Drug Information

Drug Interaction:

Interacting drugs- summary

+ Ritonavir-

Clarithromycin + Ritonavir or Ritonavir Clarithromycin

coadmin for 4 days increased the ritonavir AUC by 12% and Cmax by

15% and the clarithromycin AUC increased by 77% and Cmax by 31%.

Didanosine + Ritonovir or Ritonovir + Didanosine

coadmin for 4 days decreased the didanosine AUC by 13% and

Cmax by 16%.

Fluconazole

coadmin for 4 days increased the ritonavir AUC by12% and Cmax by

15%

Fluoxetine

concurrent use increased the ritonavir AUC by 19%

Rifampicin

coadmin decreased the ritonavir AUC by 35% and Cmax by 25%

Ritonavir +

Despramine

concurrent use increased the 2-OH desipramine metabolite AUC by

145% and the Cmax by 23%

Disulfiram / Metronidazole

ritonavir formulations contain alcohol, whih can produce reactions

when coadmin with disulfram or other drugs that produce disulfram-like

reactions

Ethinyl estra diol

coadmin decreased the ethinyl estradiol AUC by 40% and Cmax

by 32%

Narcotic analgesics

AUC of the narcotics may be increased or decreased

Ribabutin

coadmin increased the 25-O-desacetyl metabolite AUC 4-fold and the

Cmax 25 fold

Saquinavir

ritonavir extensively inhibits the metabolism of sequinavir resulting in

increased saquinavir plasma concentrations

Sulfamethoxazole

the AUC ofsulfamethoxazole was decreased by 20%.

Theophylline

coadmin decreased the theophylliine AUC by 43% and Cmax by 52%

Trimethoprim

AUC of trimethoprim decreased by 20%

Zidovudine

coadmin for 4 days decreased the zidovudine AUC by 12% and Cmax

by 27%

Indication:

HIV infection

Approved by FDA on March 6,1996

New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing

(Ref- IDMA Publication)

Name of Drug Indication Date of Approval

Ritonavir Anti HIV September 1997

FIXED DOSE COMBINATIONS APPROVED BY DCG(I)

FROM JANUARY 1961 TILL NOVEMBER 2014

Name of Drug Indication Date of Approval

1. Ritonavir 20mg + 18-01-2001

Lopenavir 80mg per ml oral solution

In the treatment of HIV infection in combination

with other retroviral agents

2.Ritonavir 33.3mg + 18-01-2001

Lopenavir 133.3mg soft gelatin capsule

In the treatment of HIV infection in combination

with other retroviral agents

Patent Expiry Date of drugs (Ref - IDMA Publication)

Chemical Category Manufacturer/ US Patent

Ingredient- Marketer Expiration Date

Ritonavir HIV/AIDS Abbott Laboratories 30-07-2013

Adverse Reaction:

Most frequent clinical adverse events were GI and neurological disturbances-

Nausea, diarrhea, vomiting, anorexia, abdominal pain, taste perversion, and circumoral an

peripheral parasthesias

Body as a whole- abdomen enlarged , accidental injury, allergic reaction, back pain, cachexia, chest pain,facial edema, diabetes mellitus, facial pain, flu syndrome, hormone level altered, hypothermia, kidney pain, neck pain,neck rigidity,pain ( unspecified ), substrenal chestpain, photosentivity reaction. (< 2% )

Cardiovascular- hemorrhage, hypotension, migraine, palpitation, peripheral vascular disorder , postural hypotension, syncope, tachcardia ( < 2% )

GI- abnormal stools, bloody diarrhea, cheilitis, cholangitis, colitis, dry mouth, dysphagia, eructation, esophagitis,gastritis, gastroenteritis, GI disorder, GI haemorrhage, gingivitis, hepatits, hepatomegaly, ileitis, liver damage, liver function tests abnormal.mouth ulcer, oral monoliasis, pancratitis, periodantal abscess, rectal disorder, tenesmus,thirst. ( < 2% )

Hematogical/ Lymphatic- anemia, ecchymosis, leukopenia, lymphadenopathy, lymphocytosis,thrombocytopenia ( < 2% )

Metabolic/Nutritional- avitaminosis, dehydration, edema, glycosuria, gout, hypercholesterolemia, peripheral edema,weight loss ( < 2% )

