not receive zalcitabine unless they are using an effective contraceptive during therapy

Lactation:

It is recommended that HIV infected women do not breast feed infants regardless of the use of antiretroviral agents

Children-

Safety and efficacy of zalcitabine in combination with zidovudine or as monotherapy in HIV infected children < 13 years have not been established.