Drug Interactions -summary-

+ Tipanavir

Aluminium and magnesium based antacids-
aluminium and magnesium antacids may decrease tipranavir absorption .
consider separating tipranavir. ritonavir dosing from antacid administration

Azole antifungals ( fluconazole ) + tipranazole / tipranavir + azole antifungals ( fluconazole,
 ketoconazole,voriconazole )
fluconazole may increase tipranazole concentrations. Dosage adjustments is not needed
High dose( > 200mg) of fluconazole, itraconazole and ketoconazole are not recommended

Clarithromycin+ Tipranavir /Tipranavir + clarithromycin
concurrent use may increase tipranavir and clarithromycin levels. Dosage adjustments
are not recommended in patients with healthy renal function

Efranavir
efranavir coadministered with tipranavir/ritonavir ( 500mg/100mg twice daily) may cause
tiprnavir concentrations to decrease

Loperamide+ tipranavir/Tipranavir + loperamide -
coadmin my decrease the concentration of both tipranavir and loperamide

Rifamycin ( rifampin ) + tipranavir/ Tipranavir + rifamycin-
coadmin of tipranavir with rifampin may lead to loss of virologic response and possible
resistence to tipranavir

St Johns wart-
coadmin may lead to loss of virologic response and posible resistence to tipranavir.
Cuncurrent use is not recommended

Tenovir + tiprnavir/Tipranavir+ tenovir-
coadmin may decrease concentrations of both tiprnavir and tenovir

Antihistamines -
coadministration  is contraindicated because of life threatening cardiac arrhythmias

Antiarrhythmics agents - (amidarone,bepiridil, flecanide, propafenone, quinidine )
coadmin is contraindicated because of life threatening cardiac arrhythmias
 
Benzodiapines ( midazolam, triazolam ) -
coadmin is contraindicated because of risk of prolonged increased sedation or
respiratory depression

HIV infection

Adverse Reactions-

Cardiovascular -  intracranial hemorrhage

CNS- dizziness, insomnia, peripheral neuropathy, sleep disorder, somnolence

Dermatologic- acquired lipodystrophy, lipoatrophy pertrophy, pruritus

GI - abnormal distention,  anorexia, dyspepsia, flatulence, gastrointrestinal reflux disease,
pancreatitis

Hematologic/lymphatic - anemia, neutropenia, thrombocytopenia

Hepatic - hepatic failure, epatitis,

Metabolic /nutritional - decreased appetite, dehydration, diabetes melitus, facial wasting,
hypercholosterolemia, hyperrglucemia, weight decreased.

Musculoskeletal - muacle cramps, myalgia

Renal - renal function impairment

Respiratory - dyspnea

Miscellaneous- hypersensitivity, influenza,-like illness, malaise, pyrexia, reaction of herpes
simplex and vercella zoster.

Lab test abnormalities- hepatic enzymes increased, liapase increased , liver function test
abnormal

Special precautions-
Coadministration with retonovir - tipranavir must be coadministered with ritonavir 200mg
to exert its therapeutic effect. Failure to corectly administer tipranavir with ritonavir will result
in reduced plasma levels of tiprnavir that is isufficient to produce antiviral effect.

Hepatic toxicity - clinical hepatitis and hepatic decompensation including fatalities reported,
Therefore, perform liver function tests prior to initiating theraphy  with tiprnavir/itonavir 
and frequently throughout the duration of treatment.

Platelet aggregation inhibition- use tiprnavir/retonovir with caution who may  be at risk of
increased bleeding from trauma and surgery.

Hepatic function impairment - tipranavir/ritonavir is contraindicated in patients with moderate to
severe hepatic impairment

Pregnancy- use tipranavir/retonivir during prgnancy only if required

Lactation- instruct mothers not to breast feed if they receiving tipranavir.

Children- safety and efficacy not established

Elderly- excercise caution while administering to elderly patients

Monitoring- perform liver functin tests prior to initiating and frequently througout the
duration of tipranavir/retonovir administration.

Perform triglyceride and cholsterol testing prior to initiating and at periodic intervals
during therapy

Indication-

HIV infection

Dosage-

Recommended dose of tiprnanvir is 500mg ( two 250mg capsules) coadministered with
ritonavir 200mg twice daily

1. Instruct patients to inform any unusual or unexplined bleeding to their doctor

2. Inform patients that tipranavir administered with ritonavir 200mg has been associated with severe
 liver diseases, including some deaths.

3. Instruct patients with signs  or symptoms of clinical hepatitis to discontinue treatment and
   seek medical help. Symptoms include, fatigue, malaise, anorexia, nausea, jaundice,
   bilirubinemia, acholic stools, liver tendrrness or hepatomegaly

4. Advice patients that liver function tests will be performed prior to initiating therapy and
   the duration of treatment

5. Excercise caution when administring to patients with liver enzyme abnormalites, or
   history of chronic liver diseases. Increased liver function fuunction testing is warranted
   in these patients.

6. Mild to moderate rash has been reported in HIV -infected men andwomen receiving
   tipranavir/ retinovir . 

7. Instruct women receiving estrogen based hormonal contraceptives to use additional or
   alternative contraceptive measures during therapy.

8. Inform patients that tipranair must be co-administered with ritonavir 200mg to ensure
   its therapeutic effects.

9. Instruct patients to take tipranavir and other concomittant antiretroviral therapy every day
   as  prescribed. If the dose is missed instruct patients to take the dose as soon as possible.
  and then return to the normal dose. Do not double the next dose.

10. Inform patients that tipranavir is not a cure for HIV-1 infections and that they may continue
    to develop oppurtunistic infections and other complicatiions associated  with HIV disease. 

Pregnancy-
Use tipranavir/retonivir during prgnancy only if required

Lactation-
Instruct mothers not to breast feed if they receiving tipranavir.

Children-
Safety and efficacy not established

Elderly-
Excercise caution while administering to elderly patients