Musculoskeletal- arthalgia, arthrosis, joint disorder, muscle cramps, muscle weakness, myositis, twitching ( < 2% )

CNS- abnormal dreams, abnormal gait, agitation, amnesia, anxiety, aphasia, ataxia, confusion, convulsions, depression, diplopia, emotional lability, euphoria, grand mal convulsions, hallucinations, hyperesthesia, incordination, libido decreased, nervousness, neuralgia, neuropathy, paralysis, peripheral neuropathy, peripheral sensory neuropathy, personality disorder, tremor, vertigo.( < 2% )

Respiratory- asthma, dyspnea, epistaxis, hiccough, hypoventilation, increased cough, interstitial pneumonia, lung disorder, rhinitis ( < 2% )

Dermatologic- acne, contact dermatitis, dry skin, eczema, folliculitis, macropapular rash. molluscm contagiosum,pruritus, psoriasis, seborrhea, urticaria, vesiculobullous rash.( < 2% )

Special senses- abnormal electro-oculogram, abnormal electroretinogram, anbnormal visionamblyopia, .blurred vision, blepharitis, ear pain, eye pain, hearing impairment, increased cerumen, iritis, parosmia, photophobia, taste loss, tinnitus, uveitis, visual field defect. ( < 2% )

GU- dysuria, hematuria, impotence, kidney calculus, kidney failure, penis disorder, polyuria,

pyelonephritis, urethritis,urinary frequency ( < 2% )

Contra-Indications:

Hypersens to the drug

Special precautions:

Lab test abnormalities- alteration in triglycerides AST, ALT,GGT,CPK, and uric acid. Perform adequate laboratory tests.

Warnings-

Hepatic function impairment- ritonavir is principally metabolised by the liver. Excercise caution when administering to patients with impoaired liver function.

Pregnancy- use during pregnacy only if clearly needed

Lactation- The US Public Health Service Centres and Disease Control and Prevention advises HIV-infected woman not to breast feed to avoid postnatal transmission of HIV to a child who may not be infected.

Children- Safety and efficacy inchildren < 12 years of age have not been established

Dosages/ Overdosage Etc:

Approved by FDA on March 6,1996

Indication:

HIV infection

Dosage: Recommended dosage is 600mg twice daily. If possible take with food.

Overdosage-

Symptoms One patient in clinical trials took rotonavir 1500mg/day for 2 days. The patient reported paresthesis which resoloved after the dose was decreased. Approximate lethal dose was found to be > 20 times the related human dose in rats and 10 times the related human dose in mice.

Treatment

1. Consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient

2. Eliminate unabsorbed drug by emesis or gastric lavage

3. Observe usual precautions to maintain the airway.

4. Administration of activated charcoal may be used to aid in the removal of unabsorbed drug.

5. Ritonavir is extensively metabolisaed by the liver and is highly protein bound. 6. Dialysis is unlikely to remove the drug.

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.

Patient Information:

1.Ritonavir is not a cure for HIV infection. Patients may continue to acquire illness associated with advanced HIV infection, including oportunistic infections.

2. Long term effects are unknown at this time. ritonavir has not shown to reduce the risk of transmitting HIV through sexual contact or blood contamination.

3. Take ritonavir every day as prescribed. Do not alter the dose or discontinue ritonavir without consulting the doctor.

4. Ritonavir reacts with certain drugs when taken together

Pharmacology/ Pharmacokinetics:

Pharmacology:

Ritonavir is an inhibitor of HIV protease with activity against the human immunodeficiency virus(HIV)

Pharmacokinetics:

After an oral dose of 600mg, peak concentration of ritonavir were acheived after 2 hours and 4 hours after dosing after fasting and non-fasting conditions.

Interaction with Food:

The manufacturer recommends taking retonavir with meals if possible

Pregnancy and lactation:

Pregnancy:

Use during pregnancy only when required

Lactation-

The US Oublic Health Service Centres and Disease Control and Prevention advises HIV-infected woman not to breast feed to avoid postnatal transmission of HIV to a child who may not be infected.

Children- Safety and efficacy inchildren < 12 years of age have not been established

Ritonavir ( *** ) -@-Antiviral agent- (FDC- List )- (1March 1996)

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Interaction with Food

Pregnancy and lactation