MILTEFOSINE Drug Interactions: What You Need to Know

INTERACTIONS In vitro and animal metabolism studies showed that miltefosine did not markedly induce or inhibit the activity of the major human cytochrome P450 enzymes [see Clinical Pharmacology ( 12.3 )] . The potential of miltefosine to interact with drug transporters has not been evaluated. IMPAVIDO did not inhibit human cytochrome P450 enzymes in vitro. IMPAVIDO did not induce cytochrome 3A activity in rats( 7 , 12.3 ).

Pregnancy ( 4.1 , 8.1 , 8.8 , 13.1 ). Sjögren-Larsson-Syndrome ( 4.2 , 12.3 ). Hypersensitivity to miltefosine or any of its excipients ( 4.3 ).

4.1 Pregnancy IMPAVIDO may cause fetal harm. IMPAVIDO is contraindicated in pregnant women. Obtain a urine or serum pregnancy test prior to prescribing IMPAVIDO <span class="opacity-50 text-xs">[see Boxed Warning and Use in Specific Populations ( 8.1 )]</span> .

4.2 Sjögren-Larsson-Syndrome IMPAVIDO is contraindicated in patients who have Sjögren-Larsson-Syndrome <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

4.3 Hypersensitivity IMPAVIDO is contraindicated in patients who are hypersensitive to miltefosine or any IMPAVIDO excipients.

AND PRECAUTIONS Embryo-Fetal Toxicity. Do not use in pregnant women. Obtain a urine or serum pregnancy test prior to initiation of therapy. Advise use of effective contraception in females of reproductive potential ( Boxed Warning , 5.1 , 8.1 , 8.8 , 13.1 ). Reproductive effects. Miltefosine caused testicular atrophy and impaired fertility in male rats and impaired fertility in female rats. Advise patients of reproductive toxicities in animal studies and that the potential effects on human fertility have not been adequately evaluated ( 13.1 ).

Renal

Effects. Monitor serum creatinine during therapy and for 4 weeks after end of therapy ( 5.3 , 6.1 ).

Hepatic

Effects. Monitor transaminases and bilirubin during therapy ( 5.4 , 6.1 ).

Gastrointestinal

Effects. Encourage fluid intake ( 5.5 ). Thrombocytopenia. Monitor platelet count during therapy for visceral leishmaniasis ( 5.6 , 6.1 ). Absorption of Oral Contraceptives. Advise use of alternative method of contraception if vomiting and/or diarrhea occur ( 5.7 ). Stevens-Johnson syndrome. Discontinue IMPAVIDO ( 5.8 ).

5.1 Embryo-Fetal Toxicity Miltefosine may cause fetal harm. Embryo-fetal toxicity, including death and teratogenicity, was observed in animals administered miltefosine prior to mating, during early pregnancy, and during organogenesis at doses lower than the maximum recommended human dose (MRHD). Do not use IMPAVIDO in pregnant women. Obtain a urine or serum pregnancy test prior to prescribing IMPAVIDO to females of reproductive potential. Advise females of reproductive potential to use effective contraception during IMPAVIDO therapy and for 5 months after completion of therapy <span class="opacity-50 text-xs">[see Boxed Warning , Contraindications ( 4.1 ) and Use in Specific Populations ( 8.1 , 8.8 )]</span> .

5.2 Reproductive Effects Females Miltefosine caused impaired fertility in rats and reversible follicular atresia and diestrus in dogs at doses approximately 1.0 and 0.2 times respectively the MRHD based on body surface area comparisons <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . Effects on human female fertility have not been formally studied.

Males

Miltefosine caused reduced viable sperm counts and impaired fertility in rats at doses approximately 0.4 times the MRHD [see Nonclinical Toxicology ( 13.1 ) ] . A higher dose in rats, approximately 1.0 times the MRHD, caused testicular atrophy and impaired fertility that did not fully reverse 10 weeks after drug administration ended. Scrotal pain and decreased or absent ejaculation during therapy have been reported during IMPAVIDO therapy [see Adverse Reactions ( 6.2 ) ] . The effects of IMPAVIDO on human male fertility have not been adequately studied. Advise women and men of the animal fertility findings, and that the potential for impaired fertility with IMPAVIDO therapy in humans has not been adequately evaluated.

5.3 Renal Effects Elevations of serum creatinine (Cr) were noted in clinical trials evaluating IMPAVIDO in the treatment of cutaneous, mucosal and visceral leishmaniasis. Monitor renal function weekly in patients receiving IMPAVIDO during therapy and for 4 weeks after end of therapy <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .

5.4 Hepatic Effects Elevations in liver transaminases (ALT, AST) and bilirubin were noted in clinical trials evaluating IMPAVIDO in the treatment of visceral leishmaniasis. Monitor liver transaminases (ALT, AST) and bilirubin during therapy in patients receiving IMPAVIDO <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .

5.5 Gastrointestinal Effects Vomiting and/or diarrhea commonly occur during IMPAVIDO administration and may result in volume depletion. Encourage fluid intake to avoid volume depletion <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .

5.6 Thrombocytopenia Thrombocytopenia during therapy has been reported in patients treated for visceral leishmaniasis. Monitor platelet count during therapy for visceral leishmaniasis <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 , 6.2 )]</span> .

5.7 Absorption of Oral Contraceptives Vomiting and/or diarrhea occurring during IMPAVIDO therapy may affect the absorption of oral contraceptives, and therefore compromise their efficacy. If vomiting and/or diarrhea occur during IMPAVIDO therapy, advise females to use additional non-hormonal or alternative method(s) of effective contraception.

5.8 Stevens-Johnson Syndrome Stevens-Johnson syndrome has been reported during IMPAVIDO therapy. Discontinue IMPAVIDO if an exfoliative or bullous rash is noted during therapy <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .